contaminated sites located in each school district. Previous studies showed that various environmental factors, such as exposure to toxic substances negatively impacts human health depending on their concentration and occurrence. Therefore, the study aims to use Geographical Information System (GIS) technology and secondary data on IEP numbers of each school district, chemical occurrence in contaminated sites, and demographic data to conduct a correlational analysis. The secondary data obtained from school districts and contaminated sites from Iowa Department of Natural Resources Facility Explorer were populated in ArcMap 10.5 (a GIS software) for generating maps and data to conduct statistical analysis. The contaminants were categorized into metals, polyaromatic hydrocarbons (PAH), and solvents with weighing factors as 1, 0.5, and 0.25. A total of 1 Superfund site and 39 CERCLA sites were identified as contaminated sites for this study. The majority of contaminants were heavy metals such as lead, arsenic, mercury, and cadmium. The mean toxic score of all contaminated sites combined was 13.4 (sd 14.4). The correlational analysis between the IEP numbers from each school districts and toxic scores from the contaminated sites was positive indicting that increased toxic score increased the number of students enrolled in the IEP program (F=23.7, p<0.0001). The correlational analysis between toxic score and demographics indicated some interesting results. Children under the age of 10 were living in areas with high toxic score and the showed mild correlation (p<0.00052). Similarly, higher number of black population resided in areas with high toxic score (p=0.0032) than the white population (p<0.0001). The result also indicated that children enrolled in IEP were predominantly among the black population (p<0.0001). The correlational analysis between household income and poverty percentage of people residing near the contaminated area indicated that people had low average household income (p=0.0002) and high poverty percentage (p=0.0203) residing in areas with higher toxic score. Regarding the educational status, less number of people with post graduate degree (p<0.0001) resided in areas with high toxic score and more number of people with no degree (p<0.0001) resided in areas with high toxic score. Finally, the study showed the increasing trend of eligible children enrolling in free and reduced lunch programs with increasing toxic scores (p=0.0012) and IEP levels (p=0.0416). This study emphasize on developing multiple exposure to correlate environmental factors contributing to the negative health outcome on people.

As urban populations and transport demand expand, Pakistani metropolitan centers face traffic congestion and environmental challenges. This research aims to assess carpooling (CP) to alleviate traffic congestion, fuel demand, and pollution. This study was conducted in Islamabad, a fast-growing city with a high percentage of personal cars in Pakistan, to assess the travelers’ perceptions, and public acceptance of CP and determine the effects on traffic congestion, fuel consumption, and CO2 emissions. The investigation of travelers' perceptions towards CP was conducted through a stated preference questionnaire survey. A total of 700 responses from one million population of Islamabad were collected as per Sloven's Formula. SPSS and Smart PLS software were used for data analysis. Various factors influencing peoples’ travel perceptions, mode choice, and tendency to carpool, were categorized to evaluate the relationship between travelers’ perception and the tendency to carpool in the presence of mode choice as a mediating variable. Confirmatory factor analysis was conducted in SMART PLS to refine the number of scale items for each variable. One-way ANOVA, step-wise and mediated multiple regression analysis was conducted in SPSS to check the direct and mediating relationship between different variables. Moreover, the probability of reducing traffic congestion and assessing fuel reduction resulting from CP was also analyzed. The findings imply that travelers’ mode choice acts as a mediator between the relationship between travelers’ perception and tendency to carpool. Furthermore, results predicted that CP might reduce 0.25 million cars on the road, about 33.6% of the total private vehicles. Thereby, saving up to 546,810 barrels per year, about 3.42% of Pakistan's total petrol consumption. The findings of this study could be helpful for transport planners, environmentalists, and policymakers to implement carpool systems. Thus, reducing traffic congestion and harmful CO2 emissions and maintaining a sustainable environment.

In order to reduce the risk of grid transient voltage instability brought about by the new energy and system dynamic loads and the increasing proportion of new energy access, this paper proposes a differentiated dynamic reactive power compensation configuration method for suppressing transient voltage dip instability. The method first establishes a dynamic reactive power device configuration index system based on a multi-binary table, and then establishes a differentiated dynamic reactive power compensation device configuration model based on the node instability risk characteristics by combining with the regional division of system transient voltage instability risk. The model takes the investment cost and suppression effect as the optimization objectives, and realizes differentiated dynamic reactive power compensation by flexibly adjusting the optimization weights of economic benefits and reactive power compensation effects in the configuration process; Compared with the traditional compensation methods, differentiated compensation can significantly improve the economic benefits of reactive power compensation configuration. Finally, taking the IEEE39 node test system as an example, the improved TLBO algorithm is used to solve the model, which verifies the accuracy and effectiveness of the method proposed in this paper.

This paper examines the importance of choice of cooking fuels in wellbeing, analysing relationships between the proportion of population with primary reliance on different types of fuels for cooking (predictor variable), and key wellbeing indices (outcome variables) - Personal Health, Social Life, Civic Engagement, Life Evaluation, Negative Experience. By combining two global datasets from Gallup and WHO, the study adds to current evidence by taking a global perspective. Controlling for demographic factors such as income per capita, age, education level, employment, etc., regression modelling of these relationships show that clean cooking fuels are influential in all of the key wellbeing indices with the exception of the Life Evaluation Index. Among the key wellbeing indices, Personal Health and Negative Experience Indices are the most strongly influenced by choice of clean cooking fuels. By adding access to electricity as an additional predictor variable, the analysis highlights the potential for integrating eCooking into national electrification plans as part of sustainable energy transitions, given that health outcomes (Personal health and Negative experience indices) appear to be as closely linked to choice of cooking fuels as to access to electricity.

Background: Neurosarcoidosis is a great mimic, and its distinction from multiple sclerosis and other disorders can be particularly troublesome. We investigated whether cerebrospinal fluid (CSF) examination could help distinguish these two conditions and propose new diagnostic criteria. Methods: Stringent hierarchical diagnostic criteria were formulated. These were then applied prospectively to 531 neurological patients in whom neurosarcoidosis entered the differential diagnosis. The CSF total protein (TP), white cell count (WCC) and angiotensin-converting enzyme (ACE) levels were measured. The CSF and serum IgG patterns after isoelectric focusing were compared. Not all CSF parameters were measured in every patient. Results: 85/531 (16%) cases examined were diagnosed with neurosarcoidosis. Only 22 of these 85 (26%) met stringent diagnostic criteria. Intrathecal synthesis of oligoclonal IgG was evident in only 1/19 (5%) who fulfilled these criteria compared to 19/59 (32%) cases who did not (p = 0.03). CSF TP levels > 1g/L were more common in patients meeting the stringent criteria compared to the remainder of the patients, i.e. 11/22 (50%) vs 14/58 (24%) (p<0.05). Eleven out of 20 cases (55%) fulfilling stringent criteria had elevated CSF WCCs, and 6/12 cases (50%) had raised CSF ACE, neither significantly different from the remaining cases. Mean CSF TP, WCC, and ACE levels did not differ significantly between any groups of patients. Interpretation: Large elevations in CSF total protein, white cell count, and ACE occur in neurosarcoidosis but are rare in multiple sclerosis. However, the diagnostic use of these tests is limited since minimal changes may occur in both conditions. In contrast, intrathecal synthesis of oligoclonal IgG is a powerful discriminator because it is very uncommon in neurosarcoidosis whilst occurring in 95-98% of cases of multiple sclerosis. This observation implies that the immunopathogenesis of the two disorders is quite different. We suggest caution in diagnosing neurosarcoidosis when intrathecal oligoclonal IgG synthesis is detected. We propose new diagnostic criteria for neurosarcoidosis for future research.

A text obtained by a Large Language Model (LLM) such as GPT4 usually has issues in terms of incorrectness and hallucinations. We build a fact-checking system 'Truth-O-Meter' which identifies wrong facts, comparing the generation results with the web and other sources of information, and suggests corrections. Text mining and web mining techniques are leveraged to identify correct corresponding sentences; also, the syntactic and semantic generalization procedure adopted to the content improvement task. To handle inconsistent sources while fact-checking, we rely on an argumentation analysis in the form of defeasible logic programming. We compare our fact checking engine with competitive approach based on reinforcement learning on top of LLM or token-based hallucination detection. It is observed that LLM content can be substantially improved for factual correctness and meaningfulness.

Fexuprazan is a potassium-competitive acid blocker approved for treating gastric acid-related diseases. Herein, we evaluated the pharmacokinetics (PKs) of single-dose and multiple-dose oral administration of fexuprazan 10 mg tablets in healthy subjects (Part 1) and investigated the bioequivalence between fexuprazan 10 mg and 40 mg tablets (Part 2). Part 1 comprised a single- and multiple-dose, 1-sequence, and 2-period design, and Part 2 comprised a single-dose, 2×2 crossover design. Eight and 23 subjects completed Parts 1 and 2, respectively. In Part 1, multiple doses accumulated twice as much as single doses. In Part 2, the geometric mean ratios [90% confidence intervals] for maximum plasma concentration (Cmax) and area under the concentration–time curve from zero to the time of the last quantifiable concentration (AUClast) of four fexuprazan 10 mg tablets to those of one fexuprazan 40 mg tablet were 1.0290 (0.9352–1.1321) and 1.0290 (0.9476–1.1174), respectively, which met bioequivalence criteria. Overall, favorable PK was observed after single and multiple administrations of one fexuprazan 10 mg tablet, and four fexuprazan 10 mg tablets were pharmacokinetically equivalent to one fexuprazan 40 mg tablet.

Interferon-beta is one of the most widely prescribed disease-modifying therapies for multiple sclerosis patients. However, this treatment is only partially effective, and a significant proportion of patients do not respond to this drug. This paper proposes an alternative fuzzy logic system based on the opinion of a neurology expert to classify relapsing-remitting multiple sclerosis patients: high, medium, and low responder to interferon-beta. Also, a pipeline prediction model trained with biomarkers associated to interferon-beta response is proposed for predicting whether patients are potential candidates to be treated with this drug, in order to avoid ineffective therapies. The classification results shows that the fuzzy system presents a 100% efficiency compared with an unsupervised hierarchical clustering method (52%). So, the performance of the prediction model is evaluated, and a 0.8 testing accuracy is achieved. Hence, a pipeline model including data standardization, data compression, and a learning algorithm, can be a useful tool for getting reliable predictions about the response to interferon-beta.

Flaxseed oil is one of the best sources of n-3 fatty acids, thus its adulteration with refined oils can lead to a reduction in its nutritional value and overall quality. The purpose of this study was to use the differential scanning calorimetry (DSC) technique to detect adulterations of cold-pressed flaxseed oil with refined rapeseed oil (RP). Based on the melting phase transition curve, parameters such as peak temperature (T), peak height (h), and percentage of area (P) were determined for pure and adulterated flaxseed oils with a RP concentration of 5, 10, 20, 30, 50% (w/w). Significant linear correlations (p ≤ 0.05) between the RP concentration and all DSC parameters were observed, except for h1. In order to assess the usefulness of the DSC technique for detecting adulterations, three chemometric approaches were compared: 1) classification models (Linear Discriminant Analysis, LDA Adaptive Regression Splines, MARS, Support Vector Machine, SVM, Artificial Neural Networks, ANNs); 2) regression models (Multiple Linear Regression, MLR, MARS, SVM, ANNs, PLS) and 3) a combined model of Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). With the LDA model, the highest accuracy of 99.5% in classifying the samples, followed by ANN&gt; SVM &gt; MARS was achieved. Among the regression models, the ANN model showed the highest correlation between observed and predicted values (R= 0.996), while other models showed goodness of fit as following MARS&gt; SVM&gt; MLR. Comparing OPLS-DA and PLS methods, higher values of R2X(cum) =0.986 and Q2 =0.973 were observed with the PLS model than OPLS-DA. These results demonstrate the usefulness of the DSC technique combined with chemometrics for predicting the adulteration of cold-pressed flaxseed oil with refined rapeseed oil.

This paper investigates the problem of cooperative standoff tracking using multiple fixed-wing unmanned aerial vehicles (UAVs) with control input constraints. In order to achieve accurate target tracking in the presence of unknown background wind and target motion, a coordinated standoff target tracking algorithm is proposed. The objective of the research is to steer multiple UAVs to fly a circular orbit around a moving target with prescribed intervehicle angular spacing. To achieve this goal, two control laws are proposed, including relative range regulation and space phase separation. On one hand, a heading rate control law based on Lyapunov guidance vector field is proposed. The convergence analysis show that the UAVs can asymptotically converge to a desired circular orbit around the target, regardless of their initial position and heading. Through rigorous theoretical proof, it is concluded that the command signal of the proposed heading rate controller will not violate the boundary constraint on heading rate. On the other hand, a temporal phase is introduced to represent the phase separation and avoid discontinuity of the wrapped space phase angle. On this basis, a speed controller is developed to achieve equal phase separation. The proposed airspeed controller met the requirement of airspeed constraint. In addition, to improve the robustness of the aircraft during target tracking, an estimator is developed to estimate the composition velocity of the unknown wind and target motion. The proposed estimator uses the offset vector between the UAV’s actual flight path and the desired orbit which is defined by Lyapunov guidance vector field to estimate the composition velocity. The stability of the estimator is proved. Simulations are conducted under different scenarios to demonstrate the effectiveness of the proposed cooperative standoff target tracking algorithm. The simulation results of indicate that, the temporal-phase-based speed controller can achieve fast convergence speed and small phase separation error. Additionally, the composition velocity estimator exhibits fast response speed and high estimation accuracy.

A new approach to the treatment of wound lesions, which are complicated by the presence of polyresistant microflora and a possible immunodeficiency background has been proposed. It involves treating the wound surface with high-intensity pulsed optical radiation of a continuous spectrum, continuously covering the entire UV range (from 200 to 400 nm), visible and near infrared region of the spectrum. A pulsed xenon lamp is used as a radiation source. A description of the design and technical characteristics of the developed device for high-intensity optical irradiation "Zarnitsa-A", which implements the proposed medical technology for wound therapy, is represented. The results of preclinical studies of the apparatus in vitro and in vivo are represented hereinafter. The article shows that the apparatus exposure has pronounced bactericidal and wound-healing properties. The apparatus action reliably provides higher rates of wound healing compared to the use of only a typical antibacterial and wound healing agent – “Levomekol” ointment.

At 100% penetration, intermittent renewable energy causes outages. To flatten the leaping supply and demand curves of renewable energy, an energy storage medium and carrier are required. The Hydrogen energy stotrage system (HydESS), which combines a proton exchange membrane (PEM)-based water electrolysis (WE) system and a fuel cell (FC), has the quickest response time, the longest duration, and the greatest storage capacity. HOMER tools for techno-economic analysis are used to evaluate the HydESS hybrid system. Kyiv, Ukraine, is appealing due to its spatial-temporal wind speed, solar irradiance, and energy security. With an LCOE of $0.245 kWh−1 and 9.3% fuel cell power output, the most feasible solution is onshore wind turbine-coupled PEMFC HydESS. As a result 1,000-kW wind power, 250-kW PEMFC, 250-kW PEMWE, and 441-kW BESS are optimized to serve a 3,900 kWh day academic residence load. When compared to a diesel generator and a BESS, the hybrid HydESS reduces CO2 emissions by 4,132 tons over a 25-year period. The LCOE of a hybrid HydESS system is determined by the SOFC lifetime rather than the PEMFC's 2% difference between 40,000 and 50,000 h with the same rated power. This study recommends accelerating PEMFC development with fluctuation-endurable materials and design.

Based on the Generalized bracket, or Beris-Edwards, formalism of non-equilibrium thermodynamics, we have recently proposed [Stephanou et al. Materials, 13, 2867 (2020)] a new differential constitutive model for the rheology of entangled polymer melts and solutions. It has amended the shortcomings of a previous model that was too strict in the values of the convective constraint release parameter for the model not to violate the second law of thermodynamics and has been shown capable of predicting a transient stress undershoot (following the overshoot) at high shear rates. In this work, we wish to further examine this model’s capability of predicting the rheological response of industrial polymer systems by extending it to its multiple-mode version. The comparison against industrial rheological data (High-Density Polyethylene resins), as compared against available experimental data in (a) Small Amplitude Oscillatory shear, (b) start-up shear, and (c) start-up uniaxial elongation, is noted to be good.

The land subsidence occurring in goafs after coal mining is a protracted process. The accurate prediction of long-term land subsidence in goafs relies heavily on the availability of long-term monitoring data. However, the scarcity of continuous long-term land subsidence monitoring data subsequent to the cessation of mining significantly hinders the accurate prediction of long-term land subsidence in goafs. To address this challenge, this study proposes an innovative method based on Interferometric Synthetic Aperture Radar (InSAR) for predicting long-term land subsidence of goafs following coal mining. The proposed method employs a concatenation approach that integrates multiple short-term monitoring data from different coal faces, each with distinct cessation times, into a cohesive and uniform long-term sequence by normalizing the subsidence rates. The method was verified using actual monitoring data from the Yangquan No.2 mine in Shanxi Province, China. Initially, coal faces with same shapes but varying cessation times were selected for analysis. Using InSAR monitoring data collected between June and December of 2016, the average subsidence rate corresponding to the duration after coal mining cessation of each coal face was back-calculated. Subsequently, a function relating subsidence rate to the duration after coal mining cessation was fitted to the data. Finally, the relationship between cumulative subsidence and the duration after coal mining cessation was derived by integrating the function. The results indicated that the relationship between subsidence rate and duration after coal mining cessation followed an exponential function for a given coal face, whereas the relationship between cumulative subsidence and duration after coal mining cessation conformed to the Knothe time function. Notably, after the cessation of coal mining, significant land subsidence persisted in the goaf of the Yangquan No.2 mine for a duration ranging from 5 to 10 years. The cumulative subsidence curve along the long axis of the coal face ultimately exhibited an inclined W-shape. The proposed method enables the quantitative prediction of residual land subsidence in goafs, even in cases where continuous long-term monitoring data are insufficient, thus providing valuable guidance for construction decisions above the goaf.

Multiple myeloma (MM) is an incurable, diverse cancer in which abnormal plasma cells produce and release monoclonal immunoglobulin (Ig), also known as monoclonal protein or M protein. MM is always preceded by monoclonal gammaglobulinemia of unknown significance (MGUS) and smoldering multiple myeloma (SMM). Diagnosis of MM is made from a bone marrow sample, which involves analysis of the appearance of plasma cells. Quantification of CD138+ plasma cells in core biopsies is performed using techniques such as immunohistochemistry, flow cytometry, fluorescence in situ hybridization (FISH) and conventional cytogenetics. Urinalysis includes total protein by immunofixation and 24-hour urine by serum protein electrophoresis. FISH probes should detect the presence of at least del 13, del 17p, t(4;14), t(11;14), t(14;16), and 1q21 amplifications. Indeed, next-generation sequencing (NGS) has become an increasingly important tool in the diagnosis and treatment of MM. It can be used to identify genetic mutations, copy number changes, and clonal structures to help determine disease prognosis and treatment strategies. NGS can identify subclonal populations of cancer cells that are resistant to therapy and may lead to disease relapse, and can be used to identify potential targets for personalized therapy. For example, NGS can identify mutations in genes involved in drug resistance, enabling the selection of drugs that may be more effective in treating a patient's cancer. This systematic review analyzes 182 papers to determine the position and role of NGS in the diagnosis of MM. We first analyze the platforms and sample types used in the selected studies, and then start discussing the results.

This paper explores the integration of multiple intelligences and artificial intelligence (AI) in language learning, focusing on its potential to enhance personalization and engagement. Drawing from existing research and studies conducted in various contexts, including the Philippines, this study aims to contribute to the understanding of the benefits, challenges, and effectiveness of this integration. The paper begins with an introduction that highlights the background and significance of integrating multiple intelligences and AI in language learning, identifying research gaps, objectives, research questions, and the theoretical framework. A literature review provides an overview of multiple intelligences theory by Howard Gardner, the role of AI in language learning, and identifies gaps in the existing literature. The methodology section outlines the research design and approach, participant selection, data collection methods, validity and reliability measures, and ethical considerations. Findings and results are presented through the analysis of qualitative data, exploring emergent themes and patterns. The discussion section critically examines the identified research gaps, discusses the validity and reliability of the study, addresses the scope and limitations, and explores the implications of the findings for theory, practice, and future research. The conclusion summarizes the key findings and contributions of the study, reflects on the achievement of research objectives, offers recommendations for further research, and provides final remarks tying together the main points of the study. This paper contributes to the existing body of knowledge by providing insights into the integration of multiple intelligences and AI in language learning and its impact on personalization, engagement, and language learning outcomes.

Multiple sclerosis (MS) is a persistent inflammatory disease affecting the central nervous system. Bruton's tyrosine kinase (BTK) is an enzyme crucial in the communication process of B cells, which have a significant impact on the development of MS. Recently, BTK inhibitors have emerged as a promising treatment strategy for MS due to their ability to modulate the immune system. In this study, an extensive literature search was performed utilizing multiple databases, such as PubMed, Embase, and Scopus to examine the potential use of BTK inhibitors in managing cognitive disorders experienced by individuals with MS. We found that BTK inhibitors targeting microglia offer potential advantages for managing neurodegeneration associated with cognitive impairments in MS patients by slowing down degeneration processes effectively. Their ability to impact microglial function and penetrate the CNS positions them as promising candidates for improving cognitive function. This study suggests that BTK inhibitors provide new possibilities for managing inflammatory and neurodegenerative phases of MS through their effects on microglia activation pathways. Further research and clinical trials are necessary to fully explore their efficacy in treating MS while addressing barriers related to cognitive impairment.

The wind observations for multiple levels (40–200 m) have been conducted for a long time (2016–2020) on Jeju Island of South Korea. This study aims at understanding the vertical and temporal characteristics of lower atmosphere. Jeju Island is a region located at mid-latitude and is affected by seasonal monsoon wind. The maximum wind speed appears in the lower layer during day time and is delayed in the upper layer during latter time in diurnal cycle. In summer season, the surface layer increases up to 160 m during day time via dominant solar radiation effect, which is higher than those for other seasons. However, the maximum wind speed in winter season appears irregularly among altitudes, and the surface layer is ~100 m, which is lower than that in summer season. It can be attributed to the increase in the mean wind speed in diurnal cycle caused by the strong northwestern wind for winter season. These results imply that the relationship between near-surface and higher altitudes is primarily affected by solar radiation and seasonal monsoon winds. These results are expected to contribute to site selection criteria for wind farms and to the assessment concerning planetary boundary layer modeling.

Organizational climate is the ascribed psychological meanings and significance associated with the procedures, policies and practices that are recognized and rewarded in the workplace, and hence mediates the effects of environmental stimuli on individuals’ response. Safety climate is a specific organizational climate, i.e., organizational climate for safety. Previous research claimed that organizational climate provides foundation for safety climate, but without elaboration on the foundational mechanisms. This paper attempts to fill up this knowledge gap. As organizational climate is a multi-dimensional phenomenon, this paper chooses two dimensions, i.e., perceived organizational support (POS) and participative decision-making (PaDM), for illustrative purposes. Drawing on an interactive approach to forming climate perceptions, this paper introduces two interactive constructs, i.e., leader-member exchange (LMX) and team member exchange (TMX), and establishes a multiple mediation model depicting the foundational effect of organizational climate on safety climate. A random sample of Hong Kong based construction personnel is used to validate the model. The results show that both POS and PaDM are positively associated with perceived safety climate, both LMX and TMX fully mediate the effect of PaDM on safety climate, and only LMX partially mediates the effect of POS on safety climate. This study sheds light on the foundational effects of organizational climate on safety climate. POS can improve the quality of reciprocal exchange about safety matters between construction personnel and their supervisors, and hence raise construction personnel’s awareness of the priority of safety. PaDM can improve the quality of reciprocal exchange about safety matters vertically and horizontally, and hence have construction personnel aware the importance of safety. In practice, this paper suggests that project managers timely recognize and reward construction personnel’s contribution, genuinely cares about their well-being, and take their suggestions seriously in making decisions. In this way, the quality of both vertical and horizontal exchange about safety matters improves, and a sound and positive safety climate ensues.

Streptococcus pneumoniae is one of the associated bacteria that can cause the rare but high mortality hematological disease known as purpura fulminans (PF) in both adults and children. Patients with PF can progress quickly to sepsis and multiorgan failure, especially in immunocompromised individuals and young children. Due to the thrombotic blockage of blood arteries in PF, there is diffuse intravascular thrombosis and hemorrhagic infarction of the skin, which evolves from ecchymosis to skin necrosis, risk of limb sequelae, sepsis and fatality. We present a case of a previously healthy 1-year and 9-month female who was admitted to the Intensive Care Unit of the National Institute of Infectious Diseases "Prof. Dr. Matei Balș"- Bucharest, Romania. The patient presented with erythematous patches on left upper limb and trunk, tachycardia, tachypnea, hypotension, anuria and altered sensorium with an indication of intubation for 8 Glasgow Coma Scale (GCS). Cerebrospinal culture grew Streptococcus pneumoniae serotype 1. She required peritoneal dialysis due to acute kidney injury (AKI) and surgeries for affected areas. After multiple organ system failures, our patient evolved rapidly to irreversible tissue necrosis and death. We aim to report a rare case of PF associated with pneumococcal meningoencephalitis in immunocompetent children to better appreciate the risk of fatal evolution when managing this disease in children. To date, few studies report favourable evolution. We discuss the etiology, rapid diagnosis and treatment of immunocompetent children with PF and the importance of interprofessional teams to increase the outcomes in patients with infectious diseases.

As required by the EU legislation and the national risk management duties, the pesticide residues were determined by four specialized laboratories in 9,924 samples taken from 119 crops of economic importance and imported foodstuffs during 2017-2021 in Hungary. The screening method applied covered 622 pesticide residues as defined for enforcement purposes. The limit of detection ranged between 0.002-0.008 mg/kg. The 1.0% violation rate was lower than in the European Union for all commodities. No residue was detectable in 45.9% of the samples. For detailed analyses of the results, eight commodities (apple, cherry, grape, nectarine/peach, sweet peppers, and strawberry) were selected as they were analyzed over 195 samples and contained most frequently residues. Besides testing their conformity with national MRLs, applying 0.3MRL action limits for pre-export control, we found that 73% of the sampled lots would be compliant with ≥90% probability based on second independent sampling. Multiple residues (2-23) in one sample were detected in 36-50% of the tested lots. Noting the provisions of integrated pest management and the major pests and diseases of selected crops, normally 3-4, exceptionally 7-9 active ingredients of different mode of actions should be sufficient for their effective and economic protection.

The home is becoming a key location for healthcare delivery, including the use of technology driven by autonomous systems (AS) to monitor and support healthcare plans. Using the example of a smart mirror, this paper describes the outcomes of focus groups with people with multiple sclerosis (MS; n=6) and people who have had a stroke (n=15) to understand their attitudes towards the use of AS for healthcare in the home. We thematic analysis to analyse the data. The results indicate that the use of such technology depends on the level of adaptability and responsiveness to the users’ specific circumstances, including their relationships with the healthcare system. A smart mirror would need to support manual entry, responsive goal setting, effective aggregation of data sources and integration with other technology, have a range of input methods, be supportive rather than prescriptive in messaging, and give the user full control of their data. Barriers to adoption include a perceived lack of portability and practicality, lack of accessibility and inclusivity, a sense of redundancy, being overwhelmed by multiple technological devices, and a lack of trust in data sharing. These results inform the development and deployment of future health technologies based on the lived experiences of people with health conditions who require ongoing care.

The present study employed a modifed QuEChERS method to systematically analyze the presence of fifteen Quinolones and seven Tetracyclines antibiotic residues in local animal food. Additionally, a multi-level-four-factor Box-Behnken design (BBD) within the framework of Response surface methodology (RSM) was utilized to evaluate the various factors affecting the detection efficiency of the sample pretreament procedure. The optimization was performed by Design Expert®, the factors including volume of the acetonitrle, the addition of formic acid, the duration of extract and the addition of EDTA were combined to experiment design until reach an optimal solution. Finally, the sample test was conducted by ultra-high performance liquid chromatography-quadrupole-linear ion trap mass spectrometry in both multiple reaction monitoring (MRM) and enhanced product ion (EPI) scan modes on a QTRAP® 5500 instrument. The overall average recoveries from actual samples fortified with 22 antibiotics at three levels ranged from 74.7 to 122.6% based on the use of matrix-fortified calibration with the variation ranging from 2.1 to 18.2% (n=6). The limits of detection and quantification were 0.3 μg kg-1 and 1.0 μg kg-1, respectively.

In an urban context, the street network can be considered the most substantial element, as its role is to create the whole urban setting. The street network is a spatial pattern that can be recognized as a linkage bonding other components of the urban context, such as buildings and open spaces. Basically, the street is not only a collection of lines that transfer people, vehicles and goods but also denote a broad range of activities and influences people’s responses. In this respect, some studies address the street as a network that entails two key elements, link and node; the link can be defined by the type of mechanism that it connects, while the node can be identified according to the analysis technique. Defining the street’s elements is a crucial step in ascertaining the expression of whatever is a link or/and a node. Thus, some scholars use the link to refer to a street, and node for the intersection, while others employ the opposite meaning. Two different viewpoints deal with spatial network analysis; the first is a technique based on topological depth, such as Space Syntax SS, and the second is Multiple Centrality Assessment (MCA) that is employed for metric analysis. This paper compares Space Syntax (SS) and Multiple Centrality Assessment (MCA) by measuring the integration and centrality of the street, and highlights the points of similarity and difference between the two techniques.

Microgrid is one of the important ways to accommodate distributed PV generation. However, the optimal planning scheme of microgrids is closely related to solar resources, load characteristics, and the key components of microgrid systems. This paper uses HOMER software to conduct collaborative planning for grid-connected PV-storage microgrids with electric vehicles in multiple scenarios. Specifically, we construct a multi-scenario capacity optimization model for PV generation, energy storage, and converters, considering both the cleanliness and economic performance of microgrids. The performance is quantified using indices such as net present cost, levelized cost of electricity, and carbon dioxide emission under multiple scenarios. Finally, we conduct extensive case studies on a business park in Wuhan, China, to compare and discuss the planning performance under multiple scenarios, as well as sensitivity analysis with specific cases.

(1) Background. Cognitive impairment in people with Multiple Sclerosis (MS) has been studied in relation to some clinical variables (e.g., motor disability and disease duration) and lifestyle fac-tors such as Cognitive Reserve (CR). However, only very few studies have considered the interac-tion of clinical variables and cognitive reserve in preserving the integrity of the neuropsychologi-cal profile. In this paper, we hypothesised that a higher level of CR might predict good cognitive efficiency by modulating the clinical outcome of the disease. (2) Methods. A sample of 100 partic-ipants with MS (age range 30-74), was recruited and assessed remotely with a questionnaire to measure CR and a cognitive screening test. Data were analysed through Generalized Additive Models. (3) Results. We found that the model analysing the interaction between CR and disease duration, and between CR and motor disability was able to explain a significant percentage of cognitive performance. In particular, higher levels of CR predicted better cognitive performance despite long disease duration, unless the motor disability was severe. (4) Conclusion. This study highlights the crucial role of CR in modulating cognitive efficiency in people with MS.

In this paper, an iterative procedure to find the solution of a nonlinear structural model is introduced. The model presents different multiplicities where parameters are randomly selected within a solvability region. To achieve this aim, a class of multipoint fixed-point iterative schemes for single roots is modified to find multiple roots, reaching the fourth order of convergence. Complex discrete dynamics techniques are employed to select the members with the most stable performance. The structural problem, as well as some academic problems involving multiple roots, are solved numerically to verify the theoretical analysis, robustness and applicability of the proposed scheme.

Eco-labels are an instrument for enabling informed food choices and supporting a demand-sided change towards a more and urgently needed sustainable food system. Lately, novel eco-labels that depict a product’s environmental life-cycle assessment on a multi-level scale are being tested across Europe’s retailers. This study elicits consumers preferences and willingness to pay (WTP) for a multi-level eco-label. A Discrete Choice Experiment was conducted in Austria. Individual partworth utilities were estimated by means of Hierarchical Bayes. Results show higher WTP for a positive evaluated multi-level label, revealing consumers’ perceived benefits of colorful multi-level labels over binary black-and-white designs. Even a negative evaluated multi-level label showed higher WTP compared to no label, pointing towards limited effectiveness of eco-labels. Respondents’ preferences for eco-labels were independent from their subjective eco-label knowledge, health consciousness, and environmental concern. The attribute “protein source” was most important, and preferences for animal-based protein source (beef) was strongly correlated with consumers’ meat attachment, implying that a shift towards more sustainable protein sources is challenging and sustainability labels have only a small impact on the meat product choice of average consumers.

Being able to complete the production of the product project on time is the prerequisite to win more tasks, many enterprises have begun to study intelligent scheduling algorithms to achieve dynamic control of the total project duration. However, the production operation time of products is highly volatile, and it is impossible to predict the possible operation time of future products. In the actual production environment, we often encounter extreme situations such as mixed production lines, multiple varieties, variable batches, etc. A dynamic optimization CPM model in the ERP/MES system with the attention mechanism (EMA-DCPM) will collect, extract and predict the operation time through artificial intelligence technology, and it can accurately predict the exact operation time of a batch of products that have not yet been produced. Through experiments, our algorithm can realize the production scheduling and get more than 200% better precision than former algorithms and realize dynamic optimization of complex projects.

A self-protective metal/ liquid microcapsule composite plating coating has been prepared in our previous research. The release speed of liquid core material from microcapsules is crucial for the coating surface properties. The aim of this paper is to study the permeability rule of liquid microcapsules within composite coatings. According to permeability experimental data’s linear characteristics, multiple linear regression is firstly used to set up permeability model of liquid microcapsules. The results show that a reliable mathematical model about membrane porosity, viscosity of core material and membrane thickness is established under ambient temperature and moisture. Meanwhile, the predictive capacity and reliability of this model are analyzed carefully.

We previously reported a novel secondary progressive multiple sclerosis (SPMS) model, progressive experimental autoimmune encephalomyelitis (pEAE), in oligodendroglia-specific Cx47-inducible conditional knockout (Cx47 icKO) mice. Based on our prior study showing the efficacy of iguratimod (IGU), an anti-rheumatic drug, for acute EAE treatment, we aimed to elucidate the effect of IGU on the SPMS animal model. We induced pEAE by immunizing Cx47 icKO mice with myelin oligodendrocyte glycoprotein peptide 35–55. IGU was orally administered from 17 to 50 days postimmunization. We also prepared primary mixed glial cell culture and measured cytokine levels in the culture supernatant after stimulation with designated cytokines (IL-1α, C1q, TNF-α) and lipopolysaccharide. A migration assay was performed to evaluate the effect of IGU on the migration ability of T cells toward mixed glial cell cultures. IGU treatment ameliorated the clinical signs of pEAE, decreased the demyelinated area, and attenuated glial inflammation on immunohistochemical analysis. Additionally, IGU decreased the intrathecal IL-6 level and infiltrating Th17 cells. The migration assay revealed reduced Th17 cell migration and IL-6 levels in the culture supernatant after IGU treatment. Collectively, IGU successfully mitigated the clinical signs of pEAE by suppressing Th17 migration through inhibition of IL-6 production by proinflammatory-activated glial cells.

Mycotoxins are fungal secondary metabolites, which can cause acute and chronic toxic effects in animals and humans. The present study aimed to determine multi-mycotoxin levels in Algerian workers using urine as target. A method based on a QuEChERS (quick, easy, cheap, effective, rugged, and safe) extraction procedure followed by LC-MS/MS (liquid-chromatography tandem mass spectrometry) was optimized and validated for determination of 11 mycotoxins in 96 urine samples. Different sorbents were tested to be used in the dispersive solid-phase extraction (d-SPE) cleanup step of QuEChERS. The final method was fit-for-purpose and showed good analytical performance in terms of specificity, linearity and precision. All samples contained at least 2 mycotoxins, being toxin-2 (T-2) the most common, which was found in 92.7% of the samples, followed by zearalenone (ZEN) with 90.6% of positive samples, and ochratoxin A (OTA) with 86.4%. T-2 levels ranged from 0.3 μg/L to 36.3 μg/L, while OTA ranged from 0.3 μg/L to 3.5 μg/L and ZEN ranged from 7.6 μg/L to 126.8 μg/L. This was the first mycotoxin biomonitoring study carried out in the Algerian population. The findings highlight the need of accurate data for better risk assessment and the development of better regulation to manage mycotoxin contamination in this country.

In recent years, drones have been used in a wide range of fields such as agriculture, transportation of goods, and security. Drones equipped with communication facilities are expected to play an active role as base stations in areas where ground base stations are unavailable, such as disaster areas. In addition, asynchronous operation is being considered for local 5G in order to support all kinds of use cases. In asynchronous operation, cross-link interference between base stations is an issue. This paper attempts to reduce the interference caused by the drone network by introducing circularly polarized antennas. Numerical analyses are conducted to validate the effectiveness of the proposed system, where SIRs (Signal-to-Interference Ratio) are shown to be improved significantly as the numerical evaluation results.

Since the beginning of the mass immunization with COVID-19 vaccines of patients with multiple sclerosis, many data on the efficacy and safety of these vaccines have been produced. Considering that MS is an autoimmune disease whose pathology can be explained by an altered immune system and that some DMTs seem to be able to decrease the antibody response against COVID-19 vaccines, we carried out this retrospective study with the aim to evaluate the safety in terms of AEFIs occurrence and the antibody response after the third dose of COVID-19 vaccines in people with MS. Third doses were administered from October 2021 to January 2022. Two hundred and ten patients (64.8% female; mean age: 46 years) received the third dose of the mRNA-based COVID-19 vaccine and were included in the study. The majority of patients (n=193) were diagnosed with RRMS and EDSS values were ≤3.0 in 72.4% of them. DMTs most commonly used by included patients were interferon Beta 1-a, dimethyl fumarate, natalizumab and fingolimod. Overall, 160 patients (68.8% female) experienced 294 AEFIs, of which about 90% were classified as short-term, while 9.2% were classified as long-term. The most commonly reported following the booster dose were pain at the injection site, flu-like symptoms, headache, fever and fatigue. Regarding the immune response, consistently with literature data, we found that patients receiving ocrelizumab and fingolimod had lower IgG titer than patients receiving other DMTs.

Chronic fatigue syndrome (CFS) and multiple sclerosis (MS) share similarities regarding their epidemiology, symptomatology and craniospinal physiology. Indeed, the cardinal feature of CFS, fatigue, is also a major factor in the symptomatology of the majority of MS patients. Recently, we have found that there is a significant reduction in the craniospinal compliance in MS which affects both the stiffness of the walls of the spinal canal and the walls of the cerebral venous system. This change in compliance brings about an alteration in the effectiveness of the pulse wave dampening in the craniospinal system. The result is an impedance mismatch between the cortical veins and their draining sinuses, leading to dilatation of these upstream veins. We deduce this dilatation can only be brought about by an increase in the pressure gradient between the vein lumen and the subarachnoid space (i.e. the transmural pressure gradient). We hypothesise that given the similarities between MS and CFS, a similar mechanism underlies the physiology of CFS. We present two case studies to highlight the expected findings in CFS patients if this hypothesis were proven to be correct.

Fragility scales are intended to help in therapeutic decisions. Here we asked if the fragility as-sessment in MM patients ≥75 years old qualified for treatment by the local physician correlates with the choice of treatment: a 2- or 3-drug regimen. Between 7/2018 to 12/2019 we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in com-pletely dependent. Patients with more than 3 comorbidities were 26.9% (53 patients). Thus, ac-cording to the Palumbo calculator, 43 patients were in the intermediate-fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received 3-drug regimens and 20.3% (40) received 2-drug regimens. In each ECOG group, more than 3/4 of patients received 3-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received 3-drug regimens. Out of 53 pa-tients with at least 4 comorbidities, 71.7% received 3-drug regimens, and the rest 2-drug regi-mens. Three-drugs regimens received 34 patients from the intermediate-fit group (79.0%), and 123 (79.9%) from the frail group. Early mortality occurred in 25 patients (12.7%). No one discon-tinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with tri-ple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations which questions the clinical utility of current fragility scales in everyday practice.

We are already more than year away from the pandemic period, followed by a year within a global economic crisis and a war in Ukraine, with the marks and the changes caused in all parameters of life becoming clear now including food choice motives of citizens worldwide. In this study we investigate the changes in food choice motives caused by the pandemic to college students in Greece in the 10 key food motives namely health, convenience, sensory, appeal, nutritional quality, moral concerns, weight control, mood and stress, familiarity, price, and shopping frequency and behavior. A self-response questionnaire survey was carried out in January to February 2023 on a sample of 1017 college students’ participants through the Google platform. Basic statistical tools, combined with cross and Chi-square tests were used in order to analyze the collected data. The results show that students exhibit quiet and very important preferences on health, convenience, weight control, and mood and stress. Food choices related to sensory appeal, nutritional quality, and familiarity is of less importance for the students, similarly to ethical concerns expect the environmental impact of the food which is high to their concern. The motive which continues to have the highest concern for students before and after the pandemic is price looking for value for money food (88.8%), not to be expensive (80.7%), and be cheap (78.7%). The shopping frequency and behavior motives, which were changed during the pandemic, have now returned to the motives of the pre pandemic period, with purchase of foods from supermarket (29%), local grocery (37.6%), and only 12.3% via online, and 20.4% by delivery, weekly or every two weeks. They prefer to cook at home full meals is now very high reaching 74.4%, avoiding eating at a restaurant or fast food (only 27% positives answers). Our findings indicate that students have already returned to their food choice motives of the period before COVID-19 except the home cooking food which is now high in their preference.

Ligand-based virtual screening (LBVS) is a promising approach for rapid and low-cost screening of potentially bioactive molecules in the early stage of drug discovery. Compared with traditional similarity-based machine learning methods, deep learning frameworks for LBVS can more effectively extract high-order molecule structure representations from molecular fingerprints or structures. However, the 3D conformation of a molecule largely influences its bioactivity and physical properties, and has rarely been considered in previous deep learning-based LBVS methods. Moreover, the relative bioactivity benchmark dataset is still lacking. To address these issues, we introduce a novel end-to-end deep learning architecture trained from molecular conformers for LBVS. We first extracted molecule conformers from multiple public molecular bioactivity data and consolidated them into a large-scale bioactivity benchmark dataset, which totally includes millions of endpoints and molecules corresponding to 954 targets. Then, we devised a deep learning-based LBVS called EquiVS to learn molecule representations from conformers for bioactivity prediction. Specifically, graph convolutional network (GCN) and equivariant graph neural network (EGNN) are sequentially stacked to learn high-order molecule-level and conformer-level representations, followed by attention-based deep multiple-instance learning (MIL) to aggregate these representations and then predict the potential bioactivity for the query molecule on a given target. We conducted various experiments to validate the data quality of our benchmark dataset, and confirmed EquiVS achieved better performance compared with 10 traditional machine learning or deep learning-based LBVS methods. Further ablation studies demonstrate the significant contribution of molecular conformation for bioactivity prediction, as well as the reasonability and non-redundancy of deep learning architecture in EquiVS. Finally, a model interpretation case study on CDK2 shows the potential of EquiVS in optimal conformer discovery. The overall study shows that our proposed benchmark dataset and EquiVS method have promising prospects in virtual screening applications.

The main problem in pursuing multiple extended targets tracking is distinguishing the origins of the measurements. The association of measurements to the possible origins within the target’s extent is difficult, especially for the occlusions or the detection blind zone which cause the intermittent measurements. To solve the problem, a hierarchical network-based tracklets data association algorithm is proposed. At the low level, the min cost network flow model is used to extract possible tracklets from the divided measurement set. At the high-level, the trajectories are estimated from the tracks produced by the previous low level network. The experimental results show that the hierarchical network-based tracklets data association algorithm outperforms the JPDA and RFS-based method when the measurement is intermittently unavailable.

Multiple sclerosis (MS) is a heterogeneous disease of the central nervous system that is governed by neural tissue loss and dystrophy during its progressive phase, with complex reactive pathological cellular changes. The immune-mediated mechanisms that promulgate the demyelinating lesions during the relapses of acute episodes are not characteristic of chronic lesions during progressive MS. This has limited our capacity to target the disease effectively as it evolves within the central nervous system white and gray matter, thereby leaving neurologists without effective options to manage individuals as they transition to a secondary progressive phase. The current review highlights the molecular and cellular sequelae that have been identified to cooperate and/or contribute to neurodegeneration that identifies individuals with progressive forms of MS. We emphasize the need for appropriate monitoring via known and novel molecular and imaging biomarkers that can accurately detect and predict progression for the purposes of newly designed clinical trials that may demonstrate efficacy of neuroprotection and potentially neurorepair. To achieve neurorepair, we focus on the modifications required in the reactive cellular and extracellular milieu, in order to enable endogenous cell growth as well as transplanted cells that can integrate and/or renew the degenerative MS plaque.

Bi-clonal gammopathy is distinguished by the presence of two different or distinct monoclonal proteins, due to a proliferation of two distinct monoclonal plasma cell clones. A single monoclonal clone can give rise to two different monoclonal proteins. In this report, we present three cases of biclonal multiple myeloma and one case of Waldenstrom's disease that exhibits two biclonal peaks. Serum protein electrophoresis showed two M bands on serum protein electrophoresis.

In response to long-lasting high levels of Metallic Trace Elements (MTEs) in urban soils, we expect soil invertebrates inhabiting urban environments to have evolved detection and avoidance and/or tolerance mechanisms to MTE pollution. In this study, I used artificial soils with concentrations of lead, zinc, copper, chromium and nickel that reflect pollution levels in soils of Parisian parks. Using choice experiments, I compared habitat preference (i.e. the occurrence of individuals in the polluted vs. unpolluted soil) and health status (i.e. body mass maintenance, mobility, mortality) between three species of endogeic earthworms – Apporectodea caliginosa, Apporectodea icterica and Allolobophora chlorotica – originating either from urban or rural grasslands. This study highlights a clear avoidance of MTE polluted soils in all three species, as well as MTE-induced health impairments, especially in A. chlorotica. Interestingly, earthworm response to MTE exposure only slightly differed between earthworms from urban and rural origin, suggesting the absence of widespread acclimatization or adaptation mechanisms to MTE pollution in cities. As a consequence, MTE pollution is expected to significantly shape earthworm spatial distribution in both urban and rural environments and, as a consequence, affect ecosystem functioning.

Purpose: The purpose of this study was to evaluate the dosimetric impact of multiple channels compared to a single channel in high dose rate (HDR) vaginal cuff brachytherapy (VCBT). Methods and materials: Sample plans of HDR VCBT from both single and multiple channel cylinders at 2.5, 3.0 and 3.5 cm in diameter were created and analyzed. The doses were prescribed either at the 0.5 cm depth with 5.5 Gy for 4 fractions or at the cylinder surface with 8.8 Gy for 4 frac¬tions, in various treatment lengths ranging from 3 to 8 cm. A 0.5 cm ring target volume called PTV_Eval was contoured for each plan and served as the target volume for dosimetric evaluation. Mean doses and the doses covering 90% (D90), 10% (D10), and 5% (D5) of PTV_Eval were calculated and compared. The same treatment lengths, same prescription regimens, same target volume contouring and same plan evaluation methods were repeated for the similar size single channel and multiple channel cylinders. Results: The mean doses of both regimens with the multi-channel cases (6.3 to 7.1 Gy) were comparable to single channel ones (6.4 and 7.5 Gy). The ranges of D90, D10 and D5 were from 3.654 to 5.04 Gy, 8.44 to 10.08 Gy and 8.84 to 10.86 Gy in the multi-channel cases, but from 5.36 to 5.76 Gy, 7.40 to 9.97 Gy and 8.16 to 11.93 Gy in the single channel cases, respectively. Conclusion: The single channel and multiple-channel cylinder deliver a similar mean dose, but with marked heterogeneity in D90, D5 and D10 for the same prescription dose and target volume. Multi-channel cylinders adequately cover the target volume, but given the heterogeneity, increased treatment time and cost are best suited for asymmetric target volumes.

Multiple myeloma (MM) is an incurable hematological cancer. It is preceded by monoclonal gammopathy of uncertain significance (MGUS), an asymptomatic phase. It has been demonstrated that early detection increases the 5-year survival rate. However, blood-based biomarkers that enable early disease detection are lacking. Metabolomic and lipoprotein subfraction variable profiling is gaining traction to expand our understanding of disease states and, more specifically, for identifying diagnostic markers in patients with hematological cancers. This study aims to enhance our understanding of multiple myeloma (MM) and identify candidate metabolites, allowing for more effective preventative treatment. Serum was collected from 25 healthy controls, 20 patients with MGUS, and 30 patients with MM. 1H-NMR (nuclear magnetic resonance) spectroscopy was utilized to evaluate serum samples. The metabolite concentrations were examined using multivariate, univariate, and pathway analysis. Metabolic profiles of the MGUS patients revealed lower levels of alanine (F.C. = 0.8, p = 0.002), lysine (FC = 0.8, p &lt; 0.001), leucine (FC=0.7, p &lt; 0.001) but higher levels of formic acid (FC=1.6, p ≤ 0.001) when compared to controls. However, metabolic profiling of MM patients compared to controls exhibited decreased levels of total Apolipoprotein-A1 (FC =0.6, p&lt;0.001), HDL-4 Apolipoprotein-A1 (FC = 0.5, p ≤ 0.001), HDL-4 Apolipoprotein-A2 (FC = 0.6, p &lt; 0.001), HDL Free Cholesterol (FC = 0.7, p &lt; 0.001), HDL-3 Cholesterol (FC = 0.5, p ≤ 0.001) and HDL-4 Cholesterol (FC = 0.5, p ≤ 0.001). Lastly, metabolic comparison between MGUS to MM patients primarily indicated alterations in lipoproteins levels: Total Cholesterol (FC = 0.6, p ≤ 0.001), HDL Cholesterol (FC = 0.7, p ≤ 0.001), HDL Free Cholesterol (FC = 0.4, p ≤ 0.001), Total Apolipoprotein-A1 (FC = 0.7, p ≤ 0.001), HDL Apolipoprotein-A1 (FC = 0.7, p ≤ 0.001), HDL-4 Apolipoprotein-A1 (FC = 0.6, p ≤ 0.001) and HDL-4 Phospholipids (FC = 0.6, p ≤ 0.001). This study provides novel insights into the serum metabolic and lipoprotein subfraction changes in patients as they progress from a healthy state to MGUS to MM, which may allow for earlier clinical detection and treatment.

This paper is concerned with the optimal linear quadratic Gaussian (LQG) control problem for discrete time-varying system with multiple input delays and multiplicative noises. The main contributions are two-fold. Firstly, when the state variables can be observed exactly, we obtain a necessary and suffcient condition for the multiple-delays system in terms of the non-homogeneous relationship between the state and costate, which is the solution to the coupled forward and backward stochastic difference equations. Secondly, when the state variables are partially observed, we derive a suboptimal linear output feedback controller for the discrete-time system based on the obtained results of the optimal LQG control. Numerical examples are shown to illustrate the proposed algorithm.

Demyelinating diseases alter myelin or the coating surrounding most nerve fibers in the central and peripheral nervous systems. The grouping of human central nervous system demyelinating disorders today includes Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorders (NMOSD) as distinct disease categories. Each disease is caused by a complex combination of genetic and environmental variables, many involving an autoimmune response. Even though these conditions are fundamentally similar, research into genetic factors, their unique clinical manifestations, and lesion pathology has helped with differential diagnosis and disease pathogenesis knowledge. This review aims to synthesize the genetic approaches that explain the differential susceptibility between these diseases, explore the overlapping clinical features, and pathological findings, discuss existing and emerging hypotheses on the etiology of demyelination, and assess recent pathogenicity studies and their implications for human demyelination. This review presents critical information from previous studies on the disease, which asks several questions to understand the gaps in research in this field.

The aim of this study was to investigate the potential of converting potato peel waste into bio ethanol using an in-house produced multi-enzyme preparation. To achieve this, a variety of pre-treatment strategies, including thermal, chemical, and thermo-chemical methods, were applied to the potato peels. These included boiling for 30 and 60 min, steam at varying pressures and times, and different concentrations of chemicals such as H2SO4, HNO3, CH3COOH, HCl, NaOH, Ca(OH)2, KOH, NH3, and H2O2, either alone or in combination with steam. The pre-treated potato peels were then enzymatically hydrolyzed using a crude multi-enzyme cocktail derived from solid-state fermentation of wheat bran by a natural variety of Aspergillus niger P-19, containing cellulases, hemicellulases, pectinase, and amylases. The most effective pre-treatment combination was found to be 3% H2SO4 followed by steam under pressure and enzymatic hydrolysis using the crude multi-enzyme preparation. This combination resulted in the highest yield of reducing sugars (141.04 ±12.31 g/l) with a 98.49% carbohydrate conversion at a 20% substrate loading, giving an ethanol yield of 43.2 g/l. Furthermore, supplementing the medium with peptone, (NH4)(H2PO4), and ZnSO4 at 0.1%w/v each with 22% and 24% solid, respectively, resulted in appreciable yields of 51.67 and 54.75 g/l, further enhancing the ethanol yield.

Appetitive traits have been associated with eating behaviors and weight in youth. However, the relationships among adults have received less attention. In this study, we measured appetitive traits among 520 female college students from a University in eastern Chinese using the Chinese translated Adults Eating Behavior Questionnaire (C-AEBQ) and found that two food approach traits (food enjoyment and emotional over-eating) were positively while two food avoidance traits (slowness in eating and satiety responsiveness) were negatively associated with BMI. Individual trait was differentially associated with eating behaviors. Specifically, a positive correlation was found between food responsiveness and higher frequency of selecting delivery food, spicy food, and sugared beverage; conversely, satiety responsiveness was associated with higher frequency of skipping meals. Using latent profile analysis, participants were classified into four appetitive patterns: food approacher, food approacher with emotional under-eating, food avoider, and food avoider with emotional over-eating. Food avoiders had significant lower BMI and higher proportion of underweight than other three patterns. Compared to food approacher, food avoiders had higher frequency of skipping breakfast, and food avoiders with emotional over-eating had higher frequency of skipping both breakfast and lunch. No significant differences were observed in food choice and dieting behavior among four appetitive patterns. The findings suggested a correlation between an individual’s appetitive pattern and eating behaviors among female college students, those with food avoidance patterns are more likely to have irregular meals, which may contribute to their low BMI. The findings provide valuable insights for female college students to cultivate a healthy eating behavior and sustain a healthy body weight.

Electrical power quality is one of the main elements in power generation systems. At the same time, it is one of the most significant challenges regarding stability and reliability. Due to different switching devices in this type of architecture, different kinds of power generators, and non-linear loads are used for different industrial processes. As a result of this, the need to classify and analyze Power quality disturbance (PQD) to prevent and analyze the degradation of the system reliability affected by the non-linear and non-stationary oscillatory nature. This paper presents A Novel Mul-titasking Deep Neural Network (MDL) for the Classification and Analysis of Multiple Electrical Disturbances. The characteristics are extracted with a specialized and adaptive methodology for non-stationary signals, Empirical Mode Decomposition (EMD). The methodology’s design, devel-opment, and various performance tests are carried out with 28 different difficulty levels, such as severity, disturbance duration time, and noise in the 20 dB to 60 dB signal range. MDL was devel-oped with a diverse data set in difficulty and noise, with a quantity of 4500 records of different samples of multiple electrical disturbances. The analysis and classification methodology has an average accuracy percentage of 95% with multiple disturbances. In addition, an average accuracy percentage of 90% in analyzing important signal aspects for studying electrical power quality such as crest factor, Per Unit voltage analysis, Short Term Flicker Perceptibility (Pst), and Total Harmonic Distortion (THD), among others.

Despite the recent approval of novel immunotherapies, as immunomodulatory drug, proteasome inhibitors and anti-CD38 monoclonal antibodies, Multiple Myeloma (MM) remains incurable and the acquisition of triple-refractoriness leads to really dismal outcomes, in even earlier lines of therapy. More recently, innovative therapeutic strategies targeting B cell maturation antigen (BCMA), highly expressed on the plasma cell surface, are drawing different future landscapes in terms of effectiveness and outcomes. Belantamab Mafodotin, a first-in-class anti-BCMA antibody drug conjugates, demonstrated good efficacy and safety profile in triple-refractory patients in the phase 2 DREAMM-2 trial and it was approved for the treatment of MM triple-exposed patients with >4 prior lines of therapy. Here, starting from Belantamab Mafodotin clinical trials also exploring combination studies and different schedules in order to improve its efficacy and toxicity, we focused on real life experiences all over the world, which have confirmed clinical trial data and encourage further Belantamab Mafodotin investigations

In this paper, we will extend the expected value of the function w.r.t the uniform probability measure on sets measurable in the Caratheodory sense to be finite for a larger class of functions, since the set of all measurable functions with infinite or undefined expected values forms a prevalent subset of the set of all measurable functions, which means "almost all" measurable functions have infinite or undefined expected values. Before we define the specific problem in section 2, we will outline some preliminary definitions. We'll then define the specific problem (along with a partial solution in section 3) to visualize the complete solution. Along the way, we will ask a series of questions to clarify our understanding of the paper.

With the proliferating of video surveillance system deployment and related applications, real-time video analysis is very critical to achieve intelligent monitoring, autonomous driving, etc. It is non-trivial to achieve high accuracy and low latency video stream analysis through the traditional cloud computing. In this paper, we propose a non-orthogonal multiple access (NOMA) based edge real-time video analysis framework with one edge server (ES) and multiple user equipments (UEs). A cost minimization problem composed of delay, energy and accuracy is formulated to improve the QoE of UEs. In order to efficiently solve this problem, we propose the joint video frame resolution scaling, task offloading, and resource allocation algorithm based on the Deep Q-Learning Network (JVFRS-TO-RA-DQN), which effectively overcomes the sparsity of the single-layer reward function and accelerates the training convergence speed. JVFRS-TO-RA-DQN consists of two DQN networks to reduce the curse of dimension, which respectively select the offloading and resource allocation action, the resolution scaling action. Experimental results show that JVFRS-TO-RA-DQN can effectively reduce the cost of transmission and computation, and have better performance in convergence compared to other baseline.

It is widely acknowledged that adolescent females are particularly at risk of low body-esteem. Low body-esteem is associated with poor mental health and other negative outcomes. Interventions to help raise body-image could have considerable impact, especially if the intervention is low-cost, easy to implement and scalable. We investigated the efficacy of an intervention where participnants could chose their own clothes to wear during a Physical Education (PE lesson) on changes in body-esteem. We hypothesized that body-esteem would improve with choice. To show that body-esteem is not a transient construct, we tested its stability when assessed in a test-retest design when completed in a classroom setting, hypothesizing body-esteem would be stable. Participants (N =110; Mage =14.9; SDage = 0.68) females completed a 14-item body-esteem scale 4 times; a) wearing school uniform in an assembly, b) during a PE lesson separated by a 2-week gap. The intervention was implemented where students got a choice of PE kit and could wear their own clothes. Findings indicate that body-esteem was stable in the classroom setting where clothes and context were stable, but improved significantly when participants were given a free choice of kit to wear during PE. We argue that this low-cost and scalable intervention represents a useful start point for helping support low body-esteem among a potentially vulnerable population.

The study sought to investigate the effect of Multi-choice Goal programming in project Portfolio Analysis, using Lagos State Project Portfolio from between 2017-2021 as a study case. Specifically, the objectives examined the effectiveness of multi-choice goal programming in analyzing the project Portfolio of Lagos State Government and investigated the possible lapses in the use of Multi-choice Goal programming in analyzing the project Portfolio of Lagos State Government. Data were gathered from the State financial Statements and analyzed using Lingo-17 Software. Based on the analysis, the study discovered that the goals formulated can be optimally and minimally attained as the positive deviational and negative deviational variables depict zero. This indicates that the cost incurred on the project portfolio was absolutely minimized during the period and at the same time; Lagos State Government derived the most preferred benefits from it. The study therefore concluded that the State minimized the project costs and at the same time maximized benefits while meeting its overall objectives.

Background: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder that has no curative treatment. Diagnosis is based on a set of criteria established by Gilman (1998 and 2008) and recently updated by Wenning (2022). We aim to determine the effectiveness of [123I]Ioflupane SPECT in MSA, especially at the initial clinical suspicion. Methods: Cross-sectional study of patients at initial clinical suspicion of MSA, referred for [123I]Ioflupane SPECT. Results: 139 patients (68 men, 71 women) were included, 104 being MSA-probable and 35 MSA-possible. MRI was normal in 89.2% while SPECT was positive in 78.45%. SPECT showed high sensitivity (82.46%) and positive predictive value (86.24), reaching maximum sensitivity in MSA-P (97.26%). Significant differences were found when relating both SPECT assessments in the healthy-sick and inconclusive-sick groups. We also found an association when relating SPECT to the subtype (MSA-C or MSA-P), as well as to the presence of parkinsonian symptoms. Lateralization of striatal involvement was detected (left side). Conclusions: [123I]Ioflupane SPECT is a useful and reliable tool for diagnosing MSA, with good effectiveness and accuracy. Qualitative assessment shows a clear superiority when distinguishing between the healthy-sick categories, as well as between the parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes at initial clinical suspicion.

The gelation time tg necessary for a solution of functional (associating) molecules to reach its gel point after a temperature jump, or a sudden concentration change, is theoretically calculated as a function of the concentration and temperature for the molecules carrying the number f of functional groups. Quite generally, tg is given by the product of the relaxation time tR and a thermodynamic factor Q. For pairwise cross-linking, and cross-linking with a fixed multiplicity k, precise values of tg are derived. For cross-linking with variable multiplicity, kinetic equation of stepwise association is derived for the reactivity pk of the functional groups, on the basis of which tg and tR are estimated. The thermodynamic factor Q is shown to generate a singularity of logarithmic divergence as the temperature (concentration) approaches the equilibrium gel point, while the relaxation time tR changes continuously across it. The retardation effect on the gelation time due to the reversibility of the cross-linking is explicitly calculated for some specific models of cross-linking. For a micellar cross-linking covering a wide range of the multiplicity, as seen in hydrophobically-modified water-soluble polymers, tR is shown to obey a formula similar to the Aniansson-Wall law.

Introduction: Unlike cigarette smoking, secondhand smoke (SHS) has not been as well described as an environmental risk for Multiple sclerosis (MS) nor as a risk factor for disease progression. We systematically reviewed the association between SHS and the risk of onset and/or progression of MS.Methods: We systematically screened MEDLINE/PUBMED, Science Direct, LILACs, and SCIELO searching for publications between January 1st , 2010, and July 5, 2021 with the following keywords: “multiple sclerosis and smoking”; “multiple sclerosis and passive smoking”; “multiple sclerosis and secondhand smoking”. An 11-year filter was applied from 2010 to 2021. Results: Fifteen articles were included in this review, which consisted of systematic reviews with meta-analysis (N = 2), systematic reviews (N = 2), and observational studies (N = 11). Both meta-analyses reported an impact of SHS on MS onset among secondhand smokers. One of the systematic reviews selected two observational studies showing the association between SHS and MS development, and one study that did not find a significant association between SHS and the risk of MS development. The other systematic review identified selected eight articles showing a relationship between SHS and MS. Seven observational studies reported higher odds of MS onset when associated with SHS. Four observational studies did not show a relationship between SHS and MS onset or progression.Discussion: Most articles showed a positive association between SHS exposure and the risk of developing MS. On the other hand, an association between SHS and a higher risk for MS progression could not be established.

Machine Learning (ML) was used to assess and predict urban air temperature (Tair) considering the complexity of the terrain features in Yerevan (Armenia). The estimation was performed based on the PLSR model with a high number (30) of input variables. The relevant parameters include a newly purposed modification of spectral index IBI-SAVI, which turned out to be strongly impacting on Tair prediction together with land surface temperature (LST). Cross-validation analysis on temperature predictions across a station-centered 1000m circular area revealed quite a high correlation (R2Val = 0.77, RMSEVal = 1.58) between predicted and measured Tair from the test set. It was concluded the remote sensing is an effective tool to estimate Tair distribution where a dense network of weather stations is not available. However, further developments will include incorporation of additional weather parameters from the weather stations such as precipitation and wind speed, and the use of non-parametric ML techniques.

Traditional grain vinegar is fermented using multiple acetic acid bacteria (AAB) at various temperatures. A single AAB showed high acid–producing ability at 30 °C with a 5% alcohol concentration and an initial pH adjusted to 4.0. Multiple AAB were similar to single AAB, but the optimal initial pH was 3.0. Acid production ability according to the type of AAB was higher in multiple AAB than that for single AAB. That is, using multiple AAB helped to increase the titratable acidity of traditional grain vinegar. In addition, increasing the titratable acidity and content of volatile flavor compounds was advantageous when two, rather than four, AAB types were mixed and used. Titratable acidity was high at medium temperatures (30 °C), but volatile flavor compounds increased at low temperatures (20 °C) under multiple AAB. A 16S rDNA–based microbiome taxonomic profiling analysis identified differences in beta diversity due to multiple AAB and fermentation temperatures. In particular, beta diversity analysis revealed a specific pattern when a mixture of Acetobacter ascedens GV–8 and Acetobacter pasteurianus GV–22 were fermented at low temperature (20 °C). Therefore, we propose the application of multiple AAB with acidic and flavor–producing properties in traditional grain vinegar.

Particles and photons appear to be total opposites; the former has rest mass which requires space to exist; the latter has kinetic energy which requires time to occur (oscillate). But they do share certain properties (e.g., quantization) that remain invariant when one is transformed (swapped) for the other. This gauge invariance is developed in some detail.The symmetry between particle and photon turns out to be one of inversion. It is the equalities of special relativity that support this inversion and the accompanying invariances: mass transformed to energy; space transformed to time. The great advantage of these symmetries (inversions) is that they provide guidance for an object little understood (the photon) based upon an object well understood (the particle). On this basis, progress can be made in the understanding of some long-standing issues: wave-particle duality, time’s arrow, the constant speed of light and nonlocality.

In engineering practice, various types of information data are affected by many factors during the collection process. For example, information data measurement errors are caused by equipment performance and the working environment. During the transmission of detection information, the signal distortion caused by energy loss and signal interference causes unpredictable detection errors in the collected information data. Through the study of fractional calculus theory, it was found that it is suitable for studying nonlinear, non-causal, and non-stationary signals, and has the dual functions of improving detection information and enhancing signal strength. Therefore, under the influence of many factors, we applied the fractional difference algorithm to the field of information data processing. Multi-sensor detection data fusion algorithm based on the fractional partial differential equation was adopted to establish its online detection data. A multi-sensor detection data fusion algorithm based on a fractional partial differential equation is established, which effectively fuses the information data detection errors caused by various influencing factors and greatly improves the detection accuracy of information data. The effectiveness of this method is proved through its application in an experiment.

This article proposes the use of intranasal rifampin as a means to improve protein homeostasis and disaggregate misfolded proteins in the age-related neurodegenerative proteinopathies. Alzheimer’s disease, Parkinson’s disease, multi-system atrophy, Lewy body dementia, frontotemporal dementia, amyotrophic lateral sclerosis and Huntington’s disease are all, at the core, proteinopathies. Although these diseases varying greatly in the specific disease-associated proteins, anatomic sites of the abnormal protein deposition and clinical presentations, what they have in common is disruption of normal “housekeeping” functions related to protein homeostasis, proteostasis. The prospect of pharmacologically augmenting autophagic capacity with a known drug repurposed to improve proteostasis is attractive; to accomplish these ends with an inexpensive drug with relative ease of delivery adds to the attractiveness. Rifampin can be delivered to the brain via the intranasal route. Rifampin has been used for decades primarily against mycobacterial infection; it has been given with intravenous, oral, intrathecal and topical routes including as eyedrops and nasal spray. Rifampin disaggregates toxic oligomers in vitro; given intranasally, rifampin improves memory and clears pathologic proteins in animal models of the proteinopathies. Rifampin acts as both a gatekeeper and a housekeeper against the abnormal proteins of these diseases. This article suggests the merit of a clinical trial with intranasal rifampin to boost protein homeostasis in the most common age-related neurodegenerative proteinopathy, Alzheimer’s disease. The primary outcome of such a trial is change in risk of Alzheimer’s pathology as measured by plasma-based amyloid peptide 42/40 testing pretreatment and follow-up testing after 6 months of intranasal rifampin.

The paper portrays a linear model for synchronous prediction of the dissolved oxygen (DO) level in a protected urban lake by using independent variables in real-time monitoring of the water quality parameters. Multi-linear regression and machine learning techniques were applied to the Dissolved Oxygen (DO) using the basic four parameters of Water Quality Index (WQI). Three real-time industry standard sensors PHEHT, CTZN, OPTOD were used for sampling, data was then interpolated through ArcGIS kriging method. 25 correlations were checked through the ML algorithm, a correlation heat map was produced and the top five relations were taken under consideration and validated by r-score and root mean squared error (RMSE) to develop the linear regression model. The performance of the model was validated through the RMSE, mean squared error (MSE), and mean absolute error (MAE) the r2 accuracy came to 0.983 when it is checked against the sample data. The suggested model can be used as a technique for unknown or malfunctioned sensor’s null DO data prediction.

This paper gives solutions to puzzles of double Wheeler’s delayed choice experiments, a photon’s passing two paths simultaneously and wave collapse velocity measure, and shows new quantum control, new quantum oscillation and new controlling photon oscillator (that can be arranged in quantum computer and quantum network as their classical correspondences) in experiments. Furthermore, this paper obtains the measured attractive state and the new useful key technology of altering state’s evolving paths for quantum systems. We discover the reason and the technological way for the present changes the past, further show their feasible experiments of new quantum control, new quantum oscillation and new quantum oscillator. Finally, this paper achieves the collapse response time t of wave, further concretely deduces the measured collapse velocity of quantum system. In the past, the collapse velocity cannot be objectively deduced and experimentally measured.

A progressive and chronic neurological condition called MSA (Multiple System Atrophy) is characterized clinically by varying degrees of dysautonomia, cerebellar ataxia, and parkinsonism. The concept of mitochondrial dysregulation in MSA is one perspective in handling this neurodegenerative disease. Damage to functional mitochondria is driven by the presence of ɑ-Synuclein-induced mitochondrial localization. The goal of MSA treatment up until now has been to reduce symptoms. One of the innovations in the treatment of MSA could be the novel idea based on mitochondrial reprogramming pathways. Mitochondrial reprogramming can be done in various ways in which the use of hydrogen, magnesium and low-dose hydrogen peroxide.

The purpose of the study is to empirically analyze the effect of quality of governance on tax revenue in South Africa. This is done by analyzing a time series dataset covering 1996 to 2020. The study used voice and accountability, regulatory quality, government effectiveness, control of corruption, political stability and rule of law as proxies of quality of governance. Multiple regression analysis was performed to test hypotheses. Based on the regression results, all quality of governance variables in South Africa have a negative effect on tax revenue except corruption control. The findings of this study also include policy recommendations. The government of South Africa must design and implement effective ways to combat poor governance, which results in a tax revenue shortfall.

The BRFSS is an annual survey conducted by each state and designed to identify trends in a representative sample of the resident population. In its 2019 field survey, the U.S. state of Georgia tested a new 3 – item module to measure the numbers of bereaved, resident adults. Bereavement means that participants answered, ‘Yes’ to the item ‘Have you experi-enced the death of a family member or close friend in the years 2018 or 2019?’. This analysis addresses two questions. Can estimates for bereavement prevalence be derived without large sampling errors, low precision, and small subsamples? Can multiple imputation techniques be applied to overcome non-response and missing data to support multivari-ate modeling? Analyses in this study were conducted under two scenarios. Scenario 1 ap-plies the complex sample weights created by the Centers for Disease Control and imputes values for missing responses. Scenario 2 treats the data as a panel – no weighting com-bined with removal of persons with missing data. Scenario 1 reflects the use of BRFSS data for public health and policy, while Scenario 2 reflects data as it is commonly used in so-cial science research. The bereavement item has a response rate (RR) of 70.8% (5206 of 7534 persons). Subgroups have RR of 55% or more. Under Scenario 1, the prevalence of bereavement is 45.38%, meaning that 3,739,120 adults reported bereaved in 2018 or 2019. The prevalence is 46.02% with Scenario 2 which removes persons with any missing data (4,289 persons). Scenario 2 overestimates the bereavement prevalence by 1.39%. An il-lustrative logistic model is included to show the performance of exposure to bereavement under each scenario. Recent bereavement can be ascertained in a surveillance survey without biases in response. This survey is limited to one US state in a single year and ex-cludes persons aged 17 years and younger.

We make use of generalized iterations of the Sacks forcing to define cardinal-preserving generic extensions of the constructible universe L in which the axioms of ZF hold and in addition either 1) the parameter-free countable axiom of choice AC* fails, or 2) AC* holds but the full countable axiom of choice AC fails in the domain of reals. In another generic extension of L, we define a set X⊆P(ω), which is a model of the parameter-free part PA2* of the 2nd order Peano arithmetic PA2, in which CA(Σ21) (Comprehension for Σ21 formulas with parameters) holds, yet an instance of Comprehension CA for a more complex formula fails. Treating the iterated Sacks forcing as a class forcing over $L_{\omega_1}$, we infer the following consistency results as corollaries. If the 2nd order Peano arithmetic PA2 is formally consistent then so are the theories: 1) PA2 + negation of AC*, 2) PA2 + AC* + negation of AC, 3) PA2* + CA(Σ21) + negation of CA.

The notion of oriented set is the basic elementary concept of the theory of changeable sets. The main motivation for the introduction of changeable sets was the sixth Hilbert problem, that is, the problem of mathematically rigorous formulation of the fundamentals of theoretical physics. In the present paper the necessary and sufficient condition of the existence of one-point time on an oriented set is established. From the intuitive point of view, one-point time is the time associated with the evolution of a system consisting of only one object (for example, from one material point). Namely, it is proven that the one-point time exists on the oriented set if and only if this oriented set is a quasi-chain. Also, using the obtained result, the problem of describing all possible images of linearly ordered sets is solved. This problem naturally arises in the theory of ordered sets.

The emerging advancements in separation and classification of various biological matters (e.g., living cells and proteins) using magnetic levitation (MagLev) technology have proven to be effective for improving disease diagnostics. MagLev technique has the capacity to detect and separate useful diagnostic biomarkers from biocomplex environments (e.g., blood and plasma), minimizing the unpleasant daunting task of sample preparations and labeling procedures. Here, we demonstrate the capability of this technique combined with image analysis and machine learning approaches for discriminating the various types of multiple sclerosis (MS) as an important model disease. To arrive at a systematic expert system, we combined robust statistical analysis with machine learning to (1) detect and remove outliers from the raw MagLev image datasets; then (2) process the images and output a low dimensional representation of massive data without losing the main statistical features; and finally (3) predict the MS clinical disease type (Relapsing-Remitting, Primary–Progressive, or Secondary–Progressive) using a classifier. This is expected to improve MS diagnostics since the current practices rely solely on clinical observation and central nervous system imaging, making management approaches are often reactional and inefficient. Thus, there is a need to identify the disease type early on. MagLev is expected to improve MS diagnostics, thereby aiding in prognosis and guiding adequate treatment choices before the patient exhibits signs of permanent neurological deficits.

Multiple sclerosis (MS) is a demyelinating autoimmune disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely used to determine the pathogenesis of the disease and evaluate new treatment strategies for MS. Therefore, we investigated the efficacy of oral administration of a Myelin Oligodendrocyte Glycoprotein (MOG) in the treatment of EAE. Female C57BL/6 mice were utilized in three groups (Control group: received PBS orally; prevention group: oral administration of MOG35-55 two weeks before EAE induction; treatment group: oral administration of MOG35-55 after EAE induction. MOG administration, both as prevention and treatment, significantly controlled clinical score, weight loss, CNS inflammation, and demyelination, mainly through the modulation of T cell proliferation, reduction of pro-inflammatory cytokines and transcription factors, including TNF-α, IFN-γ, IL-17, T-bet, and ROR-γt. MOG administration, both as prevention and treatment, also induced anti-inflammatory cytokines and transcription factors, including IL-4, TGF-β, GATA-3, and Foxp3. The results showed that oral administration of MOG, both as prevention and treatment, could efficiently control EAE development. Immunomodulatory mechanisms include the induction of Th2 and Treg cells and the suppression of pro-inflammatory Th1 and Th17 cells.

Guessing effects frequently occur in testing data in educational or psychological applications. Different item response models have been proposed to handle guessing effects in dichotomous test items. However, it has been pointed out in the literature that the oftenemployed three-parameter logistic model poses implausible assumptions regarding the guessing process. The four-parameter guessing model has been proposed as an alternative to circumvent these conceptual issues. In this article, the four-parameter guessing model is compared with alternative item response models for handling guessing effects through a simulation study and an empirical example. It turned out that model selection for item response models should be rather based on the AIC than the BIC. However, the RMSD item fit statistic used with typical cutoff values was found to be ineffective in detecting misspecified item response models. Furthermore, sufficiently large sample sizes are required for sufficiently precise item parameter estimation. Moreover, it is argued that the criterion of statistical model fit should not be the sole criterion of model choice. The item response model used in operational practice should be valid with respect to the meaning of the ability variable and the underlying model assumptions. In this sense, the four-parameter guessing model could be the model of choice in educational large-scale assessment studies.

Fringe projection profilometry(FPP) has been extensively applied in various fields for its superior fast speed, high accuracy and high data density. However, measuring some objects with high reflective surfaces or high dynamic range surfaces remains challenging for FPP. Some multiple exposure image fusion methods have been proposed and successfully improved the measurement performance for these kinds of objects. Normally, these methods have a relatively fixed sequence of exposure settings determined by artificial experience or trial and error experiments, which may decrease the efficiency of the entire measurement process and may have less robustness to various environmental lighting conditions and object reflective properties. In this paper, a novel self-adaptive multiple exposure image fusion method is proposed with two main aspects of improvement on adaptively optimizing the initial exposure and the exposure sequence. By introducing the theory of information entropy, combined with the analysis of the characterization of fringe image entropy, an adaptive initial exposure searching method is first proposed. Then, an exposure sequence generation method based on dichotomy is further described. On the base of these two improvements, a novel self-adaptive multiple exposure image fusion method for FPP as well as its detailed procedures are given. Experimental results validate the performance of the proposed self-adaptivity multiple exposure image fusion method by measuring the objects with different surface reflectivity and in different ambient lighting conditions.

Multilabel learning goes beyond standard supervised learning models by associating a sample with more than one class label. Among the many techniques developed in the last decade to handle multilabel learning best approaches are those harnessing the power of ensembles and deep learners. This work proposes merging both methods by combining a set of gated recurrent units, temporal convolutional neural networks, and long short-term memory networks trained with variants of the Adam optimization approach. We examine many Adam variants, each fundamentally based on the difference between present and past gradients, with step size adjusted for each parameter. We also combine Incorporating Multiple Clustering Centers and a bootstrap-aggregated decision trees ensemble, which is shown to further boost classification performance. In addition, we provide an ablation study for assessing the performance improvement that each module of our ensemble produces. Multiple experiments on a large set of datasets representing a wide variety of multilabel tasks demonstrate the robustness of our best ensemble, which is shown to outperform the state-of-the-art. The MATLAB code for generating the best ensembles in the experimental section will be made available at https://github.com/LorisNanni.

In recent years, new treatments have been studied for relapsed-refractory multiple myeloma (RRMM), including two CAR-T products and a variety of non CAR-T agents. Since direct comparisons between these innovative treatments are not available, indirect comparisons can be of interest. Reconstruction of individual patient data from Kaplan-Meier graphs (Shiny method) has been employed in numerous reports that have validated its performance. In the present review, we evaluated six treatments proposed for RRMM including two CAR-T products (ciltacabtagene autoleucel and idecabtagene vicleucel) and four treatments not based on a CAR-T (melflufen plus dexamethasone, isatuximab plus dexamethasone, selinexor, and belantamab). The end-point was overall survival (OS); the Shiny method was used to generate reconstructed survival curves. Our results showed statistically significant differences in OS across these treatments. Compared with pharmacological treatments, CAR-T products significantly prolonged OS with an improvement of remarkable clinical relevance. In particular, ciltacabtagene autoleucel showed better OS than idecabtagene vicleucel. As regards non CAR-T treatments, the ranking in OS was headed by isatuximab plus dexamethasone, followed by belantamab, selinexor, and melflufen plus dexamethasone. In conclusion, while the Shiny method has confirmed its validity in reconstructing individual patient data, our indirect comparisons have offered some original clues to better interpret the information on OS published in these studies.

Multiple sclerosis (MS) is a demyelinating autoimmune disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely used to determine the pathogenesis of the disease and evaluate new treatment strategies for MS. Therefore, we investigated the efficacy of oral administration of a Myelin Oligodendrocyte Glycoprotein (MOG) in the treatment of EAE. Female C57BL/6 mice were utilized in three groups (Control group: received PBS orally; prevention group: oral administration of MOG35-55 two weeks before EAE induction; treatment group: oral administration of MOG35-55 after EAE induction. MOG administration, both as prevention and treatment, significantly controlled clinical score, weight loss, CNS inflammation, and demyelination, mainly through the modulation of T cell proliferation, reduction of pro-inflammatory cytokines and transcription factors, including TNF-α, IFN-γ, IL-17, T-bet, and ROR-γt. MOG administration, both as prevention and treatment, also induced anti-inflammatory cytokines and transcription factors, including IL-4, TGF-β, GATA-3, and Foxp3. The results showed that oral administration of MOG, both as prevention and treatment, could efficiently control EAE development. Immunomodulatory mechanisms include the induction of Th2 and Treg cells and the suppression of pro-inflammatory Th1 and Th17 cells.

We report the first case of Daratumumab interference of allogeneic crossmatch tests repeatedly causing aberrant false-positive results, which inadvertently delayed transplant for a waitlisted renal patient with multiple myeloma. Daratumumab is an IgG1κ human monoclonal antibody commonly used to treat multiple myeloma, characterized by cancerous plasma cells and often leads to renal failure requiring kidney transplant, by depleting CD38-expressing plasma cells. In this case study, the patient had end-stage renal disease secondary to multiple myeloma and was continuously receiving Daratumumab infusions. The patient did not have any detectable antibodies to human leukocyte antigens but repeatedly had unexpected positive crossmatch by the flow cytometry-based method with 26 of the 27 potential deceased organ donors, implying donor-recipient immunological incompatibility. However, further review and analysis suggested that the positive crossmatches were likely false-positive as a result of interference from Daratumumab binding to donor cell surface CD38 as opposed to the presence of donor-specific antibodies. The observed intensity of the false-positive crossmatches was also highly variable, potentially due to donor- and/or cell-dependent expression of CD38. The variability of CD38 expression was, therefore, for the first time, characterized on the T and B cells isolated from various tissues and peripheral blood of 78 individuals. Overall, T cells were found to have a lower CD38 expression profile than the B cells, and no significant difference was observed between deceased and living individuals. Finally, we show that a simple cell treatment by dithiothreitol can effectively mitigate Daratumumab interference thus preserving the utility of pre-transplant crossmatch in multiple myeloma patients awaiting kidney transplant.

The Bacillus Calmette-Guérin (BCG) vaccine has been used for over one hundred years to protect against the most lethal infectious agent in human history, tuberculosis. Over four billion BCG doses have been given and, worldwide, most newborns receive BCG. A few countries, including the United States, did not adopt the WHO recommendation for routine use of BCG. Moreover, within the past several decades, most of Western Europe and Australia, having originally employed routine BCG, have discontinued its use. This review article articulates the impacts of those decisions. The associated consequences include increased tuberculosis, increased infections caused by non-tuberculous mycobacteria (NTM), increased autoimmune disease (autoimmune diabetes and multiple sclerosis) and increased neurodegenerative disease (Parkinson’s disease and Alzheimer’s disease). This review also offers an emerged zoonotic pathogen, Mycobacterium avium ss. paratuberculosis (MAP) as a mostly unrecognized NTM that may have a causal role in some, if not all, of these diseases. Current clinical trials with BCG for varied infectious, autoimmune and neurodegenerative diseases have brought this century-old vaccine to the fore due to its presumed immuno-modulating capacity. With its historic success and strong safety profile, the new and novel applications for BCG may lead to its universal use –putting the Western World back onto the road not taken.

In this paper, bikeshare data in Chicago on weather-friendly days in 2019 and 2020 were analyzed to investigate the variation in bikeshare travel before and during the pandemic. Our results show that bikeshare trips during the pandemic were much longer than prior to the pandemic. The increased rate of bikeshare usage was unbalanced spatially and varied significantly for different user types. Specifically, bikeshare was used significantly more by casual users than by subscribers, and the increase occurred much more in the outskirts of the city. The increase in bikeshare travel was associated with a reduction in travel by ride-hailing and public transit, especially in the urban periphery. The correlation of bikeshare use with the bus system was much less significant than with the rail system. Bike lanes/facilities had a mixed effect on bikeshare travel. Weekend bike trips increased in areas where there was no bike lane. Weekday trips, on the contrary, increased in the vicinity of bike greenways.

We evaluate the nested sum $\sum_{a_{n - 1} = c}^{a_n } {\sum_{a_{n - 2} = c}^{a_{n - 1} } { \cdots \sum_{a_0 = c}^{a_1 } {x^{a_0 } } } }$ where $a_n$ and $c$ are any integers and $x$ is a real or complex variable. Consequently, we evaluate multiple sums involving the terms of a general second order sequence, the Horadam sequence (W_j (a, b; p, q)), defined for all non-negative integers j by the recurrence relation W₀ = a, W₁ = b; W_j = pW_j−1 − qW_j−2 (j≥2); where a, b, p and q are arbitrary complex numbers, with p ≠ 0, q ≠ 0.

Lenalidomide-based regimens are effective treatment options for patients with relapsed/refractory multiple myeloma (RRMM). However, they are associated with an increased risk of infectious complications. This study examines the clinical factors influencing the occurrence of infection in MM patients treated with lenalidomide and dexamethasone (Rd). A retrospective analysis of all patients who received the Rd regimen between 2017-2021 at our institution was performed. The study group consisted of 174 patients and the median age was 65 years. Most patients (n=110, 63.2%) received the Rd treatment in second-line treatment. The majority of patients (64.3%) received bortezomib-based regimens in the first line of treatment. The median progression-free survival was 12.6 (95% CI: 9.5 – 16.2) months, and the median overall survival was 22.3 (95% CI: 15.9 – 28.6) months. The overall response rate was 64.1%, 12.7% of patients achieved complete response and 20.4% had a very good partial response. In multivariate logistic regression analysis, hypoalbuminemia (OR 4.2, 95%CI:1.6-11.2, p= 0.0039), autologous hematopoietic stem cell transplantation (AHSCT) before Rd (OR 2.6, 95% CI:1.0- 6.7, p= 0.048) and anemia grade ≥3 (OR 5.0, 95%CI: 1.8-14.0, p= 0.002) were independent factors related to the occurrence of infections. In conclusion, in this large cohort of RRMM patients, AHSCT before Rd regimen therapy, hypoalbuminemia and anemia during treatment were identified as three independent factors influencing the frequency of infections during Rd therapy. Patients with established risk factors may benefit from optimal supportive therapy.

Introduction: Pediatric-Onset Multiple Sclerosis (POMS) is characterized by high inflammatory disease activ-ity. Our aim was to describe the treatment sequencing and report the impact Highly Effective Disease Modifying Treatment (HET) had on disease activity. Materials and Methods: 2/5 consecutive POMS were administered HET as initial therapy after diagnosis. Data on treatment sequencing, relapses and MRIs were collected during the follow-up. Results: Our patients had an average age of 13.8 years (range 9-17) at di-agnosis and 13.4 years (range 9-16) at disease onset, 2/5 (40%) POMS were female. The pre-treatment aver-age annualized relapse rate was 1.6 (range 0.8-2.8) and the average follow-up length was 5 years (range 3-7). A total of 2/5 (40%) patients were stable on HET at initial therapy, 3/5 (60%) required an escalation to more aggressive treatment, even if two of them had been put on HET as initial treatment. Four out of five patients (80%) had No Evidence of Disease Activity-3 status (NEDA-3) at an average follow-up of 3 years (range 2-5). Conclusion: it has been observed that in a recent time period all the cases had prompt diagnosis, early HET or escalation to HET with a good outcome in 80% of the cases.

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

With growing city tourism, there is an increasing need for urban travel demand models to consider traffic generated by visitors. Existing research has concentrated on socio-demographic and journey-related factors to determine what influences the mode choice of tourists. In contrast, revealed preference data, like travel time, is almost never considered. In this article, we present the results of discrete choice modeling of city tourists’ mode choice based on revealed preference data from a survey we conducted in Kassel, Germany. We used multinomial logit models and determined the model parameters using maximum likelihood estimations. Surprisingly, travel time played a smaller role in mode choice than understood from previously established knowledge about everyday mobility. In the final model, travel time was only significant for the alternative walking. Also, most other sociodemographic and journey-related variables showed no significant influence. The final model reproduced the mode choice, but the goodness of fit was lower than expected from other research. We conclude that modeling the travel behavior of tourists is more complex than everyday mobility. An alternative approach that we suggest would be to model trip chains rather than single trips.

Multiple sclerosis (MS) and necrotizing periodontitis (NP) are two diseases whose aetiology and pathophysiology do not seem to have a common link; however, the treatment of MS with monoclonal antibodies and the decrease in humoral immunity that this entails can be a trigger or an aggravation in patients who present NP. We present a clinical case of NP in which its clinical manifestations, treatment and evolution during therapy with ocrelizumab are reflected. During the evolution of the case, a rapid progression of NP was evidenced. During her evolution, the patient suffered bilateral pneumonia due to COVID requiring treatment with corticosteroids and antibiotics, which led to clinical relief of her NP. Given this important clinical finding, we consider of great interest the regulated dental monitoring of those patients with MS before, during and after the administration of monoclonal antibodies to prevent periodontal deterioration.

Nowadays the freedom to make choices is considered of vital importance for decision-makers. Researchers investigating the psychological effects of choice provided empirical evidence about the many advantages of choice (i.e., increased intrinsic motivation, greater perception of self-determination, better performance, and greater life satisfaction). However, more recent studies demonstrated the downsides of choice. When the decision task difficulty exceeds the natural cognitive resources of human mind, the possibility to choose becomes more a source of unhappiness and dissatisfaction than an opportunity for a greater well-being. We here discuss in a detailed fashion the main findings of research in psychology and consumer behavior showing the bright sides and the downsides of choice.

The importance of statistics in biological research is inevitable. The appliance of statistics is the most powerful tool to support the scientific hypothesis and to give credibility to biological research methodology, to interpret convoluted explanations and conclusions based on the research findings. The evidences from literatures point the persistent statistical errors, selection of non-proper statistical test with the consequence of misinterpretation of the scientific results which are published in international journals. One of the most extensively used statistical tests in the field of biology (preclinical and clinical) is analysis of variance (ANOVA). ANOVA test is in place of multiple T-tests to compare the means of more than two groups at a time; and there are some important points which biologists should be aware of them to avoid possible misinterpretation of results with the consequence of wrong conclusion. Accordingly, the aim of the current review is to help biologists to understand the basic concepts of ANOVA test and reach to a more valid interpretation of achieved results.

Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow (BM) microenvironment. Despite the progress made in treatment, some MM patients still die within the first year of diagnosis. Numerous studies investigating microRNA (miRNA) expression patterns suggest they may be good prognostic markers. The primary aim of this study was to analyze the expression of selected miRNAs in the serum of MM patients subsequently treated with bortezomib-based regimens and determine their potential to predict early mortality. The study was conducted in 69 prospectively-recruited patients with newly-diagnosed MM admitted to the Department of Hematology of the Copernicus Memorial Hospital, Lodz (Poland) between 2017 and 2021. Among them, 17 patients experienced death within 12 months of diagnosis. The expression of 31 selected miRNAs was determined using miRCURY LNA miRNA Custom PCR Panel. The obtained clinical data included patient characteristics on diagnosis, treatment regimen, response to treatment, and follow-up. Differential expression analysis found two miRNAs to be significantly downregulated in the early mortality group: hsa-miR-328-3p (fold change- FC: 0.72, p=0.0342) and hsa-miR-409-3p (FC: 0.49, p=0.0357). Univariate and multivariate logistic regression analyses were performed to assess the early mortality rate. The final model consisted of hsa-miR-409-3p, hsa-miR-328-3p, age and R-ISS 3. It yielded an area under the curve (AUC) of 0.863 (95%CI: 0.761-0.965) with 88.2% sensitivity and 77.5% specificity. Further external validation of our model is necessary to confirm its clinical value.

Background: Upper extremities’ function impairments (UEFI) and gait impairment are frequently reported even in the early stages of Multiple Sclerosis (MS) disease. These motor deficits can negatively affect the quality of life (QOL) in MS patient. Exercise has been repeatedly introduced as a beneficial adjuvant therapy for MS, attenuating a wide range of physical and psychological symptoms without any side effects or increased risks of relapse or exacerbation in disease symptoms.Aim: This paper investigates the effect of multi-function swing suspension training (MFSST) program on upper and lower extremities’ function (ULEF), and QOL in MS women according to expanded disability status scale (EDSS) score.Design: Experimental method with a pre-test and post-test design with control group. Setting: The department of Sports Injuries and Corrective Exercise at the Shahid Bahonar University of Kerman.Population: Forty-seven MS women.Methods: Eligible subjects who matched the selection criteria were randomly assigned into three groups as follow: i. Intervention group A (EDSS of 2 – 4), ii. Intervention group B (EDSS of 4.5 – 6.5), and iii. Control group (EDSS of 2 – 6.5). The intervention groups have been trained by the SET program for a duration of 8 weeks. At baseline and after the intervention, the upper extremities’ function (UEF) and the lower extremities’ function (LEF) were assessed by 9-hole peg test (9HPT) and the timed 25-foot walk (T25FW) test, respectively. Moreover, participants’ QOL was measured using the Short Form questionnaire (SF-36).Results: A significant difference was found between the pre-test and post-test variables of walking speed and upper extremity endurance in intervention groups, and between the intervention groups and control group (P < 0.05). Compared to control group, both intervention groups showed improvements in all subscales of QOL, except emotional role limitation score.Conclusions: In summary, these results show that the present protocol of MFSST could be effective in improving ULEF and QOL in MS patients, showing the improvements after 4^th week. Moreover, this protocol was more useful for patients with an EDSS score of more than 4.5. Therefore, it seems that exercise therapy should be considered as a beneficial clinical intervention approach to improve ULEF and QOL in MS patients.

The object detection task is usually affected by complex backgrounds. In this paper, a new image object detection method is proposed, which can perform multi-feature selection on multi-scale feature maps. By this method, a bidirectional multi-scale feature fusion network is designed to fuse semantic features and shallow features to improve the detection effect of small objects in complex backgrounds. When the shallow features are transferred to the top layer, a bottom-up path is added to reduce the number of network layers experienced by the feature fusion network, reducing the loss of shallow features. In addition, a multi-feature selection module based on the attention mechanism is used to minimize the interference of useless information on subsequent classification and regression, allowing the network to adaptively focus on appropriate information for classification or regression to improve detection accuracy. Because the traditional five-parameter regression method has severe boundary problems when predicting objects with large aspect ratios, the proposed network treats angle prediction as a classification task. The experimental results on the DOTA dataset, the self-made DOTA-GF dataset and the HRSC 2016 dataset show that, compared with several popular object detection algorithms, the proposed method has certain advantages in detection accuracy.

To investigate the dynamics of land surface temperature (LST) in Afghanistan in the period 2000-2021 and to assess the impact of such factors as soil moisture, precipitation, and vegetation coverage on it, remotely sensed soil moisture data from Land Data Assimilation System (FLDAS), precipitation data from Climate Hazards Group Infra-Red Precipitation with Station (CHIRPS), and NDVI and LST from Moderate Resolution Imaging Spectroradiometer (MODIS) were downloaded and correlations between them were analyzed using the regression method. The result shows that the LST in Afghanistan has a slightly decreasing, but insignificant trend during the study period (R=0.2, p-value=0.25), while vegetation coverage, precipitation, and soil moisture had an increasing trend. It was revealed that soil moisture has the highest impact on LST (R=0.7, p-value=0.0007), and the soil moisture, precipitation, and vegetation coverage explain almost 80% of spring (R2=0.73) and summer (R2=0.76) LST variability in Afghanistan. The LST variability analysis done separately for Afghanistan’s rivers subbasins shows that the LST of the Amu Darya subbasin had an upward trend in the study period, while for the Kabul subbasin the trend was downward.

Background: Physical activity has been considered as a promising approach to slow down the disease process in Multiple Sclerosis (MS) patients. While the functional impairments of MS have been studied in detail, but there is limited evidence of the efficacy of exercise interventions on the Multiple Sclerosis functional composite (MSFC) score in these patients. The study aim was to in-vestigate the improvement in MSFC score by multi-function swing suspension training (MFSST) in the women with MS. Methods: The patients were divided into the intervention and control groups. A total of 47 MS patients completed the MSFC components at baseline and after the intervention. Z scores were created for each test based on control means. Results: The MSFC components showed a significant increment in comparison with the baseline levels in the four, six, and eight weeks following the first exercise session (all p<0.05). These dif-ferences in the control group were not significant. The improvement in the MSFC score and the component Z-scores in the intervention groups was found from the fourth week onwards. Conclusions: The study findings highlight that MFSST can be used as an effective treatment method in MS patients due to its positive effects on physical parameters, such as muscles strength, functional impairments, and cognitive problems.

Human ether-a-go-go-related gene (hERG) potassium channel is well-known contributor to drug-induced cardiotoxicity and therefore an extremely important target when performing safety assessments of drug candidates. Ligand-based approaches in connection with quantitative structure active relationships (QSAR) analyses have been developed to predict hERG toxicity. Availability of the recent published cryogenic electron microscopy (cryo-EM) structure for the hERG channel opened the prospect for using structure-based simulation and docking approaches for hERG drug liability predictions. In recent time, the idea of combining structure- and ligand-based approaches for modeling hERG drug liability has gained momentum offering improvements in predictability when compared to ligand-based QSAR practices alone. The present article demonstrates uniting the structure-based SILCS (site-identification by ligand competitive saturation) approach in conjunction with physicochemical properties to develop predictive models for hERG blockade. This combination leads to improved model predictability based on Pearson’s R and percent correct (represents rank-ordering of ligands) metric for different validation sets of hERG blockers involving diverse chemical scaffold and wide range of pIC50 values. The inclusion of the SILCS structure-based approach allows determination of the hERG region to which compounds bind and the contribution of different chemical moieties in the compounds to blockade, thereby facilitating the rational ligand design to minimize hERG liability.

Predation is a driving force of organismal ecology and evolution. Predator-prey interactions, constrained by other environmental factors and historical contingency, shape physical and behavioral phenotypes of organisms on both sides of the interaction arrow. Yet despite the universality of trophic interactions in biology, study of the ecology and evolution of anti-predator defense is challenging because these interactions tend to be brief and unpredictable, and thus gathering direct evidence requires patience and serendipity. The evolution of prey defenses can be studied by DNA sequencing followed by phylogenetic analysis, and the ecology can be studied by field observation and bringing tractable systems into the lab. However, animal models generally do not allow genetic manipulation, strict control of environmental variables, or detailed observation of evolution in real time, all of which are important for demonstrating evolutionary causes and consequences. Developing complementary microbial predator-prey systems can help overcome this hurdle. There is an extensive body of work on microbial experimental evolution, and many microbes come with well-characterized genomes and established methods for genetic manipulation. As understanding of microbial ecology and the mechanisms of their trophic interactions grows apace, these systems are poised to make valuable contributions to our understanding of how predator behaviors evolve, why certain anti-predator defenses evolve and not others, and how multiple defenses function together in a single defense portfolio. These systems will enable us to both test hypotheses formulated from the study of larger organisms and to propose new ones that can be tested in larger organisms with existing methods.

In this work, we have developed a non-ordinary state-based peridynamic model for multiple crack initiation and propagation due to compression-compression fatigue load. In each loading cycle, the fatigue loading is redistributed among the peridynamic solid body, leading to the progressive fatigue damage initiation and propagation in an autonomous fashion. The proposed fatigue model parameters are firstly validated by 3D numerical benchmark tests, and then it is applied to simulate widespread fatigue damage evolution of the aircraft wing corner box. The modified constitutive damage model has been implemented into the peridynamics framework at finite strain. Furthermore, the criterion algorithm from multiple initiation to propagation is discussed. It is shown that the numerical results obtained from peridynamics simulations are in general agreement with those from the experiment data. The comparison of experimental and numerical results indicates that the proposed non-ordinary state-based peridynamics fatigue model has the ability to capture the multiple crack initiation and propagation and other features of the aluminium alloy material.

Astrocytes are essential for normal brain development and functioning. They respond to brain injury and disease through a process referred to as reactive astrogliosis, where the reactivity is highly heterogenous and context dependent. Reactive astrocytes are active contributors to brain pathology and can exert beneficial, detrimental, or mixed effects following brain insults. Transforming growth factor-β (TGF-β) has been identified as one of the key factors regulating astrocyte reactivity. Genetic and pharmacological manipulation of TGF-β signaling pathway in animal models of CNS injury and disease alters pathological and functional outcomes. This review aims to provide recent understanding regarding astrocyte reactivity and TGF-β signaling in brain injury, aging, and neurodegeneration. Further, it explores how TGF-β signaling modulates astrocyte reactivity and function.

A few empirical examples document fixed alternative male mating strategies in animals. Here we focus on the polymorphism of male mating strategies in the ruff (Calidris pugnax, Aves Charadriiformes). In ruffs, three fixed alternative male mating strategies coexist and are signaled by extreme plumage polymorphism. We first present relevant data on the biology of the species. Then we review the available knowledge of the behavioral ecology of ruffs during the breeding season and we detail the characteristics of each of the three known fixed male mating strategies. We next turn to the exceptional quality results accumulated on both the structural and functional genomics of the ruff over the past few years. We show how much these genomic data can shed a new, mechanistic light on the evolution and maintenance of the three fixed alternative male mating strategies. We then look if there are sufficient indication to support frequency-dependent selection as key mechanism in maintaining these three strategies. Specifically, we search for evidences of equal fitness among individuals using each of the three strategies. Finally, we propose three lines of research avenues that will help to understand the eco-evolutionary dynamics of phenotypic differences within natural populations of this iconic model species.

Mechanical power and motion are often transmitted by the gear-rotor-bearing system. When there are fitting clearances between the housing and outer ring in bearings, complex vibration responses will be generated, which makes the operating status difficult to identify. Therefore, for analyzing dynamic responses, a dynamic model of gear-rotor-bearing systems with bearing fitting clearances is proposed. In the model, the bearing system with fitting clearances and gear pair system are combined, and the coupling relationship is determined by the gyroscopic mo-tion of the shaft. The friction force and collision force caused by fitting clearances are also con-sidered, which are simulated by the Coulomb friction model and Hertz theory. The result shows that the meshing stiffness will also be excited by the bearing displacement. When there are fit-ting clearances on the bearing, the amplitude modulation of the bearing outer raceway to the system time-domain response is intensified, and the multiple harmonic frequency of bearings and gear pairs are generated on the spectrum, as well as defect frequencies of gear pairs. As the fitting clearance is increased, the higher multiple harmonic responses will be caused. Although the response amplitude of the gearbox is increased by raising the input speed, multiple harmon-ic responses are suppressed, which makes the system mainly vibrate at the fundamental fre-quency. Then, the dynamic model and the vibration analysis are experimentally verified.

Background: The fulminant course of COVID-19, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents with a high mortality rate and still lacks a causative treatment. C-reactive protein (CRP) has been shown to increase dramatically during the disease progression and correlates with deleterious outcomes. Selective CRP apheresis can reduce circulating CRP levels fast and effective. Methods: Seven hospitalized patients with documented severe COVID-19 progression, elevated CRP plasma levels (> 100 mg/L) and signs of respiratory failure were treated with CRP apheresis. 2-12 CRP apheresis sessions were performed generally in 24 h time intervals and depending on CRP plasma levels. Results: CRP apheresis reduced CRP plasma levels by up to 84% within a few hours, without exhibiting side effects in any patient. Despite signs of severe lung infiltration in all patients, only one patient died. The other patients showed improvements within the chest x-ray after CRP apheresis and were able to recover regardless of intubation and/or ECMO (4 patients). All remaining six patients were discharged from the hospital in good clinical condition. All patients had comorbidities. Conclusions: This case series presents a mortality rate of only 14%, which is dramatically lower than expected from the presented CRP levels as well as comorbidities and ventilation require-ments. Our clinical observations regarding the here presented seven patients support the hypoth-esis that CRP is a candidate to be therapeutically targeted in the early stage of severe COVID-19.

Introduction: multiple sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS), affecting young people. Due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on the patients’ health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. Areas covered: in this review, we summarise the most up to date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. Author commentary: the current diagnostic criteria of MS rely on three pillars; MRI imaging, clinical events and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.