In the last decades we have experienced great social, cultural, and educational changes, spending more time performing tasks in near vision and less hours in outdoor activities, having more overexposure to digital screens, especially the youngest and increasingly from younger ages. It is common to see cases when performing tasks in near vision the posture or position of the head is not adequate, especially the youngest, being essential to have a correct posture of the head to avoid visual, muscular, or articular problems. We present a procedure to try to control the correct position of the head in real time when performing close-up activities. The aim is to detect the inclination of the head and to know if a bad position is adopted due to a visual problem or simply to inadequate visio-postural habits, warning us of the postural anomaly to correct it.

While numerous studies have explored the correlation between the built environment and ride-hailing demand, few have assessed their nonlinear interplay. Utilizing ride-hailing order data and multi-source built environment data from Nanjing, China, this paper uses the machine learning method, eXtreme Gradient Boosting (XGBoost), combined with SHapley Additive exPlanations (SHAP) and Partial Dependence Plots (PDP) to investigate the impact of built environment factors on ride-hailing travel demand, including their non-linear and threshold effects. The findings reveal that dining facilities have the most significant impact, with a contribution rate of 30.75%, on predicting ride-hailing travel demand. Additionally, financial, corporate, and medical facilities also exert considerable influence. The built environment factors need to reach a certain threshold or within a certain range to maximize the impact of ride-hailing travel demand. population density, land use mix and distance to the subway station collectively influence ride-hailing demand. The results are helpful for TNCs to allocate network ride-hailing resources reasonably and effectively.

This paper addresses the input coupling problem for the shape memory alloy (SMA) actuated parallel platform with completely unknown nonlinear dynamics. The problem means that in a parallel platform with multiple SMA actuators acting together, the displacement of one of the actuators will simultaneously affect the remaining actuators to change. Due to the coupling problem and nonlinear characteristics of the SMA actuators, it is not easy to control the platform to achieve bi-directional swing with completely unknown nonlinear dynamics. Therefore, a model-free adaptive sliding mode control method is proposed to improve the control accuracy of the complex motion of the platform, avoiding the complex modeling process of the SMA actuated parallel platform. Based on the model-free adaptive control (MFAC) theory, a multiple input and multiple output (MIMO) dynamic linearized mathematical model of the parallel platform is established using the online input and output data of the system. Then, a sliding mode controller is designed based on the dynamic model. A rigorous theoretical analysis proves that the proposed model-free adaptive sliding mode controller is able to stably control the SMA actuated parallel platform, and its tracking error is uniformly ultimately bounded (UUB). Finally, experiments are conducted on the established SMA actuated parallel platform. The results show that the proposed model-free controller is feasible and effective, and can control the system well to achieve the complex motion of bi-directional swing.

The optimal structural design is imperative to minimize material consumption and reduce the environmental impact of construction. Given the complexity in the formulation of structural design problems, the process of optimization is commonly performed using artificial intelligence (AI) global optimization, such as Genetic Algorithm (GA). However, the integration of AI-based optimization together with visual programming (VP) in building information modeling (BIM) projects warrants further investigation. This study proposes a workflow by combining structure analysis, VP, BIM, and GA to optimize trusses. The methodology encompasses several steps including: (i) generation of parametric trusses in Dynamo VP; (ii) performing the finite element modeling (FEM) using Robot Structural Analysis (RSA); (iii) retrieving and evaluating the FEM results interchangeably between Dynamo and RSA; (iv) finding the best solution using GA; and (v) importing the optimized model into Revit, enabling the user to perform simulations and engineering analysis, such as life cycle assessment (LCA) and quantity surveying. The feasibility of the proposed workflow was tested on benchmark problems and compared with open literature. The outcomes of this study offer insight into the opportunities and limitations of combining VP, GA, FEA, and BIM for structural optimization applications, particularly to enhance structural efficiency and sustainability in construction.

The healthcare situation in Africa is characterized by limited resources and a high burden of disease, presenting significant challenges to the healthcare systems in the region. The integration of Artificial Intelligence (AI) technologies in African healthcare holds immense potential for addressing these challenges and improving health outcomes. This paper aims to provide a comprehensive understanding of the current healthcare landscape in Africa and the urgent need for AI-driven solutions.In addition to discussing the potential applications of AI in African healthcare, such as disease diagnosis, treatment planning, and medical imaging analysis, this manuscript seeks to shed light on the specific challenges hindering the implementation of AI in the region. By providing detailed examples and case studies, we aim to offer insights into the obstacles that need to be overcome and potential solutions that can be pursued.By leveraging AI technologies, Africa has the opportunity to revolutionize its health systems, bridging the gap in access to quality healthcare across the continent. The objective of this review article is to not only highlight the potential benefits that AI can bring to African healthcare but also to emphasize the urgent need for action and collaboration in implementing and scaling up AI innovations in the region. By doing so, African countries can pave the way for improved health outcomes and ensure that their populations receive the healthcare services they deserve.

This study aims to examine the non-volatile Particle Number (PN) emissions of a retrofitted Heavy-Duty Spark-Ignition (HD-SI) engine powered by liquefied petroleum gas (LPG) under both steady-state and transient conditions. The engine was tested under seven steady-state operating points to investigate the PN behavior and Particle Size Distribution (PSD) upstream and down-stream of the Three-Way Catalyst (TWC). This analysis intends to assess the impact of including particles with diameters ranging from 10 nm to 23 nm in the total particle count, a consideration for future regulations. The study employed the World Harmonized Transient Cycle (WHTC) for transient conditions to encompass the same engine working region used in the steady-state analysis. A Dekati FPS-4000 diluted the exhaust sample to measure the PSD and PN for particle diameters between 5.6 nm and 560 nm using the TSI-Engine Exhaust Particle Sizer (EEPS) 3090. Findings indicate that PN levels tend to increase downstream of the TWC under steady-state conditions in operating points with low exhaust gas temperatures and flows (equal to or less than 500 °C and 120 kg/h). Furthermore, the inclusion of particles with diameters between 10 nm and 23 nm leads to an increase in PN emissions by 17.70% to 40.84% under steady conditions and by an average of 40.06% under transient conditions, compared to measurements that only consider particles larger than 23 nm. Notably, in transient conditions, most PN emissions occur during the final 600 seconds of the cycle, linked to the most intense phase of the WHTC.

This paper presents the PEnsemble 4 model, a sophisticated machine learning framework that integrates IoT-based environmental data to accurately forecast maize yield. With the projected significant growth in global maize demand over the next decade, the inherent risks posed by the crop’s dependence on weather conditions necessitate improved prediction capabilities. The PEnsemble 4 model, developed with high accuracy, incorporates comprehensive datasets encompassing soil attributes, nutrient composition, weather conditions, and UAV-captured vegetation imagery. By employing a combination of Huber and M estimates, the PEnsemble 4 model effectively analyzes temporal patterns in vegetation indices, specifically CIre and NDRE, which serve as reliable indicators of canopy density and plant height. In addition, this research significantly contributes to precision agriculture by offering an efficient and sustainable alternative to conventional farming practices through precise yield predictions. Notably, the PEnsemble 4 model enables earlier estimation, advancing the timeline for yield prediction from the conventional day 100 in the R6 stage to day 79 in the R2 stage. This improvement enhances decision-making processes in farming operations. The remarkable accuracy rate of 91% underscores the importance of adopting a multifaceted data approach that harnesses IoT-derived environmental insights. Additionally, the PEnsemble 4 model extends its benefits beyond yield prediction, facilitating the detection of water and crop stress, as well as disease monitoring in broader agricultural contexts. Ultimately, the PEnsemble 4 model establishes a new standard in maize yield prediction, revolutionizing crop management and protection through the synergistic utilization of IoT and machine learning technologies.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that these ER-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including total 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the PERK-UPR associated genes: p-eIF2, BCL-2, PERK, ATF4, BAX were investigated by Real-Time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression of PERK, BCL-2, p-eIF2, ATF4, BAX was found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056 and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors, may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

The modern supply chain (SC) is growing in terms of data, devices, users, and stakeholders, which introduced new security challenges and threats, especially with the reliance on centralized servers or cloud platforms. In addition, increased trust among system participants exposes the SC to a higher risk of vulnerabilities which require strong security measures. This article proposes a hybrid security framework for SC systems, BC-DRLzSC, that integrates Blockchain (BC) and Deep Reinforcement Learning (DRL) designed to operate in a zero trust (ZT) environment. In particular, we propose a decentralized BC-based approach integrated with smart contracts to manage system participant registration and authentication and to control access to system resources. BC-DRLzSC adopts a ZT architecture to reinforce SC security, which can be achieved with an advocate to verify each entity’s trustworthiness before granting or retaining access to system resources. Incorporating the ZT architecture, with BC and DRL, can potentially and significantly bolster SC system security. DRL is employed to develop a proactive attack detection model that continuously monitors the incoming traffic from authenticated nodes within the network and predicts any malicious actions. Finally, we evaluate the performance of our proposed DRL solution using the NSL-KDD dataset.

Artificial intelligence (AI) has emerged as a powerful tool for addressing the challenges posed by climate change and their impact on public health. By leveraging its capacity to analyze and predict climatic patterns, AI offers opportunities to enhance resource management and develop effective strategies for climate change mitigation. Moreover, AI can contribute to generating sustainable solutions that address the complex and interconnected nature of climate change. For example, AI can enable the optimization of energy consumption and facilitate the integration of renewable energy sources into existing systems. It can also support the development of climate models that provide timely and accurate predictions, enabling policymakers to implement proactive measures for disaster preparedness and response. Furthermore, AI-powered disease surveillance and mitigation techniques can improve public health outcomes by identifying patterns and trends in the spread of diseases in relation to climatic factors.However, the widespread adoption of AI-based solutions is not without challenges. Ethical concerns surrounding privacy and data ownership must be addressed, as the use of AI requires access to large datasets, raising potential privacy risks. Technical constraints, such as limited computational power and the need for sophisticated algorithms, also pose obstacles to the implementation of AI in climate change mitigation strategies. Furthermore, issues related to the accessibility and affordability of AI technologies must be resolved to ensure equitable distribution and maximize its potential impact on public health.To fully harness the power of AI in addressing climate change and improving public health outcomes, it is crucial to promote innovation, multidisciplinary collaboration, and open data science. Innovation can drive the development of new AI algorithms and technologies specifically tailored to address climate change challenges. Multidisciplinary approaches that bring together experts from diverse fields, including climate science, public health, and computer science, can foster a holistic understanding of complex systems and enable the design of comprehensive solutions. Finally, open data science practices, such as sharing data and algorithms, can facilitate collaboration and accelerate progress in mitigating climate change and its public health impacts.In conclusion, AI offers promising opportunities for effectively addressing climate change and its impact on public health. However, to fully realize its potential, it is essential to tackle ethical and privacy concerns, overcome technical constraints, and ensure accessibility and affordability. By promoting innovation, multidisciplinary collaboration, and open data science, we can unlock the transformative power of AI in mitigating climate change and improving public health outcomes.

This paper aims to address the exponential stability and stabilization problems for a class of delayed nonlinear Markov jump systems under randomly occurring Denial-of-Service (DoS) attack and packet loss. Firstly, the stochastic characteristics of DoS attack and packet loss are depicted by the attack success rate and packet loss rate. Secondly, a Period Observation Window (POW) method and a hybrid-input strategy are proposed to compensate for the impact of DoS attack and packet loss on the system. Thirdly, A Dynamic Event-triggered Mechanism (DETM) is introduced to save more network resources and ensure the security and reliability of systems. Then, by constructing a general common Lyapunov functional and combining with the DETM and other inequality analysis techniques, the less conservative stability and stabilization criteria for the underlying systems are derived. In the end, the effectiveness of our result is verified through a numerical example.

Recurrent pregnancy loss (RPL) affects around 2 % of women of reproductive age. Primary RPL is defined by ≥2 pregnancy losses and no normal birth delivery. In secondary RPL, the losses are after a normal pregnancy and delivery. Most cases have no clear aetiology, although primary cases are the most complex. Several gene polymorphisms have been associated with RPL. Some polymorphisms are increased in women of Asian or Caucasian race. In admixed RPL populations, the information on possible genetic links is scarce and contradictory. The study aimed to assess the frequency of two SNP in different enzymes involved in medical conditions observed during pregnancy. Microsomal epoxy hydrolase (mEPH) is involved in detoxifying xenobiotics. It is present in ovaries, and it is hormonally regulated. The endothelial nitric oxide synthase forms nitric oxide from arginine and is involved in vascular tone. Two SNPs, rs1051740 and rs1799983, were assessed. The study included 26 controls and 63 primary RPL patients. Significant differences were observed in the frequencies of both SNP (p<0.05). The frequency of mutated alleles was higher in patients. Double mutated homozygotes were encountered only in RLP patients (p<0.05). Genetic polymorphisms rs1051740 and rs1799983 may be involved in primary RPL in the Venezuelan admix population. Genetic studies could provide crucial information on the aetiology of primary RPL.

The conventional well placement was done manually by using a numerical reservoir simulator, and it required a lengthy trial-and-error process. It required great experience and expertise to manipulate the variables and uncertainties that lie on the reservoir to determine the best placement of the well. In addition, the traditional gradient-based methods such as Line-search and Trust-region were not viable in terms of maximum results obtained. Gradient-based methods were too dependent on the surface gradient of the solution and may only converge to local optima instead of global optima. Complex reservoirs have rough surfaces with high uncertainties, which hinders the traditional gradient-based method from converging to global optima. Thus, genetic algorithms were utilized to automate the manual trial-and-error process and to overcome the limitations of the traditional gradient-based method. The objectives of this study were to analyse the effect of different initial well placement distributions, the number of random solution sizes, and the crossover rate on cumulative oil production. A synthetic reservoir model built using CMG Builder was used as the testing platform for the optimization problems. Well-placement parameterization and optimization set-up were carried out using the CMG CMOST optimization tool. The integration of CMG IMEX and CMOST optimized cumulative oil production based on the objectives of the study. The results obtained showed that the higher number of random solutions used resulted in higher cumulative oil production, with more generations needed to reach the optimum solution. It can be concluded that the larger number of random solutions used increased the probability of reaching the optimum solution, but will take more generations.

The application potential of cellulosic materials in natural composites and other fields needs to be explored to develop innovative, sustainable, lightweight, functional biomass materials that are also environmentally friendly. This study investigated Typha augostifolia (Typha sp.) as a potential new raw material for extracting cellulose nanocrystals (CNCs) for application in wastewater treatment composites. Alkaline treatments and bleaching were used to remove cellulose from the stem fibers. The CNCs were then isolated from the recovered cellulose using acid hydrolysis. The study showed a few distinct functional groups (O-H, -C-H, =C-H and C-O, and C-O-C) in the Fourier Transform Infrared (FTIR) spectra. Scanning electron microscope (SEM) revealed the smooth surface of CPC and CNCs that resulted from removing lignin and hemicellulose from powdered Typha augostifolia. Based on the crystalline index, the powdered Typha augostifolia, CPC, and CNCs were 42.86%, 66.94% and 77.41%. The loss of the amorphous section of the Typha sp. fiber resulted in a decrease in particle size. It may be inferred from the features of a Typha sp. CNC that CNCs may be employed as reinforcement in composites for wastewater treatment.

As marine traffic is contributing to pollution and mostly have predictable route with repetitive load profiles, to reduce their impact on environment, hybrid system with proton exchange membrane fuel cells (PEMFC-s) and battery pack, is promising replacement. For this purpose, the numerical model of repowered existing vessel that have two diesel engines with 300 kWe is developed. The goal of this paper is to develop numerical model which analyzes and determine equivalent hybrid ship propulsion system for known traveling route. The developed numerical model consists of an interconnected system with PEMFC stack and battery pack as power sources. Numerical model is developed and optimized to meet minimal required power demand for successful route demand, which has variable loads and daily sails six-time same voyage- in total 54 nautical miles. The results have shown that equivalent hybrid power system consists of 300 kWe PEMFC stack and battery pack with 424 kWh battery and state of charge varying between 20 and 87%. To power this new hybrid power system, hydrogen tank of 7200 l holding 284.7 kg at pressure of 700 bar is needed, compared to previous system that spend 1524 kg of diesel and generate 4886 kg of CO2.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of &lt;1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

Ti and its alloys are the most commonly used materials for biomedical applications. However, bacterial infection after implant placement is still one of the significant rising complications. Therefore, the application of the antimicrobial agents into implant surfaces to prevent implant-associated infection has attracted lots of attention. Scientific papers have shown that inorganic antibacterial metal element (e.g. Ag, Cu, Zn) can be introduced to implant surfaces with the addition of metal nanoparticles or metallic compounds into electrolyte via micro-arc oxidation (MAO) technology. In this review, the effects of the composition and concentration of electrolyte and process parameters (e.g. voltage, current density, oxidation time) on morphological characteristics (e.g. surface morphology, bonding strength), antibacterial ability and biocompatibility of MAO antimicrobial coating were discussed in detail. Anti-infection and osseo-integration can be simultaneously accomplished with the selection of the proper antibacterial elements and operating parameters. Besides, MAO assisted by magnetron sputtering (MS) to endow Ti-based implant materials with superior antibacterial ability and biocompatibility was also discussed. Finally, the development trend of MAO technology in the future was forecasted.

In order to solve the problem of feature extraction of underwater acoustic signals in complex ocean environment, a new method for feature extraction from ship radiated noise is presented based on empirical mode decomposition theory and permutation entropy. It analyzes the separability for permutation entropies of the intrinsic mode functions of three types of ship radiated noise signals, and discusses the permutation entropy of the intrinsic mode function with the highest energy. In this study, ship radiated noise signals measured from three types of ships are decomposed into a set of intrinsic mode functions with empirical mode decomposition method. Then, the permutation entropies of all intrinsic mode functions are calculated with appropriate parameters. The permutation entropies are obviously different in the intrinsic mode functions with the highest energy, thus, the permutation entropy of the intrinsic mode function with the highest energy is regarded as a new characteristic parameter to extract the feature of ship radiated noise. After that, the characteristic parameters, namely, the energy difference between high and low frequency, permutation entropy, and multi-scale permutation entropy, are compared with the permutation entropy of the intrinsic mode function with the highest energy. It is discovered that the four characteristic parameters are at the same level for similar ships, however, there are differences in the parameters for different types of ships. The results demonstrate that the permutation entropy of the intrinsic mode function with the highest energy is better in separability as the characteristic parameter than the other three parameters by comparing their fluctuation ranges and the average values of the four characteristic parameters. Hence, the feature of ship radiated noise can be extracted efficiently with the method.

One of the tools for optimal crop production is regular monitoring and assessment of crops. During the growing season of fruit trees, the bloom period has increased photosynthetic rates that correlate with the fruiting process. This paper presents the development of an image processing algorithm to detect peach blossoms on trees. Images of an experimental peach orchard were acquired from the Parma Research and Extension Center of the University of Idaho using an off-the-shelf unmanned aerial system (UAS), equipped with a multispectral camera (Near-infrared, Green, Blue). The orchard has different stone fruit varieties and different plant training system. Individual tree images (high-resolution) and arrays of trees images (low-resolution) were acquired to evaluate the detection capability. The image processing algorithm was based on different vegetation indices. Initial results showed that the image processing algorithm could detect peach blossoms and demonstrate good potential as a monitoring tool for orchard management.

Fe-(9, 19, 28, 37)wt.% Cr alloys were corroded at 700 and 800 ^oC for 70 h under 1 atm of N₂, 1 atm of N₂/3.2%H₂O-mixed gas, and 1 atm of N₂/3.1%H₂O/2.42%H₂S-mixed gas. The corrosion rate of Fe-9Cr alloy increased with the addition of H₂O, and furthermore with the addition of H₂S in N₂ gas. Fe-9Cr alloy was always nonprotective. In contrast, Fe-(19, 28, 37) wt.%Cr alloys were protective in N₂ and N₂/H₂O-mixed gas because of formation of the Cr₂O₃ layer. They were, however, nonprotective in N₂/H₂O/H₂S-mixed gas because sulfidation dominated to form the outer FeS layer and the inner Cr₂S₃ layer containing some FeCr₂S₄.

Precision agriculture is a farm management technology that involves sensing and then responding to the observed variability in the field. Remote sensing is one of the tools of precision agriculture. The emergence of small unmanned aerial vehicles (sUAV) have paved the way to accessible remote sensing tools for farmers. This paper describes the comparison of two popular off-the-shelf sUAVs: 3DR Iris and DJI Phantom 2. Both units are equipped with a camera gimbal attached with a GoPro camera. The comparison of the two sUAV involves a hovering test and a rectilinear motion test. In the hovering test, the sUAV was allowed to hover over a known object and images were taken every second for two minutes. The position of the object in the images was measured and this was used to assess the stability of the sUAV while hovering. In the rectilinear test, the sUAV was allowed to follow a straight path and images of a lined track were acquired. The lines on the images were then measured on how accurate the sUAV followed the path. Results showed that both sUAV performed well in both the hovering test and the rectilinear motion test. This demonstrates that both sUAVs can be used for agricultural monitoring.

Flap surgery is a common method used to cover defects following tumor ablation, trauma, or infection. However, insufficient vascularity in the transferred flap can lead to flap necrosis and failure. Proper postoperative monitoring is essential to prevent these complications. Recently, research has explored the use of infrared thermal imaging in plastic surgery, leading to its clinical application. This study investigates the use of a forward-looking infrared (FLIR) camera to monitor blood flow in flaps. In the study, 28 rats underwent reverse McFarlane flap surgery, and their flaps were analyzed using a FLIR thermal imaging camera seven days post-surgery. Additionally, thermal images of flaps were taken on postoperative days 0, 1, 2, 3, and 7 in 22 patients. The study focused on temperature differences between normal skin and the perforator compared to the average flap temperature. Results showed that the temperature difference was higher in the necrosis group and increased over time in cases of total necrosis. A lower perforator temperature compared to the flap's average indicated vascular compromise, potentially leading to flap failure. The FLIR camera, being contact-free and convenient, shows promise for understanding and inferring the clinical progression of flaps in postoperative monitoring.

Citrus species essential oils (EOs) are significant sources of bioactive compounds and demonstrate diverse therapeutic effects. However, limited documentation exists regarding the phytochemicals associated with their biological activities. This study aims to assess the antioxidant activity, plant inhibitory properties, and brine shrimp cytotoxic effects of EOs derived from three Citrus species: C. sinensis, C. limon, and C. hystrix. Utilizing chemometric analysis and gas chromatography-mass spectrometry (GC-MS) fingerprints, the volatile components contributing to antioxidant activity were elucidated. The peels of the Citrus samples were hydro-distillated to obtain EOs, and subsequently subjected to antioxidant, plant inhibitory, and brine shrimp cytotoxic assays. The results indicated that C. limon EO exhibited the highest antioxidant activity, while C. hystrix and C. sinensis EOs demonstrated pronounced inhibitory effects against Aetrmia salina and Lactuca sativa, respectively. GC-MS analysis facilitated the identification of key compounds in each EO. Principal component analysis (PCA) and hierarchy cluster analysis (HCA) effectively categorized Citrus EOs based on their antioxidant properties, highlighting the proximity of C. limon and C. sinensis. Among the identified compounds, D-limonene, α-Terpineol, Caryophyllene, (+)-3-Carene, β-Pinene, (-)-Spathulenol, trans-p-Mentha-1(7),8-dien-2-ol, and trans-Verbenol were the most discriminating compounds affected the antioxidant activity of C.limon and C. sinensis EOs.

Myasthenia gravis (MG) is a disease characterized by typical clinical and immunopathogenic pe-culiarities, which correlate with age and sex/gender. Accordingly, MG patients show thymic al-terations and auto-antibodies productions, that can be the expression of a different pathogenetic mechanism related to age and gender. This determines, in relation to age at and sex/gender, a dif-ferent MG onset, prognosis, and outcome. Therefore, diverse MG forms can be identified, classi-fied, and characterized in relation to their different features, and precisely there are early onset and late-onset forms of MG. It has been hypothesized that the cause of appearance the two diverse forms of MG can be ascribed mainly to the diverse genetic and epigenetic factors. In this narrative review, we will analyze and discuss about the interplay of age- and sex-related factors (i.e. genet-ic and epigenetic factors) related to two different MG forms and how they contribute to their di-verse pathogenesis.

Originating in the Mediterranean, B. oleracea is grown all over the world and is highly valued for its nutritional value and variety in cooking. Its susceptibility to pests, diseases, and environmental stressors, however, poses significant challenges to sustaining consistent crop quality and productivity. The BASIC PENTACYSTEINE gene significantly impacts plant growth and responses to abiotic stresses. Nevertheless, little is known about its precise role and the underlying biological processes in B. oleracea. Eleven BPC genes in B. oleracea were identified by a thorough genome-wide investigation and categorized into three categories according to their structural traits and gene motifs. There were eight different chromosomes on which these BoBPCs were located. Comparative synteny analysis was used to reveal the evolutionary traits of potatoes, Arabidopsis, and B. oleracea. The BoBPC family genes in B. oleracea were found to have specific cis-elements linked to growth, stress responses, and hormone regulation when their promoter regions were studied. Cuticular wax synthesis expression revealed that all BoBZR1 genes, from wild to mutant, expressed at varied amounts in distinct types. Moreover, distinctive BoBPC gene expression patterns were found in the seven distinct tissues that were studied. Our thorough analysis shows that the BoBPC family is widely involved in B. oleracea developmental processes. The present findings provide an established theoretical basis for further exploration into the composition and roles of BoBPC in B. oleracea.

Despite the efforts made to stop the tuberculosis (TB) epidemic, it still remains one of the leading causes of death from an infectious disease. Previous work in the group uncovered a new family of amides which showed promising activities against Mycobacterium tuberculosis. A closer look at the literature showed that these compounds are structurally related to the DNB family of DprE1 inhibitors, so, we decided to study a wide range of substituted amides and determine their activity, focusing on unexplored structures related to the dinitrobenzamides (DNB) found in the literature. To synthesize our library of compounds we started from 3,5-dinitrobenzoic acid to form the nitroaromatic core that is characteristic of the DNB’s, to which we then added linear or cyclic amine moieties. Additionally, the impact of terminal aromatic moieties was also assessed for some derivatives, via an ether, ester, or amide bond. In order to obtain the desired derivatives, multiple synthetic approaches were used, mainly focused on nucleophilic addition/elimination reactions, SN2 reactions and Mitsunobu reactions. The activity was impacted mainly by two structural features, the addition of an aromatic moiety as a terminal group and the type of the linker. The most interesting compounds exhibited activities comparable to isoniazid and DNB1. Computational studies were also performed aimed at understanding their possible interactions with DprE1. The most active compounds are a good starting point for further development, and we plan to study an extended family of compounds based in those structures.

The marine region of the Zhongjieshan Islands is an essential component and location for enhancement and release in Zhoushan Fishing Ground. The scientific assessment of the target species' ecological carrying capacity serves as the foundation for augmentation and release efforts. Based on data from the 2021-2022 survey of biological resources in the waters of Zhongjieshan islands, the Ecopath model was built to analyze the trophic structure, energy flow, and overall characteristics of the ecosystem, as well as the ecological carrying capacity of the main enhancement and releasing species, Larimichthys crocea and Sepiella maindroni. The ecosystem's functional groups had trophic levels ranging from 1 to 3.48, with an average energy transfer efficiency of 8.11% and total flow of 2125.905 t·km-2. The ratio of total primary output to total respiration is 1.713. Zhongjieshan Islands' ecosystem was currently at an embryonic stage. The ecological carrying capacity of Larimichthys crocea and Sepiella maindroni was calculated to be 0.2325 t·km-2 and 0.1617 t·km-2, separately or individually. Larimichthys crocea and Sepiella maindroni showed enormous potential for development and release. The findings offered essential data for ecological studies on the waters of Zhongjieshan Islands, as well as a reference for enhancement and release efforts in this area.

A useful perioperative nutritional therapy for highly invasive esophageal cancer surgical cases needs to be developed. We clarified the usefulness of amino acid-enriched nutritional therapy using glutamine (Gln)/arginine (Arg)/calcium β-hydroxy-β-methylbutyrate (HMB) products on the short-term postoperative outcomes of minimally invasive esophagectomy for esophageal cancer. Altogether, 114 patients (Gln/Arg/HMB group) received perioperative nutritional therapy with Gln/Arg/HMB products, and we retrospectively investigated the change in nutritional parameters including skeletal muscle mass, occurrence of postoperative complications, and short-term postoperative outcomes in this group. The results were compared between the Gln/Arg/HMB and control groups (79 patients not receiving the Gln/Arg/HMB products). The incidence of all postoperative complications, sputum expectoration disorder, and pleural effusion of grade ≥III was significantly lower in the Gln/Arg/HMB group (62.0% vs. 38.6%, p = 0.001; 44.3% vs. 28.1%, p = 0.020; 27.8% vs. 13.2%, p = 0.011, respectively). The psoas muscle area and postoperative body weight was significantly higher at 1 month and 1 year after surgery in the Gln/Arg/HMB group than in the control group (93.5% vs. 99.9%, p &lt; 0.001; 92.0% vs. 95.4%, p = 0.006). Perioperative amino acid-enriched nutritional therapy may improve the short-term postoperative outcomes, nutritional status, and skeletal muscle mass of esophageal cancer surgical patients.

As critical biocontrol agents, Trichoderma and Metarhizium have demonstrated vast potential in disease prevention and pest control respectively. Current applications, however, are predominantly confined to singular use or simplistic combinations of the two fungi. This study innovatively utilizes Metarhizium and Trichoderma as experimental subjects, employing non-targeted metabolomics to compare the differences in metabolites between co-culture and separate fermentation. The metabolite distinctions in co-culture are meticulously analyzed using sample correlation, least squares discriminant analysis, cluster analysis, and KEGG enrichment analysis. Metabolome sequencing analysis is then applied to compare the co-culture fermentation filtrate with Trichoderma atroviride and Metarhizium anisopliae. Differential metabolite analysis found that co-culture had significantly up-regulated or down-regulated metabolites compared to singular cultures.However,significant metabolite discrepancies are discovered in singular cultures, notably the up-regulated metabolites such as osthole and spirocyclic amine, which have documented antibacterial functions that may prove effective against Fusarium graminearum. Ultimately, the findings from this research contribute to the exploration of synergistic applications of biocontrol fungi and serve as a valuable reference for future development of bio-pesticides for disease and pest control.

A challenge in building large-scale superconducting quantum processors is the precise control and manipulation of the qubit state. However, the crosstalk between the microwave control lines impedes the parallel execution of high-fidelity digital and analog quantum operations. Here, we propose and demonstrate a universal compensation protocol for calibrating the microwave signal crosstalk. We also introduce amplified error sequences to optimize the accuracy. Furthermore, we show a definitive improvement in parallel gate operations with crosstalk cancellation, demonstrating the technique's effectiveness. This work paves the way for superconducting hardware that features automated calibration of microwave crosstalk, leading to enhanced fidelities in multiqubit circuits.

Dye/salt separation has gained increasing attention in recent years, prompting the quest for cost-effective and environmentally-friendly raw materials for synthesis high performance nanofiltration (NF) membrane for effective dye/salt separation. Herein, a high-performance loose structured NF membrane was fabricated by via a simple vacuum filtration method using a green nanomaterial, 2,2,6,6-tetramethylpiperidine-1-oxide radical (TEMPO)-oxidized cellulose nanofiber (TOCNF), by sequentially filtrating larger-size and finer-size TOCNFs on a microporous substrate, followed by cross-linked with trimesoyl chloride. The resultant TCM membrane possesses a separating layer composed entirely of pure TOCNF, eliminating the need for other polymer or nanomaterials additives. TCM membranes exhibits high performance and effective dye/salt selectivity. Scanning Electron Microscope (SEM) analysis shows that the TCM membrane with Fine-TOCNF layer has a tight layered structure. Further characterizations via Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) confirm the presence of functional groups and chemical bonds of the crosslinked membrane. Notably, the optimized TCM-5 membrane exhibits a rejection rate of over 99% for various dyes (Congo red, orange yellow) and 14.2% for NaCl, showcasing a potential candidate for efficient dye wastewater treatment.

Chemical flooding methods are used to recover the remaining oil after water flooding, and surfactant-polymer (SP) flooding is an important chemical flooding technology. It is of great significance to design and screen high-performance oil displacement agents in order to overcome the increasingly challenging high temperature (&gt;70 ℃) and high salinity (>10,000 mg/L) reservoirs. Based on the characteristics of high temperature (70 ℃) and high salinity (151,000 mg/L) in the Qinghai Gasi reservoir, the performance of the SP flooding system was studied. This study considered interfacial tension, emulsification, viscosity, compatibility, and oil displacement efficiency. The selected formula demonstrated high resistance to both salinity (151,000 mg/L) and temperature (70 ℃), characterized by a low oil-water interfacial tension (10-2 mN/m) and high viscosity (18.13 mPa.s). After water flooding achieved an oil recovery rate of 64.64%, the subsequent replacement rate of crude oil increased by 26.95%, confirming that SP flooding can be used as a technology for enhancing oil recovery in high-temperature, high-salinity reservoirs represented by Qinghai Gasi reservoirs.

In this review, we outline our current understanding of the mechanisms involved in the absorption, storage, and transport of dietary vitamin A to the eye, the trafficking of rod opsin protein to the photoreceptor outer segments, which encompasses the logistical backbone required for visual function. Two key mechanisms of this process are emphasized in this manuscript: Ocular and systemic vitamin A membrane transporters, and rhodopsin transporters. Understanding the complementary mechanisms responsible for the generation and proper transport of the retinylidene opsin to the photoreceptor outer segment will eventually shed light on the importance of genes encoded by these proteins, and their relationship on normal visual function and in the pathophysiology of retinal degenerative diseases.

Omicron SARS-CoV-2 variants have dominated the strains of COVID-19 circulating worldwide for the last two years. Although the mortality rate of the COVID-19 Omicron variants is only approximately half that of previous variants, vaccines effective against Omicron are needed. Demonstrating that a SARS-CoV-2 vaccine can protect against Omicron in an in vivo infection model, particularly in that of Syrian hamsters, is important for the preclinical characterization of SARS-CoV-2 vaccines. Here, we report on the evaluation of W-PreS-O for its ability to protect Syrian hamsters against infection by Omicron. W-PreS-O is a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron adsorbed to aluminum hydroxide. The Syrian hamsters were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo), and then they were infected with Omicron BA.1. Non-infected and non-vaccinated animals served as controls. Neutralizing antibody (nAB) titers, weight, lung symptoms (i.e., edema and pneumonia index), and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. W-PreS-O-vaccinated hamsters developed robust nABs against Omicron, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. Our data provide compelling evidence demonstrating that the W-PreS-O vaccine has protective effect against Omicron in a Syrian hamster in vivo infection model. W-PreS-O is therefore a highly promising candidate vaccine for Omicron infections, and it should be further evaluated in clinical studies.

Introduction: Parkinson’s disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce. Methods: Demographic and treatment data of a cohort of PD carriers of recessive genes (9 homozygous or compound heterozygous PRKN carriers, 4 Heterozygous PRKN carriers and 3 biallelic PINK1 carriers) were evaluated. Results: The average Levodopa Equivalent daily dose (LEDD) was 806.8±453.5 (range 152-1810) in PRKN carriers and 765±96.6 (range 660-850) in PINK1 carriers. The majority responded to low/moderate doses of Levodopa. The response to Dopamine Agonists (DA) was often favorable both as initial and longitudinal therapy. 8/13 PRKN and 1/3 PINK1 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate Levodopa or DA. Conclusions: In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any Levodopa treatment decades after disease initiation. DA or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments will be further discussed.

The study evaluated the regenerative responses of the lacrimal functional unit (LFU) after Lacrimal Gland (LG) ablation. The LG of Wistar rats were submitted to G1) partial LG ablation, G2) partial ablation and transplantation of an allogeneic LG, or G3) total LG ablation, (n=7-10/group). The eye wipe test, slit-lamp image, tear flow, and histology were evaluated. RT-PCR analyzed inflammatory and proliferation mediators. The findings were compared to naïve controls after 1 and 2 months (M1 and M2). G3 presented increased corneal sensitivity, and the 03 groups have shown corneal neovascularization. Histology revealed changes in LG, and corneal inflammation. In the LG, there was an increase in MMP-9 mRNA of G1 and G2 at M1 and M2 and RUNX-1 at M1 and M2 in G1 and RUNX-3 mRNA at M1 in G1, and in G2 at M2. TNF-α mRNA rose in the corneas of G1 and G2 at M2. There was an increase in the IL-1β mRNA in the Trigeminal Ganglion of G1 at M1. Without changes in tear flow or evidence of LG regeneration, LG ablation or grafting are unreliable models for dry eye or LG repair in rats. The surgical manipulation extended inflammation to the LFU.

Pregnancy is a complex biological process which is associated with significant metabolic and hemodynamic changes of the maternal body which allow a normal fetal growth. The inability to adapt to these changes can affect the cardiovascular health. During pregnancy, women may experience mood swings, anxiety and emotional ambivalence. These symptoms can lead to stress and have a negative impact on the mental well-being of expectant mothers. It is crucial to know the aspects that can influence the development of cardiovascular problems among pregnant women in order to manage these cases properly. The current narrative review explores and summarizes the evidence regarding the impact of stress and anxiety on cardiovascular health in pregnant women. Understanding the physiological adaptations that the body undergoes throughout pregnancy is crucial for educating and supporting individuals as well as healthcare professionals. This enables them to recognize any risk factors or pathological conditions that may exacerbate pregnant women's health. In order to reduce maternal morbidity and mortality from cardiovascular disease, a psychological and cardiovascular risk factor screening that is done either before or during pregnancy may be able to identify situations that call for particular medical and/or psychological therapies.

Gardasil 4, a human papilloma virus vaccine, has been shown to protect against various cancers, including cervical cancer. Common side effects include injection site pain, fever, headaches, and muscle aches. In some individuals, the severe side effect of postural orthostatic tachycardia syndrome (POTS) has been reported. POTS is characterized by the abnormal response of lightheadedness, blurry vision, and dizziness while transitioning to an upright posture. POTS predominately affects women, with more than eighty-five (85) percent of POTS patients being female. POTS on average, takes five years and eleven months to receive the diagnosis. Additionally, ​A strong association between POTS and Ehlers Danlos Syndrome Type III (EDS) exists. Eighty (80) percent of patients with EDS have POTS. This severe side effect dictates that providers need to be aware of this strong association of HPV vaccinations and POTS. ​In this report we will present a case of a young women with a past medical history significant for EDS type III who was diagnosed with POTS after receiving Gardasil 4 vaccination. This case demonstrates the need for physicians to be aware of the association of POTS with EDS type III and HPV vaccination. Physician awareness of the associations, signs and symptoms of POTS and earlier testing at the first presentation of signs and symptoms will limit the negative impact on patient’s quality of life.

Recent events concerning jet fuel contamination of drinking water have shown that we need a better understanding of the effects of ingested jet fuel. To this end, a reproductive study with in-gested jet fuel in rats was undertaken with relatively high concentrations of Jet Propellant (JP)-5 along with a human estrogen receptor activation in vitro assay using JP-5, JP-8, and an alternative jet fuel derived from the camelina plant to help evaluate potential effects of ingested jet fuel. Results of the in vivo study provided evidence that JP-5 can act as an endocrine disruptor, with specific observations including altered hormone levels with JP-5 exposure (significantly lower estradiol levels in male rats and significantly increased Dehydroepiandrosterone levels in females), indi-cations of abnormal estrous cycles, and a decreased male/female offspring ratio. The in vitro hormone receptor activation assay indicated JP-5 and JP-8 are capable of upregulating human estrogen receptor (ER) activity, while the alternative jet fuel derived from the camelina plant was not active in the ER assay. The jet fuels were not able to activate androgen or glucocorticoid re-ceptors in further in vitro assays. These results infer potential endocrine disruption associated with JP-5, with activation of the estrogen receptor as one potential mechanism of action.

Blocking the interaction of the SARS-CoV-2 spike protein with the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim in this study was to explore the efficacy of TCM treatments for SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. The antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis was found to be effective against SARS-CoV-2 infection through affecting the interaction of viral spike protein with the hACE2 protein. The active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside, respectively, found in S. baicalensis, exhibited strong inhibitory activities, targeting the viral spike protein or hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors of the interaction of the Omicron spike protein and hACE2 receptor from S. baicalensis. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed.

TAU is the main disease driver in Alzheimer’s and many other sporadic and genetic tauopathies. TAU is differently spliced, the role of individual splice-isoforms unclear. Murine Mapt-KO mice are healthy, and protected from Alzheimer’s, but no such case has been reported in humans. Using gnomad database, we here demonstrate that the only isoform expressed during fetal human brain development is intolerant to mutation, while other brain and peripheral nervous system TAU isoforms are dispensable. With TAU targeted therapies for Alzheimer’s and other tauopathies on the rise, we caution that TAU is essential human brain development.

Shiga toxin-producing Escherichia coli (STEC) are notorious foodborne pathogens capable of causing severe diarrhea and other life-threatening complications in humans. Cattle remain a major reservoir and asymptomatic carriers of STEC. In reservoir animals, the rectoanal junction (RAJ) serves as the primary colonization site of STEC playing a critical role in its transmission to humans through contaminated food sources. However, the molecular mechanisms behind the adaptation of STEC in the RAJ of the asymptomatic reservoir host and its subsequent infection of human colonic epithelial cells in an event of a foodborne transmission to cause diarrhea remain largely unexplored. This study aimed to unravel the intricate dynamics of STEC O157:H7 serotype in these two distinct host environments: bovine RAJ cells and human colonic epithelial cells, during initial colonization. In this context, comparative transcriptomics analysis was employed to investigate the differential gene expression profiles of STEC O157:H7 during its interaction with these cell types. The bacterial cells were cultured under controlled conditions to simulate the microenvironments of both bovine RAJ and human colonic epithelial cells. Using high-throughput RNA sequencing, we identified key bacterial genes and regulatory pathways that were significantly modulated in response to each specific host environment. Our findings reveal distinct expression patterns of bacterial genes involved in virulence, including adherence, metal iron homeostasis and stress response in STEC O157:H7 grown in bovine RAJ cells as op-posed to human colonic epithelial cells six hours post-infection. Additionally, the comparative analysis highlights the potential role of certain genes in host adaptation and tissue-specific pathogenicity. Furthermore, this study sheds light on the potential factors contributing to the survival and persistence of STEC O157:H7 in the bovine reservoir, and its ability to colonize in-testinal epithelium and cause disease in humans.

Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4+ T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD+ T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.

Few studies have examined the pros and cons of integrated TB and HIV service delivery in public healthcare facilities, and even fewer have proposed conceptual models for improved integration. This study intends to fill that vacuum by outlining the development of a facility-based paradigm for integrating TB, HIV and patients services. The design of the proposed model were in stages that involved the evaluation of existing TB-HIV integration model and synthesis of both quantitative and qualitative data from the study sites which were selected public healthcare facilities at both rural and peri-urban settings in Oliver Reginald (O.R) Tambo District Municipality in Eastern Cape, South Africa. Secondary data on 2009-2013 TB-HIV clinical outcomes were obtained from multiple sources for quantitative analysis. Qualitative data involved focus group discussions among patient and heath care staff, which was thematically analysed. The development of a possibly better model and validation of this model show that the district's health system was reinforced by the model's guiding principles, which placed a strong emphasis on inputs, processes, outcomes, and integration effects.The model is adaptable to different healthcare delivery systems but will require support from healthcare stakeholders and professionals to be successful.

One of the most used markers of cancer stem cells in several cancers, including colorectal cancer and breast cancer, is CD44. CD44 is a glycoprotein that traverses the cell membrane and binds to many ligands including hyaluronan resulting in activation of signaling cascades. Several reports have shown conflicting data on the expression of CD44 and that the expression depends on modes of investigations and subtypes of cancers. In addition, the correlation between CD44 expression and drug resistance, immune infiltration, EMT, metastasis and patients prognosis in several cancer types remains unclear. This study investigated CD44 expression in several cancers and explored its relationship with tumorigenesis using various publicly available databases, including The Cancer Genome Atlas, GEPIA, Oncomine, Genomics of Drug Sensitivity in Cancer and Tumor Immune Estimation Resource. Our analysis reveals that CD44 is differentially expressed in different cancers. CD44 expression is significantly associated with cancer patients’ survival in gastric, pancreatic and colorectal cancers. In addition, CD44 expression is closely linked with immune infiltration and immune suppressive features in pancreatic, colon adenocarcinoma and stomach cancer. High CD44 expression was significantly correlated with the expression of drug resistance-, EMT- and metastasis- linked genes. Tumors expressing high CD44 have higher mutation burden and afflict older patients than tumors expressing low CD44. Cell lines expressing high CD44 are more resistant to anti-cancer drugs compared to those expressing low CD44. Protein-protein interaction investigations and functional enrichment analysis showed that CD44 interacts with gene products related to cell-substrate adhesion, migration, platelet activation, and cellular response to stress. KEGG pathway analysis revealed that these genes play key roles in biological adhesion, cell component organization, locomotion, G-α-signaling and the response to stimulus. Overall, this investigation reveals that CD44 play significant roles in tumorigenesis, can be used as a prognostic biomarker in several cancers and can be therapeutically targeted in cancer therapy.

Chronic gastro-abdominal pain with altered bowel habits are associated with pathologies including gastroenteritis, autoimmune and inflammatory bowel disease, and irritable bowel syndrome (IBS). In IBS, diagnostic evidence of infection or inflammation are absent, yet symptoms nonetheless include chronic abdominal pain and alterations of stool frequency and consistency, with most common subtypes including diarrhea-predominant (IBS-D) or constipation predominant (IBS-C). [1, 2] IBS is a common clinical complaint in westernized nations, with females more frequently diagnosed than males [3]. Obesity is also associated with increased likelihood of chronic pain [4], and is associated with intestinal dysbiosis, and systemic inflammatory signatures [5]. Improving personalized medicine therefore requires patient stratification based on a combination of biological factors contributing to the individual’s symptom and biomarker spectrum. The “buffy coat” method isolates leukocytes and PBMCs from whole blood, comprises the immune cell population in peripheral blood. These cells are relatively inactive but are primed to respond to generalized and localized immune activation signals; they are under active investigation as diagnostic biomarkers [6]. Collection of buffy coat is a standard method in clinical laboratories; detection of immune activation via RNA expression biomarkers will be informative of differential biological response, and be tractable to collect in clinical settings. Results of differential expression, pathway analysis, and cell-type abundance analysis from buffy coat RNA, is presented here using variables for BMI, Gender, and IBS-subtype from publicly available Nanostring RNA expression and phenotypic data from the NCBI GEO database.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose dependent peak viral loads between days 2 and 5 post infection; and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assays lower limit of quantitation and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasures development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

Bicycle transport stands at the forefront of sustainable mobility initiatives, a cornerstone of European Union policy. While support for cycling is crucial, its advancement hinges upon the presence of high-quality, secure infrastructure for cyclists. Safety emerges as a paramount concern, influencing the viability of cycling as a mode of transportation, yet its perception varies among user demographics. Considering this, this article endeavours to examine and contrast cycling infrastructure across various European nations, alongside analysing statistics pertaining to fatal traffic accidents involving cyclists. In our paper, we have chosen the Netherlands as a representative of building quality cycling infrastructure with many years of experience, and two countries that are developing conditions for cyclists, Slovakia and Poland. We have applied a correlation between the length of the transport infrastructure and the number of cyclists killed. The findings point to the substantial correlation between the quality of cycling infrastructure and the incidence of accidents. This correlation underscores the pressing need for robust infrastructure development and safety measures to bolster cycling as a safe and viable transportation option. We have employed the Shapiro-Wilk test for normal distribution to verify the input data and process the Pearson correlation to investigate the correlation between cycling infrastructure and road accident fatalities of cyclists.

This survey of research literature is an overview of the current state of science addressing DSM-5 diagnostic criteria as it relates to identifying Autism Spectrum Disorder (ASD) in young children. Selected sources are of high quality and have been published since 2020 in peer-reviewed journals relevant to children’s health. The narrative is organized from the earliest to the most recent publications and is divided into sections around categories and themes that highlight the main arguments, findings, and controversies identified by researchers. There are indications in the literature that while ASD can be identified and differentiated from other developmental disorders in young children, doing so requires that clinicians who have relied on the DSM-5 should also use multiple measures, including other formalized screening tools as assessments that gather observational input from parents and caregivers, as well as findings from physical examinations, laboratory investigations, and magnetic resonance imagining (MRI). This high level of corroboration points to an emerging diagnosis paradigm through which transdiagnostic approaches to early diagnosis and intervention may exist.

This paper aims to demonstrate how the detection of communities for epidemiological networks can be used to reduce the dimensionality of optimal control problems. A range of planted partition stochastic blockmodels are generated, where the underlying communities in the model vary in detectability. A high-performance computing workflow is then used to simulate and estimate reduced model dynamics for the networks, which in turn is used to find optimal control solutions.

Non-isocyanate polyurethane synthesis by non-Sn catalysis is an essential challenge toward green polyurethane synthesis. Bismuth compounds are attractive candidates due to their low cost, low toxicity, and availability to urethane chemistry. We applied various Bi catalysts to the self-polycondensation of a bishydroxyurethane monomer and found BiCl3 to be an excellent catalyst through optimization. The catalytic activity and price of BiCl3 are comparable to those of Bu2SnO, while its toxicity is significantly low. BiCl3 is, therefore, a promising alternative to Sn-based catalysts in non-isocyanate polyurethane synthesis.

Dynamic virtual testing by Hardware in the Loop (HIL) real time simulation systems is common to minimize physical tests to validate and verify control algorithms, logics and software, under normal and emergency conditions. The accurate but costly HIL models setup activities could have an extended use to simulate faulty conditions that are seldom observable in the real system, yet they must be detected in advance and recognized. Data driven diagnostic methods have reached a mature development, in various sectors, proving effective in early detecting slowly varying deviations from nominal patterns of signals, even without a priori knowledge of their nature and behavior. These methods rely on vast amount of data logged from real systems that are ever and ever richer of monitoring telemetries that are worth being exploited. However, due to the usually reliable and safe systems being managed, it is often difficult to collect enough data on anomalous situations to validate fault detection and isolation and limit false positives. HIL model-based simulations allow generating and observing operational domains or transients rarely observed in real operations. This allows identifying the signals that are most correlated to faults and that could be selected to setup data-based diagnostic models of parts or subsystems, which are more suitable than the whole HIL model for online diagnostics, as well as to identify the features and trends that are most symptomatic of anomalous conditions.

The multiphase motors due to their reliability find new areas of application in the industry and transportation. Developing of any system with multiphase motors at first requires elaborate model of the system, define control mode and controllers. The model of control system for the six-phase drive is based on its conventional d-q mathematical model and indirect field-oriented control. Simulink model of six-phase drive with indirect field-oriented control and simulated with two types PID and PID fuzzy controllers. The simulation results, reflecting step response and provided speed reference law as well as load application at constant speed, are presented and analyzed. Fuzzy controller with 49 rules is considered and applied. Six-phase electric drive with field-oriented control at well-tuned PID controller has good step response specifications: settling time 0.13 s at starting without load, step response has no overshoot, small about 1 % short time decrease of speed at load of 5 Nm application. The system employing PID fuzzy controller shows slightly better results in response to torque application: the decrease in speed 1 % is eliminated in shorter time. Simulation results indicate the robustness of both systems with six-phase drive to disturbance and provide high quality transient specifications at determined reference speed.

Heterometallic rare-earth clusters have garnered much attention because of their interest-ing solid-state structures and versatile applications in catalysis and material and polymer chemistry over the last four decades. Particular interest is rare earth–transition metal co-ordination compounds that behave as single-molecule magnets (SMMs) because of their potential use in information storage, spintronic devices, and magnetic refrigeration sys-tems. Another implementation involves using lanthanide clusters in luminescent-based sensing for environmental protection and security screening or in photocatalytic energy conversion reactions. Heterometallic rare earth complexes offer the promise of catalytic performance of many organic reactions due to their high oxygenophilicity, Lewis acidity, high coordination numbers, and ability to change the coordination environment quickly. Therefore, they are commonly applied as catalysts in asymmetric synthesis, oxidation re-actions, and CO2 conversions or as initiators in ring-opening polymerization and copoly-merization of cyclic monomers. They are also attractive single-source molecular precur-sors for functional inorganic materials. This review focused on the unique features and properties of the heterometallic rare earth complexes, which are closely correlated with their molecular structure. Our summary is a valuable resource, providing researchers with an insightful exploration of the heterometallic rare-earth complexes that demonstrated multimetallic synergy and cooperativity effects in various applications.

The inherited ‘EIA’ process at Brexit is based on a ‘Project’ period from Inception tothe start of construction works. The ‘Incompleteness’ of the process covers andidentifies stages that will impact on the environmental cycle: construction period,operational life, de-commissioning and a return to acceptable environmental footprint.A master environment structure-plan framework is required to commence with theupgrading of the complete ‘EIA’ process, embracing separate limbs for the UK’spriority environmental targets for climate change, and other major adverse effectswhich result in serious ‘harm’ to the UK environment. The identification of the processfor ‘incompleteness’ requires effective sustainability, and inclusion of effectivemanagement tools, for the essential ‘monitoring/control/recording’ proceduresthroughout the project life and the natural environmental cycle. This will allow theopportunity for a new approach to a structured ‘Suite of EIAR Directives’, to enable a‘EIAR’ regime that ‘will remain fit and proper for UK purpose’.

Regardless of the SARS-CoV-2 pandemic containment, it remains paramount to comprehensively understand its underlying mechanisms to mitigate potential future health and economic impacts, comparable to those experienced throughout the course of the pandemic. The angiotensin-converting enzyme 2 (ACE2) provide anchorage for SARS-CoV-2 binding, thus implicating that ACE and ACE2 might contribute to the variability in infection severity. This study aimed to elucidate predisposing factors influencing the disease course among people infected by SARS-CoV-2, focusing on angiotensin-converting enzyme (ACE) and ACE2 polymorphisms. Notably, despite similar demographics and comorbidities, COVID-19 patients exhibit substantial differences in prognosis. Genetic polymorphisms in ACE and ACE2 have been implicated in disease progression, prompting our investigation into their role in COVID-19 evolution. Using next-generation sequencing (NGS), we analyzed ACE and ACE2 genes in a sample group comprising six subjects infected by SARS-CoV-2. Our findings revealed a correlation between specific polymorphisms and COVID-19 outcomes. Specifically, ACE and ACE2 intronic deletions were observed in all deceased patients, suggesting a potential association with mortality. These results highlight the significance of genetic factors in shaping the clinical course of COVID-19, emphasizing the importance of further research into the impact of genetic variations on COVID-19 severity.

Chaga (Inonotus obliquus) is a pathogenic fungus that grows mostly on birch species (Betula pendula and B. pubescens) and has traditionally been used as an anti-cancer medicine. The study aimed to compare the chemical composition and cytotoxic activity of chagas growing on both Betula spp. on various cancer cell lines. The freeze dried extracts contained triterpenes inotodiol, lanosterol betulin and betulinic acid typical to conks growing on Betula species. The cytotoxic activity of chaga growing on Betula pendula and B. pubescens 80% ethanolic extracts against thirty-one human cancer cell lines has been evaluated by a sulforhodamine B assay. The strongest inhibitions were observed with chaga (growing on B. pendula) extract on the HepG2 and CAL-62 cell line, and with chaga (from B. pubescens) extract on HepG2 cell line, with IC50 values of 37.71, 43.30, and 49.99 μg/mL, respectively. The chaga extracts from B. pendula exert somewhat stronger effects on most cancer cell lines studied than B. pubescens extracts. This study highlight the potential of chaga as a source of bioactive compounds with selective anti-cancer properties, encouraging further exploration of its therapeutic mechanisms and potential applications in cancer treatment.

In the present study, a multilayer high barrier thin blown film based on a polybutylene adipate terephthalate (PBAT) blend with polyhydroxyalkanoate (PHA), and composed of four layers, including a cellulose nanocrystals (CNC) barrier layer and an electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) hot-tack layer, was characterized in terms of surface roughness, surface tension, migration, mechanical and peel performance, barrier properties and disintegration rate. The results showed a material with a smooth surface. The overall migration test showed that the material was suitable for its use as a food contact layer. The addition of the CNC interlayer had a significant effect on the mechanical properties of the system, drastically reducing the elongation at break and, thus, the flexibility of the material. However, the material retained its elastic modulus and tensile strength. The CNC coating had a negative impact on the peeling strength, weakening the inherently strong interlayer adhesivity of the electrospun PHBV fibers. The multilayer had a good barrier to water vapor, and especially to oxygen, with its permeance reduced by up to a 90 % when the CNC layer was present. Finally, the monolayer blend film disintegrated in a period of less than 55 days in a laboratory-scale composting experiment, while the multilayer system disintegrated in 60 days. Overall, the multilayer system formed a fully compostable structure with great potential for use in food packaging applications.

Delta 9 tetrahydrocannabinol (Δ-9-THC or THC), the primary psychoactive constituent of marijuana, has been found to affect the human body in a variety of ways. According to the Substance Abuse and Mental Health Services Administration (SAMHSA) of the U.S. Department of Health and Human Services, the amount of THC in marijuana has steadily climbed over the past few decades, with today's marijuana having three times the concentration of THC compared to 25 years ago. Inhalation is a major route of exposure, allowing substances to enter the body via the respiratory tract. Therefore, it is imperative to understand the molecular underpinning of THC exposure in the lung epithelium, as lung cells receive significant amounts of THC during marijuana smoking. In this study, the transcriptional alterations caused by various concentrations of THC in non-cancerous human bronchial epithelial cell line (BEAS-2B) were studied. THC exposure (0, 800, 1000, 1200, and 1500 ng/mL) caused a significant dose-dependent decrease in cell viability after 24-hour exposure. Transcriptome analysis showed a distinct dose-dependent response. HIF-1 signaling, ferroptosis, AMPK signaling, and immunogenic pathways were activated by upregulated genes associated with dosing concentration of THC. Glutathione and fatty acid metabolic pathways were significantly altered by THC-dependent downregulated genes. and downregulated genes and their associated pathways in BEAS-2B cells. Ingenuity Pathway Analysis revealed several top canonical pathways altered by THC exposure, among which ferroptosis, NRF-2 mediated oxidative stress response, caveolar mediated endocytosis (loss of cell adhesion to the substrate), tumor microenvironment, HIF1alpha signaling, and the unfolded protein response pathways were the major pathways affected. The top genes that were significantly altered as a result of THC exposure were HMOX1, CDK7, HLA-C, and SLC39A4. Present results suggested that THC exposure can induce a variety of effects, including cell death, which may involve ferroptosis and the NRF-2 signaling pathway. Moreover, the Δ-9-THC-induced cell death was ameliorated by inhibiting the ferroptosis pathway. In contrast, the ferroptosis agonist exacerbated the cell death process, suggesting that Δ-9-THC utilizes the ferroptosis pathway to induce cell death in bronchial epithelial cells.

Chemotherapy treatment against pancreatic ductal adenocarcinoma (PDAC) is thwarted by tumoral activation of multiple therapy-resistance pathways. The growth hormone (GH) – GH receptor (GHR) pair is a covert driver of multimodal therapy resistance in cancer, and is overexpressed in PDAC tumors, yet the therapeutic potential of targeting the same has not been explored. Here, we report that GHR expression is a negative prognostic factor in patients with PDAC. Combinations of gemcitabine with different GHR antagonists (GHRAs) markedly improve therapeutic outcomes in nude mice xenografts. Employing cultured cells, mouse xenografts, and analyses of the human PDAC transcriptome, we identified that attenuation of the multidrug transporter and epithelial-to-mesenchymal transition programs in the tumors underlie the observed augmentation of chemotherapy efficacy by GHRAs. Moreover, in human PDAC patients, GHR expression strongly correlates with a gene signature of tumor-promotion and immune-evasion, which corroborate with that in syngeneic tumors in wild-type vs. GH transgenic mice. Overall, we found that GH action in PDAC promoted a therapy-refractory gene signature in vivo, which can be effectively attenuated by GHR antagonism. Our results collectively present a proof of concept towards considering GHR antagonist to improve chemotherapeutic outcome in the highly chemoresistant PDAC.

There are different ways to analyse energy absorbance (EA) in the human auditory system. In previous research, we developed a complete finite element model (FEM) of the human auditory system. In this mentioned work, the external auditory canal (EAC), middle ear, and inner ear (spiral cochlea, vestibule, and semi-circular canals) were modelled based on human temporal bone histological sections. Multiple acoustic, structure and fluid-coupled analyses were conducted using the FEM to perform harmonic analyses in the 0.1–10 kHz range. Once the FEM had been validated with published experimental data, the FEM numerical results were used to calculate the EA or energy reflected (ER) by the tympanic membrane. This EA was also measured in clinical audiology tests which were used as a diagnostic parameter. A mathematical approach was developed to calculate the EA and ER, with numerical and experimental results showing adequate correlation up to 1 kHz. Another published FEM had adapted its boundary conditions to replicate experimental results. Here, we recalculated those numerical results by applying the natural boundary conditions of human hearing and found that the results almost totally agreed with our FEM. This boundary problem is frequent and problematic in experimental hearing test protocols: the more invasive they are, the more the results are affected. One of the main objectives of using FEMs is to explore how the experimental test conditions influence the results. Further work will still be required to uncover the relationship between the middle ear structure and EA to clarify how to best use FEMs. Moreover, the FEM boundary conditions must be more representative in future work to ensure their adequate interpretation.

Pancreatic Ductal Adenocarcinoma (PDAC) is the most frequent infiltrating type of pancreatic cancer. The poor prognosis is due to the absence of specific biomarkers, aggressiveness and treatment resistance. PDAC is a deadly malignancy bearing distinct genetic alterations, the most common being those that cause cancer-causing versions of the KRAS gene. Cannabigerol (CBG) is a non-psychomimetic cannabinoid with anti-inflammatory property. Regarding CBG anticancer ef-fect, up to now there are only few evidence in human cancers. We investigated CBG effects on PDAC cell lines, PANC-1 and MIAPaCa-2. It was investigated CBG activity on cell viability, cell death and its effect of EGFR-RAS-associated signalling. Moreover, the potential synergistic effect of CBG in combination with gemcitabine (GEM) and paclitaxel (PTX) was investigated. MTT was applied to investigate CBG effect on PDAC cell lines viability. Annexin-V and Acridine Orange staining followed by cytofluorimetric analysis and Western blot were used to evaluate CBG effect on cell death. Modulation of EGFR-RAS-associated pathways was determined by Western Blot analysis and Milliplex multiplex assay. Moreover, by MTT data and Synergy finder software analysis the effect of the combination of CBG and chemotherapeutic drugs, was determined.

Gastric mixing relies both on enzymatic reactions and mechanical solicitations through antral contraction waves (ACWs). This work aims at discussing the influence of ACWs frequency and digesta viscosity on human gastric mixing efficiency by comparison with that of a soft elastic reactor (SER), that induces mixing by vibration of its wall in a similar way as ACWs promote stomach motility. The SER mixing curve was considered in order to determine the flow regime reached during gastric mixing. The number of contractions required to achieve homogenization was found to depend on the viscosity of the stomach content and the ACWs amplitude. Moreover, it was deduced from the same range of SER and ACWs operating points that the mechanical solicitation provided by human peristalsis was low and that gastric mixing was confined in laminar regime. Further efforts are needed to investigate the role of other physiological processes such as gastric secretions and emptying in overall gastric mixing performance.

Objectives: The term "inflammageing” describes the process of inflammation-induced aging that leads living cells to a state of permanent cell cycle arrest due to chronic antigenic irritation. This in vitro study aimed to shed light on the mechanisms of “inflammageing” on human oral cells. Methods: Primary cultures of human gingival fibroblasts (hGFs) were exposed to variable pro-inflammatory stimuli, including lipopolysaccharide (LPS), Tumor Necrosis Factor-alpha (TNFa), and gingival crevicular fluid (GCF) collected from active periodontal pockets of systemically healthy patients. Inflammageing was studied through two experimental models, employing either late-passage (“aged”) cells (p.10) that were exposed to the pro-inflammatory stimuli or early-passage (“young”) cells (p.1) continuously exposed during a period of several passages (up to p.10) to the above-mentioned stimuli. Cells were evaluated for the expression of beta-galactosidase activity (histochemical staining), senescence-associated genes (qPCR analysis), and biomarkers related to a Senescence Associated Secretory Phenotype (SASP), through proteome profile analysis and bioinformatics. Results: A significant increase (p<0.05) of beta-galactosidase-positive cells was observed after exposure to each pro-inflammatory stimulus. The senescence-associated gene expression included upregulation for CCND1 and downregulation for SUSD6, and STAG1, a profile typical for cellular senescence. Overall, pro-inflammatory priming of late-passage cells caused more pronounced effects in terms of senescence, than long-term exposure of early-passage cells to these stimuli. Proteomic analysis showed induction of SASP, evidenced by upregulation of several pro-inflammatory proteins (IL-6, IL-10, IL-16, IP-10, MCP-1, MCP-2, M-CSF, MIP-1a, MIP-1b, TNFb, sTNF-RI, sTNF-RII, TIMP-2) implicated in cellular aging and immune responses. The least potent impact on the induction of SASP was provoked by LPS and the most pronounced by GCF. Conclusion: This study demonstrates that long-term exposure of hGFs to various pro-inflammatory signals induced or accelerated cellular senescence with the most pronounced impact noted for the late-passage cells. The outcome of this analyses provides insights into oral chronic inflammation, as a potential confounder of age-related diseases.

Background: Although autophagy is a pro-survival process of tumor cells, in particular conditions and when differently regulated by specific signals it can stimulate cell death. We previously demonstrated that the selective stimulation of the M2 muscarinic receptor subtype (M2 mAChR) negatively controls cell proliferation and survival and causes oxidative stress and cytotoxic and genotoxic effects in both GBM cell lines and GBM stem cells (GSCs). In this work, we have evaluated whether autophagy was induced as a downstream mechanism of the observed cytotoxic processes induced by M2 mAChR activation by the orthosteric agonist APE or the dualsteric agonist N-8-Iper. Methods: To assess the activation of autophagy, we analyzed the expression of LC3B by Western blot analysis and in LC3B-EGFP transfected cell lines. Apoptosis was assessed by Caspases 3 and 9 protein expression. Results: Our data indicate that activation of M2 mAChR by N-8-Iper promotes autophagy in both U251 and GB7 cells lines as suggested by the LC3B-II expression level and analysis of the transfected cells by fluorescence microscopy. Autophagy induction by M2 mAChRs is regulated by the decreased activity of the PI3K/AKT/mTORC1 pathway and upregulated by the pAMPK expression. Downstream autophagy activation, the increase of apoptosis was also observed in both cell lines after treatment with the two M2 agonists. Conclusions: N-8-Iper treatment causes autophagy via pAMPK upregulation, followed by apoptosis in both investigated cell lines. In contrast, the absence of autophagy in APE-treated GSC cells seems to indicate that cell death could be triggered by mechanisms alternative to those observed for N-8-Iper.

We have identified a new human voltage-gated potassium channel (hKv1.3) blocker, NnK-1, in the jellyfish Nemopilema nomurai, based on its genomic information. The gene sequence encoding NnK-1 contains 5,408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is 894 nucleotides long and encodes 297 amino acids, containing five presumptive ShK-like peptides. An electrophysiological assay demonstrated that the chemically synthesized fifth peptide, NnK-1, is an effective hKv1.3 blocker. A multiple sequence alignment with cnidarian Shk-like peptides, which have Kv1.3-blocking activity, revealed that four residues (3Asp, 25Lys, 33Lys, and 34Thr) of NnK-1, together with six cysteine residues, are conserved. Therefore, we hypothesize that these four residues are crucial for the binding of the toxins to voltage-gated potassium channels.

Three tiny bones compose the human ossicular chain: malleus, incus and stapes. Also known as auditory ossicles, they are united by joints in the middle ear cavity of the petrous part of the temporal bone. Completely developed 2 years after birth, the ossicular chain is involved in the physiological process of hearing, by which sound waves from the environment are converted into electrochemical impulses. In the last 500 years, most studies have focussed on the morphogenesis, morphological variability and clinical pathology of the ossicular chain, whilst only a few studies have added relevant knowledge to anthropology and forensic science. The auditory ossicles and the enclosing petrous bone are some of the hardest in the human skeleton. This reflects in a relative resistance to fire. In the post mortem period and in favourable circumstances, the auditory ossicles can fossilize and survive for millions of years. Post mortem loss in skeletal or decomposed remains can be ascribed to their destruction or physical displacement, by either macro-micro-faunal action and/or any other natural or artificial disturbance. Physical displacement is closely connected to the depositional environment of the skeletal remains, such as burial, entombment (sarcophagus, coffin, vault…), submersion or exposure to natural elements. Auditory ossicles can be recovered in situ, or very close to their anatomical location, when the skeletal material has been involved in an archaeological excavation. In the case of accessible or disturbed remains, scavengers may remove the tiny ossicles, and/or they can slip out of the middle ear cavity following skull movements. Entombment offers an effective protection against the displacement of the auditory ossicles, whereas aquatic submersion and aquatic movement almost invariably displace them. The preservation of the human auditory ossicles should be critically considered in the comprehensive context of any forensic investigation on human remains, since it can assist the reconstruction of their taphonomic history. Taphonomic histories of remains can add crucial information to forensic investigations (e.g., the Post Mortem Interval, PMI). The aim of this study, limited by scarce relevant literature, is to discuss the potential role of the ossicular chain, detected by post mortem imaging techniques, as a taphonomical indicator in decomposing and/or skeletonized bodies.

Background Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. Methods: We intravenously administered the clinical product “CL2020” containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020 and 12 received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to 3 CL2020-treated animals to selectively ablate human cell functions. Results: Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Conclusions: Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.

With limited state budget, developed nation public higher education have increased their fees making education expensive for most developing nation students. Some developing nations have set up regional low-cost education hubs to attract developed nation universities to offer their reputable degree programs. However, the intense competition for student enrolment in both has led to the marketisation of education. Students as paying customers need to experience satisfying stress-free teaching and learning to sustain enrolment. With employers increasingly unhappy with the quality of human capital, has the marketisation of higher education led to nominal human capital development? Can substantive human capital be developed in the new normal of marketisation of higher education? An adaptation of randomised control trials was used to measure learning outcomes desired by future employers for two teaching and learning approaches namely students as customers (n=497) and employers as customers (n=355). Findings show both approaches have good learning outcomes with the latter generally more superior. However, the former leads to nominal learning outcomes. This research extends the literature on achieving substantive learning outcomes conducive to employability. Implications for student satisfaction, lecturer professionalism, employability and quality assurance are discussed.

Human disturbance, such as trampling, is an integral component of global change, yet we lack a comprehensive understanding of its effects on alpine ecosystems. Many alpine systems are seeing a rapid increase in recreation, and in understudied regions, such as the Coast Mountains of British Columbia, disturbance impacts on alpine plants remain unclear. We surveyed disturbed (trail-side) and undisturbed (off-trail) transects along elevational gradients of popular hiking trails in the T’aḵ’t’aḵ’múy̓in tl’a In̓inyáx̱a7n region (Garibaldi Provincial Park), Canada, focusing on dominant shrubs (Phyllodoce empetriformis, Cassiope mertensiana, Vaccinium ovalifolium) and graminoids (Carex spp). We used a hierarchical Bayesian framework to test for disturbance by elevation effects on total plant percent cover, maximum plant height and diameter (growth proxies), and buds, flowers, and fruits (reproduction proxies). We found that trampling reduces plant cover and impacts all species, but that effects vary by species and trait, and disturbance effects only vary with elevation for one species’ trait. Growth traits are more sensitive to trampling than reproductive traits, which may lead to differential impacts on population persistence and species level fitness outcomes. Our study highlights that disturbance responses are species-specific, and this knowledge can help land managers minimize disturbance impacts on sensitive vegetation types.

Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) isolates are one of the most difficult pathogens to treat. Cefiderocol, a chlorocatechol-substituted siderophore antibiotic, was approved by the U.S. Food and Drug Administration (FDA) in 2019 indicated for the treatment of infections due to CRAB infections. Despite the initial positive treatment outcomes with this antimicrobial, recent studies reported higher than all-cause mortality rate in patients treated with cefiderocol. The cause(s) behind these outcomes remains unconfirmed. A plausible hypothesis is heteroresistance, a phenotype characterized by the survival of a small proportion of cells in a population seemingly isogenic. Recent results have shown that the addition of human fluids to CRAB cultures leads to cefiderocol heteroresistance. Here we describe molecular and phenotypic analyses of CRAB heteroresistant bacterial subpopulations to better understand the nature of the less-than-expected successful outcomes after cefiderocol treatment. Methods: Isolation of heteroresistant variants of the CRAB strain AMA40 was carried out in cultures supplemented with cefiderocol and human pleural fluid (HPF). Two AMA40 variants, AMA40 IHC1 and IHC2, were subjected to whole genome sequencing and transcriptional analysis to identify mutations and expression changes associated with cefiderocol heteroresistance. The impact of these mutations on the pharmacodynamic activity of cefiderocol was assessed via susceptibility testing, EDTA and boronic acid inhibition analysis, biofilm formation, and static time-kill assays. Results: Heteroresistant variants AMA40 IHC1 and AMA40 IHC2 have 53 chromosomal mutations, of which 40 are common to both strains. None of the mutations occurred in genes associated with high affinity iron-uptake systems or β-lactam resistance. However, transcriptional analyses showed significant modifications in levels of expression of genes associated with these functions. The blaNDM-1 and blaADC-2, as well as various iron-uptake system genes, were expressed at higher levels than the parental strain. On the other hand, the carO and ompA genes’ expression was reduced. One of the mutations common to both heteroresistant strains mapped within pipA, a gene associated with iron homeostasis in other species. Static time-kill assays showed that supplementing cation-adjusted Mueller-Hinton broth with human serum albumin, the main protein component of HPF, considerably reduced cefiderocol killing activity for all three strains tested. Notably, collateral resistance to amikacin was observed in both variants. Conclusions: We conclude that exposing CRAB to fluids containing high HSA facilitates the rise of heteroresistance associated with point mutations and upregulation of genes coding for β-lactamases and biofilm formation.

Prostate cancer contributes to cancer-related deaths globally, and the etiology of this disease is not yet fully understood. While Human Papillomavirus (HPV) has been associated with several types of cancer, including cervical, anal, and oropharyngeal cancer, studies investigating the relationship between HPV and prostate cancer have shown mixed results. This systematic review aimed to evaluate the causative association between HPV and prostate cancer using Bradford Hill's criteria. A comprehensive search of PubMed was conducted, and 60 out of 482 studies were included in the review. The included studies were evaluated based on nine Bradford Hill criteria, and information on the identification and transmission of the virus and potential oncogenic mechanisms was also extracted. The strength of association criterion was not met, and other criteria, such as consistency and coherence, were not fulfilled. However, biological plausibility was supported, and potential oncogenic mechanisms were identified. While some studies have reported the presence of HPV in prostate cancer tissues, the overall quality of evidence remains low, and the association between HPV and prostate cancer is weak. Nevertheless, the prostate is a potential reservoir for the transmission of HPV, and the HPV E6 and E7 oncoproteins and inflammation are likely to be involved in any oncogenic mechanisms. Further studies with a higher level of evidence are needed to establish a definitive link between HPV and prostate cancer.

Hypoxic-ischemic encephalopathy (HIE) secondary to perinatal asphyxia occurs when the brain does not receive enough oxygen and blood. A surrogate marker for ‘intact survival’ is necessary for the successful management of HIE. The severity of HIE can be classified based on clinical presentation, including presence of seizures, using a clinical classification scale called Sarnat staging; however, Sarnat staging is subjective and the score changes over time. Furthermore, seizures are difficult to detect clinically and are associated with a poor prognosis. Therefore, a tool for continuous monitoring on the cot side is necessary, for example, electroencephalogram (EEG) that non-invasively measures the electrical activity of the brain from the scalp. Then, multimodal brain imaging, when combined with functional near-infrared spectroscopy (fNIRS), can capture the neurovascular coupling (NVC) status. In this study, we first tested the feasibility of a low-cost EEG-fNIRS imaging system to differentiate between normal, hypoxic, and ictal states in a perinatal ovine hypoxia model. Here, the objective was to evaluate a portable cot side device and autoregressive (ARX) modelling to capture the perinatal ovine brain states during a simulated HIE injury. So, ARX parameters were tested with a linear classifier using a single differential channel EEG, with varying states of tissue oxygenation detected using fNIRS, to label simulated HIE states in a perinatal ovine hypoxia model. Then, we showed the technical feasibility of the low-cost EEG-fNIRS device and ARX modeling with support vector machine classification for a human HIE case series with and without sepsis. The classifier trained with the ovine hypoxia data labelled ten severe HIE human cases (with and without sepsis) as “hypoxia” group and the four moderate HIE human cases as the “control” group. Furthermore, we showed the feasibility of experimental modal analysis (EMA) based on the ARX model to investigate the NVC dynamics using EEG-fNIRS joint-imaging data that differentiated six severe HIE human cases without sepsis from four severe HIE human cases with sepsis. In conclusion, our study showed the technical feasibility of EEG-fNIRS imaging, ARX modeling of NVC for HIE classification, and EMA that may provide a biomarker to detect sepsis effects on the NVC in HIE.

Human induced pluripotent stem cell (hiPSC)-derived neural cells have been used at the preclinical stage of drug development. As previously reported, hiPSC-derived neurons exhibit greater tolerance to excitotoxicity than that of primary cultures of rodent neurons; however, the underlying mechanisms remain unknown. We therefore investigated the functions of L-glutamate (L-Glu) transporters, the most important machinery used to maintain low extracellular L-Glu concentrations, in hiPSC-derived neural cells. We also clarified the contribution of each L-Glu transporter subtype. At 63 days in vitro (DIV), we detected neuronal circuit functions in hiPSC-derived neural cells by a microelectrode array system (MEA). Exposure to 100 μM L-Glu for 24 hrs did not affect the viability of these 63 DIV neural cells. Pharmacological inhibition of excitatory amino acid transporter 1 (EAAT1) and EAAT2 blocked almost 100% of L-Glu uptake. In this condition, L-Glu exposure dramatically decreased cell viability. These results suggest that in hiPSC-derived neural cells, EAAT1 and EAAT2 are predominant L-Glu transporters, and their uptake potentials are stronger than those of primary cultures of rodent neurons. Furthermore, hiPSC-derived neural cells may be useful for screening drugs that target L-Glu transporters.

It is crucial to immediately curb the spread of a disease once an outbreak is identified in a pandemic. An agent based simulator will enable the policymakers to evaluate the effectiveness of different hypothetical strategies and policies with a higher level of granularity. This will allow them to identify the vulnerabilities and asses the threat level more effectively, which in turn can be used to build resilience within the community against a pandemic. This study proposes a PanDemic SIMulator (PDSIM ) which is capable of modeling complex environments while simulating realistic human motion patterns. The ability of PDSIM to track the infection propagation patterns, contact paths, places visited, characteristics of people, vaccination, and testing information of the population, allows the user to check the efficacy of different containment strategies and testing protocols. The results obtained based on the case studies of Covid-19 are used to validate the proposed model. However, it is highly extendable to all pandemics in general, enabling robust planning for more sustainable communities.

UVA radiation inducing oxidative stress is harmful for the skin cells. The most sensitive are dermal fibroblasts. Exposure of the cells to prolonged UVA radiation induces apoptosis. Although, skin cells have a number of defense mechanisms that protect them against UV-induced oxidative stress, they are insufficient during long-lasting UV exposure. Therefore, there is a need for effective skin protection compounds with cytoprotective and antioxidant properties. One of their sources is Amaranthus cruentus L. seed oil, rich in unsaturated fatty acids, squalene, vitamin E derivatives, and phytosterols. The aim of this study was to evaluate whether Amaranthus cruentus seed oil evokes protective effect on the apoptosis stimulated by UVA radiation in human skin fibroblasts. UVA radiation at an applied dose of 10 J/cm2 caused a significant reduction in the survival of human skin fibroblasts and directed them into apoptosis pathway. Increased expression of p53, caspase 3, and caspase 9 and PARP proteins in UVA-treated fibroblasts suggests the intrinsic mechanism of apoptosis. The application of Amaranthus cruentus seed oil at 0.1% and 0.15% concentrations to UVA-treated cells decreased the expression of these proteins, which was accompanied by increased cell survival. Similarly, the UVA-dependent decrease in expression of p-Akt and mTOR proteins was restored, under the effect of studied oil. The molecular mechanism of this phenomenon is related to the stimulation of antioxidant processes through activation of Nrf2. This suggests that Amaranthus cruentus seed oil stimulate the antioxidant system in fibroblast cells and prevent the effects of UVA-induced oxidative stress and may find application in pharmacy and cosmetology as a sun- protective substance.

For the replacement of lost contractile elements in the treatment of coronary heart disease, the most promising approaches to obtain cardiomyocytes by cardiac differentiation of pluripotent cells. The aim of this work is to develop a technology for the formation of a functional layer of cardiomyocytes differentiated from iPSCs, capable of generating rhythmic activity and synchronous contractions. To accelerate cardiomyocyte maturation, the renal subcapsular transplantation model was used in SCID mice. After explantation, the formation of cardiomyocyte contractile apparatus was assessed by fluorescence and electron microscopy, and calcium ion oscillation in the cytoplasm was assessed by visualization of the fluorescent calcium binding dye Fluo-8. It was shown that human iPSC-derived cardiomyocyte cell layers transplanted (for up to 6 weeks) under SCID mouse kidney fibrous capsules begin to form an ordered contractile apparatus and retain functional activity and the ability to oscillate calcium ion fluxes after explantation from the body.

Generative large language models (LLMs), e.g., ChatGPT, have demonstrated remarkable proficiency across several NLP tasks such as machine translation, question answering, text summarization, and natural language understanding. Recent research has shown that utilizing ChatGPT for assessing the quality of machine translation (MT) achieves state-of-the-art performance at the system level but performs poorly at the segment level. To further improve the performance of LLMs on MT quality assessment, we conducted an investigation into several prompting methods. Our results indicate that by combining Chain-of-Thoughts and Error Analysis, a new prompting method called Error Analysis Prompting, LLMs like ChatGPT can \textit{generate human-like MT evaluations at both the system and segment level}. Additionally, we discovered some limitations of ChatGPT as an MT evaluator, such as unstable scoring and biases when provided with multiple translations in a single query. Our findings aim to provide a preliminary experience for appropriately evaluating translation quality on ChatGPT while offering a variety of tricks in designing prompts for in-context learning. We anticipate that this report will shed new light on advancing the field of translation evaluation with LLMs by enhancing both the accuracy and reliability of metrics. The project can be found at https://github.com/Coldmist-Lu/ErrorAnalysis_Prompt.

Acanthamoeba keratitis (AK) is a blinding corneal infection caused by the protozoan Acanthamoeba. The long-term course of AK suggests the host immunity could not kill Acanthamoeba rapidly. The immune status is still unclear in the late stage of AK. The comparative transcriptome analysis was made based on the bulk RNA sequencing of cornea tissues from AK patients and donors. Differentially expressed genes and enriched signaling pathways were calculated. CIBERSORT algorithm was used for Immune infiltration analysis of cornea tissue between AK and normal controls. A total of 2668 differentially expressed genes, including 1477 upregulated genes and 1191 downregulated genes, were detected. Gene Ontology analysis revealed that the pathways were significantly enriched in leukocyte migration, regulation of T cell activation, the external side of plasma membrane, collagen-containing extracellular matrix, immune receptor activity and cytokine binding. KEGG pathway analysis showed that the pathways were significantly enriched in the cytokine-cytokine receptor interaction, hematopoietic cell lineage and Staphylococcus aureus infection pathway. The immune infiltration profiles varied little between AK and normal controls. Compared with normal tissue, cornea tissue of AK contained a higher proportion of M0 macrophages and CD8 T cells, while resting memory CD4 T cells contributed to a relatively lower portion (P &lt; 0.05). Finally, the expression levels of cell markers and SLAMF7/STAT6 pathway were confirmed by histopathology examinations, RT-qPCR and western blot.

Individual differences in the responsiveness of the brain to transcranial electrical stimulation (tES) is increasingly demonstrated in large variability in the tES effects. Anatomically detailed computational brain models have been developed to address this variability; however, static brain models are not ‘realistic’ in accounting for the dynamic state of the brain. Therefore, human-in-the-loop optimization is proposed in this perspective article based on an extensive systems analysis of the tES neurovascular effects. First, modal analysis was conducted using a physiologically detailed neurovascular model that found stable modes in the 0 Hz to 0.05 Hz range for the pathway for vessel response through the smooth muscle cells, measured with functional near-infrared spectroscopy (fNIRS). tES effects in the 0 Hz to 0.05 Hz range can also be measured with functional magnetic resonance imaging (fMRI)-tDCS data with a maximum TR=10sec. Therefore, we investigated an open-source fMRI-tDCS dataset that used a TR=3.36sec. We found that both the anodal tDCS condition and sham tDCS condition had similar Finite Impulse Response at the region of interest underlying the anode and a remote location, which indicated a global hemodynamic effect of sham tDCS beyond the intended transient sensations. Here, transient sensations can have arousal effects on the hemodynamics so we conducted a healthy case series for black box modeling of fNIRS-pupillometry of short-duration tDCS effects. The block exogeneity test rejected the claim that tDCS is not a 1-step Granger-cause of the fNIRS total hemoglobin changes (HbT) and pupil dilation changes (p<0.05). Also, grey-box modeling using fNIRS of the tDCS effects in chronic stroke showed HbT response to be significantly different (paired-sample t-test, p<0.05) between the ipsilesional and the contralesional hemisphere for primary motor cortex tDCS and cerebellar tDCS which was subserved by the smooth muscle cells. Here, our perspective is that various physiological pathways subserving tES effects can lead to state-trait variability that can be challenging for clinical translation. Therefore, we conducted a case study on human-in-the-loop optimization using our reduced dimension model and a stochastic, derivative-free Covariance Matrix Adaptation Evolution Strategy. Future studies need to investigate human-in-the-loop optimization of tES for reducing inter-subject and intra-subject variability in tES effects.

The ongoing COVID-19 pandemic dictated new priorities in biomedicine research. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is a single-stranded positive-sense RNA virus. In this pilot study, we optimized our padlock assay to visualize genomic/subgenomic regions using formalin-fixed paraffin-embedded placental samples obtained from a confirmed case of COVID-19. SARS-CoV-2 RNA was localized in trophoblastic cells. We also checked the presence of the virion by immunolocalization of its glycoprotein spike. In addition, we imaged mitochondria of placental villi keeping in mind that the mitochondrion has been suggested as a potential residence of the SARS-CoV-2 genome. Indeed, we observed a substantial overlapping of SARS-CoV-2 RNA and mitochondria in trophoblastic cells. This intriguing linkage correlated with an aberrant mitochondrial network. Overall, to our knowledge, this is the first study that provides the evidence of a co-localization of the SARS-CoV-2 genome and mitochondria in SARS-CoV-2 infected tissue. These findings also support the notion that SARS-CoV-2 infection could reprogram mitochondrial activity in highly specialized maternal/fetal interface.

SARS-CoV-2 caused a large outbreak since its emergence in December 2019. The COVID-19 diagnosis became a priority to isolate and treat infected individuals in order to break the contamination chain. Currently, the reference test for COVID-19 diagnosis is the molecular detection (RT-qPCR) of the virus from nasopharyngeal swab (NPS) samples. Although this sensitive and specific test remains the gold standard, it has several limitations, such as the invasive collection method, the relative high cost and the duration of the test. Moreover, the material shortage to perform tests due to the discrepancy between the high demand for tests and the production capacities puts additional constraints on RT-qPCR. Here, we propose a PCR-free method for diagnosing SARS-CoV-2 based on Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling and machine learning (ML) models from salivary samples. Kinetic saliva samples were collected at enrollment and ten and thirty days later (D0, D10 and D30), to assess the classification performance of the ML models compared to the molecular tests performed on NPS specimens. Spectra were generated using an optimized protocol of saliva collection and successive quality control steps were developed to ensure the reliability of spectra. A total of 360 averaged spectra were included in the study. At D0, the comparison of MS spectra from SARS-CoV-2 positive patients (n=105) with healthy healthcare controls (n=51) revealed nine peaks that significantly distinguished the two groups. Among the five ML models tested, Support Vector Machine with Linear Kernel (SVM-LK) provided the best performance on the training dataset (accuracy = 85.2 %, sensitivity = 85.1 %, specificity = 85.3 %, F1-Score = 85.1 %). The application of the SVM-LK model on independent datasets confirmed it performances with 88.9% and 80.8% of correct classification for samples collected at D0 and D30, respectively. Conversely, at D10, the proportion of correct classification fallen to 64.3%. The analysis of saliva samples by MALDI-TOF MS and ML appears as an interesting supplementary tool for COVID-19 diagnosis, despite the mitigated results obtained for convalescent patients (D10).

The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans and cell culture. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. Organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging and to design personalized approaches for prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging paving the way to personalized interventions targeting the biology of aging.

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

Conventionally, eukaryotic mRNAs were thought to be monocistronic, leading to the translation of a single protein. However, large-scale proteomics has led to a massive identification of proteins translated from mRNAs of alternative ORF (AltORFs), in addition to the predicted proteins issued from the reference ORF or from ncRNAs. These alternative proteins (AltProts) are not represented in the conventional protein databases and this “Ghost proteome” was not considered until recently. Some of these proteins are functional and there is growing evidence that they are involved in central functions in physiological and physiopathological context. Based on our experience with AltProts we have got interested in finding out their involvement in development of the SARS-CoV-2 virus, responsible for the 2020 Covid-19 outbreak. Thus, we have scrutinized the recently published data by Krogan and coworkers (2020) on the SARS-CoV-2 interactome with host cells by co-IP in the perspective of drug repurposing. The initial work has revealed the interaction between 332 human cellular RefProts with the 27 viral proteins. Re-interrogation of this data using 23 viral targets and including AltProts, followed by enrichment of the interaction networks, leads to identify 218 RefProts (in common to initial study) plus 56 AltProts involved in 93 interactions. This demonstrates the necessity to take into account the Ghost proteome for discovering new therapeutic targets and establish new therapeutic strategies. Missing the ghost proteome in the drug metabolism and pharmacokinetic (DMPK) drug development pipeline will certainly be a major limitation to the establishment of efficient therapies.

— In a smart healthcare system," Human Activity Recognition (HAR)" is considered as an efficient approach in pervasive computing from activity sensor readings. The "Ambient Assisted Living (AAL)" in the home or community helps the people to provide independent care and enhanced living quality. However, many AAL models are restricted to multiple factors that include both the computational cost and system complexity. Moreover, the HAR concept has more relevance because of its applications, such as content-based video search, sports play analysis, crowd behavior prediction systems, patient monitoring systems, and surveillance systems. This paper attempts to implement the HAR system using a popular deep learning algorithm, namely "Recurrent Neural Network (RNN)" with the activity data collected from smart activity sensors over time, and it is publicly available in the "UC Irvine Machine Learning Repository (UCI)". The proposed model involves three processes: (1) data collection, (b) optimal feature learning, and (c) activity recognition. The data gathered from the benchmark repository was initially subjected to optimal feature selection that helped to select the most significant features. The proposed optimal feature selection method is based on a new meta-heuristic algorithm called "Colliding Bodies Optimization (CBO)". An objective function derived from the recognition accuracy has been used for accomplishing the optimal feature selection. The proposed model on the concerned benchmark dataset outperformed the conventional models with enhanced performance.

In this study, two heterogeneous fluorescence immunoassays using CdSe/ZnS quantum dot (QD) to label anti-progesterone antibody (P4Ab) for the determination of progesterone (P4) were performed in the wells of a 96-well microtiter plate. First, P4Ab was conjugated to hydrophilic CdSe/ZnS QDs via ethyl-3-(dimethylaminopropyl) carbodiimide(EDC)-N-hydroxysuccinimide) chemistry(NHS) (QDs-P4Ab conjugates). The QDs-P4Ab conjugate was employed as a second antibody in a sandwich assay, where the P4Ab was immobilized onto the 3-aminopropyltrimethoxysilane (APTMS) sol-gel membrane of the wells of a 96-well microtiter plate, and P4 was bound between the immobilized P4Ab and the QDs-P4Ab conjugate. In this assay, the fluorescence intensity of the QDs increased with increasing P4 concentrations. This assay had a detection limit of 553.9 pg/ml and a sensitivity of 18,251.96 pg/ml with a linear range of 2,184.6 – 117,082 pg/ml. In the direct binding assay, P4 was directly bound to the QDs-P4Ab conjugates immobilized onto the APTMS sol-gel membrane of the wells of a 96-well microtiter plate. In this direct binding assay the fluorescence intensity of the QDs decreased with increasing P4 concentrations, and this assay had a linear range of 28.95 – 26,607.7 pg/ml with a detection limit of 3.32 pg/ml and a sensitivity of 987.24 pg/ml. These fluorescence immunoassays have been successfully applied for the determination of P4 in real human serum, and the results were well correlated with those of a certified radioimmunoassay (RIA) method.

Human tuberculosis (TB) is caused mainly by Mycobacterium tuberculosis (MTB) and M. africanum (MAF) remains a major global health threat. The varying response of different host to contact with the TB bacteria, indicates the importance of host genetics in susceptibility to TB disease. We explored the association among selected human/host genomic variants and disease caused by the two causative pathogens in Ghana through a case control study. MTBC isolates (323) recovered from pulmonary TB patients recruited between 2016 and 2018 were genotyped using spoligotyping. A selection of 29 SNPs from MTB-related genes with high frequency among African populations were genotyped using a TaqMan® SNP Genotyping Assay and iPLEX Gold Sequenom Mass Genotyping Array. Associations between MTBC lineages and host variables were assessed using univariate and multivariate logistic regression. The prevalence of MTB and Maf among the participants were 79% and 21% respectively. Association analysis between the controls and MAF showed that rs2695342 variant on the SIC11A1 gene have the propensity to confer susceptibility to MAF infections (P = 0.093, OR = 8.35, 95% CI = 0.70 – 99.24) whilst the rs17048476 (P = 0.088, OR = 1.57, 95% CI = 0.93 – 2.63) and rs1482868 (P = 0.095, OR = 0.60, 95% CI = 0.33 – 1.09) were observed to be only suggestive. Our findings implicate SLC11A1 as a potential susceptibility gene of substantial interest for TB caused by MAF which is an important pathogen in West Africa and highlight the need for in-depth host pathogen studies in West Africa.

The rising incidence of complex illnesses and their costs have revolutionized basic research, patient management, and societal needs. Between 70 to 90% of the risk of developing a disease is due to the air we breathe, the water we drink, and the surroundings in which we work and live. Visibly polluted, infectious or not, the fact remains that we are more than ever exposed to environmental risks. Air pollution is the fourth most prevalent deadly risk factor worldwide and by far the leading risk factor for hundreds of diseases, including respiratory infections, inflammatory illness, and cancer. Thus, an unhealthy environment can be considered as a pandemic, affecting 280 million people and claiming 12 million deaths every year. Although critical for identifying of the people at risk, the causal environment components (pollutants and/or the microbiome), and the affected physiological mechanisms are not well understood. Herein, we consider the dysregulation of macroautophagy (hereafter referred to as ‘autophagy’), as the mechanism at the heart of an immediate response to environmental stress. We discuss the missing link between the autophagy gene variations, and the exposome in the susceptibility, prognosis, and management of complex diseases when embracing personalized medicine.

The formation of sinkholes in Winkler County, Texas is concerning due to the amount of oil and gas infrastructure and the potential for catastrophic losses. Evidences of new and potential sinkholes have been documented, and determining the cause of these sinkholes is paramount to mitigate the devastating consequences thereof. Studies shown that the Wink sinkholes result from both natural and anthropogenic influences. Data depicting land-cover changes, alterations in the hydrologic systems, climate changes, and oil and gas activity were analyzed in an effort to better understand the link between these processes and sinkhole formation. Results indicate that the combination of these processes lead to the current state; Land cover changes were highest in shrub versus grasses, undeveloped to developed and croplands. Rises in temperature and a decrease in precipitation indicate a shift towards a more arid climate. Changes to the hydraulic system are a direct result of these land cover changes while the groundwater quality depict an environment prone to dissolution. Historical oil and gas activities have created pathways of meteoric water infiltration to the underlying limestone and evaporite formation. The combination of these processes create an environment that accelerates sinkhole formations. Understanding these processes allows for the development and implementation of better land practices, better groundwater protections, and the need for monitoring and maintaining aging oil and gas infrastructure.

Red djulis (Chenopodium formosanum) is a native cereal plant in Taiwan; it contains abundant polyphenols, betalian and dietary fiber. The appearance of red djulis is bright red. Therefore, it is also called the “ruby of cereals”. The antioxidative activity of red djulis extract is well-understood. However, the antiaging function still remains unclear. This study examined the potential of red djulis extract for enhancing collagen secretion and preventing cutaneous aging using red djulis extracts. The red djulis extracts are comprised of an abundant active component that can effectively enhance the ability of collagen secretion of dermal fibroblasts, prevent the glycation of collagen and resist the damage of ultraviolet light exposure. After fibroblast treatment with red djulis extracts, TGM1, KRT1, KRT10 and SOD2 genes were up-regulated significantly by 2.3, 4.3, 4.4 and 27.3 times, respectively, compared to those of the control group. Additionally, it can increase COL1A2 gene expression by 43% and decrease MMP9 gene expression 33%. Therefore, it was demonstrated that red djulis extracts affect gene expressions related to the skin barrier, antioxidation and collagen. Moreover, we found positive effects on skin barrier integrity, endogenous antioxidant activity and skin collagen-preservation. The preparation of the red djulis extracts is environmental friendly and can promote the economic value of Chenopodium formosanum; thus, the proposed extract is suitable for applications in the development of food products, especially beverages, skin care and cosmetic products.

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

Triploidy in cancer is associated with poor prognosis but its origins remain unclear. Here, we attempted to differentiate between random chromosomal and whole-genome origins of cancer triploidy. In silico meta-analysis was performed on 15 male malignant and 5 benign tumour cohorts (2928 karyotypes) extracted from the Mitelman Database, comparing their ploidy and combinations of sex chromosomes. A distinct near-triploid fraction was observed in all malignant tumour types, being especially high in seminoma. For all tumour types, X-chromosome doubling, predominantly observed as XXY, correlated strongly with the near-triploid state (r≈0.9, p<0.001), negatively correlated with near-diploidy, and did not correlate with near-tetraploidy. A smaller near-triploid component with a doubled X-chromosome was also present in 3 of 5 benign tumour types, especially notable in colon adenoma. Principal Component Analysis revealed a non-random correlation structure shaping the X-chromosome disomy distribution across all tumour types. We suggest that doubling of the maternal genome followed by pedogamic fusion with a paternal genome (a possible mimic of the fertilization aberration, 69, XXY digyny) associated with meiotic reprogramming may be responsible for the observed rearrangements of genome complements leading to cancer triploidy. The relatively frequent loss of the Y-chromosome results secondary from chromosome instability.

Prefrontal cortex (PFC) is one of the brain regions with more prominent changes in human aging. The molecular processes related to the aging cognitive decline and mood changes are not completely understood. In order to improve our knowledge, we integrated transcriptomic data of four studies of human PFC from old people -58-80 years old- compared with young people -20-40 years old- using a meta-analytic approximation combined with molecular signature analysis. We identified 1816 differentially expressed genes -561 up-regulated and 1256 down-regulated. Pathway analysis revealed down-regulation of synaptic genes with conservation of gene expression of other neuronal regions. Additionally, we identified up-regulation of markers of astrogliosis with transcriptomic signature compatible with A1 neurotoxic astrocytes and A2 neuroprotective astrocytes. Response to interferon is related to A1 astrocytes and the A2 phenotype is mediated in aging by activation of SHH pathway and up-regulation of metallothioneins I and genes of the family EZR -ezrin, radixin, and moesin-. The main conclusions of our study are the confirmation that in aged PFC there is a global dysfunction of the synapses and we reported for the first time opposite phenotypes of astrogliosis because of brain aging.

We investigated whether post-exercise capsinoids (CSN) supplementation could enhance muscle glycogen resynthesis via GLUT4/Akt expressions in human skeletal muscle. Nine male college students (aged 21.4±0.2 years, BMI 21.9±1.3 kg/m2, VO2max 47.1±1.8 ml/kg/min) participated in this crossover designed study, and completed a 60-min cycling exercise at 70% VO2max. Immediately after exercise, participants consumed high-carbohydrate diet (2 g carb/kg bodyweight) with CSN (12 mg, single dosage) or placebo. Biopsied muscle samples (vastus lateralis) were obtained immediately (0h) and 3h after exercise. Blood and expired gas samples were collected before and after exercise. We found oral CSN supplementation immediately after exercise was unable to enhance glycogen resynthesis in exercised human skeletal muscle. Despite, CSN could alter the energy reliance on fat oxidation during post-exercise recovery, based on gaseous exchange measurement (NEFA and glycerol). We further identified no significant differences in postprandial glucose/insulin area under curve in both trials. Western blot data showed no significant response of p-Akt/Akt ratio with CSN during post-exercise recovery. Inconsistent with glycogen levels, muscle GLUT4 expression was significantly elevated at 3h in CSN trial. Our findings emphasize the necessity of further evidences to confirm the ergogenic properties of CSN in connection with glycogen recovery in exercised human skeletal muscle.

Human mesenchymal stem cells (hMSCs) constitute of cells having potential of self-renewal and proliferation and are commonly isolated from bone marrow aspirates of large bones. The osteogenic potential of these stem cells has been extensively exploited by scientists during the last many years for the biological evaluation of synthetic scaffolds with applications in tissue engineering. Current work aimed to synthesize N-arylhydrazone derivatives of orotic acid and their evaluation as stimulators of human mesenchymal stem cells. Some of the analogs show good to moderate proliferation rate.

Horses’ ability to adapt to new environments and to acquire new information plays an important role in handling and training. Social learning in particular would be very adaptive for horses as it enables them to flexibly adapt to new environments. In the context of horse handling, social learning from humans has been rarely investigated but could help to facilitate management practices. We assessed the impact of human demonstration on spatial problem-solving abilities in horses using a detour task. In this task, a bucket with a food reward was placed behind a double-detour barrier and horses (n = 16) received a human demonstration or no demonstration. Horses were allocated to two test groups of 8 horses each, which experienced the two treatments in a counterbalanced order. We found that horses did not solve the detour task faster with human demonstration. However, both test groups improved rapidly over trials. Our results suggest that horses prefer to use individual rather than social information when being confronted with a spatial problem-solving task.

Enamel matrix derivative (EMD) is used for periodontal tissue regeneration therapy, and can induce mineralization in dental pulp cells (DPCs). We designed a synthetic peptide (SP) derived from the response of cells to EMD, and investigated the effect of the SP on potentiating osteogenesis in DPCs, which have a critical role of dental pulp homeostasis. DPCs were treated with 0, 10, 100, or 1000 ng/mL SP to determine its effect on cell proliferation, cell migration, cell differentiation, and mineralization. We then examined the molecular effects of the SP, focusing on changes in the mitogen-activated protein kinases (MAPK) signaling pathway in these cells. The SP significantly promoted DPC proliferation and migration. Cultures treated with the SP also showed an enhanced expression of markers of osteogenic differentiation and mineralization. The SP also induced the activation of MAPK signaling pathway components. These results suggest that our SP could promote the dental pulp tissue repair by hard tissue formation and the mineralization through activating MAPK signaling pathway. This study provides the first evidence that SP might be a new material for dental pulp tissue treatment.

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