Traumatic brain injury (TBI) is a major leading cause of death and disability. While previous studies regarding focal pathologies following TBI have been done, there is a lack of information concerning the role of analgesics and their influences on injury pathology. Buprenorphine (Bup), an opioid analgesic, is a commonly used analgesic in experimental TBI models. Our previous studies investigated the acute effects of Buprenorphine-sustained release-Lab (Bup-SR-Lab) on diffuse neuronal/glial pathology, neuroinflammation, cell damage, and systemic physiology. The current study investigated the longer-term chronic outcomes of Bup-SR-Lab treatment at 4 weeks following TBI utilizing a central fluid percussion injury (cFPI) model in adult male rats. Histological assessments of physiological changes, neuronal damage, cortical and thalamic cytokine expression, microglial and astrocyte morphological changes, and myelin alterations were done, as we had done in our acute study. In the current study the Whisker Nuisance Task (WNT) was also performed pre- and 4w post-injury to assess changes in somatosensory sensitivity following saline or Bup-SR-Lab treatment. Bup-SR-Lab treatment had no impact on overall physiology or neuronal damage at 4w post-injury regardless of region or injury, nor did it have any significant effects on somatosensory sensitivity. However, greater IL-4 cytokine expression with Bup-SR-Lab treatment was observed compared to saline treated animals. Microglia and astrocytes also demonstrated region-specific morphological alterations associated with Bup-SR-Lab treatment, in which cortical microglia and thalamic astrocytes were particularly vulnerable to Bup-mediated changes. There were discernable injury-specific and region-specific differences regarding myelin integrity and changes in specific myelin basic protein (MBP) isoform expression following Bup-SR-Lab treatment. This study indicates that use of Bup-SR-Lab could impact TBI-induced glial alterations in a region-specific manor 4w following diffuse brain injury.

Horse riding therapy, also known as hippotherapy, is a popular treatment for children with cerebral palsy (CP). However, the need for trained therapists, massive land use, and expensive maintenance of the horse ranch makes hippotherapy not affordable or even available for most patients in Indonesia. This problem motivates us to consider mechanical horse riding simulator machines to replace actual horse hippotherapy. However, most patients are children and are easily bored when asked to do monotonous activities for an extended period. The room setting also does not give the patient visual inputs that usually help motivates the children in real-horse hippotherapy activities. To solve this problem, we designed an exercise game (exergaming) software which we named \textit{Sirkus Apel}, providing the patients with fun activities while doing the therapy. We also design an inertial sensor-based controller that lets the patients control the in-game horse by their back movements, which also benefits CP patients. To make the visual input enjoyable to the user while also considering the user's safety, we built a convex mirror-based dome virtual reality to provide an immersive 3-D experience. We then project the game content to the dome to provide an immersive experience to the patients making it as if they are riding a real horse inside the game.

Cancer invasion through basement membranes represents the initial step of tumor dissemination and metastasis. However, little is known about how human cancer cells breach basement membranes. Here, we used a 3-dimensional in vitro invasion model consisting of cancer spheroids encapsulated by a basement membrane and embedded in 3D collagen gels to visualize the early events of cancer invasion by confocal microscopy and live-cell imaging. Human breast cancer cells generated large numbers of basement membrane perforations, or holes, of varying sizes that expanded over time during cell invasion. We used a wide variety of small molecule inhibitors to probe the mechanisms of basement membrane perforation and hole expansion. Protease inhibitor treatment (BB94), led to a 63% decrease in perforation size. After myosin II inhibition (blebbistatin), basement membrane perforation area decreased by only 15%. These treatments produced correspondingly decreased cellular breaching events. Interestingly, inhibition of actin polymerization dramatically decreased basement membrane perforation by 80% and blocked invasion. Our findings suggest that human cancer cells can primarily use proteolysis and actin polymerization to perforate the BM and to expand perforations for basement membrane breaching, with a relatively small contribution from myosin II contractility.

The ability to directly look into genome sequences has opened great opportunities in plant breeding. Yet, the assembly of full-length chromosomes remains one of the most difficult problems in modern genomics. Genetic maps are commonly used in de novo genome assembly and are constructed on the basis of a statistical analysis of the number of recombination rather than physical distance in base pairs. This may affect the accuracy of the ordering and orientation of scaffolds within the chromosome, especially in the region of recombination suppression. Here we report the use of Tyr-FISH for validation of genetic and pseudochromosome maps. For probe design we developed a pipeline that is based on selection of a unique sequence with minimal potential fluorescent background arising from non-specific in situ hybridization. In total of 24 unique genes were located on physical chromosomes 2 and 6. The order of markers has been corrected by integration genetic and cytogenetic maps. Tyr-FISH mapping showed that the order of 23.1% (chromosome 2) and 27.3% (chromosome 6) of the tested genes differed between physical chromosomes and pseudochromosomes. Also the position of the mlh1 gene, which was not on the genetic map, was defined on physical chromosome 2. The results suggest the possibility of Tyr-FISH mapping of any gene that may not be neither on the genetic map nor in the assembly. Hence, Tyr-FISH provides valuable information for the improvement of the genome assembly.

We present a compact polarimeter for 3He ions with special emphasis on the analysis of short-pulsed beams accelerated during laser-plasma interactions. We discuss the specific boundary conditions for the polarimeter, such as the properties of laser-driven ion beams, the selection of the polarization-sensitive reaction in the polarimeter, the representation of the analyzing-power contour map, the choice of the detector material used for particle identification, as well as the production procedure of the required deuterated foil-targets. The assembled polarimeter has been tested using a tandem accelerator delivering unpolarized 3He ion beams, demonstrating good performance in the few-MeV range. The statistical accuracy and the deduced figure-of-merit of the polarimetry are discussed, including the count-rate requirement and the lower limit of accuracy for beam-polarization measurements at a laser-based ion source.

Healthcare workers (HCWs) in long-term care (LTC) faced and continue to experience significant emotional and psychological distress throughout the pandemic. Despite this, little is known about the unique experiences of LTC workers. This scoping review synthesizes existing research on the experiences of HCWs in LTC during the COVID-19 pandemic. Following Arksey and O’Malley’s framework, data were extracted from six databases from inception of the pandemic to June 2022. Among 3,808 articles screened, 40 articles were included in the final analysis. Analyses revealed three interrelated themes: carrying the load (moral distress); building pressure and burning out (emotional exhaustion); and working through it (a sense of duty to care). Given the impacts of the pandemic on both HCW wellbeing and patient care, every effort must be made to address the LTC workforce crisis and evaluate best practices for supporting HCWs experiencing mental health concerns during and post-COVID-19.

Pre-trained Language Models (PTLM) have remarkable and successful performance in solving lots of NLP tasks nowadays. And previous researchers have created many SOTA models and these models are included in many long surveys(Qiu et al., 2020). So, we would like to conduct a simple and short survey on this topic to help researchers understand the sketch of PTLM more quickly and comprehensively. In this short survey, we would provide a simple but comprehensive review of techniques, benchmarks, and methodologies in PTLM. And we would also introduce the applications evaluation of PTLM in this simple survey.

Antimicrobial resistance (AMR) is an increasingly pressing threat to human, animal, and environmental health. Reducing the use of antibiotics in agriculture has been identified as a key way to curb the spread of AMR. However, the effect of such policies on AMR prevalence, and their broader impacts on agricultural, health, and economic outcomes at the population level have proven very difficult to estimate and compare. This paper draws on and formalises ideas presented at the JPIAMR New Perspectives on Bacterial Drug Resistance workshop in June of 2022. With reference to emerging literature on the topic, it proposes a quantitative framework for estimating the relevant causal relationships needed to quantify the cross-sectoral impacts of AMR policies in agriculture, and for comparing these outcomes in like terms in a way which can feed directly into policy decision-making, notably without prohibitive data requirements. The ability of researchers to apply frameworks such as this will be increasingly necessary in order to holistically capture the impacts of AMR policies and to situate them in the broader policy context; especially where the mechanisms of transmission are opaque or complex, where data availability is limited; and where policymakers must allocate scarce resources among many competing objectives.

Multisubunit RNA polymerases (RNAP) carry out transcription in all domains of life; during vi-rus infection, RNAPs are targeted by transcription factors encoded by either the cell or the virus, resulting in the global repression of transcription with distinct outcomes for different host-virus combinations. These repressors serve as versatile molecular probes to study RNAP mechanisms, as well as they aid the exploration of druggable sites for the development of new antibiotics. Here, we review the mechanisms and structural basis of RNAP inhibition by the viral repressor RIP and the crenarchaeal negative regulator TFS4, which follow distinct strategies. RIP operates by occluding the DNA-binding channel and mimicking the initiation factor TFB/TFIIB. RIP binds tightly to the clamp and locks it into one fixed position, thereby preventing conformational oscil-lations that are critical for RNAP function as it progresses through the transcription cycle. TFS4 engages with RNAP in a similar manner to transcript cleavage factors such as TFS/TFIIS through the NTP-entry channel; TFS4 interferes with the trigger loop and bridge helix within the active site by occlusion and allosteric mechanisms, respectively. The conformational changes of RNAP described above are universally conserved and are also seen in inactive dimers of eukaryotic RNAPI and several inhibited RNAP complexes of both bacterial and eukaryotic RNA polymer-ases, including inactive states that precede transcription termination. A comparison of target sites and inhibitory mechanisms reveals that proteinaceous repressors and RNAP-specific antibiotics use surprisingly common ways to inhibit RNAP function.

Background: Cyber Security is to protect online data and software from cyber threats. These cyberattacks are typically intended to gain access to, change, or delete sensitive information; extort money from users; or disrupt regular corporate activities. It is difficult to keep up a regular follow up with new technologies so it is necessary to keep the important data safe from cyber threats. There are many types of cyber threats; malware, ransom-ware, social engineering, phishing etc. To prevent cyber-attacks one can use password manager tools like LastPass and others. People also use two factor authentication for double security on their accounts. Methods: Boards such as the National Institute of Standards and Technology (NIST) are developing frameworks to assist firms in understanding their security risks, improving cybersecurity procedures, and preventing cyber assaults. The fight against cybercrimes and attack, rganisations needed a strong base there are 5 types of cyber securities; Critical Infrastructure Security, application security, network security, cloud security and (IoT) Security. In the modern time US is highly based on computers and on different software so it is really important for US to be more conscious about the security as they get many threats almost everyday for hacking their data and accounts.Results and Conclusion: Nowadays, even small businesses rarely recover their loss from the cyber-attacks and many back-off from continuing their businesses after being target of hackers. The first cybercrime attack was recorded on 1988 by a graduate student. Now that large companies and even small businesses are aware of cyber-attacks so they try their best to take every precaution to prevent the hacking with double security and password manager tools.

In many Bayesian computations, first, we obtain the expression of the joint distribution of all the unknown variables given the observed data. In general, this expression is not separable in those variables. Thus, obtaining their marginals for each variable and computing the expectations are difficult and costly. This problem becomes even more difficult in high dimensional quandaries, which is an important issue in inverse problems. We may then try to propose a surrogate expression with which we can do approximate computations. Often a separable expression approximation can be useful enough. The Variational Bayesian Approximation (VBA) is a technique that approximates the joint distribution $p$ with an easier, for example separable, one $q$ by minimizing Kullback–Leibler Divergence $KL(q|p)$. When $q$ is separable in all the variables, the approximation is also called Mean Field Approximation (MFA) and so $q$ is the product of the approximated marginals. A first standard and general algorithm is alternate optimization of $KL(q|p)$ with respect to $q_i$. A second general approach is its optimization in the Riemannian manifold. However, in this paper, for practical reasons, we consider the case where $p$ is in the exponential family and so is $q$. For this case, $KL(q|p)$ becomes a function of the parameters $\thetab$ of the exponential family. Then, we can use any other optimization algorithm to obtain those parameters. In this paper, we compare three optimization algorithms: standard alternate optimization, a gradient-based algorithm and a natural gradient algorithm and study their relative performances on three examples.

Technological advancements and innovations have profoundly changed the lives of people giving rise to smart environments, cities, and societies. As homes are the building block of cities and societies, smart homes are critical to establishing smart living and are expected to play a key role in enabling smart cities and societies. The current academic literature and commercial advancements on smart homes have mainly focused on developing and providing smart functions for homes to provide security management and facilitate the residents in their various activities such as ambiance management. Homes are much more than physical structures, buildings, appliances, operational machines, and systems. Homes are composed of families and are inherently complex phenomena underlined by humans and their relationships with each other, subject to individual, intragroup, intergroup, and intercommunity goals. There is a clear need to understand, define, consolidate existing research, and actualize the overarching roles of smart homes, the roles of smart homes that would serve the needs of future smart cities and societies. This paper introduces our data-driven parameter discovery methodology and uses it to provide, for the first time, an extensive, rather fairly comprehensive, analysis of the families and homes landscape seen through the eyes of academics and the public using over a hundred thousand research papers and nearly a million tweets. We develop a methodology using deep learning, natural language processing (NLP), and big data analytics methods and apply it to automatically discover parameters that capture a comprehensive knowledge and design space of smart families and homes comprising social, political, economic, environmental, and other dimensions. The 66 discovered parameters and the knowledge space comprising 100s of dimensions are explained by reviewing and referencing over 300 articles from the academic literature and tweets. The knowledge and parameters discovered in this paper can be used to develop a holistic understanding of matters related to families and homes facilitating the development of better, community-specific, policies, technologies, solutions, and industries for families and homes, leading to strengthening families and homes, and in turn, empowering sustainable societies across the globe.

At present, foods containing cannabidiol (CBD) and other cannabinoids are internationally being widely advertised and sold in increasing quantities. In the European Union (EU), these products require pre-marketing authorisation under the novel food regulation, so that all available CBD oils and CBD-containing food supplements in the EU are currently placed on the market with an infringement of the food laws. Currently, 19 CBD applications are under assessment at the European Food Safety Authority (EFSA). During the initial assessment of the application files, EFSA located several knowledge gaps that need to be addressed before the safety evaluation of CBD can be concluded. Namely, the effect of CBD on the liver, gastrointestinal tract, endocrine system, nervous system, psychological function, and reproductive system needs to be clarified. Nevertheless, the available literature allows a benchmark dose (BMD)-response modelling of several bioassays, resulting in a BMD lower confidence limit (BMDL) of 20 mg/kg bw/day for liver toxicity in rats. Human data in healthy volunteers found increases in the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a study at 4.3 mg/kg bw/day, which was defined by EFSA as a lowest observed adverse effect level (LOAEL). The EFSA panel currently concluded that the safety of CBD as a novel food cannot be evaluated, leading to a so-called clock stop of the applications until the applicants provide the required data. Meanwhile, the authors suggest that CBD products still available on the EU market despite the lack of authorisation must be considered as “unsafe”. Products exceeding a reference dose of 10 mg/day must be considered as being “unfit for consumption” (Article 14(1) and (2) (b) of Regulation No 178/2002), while the ones in exceedance of the human LOAEL must be considered “injurious to health” (Article 14(1) and (2) (a) of Regulation No 178/2002).

This short paper demonstrates that the galactic spiral equations developed from ROTASE model can be used to morphologically simulate the phyllotactic spiral-ring patterns of plants. It is also noticed during this project that although the numbers in the Fibonacci sequence dominate the phyllotactic numbers, there are still significant phyllotactic numbers are not in the Fibonacci sequence, however, most of those numbers are well fit into a Fibonacci sibling sequence starting with numbers 0 and 2. Many plants show the phyllotactic number pairs of 10-16, 16-26 and 26-42 from the Fibonacci sibling sequence, which is the second dominated sequence in the phyllotaxis.

Natural products (NPs) are a rich source of structurally novel molecules, and the chemical space they encompass is far from being fully explored. Over history, NPs have represented a significant source of bioactive molecules and have served as a source of inspiration for developing many drugs on the market. On the other hand, computer-aided drug design (CADD) has contributed to drug discovery research, mitigating costs and time. In this sense, compound databases represent a fundamental element for the CADD. This work reviews the progress toward developing compound databases of natural origin, particularly databases developed in Latin America, and their practical applications in the drug discovery area. We also survey the computational methods, emphasizing chemoinformatic approaches to profile natural product databases.

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. Here, I explore the possibility that the accumulation of lipofuscin to some extent underlies all other categories of age-related damage as defined by Dr. Aubrey de Grey. I do not think that lipofuscin removal will reverse/prevent all forms of aging, just the major component facing us currently. It may suffice for the next few hundred years by itself. In this piece, I will review what is known about lipofuscin accumulation from evolutionary and mechanistic standpoints and discuss ways of removing it from post-mitotic cells (and then the body).

Purpose – Extend the Blade Element Momentum Theory (BEMT) such that rotors with pronounced cone and axis angle (tilt or yaw) can be calculated. Derive an equation for the speed ratio (lambda) as a function of Tip Speed Ratio (TSR), radius, blade, cone and axis angle. This converts the BEMT into an Unsteady BEMT or UBEMT. Present the Wagner rotor as one such rotor geometry. --- Methodology – Literature review and calculations. --- Findings – The UBEMT can be used to calculate highly unconventional rotor geometries. --- Research Limitations – Although the aerodynamic coefficients used in the UBEMT are from measurements in steady flow conditions, they can be used with success. --- Practical Implications – Also conventional Horizontal Axis Wind Turbines (HAWT) with noticeable cone and axis angle should be calculated with the UBEMT. The accuracy of power calculations of these HAWTs can be slightly improved. --- Originality – Analytic equations for rotors with cone and axis angle have barely been discussed.

Mining is an important industry, accounting for 6.9% of global GDP. However, global development promotes accelerated demand, resulting in the accumulation of hazardous waste in land, sea, and air environments. It reached 7 billion tonnes of mine tailings generated yearly worldwide, and 19 billion solid tailings will be accumulated by 2025. Adding to this, the legacy of environmental damage from abandoned mines is worrying; in Canada there are around 10,000 abandoned mines, 50,000 in Australia, 6,000 in South Africa, and 9,500 coal mines in China, reaching 15,000 by 2050. In this scenario, restoration techniques from mining tailing have become increasingly discussed among scholars due to their potential to offer benefits towards reducing tailings levels, thereby reducing environmental pressure for the correct management and adding value to previously discarded waste. This review paper explores available literature on the main techniques of mining tailing recycling and reuse and discusses leading technologies, including the benefits and limitations, as well as emerging prospects. The findings of this review serve as a supporting reference for decision-makers concerning the related sustainability issues associated with mining, mineral processing, and solid waste management.

Background: This study aimed to examine the course of Depression and anxiety in COVID-19 survivors with a psychiatric history compared with those without a psychiatric history. Methods: A web-based cross-sectional survey for COVID-19 survivors was conducted from July to September 2021. 6016 COVID-19 survivors, the accuracy of whose responses was determined to be assured, were included in analyses. Exposures included psychiatric history and time since COVID-19 infection, and the main outcomes and measures included severity of depression and anxiety, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Results: Mean severity of PHQ-9 and GAD-7 were significantly higher in participants with a psychiatric history than in those without a psychiatric history. Two-way analysis of covariance for PHQ-9 showed a significant main effect of the presence of psychiatric history and a significant interaction effect of psychiatric history × time since infection. Two-way analysis of covariance for the GAD-7 score revealed a significant main effect of the presence of psychiatric history and time since COVID-19 infection and the interaction effect of these factors. Conclusions: The course of depression and anxiety was more severe in COVID-19 survivors with a psychiatric history than in those without a psychiatric history.

Housing is always crucial for the sustainable development of communities, specifically in urban areas, due to the population density of cities. The present study constructs its own structure on the basis of the recent papers investigating various sustainability factors for the urban housing sector. By doing a comprehensive systematic literature review, one of the most extensive lists of urban housing sustainability factors is gathered from 118 recent related papers. The factors are prioritized by their frequency of investigation and categorized by their scale(s) and sector(s) of influence. According to the results, the top three significant factors affecting urban housing sustainability are “natural resource or energy consumption/efficiency of the building/equipment (during the construction, operation, etc.)”, “materials performance (durability, cost, thermal capacity, permeability, ability to re-use, recycled, eco-friendly materials)”, and “access to public services/infrastructure: availability/quality of services and/or distance/time of travel time to the services (public transport, education/health/shopping/leisure facilities, parks, etc.)”. By analyzing the results with an integrative approach, it is understood that environmental factors are the most considered ones (more considered than the factors with influence on all sustainability sectors) where institutional factors received the least attention. Also, the most significant measures are the ones that have impacts on both ‘building’ and ‘neighborhood/community’ scales. It should be noticed that the neighborhood/community scale indicators are seen, almost, as important as the measures that affect the building itself. The results of this study can be helpful in establishing future housing-related policies, and also in having more efficient housing sustainability assessment tools.

This paper presents additional results of the generalized bathtub model for urban networks, including a simpler derivation and exact solutions for uniformly distributed trip lengths. It is shown that in steady state this trip-based model is equivalent to the more parsimonious accumulation-based model, and that the trip-length distribution has merely a transient effect on traffic dynamics, which converge to the same point in the macroscopic fundamental diagram (MFD). To understand the statistical properties of the system, a queueing approximation method is proposed to compute the network accumulation variance. It is found that (i) the accumulation variance is much larger than predicted by traditional queueing models, due to the nonlinear dynamics imposed by the MFD, (ii) the trip-length distribution has no effect on the accumulation variance, indicating that the proposed formula for the variance might be universal, (iii) the system exhibits critical behavior near the capacity state where the variance diverges to infinity. This indicates that the tools from critical phenomena and phase transitions might be useful to understand congestion in cities.

Iron overnutrition has been implicated with higher risk of developing metabolic and cardiovascular diseases, including metabolic syndrome (MetS), while iron deficiency anemia exacerbates many underlying chronic conditions. Hemoglobin (Hb) concentration in the blood, which reflects a major functional iron (i.e., heme iron) in the body, may serve as a surrogate of iron nutrition status. We conducted sex-specific observational association studies where we carefully titrated the association between Hb deciles and MetS and its components among the Taiwanese Han Chinese (HC) from the Taiwan Biobank and Europeans of White ancestry from the UK Biobank, representing two large ethnicities. Our data show that at higher-than-normal levels of Hb, increasing deciles of Hb concentration were significantly associated with MetS across all sex subgroups in both ethnicities, with the highest deciles resulting in up to three times greater risks than the reference group [Taiwanese HC: OR=3.17 (95% CI, 2.75-3.67) for Hb >16.5 g/dL in men, OR=3.11 (2.78-3.47) for Hb >14.5 g/dL in women; European Whites: OR=1.89 (1.80-1.98) for Hb >16.24 g/dL in men, OR=2.35 (2.24-2.47) for Hb >14.68 g/dL in women]. The association between stronger risks and increasing Hb deciles was similarly observed with all metabolic components except diabetes. Here we found that both the highest Hb decile groups and contrarily the lowest ones, with respect to the reference, were associated with higher odds of diabetes in both ethnic groups [e.g., Taiwanese HC men: OR=1.64 (1.33-2.02) for Hb >16.5 g/dL, OR=1.71 (1.39-2.10) for Hb <13.5 g/dL; European Whites women: OR=1.39 (1.26-1.45) for Hb >14.68 g/dL, OR=1.81 (1.63-2.01) for Hb <12.39 g/dL]. These findings confirm that elevated Hb concentrations, a potential indicator of iron overnutrition, may play a role in the pathophysiology of MetS and metabolic components.

To scientifically and effectively evaluate the service capacity of expressway service areas (ESAs) and improve the management level of ESAs, we propose a method for the recognition of vehicles entering ESAs (VeESAs) and estimation of vehicle dwell times using ETC data. First, the ETC data and their advantages are described in detail, and then the cleaning rules are designed according to the characteristics of the ETC data. Second, we established feature engineering according to the characteristics of VeESA, and proposed the XGBoost-based VeESA recognition (VR-XGBoost) model. Studied the driving rules in depth, we constructed a kinematics-based vehicle dwell time estimation (K-VDTE) model. The field validation in Part A/B of Yangli ESA using real ETC transaction data demonstrates that the effectiveness of our proposal outperforms the current state of the art. Specifically, in Part A and Part B, the recognition accuracies of VR-XGBoost are 95.9% and 97.4%, respectively, the mean absolute errors (MAEs) of dwell time are 52 s and 14 s, respectively, and the root mean square errors (RMSEs) are 69 s and 22 s, respectively. In addition, the confidence level of controlling the MAE of dwell time within 2 minutes is more than 97%. This work can effectively identify the VeESA, and accurately estimate the dwell time, which can provide a reference idea and theoretical basis for the service capacity evaluation and layout optimization of the ESA.

Growing water shortages for large regions of the arid regions of the world, are likely to become more recurrent as climate change impacts grow. Countries across the world are facing water security difficulties that stem from population growth, urbanization, and rapid industrialization. The use of behavioral nudges methods implemented to encourage a socially desired behavior at a low to zero cost, has been an effective method at reducing water consumption in places where they have been deployed. For example, studies in California USA, Barcelona Spain, and Australia indicate that adoption of nudges give significant positive results in water consumption reduction. We describe some of the barriers that make it difficult to implement behavioral nudges to address the water crises in Sub-Saharan Africa (SSA). We investigate the literature available in Sub-Saharan Africa and discover that the application of behavioral nudges has been sparingly used for reasons that are not obvious at first glance. Second, we find that the potential impediments to the use of behavioral nudges in SSA to be awareness, inadequate access to science and technology, political systems that are poorly suited for implementing nudging, abundance of multiple ethnic groups that speak different languages, along with other barriers that could challenge implementation of behavioral nudges. In light of those barriers, we present a conceptual model with a potential to address these barriers to behavioral nudging a workable solution in SSA.

Aim. To identify factors associated with mortality with tuberculosis diagnosis in the indigenous population in Peru 2015-2019. Methods. Case-control study nested in a retrospective cohort, using the registry of persons belonging to indigenous peoples of the National Tuberculosis Prevention and Control Strategy of the Ministry of Health of Peru. A descriptive analysis was applied, and then bivariate and multiple logistic regression was used to evaluate associations between the variables and the outcome (live-deceased), the results were presented as OR with their respective 95% confidence intervals. Results. The mortality rate of the total indigenous population of Peru was 1.75 deaths per 100,000 indigenous people diagnosed with TB. The community of Kukama kukamiria - Yagua reported 505 (28.48%) individuals. The final logistic model showed that indigenous men (OR=1.93; 95% CI: 1.001-3.7), with a history of HIV prior to TB (OR=16.7; 95% CI: 4.7-58.7) and indigenous people in old age (OR=2.95; 95% CI: 1.5-5.7), are factors associated with a greater chance of dying from TB. Conclusions. It is important to reorient health services among indigenous populations, especially those related to improving the timely diagnosis and early treatment of TB-HIV co-infection, to ensure comprehensive care for this population, considering that they are vulnerable groups.

In Qinglong ore field, paleo-oil reservoir is found to be associated with antimony deposits, and they have close genetic relationship. In this study, aromatics geochemistry of paleo-oil reservoir bitumen was studied to further discuss the thermochemical sulfate reduction (TSR) reaction and the mechanism of antimony mineralization. A total of 124 aromatic compounds were identified by Gas chromatography-mass spectrometry (GC–MS) analysis in bitumen samples, including abundant phenanthrene series, dibenzothiophene series, fluoranthene series, chrysene series, and a small number of fluorene series, naphthalene series, dibenzofuran series, biphenyl series, triaromatic steroid series. Aromatic parameters such as trimethylnaphthalene index (TMNr), methylphenanthrene index (MPI), methylphenanthrene distribution fraction (MPDF, F1 and F2), methyldibenzothiophene parameter (MDR), C28TAS-20S/(20R+20S), and benzofluoranthene/benzo[e]pyrene indicate Qinglong paleo-oil reservoir is in over maturity level. The abundance of phenanthrene and chrysene aromatic compounds and a small amount of naphthalene series, benzofluoranthene, fluoranthene, pyrene, anthracene, retene, perylene and biphenyl suggest that the parent material of the paleo-oil reservoir was mainly low aquatic organisms, mixed with a small amount of higher plant. The detected a certain number of compounds, such as retene, triaromatic steroid series and perylene, the ternary diagram of DBF–DBT–F and binary plot of Pr/Ph–DBT/P, DBT/(F+DBT)–DBF/(F+DBF) and Pr/Ph–DBT/DBF reveal that the source rock of the paleo-oil reservoir was formed in the marine environment of weak oxidation and weak reduction. The comprehensive analysis shows that the Qinglong paleo-oil reservoir originated from Devonian source rocks, just like other paleo-oil reservoirs and natural gas reservoirs in the Nanpanjiang basin. Abundant dibenzothiophene series were detected, indicating that the paleo-oil reservoir underwent a certain degree of TSR reaction. We believe that the paleo-gas reservoir formed by the evolution of paleo-oil reservoir participated in antimony mineralization, that is, hydrocarbon organic matter acted as reducing agent and transformed SO42− in oilfield brine into H2S through TSR, providing reduced sulfur and creating environmental conditions for mineralization.

Most existing cancer therapies negatively affect normal tissue as well as cancerous tissue. A potentially effective strategy for treating cancer that precludes off-target damage and could be an option for most patients would involve targeting one or more mutations that are ubiquitous in the given patient’s tumor(s). To effect this strategy, one would employ multi-region sequencing of a patient’s primary tumor and metastases to seek out mutations that are shared between all or at least most regions. Once the target or targets are known, one would ideally rapidly generate a molecular switch for at least one of said ubiquitous mutations that can distinguish the mutated DNA, RNA, or protein from the wild-type version and subsequently trigger a therapeutic response. I propose that the therapeutic response involve the replication of an oncolytic virus or intracellular bacterium, as any mutation can theoretically be detected by a vector that enters the cell - and automatic propagation could be very helpful. Moreover, the mutation “signal” can be easily enhanced through transcriptional and translational (if the target is an intracellular protein) enhancement. Importantly, RNA may make the best target for the molecular switches in terms of amplification of the signal and ease of targeting.

An overview is presented of several diverse branches of work in the area of effectively 2D fluid equilibria which have in common that they are constrained by an infinite number of conservation laws. Broad concepts, and the enormous variety of physical phenomena that can be explored, are highlighted. These span, roughly in order of increasing complexity, Euler flow, nonlinear Rossby waves, 3D axisymmetric flow, shallow water dynamics, and 2D magnetohydrodynamics. The classical field theories describing these systems bear some resemblance to perhaps more familiar fluctuating membrane and continuous spin models, but the fluid physics drives these models into unconventional regimes exhibiting large scale jet and eddy structures. From a dynamical point of view these structures are the end result of various conserved variable forward and inverse cascades. The resulting balance between large scale structure and small scale fluctuations is controlled by the competition between energy and entropy in the system free energy, in turn highly tunable through setting the values of the conserved integrals. Although the statistical mechanical description of such systems is fully self-consistent, with remarkable mathematical structure and diversity of solutions, great care must be taken because the underlying assumptions, especially ergodicity, can be violated or at minimum lead to exceedingly long equilibration times. Generalization of the theory to include weak driving and dissipation (e.g., non-equilibrium statistical mechanics and associated linear response formalism) could provide additional insights, but has yet to be properly explored.

Monkeypox, once a rare zoonotic disease, was endemic to some African countries since its original identification among humans in 1970. Since then, cases in non endemic regions were linked to returning travelers or those who had contact with transported animals. The causative agent, Monkeypox virus, belongs to Orthopoxviruses, the same family as Variola; the causative organism for smallpox. Although most Monkeypox outbreaks until recently were linked to zoonotic transmission, secondary human-human transmission in smallpox unvaccinated individuals was observed in a small proportion of overall cases. Smallpox was declared eradicated in 1980 and since its eradication, monkeypox virus is the most significant poxvirus to cause human disease. The 2022 monkeypox outbreak marks a significant paradigm shift in the human and poxvirus association, with new modes of transmission, concerns of viral evolution and entrenchment as a sexually transmitted disease. Monkeypox clinically resembles smallpox but is far milder. At this time there are no approved therapies for monkeypox and antiviral agents effective against smallpox are being utilized. Additionally, preventive strategies being utilized include smallpox vaccination like JYNNEOS and ACAM2000. In this narrative review, we discuss the virology, epidemiology, transmission, clinical manifestations, diagnosis, management and prevention strategies associated with monkeypox.

Two mononuclear Ru(III) complexes of formula trans-[RuCl4(Hgua)(dmso)]·2H2O (1) and trans-[RuCl4(Hgua)(gua)]·3H2O (2) [Hgua = protonated guanine (gua), dmso = dimethyl sulfoxide] have been synthesized and characterized magnetostructurally. Compounds 1 and 2 crystallize in the monoclinic system with space groups P21/n and Pc, respectively. Each Ru(III) ion in 1 and 2 is six-coordinate and bonded to four chloride ions and one (1) or two (2) nitrogen atoms from guanine molecules and one sulfur atom (1) of a dmso solvent molecule, generating quasi regular octahedral geometries in both cases. In their crystal packing, the Ru(III) complexes are self-assembled mainly through an extended network of N-H⋯Cl hydrogen bonds and π⋯Cl type intermolecular interactions, forming novel supramolecular structures based on this paramagnetic 4d metal ion. Variable-temperature dc magnetic susceptibility measurements performed on microcrystalline samples of 1 and 2 show a different magnetic behavior. While 1 is a ferromagnetic compound at low temperature, 2 exhibits a behavior typical of noninteracting mononuclear Ru(III) complexes with S = 1/2. Ac magnetic susceptibility measurements reveal slow relaxation of the magnetization in the presence of external dc fields only for 2, hence indicating the occurrence of field-induced single-ion magnet (SIM) phenomenon in this mononuclear guanine-based Ru(III) complex.

Traditional soil characterization methods are time consuming, laborious and invasive and do not allow long-term repeatability of measurements. The overall aim of this paper was to assess and model spatial variability of the soil in an olive grove in south Italy by using data from two sensors of different type: a multi-spectral on-board drone radiometer and a hyperspectral visible-near infrared-shortwave infrared (VIS-NIR-SWIR) reflectance radiometer as well as sample data, to arrive at a delineation of homogeneous areas. The hyperspectral data were processed using continuum removal methodology to obtain information about the content and composition of clay. Differently, the multispectral data were firstly upscaled to the support of soil data using geostatistics and taking into account change of support. Secondly, the two-sensor data were integrated with soil granulometric properties by using the multivariate geostatistical techniques of multi-collocated cokriging and factor cokriging, in order to achieve a more exhaustive and finer-scale soil characterisation. The paper shows the impact of change of support on the uncertainty of soil prediction that can have a significant effect on decision making in Precision Agriculture. Moreover, four regionalised factors at two different scales (two per each scale) were retained and mapped. Each factor provided a different delineation of the field with areas characterised by different granulometry and clay composition. The applied method is sufficiently flexible and could be applied to any number and type of sensors.

Over a billion people around the world are disabled, among them, 253 million are visually impaired or blind, and this number is greatly increasing due to ageing, chronic diseases, poor environment, and health. Despite many proposals, the current devices and systems lack maturity and do not completely fulfill user requirements and satisfaction. Increased research activity in this field is required to encourage the development, commercialization, and widespread acceptance of low-cost and affordable assistive technologies for visual impairment and other disabilities. This paper proposes a novel approach using a LiDAR with a servo motor and an ultrasonic sensor to collect data and predict objects using deep learning for environment perception and navigation. We adopted this approach in a pair of smart glasses, called LidSonic V2.0, to enable the identification of obstacles for the visually impaired. The LidSonic system consists of an Arduino Uno edge computing device integrated into the smart glasses and a smartphone app that transmits data via Bluetooth. Arduino gathers data, operates the sensors on smart glasses, detects obstacles using simple data processing, and provides buzzer feedback to visually impaired users. The smartphone application collects data from Arduino, detects and classifies items in the spatial environment, and gives spoken feedback to the user on the detected objects. In comparison to image processing-based glasses, LidSonic uses far less processing time and energy to classify obstacles using simple LiDAR data, according to several integer measurements. We comprehensively describe the proposed system's hardware and software design, construct their prototype implementations, and test them in real-world environments. Using the open platforms, WEKA and TensorFlow, the entire LidSonic system is built with affordable off-the-shelf sensors and a microcontroller board costing less than $80. Essentially, we provide designs of an inexpensive, miniature, green device that can be built into, or mounted on, any pair of glasses or even a wheelchair to help the visually impaired. Our approach affords faster inference and decision-making using relatively low energy with smaller data sizes as well as faster communications for the edge, fog, and cloud computing.

Any change in the amount and annual distribution of rainfall causes a major socioeconomic and environmental problem where rainfed agriculture is predominant. For that reason, the objective of this study was to determine the long-term variability and trends of precipitation in the Wabi Shebele River Basin (WSRB), Ethiopia. The basin was discretized into 7 local agroclimatic zones (ACZ) based on annual rainfall and elevation. In this study, the coefficient of variation (CV) was used to check the variability of rainfall and modified Mann-Kendall (MK) and Innovative Trend Analysis (ITA) methods were used to detect rainfall trends. For each ACZ, stations with long-term records and less than 10 % missing data were selected for further analysis. The mean annual rainfall in the basin ranges from 227.2 mm to 1047.4 mm. The study revealed most of the ACZs showed a very high variation in Belg/Spring season rainfall (CV % > 30) than Kiremt/Summer and annual rainfall. Trend analysis revealed that no uniform trend was detected among ACZs at each temporal scale. But, most ACZ in the arid and semi-arid areas showed a non-significant decreasing trend. In comparison, a similar result was observed using MK and ITA methods.

Thanks to the continued development of experimental structural biology and the half-a-century old Protein Data Bank, 2021 saw a big step forward in the development of protein structure prediction with deep learning algorithms. Recently, DeepMinds AlphaFold has determined the structures of ∼ 200 million proteins from 1 million species. The speed of this progress raise the question of what becomes possible for computational drug discovery and design when we have a systems-wide account of the structures and motions of most proteins. Therefore, this article puts forward the concept of a general intermolecular binding affinity calculator (GIBAC): Kd = f(molA, molB, envPara), towards the acceleration of traditional computer-aided drug design (CADD) and artificial intelligence-integrated drug discovery (AIDD), for both small molecules and biologics such as therapeutic proteins.

Background: A novel virulent coronavirus is what causes Novel Corona-virus Disease 2019 (nCOVID 19). It results in severe respiratory distress syndrome and potentially fatal infectious pneumonia. On March 12, 2020, the World Health Organization first labeled it a pandemic, which was then followed on the same day by a community health emergency of global concern. Vaccines against this deadly virus are now being created. Many drugs with different uses have been repurposed and tested for the prevention and treatment of the infection. Objective: The purpose of this review is to provide an in-depth analysis of data on possible pharmacological targets and available coronavirus treatments. Methods: Following the review protocol, a literature search was conducted. Results: Chloroquine phosphate and hydroxychloroquine, Remdesivir, and Lopinavir-Ritonavir in combination with or without interferon and convalescent plasma therapy are the main treatment candidates, according to the World Health Organization. This review article has elaborated on the current evidence of prospective pharmacological targets and related ongoing research, including inflammatory chemicals, bioactive peptides, beta cells, platelets, and the Angiotensin I Converting Enzyme 2 Receptor. This information was gathered from published journals. In addition, stories of medications and biological products like interferons and vaccinations that are utilized or could be utilized have been provided. Conclusion: There are a variety of pharmacological targets and therapeutic strategies that need more study.

This paper presents a novel theoretical and computational methodology for the generation of an onset turbulent field with prescribed properties in the numerical simulation of an arbitrary viscous flow. The methodology is based on the definition of a suitable distribution of volume force terms in the right–hand side of the Navier–Stokes equations. The distribution is represented by harmonic functions that are randomly variable in time and space. The intensity of the distribution is controlled by a simple PID strategy in order to obtain that the generated turbulent flow matches a prescribed turbulence intensity. A further condition is that a homogeneous isotropic flow is es- tablished downstream of the region where volume force terms are imposed. Although it is general, the proposed methodology is primarily intended for the computational modelling of hydrokinetic turbines in turbulent flows representative of tidal or riverine installations. A first numerical applica- tion is presented by considering the injection of homogeneous and isotropic turbulence with 16% intensity into a uniform unbounded flow. The analysis of statistical properties as auto-correlation, power spectral density, probability density functions, demonstrates that the generated flow tends to achieve satisfactory levels of stationarity and isotropy, whereas the simple control strategy used determines overestimated turbulent intensity levels.

Cobalamin is an essential nutrient required for the normal functioning of cells. Its deficiency can lead to various pathological states. Hydroxocobalamin (HOCbl) and cyanocobalamin (CNCbl) are the forms of vitamin B12 that are most commonly used for supplementation. There is substantial evidence indicating that cobalamins can both suppress and promote oxidative stress; however, the mechanisms underlying these effects are poorly understood. Here, it was shown that the oxidation of thiols catalyzed by HOCbl and CNCbl is accompanied by ROS production and induces, under certain conditions, oxidative stress and cell death. The form of vitamin B12 and the structure of thiol play a decisive role in these processes. It was found that the mechanisms and kinetics of thiol oxidation catalyzed by HOCbl and CNCbl differ substantially. It was discussed how these differences may explain different levels of ROS production and cytotoxicity induced by combinations of thiols with HOCbl and CNCbl. On the whole, the data obtained provide a new insight into the redox processes in which cobalamins are involved and might be helpful in developing new approaches to the treatment of some cobalamin-responsive disorders in which oxidative stress is an important component. In addition, these data may be useful for a better understanding of mechanisms underlying induction of different types of death of cancer cells and in a search for new targets for anticancer therapy.

Tissue programmed death ligand-1 (PD-L1) protein expression is predictive of immune checkpoint inhibitor (ICI) benefit. However, tissue PD-L1 can be fraught with tissue acquisition and heterogeneity limitations. Plasma testing can overcome these limitations. However, the overall survival (OS) predictive benefit of plasma PD-L1 assays have not been well characterized. Patients with stage IV non-small cell lung cancer (NSCLC) and plasma cfRNA PD-L1 by PCR expression were identified and assessed for OS. 16 patients treated with front-line ICI-based regimens were assessed and represented a real-world patient population with over half with a performance status of 2 or greater. 10 contemporaneous patients at the same institution treated with chemotherapy alone were also identified and assessed. With a median follow-up of 33 months, median OS was 13 months with a 30% 3-year OS for the ICI treated patients compared to a median OS of 3 months and a 10% 3-year OS for those treated with chemotherapy alone. Comparative log-rank test p-value = 0.014 and a hazard ratio 0.376 (95%-CI 0.134-1.057). Plasma cfRNA PD-L1 was associated with a statistically significant survival benefit from ICI-based treatment compared to chemotherapy in the first line treatment of a real-world patient population of advanced NSCLC.

Viral variant analysis is a bedrock of the disease surveillance. When combined with temporospatial analysis variant analysis can further the knowledge of disease spread in a study area. This paper suggests a method to perform the analysis in an operational setting which will allow for real-time surveillance of viral variants and allow local public health professionals to rapidly respond to changes in the evolution of the disease. This method includes three main subprocesses: preprocessing, analysis, and rendering. This method can be performed across multiple software platforms. A use case is given in which it was found that this method helped a hospital system understand the spread of SARS-CoV-2 in Northeast, Ohio.

(1)Aims of the study: calculating the underreporting ratio for two different kinds of medications (antiglaucoma and artificial tear) and characterizing the features influencing the reporting of adverse drug reactions (ADRs) in spontaneous reporting; (2) Methods: the underreporting ratio was calculated by comparing the adverse drug reactions reported in the spontaneous reporting database for every 10,000 defined daily doses marketed and the adverse drug reactions from an active surveillance study for every 10,000 defined daily doses used for different drugs (antiglaucoma and artificial tear). The factors related to the report in spontaneous reporting through statistical tests were also determined; (3) Results: The underreporting ratio of spontaneous reporting was 0.006029% for antiglaucoma and 0.003552% for artificial tear; additionally, statistically significant differences were found for severity, unexpected adverse drug reactions, and incidence of adverse drug reactions in females; (4) Conclusions: the underreporting ratio of ophthalmic medications, especially in Latin America, shows higher rates than those reported in the literature. On the other hand, gender, seriousness, severity, and unexpected adverse drug reactions influence spontaneous reporting.

Adaption of laser communication terminals to airborne and lean-satellite platforms is now a vogue, made possible due to the progressing advancements in lightweight components and compactness of onboard electro-optical transceivers and control systems. This enables highly secured and superior data-transmission rates beyond multiple Gigabit/second on CubeSats and drones compared to Megabit/second rates offered by similar radio-transceivers form factors. However, laser-transmission links require a very stringent beam-pointing stability because they are easily perturbed by attitude variations and micro-vibrations generated by the host platform’s propulsion system or other mechanically active subsystems in proximity with the transmitter’s optical head. Severe line-of-sight jitter causes the downlink laser beam to drift from the targeted receiving system’s field-of-view, inducing pointing errors, increasing signal outage probability and information loss. We experimentally examine the platform jitter generated by the propellers of an hexacopter drone during ground operation and the attitude-control unit’s reaction wheels in a 6U CubeSat structure. We determined the vibration spectrum unique to these platforms and accordingly prescribe requirements for applicable optical fine pointing and disturbance isolation or suppression systems needed to achieve a high-fidelity laser-communication link.

One of the mechanisms used in the management and cure of atherosclerosis is reverse cholesterol transfer (RCT), which plays a vital role in the export of cholesterol from peripheral cells. Cholesterol efflux from macrophages in the subintima of the vessel wall is a critical part of RCT. ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) are involved in the transfer of cholesterol from arterial macrophages to extracellular high-density lipoprotein cholesterol (HDL). The HDL then transports esterified cholesterol to the liver for elimination. An important factor in the reverse cholesterol transport and excretion of extracellular cholesterol is HDL. Atherogenesis can be prevented by altering the processes of RCT and cholesterol efflux, and this might lead to novel treatment options for cardiovascular disease. Research of novel modifying variables for RCT and cholesterol efflux is necessary. A better understanding of RCT's molecular processes has been gained via research, allowing for the creation of new treatments that make use of RCT's potential for pharmacological improvement. The purpose of this review is to provoke discussion on the potential impact of selected flavonoids on cholesterol efflux on the progression of atherosclerosis (Fig. 1.).

Severe Acute Respiratory Syndrome Coronavirus 2 commonly known as SARS-CoV-2 is the utmost challenging pandemic that attracted scientific community to discover therapeutics as well as vaccination solutions to control SARS-CoV-2. Different diagnostic and detection methods have been improved and re-introduced from the previous observations of SERS and MERS. Due to the high mortality rate and fast spread, researchers all around the globe gathered to develop an effective vaccine. The review article summarizes various types of vaccines, mutants of virus, strategies in tackling virus, vaccine development and its global distribution with the focus on the use of mix and match of vaccines to fight the virus. The reported studies depict the design and production of successful COVID-19 vaccines with good efficacy as the selected vaccine population embrace high-risk personages i.e. above the age of 60, frontline workers and other essential service workers. We have targeted at delivering an outline of the determinations devoted to an effectual vaccine for novel Covid-19 that has restricted the domain by means of human health, economy, as well as life.

Three physical elements are missing from the conventional formalism of quantum photonics: 1) the quantum Rayleigh spontaneous and stimulated emissions; 2) the unavoidable parametric amplification; and 3) the mixed time-frequency spectral structure of a photonic field which specifies its duration or spatial extent. As a single photon enters a dielectric medium, the quantum Rayleigh scattering prevents it from propagating in a straight-line, thereby destroying any possible entanglement. A pure dynamic and coherent state composed of two consecutive number states, delivers the correct expectation values for the number of photons carried by a photonic wave front, its complex optical field, and phase quadratures. The intrinsic longitudinal and lateral field profiles associated with a group of photons for any instantaneous number of photons are independent of the source. These photonic properties enable a step-by-step analysis of the correlation functions characterizing counting of coincident numbers of photons or intensities with unity visibility interference, spanning the classical and quantum optic regimes

The Internet of Things (IoT) is experiencing widespread adoption across industry sectors ranging from supply chain management to smart cities, buildings, and health monitoring. However, most software architectures for IoT deployment rely on centralized cloud computing infrastructures to provide storage and computing power, as cloud providers have high economic incentives to organize their infrastructure into clusters. Despite these incentives, there has been a recent shift from centralized to decentralized architecture that harnesses the potential of edge devices, reduces network latency, and lowers infrastructure cost to support IoT applications. This shift has resulted in new edge computing architectures, but many still rely on centralized solutions for managing applications. A truly decentralized approach would offer interesting properties required for IoT use cases. To address these concerns, we introduce a decentralized architecture tailored for large scale deployments of peer-to-peer IoT sensor networks and capable of run-time application migration. The solution combines a blockchain consensus algorithm and verifiable random functions to ensure scalability, fault tolerance, transparency, and no single point of failure. We build on our previously presented theoretical simulations with many protocol improvements and an implementation tested in a use case related to monitoring a Slovenian cultural heritage building located in Bled, Slovenia.

Some concepts/hypotheses have been proposed to explain the general rules behind the complexity of tumorigenesis. Characterization of the property of cancer cells and neural stem cells indicates that neural stemness underlies tumorigenicity and pluripotency, leading to the proposal that tumorigenesis represents a process of progressive loss of original cell identity and gain of neural stemness. This reminds of a most fundamental process required for the development of the nervous system and body axis during embryogenesis, i.e., embryonic neural induction. The principle of neural induction is that, in response to extracellular signals that are secreted by the Spemann-Mangold organizer in amphibians or the node in mammals and inhibit epidermal fate in ectoderm, the ectodermal cells assume the neural default fate and turn into neuroectodermal cells. These cells further differentiate into the nervous system and also some non-neural cells via interaction with adjacent tissues. Failure in neural induction leads to failure of embryogenesis, and ectopic neural induction due to ectopic organizer or node activity or activation of embryonic neural genes causes a formation of secondary body axis or conjoined twins. A similar principle underlies tumorigenesis. Increasing evidence has demonstrated that the core property of cancer cells is neural stemness. Therefore, cancer cells are cells with the loss of original cell identity and gain of neural stemness, and consequently tumorigenicity and pluripotency, due to various intra-/extracellular insults in postnatal animals. Unlike that pluripotent cells (embryonic pluripotent cells, neural stem cells and cancer cells) can differentiate and integrate into embryonic development, cancer cells are capable of self-renewal and differentiation, but cannot integrate into normal tissues in a 2 postnatal animal, ultimately leading to tumor formation. Neural induction and the unique property of neural stemness provide an inclusive explanation for embryogenesis, conjoined twin formation and tumorigenesis. Based on these findings, I discuss about some confusion in cancer research, e.g., epithelial-mesenchymal transition, and propose to distinguish the causality and associations, and the causal and supporting factors involved in tumorigenesis, and suggest revisiting the focus of cancer research. Integration of evidence from developmental and cancer biology indicates that neural stemness determines tumorigenicity and pluripotency, and neural induction drives embryogenesis in gastrulating embryos but a similar process drives tumorigenesis in a postnatal animal.

Cholesterol-derived bile acids (BAs) affect numerous physiological functions such as glucose homeostasis, lipid metabolism and absorption, intestinal inflammation and immunity, as well as intestinal microbiota diversity. Diet influences the composition of the BA pool. The present study analyzes the impact of a dietary supplementation with a freeze-dried blueberry powder (BBP) on the fecal BA pool composition. The diet of 11 men and 13 women at risk for metabolic syndrome was supplemented with 50g/day of BBP for 8 weeks, and feces were harvested before (pre) and after (post) BBP consumption. BAs were profiled using liquid chromatography coupled to tandem mass spectrometry. No significant changes in total BAs were detected when comparing pre- vs post-BBP consumption samples. However, post-BBP consumption samples exhibited significant accumulations of glycine-conjugated BAs (p=0.04), glycochenodeoxycholic (p=0.01) and glycoursodeoxycholic (p=0.01) acids, as well as a significant reduction (p=0.03) of the secondary BA levels, when compared to pre-BBP feces (p=0.03). In conclusion, the fecal bileacidome is significantly altered after the consumption of BBP for 8 weeks. While additional studies are needed to fully understand the underlying mechanisms and physiological implications of these changes, our data suggest that the consumption of blueberries can modulate toxic BAs elimination.

Genomics involving tens of thousands of genes is a complex system determining phenotype. An interesting and vital issue is that how to integrate highly sparse genetic genomics data with a mass of minor effects into prediction model for improving prediction power. We find that deep learning method can work well to extract features by transforming highly sparse dichotomous data to lower dimensional continuous data in a non-linear way. This idea may provide benefits in risk prediction based on genome-wide data associated e.g. integrating most of the information in the genotype data. Hence, we developed a multi-stage strategy to extract information from highly sparse binary genotype data and applied it for risk prediction. Specifically, we first reduced the number of biomarkers via a univariable regression model to a moderate size. Then a trainable auto-encoder was used to extract compact representations from the reduced data. Next, we performed a LASSO problem process over a grid of tuning parameter values to select the optimal combination of extracted features. Finally, we applied such feature combination to two prognostic models, and evaluated predictive effect of the models. The results of simulation studies and real data applying indicated that these highly compressed transformation features could better improve predictive performance and did not easily lead to over-fitting.

The article affords the question of lifelong learning in Europe using data from the European Innovation Scoreboard-EIS in the period 2010-2019 for 36 countries. The econometric analysis is realized using WLS, Dynamic Panel, Pooled OLS, Panel Data with Fixed Effects and Random Effects. The results show that lifelong learning is, among other variables, positively associated to “Human Resources” and “Government procurement of advanced technology products” and is negatively associated, among others, to “Average annual GDP growth” and “Innovation Index”. A clusterization is realized using the k-Means algorithm with a confrontation between the Elbow Method and the Silhouette Coefficient. Subsequently, a Network Analysis was applied with the distance of Manhattan. The results show the presence of 4 complex and 2 simplified network structures. Finally, a comparison was made among eight machine learning algorithms for the prediction of the value of lifelong learning. The results show that the linear regression is the best predictor algorithm and that the level of lifelong learning is expected to growth on average by 1.12%.

Rising sensitivity of the loads with respect to power quality has grown-up the consideration of power system study and power quality enhancement systems. The fluctuation of voltage outside the normal working range due to faults may lead to unsuitable interruption of wind turbines. This thesis present 1.5MW grid connected Adama Ⅰ Wind Farm in Ethiopia with the objectives to capture the optimal power from the wind and ensure voltage source for sensitive load. This paper deals with the effective voltage sag mitigation and Harmonic distortion effectively met IEEE 519-1992 standard under all Phase to ground fault compensation by using Dynamic Voltage Restorer (DVR), to regulate the terminal voltage of the wind farm and safe operation of sensitive load. The DVR utilizes a feed forward control-based algorithm to generate PWM. The simulation results are going to be carried out by MATLAB-Simulink to verify the operation and effectiveness of DVR during balanced voltage sag and swell conditions.

Emergent physics education research (PER) literatures have been disseminated through academic publications within the community. The growing body of literatures over years challenge Indonesian PER scholars to understand how the research community has been progressed and what possible future work that should be emphasized. Nevertheless, previous traditional method of thematic analysis performed serious limitation when the number of PER literatures exponentially increased. Dealing with this large volume of publications, one of the machine learning studies namely natural language processing (NLP) was employed in this study to automate our thematic analysis among Indonesian PER literatures that are still limited to be explored. One of the well-known NLP algorithm, latent Dirichlet allocation (LDA), has been performed to extract Indonesian PER topics and their associated development between 2014 and 2021. A total of 852 papers (~ 4 to 8 pages each) were collectively downloaded from five international conference proceedings organized by Indonesian PER researchers. Before their topics were modeled through LDA algorithm, our data corpus should be previously preprocessed through several common procedures of established NLP studies. Findings revealed that LDA has thematically quantified Indonesian PER topics and described their distinct development over certain period. The identified topics from this study demonstrated that Indonesian PER community has established robust development in eight distinctive topics to the present. They begin with initial interest in focusing research on physics laboratory and following the research based instruction in the late 2015. Indonesian PER scholars sustained to study continuous topic on 21st century skill until 2019 which gave way to a focus on developing relevant educational technology to address several forms of students’ performance including scientific literacy and problem solving. There is still lack of Indonesian PER literatures that have been attempted to address qualitative aspects of physics teaching and learning.

Deep neural networks (DNN) have successfully delivered a cutting-edge performance in several fields. With the broader deployment of DNN models on critical applications, the security of DNNs becomes an active and yet nascent area. Attacks against DNNs can have catastrophic results, according to recent studies. Poisoning attacks, including backdoor and Trojan attacks, are one of the growing threats against DNNs. Having a wide-angle view of these evolving threats is essential to better understand the security issues. In this regard, creating a semantic model and a knowledge graph for poisoning attacks can reveal the relationships between attacks across intricate data to enhance the security knowledge landscape. In this paper, we propose a DNN Poisoning Attacks Ontology (DNNPAO) that would enhance knowledge sharing and enable further advancements in the field. To do so, we have performed a systematic review of the relevant literature to identify the current state. We collected 28,469 papers from IEEE, ScienceDirect, Web of Science, and Scopus databases, and from these papers, 712 research papers were screened in a rigorous process, and 55 poisoning attacks in DNNs were identified and classified. We extracted a taxonomy of the poisoning attacks as a scheme to develop DNNPAO. Subsequently, we used DNNPAO as a framework to create a knowledge base. Our findings open new lines of research within the field of AI security.

This paper investigates whether currency risk is priced differently in the different sectors (industrial, financial, and basic materials) of equity markets in a sample of developed United States of America (USA) and developing economies (Brazil, India, Poland, and South Africa). The paper makes use of the following techniques: (i) Univariate Autoregressive Fractionally Integrated Moving Average and Exponential General Autoregressive Conditional Heteroskedastic (ARFIMA-EGARCH), (ii) the Markov-Switching method (MS), and (iii) the Canonical Vine Copulas (C-Vine) techniques. Using a sample of daily data made of the foreign exchange rate against the domestic currency and equity market sectors; our findings show that there is an asymmetry effect between equities markets and the foreign exchange rate: there is a heterogeneous, strong, and positive dependence between the two. Higher equities prices are associated with depreciation of local currencies, according to US dollar (USD) exchange rates. In addition, we find that the selected emerging economies are pricing a positive and considerable currency risk. The pricing of currency risk has a varied effect in both regimes representing the states of the economy. In fact, when currency risk pricing has a beneficial impact on certain sectors of the economy, investors predict better returns.

In this article we investigate the determinants of marketing or organizational innovators in Europe for 36 countries in the period 2010-2019. We have used data from the European Innovation Scoreboard-EIS of the European Commission. We perform different econometric models i.e. Dynamic Panel, Pooled OLS, Panel Data with Fixed Effects, Panel Data with Random Effects, WLS. Results show that the level of marketing or organizational innovators in positively associated, among others variables to “Innovation Index”, “Innovators” and “Knowledge Intensive Service Exports”, while is negatively associated with “Sales Impacts”, “Foreign Controlled Enterprises Share of Value Added” and “Government procurement of advanced technology products”.

Scientific, technical and bioinformatics advances have made it possible to establish analytics-based molecular biosimilarity for the approval of biosimilars. If the molecular structure and other product- and process-related attributes are comparable within the limits of testing then a biosimilar candidate would have safe safety and efficacy as its reference products. The current model of animal and human testing becomes redundant since all of these studies have much lower sensitivity and reproducibility in confirming biosimilarity. The recent AI-based protein structure prediction model has confirmed that the 3D structure can be predicted from the amino acid sequence, reducing the need for structural analysis; however, the new test methods based on MS are millions of times more sensitive and accurate. While the regulatory agencies have begun waiving animal testing and, in some cases, clinical efficacy testing, removing clinical pharmacology profiling brings a dramatic paradigm shift, reducing development costs without compromising safety and efficacy. Also shared is a list of 160+ products ready to enter as biosimilars. Major actions from regulatory agencies and developers are required to make this paradigm shift.

Purpose: The study aimed to investigate if there were any links between liver function biomarkers and immunoglobulins levels in serum, and Toll-like receptors (TLRs) and neuropilin-1 (NRP1) in COVID-19 patients. The study also aimed to assess the accuracy—sensitivity, specificity, and area under the curve (AUC) by the receiver operator curve (ROC) analysis for immunoglobulins levels and TLRs expressions. Patients and Methods: This study included 150 patients (100 patients with confirmed COVID-19 and 50 healthy volunteers as a control group). Patients with COVID-19 were subdivided into two groups according to the severity of symptoms (moderate and severe, with 50 patients each). Serum C-reactive protein (CRP), alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), albumin, lactate dehydrogenase (LDH), immunoglobulin (Ig) G, and IgM levels were estimated. TLRs (TLR2 and TLR4) and NRP1 gene expression in blood samples were investigated using quantitative real-time polymerase chain reaction (qRT-PCR). ROC analysis was also applied to determine the accuracy of various detected parameters in predicting the possibility of COVID-19 infection. Results: In COVID-19 patients, serum parameters related to liver function, except serum albumin, CRP, IgG, IgM, and TLR2, TLR4, and NRP1 mRNA expression levels, significantly elevated compared to controls. Severe COVID-19 patients exhibited significantly higher liver enzymes (ALT, AST and LDH), CRP, and TLR2 mRNA expression levels and lower albumin levels than the moderate group. In the moderate and severe groups, ALT, CRP, TLR2, and TLR4 had a significant positive correlation with IgM levels. ALT, AST, LDH, CRP, TLR2, and TLR4 showed a significant positive correlation with IgG levels in both groups. In both the moderate and severe groups, NRP1 expression was found to be significantly correlated with CRP, IgG, IgM, TLR2, and TLR4. In contrast, serum albumin levels exhibited a significant negative correlation with IgG and IgM levels only in the severe group, but they showed a significant negative correlation with TLR2, TLR4, and NRP1 expression in both moderate and severe groups. Serum ALT and AST activities were positively correlated with NRP1 expression in the moderate group but not in the severe group and as well as TLR2 and TLR4 expression in both the moderate and severe groups. ROC analysis indicated that AUC was higher than 0.800 for serum IgM level and TLR4 gene expression in moderate COVID-19 group. Conclusions: The increased liver function biomarkers in serum and NRP1 expression are closely correlated with sustained activations in humoral and innate immune responses during COVID-19 infection. As a result, TLR2, TLR4, and NRP1 could be targets for limiting COVID-19 infection and impairment effects on liver function. Moreover, detection of IgM level in serum and TLR4 expression in blood have a good accuracy in predicting the possibility of infection with COVID-19 in moderate cases.

Segmentation is an important step in medical imaging. In particular, machine learning, especially deep learning, has been widely used to efficiently improve and speed up the segmentation process in clinical practice. Despite the acceptable segmentation results of multi-stage models, little attention was paid to the use of deep learning algorithms for brain image segmentation, which could be due to the lack of training data. Therefore, in this paper, we propose a Generative Adversarial Network (GAN) model that performs transfer learning to segment MRI brain images.Our model enables the generation of more labeled brain images from existing labeled and unlabeled images. Our segmentation targets brain tissue images, including white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). We evaluate the performance of our GAN model using a commonly used evaluation metric, which is Dice Coefficient (DC). Our experimental results reveal that our proposed model significantly improves segmentation results compared to the standard GAN model. We observe that our model is 2.1–10.83 minutes faster than stat-of-the-art-models.

With the advancement of long-read sequencing technologies and their more widespread use for bacterial genomics, several methods for generating genome assemblies from error-prone long reads have been developed. These are complemented by various tools for assembly polishing using either long reads, short reads, or reference genomes. End users are therefore left with a plethora of possible combinations of programs for obtaining a final trusted assembly. Hence, there is also the need for measuring completeness and accuracy of such assemblies, for which, again, several evaluation methods implemented in various programs are available. In order to automatically run all these programs, I developed two workflows for the workflow management system Snakemake for bacterial genome assembly and evaluation of assemblies, which provide end users with an easy-to-run method for both tasks. The workflows are available as open source software under the MIT license at https://github.com/pmenzel/ont-assembly-snake and https://github.com/pmenzel/score-assemblies.

Background: Anemia is one of the most frequent diseases worldwide, affecting a third of the general population. Anemia in general and in particular, iron-deficient anemia (IDA), has been associated to a higher risk of thrombotic manifestations, including ischemic stroke and cerebral venous thrombosis (CVT), as well as systemic extra cerebral arterial and venous thrombosis. Despite these data, anemia is seldom considered as an etiological factor of stroke. Methods: An individual case encompassing all known neurovascular and systemic arterial and venous thrombotic manifestations related to IDA is presented with the focus on clinical reasoning issues in the diagnostic pathways, starting from the neuroradiological signs. The main questions have been identified and addressed in a narrative review of the most relevant data in the literature from a pragmatic and clinical viewpoint. Results and Discussion: The presented case concerns a 46 years old man admitted to the Stroke Unit because of acute is-chemic stroke with multiple thrombi in large intracranial and extracranial vessels, multifocal ischemic lesions in several arterial territories and the concurrent finding of asymptomatic CVT, pulmonary embolism with lung infarction and aortic thrombosis. An extended diagnostic work-up excluded the main etiologies (arterial dissection, cardiac embolism, genetic and acquired prothrombotic disorders, as cancer and antiphospholipid syndrome), except for a severe IDA, such as to require blood transfusions followed by anticoagulant therapy for the several thrombotic manifestations. Neuroimaging and systemic vascular findings have been analyzed and the main issues proposed by the case in the diagnostic pathway have been identified and discussed in a pragmatic clinical road map reviewing the data provided by the literature. Conclusions: IDA is a common but treatable condition that, independently or synergically, may increase the risk of thrombotic events. The diagnostic and therapeutic approach has not yet defined and each case should be individually addressed in a pragmatic clinical road map.

Purpose: We assessed if a CXR AI algorithm can detect missed or mislabeled chest radiographs (CXRs) findings in radiology reports. Methods: We queried multi-institutional radiology reports search database of 13-million reports to identify all CXRs reports with addendums from 1999-2021. Of the 3469 CXR reports with an addendum, a thoracic radiologist excluded reports where addendum was created for typographic errors, wrong report template, missing sections, or uninterpreted signoffs. The remaining reports with addendum (279 patients) with errors related to side-discrepancy or missed findings such as pulmonary nodules, consolidation, pleural effusions, pneumothorax, and rib fractures. All CXRs were processed with an AI algorithm. Descriptive statistics were performed to determine the sensitivity, specificity, and accuracy of AI to detect missed or mislabeled findings. Results: AI had high sensitivity (96%), specificity (100%), and accuracy (96%) for detecting all missed and mislabeled CXR findings. The corresponding finding-specific statistics for AI were nodules (96%, 100%, 96%), pneumothorax (84%, 100%, 85%), pleural effusion (100%, 17%, 67%), consolidation (98%, 100%, 98%), and rib fractures (87%, 100%, 94%). Conclusion: The CXR AI could accurately detect mislabeled and missed findings. Clinical Relevance: The CXR AI can reduce the frequency of errors in detection and side-labeling of radiographic findings.

The Internet of Things (IoT) has become one of the most attractive domains nowadays. It works by creating a special network between physical devices such as vehicles, home equipment, and other items. In recent days, the common technologies of communication such as Wi-Fi and 2G/3G/4G cellular are insufficient for the IoT networks because they are designed to serve appliances with immense processing capabilities such as laptops and PCs. Moreover, most of these technologies are centralized and use an existing infrastructure. Currently, the new communication technologies such as Z-Wave, 6LowPAN, and Thread are dedicated to the IoT and have been developed to meet its requirements. These technologies can handle many factors such as range, data requirements, security, power demands, and battery life. Nevertheless, the security issues in IoT systems have major concerns and matters because vulnerabilities in such systems may result in fatal catastrophes. In this paper, an enhanced IoT security framework for authentication and authorization is proposed and implemented to protect the IoT protocols from different types of attacks such as man-in-the-middle attack, reply attack, and brute force attack. The proposed framework combines an enhanced token authentication that has identity verification capabilities and a new sender verification mechanism on the IoT device side based on time stamp, which in turn can mitigate the need for local identity verification methods in IoT devices. The proposed IoT security framework is tested using security analysis with different types of attacks compared with previous related frameworks. The analysis shows the high capability of the proposed framework to protect IoT networks against many types of attacks compared with current available security frameworks. Finally, the proposed framework is developed using Windows application to simulate the framework phases, check its validity through the real network, and calculate the payload time is adds.

This research was carried out with the objective of analyzing the principles of social and solidarity economy in the community funds of the rural sector of Pichincha, Ecuador. Small organizations promote microcredits for local, social and economic development, representing an alternative to those managed by traditional banks. The research was descriptive, non-experimental field research. The population analyzed consisted of 220 community funds, and the size of the representative sample was 49 community organizations that practice solidarity finance. The data were collected through online questionnaires using a Likert scale, and the validity of this approach was judged by experts; the reliability of the instrument obtained was 0.95 using the Cronbach’s alpha method. The results highlight that in these organizations, the following traits prevail: associativity, self-management and organization. However, autonomy and solidarity have a negative valuation, which shows that strategies must be rethought to achieve the empowerment of the financial service. This will allow them to be sustainable and to expand with more benefits that promulgate financial activity and promote structures in rural community networks that promote local development and strengthen deficient principles as a basis for generating a greater benefit to the partners.

Several red seaweeds have shown to inhibit enteric CH₄ production; however, adaptation of fermentation parameters to their presence is not well understood. The objective of this study was to examine the effect of three red seaweeds (Asparargopsis taxiformis, Mazzaella japonica, Palmaria mollis) on in vitro fermentation, CH₄ production, and adaptation using the rumen simulation technique (RUSITEC). The experiment was conducted as a completely randomized design with four treatments, duplicated in two identical RUSITEC apparatus equipped with eight fermenter vessels each. The four treatments included the control (barley straw and barley silage) and the three red seaweeds added to the control diet at 2% diet DM. The experimental period was divided into four phases including a baseline phase (d 0-7; no seaweed included), adaptation phase (d 8-11; seaweed included in treatment vessels), intermediate phase (d 12-16) and a stable phase (d 17-21). The digestibility of organic matter (P = 0.04) and neutral detergent fibre (P = 0.05) was decreased by A. taxiformis during the adaptation phase, but returned to control levels in the stable phase. A. taxiformis supplementation resulted in a decrease (P < 0.001) in molar proportions of acetate, propionate and total volatile fatty acid (VFA) production, with an increase in molar proportions of butyrate, caproate, and valerate; the other seaweeds had no effect (P > 0.05) on molar proportions or production of individual VFA. A. taxiformis was the only seaweed to suppress CH₄ production (P < 0.001), with the suppressive effect increasing (P < 0.001) across phases. Similarly, A. taxiformis increased (P < 0.001) the production of hydrogen (H₂, %, mL/d) across the adaptation, intermediate and stable phases, with the intermediate and stable phases having greater H₂ production than the adaptation phase. In conclusion, M. japonica and P. mollis did not impact rumen fermentation or inhibit CH₄ production within the RUSITEC. In contrast, we conclude that A. taxiformis is an effective CH₄ inhibitor and its introduction to the ruminal environment requires a period of adaptation; however, the large magnitude of CH₄ suppression by A. taxiformis inhibits VFA synthesis, which may restrict production performance in vivo.

Inorganic pollutants in Colombian cocoa (Theobroma cacao L.) agrosystems cause problems in the production, quality, and exportation of this raw material. There has been an increased interest in bioprospecting studies of different fungal species focused on the biosorption of heavy metals. Furthermore, fungi constitute a valuable, profitable, ecological, and efficient natural soil resource that could be considered in the integrated management of cadmium mitigation. In this study, we report a new species of Talaromyces, isolated from cocoa soil from San Vicente de Chucurí-Colombia. The characterization of the culture was performed on six different standardized media and was distinguished by characteristic colony morphology: biverticillate and monoverticillate penicilli, acerose phialides, and slightly globose smooth-walled conidia. Culture was featured by bright yellow mycelium in young culture on CYA and CYAS medium. Colonies grew faster on Malt and Oat agar, attaining 36 and 32 mm diameter after seven days at 20 ºC. High acid production on CREA medium at 20-30 ºC was observed. Phylogenetic analysis was based on the ITS region and the RPB2, Calmodulin (CaM) and β-Tubulin genes that indicate that it is new to science and is named Talaromyces santanderensis sp. nov. This new species belongs to the Talaromyces section and is closely related to T. lentulus and related to T. soli, T. tumuli and T. pratensis (inside the T. pinophilus species complex) in the inferred phylogeny. Mycelia growth of the fungal strains was subjected to a range of 0-400 ppm Cd and incorporated into malt extract agar (MEA) in triplicates. Fungal radial growth was recorded every three days over a 13-days incubation period and In vitro cadmium tolerance tests showed a high tolerance index = 0,81 when the mycelium was exposed to 300 ppm of Cd. Results suggest T. santanderensis showed tolerance to Cd concentrations that exceed the permissible limits for contaminated soils, and it is promising for its use in bioremediation strategies to eliminate Cd from highly contaminated agricultural soils.

This paper presents a modular approach to generic exergame design that combines custom physical exercises in a meaningful and motivating story. This aims to provide a tool that can be individually tailored and adapted to people with different needs, making it applicable to different diseases and states of disease. The game is based on motion capturing and integrates four example exercises that can be configured via our therapeutic web platform "Blexer-med". To prove the feasibility for a wide range of different users, evaluation tests were performed on 14 patients with various types and degrees of neuromuscular disorders, classified into three groups based on strength and autonomy. Users were free to choose their schedule and frequency. Game scores and three surveys (before, during, and after the intervention) showed similar experiences for all groups, with the most vulnerable having the most fun and satisfaction. The players were motivated by the story and by achieving high scores. The average usage time was 2.5 times per week, 20 minutes per session. Pure exercise time was about half the game time. The concept has proven feasible and forms a reasonable basis for further developments. The full 3D exercise needs further fine-tuning to enhance fun and motivation.

Heart rate (HR) and respiratory rate (RR) are two vital parameters of the body medically used for diagnosing short/long term illness. Out-of-the-body, non-contact HR/RR measurement remains a challenge due to imprecise readings. “Invisible” wearables integrated into day-to-day garments has the potential to produce precise readings with comfortable user experience. Sleep studies and patient monitoring benefit from “Invisibles” due to longer wearability without significant discomfort. This paper suggests a novel method to reduce the footprint of sleep monitoring devices. We use a single silver-coated nylon fabric band integrated into a substrate of standard cotton/nylon garment as a resistive elastomer sensor to measure air and blood volume change across the chest. We introduce a novel event-based architecture to process data at the edge device and describe two algorithms to calculate real-time HR/RR on ARM Cortex-M3 and Cortex-M4F microcontrollers. RR estimations show a sensitivity of 99.03% and a precision of 99.03% for identifying individual respiratory peaks. The two algorithms used for HR calculation show a mean absolute error of 0.81±0.97 and 0.86±0.61 beats/minute compared to a gold standard ECG-based HR. The event-based algorithm converts the respiratory/pulse waveform into instantaneous events, therefore, reducing the data size by 40-140 times and requires 33% less power to process and transfer data. Further, we show that events hold enough information to reconstruct the original waveform, retaining pulse, and respiratory activity. We suggest fabric sensors and event-based algorithms would drastically reduce the device footprint and increase the performance for HR/RR estimations during sleep studies providing better user experience.

Cancer-related fatigue is a common, burdensome symptom of cancer and side-effect of chemotherapy. While a Mediterranean Diet (MedDiet) promotes energy metabolism and overall health, its effects on cancer-related fatigue remain unknown. In a randomized controlled trial, we evaluated a rigorous MedDiet intervention for feasibility and safety as well as preliminary effects on cancer-related fatigue and metabolism compared to usual care. Participants had stage I-III cancer and at least 6 weeks of chemotherapy scheduled. After baseline assessments, randomization occurred 2:1, MedDiet:usual care. Measures were collected at baseline, week 4, and week 8 including MedDiet adherence, dietary intake, and blood-based metabolic measures. Mitochondrial respiration from freshly isolated T cells was measured at baseline and 4 weeks. Participants (n=33) were 51.0±14.6 years old, 94% were female, and 91% were being treated for breast cancer. The study was feasible, with 100% completing the study and >70% increasing their MedDiet adherence at 4 and 8 weeks compared to baseline. Overall, the MedDiet intervention vs. usual care had a small-moderate effect on change in fatigue at weeks 4 and 8. For those with a baseline MedDiet score<5 (n=21), the MedDiet intervention had a moderate-large effect of 0.67 and 0.48 at weeks 4 and 8, respectively. The MedDiet did not affect blood-based lipids, though it had a beneficial effect on fructosamine (ES= -0.55). Fatigue was associated with mitochondrial dysfunction including lower basal respiration, maximal respiration, and spare capacity (p<0.05 for FACIT-F fatigue subscale and BFI, usual fatigue). In conclusion, the MedDiet was feasible and attenuated cancer-related fatigue among patients undergoing chemotherapy, especially those with lower MedDiet scores at baseline.

The transcriptional response of human blood leukocytes to SARS-CoV-2 infection was investigated focusing on the differences between mild and severe cases and between age subgroups. Weighted gene co-expression network analysis and comparative gene expression analysis were used. Three transcriptional modules positively associated with the traits of interest and their respective high hierarchy genes were identified. Enrichment analyses showed that the yellow module, associated with severe cases and older patients, had an overrepresentation of genes involved in inflammatory and innate immune responses, and neutrophil activation. The magenta and black modules, associated with disease severity and younger patients, contained genes related to innate immunity and inflammation and genes that regulate those responses. Subnetworks for these modules were constructed using genes enriched for innate immunity, inflammation, immunoregulation and differentially expressed genes (severe vs. mild). Their analysis evidenced that immunoregulatory functions are more activated in the modules associated with younger patients, what may help to explain the better disease course and faster recovery observed in younger COVID-19 patients. Comparative gene expression analysis between severe and mild groups, followed by gene enrichment and normalized gene expression analyses, revelated a set of 23 potential biomarkers for COVID-19 severity, of which 13 are newly described.

Background Nitrous Oxide (N₂O) is a dissociative anaesthetic that is sometimes used recreationally. The prevalence of N₂O use is difficult to quantify but appears to be increasing. Research on N₂O harms and application of harm reduction strategies are limited. The aim of this mixed method systematic review was to collate and synthesise the disparate body of research on recreational nitrous oxide use to inform harm reduction approaches tailored for young people. Methods To identify publications reporting recreational use of N₂O, a search of public health, psychology and social science databases was conducted. Databases included PubMed, CIHNAL, PsycINFO, Scopus and Web of Science. Gray literature and Google advanced search were also used. Due to limited published literature on the recreational use of N₂O, no limit was placed on publication date or study type. A thematic synthesis extracted descriptive and analytical themes from the selected studies. Quality appraisal was conducted using the CASP Tool for Qualitative studies and the Joanna Briggs Institute case report assessment tool Results The search retrieved 407 reports. Thirty-four were included in the final analysis including sixteen case reports. The included studies were primarily concerned with raising awareness of the apparently increasing use and subsequently increasing harms of recreational N₂O use. There was limited reference to policy or legislative responses in any published studies, no suggestions for harm reduction strategies or application of service level responses. In general, individuals lack awareness of N2O related harms. Conclusion The review found three key areas that deserve further consideration including: 1) policy, 2) service delivery, and 3) harm associated with N₂O use. We recommend a top-down (policy) and bottom-up (services delivery/services users) approach to harm reduction for N₂O use which also includes further consultation and research with both groups. Future research could explore young people’s experience of N₂O use including benefits and problems to inform contextually relevant harm reduction strategies.

Measurement uncertainty is typically expressed in terms of a symmetric interval , where denotes the measurement result and the expanded uncertainty. However, in the case of heteroscedasticity, symmetric uncertainty intervals can be misleading. In this paper, a different approach for the calculation of uncertainty intervals is introduced. This approach is applicable when a validation study has been conducted with samples with known concentrations. It will be shown how, under certain circumstances, asymmetric uncertainty intervals arise quite naturally and lead to more reliable uncertainty intervals.

At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in male and female patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (p-value = 1.33×10^-8 calculated with the Yates-corrected Chi-square test under the assumption of dominant inheritance) was discovered in female patients. Associations of AD and related clinical measures with seven other single nucleotide polymorphisms listed in previous GWAS of psychiatric and addiction traits were differently replicated in male and female patients. The bioinformatic analysis showed that regulatory elements in the eight associated linkage disequilibrium blocks define the expression of 80 protein-coding genes. Nearly 68% of these and of 120 previously published coding genes associated with alcohol phenotypes directly interact in a single network. This study indicates that a number of genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The results also suggest the genetic basis of sex-specific psychiatric comorbidities of AD.

This paper presents an approach to the application of the Model-Based Systems Engineering (MBSE) and Model-Based Systems Architecting (MBSA) principles to develop a Model-Based Pattern Language (MBPL). It takes too long for systems engineers and architects to develop a new system from scratch, particularly new space-based systems derived from the existing space systems architectures. A pattern language is a holistic view of reusable logical model artifacts; many are interdisciplinary and introductory, if at all. The results are mostly a combination of the application-specific logical solution, which further results in the best possible overall solution. The main benefit of the pattern language is reducing the time and validation required to generate a new space-based system architecture; this approach will develop top-level requirements in the initial phase of the system development. The rationale of the methodology proposed by the paper is as follows, collect, and decompose published literature and other open-source information available on space system architectures and system models; develop SysML models for systems, subsystems, products, assembly, subassembly level, and mission-specific requirements using CAMEO SysML software. Arrange these patterns to develop a functional ontology and construct a logical architecture pattern library. This approach created, updated, and managed SysML pattern language, which evaluated the expedited new model construction. Again, our objective is to develop a logical pattern language using public domain information and evaluate patterns by constructing a new space mission concept—for example, planetary surface habitat.

Dementia patients express a set of problematic and deteriorating symptoms, along self-care dependency. Overtime, the mental health of family caregivers of persons with dementia may suffer, putting them at a high risk for psychopathology, which may be associated with endangered wellbeing of demented people. This cross-sectional study examined the psychometric properties of the Depression Anxiety Stress Scale 8-items (DASS-8), DASS-12, DASS-21 in a convenient sample of 571 caregivers from northern Italy and southern Switzerland (Mean age = 53, SD = 12, range = 24–89 years). A bifactor structure of the three measures had the best fit; some items of the DASS-12/DASS-21 failed to load on their domain-specific factors. The three-factor structure was invariant across various groups (e.g., gender, education, etc.), expressed adequate reliability and convergent validity, and had strong positive correlation with the 3-item UCLA Loneliness Scale (UCLALS3). Dementia type had no effect on distress scores, which were higher among females, adult children caregivers, those caring for dependent patients, and those who received help with care. For 54.9 and 38.8% of the latter, care was provided by relatives and health professionals, respectively. Since the DASS-8 expresses adequate psychometrics comparable with the DASS-21, it may be used as a brief measure of distress in this population.

The quest for sustainable health, environmental protection and conservation of beneficial organisms makes the use of biopesticides a desirable option. This research aimed to identify botanicals used in the management of farm and household pest in Plateau State, Nigeria. A cross sectional study was carried out using semi-structured questionnaires and on the spot face-to-face interviews. The main issues captured include the pest, plants used to managed the pest, parts used, cultivation status, availability, effect on pest, formulation methods and modes of application. The quantitative data were analyzed using the Frequency of Citation (FC), Relative Frequency of Citation RFC (%) and Use Value (UV). A total of 45 plant species belonging to 42 genera, 20 orders and 30 families were found to be useful in the management of 15 different pests. The FC, RFC(%) and UV values identified the most popularly used plants as: Hyptis suaveolens, Vernonia amygdalina, Azadirachta indica, Canarium schweinfurthii and Euphorbia unispina and Erythrophloem africanum. Plants that showed broad activity include Azadirachta indica (7 uses), Erythrophloem africanum, Khaya senegalensis and Vernonia amygdalina. The perception of the respondents indicated that most of the biopesticides are available, affordable, effective, eco-friendly and safe. This survey provides a pathway for formulation of biopesticides.

Every year around 800 000 people commit suicide, this represents one death every 40 seconds. In the search for possible biological biomarkers associated with suicide and/or psychiatric disorders, serum cholesterol levels have been extensively explored. Several studies have indicated that cholesterol and associated proteins, especially apolipoproteins (Apos), may play an important role in the diagnosis, prognosis, and susceptibility of suicide. Here, we describe the current knowledge and findings in the relationship between apolipoproteins and suicide.

In our recently published papers, considering Planck mass based light speed growing black hole universe and scaled Hawking’s black hole temperature formula, we have developed a simple procedure for estimating the current Hubble parameter and current cosmic mass. In addition to that, without considering galactic dark matter, starting from 10 km/sec to 500 km/sec, we have tried to fit the observed galactic flat rotation speeds with a concept of super gravity of galactic baryonic mass. To estimate the equivalent mass of currently hypothecated galactic dark matter, we have introduced a timely increasing cosmological reference mass unit. Its current magnitude seems to be around 200 million solar masses. In this paper, considering 200 million solar masses as a characteristic representation of cosmic weak interaction mass unit, we have developed a simple formula for its estimation. We would like to appeal that, weak interaction boosts the gravity of galaxies in proportion with their virtual dark mass as (galactic baryonic mass)^3/2 / (200 million solar masses)^1/2. With further study- dark matter existence and physical properties can be understood in a theoretical approach.

Background: The COVID-19 pandemic has seen a considerable expansion in the way work settings are structured with a continuum emerging between working fully in-person and from home. The pandemic has also exacerbated many risk factors for poor mental health in the workplace, especially in public-facing jobs. Therefore, we sought to test the potential relationship between work setting and self-rated mental health. Methods: We modeled the association of work setting (only working from home, only in-person, hybrid) on self-rated mental health (Excellent/Very Good/Good vs. Fair/Poor) in an online survey of Canadian workers during the 3rd wave of COVID-19. Mediating effects of vaccination, masking, and distancing were explored due to the potential effect of COVID-19 related worries on mental health among those working in-person. Results: Among 1,576 workers, most reported hybrid work (77.2%). Most also reported good self-rated mental health (80.7%). Exclusive work from home (aOR: 2.79, 95%CI:1.90,4.07) and exclusive in-person work (aOR: 2.79, 95%CI: 1.83,4.26) were associated with poorer self-rated mental health than hybrid work. Vaccine status mediated only a small proportion of this relationship (7%), while masking and physical distancing were not mediators. Conclusion: Hybrid work arrangements were associated with positive self-rated mental health. Compliance to vaccination, masking, and distancing did not meaningfully mediate this relationship.

Antimicrobial resistance (AMR) has been a serious threat to human health, and combination therapy is proved to be an economic and effective strategy to fight the resistance. However, the abuse of drug combinations would conversely accelerate the spread of AMR. To guide the practice, some regularity conclusions had been drawn in our previous work. Based on those experimental data, here the power function (y=ax^b, a>0) correlation between the mutant selection index (SI) (y) of one agent and the ratio value (x) of two agents in a drug combination was established, and two rules a₁ × MIC₁ = a₂ × MIC₂ and b₁ + b₂ = -1 were discovered from both equations of y=a₁x^b1 and y=a₂x^b2 for two agents in drug combinations. Simultaneously, it was found that one agent with larger MPC alone for drug combinations would present a larger |b| and show greater potency for narrowing itself MSW and preventing the resistance. Another, a new concept as mutation-preventing selection index (MPSI) was proposed and used for evaluating the mutation-preventing potency difference of two agents in drug combinations, and the positive correlation between the MPSI and the mutant prevention concentration (MPC) or minimal inhibitory concentration (MIC) was subsequently established. Inspired by this, the significantly positive correlation, contrary to previous reports, between the MIC and the corresponding MPC of antimicrobial agents against pathogenic bacteria was established using one hundred and eighty-one of data pairs reported. These above together indicate that the MPCs in alone and combination are very important indexes for drug combinations to predict the mutation-preventing effects and the trajectories of collateral sensitivity, and the MPC of an agent can be roughly calculated from its corresponding MIC. Subsequently, this was further verified and improved by the antibiotic exposure to forty-three groups designed as different drug concentrations and various proportions. Based on these, the diagram of the mutation-preventing effects and the resistant trajectories of drug combinations with different concentrations and ratio of two agents was presented, and the C/MPC for the agent with larger proportion in drug combinations is the key to judge whether the resistance and the collateral sensitivity occur to two agents. Furthermore, the stress factors 1/MPC alone of two agents, together with their SI in combination, are the key to predict the mutation-preventing effects, and control the trajectories of collateral sensitivity. Combined the discussion and analyses for the above results and previous work, a preliminary scheme for antimicrobial combinations preventing the AMR was further proposed for subsequent improvement research and clinic popularization. Moreover, some other proposals and regularity conclusions related to preventing the AMR, involving fractional inhibitory concentration index (FICI), mutant selection index (SI), and pharmacokinetic parameters (t_1/2, AUC₂₄/MPC, C_max/MPC, and f %T > MPC, etc.), were analyzed and discussed, and finally some similar conclusions were speculated for triple or multiple drug combinations.

Working memory refers to the capability of the nervous system to selectively retain short-term memories in an active state. The long-standing viewpoint is that neurons play an indispensable role and working memory is encoded by synaptic plasticity. Furthermore, some recent studies have shown that calcium signaling assists the memory processes and the working memory might be affected by the astrocyte density. Over the last few decades, growing evidence has also revealed that astrocytes exhibit diverse coverage of synapses which are considered to participate in neuronal activities. However, very little effort has yet been made to attempt to shed light on the potential correlations between these observations. Hence, in this article we will leverage a computational neuron-astrocyte model to study the short-term memory performance subject to various astrocytic coverage and we will demonstrate that the short-term memory is susceptible to this factor. Our model may also provide plausible hypotheses for the various sizes of calcium events as they are reckoned to be correlated with the astrocytic coverage.

The aim of this study was to investigate the spatio-temporal association between socio-economic deprivation and the incidence of COVID-19 and how this association changes through the seasons and due to the existence of restrictive public health measures. A retrospective observational study was conducted among COVID-19 cases that occurred in the Apulia region from 29 February 2020 to 31 December 2021, dividing the period into four phases with different levels of restrictions. A generalized estimating equations model was applied to test the independent effect of deprivation on the incidence rate of COVID-19, taking into account age, sex, and regional incidence rate as possible confounding effects and covariates such as season and levels of restrictions as possible modifying effects. The highest incidence rate was in areas with a Very High deprivation Index (DI) in winter (107.2 for 100,000 ab. ± 7.5), while in autumn, the highest Rate Ratio (RR) was estimated between Very High vs. Low DI (3.83, p<.001). During total lockdown, no RR between areas with different levels of DI was significant, while during soft lockdown, areas with Very High DI were more at risk than all other areas. The effects of social inequalities on incidence rate of COVID-19 change in as-sociation with the seasons and restrictions on public health. Disadvantaged areas showed a higher incidence rate of COVID-19 in the cold seasons and in the phases of soft lockdown.

Disasters such as the 2015-2018 drought in South Africa usually negatively impact agricultural water, especially in smallholder farming systems. This study assessed the availability of irrigation water, performance of irrigation infrastructure, and water governance systems in Genadendal, Western Cape, with a focus on smallholder farmers. Data for streamflow, dam levels, and rainfall were acquired from water institutions and analysed using Microsoft Excel. The performance of the infrastructure and water governance were assessed based on the perceptions of smallholder farmers and key informants. A questionnaire was administered to eight smallholder farmers, followed by a focus group discussion with 15 smallholder farmers. Interviews were conducted with eight key informants who worked in water-related institutions. Qualitative data from the interviews were analysed using thematic content analysis. The study showed adequate agricultural water resources during the 2015-2018 drought period for the smallholder farmers who relied on water from dams. However, smallholder farmers who relied on the Riviersonderend River experienced severe water shortages during the same period. The findings also showed that there was poor performance of irrigation water infrastructure due to inadequate maintenance. Lack of coordination among institutions, insufficient funding, political interference, fragmentation of roles and responsibilities, lack of human resources, and farmers’ lack of participation and commitment in water resources management contributed to the dysfunctionality of irrigation water governance systems, leading to water insecurity. This study recommends adequate funding for the operation and maintenance of infrastructure. Furthermore, water institutions need to support smallholder farmers with training skills in agricultural water management and infrastructure maintenance. Further studies are recommended to quantify the water lost due to the poor performance of water infrastructure and to develop effective water governance in Genadendal.

We measured the ring collection coefficient of bromide anion oxidation products in a neutral and slightly alkaline medium on a rotating ring-disk electrode (glassy carbon disk, platinum ring) varying the following parameters: disk electrode rotation velocity, sodium bromide concentration, pH of the medium (in the range of 6 – 12), anode current on the disk and the electroreduction potential of the bromide anion oxidation products on the ring. The data obtained is presented via dependences of the cathode ring current to the disk current ratio vs the ring electrode potential. The analysis of the results was carried out by comparing the experimental polarization curves of the ring electrode with the data of cyclic voltammetry in model solutions to determine the electrical activities of various bromine compounds in positive oxidation states. We claim that RRDE method could be used to obtain quantitative and qualitative data on the electrooxidation of bromide ion in neutral and alkaline solutions. For the most effective regeneration of the spent oxidizer the values of pH &gt; 10 and moderate concentrations of NaBr should be used.

Background: The trends in the role of the germline in epigenetic transgenerational inheritance starts with the environmental factors acting on the first generation of a gestating mother. These factors influence the developing second-generation fetus by altering gonadal development, thereby reprogramming the primordial germ cell DNA methylation and leading to consequences that would be seen along generations. Objective: Despite these epigenetic factors now surfacing, the few available studies are on animal-based experiments and to make follow up on human intergenerational trials might take decades. To this response, this study aimed to determine the influence of parental energy, toxicant exposure, age and nutrient restriction on the early life of offspring growth in Gambia. Method: The study was on population-based observational study on parental energy influence, toxicant exposure, age, and nutrient restriction on offspring growth in Gambia. Results: This study showed that parents who worked in industrial areas were more likely to have offspring with poor psychosocial skills. In addition, mothers who are exposed to oxidative stress and high temperature are more likely to have offspring with poor psychosocial skills. Mothers who consumed a high protein diet were almost three more likely to have infants with good psychosocial skills in their offspring. Furthermore, there was a negative correlation between maternal stress during pregnancy and psychosocial skills of offspring. Conclusion: This study was able ascertain if maternal diet during gestation, toxicant exposure, maternal stress and parental smoking habits have influence on the early life of offspring. While the study is recommending a large sample size study to eliminate selection bias, there should be an increased level of awareness of mothers on their offspring's health and their husbands' lifestyles that might influence the adulthood health of offspring.

(1) Background: Painful nervus intermedius neuropathy (e.g., geniculate neuralgia) involves continuous or near-continuous pain affecting the distribution of the intermedius nerve(s). The diagnosis of this entity is challenging, particularly when the clinical and demographic features do not resemble the typical presentation of this condition. To the best of our knowledge, only three case reports have described the occurrence of nervus intermedius neuropathy in young patients. (2) Case Description: A 13-year-old female referred to the Orofacial Pain clinic with a complaint of pain located deep in the right ear and mastoid area. The pain was described as a constant throbbing and dull, with an intensity of 7/10 on numerical rating scale, characterized by superimposed brief paroxysms of severe sharp pain. The past treatments included ineffective pharmacological and irreversible surgical approaches. After a comprehensive evaluation, a diagnosis of idiopathic painful nervus intermedius neuropathy was given, which was successfully managed with the use of gabapentin. (3) Conclusions and Practical Implications: The diagnosis and treatment of neuropathic pain affecting the nervus intermedius can be challenging due to the complex nature of the sensory innervation of the ear. The diagnosis can be even more challenging in cases of atypical clinical and demographic presentations, which in turn may result in unsuccessful, unnecessary, and irreversible treatments. Multidisciplinary teams and constant knowledge update are fundamental to provide good quality of care to our patients and to not overlook any relevant signs or symptoms.

Inflationary model provides a conceptual explanation of the horizon problem, the flatness problem and may also suppress the over abundant magnetic monopoles predicted by Grand Unified Theories. Although various inflationary models have been proposed since 1981, difficulties like fine tuning is not only unsolved but also becomes severer in confrontation with data of Planck Satellite. This paper proposes an alternative model of inflation: the spontaneous symmetry breaking phase transition at early universe is only responsible for the production of magnetic monopoles expected by Grand Unified Theories; it is the subsequent energy release of monopole annihilation that drives the inflation. As a result, the early universe underwent a free expansion with a heat source originating in the annihilation, which expects a smooth, plateau-like potential consistent with the observational data. Beside interpreting a number of long standing inflationary problems, the new scenario predicts a significant increase of entropy during the inflation, and tends to produce large scale structures exceed scale of 300 million light-years correlated with a CMB smoothen and flatten by a simple dynamical mechanism.

Nowadays molecular research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’ therefore it is possible to discover complex relationships between cytophysiology and tumor cells. Signal transducer and activator of transcription 3 (STAT3) belongs to the family of latent cytoplasmic transcription factors called STATs which comprises seven members: STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6. Those proteins play important role in cytokine-activated gene expression by transducing signals from the cell membrane to the nucleus. Abnormal prolonged activation results in tumorigenesis, metastasis, cell proliferation, invasion, migration and angiogenesis. Inhibition of this transcription factor inhibits previously mentioned effects in cancer cells whereas normal cells are not affected. Hence STAT3 might be a viable target for cancer therapy.

Cryptocurrencies are now the most popular investment instruments among millenials. Crypto offers great returns in a short period of time. Prior to COVID-19, Crypto experienced significant price fluctuations accompanied by an increase in the number of high transaction volumes. This situation was disrupted by the presence of the COVID-19 which made the world economy devastated, marked by the decline of stock prices in the world, especially in Indonesia. A paired test was conducted in this study to compare the state of Crypto before and during COVID-19 with the variables of Risk, Transaction Volume, Return, and Sharpe Performance. The results showed that there was a significant difference in the variables of Transaction Volume and Return. However, there was no significant difference in the Risk and Sharpe performance before and during COVID-19. This study shows that despite the COVID-19 pandemic, the enthusiasm of investors who transact crypto assets is not affected and they still get returns in accordance with the investments made. The high risk will be followed by a high standard deviation, so that the Sharpe Performance is small. Cryptocurrencies still have many gaps to research, such as regulation, so that many countries have not legalized Crypto transactions. If there is no regulation for Crypto, it is certain that an increase in cybercrime harms crypto investors and threatens global financial stability. Nevertheles, with or without COVID-19, investment transactions gain and lose based on confidence in the limited market. Therefore, the success of confidence fluctuations in crypto encourages the emergence of alternative coins created by investors to conduct an Initial Coin Offering (ICO).

Objective: The purpose of this study was to investigate the effects of Crocin on brain neuroterophins, cognition, sensory and motor dysfunction and compare to fingolimod effects in experimental model of demyelination with Ethidium Bromide EB in female Wistar rats. Methods: Animals were assigned in to 8 groups; Sham, Sham operated (ShOp), EAE, crocin treated (Cr5,10,20 mg/kg), Vehicle, Fingolompd (Fing) and fingolimod + crocin (Cr+Fing). Demyelination was induced by single dose injection of 10 μl of EB 0.1% into the fourth ventricle of the brain. Crocin and fingolimod were applied for 21 days, daily, oral gavage. BDNF, NGF1, nerve conduction velocities, tail flake latency, balance and behavioral variables were sampled and analyzed by paired t-test and ANOVA test with repeated post hoc measurements. Results: The results showed that crocin improves all studied factors, but remarkable imrovments were observed in dosage of 10 mg/kg. Crocin (10mg/kg) and fingolimod (1mg/kg) significantly improved cognition variables in open field test, sensory and motor nerve conduction velocity, tail flick latency and clinical signs (p<005). In addition, applying of crocin co-administered with fingolimod led to significant increases in all assessed factors, greater than crocin or fingolimod intervention alone (α≤0.001). Conclusion: Based on the current findings, crocin can improve the level of brain neurotrophins, exploratory behavior and nerve conduction after demyelination as close as fingolimod results. So, crocins can be considered as a neuro supportive agent in the management of degenerative diseases maybe similar to fingolimod mechanism.

A common requirement of embedded software in charge of safety tasks is to guarantee the identification of those Random Hardware Failures (RHFs) that can affect digital components. RHFs are unavoidable. For this reason, functional safety standards, like the ISO 26262 devoted to automotive applications, require embedded software designs able to detect and eventually mitigate them. For this purpose, various software-based error detection techniques have been proposed over the years, focusing mainly on detecting Control Flow Errors. Many Control Flow Checking (CFC) algorithms have been proposed to accomplish this task. However, applying these approaches can be difficult because their respective literature gives little guidance on the their practical implementation in high-level programming languages, and they have to be implemented in low-level code, e.g., assembly. Moreover, the current trend in the automotive industry is to adopt the so-called Model-Based Software Design approach, where an executable algorithm model is automatically translated into C or C++ source code. This paper presents two novelties: firstly, the compliance of the experimental data on the capabilities of Control Flow Checking (CFC) algorithms with the ISO 26262 automotive functional safety standard; Secondly, by the implementation of the CFC algorithm in the application behavioral model is automatically translated. There is no need to modify the code generator. The assessment was performed using a novel fault injection environment targeting a RISC-V (RV32I) microcontroller.

Phospholipid metabolism, including phosphatidylcholine (PC) biosynthesis, is crucial for various biological functions and is associated to longevity. Phosphatidylethanolamine N-methyltransferase (PEMT) is a protein that catalyzes the biosynthesis of PC, the levels of which change in various organs such as brain and kidney during aging. However, the role of PEMT for systemic PC supply is not fully understood. To address how PEMT affects aging-associated energy metabolism in tissues responsible for nutrient absorption, lipid storage and energy consumption, we employed NMR-based metabolomics to study liver, plasma, intestine (duodenum, jejunum, ileum), brown/white adipose tissues (BAT, WAT), and skeletal muscle of young (9–10 weeks) and old (96–104 weeks) wild-type (WT) and PEMT knockout (KO) mice. We found that the effect of PEMT-knockout was tissue-specific and age-dependent. Deficiency of PEMT affected the metabolome of all tissues examined, among which the metabolome of BAT from both young and aged KO mice was dramatically changed in comparison to WT mice, whereas the metabolome of jejunum was only slightly affected. As for aging, the absence of PEMT increased the divergence of metabolome during aging of liver, WAT, duodenum and ileum and decreased the impact on skeletal muscle. Overall, our results suggest that PEMT plays a previously unexplored critical role in both aging and energy metabolism.

Inflammatory reaction after ischemia-reperfusion contributes significantly to prognosis, and microglia activation is the main resource of inflammation in nervous system. STAT5 is proving to be a highly effective anti-inflammatory therapy with great potential, and inhibition of STAT5 has demonstrated significant anti-inflammation and therapeutic effects, but rarely focus on mechanism of neuroinflammation and brain injury from ischemia-reperfusion. It is the first time to found that the anti-inflammation of dauricine is mainly through STAT5-NF-κB pathway, might act as a STAT5 inhibitor. Dauricine suppressed the inflammation cytokines Eotaxin, KC, TNF-α, IL-1α, IL-1β, IL-6, IL-12β, IL-17α, and also inhibited the microglia activation. STAT5b mutant at Tyr-699 reversed the protective effect of dauricine on oxygen-glucose deprivation-reperfusion injury of neurons, and reactivated the suppression of dauricine on P-NF-κB of microglia. These results suggest that dauricine might suppress the neuroinflammation and protect the neuron from the injury of post-ischemia-reperfusion via mediating the microglia activation through STAT5-NF-κB pathway, and ss a potential therapeutic target for neuroinflammation, STAT5 needs to be raised concern in ischemic stroke.

Recent biotechnological innovations make feasible the new paradigm of creating biological neural circuits de novo. With advances in protein, cell and tissue engineering techniques, as well as cellular reprogramming methods, we are entering an era where the construction of neural circuits can open completely new ways for studying nervous systems and for treating nervous system disorders. I explore here three technologies, namely cellular engraftment, neuronal reprogramming and transsynaptic molecule engineering, and delineate how they are being used in a variety of basic research and translational medicine contexts. In basic neuroscience, neural circuit construction methods are enabling ways to study causality in neural development (e.g. neural precursor differentiation and migration) and circuit function (e.g. excitation/inhibition balance, neural population dynamics). In translational neuroscience, they are providing opportunities for the targeted correction of circuit malfunction in brain disorders, both psychiatric (e.g. schizophrenia) and neurological (e.g. Parkinson’s, Huntington’s and Alzheimer’s disease, as well as epilepsy). I discuss the challenges that these methods currently face, such as targeting specificity and cell survival, and outline future paths and opportunities to realize the full potential of technologies for creating new biological neural circuits.

Hydrostatic bearings for liquid rocket engine turbopumps provide distinctive advantages including high load capacity even with low viscosity cryogenic fluid and extending a life span by minimizing friction and wear between rotor and bearing surfaces. Application of hydrostatic bearings into turbopumps demands reliable test data base with well-quantified operating parameters and experimentally validated accurate performance predictive tools. The present paper shows the comprehensive experimental data and validation of predicted static load characteristics of hydrostatic journal bearings lubricated with air, water, and liquid nitrogen. Extensive experiments for static load characteristics of hydrostatic bearings are conducted using a turbopump rotor-bearing system simulator while increasing supply pressure (Ps) into the test bearings. The test results demonstrate notable effects of the test fluids and their temperatures, as well as Ps, on the bearing performance. In general, the measured bearing flow rate, rotor displacement, and stiffness of the test bearings steadily increase with Ps. The static load bearing characteristics predictions considering flow turbulence and compressibility matched well with the experimental results. The work with an independent test data and engineering computational programs will further the implementation of hydrostatic bearings in high performance turbopump shaft systems with improved efficiency and enhanced reusability of liquid rocket engine sub-systems.

Transient global amnesia (TGA) is an uncommon clinical syndrome characterized by a loss of short-term memory and disorientation that resolves in twenty-four hours. The etiology is unknown and the diagnosis is made by exclusion of other possible etiologies that may cause similar patterns and the reversibility of the condition in less than 24 hours. Here we report a 60-year-old male presented with sudden onset of disorientation and short-term memory loss early in the morning while at home and started to ask his whereabouts and what happened. He had no history of significant medical or psychiatric disease. There was no history of previous similar episodes. He had no recent history of sleep problems, head trauma, substance abuse, or loss of consciousness. He had no history of seizure disorder, or migraine. A neurologic examination revealed a normal wakefulness state with mild disorientation, and short-term memory impairment. He had score of 18/30 on mini-mental state examination (which later returned to normal baseline in 24 hours). Extensive lab investigations did not show any abnormal findings. Brain MRI did not show any acute cerebral pathology. The EEG was negative for any abnormal cerebral activity. His memory improved and returned to normal baseline over the course of a 20-hour from the onset. After exclusion of potential causes and the patient returned to normal state of memory, the diagnosis of transient global amnesia was made. At the follow-up visit, the patient was in a state of normal function without a recurrence of memory impairment. Here we presented this interesting case of transient global amnesia. TGA is diagnosis of exclusion and important to keep in mind when evaluating a patient with acute onset of short-term memory impairment, especially when etiological investigation revealed no potential cause.

The primary considerations while producing rice (Oryza sativa L.) include improving its nutritional quality and production. To tackle widespread hunger globally, better nutritional, high-yielding rice cultivars need to be developed. The conventional ways are to increase the production of rice and add balanced nutrients in the daily diet to fulfill the need of yield and nutrient quality. This article focuses on nutritional strategies for rice and illustrates the availability of omics technologies. Current advancements providing many methodologies and approaches for exploring genetic resources and for understanding the molecular mechanisms involved in trait formation have been highlighted. Studying the genetic influences of various characteristics has been proven to expedite crop breeding processes. In this perspective, genome-wide association research, genome selection (GS), and QTL mapping are all genetic analysis that helps in increasing the nutritional content of rice. Implementation of several omic techniques are effective approaches to enhance and regulate the nutritional quality of rice cultivars. Advancements in different types of omics including genomics and pangenomics, transcriptomics, metabolomics, nutrigenomics, and proteomics are also relevant to rice development initiatives. This review article compiles genes, locus, mutants and all omic approaches for rice enhancement. This knowledge will be very useful for now and for the future regarding rice studies.

The objective of this study was to evaluate the drying kinetics of the mass of jambu leaves and mass of jambu leaves in foam mat at different temperatures (50, 60 and 70 °C and thickness of 1.0 cm). The physicochemical characterization of the materials was performed before and after drying. Twelve different drying models were fitted to the drying kinetics data and the thermodynamic properties were calculated. The physicochemical parameters for the mass of leaves and foam after drying were moisture content from 2 to 7%, ash from 13 to 17%, protein content from 22 to 30%, lipids from 0.6 to 4% and total titratable acidity from 0.20 to 0.28% of tartaric acid. Wang & Singh and Midilli models were recommended for describing the drying kinetics. The use of foam mat promoted higher values of effective diffusion coefficient and activation energy and lower values of enthalpy and entropy, thus enhancing the reduction of drying time.

Desmin is the major intermediate filament protein of all three muscle cell types and connects different cell organelles and multi-protein complexes like the cardiac desmosomes. Several pathogenic mutations in the DES gene cause different skeletal and cardiac myopathies. However, the significance of the majority of DES missense variants is currently unknown since functional data are lacking. To determine whether desmin missense mutations within the highly conserved 1A coil domain cause a filament assembly defect, we generated a set of variants with unknown significance and analyzed systematically the filament assembly in transfected SW13 and H9c2 cells using confocal microscopy. We found that mutations in the N-terminal part of the 1A coil domain affect the filament assembly leading to the cytoplasmic desmin aggregation. In contrast, mutant desmin in the C-terminal part of the 1A coil domain form filamentous structures comparable to wild-type desmin. Our findings suggest that the N-terminal part of the 1A coil domain is a hot spot for pathogenic desmin mutations, which affect the desmin filament assembly leading in consequence to skeletal and/or cardiac myopathies. This study may have relevance for the genetic counselling of patients carrying variants in the 1A coil domain of the DES gene.

This study focuses on cardiovascular effects, particularly myocarditis and pericarditis events, after BNT162b2 mRNA COVID-19 vaccine injection in Thai adolescents. This prospective cohort study enrolled students from two schools aged 13–18 years who received the second dose of the BNT162b2 mRNA COVID-19 vaccine. Data including demographics, symptoms, vital signs, ECG, echocardiography and cardiac enzymes were collected at baseline, Day 3, Day 7, and Day 14 (optional) using case record forms.We enrolled 314 participants; of these, 13 participants were lost to follow up, leaving 301 participants for analysis. The most common cardiovascular effects were tachycardia (7.64%), shortness of breath (6.64%), palpitation (4.32%), chest pain (4.32%), and hypertension (3.99%). Seven participants (2.33%) exhibited at least one elevated cardiac biomarker or positive lab assessments. Cardiovascular effects were found in 29.24% of patients, ranging from tachycardia, palpitation, and myopericarditis. Myopericarditis was confirmed in one patient after vaccination. Two patients had suspected pericarditis and four patients had suspected subclinical myocarditis. Conclusion: Cardiovascular effects in adolescents after BNT162b2 mRNA COVID-19 vaccination included tachycardia, palpitation, and myocarditis. The clinical presentation of myopericarditis after vaccination was usually mild, with all cases fully recovering within 14 days. Hence, adolescents receiving mRNA vaccines should be monitored for side effects. Clinical Trial Registration: NCT05288231

Bacillus veleznesis RB.EK7 was recently found as a potent rhizobacterial strain for effective management of black pepper root-knot nematodes. This work aimed to produce, purify, and elucidate the chemical structures of antinematode compounds (ANCs). Concerning cost-effectiveness and environmental issues, this study used organic wastes for the bioproduction of ANCs. Among various substrates, shrimp shells powder was the most suitable carbon/nitrogen source to produce ANCs. The fermentation process for enhancement of antinematode activity was investigated. The targeting ANCs were purified from the fermented culture broth, and their structures were elucidated. Two active compounds were thymine (1) and hexahydropyrrolo [1,2-a]pyrazine-1,4-dione (2). Notably, for the first time, these purified compounds showed potential and moderate anti- J2 nematodes and anti-eggs hatching, respectively. The docking study results indicated that the potent antinematode effect of these compounds may be possibly due to the inhibition of the targeting enzyme acetylcholinesterase. The data of this work suggest that organic waste SSP can be potentially reused for the production of thymine and hexahydropyrrolo [1,2-a] pyrazine-1,4-dione with promising use for the management of black pepper nematodes.

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