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Objectives: To evaluate the utility of regression analysis in the assessment of conduction slowing in diabetic distal symmetrical polyneuropathy (DSP) and in identifying superimposed demyelination beyond fiber loss. Background: Causes of conduction slowing beyond pure axonal loss has been attributed to an additional demyelinating component. We therefore evaluated the utility of regression analysis in the assessment of conduction slowing in diabetic DSP and in identifying superimposed demyelination beyond fiber loss. Methods: We previously established regression analysis to develop confidence intervals that assess the range of conduction slowing from primary demyelination in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). In this study, by using the regression equations, we analyzed conduction slowing in patients with diabetic DSP. Results: Mean conduction velocity (CV) was significantly slower in diabetic DSP than in the non-diabetic DSP for all tested nerves. More patients were found to fulfill the regression equation criteria in the diabetic group compared to the non-diabetic group (47.0 % vs. 23.3 %). The estimated likelihood of having more than two motor nerves with CV slowing in the demyelination range by American Academy of Neurology or regression equations criteria was significantly higher in the diabetic DSP (0.73) compared to non-diabetic DSP (0.52). Conclusions: Conduction slowing in diabetic DSP beyond what is expected exclusively from axonal loss could be identified by regression analysis.

Background: Radixin is an ERM family protein that includes radixin, moesin, and ezrin. The importance of ERM family proteins has been attracting more attention, and studies on the roles of ERM in biological function and the pathogenesis of some diseases are accumulating. In particular, we have found that radixin is the most dramatically changed ERM protein in elevated glucose-treated Schwann cells. Method: We systemically review the literature on ERM, radixin in focus, and update the roles of radixin in regulating cell morphology, interaction, and cell signaling pathways. The potential of radixin as a therapeutic target in neurodegenerative diseases and cancer was also discussed. Results: Radixin research has focused on its cell functions, activation, and pathogenic roles in some diseases. Radixin and other ERM proteins maintain cell shape, growth, and motility. In the nervous system, radixin has been shown to prevent neurodegeneration and axonal growth. The activation of radixin is through phosphorylation of its conserved threonine residues. Radixin functions in cell signaling pathways by binding to membrane proteins and relaying the cell signals into the cells. Deficiency of radixin has been involved in the pathogenic process of diseases in the central nervous system and diabetic peripheral nerve injury. Moreover, radixin also plays a role in cell growth and drug resistance in multiple cancers. The trials of therapeutic potential through radixin modulation have been accumulating. However, the exact mechanisms underlying the roles of radixin are far from clarification. Conclusions: Radixin plays various roles in cells and is involved in developing neurodegenerative diseases and many types of cancers. Therefore, radixin may be considered a potential target for developing therapeutic strategies for its related diseases. Further elucidation of the function and the cell signaling pathways that are linked to radixin may open the avenue to finding novel therapeutic strategies for diseases in the nervous system and other body systems.

Objective: To develop a novel strategy for identifying acquired demyelination in diabetic distal symmetrical polyneuropathy (DSP). Background: Motor nerve conduction velocity (CV) slowing in diabetic DSP exceeds expectations for pure axonal loss thus implicating superimposed acquired demyelination. Methods: After establishing demyelination confidence intervals by regression analysis of nerve conduction data from chronic inflammatory demyelinating polyneuropathy (CIDP), we prospectively studied CV slowing in 90 diabetic DSP patients with and without at least one motor nerve exhibiting CV slowing (groups A and B) into the demyelination range by American Academy of Neurology (AAN) criteria respectively and 95 amyotrophic lateral sclerosis (ALS) patients. Simultaneously, secretory phospholipase A2 (sPLA2) activity was assessed in both diabetic groups and 46 healthy controls. Results: No ALS patient exhibited CV slowing in more than two motor nerves based on AAN criteria or the confidence intervals. Group A demonstrated a significantly higher percentage of patients as compared to group B fulfilling the above criteria, with an additional criterion of at least one motor nerve exhibiting CV slowing in the demyelinating range and a corresponding F response in the demyelinating range by AAN criteria (70.3 % vs. 1.9 %; p

Abstract Introduction Intravenous immunoglobulin (IVIG) is recommended as first-line therapy for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), an immune-mediated neuropathy. The clinical profile of patients with CIDP newly initiating IVIG is poorly characterized. This claims-based cohort study describes characteristics of US patients with CIDP initiating IVIG treatment. Methods Adult immunoglobulin (IG)-naïve patients with CIDP diagnosed between 2008 and 2018 and a subgroup of patients subsequently initiating IVIG were identified in the Merative MarketScan Research Databases. Demographics, clinical characteristics, and diagnostic procedures were described for patients initiating IVIG. Results Of 32,090 patients with CIDP identified, 3975 (mean age 57 years) subsequently initiated IVIG. In the 6 months prior to IVIG initiation, diagnoses of comorbidities including neuropathy (75%), hypertension (62%), and diabetes (33%) were frequent, as were CIDP features/symptoms/markers of functional status including chronic pain (80%), difficulty walking (30%), and weakness (30%). CIDP-related laboratory/diagnostic procedures were performed in approximately 20– > 40% of patients in the 3 months prior to IVIG initiation (63.7% underwent electrodiagnostic/nerve conduction testing in the 6 months prior to IVIG initiation). Patient characteristics by initial IVIG product differed only in IVIG initiation year, US geographic region, and insurance type. Comorbidities, CIDP severity or functional status markers, and other clinical variables were generally well balanced across initial IVIG product groups. Conclusion A heavy burden of symptoms, comorbidities, and diagnostic testing exists in patients with CIDP initiating IVIG. Characteristics of patients with CIDP initiating different IVIG products are well balanced, suggesting an absence of clinical or demographic determinants underlying IVIG selection.

Abstract Introduction Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare progressive or relapsing inflammatory disease. Intravenous immunoglobulin (IVIG) is recommended as a first-line therapy. The aim of this study was to describe real-world treatment patterns and outcomes of patients with CIDP in the Define initiating IVIG treatment. Methods This cohort study used health insurance claims data from the Merative MarketScan Research Databases (2008–2018). Adult patients (≥ 18 years old) with CIDP without prior immunoglobulin treatment were identified using International Statistical Classification of Diseases and Related Health Problems (ICD) codes, and patients subsequently initiating IVIG were included in the analysis. Real-world IVIG treatment patterns and treatment and safety outcomes (assessed via ICD codes) were described. Results In total, 3975 patients (median age 58 years) with CIDP who initiated IVIG were identified. After the initial IVIG loading period, patients received IVIG at a median dosing interval of 21 days (quartile [Q]1, Q3: 7, 28), and continued treatment for a median of 129 days (Q1, Q3: 85, 271). After the 2-year follow-up period, 55% of patients had discontinued all IVIG treatment; more than one-half of these discontinuations occurred within 4 months. Diagnoses of impaired functional status were evident in more than 30% of patients at baseline, but at lower rates during follow-up. Rates of new-onset safety outcomes after IVIG treatment were low. Conclusion This real-world analysis of IVIG treatment patterns and treatment and safety outcomes of patients with CIDP who initiated IVIG highlights the unmet need for improved long-term management. Further research is needed to evaluate the use of functional status measures as endpoints for immunoglobulin treatment effectiveness.

Objective: Since motor nerve conduction slowing can occur due to loss of large axons, we investigate the conduction slowing profile in amyotrophic lateral sclerosis (ALS) and identify the limits beyond which the diagnosis of exclusive axonal loss is unlikely. Methods: First, using linear regression analysis, we established the range of motor conduction slowing in 76 chronic inflammatory demyelinating polyneuropathy (CIDP) patients. Demyelinating range confidence intervals were defined by assessing conduction velocity (CV), distal latency (DML), and F-wave latency (F) in relation to distal compound muscle action potential (CMAP) amplitude of median, ulnar, fibular, and tibial nerves. Results were subsequently validated in 38 additional CIDP patients. Then, the newly established demyelination confidence intervals were used to investigate the profile of conduction slowing in 95 ALS patients. Results: CV slowing, prolonged DML, and abnormal F were observed in 22.2%, 19.6%, and 47.1% of the studied nerves respectively in ALS patients. When slowing occurred, it affected more than one segment of the motor nerve, suggesting that CMAP amplitude dependent conduction slowing caused by an exclusive loss of large axons is the main mechanism of slowing. No ALS patient had more than 2 nerves with CV slowing in the confidence interval defined by the regression equations or the American Academy of Neurology (AAN) research criteria for CIDP diagnosis. Conclusions: The presence of more than two motor nerves with CV slowing in the demyelinating range defined by the regression analysis or AAN criteria in ALS patients suggests the contribution of acquired demyelination or other additional mechanisms exist in the electrodiagnostic profile of ALS.

In this manuscript, we introduce a three dimension metric type spaces so called $ J $-metric spaces. We prove the existence and uniqueness of a fixed point for self mappings in such spaces with different types of contractions. We use our result to prove the existence and uniqueness of a solution of the following fractional differential equations such as $ \mathcal{(P)}:\left\{ \begin{array}{ccl} D^{\lambda}x(t) & = & f(t,x(t)) = Fx(t) \;{\rm{ if }}\; t\in I_0 = (0,T] \\ x(0) & = & x(T) = r \\ \end{array} \right\} . $ Moreover, we present other applications to systems of linear equations and Fredholm type integral equation.

This study aims to establish a new fixed point theorem in the framework of $ S^{JS} $-metric spaces, recently introduced by Beg et al. We propose different principles of contraction using various techniques. The theorems obtained represent a new framework for other future work in the considered space. Also, we provide two applications of our results to linear system of equations and the following fractional differential equation $ \mathcal{(P)}:\left\{ \begin{array}{ccl} D^{\lambda}x(t) & = & f(t, x(t)) = Fx(t) \mbox{ if } t\in I_0 = (0, T] \\ x(0) & = & x(T) = r \ \end{array} \right\}. $ These applications show the effectiveness of our approach as a powerful tool for solving several types of differential equations.

Abstract In this paper, we initiate a new extension of b-metric spaces, called controlled metric-like spaces, by changing the condition [ ℘ ( s , r ) = 0 ⇔ s = r ] by [ ℘ ( s , r ) = 0 ⇒ s = r ] $$ \bigl[\wp (s,r)=0 \Leftrightarrow s=r\bigr]\quad \text{by } \bigl[\wp (s,r)=0 \Rightarrow s=r\bigr] $$ and that means basically we may have a non-zero self-distance. We prove some fixed point theorems which generalize many results in the literature. Also, we present an interesting application to illustrate our results by considering controlled metric-like spaces endowed with a graph.

For a given mapping f in the framework of different spaces, the fixed-point equations of the form fx=x can model several problems in different areas, such as differential equations, optimization, and computer science. In this work, the aim is to find the best proximity point and to prove its uniqueness on partial metric spaces where the symmetry condition is preserved for several types of contractive non-self mapping endowed with a graph. Our theorems generalize different results in the literature. In addition, we will illustrate the usability of our outcomes with some examples. The proposed model can be considered as a theoretical foundation for applications to real cases.

In this paper, we introduce grand weighted Herz–Morrey spaces with a variable exponent and prove the boundedness of fractional integrals on these spaces.

Time, quality and cost are the most critical performance indicators in project management. It has always been considered a tough challenge for project managers to optimize them simultaneously. This paper aims at establishing a simulation-based integer linear programming tool that helps project managers, at the preliminary stages, to assess the risks related to the feasibility and profitability of the projects within the framework of a stochastic discrete time-cost-quality tradeoff problem. The computational experiments on a wide range of benchmark instances from the literature were performed, and the results were compared with those of the deterministic version of the problem. The proposed approach is able to assess the impact of the stochastic behavior of the duration and the quality of the tasks on the cost, duration, and quality of the whole project. Moreover, the simplicity and the reduced time required for the computation of large size networks revealed to be very promising for giving a practical solution for real-life projects.

Over the last few decades, a certain interesting class of functional equations were developed while obtaining the generating functions of many system distributions. This class of equations has numerous applications in many modern disciplines such as wireless networks and communications. The Ulam stability theorem can be applied to numerous functional equations in investigating the stability when approximated in Banach spaces, Banach algebra, and so on. The main focus of this study is to analyse the relationship between functional equations, Hyers–Ulam–Rassias stability, Banach space, quasi-beta normed spaces, and fixed-point theory in depth. The significance of this work is the incorporation of the stability of the generalised additive functional equation in Banach space and quasi-beta normed spaces by employing concrete techniques like direct and fixed-point theory methods. They are powerful tools for narrowing down the mathematical models that describe a wide range of events. Some classes of functional equations, in particular, have lately emerged from a variety of applications, such as Fourier transforms and the Laplace transforms. This study uses linear transformation to explain our functional equations while providing suitable examples.

In this manuscript, we introduce the concept of intuitionistic fuzzy controlled metric-like spaces via continuous t-norms and continuous t-conorms. This new metric space is an extension to intuitionistic fuzzy controlled metric-like spaces, controlled metric-like spaces and controlled fuzzy metric spaces, and intuitionistic fuzzy metric spaces. We prove some fixed-point theorems and we present non-trivial examples to illustrate our results. We used different techniques based on the properties of the considered spaces notably the symmetry of the metric. Moreover, we present an application to non-linear fractional differential equations.

In this paper, we consider the basic makespan minimization problem on identical parallel machines. The aim of this study is to solve, to optimality the hard instances of the literature. We present an integer linear program based on an innovative arc-flow model inspired from the duality between the bin packing problem and the parallel-machine scheduling problem. The proposed mathematical model is tested on a large set of hard instances. The results of computational experiments attest the efficiency of the new approach and prove that it outperforms the existing ones. In addition to its efficiency, the proposed method is simple and easy to use.

Fixed point theory is a very important tool in mathematics and applied sciences. Latterly, many application examples have been presented for communication network and computer science fields. The proposed schema can be considered as a theoretical foundation for such a type of applications. In this paper, we introduce the notion of the Gm-contraction to generalize and extend the notion of G-contraction. We investigate the existence and uniqueness of the fixed point for such contractions in M-metric space endowed with a graph. Our results extend and generalize various results in the existing literature, in particular the results of Jachymski. Some examples are included, which illustrate the results proved herein.

Recently, Mlaiki et al. introduced the notion of a controlled metric type space which is a generalization of the b-metric space. In this work, we define the controlled partial metric type space and give some fixed-point theorems for extensions of Kannan contraction in this space with suitable conditions. Moreover, as an application, we derive a fixed-point theorem for graphic contraction on the considered metric space endowed with a graph.

In this paper, we ensure the existence and uniqueness of a best proximity point in rectangular metric spaces endowed with a graph structure.

In this article, in the sequel of extending b-metric spaces, we modify controlled metric type spaces via two control functions α ( x , y ) and μ ( x , y ) on the right-hand side of the b - triangle inequality, that is, d ( x , y ) ≤ α ( x , z ) d ( x , z ) + μ ( z , y ) d ( z , y ) , for all x , y , z ∈ X . Some examples of a double controlled metric type space by two incomparable functions, which is not a controlled metric type by one of the given functions, are presented. We also provide some fixed point results involving Banach type, Kannan type and ϕ -nonlinear type contractions in the setting of double controlled metric type spaces.

The objective of this paper is to establish the existence and uniqueness of fixed points on rectangular metric-like spaces endowed with a graph. We introduce the notion of some generalized G-contractions principle. The usefulness of the considered metric space in real work is highlighted. The obtained results generalize some notes in the literature. Some examples are presented to support the main results.

In this article, we introduce a new extension of b-metric spaces, called controlled metric type spaces, by employing a control function α ( x , y ) of the right-hand side of the b-triangle inequality. Namely, the triangle inequality in the new defined extension will have the form, d ( x , y ) ≤ α ( x , z ) d ( x , z ) + α ( z , y ) d ( z , y ) , for all x , y , z ∈ X . Examples of controlled metric type spaces that are not extended b-metric spaces in the sense of Kamran et al. are given to show that our extension is different. A Banach contraction principle on controlled metric type spaces and an example are given to illustrate the usefulness of the structure of the new extension.

Damage to normal human brain cells from exposure to ionizing radiation may occur during the course of radiotherapy or from accidental exposure. Delayed effects may complicate the immediate effects resulting in neurodegeneration and cognitive decline. We examined cellular and molecular changes associated with exposure of neural stem/progenitor cells (NSPs) to 137 Cs γ-ray doses in the range of 0 to 8 Gy. Subventricular zone NSPs isolated from newborn mouse pups were analyzed for proliferation, self-renewal, and differentiation, shortly after irradiation. Strikingly, there was no apparent increase in the fraction of dying cells after irradiation, and the number of single cells that formed neurospheres showed no significant change from control. Upon differentiation, irradiated neural precursors did not differ in their ability to generate neurons, astrocytes, and oligodendrocytes. By contrast, progression of NSPs through the cell cycle decreased dramatically after exposure to 8 Gy ( p