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.

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.

With the increased availability of sequence data and even of fully sequenced and assembled genomes, phylogeny estimation of very large trees (even of hundreds of thousands of sequences) is now a goal for some biologists. Yet, the construction of these phylogenies is a complex pipeline presenting analytical and computational challenges, especially when the number of sequences is very large. In the last few years, new methods have been developed that aim to enable highly accurate phylogeny estimations on these large datasets, including divide-and-conquer techniques for multiple sequence alignment and/or tree estimation, methods that can estimate species trees from multi-locus datasets while addressing heterogeneity due to biological processes (e.g., incomplete lineage sorting and gene duplication and loss), and methods to add sequences into large gene trees or species trees. Here we present some of these recent advances and discuss opportunities for future improvements.

This study explored father involvement as a social determinant of child health within the context of macro-environmental changes in Mongolia. Using data for children aged 3-4 from UNICEF’s Multiple Indicator Cluster Surveys, this cross-sectional analysis examined the association between father presence and engagement with child health and educational outcomes. Multivariate regression modeling was employed to identify associations between father presence, engagement, and child outcomes including fever, respiratory illness, diarrhea and preschool attendance. In unadjusted analyses, father engagement was associated with higher odds of pre-school attendance (OR=1.12; 95% CI 1.04-1.20) but not with child illness (OR=1.04; 95% CI 0.95-1.14). Father engagement was no longer associated with pre-school attendance after controlling for potentially confounding variables (ORadj = 0.95; 95% CI 0.88-1.03). Unadjusted and adjusted analyses showed that father presence was not associated with acute illness or preschool attendance. Results also suggest that a larger proportion of children were engaged in activities by their mother compared to their father or other adults. Data indicate that father presence and engagement were not associated with child illness or pre-school attendance. Factors such as maternal education, household wealth, and region of residence are stronger predictors of preschool attendance and should continue to be considered for promoting child health and development in Mongolia.

Tremor is a prevalent symptom associated with multiple conditions, including Essential Tremor (ET), Parkinson’s disease (PD), multiple sclerosis (MS), stroke, and trauma. The surgical management of tremor evolved from stereotactic lesions to deep-brain stimulation (DBS), which allowed safe and reversible interference with specific neural networks. This paper reviews the current literature on DBS for tremor, starting with a detailed discussion of current tremor targets (Vim, Raprl, caudal Zi, Vo and STN) and continuing with a discussion of results obtained when performing DBS in the various aforementioned tremor syndromes. Future directions for DBS research are then briefly discussed.

Multiple Sclerosis (MS) is a complex disease of the central nervous system (CNS) that involves the intricate interplay of different immune cells going awry leading to inflammation, demyelination, and neurodegeneration. Its diagnosis is quite arduous because of the baffling number of symptoms it elicits and the varied clinical manifestation it presents. The simplified criteria (in form of Macdonald’s Criteria) which have got modified several times is now the single most important criteria accepted by neurology bodies for diagnosing MS. Biomarkers from time to time have been explored to simplify the diagnosis and prognosticate MS along with anecessity to monitor treatment outcome. In recent years, research on biomarkers has advanced rapidly due to their ability to be easily and rapidly measured, their specificity, safety, and their ability to yield precise results. Biomarkers are classified into various categories including predictive, diagnostic, prognostic, related to disease activity, and monitoring treatment outcome. Each representative of the disease activity category reflects a variety of pathological processes of MS such as neuroaxonal loss, gliosis, demyelination, disability progression, remyelination, etc. This review discusses several promising serum and cerebrospinal fluid biomarkers and imaging biomarkers used in clinical practice. Myelin oligodendrocyte glycoprotein antibody disease which is recently recognized as a definite disease will also be discussed. Furthermore, it sheds light on the criteria and the challenges a biomarker faces to be considered as a standard one.

The prevalence of food allergy has increased over the last decades and consequently the food labeling policies have improved over the time in different countries to regulate allergen presence in foods. In particular, Reg 1169 in EU mandates the labelling of 14 allergens whenever intentionally added to foods, but the inadvertent contamination by allergens still remains uncovered topic. In order to warn consumers on the risk of cross-contamination occurring in certain categories of foods, a precautionary allergen labelling system has been put in place by food industries on voluntary basis. In order to reduce the overuse of PAL, reference doses and action limits have been proposed by the VITAL project representing a guide in this jeopardize scenario. Development of sensitive and reliable mass spectrometry methods are therefore of paramount importance in this regard to check the contamination levels in foods. In this paper we describe the development of a managed time MRM method based on a triple quadrupole platform for milk and egg quantification in processed food. The method was in house validated and allowed to achieve levels of proteins lower than 0.2mg of total milk and egg proteins respectively in cookies, challenging the doses recommended by VITAL. The method was finally applied to cookies labeled as milk and egg-free. This method could represent in perspective a promising tool to be implemented along the food chain to detect even tiny amounts of allergens contaminating food commodities.

Cannabidiol is a well-known non-psychotropic phytocannabinoid from Cannabis sativa, which exerts a broad range of neuropharmacological activities in the central nervous systems. Over the past years, compelling evidence from preclinical and clinical studies support therapeutic potentials of cannabidiol in various neurological disorders, including neurodegenerative diseases. Neurodegenerative diseases are characterized by the accumulation of misfolded or aggregated protein due to the defective protein homeostasis or proteostasis network, termed as proteinopathies. Because of its role in the protein homeostasis network, cannabidiol could be a potent molecule to revert not only age-associated neurodegeneration but also other protein misfolding disorders. In this review, we discuss the potentiality of cannabidiol as a pharmacological modulator of the proteostasis network, highlighting its neuroprotective and aggregates clearing system inducing potentials in the neurodegenerative diseases.

As of today, 20 disease modifying drugs (DMD) have been approved for the treatment of relapsing multiple sclerosis (MS) and, based on their efficacy, they can be grouped into moderate-efficacy DMDs and high-efficacy DMDs. The choice of the drug mostly relies on the judgement and experience of neurologists and the evaluation of therapeutic response can only be obtained by monitoring clinical and magnetic resonance imaging (MRI) status during follow up. In an era where therapies are focused on personalization, the aim of this study is to develop a modeling infrastructure to predict the evolution of relapsing MS and the response to treatments. We built a computational modeling infrastructure named UISS (Universal Immune System Simulator) able to simulate the main features and dynamics of the immune system activities. We extended UISS to simulate all the underlying MS pathogenesis and its interaction with the host immune system. This simulator is a multi-scale, multi-organ, agent based simulator with an attached module capable of simulating the dynamics of specific biological pathways at the molecular level. We simulated six MS patients with different relapsing-remitting courses. These patients were characterized on the basis of their age, sex, presence of oligoclonal bands, therapy and MRI lesion load at onset. The simulator framework is made freely available and can be used following the links provided in the availability section. Even though the model can be further personalized employing immunological parameters and genetic information, based on the available data we generated a few simulation scenarios for each patient, including those who matched the real clinical and MRI history. Moreover, for two patients, the simulator anticipated the timing of subsequent relapses, which really occurred, suggesting that UISS may have the potential to assist MS specialists in predicting the course of the disease and the response to treatment.

For a dynamical system, it is known that the existence of a Lyapunov density implies almost global stability of an equilibrium. It is then natural to ask whether the existence of a common Lyapunov density for a nonlinear switched system implies almost global stability, in the same way as a common Lyapunov function implies global stability for nonlinear switched systems. In this work, the answer to this question is shown to be affirmative as long as switchings satisfy a dwell-time constraint with an arbitrarily small dwell time. As a straightforward extension of this result, we employ multiple Lyapunov densities in analogy with the role of multiple Lyapunov functions for the global stability of switched systems. This gives rise to a minimum dwell time estimate to ensure almost global stability of nonlinear switched systems, when a common Lyapunov density does not exist. The results obtained for continuous-time switched systems are based on some sufficient conditions for the almost global stability of discrete-time non-autonomous systems. These conditions are obtained using the duality between Frobenius-Perron operator and Koopman operator.

Motivated by the theoretical model of health insurance choice with Flexible Spending Accounts (FSAs) presented in Cardon 2012, this study investigates the determinants of optional coverage (SSP) and flexible spending accounts (FSA) enrollment, among the privately insured in post-affordable-care-act (ACA) USA. To this end, we rely on semi-parametric bi-variate probit methods, along with a pooled cross-section of the 2015-2016 National Health Interview Surveys. As predicted by the theoretical model, we find that SSP and FSA are complement health solutions with a positive correlation. Our results emphasize that the most important trigger factors influencing the joint probability of SSP and FSA adoption include not only insurance premium cost, but also age, education, marital status, number of work hours, region of residency, citizenship status, and annual health expenditure level. We find that controlling for these latter factors, health status is not significant especially for FSA adoption. In addition, despite the fact that the relative frequency of individuals with FSA rises with increasing levels of medical expenditure, ACA restrictions on FSA tax exclusion to an annual adjusted maximum of $2600 (in 2017 $s) seems to adversely burden individuals with greater medical expenditure, thereby reducing their likelihood of FSA enrollment in post-ACA USA. Understanding these factors is very crucial to US health care market's stakeholders, including insurance companies, firms looking to design their health insurance offerings, but also policy-makers interested in providing new tailored health solutions for reducing health risks.

If environmental exposures are shown to cause an adverse health outcome, reducing exposure should reduce the disease risk. Links between exposures and outcomes are typically based on ‘associations’ derived from observational studies, and causality may not be clear. Randomised controlled trials to ‘prove’ causality are often not feasible or ethical. Here the history of evidence that tobacco smoking causes lung cancer – in observational studies – is compared to that of low sun exposure and/or low vitamin D status as causal risk factors for the autoimmune disease, multiple sclerosis. Evidence derives from in vitro and animal studies, as well as ecological, case-control and cohort studies, in order of increasing strength. For smoking and lung cancer, the associations are strong, consistent, and biologically plausible – the evidence is coherent or ‘in harmony’. For low sun exposure/vitamin D as risk factors for MS, the evidence is weaker, with smaller effect sizes, but coherent across a range of sources of evidence, and biologically plausible. The association is less direct – smoking is directly toxic and carcinogenic to the lung, but sun exposure/vitamin D modulate the immune system, which in turn may reduce the risk of immune attack on self-proteins in the central nervous system. Opinion about whether there is sufficient evidence to conclude that low sun exposure/vitamin D increase the risk of multiple sclerosis, is divided. General public health advice to receive sufficient sun exposure to avoid vitamin D deficiency (<50nmol/L) should also ensure any benefits for multiple sclerosis.

Personalized medicine is an aspect of the P4 medicine (predictive, preventive, personalized and participatory) based precisely on the customization of all medical characters of each subject. In personalized medicine, the development of medical treatments and drugs is tailored to the individual characteristics and needs of each subject, according to the study of diseases at different scales from genotype to phenotype scale. To make concrete the goal of personalized medicine, it is necessary to employ high-throughput methodologies such as Next Generation Sequencing (NGS), Genome-Wide Association Studies (GWAS), Mass Spectrometry or Microarrays, that are able to investigate a single disease from a broader perspective. For example, by using genotyping microarrays (e.g. collections of Single Nucleotide Polymorphism - SNP) it is possible to uncover the reasons (i.e. mutation in genes) because a treatment works properly in some patients (for example absence of mutated genes), but it does not work (presence of mutated genes) in others. A side effect of high-throughput methodologies is the massive amount of data produced for each single experiment, that poses several challenges (e.g. high execution time and required memory) to bioinformatic software. Thus a main requirement of modern bioinformatic software is the use of good software engineering methods and efficient programming techniques, able to face those challenges, that include the use of parallel programming and efficient and compact data structures. Thus, to exploit all the potential of this massive amount of data in the short possible time (before that data becomes obsolete), the necessity to develop parallel software tools for efficient data collection and analysis arise. Moreover, due to the heterogeneity of the data produced by the different kinds of experimental platforms, it is necessary to automatize in a comprehensive software pipeline, the various steps that compose a bioinformatic analysis, such as: the preprocessing of raw data to remove noise or corrupted data; the annotation of data with external knowledge (e.g. Gene Ontology), and the integration of molecular data with clinical data. It should be noted that such steps are necessary to make statistical or data mining analysis more effective. This paper presents the design and the experimentation of a comprehensive software pipeline, named microPipe, for the preprocessing, annotation and analysis of microarray-based SNP genotyping data. A case study in pharmacogenomics is presented. The main advantages of using microPipe are: the reduction of errors that may happen when trying to make data compatible among different tools; the possibility to analyze in parallel huge datasets; the easy annotation and integration of data.

Remote sensing image registration plays an important role in military and civilian fields, such as natural disaster damage assessment, military damage assessment and ground targets identification, etc. However, due to the ground relief variations and imaging viewpoint changes, non-rigid geometric distortion occurs between remote sensing images with different viewpoint, which further increases the difficulty of remote sensing image registration. To address the problem, we propose a multi-viewpoint remote sensing image registration method which contains the following contributions. (i) A multiple features based finite mixture model is constructed for dealing with different types of image features. (ii) Three features are combined and substituted into the mixture model to form a feature complementation, i.e., the Euclidean distance and shape context are used to measure the similarity of geometric structure, and the SIFT (scale-invariant feature transform) distance which is endowed with the intensity information is used to measure the scale space extrema. (iii) To prevent the ill-posed problem, a geometric constraint term is introduced into the L2E-based energy function for better behaving the non-rigid transformation. We evaluated the performances of the proposed method by three series of remote sensing images obtained from the unmanned aerial vehicle (UAV) and Google Earth, and compared with five state-of-the-art methods where our method shows the best alignments in most cases.

There are many features of homeostasis worth investigating such as how it works (information pathways, set point processing), where its command and control processors are located in the cell, the language used and how homeostasis interacts with all aspects of an organism's functional maintenance and development. All are necessary and valid inquiries, but this paper examines the implications of ignoring it as a factor of disease causation. Alternatively when properly understood the homeostasis profile becomes a rational explanation for any individual’s range of health; where some areas are very resistant to disease (resilient) and other areas of homeostasis are dysfunctional leading to minor, moderate or very susceptible tendencies to disease (lack of resilience in homeostasis). An understanding of this phenomenon, its interactions with gene expression (epigenetics) is necessary in order to evaluate the solutions for acute and chronic diseases. By this method diseases can be defined more precisely as specific susceptibilities in homeostasis, leading to a method to restore specific homeostasis functions.

Scanning underwater areas, using magnetometers, in search of unexploded ordnance is a difficult challenge, where machine learning methods can find a significant application. However, this requires the creation of a set enabling the training of prediction models. Such a task is difficult and costly due to the limited availability of relevant data. To meet this challenge in the article, we propose the use of numerical modeling to solve this task. The conducted experiments allow us to conclude that it is possible to obtain high compliance of the numerical model with the results of physical tests. In addition, the paper discusses the methodology of simplifying the computational model, allowing for almost three times reduction of the calculation time. In addition, in the work we present the methodology of creating an appropriate data set, enabling the generation of any number of training samples.

In this paper, we consider the relation of more than four harmonic points in a line. For this purpose, starting from the dependence of the harmonic points, Desargues’ theorems, and perspectivity, we note that it is necessary to conduct a generalization of the Desargues’ theorems for projective complete n-points, which are used to implement the definition of the generalization of harmonic points. We present new findings regarding the uniquely determined and constructed sets of H-points and their structure. The well-known fourth harmonic points represent the special case (n=4) of the sets of H-points of rank 2, which is indicated by P42.

By the study of the pattern book Ying Zao Fa Shi (building regulations of Song Dynasty, 1103 AD), while analyzing the combining and dimensioning rule of timber framework and tile work, a model self-generating program has been compiled for the first time. The operating framework has been firstly defined, while solving the issues of clustering principle, connecting method, output classification, etc. with the detailed description of algorithm theory. Taking the corner bracket set and nine-ridge roof for example, after the compilation and debug by Grasshopper, according to various input parameters, various models have been generated automatically by the plugin, proving the velocity and the veracity of the algorithm.

The complete-lattice approach to optimization problems with a vector- or even set-valued objective already produced a variety of new concepts and results and was successfully applied in finance, statistics and game theory. For example, the duality issue for multi-criteria and vector optimization problems could be solved using the complete-lattice approach, compare [11]. So far, it has been applied to set-valued dynamic risk measures (in the stochastic case), as discussed in Feinstein, Rudloff etc. (see [11], for example), but it has not been applied to deterministic calculus of variations and optimal control problems. In this paper, the following problem of set-valued optimization is considered: minimize the functional $$ \overline J_t[y]=\int_0^t \overline L(s,y(s),\dot y(s))\ ds + U_0(y(0)) $$ over all admissible arcs $y$, where $\overline L$ is the associated multifunction to a vector-valued Lagrangian $L$, the integral is in the Aumann sense and $U_0$ is the initial cost. A new concept of \emph{value function}, for which a Bellman's optimality principle holds, is introduced. Also the classical result of the Hopf-Lax formula holds for the generalized value function. Finally, a derivative with respect to the time $t$ and a directional derivative with respect to $x$ of the value function are defined, based on ideas close to the concepts in [12]. The value function is proved to be solution of a suitable Hamilton-Jacobi equation.

The Pythagorean fuzzy set (PFS), which is characterized by a membership and a non-membership degree and the square sum of them is less or equal to one, can act as an effective tool to express decision makers’ fuzziness and uncertainty. Considering that the Heronian mean (HM) is a powerful aggregation operator which can take the interrelationship between any two arguments, we study the HM in Pythagorean fuzzy environment and propose new operators for aggregating interval-valued Pythagorean fuzzy information. First, we investigate the HM and geometric HM (GHM) under interval-valued intuitionistic fuzzy environment and develop a series of aggregation operators for interval-valued intuitionistic fuzzy numbers (IVIFNs) including interval-valued intuitionistic fuzzy Heronian mean (IVIFHM), interval-valued intuitionistic fuzzy geometric Heronian mean (IVIFGHM), interval-valued intuitionistic fuzzy weighted Heronian mean (IVIFWHM) and interval-valued intuitionistic fuzzy weighted geometric Heronian mean (IVIFWGHM). Second, some desirable and important properties of these aggregation operators are discussed. Third, based on these aggregation operators, a novel approach to multi-attribute decision making (MADM) is proposed. Finally, to demonstrate the validity of the approach, a numerical example is provided and discussed. Moreover, we discuss several real-world applications of these operators within policy-making contexts.

In this paper, we observe that if X is a set and (Bin(X), □) is the semigroup of binary systems on X, then its center ZBin(X) consists of the locally-zero-semigroups and that these can be modeled as (simple) graphs and conversely. Using this device we show that we may obtain many results of interest concerning groupoids by reinterpreting graph theoretical properties and at the same time results on graphs G may be obtained by considering them as elements of centers of the semigroups of binary systems (Bin(X), □) where X = V(G), the vertex set of G.

Software fault prediction is the very consequent research topic for software quality assurance. Data driven approaches provide robust mechanisms to deal with software fault prediction. However, the prediction performance of the model highly depends on the quality of dataset. Many software datasets suffers from the problem of class imbalance. In this regard, under-sampling is a popular data pre-processing method in dealing with class imbalance problem, Easy Ensemble (EE) present a robust approach to achieve a high classification rate and address the biasness towards majority class samples. However, imbalance class is not the only issue that harms performance of classifiers. Some noisy examples and irrelevant features may additionally reduce the rate of predictive accuracy of the classifier. In this paper, we proposed two-stage data pre-processing which incorporates feature selection and a new Rough set Easy Ensemble scheme. In feature selection stage, we eliminate the irrelevant features by feature ranking algorithm. In the second stage of a new Rough set Easy Ensemble by incorporating Rough K nearest neighbor rule filter (RK) afore executing Easy Ensemble (EE), named RKEE for short. RK can remove noisy examples from both minority and majority class. Experimental evaluation on real-world software projects, such as NASA and Eclipse dataset, is performed in order to demonstrate the effectiveness of our proposed approach. Furthermore, this paper comprehensively investigates the influencing factor in our approach. Such as, the impact of Rough set theory on noise-filter, the relationship between model performance and imbalance ratio etc. comprehensive experiments indicate that the proposed approach shows outstanding performance with significance in terms of area-under-the-curve (AUC).

Contact with nature is suggested to be as an important resource for human health and well-being. Stress alleviation and reduction of mental fatigue are main instances of improvement of human health and well-being in contact with nature. Although the term restoration experience in contact with nature has been used repeatedly for concepts of stress alleviation and reduction of mental fatigue, these refer to different sets of theories and research studies. In this paper, by reviewing the nature-health related theories of Biophilia, Stress Recovery Theory, Attention Restoration Theory and Supportive Environment Theory (SET), the similarities and differences between these two concepts have been discussed. Moreover, the measurement approach instruments based on different study methodologies and aims are provided. This paper could provide information for future studies with focus on factors to be of benefit for restoration experience in design and planning of natural landscape environments with the aim of health and well-being development.

In this paper, firstly, some questionable formulas and conceptual oversights of previous reduced sigma set unscented transformation (UT) methods are revised through theoretical analysis. Then the revised UT methods based Kalman filters are used in a GPS/INS tightly-coupled system. The Kalman filter flows are the kind of square-root, since the square-root unscented Kalman filters (SRUKFs) can guarantee the stability of the system. By using the reduced sigma set SRUKFs (which contain simplex sigma set square-root unscented Kalman filter (S-SRUKF), spherical simplex sigma set square-root unscented Kalman filter (SS-SRUKF) and minimum sigma set square-root unscented Kalman filter (M-SRUKF)), the computation cost is greatly saved compared with the standard SRUKF, while the accuracy of the GPS/INS tightly-coupled system still maintained. The structure of the GPS/INS tightly-coupled system is in the form of error state, and the time updates of the state and the state covariance of SRUKFs are directly estimated without using UT, thus the computational time is also greatly saved. The pseudo-satellite is introduced to aid the system when the observation information is deficient, for example, when the GPS signal is deficient in the maneuver environment. By using the pseudo-satellite, the optimal performance of the system is guaranteed. Experiment of unmanned aerial vehicle (UAV) showed that the pseudo-satellite aided mechanism worked well.

Let  β= (((24!)!)!)!, and let {${\mathcal P}_{n^2+1}$} denote the set of all primes of the form {$n^2+1$}. Let ${\mathcal M}$ denote the set of all positive multiples of elements of the set {${\mathcal P}_{n^2+1} \cap (\beta,\infty)$}. The set {${\mathcal X}=\{0,\ldots,\beta\} \cup {\mathcal M}$} satisfies the following conditions: (1) ${\rm card}({\mathcal X})$ is greater than a huge positive integer and it is conjectured that ${\mathcal X}$ is infinite, (2)} we do not know any algorithm deciding the finiteness of ${\mathcal X}$, (3)~a~known and short algorithm for every {$n \in N$} decides whether or not {$n \in {\mathcal X}$}, (4) a known and short algorithm returns an integer~$n$ such that ${\mathcal X}$ is infinite if and only if ${\mathcal X}$ contains an element greater than $n$. The following problem is open: {\em simply define a set {${\mathcal X} \subseteq N$} such that ${\mathcal X}$ satisfies conditions (1)-(4), and \underline{we do not know any representation of~~${\mathcal X}$~~as a finite union of sets whose definitions are simpler than} \underline{the definition of ${\mathcal X}$}} {\tt (5)}. Let {$f(1)=2$}, {$f(2)=4$}, and let {$f(n+1)=f(n)!$} for every integer {$n \geqslant 2$}. For a positive integer $n$, let {$\Psi_n$} denote the following statement: {\em if a system of equations ${\mathcal S} \subseteq \Bigl\{x_i!=x_k: i,k \in \{1,\ldots,n\}\Bigr\} \cup \Bigl\{x_i \cdot x_j=x_k: i,j,k \in \{1,\ldots,n\}\Bigr\}$ has only finitely many solutions in positive integers \mbox{$x_1,\ldots,x_n$}, then each such solution \mbox{$(x_1,\ldots,x_n)$} satisfies {$x_1,\ldots,x_n \leqslant f(n)$}.} We prove that for every statement $\Psi_n$ the bound {$f(n)$} cannot be decreased. The author's guess is that the statements {$\Psi_1,\ldots,\Psi_9$} are true. We prove that the statement $\Psi_9$ implies that the set ${\mathcal X}$ of all {non-negative} integers $k$ whose number of digits belongs to {${\mathcal P}_{n^2+1}$} satisfies conditions {\tt (1)-(5)}.

The United Nations’ Agenda 2030 has established a series of Sustainable Development Goals to address global challenges, including poverty, food insecurity, access to education, and social inequality. In this context, charitable organizations such as Caritas play a crucial role in mitigating the negative effects of these challenges and promoting fair and sustainable development. This study aims to analyze prevalent needs among individuals seeking assistance from Caritas in Campania and examine how the organization contributes to achieving the Agenda 2030 Goals in the region. The statistical investigation techniques considered include tandem analysis [], which considers a dimension-reduction technique, such as multiple factor analysis, and, then cluster analysis to identify similar groups of individuals. These exploratory data analysis methods have allowed for the identification of common needs, including food assistance, support for education, employment, and housing assistance. Subsequently, Caritas programs and initiatives aimed at meeting these needs and promoting sustainable development are explored. The results indicate that Caritas plays a significant role in addressing the urgent needs of the vulnerable population in Campania and contributes to the goals of Agenda 2030, particularly those related to poverty alleviation, immigration, health promotion, education, employment, and reduction of social inequalities. This study provides an important perspective on the relevance and effectiveness of Caritas’ work in the context of Agenda 2030.

E-waste management (EWM) refers to the operation-management of discarded or unproductive electronic devices and components, a challenge exacerbated due to overindulgent urbanization. This article presents a multidimensional cost-function-based analysis of the EWM framework structured on three modules - environmental, economic, and social uncertainties - which contemplate the 3 pillars of sustainability in an e-waste recycling plant, including the production-delivery-utilization process. The framework incorporates material recovery from a single e-waste facility provisioning for chemical and mechanical recycling. Each module is ranked using independent Machine Learning (ML) protocols: a) Analytical Hierarchical Process (AHP) and b) combined AHP and Principal Component Analysis (PCA). From a long list of possible contributors, the model identifies and ranks two key sustainability contributors to the EWM supply chain: overall energy consumption and volume of carbon dioxide generated. Another key finding is a precise time window for policy resurrection, which for the data considered, happens to be 400-600 days from the start of operation. Another interesting outcome is the quality of prediction using a combination of AHP and PCA, which consistently produced better results than any of these ML methods individually implemented. Model outcomes have been verified using a case study to outline a future E-waste sustained roadmap.

Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia giving rise to oligodendrocytes, the myelin forming cells in the central nervous system (CNS). While OPCs are highly proliferating during development, they become relatively quiescent during adulthood, when their fate is strictly influenced by the extracellular context. In traumatic injuries and chronic neurodegenerative conditions including those of autoimmune origin, oligodendrocytes undergo apoptosis, and demyelination starts. Adult OPCs become immediately activated, they migrate at the lesion site and proliferate to replenish the damaged area, but their efficiency is hampered by the presence of a glial scar, a barrier mainly formed by reactive astrocytes, microglia, and the deposition of inhibitory extracellular matrix components. If, on one hand, glial scar limits the lesion spreading, it also blocks tissue regeneration. Therapeutic strategies aimed at reducing astrocyte or microglia activation and shifting them toward a neuroprotective phenotype have been proposed, whereas the role of OPCs has been largely overlooked. In this review, we have considered glial scar from the perspective of OPCs, analysing their behaviour when lesions originate and exploring the potential therapies aimed at sustaining OPCs to efficiently differentiate and promote remyelination.

By repeated unloading and loading of the excavation dynamic and static loads, repeated train dynamic and static loads of multi-factors, the underpass tunnel, cross tunnel engineering influence area rock layer, the existing tunnel structure of the three constitutes a multifaceted structure, multi-factor interaction system. Existing tunnels into the prediction theory model of the new tunnel excavation process of dynamic and static loads, dynamic and static loads of existing tunnels are mostly analyzed individually, the results of synergistic analysis needs to be improved. Based on the theory of the current layer method, the paper comprehensively considers the stiffness of the existing tunnel, the stiffness of the new tunnel, the excavation method load and the existing tunnel load, coupled with Peck's empirical formula, the theoretical model of deformation prediction for excavation of a two-lane highway tunnel under the tunnel through the existing railroad is proposed, and verified and optimized by numerical calculations and monitoring data, which proves the applicability and reliability of the theoretical model in the similar strata and the project promotion.

Understanding the optimal strategy for a real estate investment and how performance changes based on characteristics is crucial for optimising the achievable return. This is prominent in tourist areas such as Paphos where there is no clear distinction as to whether short or long-term approaches are optimal. The study aimed to develop a model for predicting the optimal rental strategy whilst assessing which model performed best and which property attributes impacted its return the greatest. Short-term data was collected from AirDNA and long-term data was manually collected from real estate agents websites. Furthermore, Random Forest, K-Nearest Neighbour and Multiple Linear Regression models were created to predict the highest and best use for each property. Model accuracy varied between data sets with the best performing model for short-term properties being Random Forest (R-Squared: 0.843), and Distance-Based Multiple Linear Regression for long-term approach (R-Squared: 0.843). The study demonstrated that accurate models could be created to predict the optimal rental strategy with the number of bedrooms being the main driver for rental income, followed by luxury finishes and the presence of a pool. It found that locational characteristics didn’t impact the returns significantly assuming that the property was located within a tourist area.

Estimating parameters for multiple datasets can be time consuming, especially when the number of datasets is large. One solution is to sample from multiple datasets simultaneously using Bayesian methods such as adaptive multiple importance sampling (AMIS). Here we use the AMIS approach to fit a von Misses distribution to multiple datasets for wind trajectories derived from a Lagrangian Particle Dispersion Model driven from a 3D meteorological data. The primary objective is to characterise the uncertainties in wind trajectories in a form that can be used as inputs for predictive models of wind-dispersed insect pests and pathogens of agricultural crops for use in evaluating risk and in planning mitigation actions. Our results show that AMIS can significantly improve the efficiency of parameter inference for multiple datasets.

The development of multiple drug resistant (MDR) cancer all too often signals the need for alternative toxic therapy or palliative care. Our recent in vivo and in vitro studies using canine MDR lymphoma cancer cells demonstrated that the Anaphase Promoting Complex (APC) is impaired in MDR cells compared to normal canine control and drug sensitive cancer cells. Here, we sought to establish whether this phenomena is a generalizable mechanism independent of species, malignancy type or chemotherapy regime. To test the association of blunted APC activity with MDR cancer behavior, we used matched parental and MDR MCF7 human breast cancer cells, and a patient derived xenograft (PDX) model of human breast cancer. We show that APC activating mechanisms, such as APC subunit 1 (APC1) phosphorylation and CDC27/CDC20 protein associations, are reduced in MCF7 MDR cells when compared to chemosensitive matched cell lines. Consistent with impaired APC function in MDR cells, APC substrate proteins failed to be effectively degraded. Similar to our previous observations in canine MDR lymphoma cells, chemical activation of the APC using Mad2 Inhibitor-1 (M2I-1) in MCF7 MDR cells enhanced APC substrate degradation and resensitized MDR cells in vitro to the cytotoxic effects of the alkylating chemotherapeutic agent, Doxorubicin (DOX). Using cell cycle arrest/release experiments we show that chemo-sensitive and -resistant MCF7 cells progress through the cell cycle at similar rates, but mitosis is delayed in MDR cells with elevated substrate levels. When treated with M2I-1, MDR cells progress through mitosis at a faster rate that coincides with reduced levels of APC substrates. In our PDX model, mice growing a clinically-MDR human breast cancer tumor show significantly reduced tumor growth when treated with M2I-1, with evidence of increased DNA damage and apoptosis. Thus, our results strongly support the hypothesis that APC impairment is a driver of aggressive tumor development and that targeting the APC for activation has the potential for meaningful clinical benefits in treating recurrent cases of MDR malignancy.

The goal was to model the irrigated (IBY) and rainfed (RBY) bean yields, as a function of essential climatic variables (ECVs), in the center (Culiacán) and south (Rosario) from Sinaloa. In Sinaloa, and for the period 1982–2013 (October–March), the following were calculated: a) temperatures. b) average degree days for the bean, c) cumulative potential evapotranspiration and d) cumulative effective precipitation. For ECVs, from the European Space Agency, e) daily soil moisture. f) IBY and RBY, from the Agrifood and Fisheries Information Service. Multiple linear regressions were applied, which modeled IBY–RBY (dependent variables), as a function of ECVs (independent variables). Then, to establish each Pearson correlation (PC) as significantly different from zero, a hypothesis test was applied: PC vs Pearson's critical correlation (CPC). The four models obtained were significantly predictive: IBY–Culiacán (PC = 0.590 > CPC = |0.349|), RBY–Culiacán (PC = 0.734 > CPC = |0.349|), IBY–Rosario (PC = 0.621 > CPC = |0.355|) and RBY–Rosario (PC = 0.532 > CPC = |0.349|). This study is the first in Sinaloa to predict IBY and RBY based on ECVs, contributing to the production of sustainable food.

Background: Neuromuscular electrical stimulation (NMES) has beneficial effects on physical functions in Multiple Sclerosis (MS) patients. However, the neurophysiological mechanisms underlying these functional improvements are still unclear. This study aims at comparing acute responses in spinal excitability, as measured by soleus Hoffmann reflex (H-reflex), between MS patients and healthy individuals, following three experimental conditions involving the ankle planta flexor muscles: 1) passive NMES (pNMES); 2) NMES superimposed to isometric voluntary contraction (NMES+); and 3) isometric voluntary contraction (ISO). Methods: 20 MS patients (MSp) and 20 healthy individuals as control group (CG) took part in a single experimental session. During each condition, participants performed 15 repetitions of 6 seconds at 20% of maximal voluntary isometric contraction, with 6 seconds of recovery between repetitions. Before and after each condition, H-reflex amplitudes were recorded. Results: In MSp, H-reflex amplitude did not change following any experimental condition (ISO: p = 0.506; pNMES: p = 0.068; NMES+: p = 0.126). In CG, H-reflex amplitude significantly increased following NMES+ (p = 0.01), decreased after pNMES (p = 0.000) and was unaltered following ISO (p = 0.829). Conclusion: the different H-reflex responses between MS and CG might reflect a reduced ability of MS patients in modulating spinal excitability.

Object detection is important in many applications, such as autonomous driving. While 2D images are lack of depth information and are sensitive to environmental conditions, 3D point cloud can provide accurate depth information and a more descriptive environment. However, sparsity is always a challenge in single-frame point cloud object detection. This paper introduces a two-stage proposal-based feature fusion method for object detection using multiple frames. The proposed method, called proposal features fusion (PFF), utilizes a cosine-similarity approach to associate proposals from multiple frames and employs an attention weighted fusion module to merge features from these proposals. It allows for feature fusion specific to individual objects and offers lower computational complexity while achieving higher precision. The experimental results on the nuScenes dataset demonstrate the effectiveness of our approach, achieving a mAP of 46.7%, which is 1.3% higher than the state-of-the-art 3D object detection method.

Dielectric elastomer actuators (DEAs) offer robust, high energy density solutions for soft robotics. The proposed end effector consists of three spring roll configuration DEAs, each acting as a robotic finger, using a 3M VHB-F9473PC adhesive membrane. The lateral force, bending angle and response time of the actuator are measured experimentally and compared with the predictions of an analytical model. The cylindrical actuator measures 70 mm in length and 15 mm in diameter and achieved a lateral force of 30 mN, a bending angle of 6.8 ° and a response time of ≈ 1 s. Spring roll configuration DEAs are shown to reduce the effects of viscoelasticity seen in the membrane, making the actuator more controllable at higher voltages. The dielectric constant of the membrane is shown to be a limiting factor of actuation, with a decrease in dielectric constant resulting in larger actuation. The end effector successfully gripped numerous light objects for extended periods, showing the applicability of spring roll DEAs for soft end effectors.

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.

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.

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.

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.

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.

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.

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.

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.

Traditional silicon binary circuits continue to face challenges such as high leakage power dissipation and large area of interconnections. Multiple-Valued Logic (MVL) and nano-devices are two feasible solutions to overcome these problems. In this paper, we present a novel method to design ternary logic circuits based on Carbon Nanotube Field Effect Transistors (CNFETs). The proposed designs use the unique properties of CNFETs, e.g., adjusting the Carbon Nanotube (CNT) diameters to have the desired threshold voltage and have the same mobility of P-FET and N-FET transistors. Each of our designed logic circuits implements a logic function and its complementary via a control signal. Also, these circuits have a high impedance state which saves power while the circuits are not in use. We show a more detailed application of our approach by designing a two-digit adder-subtractor circuit. We simulate the proposed ternary circuits using HSPICE via standard 32nm CNFET technology. The simulation results indicate the correct operation of the designs under different process, voltage and temperature (PVT) variations. Moreover, we designed a two-digit adder/subtractor and a power efficient ternary logic ALU based on the proposed gates. Simulation results show that the two-digit adder/subtractor using our proposed gates has 12X and 5X lower power consumption and PDP (power delay product) respectively, compared to previous designs.

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

Optimizing the NACA0015 airfoil which is widely applied in small-scale vertical axis wind turbine to make it has a better aerodynamic performance. In the optimization process, using CST parameterization method to perturb the airfoil geometry, the thickness and camber of the airfoil are selected as the constraint, and the value of the maximum tangential force coefficient is chosen as the objective function, the genetic algorithm based on non-dominated sorting (NSGA-II)is selected as an optimization method, calculates the aerodynamic performance of the airfoil by applying the approach of combining XFOIL program and Viterna-Corrigan post-stall mode ,and establishes the optimizing process by the optimization software modefrontier for NACA0015 airfoil’s muti-point optimization, validate the airfoil’s performance with CFD finally. The result illustrates that, by comparing with the NACA0015 airfoil, the optimized airfoil’s lift to drag ratio is improved over a wide range of attack angles, the stall performance is more gentle. The maximum lift coefficient, the maximum lift-drag ratio and the maximum tangential force coefficient are increased by 7.5%,9 and 8.87%, respectively. The optimized airfoil has a wide variable condition performance, more suitable for the operating conditions of a vertical axis wind turbine. Finally, predict the rotor efficiency with optimized airfoil and NACA0015 airfoil for different tip speed ratios and different solidities with multiple streamtube model, the result shows the rotor with optimized airfoil has a higher efficiency.

Traditional gene set enrichment analysis falters when applied to large genomic domains, where neighboring genes often share functions. This spatial dependency creates misleading enrichments, mistaking mere physical proximity for genuine biological connections. Here we present Spatial Adjusted Gene Ontology (SAGO), a novel cyclic permutation-based approach, to tackle this challenge. SAGO separates enrichments due to spatial proximity from genuine biological links by incorporating the genes' spatial arrangement into the analysis. We applied SAGO to various datasets in which the identified genomic intervals are large, including replication timing domains, H3K9me3 and H3K27me3 large domains, HiC compartments and lamina associated domains (LADs). Intriguingly, applying SAGO to prostate cancer samples with large copy number alteration (CNAs) domains eliminated most of the enriched GO terms, thus helping to accurately identify biologically relevant gene sets linked to oncogenic processes, free from spatial bias.

This work is divided into two parts. In the first one the combinatorics of a new class of randomly generated objects, exhibiting the same properties as the distribution of prime numbers, is solved and the probability distribution of the combinatorial counterpart of the n-th prime number is derived, together with an estimate of the prime-counting function π(x). A proposition equivalent to the Prime Number Theorem (PNT) is proved to hold, while the equivalent of the Riemann Hypothesis (RH) is proved to be false with probability 1 (w.p. 1) for this model. Many identities involving Stirling numbers of the second kind and harmonic numbers are found, some of which appear to be new. The second part is dedicated to generalizing the model to investigate the conditions enabling both PNT and RH. A model representing a general class of random integer sequences is found, for which RH holds w.p. 1. The prediction of the number of consecutive prime pairs, as a function of the gap d, is derived from this class of models and the results are in agreement with empirical data for large gaps. A heuristic version of the model, directly related to the sequence of primes, is discussed and new integral lower and upper bounds of π(x) are found.

The objective of the paper is to introduce new similarity measure for single valued neutrosophic sets based on logarithm function. We define logarithm similarity measure and their weighted similarity measure for single valued neutrosophic sets. Then we define hybrid logarithm similarity measure and weighted hybrid logarithm similarity measure for single valued neutrosophic sets. We prove the basic properties of the proposed measures. We then define an entropy function using logarithm function to determine unknown attribute weights. We develop a novel multi attribute group decision making strategy for single valued neutrosophic sets based on the weighted hybrid logarithm similarity measure. We address an illustrative example to demonstrate the effectiveness and aptness of the proposed strategies. We conduct a sensitivity analysis of the developed strategy. We also make a comparison between the obtained results from proposed strategies and different existing strategies in the literature.

The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally for the first time in order to integrate neurodegeneration within the energetics of the cancer acid-base conceptual frame. At all levels of study, molecular, biochemical, metabolic and clinical, the intimate nature of both processes appears to be opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranged original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) becomes an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Also within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth.

The current work reports the upper bound of the state variable of the of the Pointwise Steady Fluid Flow Approximation (PSFFA) model of non-stationary M/Ek/1 queueing system.

There are many applications of anomaly detection in IoT domain. IoT technology consists of large number of interconnecting digital devices not only generating huge data continuously but also making real-time computations. Since IoT devices are highly exposed due to Internet, they frequently meet with the challenges of illegitimate accesses in the form of intrusions, anomaly, fraud, etc. Identifying these illegitimate accesses in IoT domain can be an exciting research problem. In numerous applications fuzzy clustering and rough set theory have been successfully employed. As the data generated in IoT domains are high-dimensional, the clustering methods used for lower dimensional data cannot be applied efficiently. In this article, mixed approaches consisting of nano topology and fuzzy clustering techniques are proposed for anomaly detection. First of all, the nano topology is generated to find lower dimensional apace and then a couple of well-known fuzzy clustering techniques are employed on it for the efficient anomaly detection. The effectiveness of the proposed approaches is evaluated using time-complexity analysis, experimental studies with a synthetic dataset and a real-life dataset along with comparative studies with traditional fuzzy clustering approaches namely fuzzy c-means clustering (FCM) algorithm, Gustafson-Kessel (GK) Algorithm, Gath-Geva (GG) Algorithm, Mahalanobis Distance based Fuzzy C-Means algorithm (M-FCM), and Common Mahalanobis Distance based Fuzzy C-Means algorithm (CM-FCM). Experimentally, it has been found that the proposed approaches outperform the aforesaid algorithms in terms of detection rates, accuracy rates, false alarm rates and computational times.

Finding anomalies in the real-time system is recognized as one of most challenging study in information security. It has so many applications like IoT, and Stock-Market. In any IoT system the data generated are real-time, and temporal in nature. Since due to the extreme exposure to Internet and interconnectivity of devices, the IoT systems often face issues like fraud, anomalies, intrusions etc. Discovering anomaly in such domain can be interesting. Clustering and rough set theory have been tried in many cases. Considering the time-stamp associated with IoT data, time-dependent patterns like periodic clusters can be generated which could be helpful for the efficient detection of anomalies by providing more in-depth analysis of the system. In this paper, a mixed method comprising of nano topology, a modified k-means clustering and an interval superimposition technique is used for finding fuzzy periodic clusters in the subspace generated by the nano topology. For every clusters there will be an associated sequence of time-intervals where it exists. The sequence time-intervals accompanying with each clusters may exhibit some remarkable patterns. For example, there may exist different types of periodicity namely yearly, monthly, daily, and hourly etc. For finding such fuzzy periodicity, an operation called interval-superimposition has been used. The time-intervals associated with each cluster are superimposed if they have reasonable overlapping. Each superimposed time-interval generates a fuzzy time-interval. The data instances are thought to be anomalous if they either belong to sparse clusters or don't belong to any clusters. The efficacy of the method can be assessed by means of both time-complexity analysis and comparative studies with existing clustering-based anomaly detection algorithms with a real-life and a synthetic dataset. It can been found experimentally that our method can extract anomaly with 98% of accuracy and it runs cubic time approximately.

In this paper, we introduce a new class of open sets that is called is*-open set . Also, we present the notion of is*-continuous, is*-open, is*-irresolute, is*-totally continuous, and is-contra-continuous mappings, and we investigate some properties of these mappings. Furthermore, we introduce some is*-separation axioms, and is*-mappings are related with is*-separation axioms. . .

Myocardial infarction, more commonly known as heart attack, is a huge health problem around the world. It is a result of inadequate blood supply to certain parts of the heart and death of heart muscle cells in that region. Although it has been around for a long time, newer and newer ways of probing myocardial infarction is being followed. Bioinformatics and Systems Biology are relatively recent fields to try to give new insights into myocardial infarction. Following the footsteps of others, this in silico study has tried to chime in on the investigation into myocardial infarction. The study began with the gene expression omnibus dataset uploaded to the NCBI from a whole-genome gene expression analysis carried out at Mayo Clinic in Rochester, Minnesota. From the dataset, differentially expressed genes following first-time myocardial infarction were identified and classified into up-regulated and down-regulated ones. Gene Set Enrichment Analysis (GSEA) was carried out on the up-regulated genes which were statistically significant and corresponded with the NCBI generated annotations. Protein-Protein Interaction Network for these genes was constructed. GSEA revealed 5 transcription factors, 5 microRNAs and 3 pathways significantly associated with them. From the Protein-Protein Interaction Network, 6 key proteins (hub nodes) have been identified. These 6 proteins may open a new window of opportunity for the discovery/design of new drugs for mitigating the damage caused by myocardial infarction.

The aim of this article is introduced the concept of double framed T-soft fuzzy set (DFT-soft fuzzy set) which is the combination of soft set and fuzzy set. We also defined the notions and apply this concept in BCK/BCI-algebras. By using example, we also discussed the concept of double framed T-soft fuzzy algebra (DFT-soft fuzzy algebra) and double framed B-soft fuzzy algebra (DFB-soft fuzzy algebra) and also investigated their properties. Each double framed T-soft fuzzy algebra is double framed B-soft fuzzy algebra but by using example, we proved that converse may or may not be possible.

Various short-range radars, such as impulse-radio ultra-wideband (IR-UWB) and frequency-modulated continuous-wave (FMCW) radars, are currently employed to monitor vital signs, including respiratory and cardiac rates (RR and CR). However, these methods do not consider the motion of an individual, which can distort the phase of the reflected signal, leading to inaccurate estimation of RR and CR because of a smeared spectrum. Therefore, motion compensation (MOCOM) is crucial for accurately estimating these vital rates. This paper proposes an efficient method incorporating MOCOM to estimate RR and CR with super-resolution accuracy. The proposed method effectively models the radar signal phase and compensates for motion. Additionally, applying the super-resolution technique to RR and CR separately further increases the estimation accuracy. Experimental results from the IR-UWB and FMCW radars demonstrate that the proposed method successfully estimates RR and CR even in the presence of body movement.

Traffic anomaly detection is crucial for urban management, yet current research is often confined to small-scale endeavors. This study collected nine months of real-time Wuhan traffic monitoring data from Amap. We proposed Traffic-ConvLSTM, a multi-scale spatial-temporal technique based on long and short-term memory networks (LSTM) and convolutional neural networks (CNN) to effectively achieve long-term anomaly detection at the city level. First, we convert the traffic flow data into image representation, which enables the capture of the spatial correlation between traffic flow and roads and the correlation between traffic flow and roads, as well as the surrounding environment. Second, The model utilizes convolution kernels of different sizes to extract spatial features at road-level, regional-level, and city-level scales, while incorporating temporal features of different time steps to capture hourly, daily, and weekly dynamics. Additionally, varying weights are assigned to the convolution kernels and temporal features of varying spatio-temporal scales to capture the heterogeneous strengths of spatio-temporal correlations within patterns of traffic anomalies. The proposed Traffic-ConvLSTM model exhibits improved performance over existing techniques in the task of identifying long-term and large-scale traffic anomaly occurrences. Furthermore, the analysis reveals significant traffic anomalies during holidays and urban sporting events. The diverse travel patterns observed in response to various activities offer insights for large-scale urban traffic anomaly management, providing recommendations for city-level traffic control strategies.

Serum neurofilament light chain (sNfL) levels have been proposed as a biomarker of the clinical activity, disability progression, and response to treatment of people with multiple sclerosis (PwMS); however, questions remain about its implementation in clinical practice. Ocrelizumab (OCR) has proven effective to improve clinical and radiological outcomes and to reduce sNfL levels. This real-life study followed the sNfL levels of 30 PwMS treated for 12 months with OCR and evaluated the usefulness of this biomarker for the short-term prognosis, considering expanded disability status scale (EDSS), annualized relapse rate (ARR), radiological activity, and NEDA-3 values. OCR reduced the ARR in 83% of PwMS and the radiological activity in 80%. Their EDSS was maintained, while NEDA-3 was achieved in 70% at 12 months. OCR produced an early reduction in sNfL levels (at 3 months). At baseline, greater MRI-evaluated radiological activity was associated with higher sNfL levels. sNFL levels over the first 12 months of treatment did not predict a suboptimal response or sustained control of the disease. Longer-term studies are needed to explore the predictive usefulness of sNfL levels in PwMS treated with high-efficacy drugs

Film cooling technology is of great significance to enhance the performance of aero-engines and extend service life. With the increasing requirements for film cooling efficiency, researchers and engineers have carried out a lot of work on the precision and digital measurement of cooling holes. Based on the above, this paper outlines the importance and principles of film cooling technology, reviews the evolution of cooling holes. Also, this paper details the traditional measurement methods of the cooling hole used in current engineering scenarios with their limitations and categorizes digital measurement methods into five main types, including probing measurement technology, optical measurement technology, infrared imaging technology, computer tomography(CT) scanning technology, and composite measurement technology. The five types of methods and integrated automated measurement platforms are also analyzed. Finally, through a generalize and analysis of cooling hole measurement methods, this paper points out technical challenges and future trends, providing a reference and guidance for forward researches.

Tularemia is a zoonotic disease caused by {\it Francisella tularensis} bacteria, a gram-negative coccobacillus-shaped bacterium. There are multiple transmission routes of the infection to humans such as consumption of contaminated food or water, handling of infected animals or bites from {\it haematophagous} arthropods (such as ticks, deer flies, or mosquitoes). In this study we focus on transmission via the bites of ticks and developed a deterministic model of ordinary and impulsive differential equations to gain insight in the differential effect of prescribed fire on {\it Demacenta variablis} and {\it Amblyomma americanum} ticks and the prevalence of tularemina. We found that prescribed fire differentially reduce the number of the two ticks with {\it A. americanum} reduced the least compare to {\it D. variablis} subsequently leading to differential increase of tularemia new infected cases in humans and rodents. Our result further indicates that the spatial arrangement of burn against unburn areas may not matter as either arrangement led to fewer ticks and reduction in tularemia transmission when prescribed fire was implemented. The results of this study provide important new understandings of the intricate effect of prescribed fire on tick species, and the dynamics of the tick-borne disease, tularemia disease in this study.

Resistance to therapy and disease progression are the main causes of mortality in most cancers. In particular, the development of resistance is an important limitation affecting the efficacy of therapeutic alternatives for cancer, including chemotherapy, radiotherapy, and immunotherapy. Signaling pathways are largely responsible for the mechanisms of resistance to cancer treatment and progression, and multiple myeloma is no exception. p38 mitogen-activated protein kinase (p38) is downstream of several signaling pathways specific to treatment resistance and progression. Therefore, in recent years, developing therapeutic alternatives directed at p38 MAPK has been of great interest, in order to reverse chemotherapy resistance and prevent progression. In this review, we discuss recent findings on the role of p38, including recent advances in our understanding of its expression and activity as well as its isoforms, and its possible clinical role based on the mechanisms of resistance and progression in multiple myeloma.

Gradual disability worsening in Multiple Sclerosis (MS) is indicative of confirmed progression that mostly involves progression independent of relapse activity (PIRA) and is associated with neurodegeneration. Insights from pathology reveal grey matter involvement (neocortex, hippocampus, spinal cord, and deep grey matter structures) and microglia activation in early stages of MS. Cortical lesions result in thinning and atrophy and are considered accurate predictors of disability progression and cognitive decline.Neuroimaging biomarkers, such as high-resolution 7T MR images and TSPO-PET, have been examined for the detection of cortical pathology linked to cognitive deficits and thus progression, but are limited in clinical practice due to availability, time constraints, and cost.Electroencephalography (EEG) emerges as a non-invasive, cost-effective tool that reflects cortical activity in MS. Its potential in monitoring cognitive impairment is explored by focusing on nonlinear EEG analysis. The MuST PREDICT^TM project aims to extract linear and nonlinear EEG features, investigating their role in predicting disease progression and optimizing treatment. The study employs retrospective, cross-sectional, and prospective designs, utilizing EEGs from various MS forms, cognitive assessments, serum/cerebrospinal fluid biomarkers and neuroimaging. The methodology involves time-based and spectral feature extraction, employing artificial intelligence classifiers and brain criticality-based approaches.The conceptual framework of an innovative modality is herein presented, that would EEG for early MS progression detection. Standardization of the methodology could lead to the creation of a digital tool for better prognostication and treatment strategy optimization.

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.

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.

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.

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.

NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As a result of its central role in so many important cellular processes, NF-κB dysregulation has been implicated in the pathology of important human diseases. NF-κB activation causes inappropriate inflammatory responses in diseases including rheumatoid arthritis (RA) and multiple sclerosis (MS). Thus, modulation of NF-κB signaling is being widely investigated as an approach to treat chronic inflammatory diseases, autoimmunity and cancer. The emergence of COVID-19 in late 2019, the subsequent pandemic and the huge clinical burden of patients with life-threatening SARS-CoV-2 pneumonia led to a massive scramble to repurpose existing medicines to treat lung inflammation in a wide range of healthcare systems. These efforts continue and these efforts continue to be con-troversial. Drug repurposing strategies are a promising alternative to de-novo drug development, as they minimize drug development timelines and reduce the risk of failure due to unexpected side effects. Different experimental approaches have been applied to identify existing medicines which inhibit NF-κB that could be repurposed as anti-inflammatory drugs.

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

We are concerned with the use of some classical spectral collocation methods as well as with the new software system Chebfun in order to compute high order (index) eigenpairs of singular as well as regular Schrodinger eigenproblems. We want to highlight both the qualities as well as the shortcomings of these methods and evaluate them vis-a-vis the usual ones. In order to resolve a boundary singularity we use Chebfun with the simple domain truncation technique. Although this method is equally easy to apply with spectral collocation, things are more nuanced in the case of these methods. A special technique to introduce boundary conditions as well as a coordinate transform which maps an unbounded domain to a nite one are the ingredients. A challenging set of "hard" benchmark problems, for which usual numerical methods (f. d., f. e. m., shooting etc.) fail, are analysed. In order to separate "good"and "bad"eigenvalues we estimate the drift of the set of eigenvalues of interest with respect to the order of approximation and/or scaling of domain parameter. It automatically provides us with a measure of the error within which the eigenvalues are computed and a hint on numerical stability. We pay a particular attention to problems with almost multiple eigenvalues as well as for problems with a mixed (continuous) spectrum. In the latter case we try to numerically highlight its existence. Special attention will be paid to the higher eigenpairs (the pair of eigenvalue and the corresponding eigenfunction approximated by an eigenvector spanning its nodal values).

In this paper, we present an extended version of the Hadi-Vencheh model for multiple criteria ABC inventory classification. The proposed model is a nonlinear weighted product model (WPM) which determines a common set of weights for all the items. Our proposed nonlinear WPM incorporates multiple criteria with different measure units, without converting the performance of each inventory item in terms of each criterion into a normalized attribute value, thereby providing an improvement over the model proposed by Hadi-Vencheh. Our study mainly includes various criteria for ABC classification, and demonstrates an efficient algorithm for solving nonlinear programming problems in which the feasible solution set does not have to be convex. The algorithm presented in this study improves the solution efficiency of the Canonical Coordinates Method (CCM) algorithm substantially when applied to large scale, nonlinear programming problems. The modified algorithm was tested to compare our proposed model results to the results derived using the Hadi-Vencheh model and demonstrate the algorithm's efficacy. The practical implications of the study are to develop an efficient nonlinear optimization solver by optimizing the quality of existing solutions, thus improving time and space efficiency.

Soil quality assessment based on crop yields and identification of key indicators of it can be used for better management of agricultural production. In the current research, the weighted additive soil quality index (SQIw), factor analysis (FA) and multiple linear regression (MLR) method are used to assess the soil quality of rainfed winter wheat fields with two soil orders on 53.20 km2 of agricultural land in western Iran. A total of 18 soil quality indicators were determined for 100 soil samples (0-20 cm depth) from two soil orders (Inceptisols and Entisols). The soil properties measured were: pH, soil texture, organic carbon (OC), cation exchange capacity (CEC), electrical conductivity (EC), soil microbial respiration (SMR), carbonate calcium equivalent (CCE), soil porosity (SP), bulk density (BD), exchangeable sodium percentage (ESP), mean weight diameter (MWD), available potassium (AK), total nitrogen (TN), available phosphorus (AP), available Fe (AFe), available Zn (AZn), available Mn (AMn), and available Cu (ACu). Mean wheat grain yield for the two years for all of the 100 sampling sites was also gathered. The SQIw was calculated using two weighting methods (FA and MLR) and maps were created using a digital soil mapping framework. The soil indicators taken in the minimum data set (MDS) were AK, clay, CEC, AP, SMR, and sand. The correlation between the MLR weighting technique (SQI-M) and the rainfed wheat yield (r=0.62) was slightly larger than that the correlation of yield with the FA weighted technique (SQI-F) (r=0.58). Results showed that the means of both SQI-M and SQI-F and rainfed wheat yield for Inceptisols were higher than for Entisols although these differences were not statistically significant. Both SQI-M and SQI-F showed that areas with Entisols had lower proportions of good soil quality grades (Grade I and II), and higher proportions of poor soil quality grades (Grade IV and V) compared to Inceptisols. Based on these results, soil type must be considered for soil quality assessment in future studies to maintain and enhance soil quality and sustainable production. The overall soil quality of the study region was of poor and moderate grades. To improve soil quality, it is therefore recommended that effective practices such as the implementation of scientific integrated nutrient management involving the combined use of organic and inorganic fertilizers in rainfed wheat fields be promoted.

The formation of high-melting-point Cu₆Sn₅ interconnections is crucial to overcome the collapse of Sn-based micro-bumps and produce reliable intermetallic interconnections in three-dimensional (3D) package. However, because of the multiple reflows in 3D package manufacturing, Cu₆Sn₅ interconnections will experience the cyclic polymorphic transitions in the solid state. The repeated and abrupt change in the Cu₆Sn₅ lattice due to the cyclic polymorphic transitions can cause extreme strain oscillations, producing damages at the surface and in the interior of the Cu₆Sn₅ matrix. Moreover, because of the polymorphic-transition-induced grain splitting and superstructure phase formation, the reliability of Cu₆Sn₅ interconnections will thus face great challenges in 3D package. In addition, the Cu₆Sn₅ polymorphic transition is structure-dependent, and the η′↔η polymorphic transition will occur at the surface while the η′↔ηs↔η polymorphic transition will occur in the deep matrix. Our results can provide in-depth understandings of structural evolution and damage mechanism of Cu₆Sn₅ interconnections in real 3D package manufacturing.

The spatial formation of coherent random laser modes in strongly scattering disordered random media is a central feature in the understanding of the physics of random lasers. We derive a quantum field theoretical method for random lasing in disordered samples of complex amplifying Mie resonators which is able to provide self-consistently and free of any fit parameter the full set of transport characteristics at and above the laser phase transition. The coherence length and the correlation volume respectively is derived as an experimentally measurable scale of the phase transition at the laser threshold. We find that the process of stimulated emission in extended disordered arrangements of active Mie resonators is ultimately connected to time-reversal symmetric multiple scattering in the sense of photonic transport while the diffusion coefficient is finite. A power law is found for the random laser mode diameters in stationary state with increasing pump intensity.

Multiple lines of evidence indicate that CD8$^+$ T cells are important in the control of HIV-1 (HIV) replication. However, CD8$^+$ T cells induced by natural infection cannot eliminate the virus or reduce viral loads to acceptably low levels in most infected individuals. Understanding the basic quantitative features of CD8$^+$ T-cell responses induced during the course of HIV infection may therefore inform us about the limits that HIV vaccines, which aim to induce protective CD8$^+$ T-cell responses, must exceed. Using previously published experimental data from a cohort of HIV-infected individuals with sampling times from acute to chronic infection we defined the quantitative properties of CD8$^+$ T-cell responses to the whole HIV proteome. In contrast with a commonly held view, we found that the relative number of HIV-specific CD8$^+$ T-cell responses (response breadth) changed little over the course of infection (first 400 days post-infection), with moderate but statistically significant changes occurring only during the first 35 symptomatic days. This challenges the idea that a change in the T-cell response breadth over time is responsible for the slow speed of viral escape from CD8$^+$ T cells in the chronic infection. The breadth of HIV-specific CD8$^+$ T-cell responses was not correlated with the average viral load for our small cohort of patients. Metrics of relative immunodominance of HIV-specific CD8$^+$ T-cell responses such as Shannon entropy or the Evenness index were also not significantly correlated with the average viral load. Our mathematical-model-driven analysis suggested extremely slow expansion kinetics for the majority of HIV-specific CD8$^+$ T-cell responses and the presence of intra- and interclonal competition between multiple CD8$^+$ T-cell responses; such competition may limit the magnitude of CD8$^+$ T-cell responses, specific to different epitopes, and the overall number of T-cell responses induced by vaccination. Further understanding of mechanisms underlying interactions between the virus and virus-specific CD8$^+$ T-cell response will be instrumental in determining which T-cell-based vaccines will induce T-cell responses providing durable protection against HIV infection.

(1) Background: Evidence-based policymaking requires data about the local population's socioeconomic status (SES) at detailed geographical level, however, such information is often not available, or is too expensive to acquire. Researchers have proposed solutions to estimate SES indicators by analyzing Google Street View images, however, these methods are also resource-intensive, since they require large volumes of manually labeled training data. (2) Methods: We propose a methodology for automatically computing surrogate variables of SES indicators using street images of parked cars and deep multiple instance learning. Our approach does not require any manually created labels, apart from data already available by statistical authorities, while the entire pipeline for image acquisition, parked car detection, car classification, and surrogate variable computation is fully automated. The proposed surrogate variables are then used in linear regression models to estimate the target SES indicators. (3) Results: We implement and evaluate a model based on the proposed surrogate variable at 30 municipalities of varying SES in Greece. Our model has $R^2=0.76$ and a correlation coefficient of $0.874$ with the true unemployment rate, while it achieves a mean absolute percentage error of $0.089$ and mean absolute error of $1.87$ on a held-out test set. Similar results are also obtained for other socioeconomic indicators, related to education level and occupational prestige. (4) Conclusions: The proposed methodology can be used to estimate SES indicators at the local level automatically, using images of parked cars detected via Google Street View, without the need for any manual labeling effort.

For improving the tracking accuracy and model switching speed of maneuvering target tracking in nonlinear systems, a new algorithm named interacting multiple model fifth-degree spherical simplex-radial cubature filter (IMM5thSSRCKF) is proposed in this paper. The new algorithm is a combination of the interacting multiple model (IMM) filter and fifth-degree spherical simplex-radial cubature filter (5thSSRCKF). The proposed algorithm makes use of Markov process to describe the switching probability among the models, and uses 5thSSRCKF to deal with the state estimation of each model. The 5thSSRCKF is an improved filter algorithm, which utilizes the fifth-degree spherical simplex-radial rule to improve the filtering accuracy. Finally, the tracking performance of the IMM5thSSRCKF is evaluated by simulation in a typical maneuvering target tracking scenario. Simulation results show that the proposed algorithm has better tracking performance and quicker model switching speed when disposing maneuver models compared with IMMUKF, IMMCKF and IMM5thCKF.

Continuation methods are presented that are capable of treating frequency-domain flutter equations including multiple nonlinearities represented by describing functions. A small problem demonstrates how a series of continuation processes can find all limit-cycle oscillations within a specified region with a reasonable degree of confidence. Curves of the limit-cycle amplitude variation with velocity, indicating regions of stability and instability with colors give a compact view of the nonlinear behavior throughout the flight regime. A continuation technique for reducing limit-cycle amplitudes by adjusting various system parameters is presented. These processes are economical enough to be a routine part of aircraft design and certification.

Synthetic Aperture Radar has been extensively used in numerous fields and can gather a wealth of information about the area of interest. This large-scene data-intensive technology puts a high value on automatic target recognition (ATR) which can free the utilizers and boost the efficiency. Recent advances in artificial intelligence have made it possible to create a deep learning-based SAR ATR that can automatically identify target features from massive input data. In the last 6 years, intensive research has been conducted in this area, however, most papers in the current SAR ATR field used recurrent neural network (RNN) and convolutional neural network (CNN)-varied models to deepen the regime’s understanding of the SAR images. To equip SAR ATR with updated deep learning technology, this paper tries to apply a lightweight vision transformer (LViT)-based model to classify SAR images. The entire structure was verified by an open- accessed SAR data set and recognition results show that the final classification outcomes are robust and more accurate in comparison with referred traditional network structures without even using any convolutional layers.

Genomic selection (GS) can accelerate variety improvement when training set (TS) size, and its relationship with the breeding set (BS) are optimized for prediction accuracies (PA) of genomic prediction (GP) models. Sixteen GP algorithms were run on phenotypic best linear unbiased predictors (BLUPs) and estimators (BLUEs) of resistance to both fall armyworm (FAW) and maize weevil (MW) in a tropical maize panel. For MW resistance, 37% of the panel was the TS, and BS was the remainder whilst for FAW, random-based training sets (RBTS) and pedigree-based training sets (PBTS) were designed. PAs achieved with BLUPs varied from 0.66 to 0.82 for MW resistance traits, and, for FAW resistance, 0.694 to 0.714 for RBTS of 37%, and 0.843 to 0.844 for RBTS of 85%, and, these were at least two-fold those from BLUEs. For PBTS, FAW resistance PAs were generally higher than those for RBTS, except for one dataset. GP models generally showed similar PAs across individual traits whilst the TS designation was determinant since a positive correlation (R=0.92***) between TS size and PAs was observed for RBTS and, for the PBTS, it was negative (R=0.44**). This study pioneers the use of GS for maize resistance to insect pests in sub-Saharan Africa.

In the present study. At first, some properties of r-fuzzy soft β-closed sets are introduced on fuzzy soft topological spaces based on the paper Aygunoglu et al. (Hacet. J. Math. Stat. 2014, 43, 193-208). Also, we define the closure and interior operators with respect to the classes of r-fuzzy soft β-closed and r-fuzzy soft β-open sets, and investigate some of their properties. In addition, the concept of r-fuzzy soft β-connected sets is introduced and characterized with help of fuzzy soft β-closure operators. Thereafter, some properties of a fuzzy soft β-continuity are studied. Furthermore, we introduce and study the concepts of fuzzy soft almost (weakly) β-continuous functions, which are weaker forms of a fuzzy soft β-continuity. Also, the relationships between these classes of functions are specified with the help of some illustrative examples. Finally, we explore new types of fuzzy soft functions called, fuzzy soft β-irresolute (strongly β-irresolute, β-irresolute open, β-irresolute closed and β-irresolute homeomorphism) functions, and discuss some properties of them. Also, we show that fuzzy soft strongly β-irresolute → fuzzy soft β-irresolute → fuzzy soft β-continuity, but the converse may not be true.

Extracting entities from large volumes of chicken epidemic texts is crucial for knowledge sharing, integration, and application. However, Named Entity Recognition (NER) encounters significant challenges in this domain, particularly due to the prevalence of nested entities and domain-specific named entities, coupled with a scarcity of labeled data. To address these challenges, we compiled a corpus from 50 books on chicken diseases, covering 28 different disease types. Utilizing this corpus, we developed a nested NER model, MFGFF-BiLSTM-EGP. This model integrates the Multiple Fine-Grained Feature Fusion (MFGFF) module with a BiLSTM neural network and employs an Efficient Global Pointer (EGP) for predicts the entity location encoding. In MFGFF module we designed three encoders, character encoder, word encoder and sentence encoder, this design effectively captures fine-grained features and improves the recognition accuracy of nested entities. Experimental results show that the model performs robustly, with F1 scores of 91.98%, 73.32%, and 82.54% on the CDNER, CMeEE V2, and CLUENER datasets, respectively, outperforming other commonly used NER models. Specifically, on the CDNER dataset, the model achieved an F1 score of 79.68% for nested entity recognition. This research not only advances the development of knowledge graph and intelligent question-answering system for chicken diseases but also provides a viable solution for extracting disease information that can be applied to other livestock species.

In mountain-gorge areas, the rock creep is the critical process for high rock slopes failure. During long-term rock creep, slopes might encounter earthquakes and form further creep after earthquakes. This complex mechanical response process can easily lead to the slope failure. Based on a high rock slope in the Nujiang River Basin, this paper analyzes deformation characteristics and dynamic response characteristics by using FLAC3D software, considering combined effects of multiple earthquakes and long-term creep. Results show that when the amplitude increases, the shear strength of the slope decreases and the risk of instability increases under combined actions of creep and earthquakes. Earthquakes promote the development of creep and induce the accumulation of damage on the slope surface and in the slope. The delayed effect becomes more pronounced as the slope height increases. We need to consider deformation differences of the slope further. The ground motion response on the slope surface is stronger than those in the slope, with the peak occurring at the top of the slope. Earthquakes have a greater impact on the middle and top of the slope surface, where cumulative damage and crack development begin. Reinforcement should be considered in these two places. Vertical earthquake has a great effect on the dynamic response. The phenomenon of slope resonance leads to a larger MPGA in the vertical direction than in the horizontal direction. Nonlinear and damping characteristics of the slope and the frequency of seismic waves cause the MPGA to decrease with the increase of amplitudes. This study could promote the development of high rock slope failure mechanism and provide references for the prevention of landslides in the Nujiang River Basin.

This research provides an in-depth analysis of drought impacts in West Pokot, Kenya, utilizing both remote sensing surveys and focus group discussions. The study commenced by assessing the impact of drought on vegetation health via spatial sensors. It then utilized surveys and focus group discussions (FGDs) to engage farmers from the most drought-affected areas in Kacheliba and Sigor sub-counties. The analysis of remote sensing data from 1990 to 2022 highlighted that Sigor and Kacheliba experienced significant drought events during the years 1995, 2000, 2002, 2005, and 2009, and 1991, 1995, 2000, 2005, and 2019, respectively. This study delves into both the meteorological and socio-economic effects on local communities. Using the Multinomial Logistic Regression (MLR) model with the glm function, the research uncovered the impacts of so-cio-economic factors and agricultural practices on household livestock production. Additionally, the study employed Multiple Correspondence Analysis (MCA) to explore the dynamics between livestock production, community resilience, and crop production. The findings underscore the urgent need for tailored interventions to enhance community resilience in the face of increasing climatic extremes, serving as a blueprint for similar arid and semi-arid regions worldwide.

Fermatean fuzzy sets (FFSs) are a versatile tool for handling uncertain problems and have shown great effectiveness in practical applications. However, many existing Fermatean fuzzy similarity measures exhibit counter-intuitive situations, making it challenging to accurately measure the similarity or difference between FFSs. To address this issue, several similarity and distance measures for FFSs are proposed, inspired by the Tanimoto similarity measure. The properties of the proposed measures are also explored, along with several comparative examples with existing measures for FFSs, which illustrate their superior performance in processing fuzzy information from FFSs. The proposed measures have effectively overcome the counter-intuitive challenges posed by many existing measures and significantly outperforms existing measures in differentiating different FFSs. Furthermore, we demonstrate the practical applicability of the proposed measures in solving pattern recognition, medical diagnosis and multiple-attribute decision-making problems.

Sphingosine 1-phosphate (S1P) is a signaling lipid molecule involved in various cellular processes. It is important to develop a quantitative method for S1P to determine endogenous levels and to investigate its functions. Especially since S1P is a tiny lipid component of most biological samples, highly sensitive analysis by LC-MS/MS is required. The main challenge in S1P analysis by chromatography is peak broadening due to the presence of a polar phosphate and zwitterion formation in S1P. In this study, we used hydrogen fluoride (HF) to efficiently remove a phosphate and then analyzed the surrogate, sphingosine, as a sharp peak by LC-ESI-MS/MS. We optimized the dephosphorylation reaction in terms of reaction time, temperature, and HF concentration. Multiple reaction monitoring (MRM) for dephosphorylated form of S1P and C17-S1P as internal standard at m/z transition 300.4&gt;282.4 (quantification ion), 300.4&gt;262.4 (qualification ion), 286.3&gt;268.2 (internal standard). This method was validated by essential parameters such as specificity, linearity, range, LOQ, LOD, accuracy, precision, and repeatability. To confirm this new method, we quantified S1P levels in various serum products (100.02 ~ 284.38 nM). To apply the method in vivo, we analyzed S1P in plasma and kidney tissues obtained from a chronic kidney disease (CKD) mouse model. S1P levels were increased only in CKD kidney tissue but not in plasma. In conclusion, by applying the dephosphorylation step with HF, we established a new sensitive LC-MS/MS quantitative method for S1P that can be applied to biological samples.

The short-term intake (ESTI) of Hungarian consumers to pesticide residues was assessed based on 2331 test results obtained during 2017-2021 monitoring program in the frequently analyzed apples, sour cherries, table grapes, peaches, nectarines, peppers and strawberries (23.5% of all samples taken from 119 crops). The age-specific consumption data were obtained from two representative national food consumption surveys (2009 and 2018-2020). The exposure was characterized with Hazard Quotient and Hazard Index considering the acute reference doses of pesticide residues detected in the samples. When ESTI was calculated with all detected “single“ residues and variability factor of 3.6, recommended for evaluation of monitoring results, the HI only exceeded 1 for children &lt;3 years old eating grape (1.50-1.81). HI was &lt;1 when any of the 6 foods were eaten together within one day. Between forty and fifty percent of samples contained 2-23 residues. Though, the individual residue concentrations were below the corresponding MRLs, multiple residues being present in one sample resulted in maximum HI values in apples (1.14); grapes (6.57); peaches and nectarines (2.57); strawberries (2.74); peppers (10.44). Residues with low ARfD values contributed most. Applying HI is simple, but provides only point estimates; therefore, it should only be used in first-tier risk assessment.

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.

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.

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.

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.

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.

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.

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.

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.

Photovoltaic (PV) generation is potentially uncertain. Probabilistic PV generation forecasting methods have been proposed with prediction intervals (PIs). However, several studies have dealt with geographically distributed PVs in a certain area. In this study, a two-step probabilistic forecast scheme is proposed for geographically distributed PV generation forecasting. Each step of the proposed scheme adopts ensemble forecasting based on three different machine-learning methods. In this case study, the proposed scheme was compared with conventional non-multistep forecasting. The proposed scheme improved the reliability of the PIs and deterministic PV forecasting results through 30 days of continuous operation with real data in Japan.

Targeted radionuclide therapy (TRT) has recently seen a surge in popularity, with the use of radionuclides conjugated to small molecules and antibodies. Similarly, immunotherapy also has shown promising results – an example being chimeric antigen receptor (CAR) T-cells therapy in hematologic malignancies. Moreover, TRT and CAR T therapies possess unique features that require special consideration when determining how to dose, time, and sequence combination treatments, including the distribution of TRT dose in the body, the decay rate of the radionuclide, and the proliferation and persistence of the CAR-T cells. These characteristics complicate additive or synergistic effects of combination therapies and warrant a mathematical treatment which includes these dynamics in relation to the proliferation and clearance rates of the target tumor cells. Here we combine two previously published mathematical models in a multiple myeloma setting to explore the effects of dose, timing, and sequencing of TRT and CAR-T cell based therapies. We find that for a fixed TRT and CAR-T cell dose, the tumor proliferation rate is the most important parameter in determining the best timing of TRT and CAR T therapies.