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

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

Background and Objectives: Daratumumab, a monoclonal antibody against CD38, has shown promising results in multiple myeloma (MM). We aimed to analyze its efficacy in newly diagnosed patients with MM. Materials and Methods: A search was conducted in PubMed, Cochrane, and Clinicaltrials.gov using the MeSH terms “daratumumab” or “Darzalex” and “multiple myeloma” covering the period until 2024. The Mantel-Haenzel formula was used to calculate the pooled risk ratio (RR), and the Generic Inverse Variance method was used to determine the pooled hazard ratio for disease progression, using RevMan version 5.4 at 95% confidence interval (CI). A P value of less than 0.05 was significant. Results: A total of 6 phase-III RCTs were analyzed. The use of daratumumab was associated with 39% fewer events of progression of disease or deaths in the TE group (RR= 0.61; 95% CI= 0.39 to 0.93; p=0.02) and 29% lower in the TIE group (RR= 0.71; 95% CI= 0.53 to 0.94; p=0.02). The hazard ratio for progression or death with daratumumab group versus control in both transplant eligible (TE) (HR= 0.44; 95% CI= 0.35 to 0.57; p&lt;0.00001) or transplant ineligible (TIE) (HR= 0.47; 95% CI= 0.38 to 0.59; p&lt;0.00001) group was significantly lower. Daratumumab significantly increased overall response rate (ORR) (RR= 1.20; 95% CI= 1.11 to 1.30 ; p&lt;0.00001) and complete response (CR) (RR= 1.34; 95% CI= 1.02 to 1.76; p=0.04) in the TIE group only. Conclusions: Daratumumab showed benefits in both TE and TIE patients with newly diagnosed multiple myeloma. It significantly reduced the risk of disease progression or death and improved clinical outcomes regarding ORR and CR, suggesting an effective treatment option in these patient groups.

We present 4 cases of patients diagnosed with multiple myeloma initially treated without monoclonal antibodies. It was decided to provide the benefit of the drug after maintenance with lenalidomide was initiated to consolidate the post-maintenance response followed by monitoring without any kind of treatment. In this series of 4 cases 100% of the patients achieved a strict complete response with undetectable Minimal Residual Disease (MRD) for flow cytometry after post-maintenance consolidation with daratumumab regardless of the scheme used as induction/consolidation, as well as whether they had received HSCT. Until the last follow-up the patients are under surveillance with no evidence of progression. It should be noted that 3 of 4 of these patients debuted with high-risk disease.

To explore more effective and safer mobilization strategies for multiple myeloma (MM) patients, we conducted a prospective trial comparing single-dose etoposide (375 mg/m2 for one day) plus G-CSF versus G-CSF alone followed by risk-adapted plerixafor. After randomization, 27 patients in the etoposide group and 29 patients in the G-CSF alone group received mobilization regimens. Six (22.2%) patients in the etoposide group and 15 (51.7%) patients in the G-CSF alone group received a risk-adapted plerixafor based on a peripheral blood CD34+ cell count of less than 15/mm3 (P = 0.045). The median total count of CD34+ stem cells collected was significantly higher in the etoposide group (9.5 × 106/kg vs. 7.9 × 106/kg; P = 0.018), but the optimal collection (CD34+ cell count ≥ 6 × 106/kg) rates were not significantly different between the etoposide group and the G-CSF alone groups (96.3% vs. 82.8%; P = 0.195). The rate of collected CD34+ stem cells of 8.0 × 106/kg or grater was significantly higher in the etoposide group (77.8% vs 44.8%; P = 0.025). Meanwhile, the rates of adverse events of were relatively low, with no neutropenic fever or septic shock observed in either group. After transplantation, the median days to neutrophil and platelet engraftment were not significantly different between the two groups (P =1.000 in both). Thus, both single-dose etoposide plus G-CSF and G-CSF alone with risk-adapted plerixafor were effective and safe, but the former may be the better option for patients who are expected to receive two or more transplantations.

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

Banana (Musa spp.) is an important crop to the economies of many developing countries. In the north of Argentina, a sub-tropical region, banana plants grow in a suboptimal environment that limits yield because only one harvest per year is achieved. The objective of this work was to characterize the agroecological aptitude of Formosa, Argentina, for banana production, through the behavior of three varieties of international use: Willians, Jafa and Gran Enano, evaluated during five consecutive campaigns. The three-way data analysis technique called Multiple Factor Analysis (MFA) was used for evaluating varieties’ performances across cycles of production. The results allowed inferring the existence of genotype x environment (GEI) interaction, corroborated by two-way factorial ANOVA. In order to determine how this suboptimal environment affects the development of each genotype of this perennial crop, Dual Multiple Factor Analysis (DMFA) was applied to jointly analyze the correlation structure among traits contributing to the performance of each variety at each campaign. The correlation structures between variables were different in each population and varied among campaigns. All traits showed a great variation across years and genotypes, the fruit peel thickness being the most discrepant throughout the campaigns. However, Formosa appeared as a promising subtropical agroecological environment to produce banana because varieties’ performances were acceptable for large scale production systems. In addition to evaluating the adequate aptitude for cultivating banana in Formosa considering the significant effect of GEI, this research makes a methodological contribution by proposing the use of three-way data analysis MFA and DMFA in Agronomy Science.

Euler sums are alternating (or level two) extension of multiple zeta values (MZVs). Kaneko and Tsumura initiated the study of multiple T-values (MTVs), another level two generalization, by restricting the summation indices in the definition of MZVs to a fixed parity pattern. In this paper, we shall study finite MTVs and their alternating versions which are level two and level four variations of finite MZVs, respectively. We conjecture that all finite MZVs are in the Q-span of finite MTVs which in turn apparently lie in the span of finite Euler sums, and the inclusions are both proper. We shall first provide some structural results for Euler sums of small weights, guided by the author's previous conjecture that the finite Euler sum space of weight w is isomorphic to a quotient Euler sum space of weight w. Then, by utilizing some well-known properties of the classical alternating MTVs, we shall derive a few important Q-linear relations among the finite alternating MTVs, including the reversal, linear shuffle and sum relations. We then compute the upper bound for the dimension of the Q-span of weight w finite (alternating) MTVs for w<9, both rigorously using the newly discovered relations and numerically aided by computers.

This paper presents a new theory explaining the pathological mechanisms of multiple sclerosis (MS). MS is triggered by persistently activated immune cells, mainly B cells, as in reactivated Epstein-Barr virus infection. Activated immune cells release cytokines, the main one here being TNFa. A major role of TNFa is to support immune cell motility and tissue penetration, by promoting the breakdown of ceramide products that stabilize membranes (sphingomyelin (SPM) and galactosylceramide (GalCer)), by stimulating membrane breakdown via ceramide 1-phosphate-induced liberation of arachidonic acid, and by promoting the production of sphingosine 1-phosphate, a ceramide product that promotes immune motility. These ceramide products are expressed in endothelial cells, including the blood-brain barrier, and have a large presence in myelin. Thus, excessive cytokine release both allows immune penetration into the brain, and impairs existing myelin sheaths. SPM and GalCer are essential for myelin maintenance but not for its synthesis, explaining the dominant relapsing-remitting nature of the disease. The theory is supported by diverse evidence, and supports modern B cell-based treatment directions.

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammation, demyelination, and neurodegeneration within the central nervous system. Brain plasticity, the brain's ability to adapt its structure and function, plays a crucial role in mitigating MS's impact. This paper explores the potential benefits of lifestyle changes and nutraceuticals on brain plasticity in MS population. Lifestyle modifications, including physical activity and dietary adjustments, can enhance brain plasticity by upregulating neurotrophic factors, promoting synaptogenesis, and reducing oxidative stress. Nutraceuticals, such as vitamin D, omega-3 fatty acids, and antioxidants like alpha-lipoic acid, have shown promise in supporting brain health through anti-inflammatory and neuroprotective mechanisms. Regular physical activity has been linked to increased levels of brain-derived neurotrophic factor and improved cognitive function. Dietary interventions, including caloric restriction and the intake of polyphenols, can also positively influence brain plasticity. Integrating these lifestyle changes and nutraceuticals into the management of MS could provide a complementary approach to traditional therapies, potentially improving neurological outcomes and enhancing the quality of life for MS population.

Multiple Myeloma (MM), is a hematological malignancy and poses significant therapeutic challenges. This review synthesizes evidence from pivotal clinical trials to guide induction treatment for transplant-eligible (TE), newly diagnosed MM (NDMM) patients. Emphasizing the evolution from three-drug to four-drug induction therapies, we highlight the integration of monoclonal antibodies, particularly CD38 recombinant monoclonal antibody agents, into treatment regimens. Our analysis includes a comprehensive literature review of research from major databases and conferences conducted between 2010 and 2024, culminating in the detailed evaluation of 47 studies. The findings underscore the superiority of quadruple regimens in TE NDMM, notably those incorporating daratumumab, in achieving superior responses including progression-free survival (PFS), minimal residual disease (MRD) negativity, overall response rate (ORR), and overall survival (OS) when compared to triple-drug regimens. As treatment regimens evolve with additional agents, the improved outcomes with treatment-related adverse events should be carefully balanced. This review advocates for a paradigm shift towards quadruple induction therapies for TE NDMM, offers a detailed insight into the current landscape of MM treatment, and reinforces a new standard of care.

Background: over the past 20 years, the treatment scenario of multiple sclerosis (MS) has radically changed and an ever-increasing number of disease-modifying treatments has emerged. Among high efficacy treatment agents, monoclonal antibodies (mAbs) have become a mainstay in the MS patient’s treatment due to their targeted mechanism, high efficacy and favorable risk profile. The latter varies from drug to drug and a skin cancer warning has emerged with sphingosine 1-phosphate receptors inhibitors. Several cases of skin malignancy in people with MS (pwMS) undergoing therapy with mAbs have also been described, but dermatological follow-up is not currently indicated. Objectives: the aim of this review is to investigate cases of cutaneous ma-lignancy during mAbs therapy and to explore possible pathophysiological mechanisms to evaluate the potential need for regular dermatological follow-up in pwMS treated with mAbs. Methods: literature search for original articles and review in PubMed. No date restrictions. Results: 1019 results were retrieved. Duplicates were removed using Endnote and manually. Only peer-reviewed studies published in English were considered for inclusion. At the end of these screening procedures, 54 studies published between 2001 and 2023 that met the objectives of this review were selected and reported. Conclusions: the available data do not show a clear link be-tween monoclonal antibody (mAb) treatment in pwMS and the risk of skin cancer. At present, these treatments remain contraindicated for people with cancer. Dermatological screening is ad-visable before starting mAb treatment in pwMS, and subsequent follow-up should be individual-ised according to each patient's risk profile.

Multiple Sclerosis (MS) is a chronic autoimmune disorder characterized by the demyelination of neural fibers in the central nervous system. Understanding the impact of demyelination on neural network efficiency is crucial for elucidating the pathophysiological mechanisms underlying MS. This study aims to model the effects of demyelination on neural network efficiency, specifically focusing on how increased resistance and path lengths due to demyelination correlate with the clinical symptoms of MS. We employed a graph-theoretical approach to simulate neural networks, introducing varying degrees of demyelination. The demyelination was represented by increasing the resistance (weights) of selected edges within the network, affecting both random and clustered distributions of network connections. The primary metric analyzed was the average shortest path length, indicative of network efficiency. The models demonstrated a significant increase in the average shortest path length in demyelinated networks compared to intact ones. Specifically, networks with clustered demyelination exhibited localized inefficiencies, correlating with the focal nature of MS lesions. The increase in path length was associated with reduced signal transmission efficiency, providing insights into a range of MS symptoms including motor and sensory impairments, cognitive dysfunction, visual disturbances, and fatigue. The graph-theoretical model of neural network demyelination offers a novel perspective on how structural changes in the brain's connectivity due to MS can lead to diverse clinical manifestations. While the model simplifies the complexity of neural networks, it underscores the potential of computational approaches in understanding and predicting the course of neurological disorders like MS.

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

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

Multiple Sclerosis (MS) is a progressive neurodegenerative disease that affects more than 2 million people worldwide. Increasing knowledge about MS in different populations has advanced our understanding of disease epidemiology and variation in the natural history of MS among White and minority populations. In addition to differences in incidence, African American (AA) and Hispanic patients have greater disease burden and disability in earlier stages of disease compared to White patients. To further characterize MS in AA and Hispanic populations, we conducted a retrospective chart analysis of 112 patients treated at an MS center in Houston, Texas. Here, we describe differences in clinical presentation, MRI findings, treatment regimens, disability progression, and relapse rate. We found that patients who were evaluated by a neurologist at symptom onset had significantly decreased odds of greater disability [defined as Expanded Disability Status Scale (EDSS) &gt; 4.5] at last presentation compared to patients who were not evaluated by a neurologist (OR: 0.04, 95% CI: 0.16-0.9). We also found that active smokers had significantly increased odds of greater disability both at diagnosis and at last clinical encounter compared to nonsmokers (OR: 2.44, 95% CI: 1.10-7.10, OR= 2.44, 95% CI: 1.35-6.12, p= 0.01, respectively). Assessment of the degree of brain atrophy and progression over time along with enumeration of T1, T2, and gadolinium-enhancing brain lesions did not reveal differences across groups.

While there are many models of epidemic evolution perhaps the basis for such models finds itself in the lumped behavior expressed through the so-called SIR model (Susceptible, Infectious, Recovered) from which spring many related models. This paper discusses multiple analytic solutions to that equation including those that are available in closed analytic form and those for which at least one final integral has to be done numerically, so-called quasi-analytic solutions. The solutions are intrinsically time-dependent of course. The hope is that such an investigation will lead to a better understanding of when and how models can be of use in studying the dynamical evolution of diseases including, perhaps, the great influenza pandemic of 1918 together with later pandemics and epidemics not excluding the Covid-19 pandemic of the present day.

Dengue is one of the life-threatening common neglected tropical diseases of the world, yet to develop any therapeutic for its treatment and prevention. Although there is a licensed vaccine reported, but becomes less efficacious due to the presence of multiple serovars of the dengue virus (DENV). Thus, an efficacious dengue vaccine potent to work against all the serovars is very crucial and time-demanding. Here we used a comprehensive hierarchical reverse vaccinology approach to design an epitope-based vaccine, targeted against multiple serovars of the DENV. Conservancy and population coverage analysis of the promiscuous epitopes revealed the robust immune response against multiple serovars of the DENV and various ethnicities. Final vaccine constructs comprising of B and T-cell epitopes, Universal pan-HLA DR or PADRE (AKFVAAWTLKAAA) sequence, and an adjuvant (β-defensin) at N-terminal of the construct with suitable linkers. Physiochemical properties and secondary structure profiling of the vaccine protein secured its hydrophilic, thermostable, and other structural nature. Molecular docking analysis indicates the deep binding of the proposed vaccine in the binding groove of the human immune TLR4 receptor present on the dendritic cell. In addition, disulfide engineering was coped to extend its stability. Furthermore, molecular dynamics simulation of the modeled vaccine-TLR8 complex showed minimum deformability. Finally, in silico cloning approach of the vaccine construct within an expression vector (pET28a+) assure good expression. Proposed vaccine may give novel insights for treatment of dengue patients.

In recent decades, power consumption has become an essential factor in attracting the attention of integrated circuit (IC) designers. Multiple-valued logic (MVL) and approximate computing are some techniques that could be applied to integrated circuits to make power-efficient systems. By utilizing MVL-based circuits instead of binary logic, the information conveyed by digital signals increases, and this reduces the required interconnections and power consumption. On the other hand, approximate computing is a class of arithmetic computing used in systems where the accuracy of the computation can be traded-off for lower energy consumption. In this paper, we propose novel designs for exact and inexact ternary multipliers based on carbon-nanotube field-effect transistors (CNFETs). The unique characteristics of CNFETs make them a desirable alternative to MOSFETs. The simulations are conducted using Synopsys HSPICE. The proposed design is compared against existing ternary multipliers. The results show that the proposed exact multiplier reduces energy consumption by up to 6X. At the same time, the best inexact design improves energy efficiency by up to 35X compared to the latest state-of-the-art methods. Using the imprecise multipliers for image processing provides evidence that these proposed designs are a low-power system with an acceptable error.

In this paper, a technique of image watermarking using multiple images as watermarks is presented. The technique is based on transform domain functions including discrete wavelet transform (DWT), discrete cosine transform (DCT) and singular value decomposition (SVD) with an image as the host signal i.e. the watermarks will be used as proofs of the authenticity of the host image. The technique is executed by performing multilevel DWT followed by applying DCT and SVD to both the host and watermark. Multiple watermarks are used for the insurance of better security level. The scheme is immune to common image processing operations & some attacks and exhibits PSNR of 108.3781dB, normalized cross correlation (NCC) over 0.99 and normalized correlation (NC) over 0.99.

Assuming the Multiple Point Principle (MPP) as a new law of Nature, we considered the existence of the two degenerate vacua of the Universe: a) the first Electroweak (EW) vacuum at $v_1\approx 246$ GeV—“true vacuum”, and b) the second Planck scale “false vacuum” at $v_2 \sim 10^{18}$ GeV. In these vacua, we investigated different topological defects. The main aim of the paper is an investigation of the black-hole-hedgehogs configurations as defects of the false vacuum. In the framework of the $f(R)$ gravity, described by the Gravi-Weak unification model, we considered a black-hole solution, which corresponds to a “hedgehog”—global monopole, that has been “swallowed” by the black-hole with mass core $M_{BH}\sim 10^{18}$ GeV and radius $\delta\sim 10^{-21}$ GeV$^{-1}$. Considering the results of the hedgehog lattice theory in the framework of the $SU(2)$ Yang-Mills gauge-invariant theory with hedgehogs in the Wilson loops, we have used the critical value of temperature for the hedgehogs’ confinement phase ($T_c\sim 10^{18}$ GeV). This result gave us the possibility to conclude that the SM shows a new physics (with contributions of the $SU(2)$-triplet Higgs bosons) at the scale $\sim 10$ TeV. This theory predicts the stability of the EW-vacuum and the accuracy of the MPP.

We previously reported that in multiple sclerosis (MS) patients with a progressive form of the disease, spinal cord periplaques extend distance away from plaque borders and are characterized by the co-occurrence of partial demyelination, astrocytosis and low-grade inflammation. However, transcriptomic analyses comparing periplaques to adjacent normal-appearing white matter (NAWM) areas did not allow providing a comprehensive view of molecular events in astrocytes vs oligodendrocytes. Here, we re-assessed our transcriptomic data with the aim of identifying functionally-relevant co-expression networks that would reflect astrocyte vs oligodendrocyte molecular signatures in periplaques. We identified an astrocytosis-related gene module comprising GFAP, the hub gene CX43/GJA1 and a set of transcripts forming a TGFB/SMAD1/SMAD2 genomic signature. Partial demyelination was characterized by a co-expression network which, besides myelin genes, comprised a highly significant number of translation/elongation-related genes. Interestingly, the main oligodendrocyte-related hub we identified was NDRG1, a gene previously shown to be specifically silenced in the NAWM of MS patients. This result indicated that NDRG1 down-regulation could be an important event in the process of periplaque partial demyelination. To establish a putative link between NDRG1 down-regulation and a cytokine/chemokine signature, we then sought to identify cytokine/chemokine genes whose mRNA levels inversely correlated with those of NDRG1. Following this approach we found 5 candidate immune-related genes whose up-regulation associated with NDRG1 down-regulation: TGFB1, PDGFC, IL-17D, IL-33, and IL-12A. From these results we propose that in the spinal cord of MS patients with progressive forms of the disease, TGFB1 may limit acute inflammation but concurrently induce astrocytosis and an alteration of oligodendrocytes terminal differentiation.

2,5-Dihydroxyacetophenone (DHAP) is an active compound obtained from Radix Rehmanniae Preparata, which is widely used as a herbal medicine in many Asian countries. DHAP has been found to possess anti-inflammatory, anti-anxiety, and neuroprotective qualities. For the present study, we evaluated the anti-cancer effects of DHAP on multiple myeloma cells. It was discovered that DHAP downregulated the expression of oncogenic gene products like Bcl-xl, Bcl-2, Mcl-1, Survivin, Cyclin D1, IAP-1, Cyclin E, COX-2, and MMP-9, and upregulated the expression of Bax and p21 proteins, consistent with the induction of G2/M phase cell cycle arrest and apoptosis in U266 cells. DHAP inhibited cell proliferation and induced apoptosis, as characterized by the cleavage of PARP and the activation of caspase-3, caspase-8, and caspase-9. Mitogen-activated protein kinase (MAPK) pathways have been linked to the modulation of the angiogenesis, proliferation, metastasis, and invasion of tumors. We therefore attempted to determine the effect of DHAP on MAPK signaling pathways, and discovered that DHAP treatment induced a sustained activation of JNK, ERK1/2, and p38 MAPKs. DHAP also potentiated the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. Our results suggest that DHAP can be an effective therapeutic agent to target multiple myeloma.

Maize is an important staple food crop in sub-Saharan Africa (SSA). However, the average grain yield on farmers’ fields falls considerably short of the demand of the region’s population. In addition, the normal endosperm maize widely consumed in SSA is deficient in vitamin A. Drought, a consequence of climate change, is a major constraint to maize production, resulting in seasonal low grain yield in farmers’ fields. The objectives of this study were to assess the performance of newly developed extra-early maturing provitamin A hybrids under managed drought and well-watered conditions, compare the outcomes of multiple trait base-index and multi-trait genotype-ideotype distance index selection procedures, and identify drought-tolerant hybrids with stable performance across contrasting environments for commercialization in SSA. One hundred and ninety provitamin A hybrids and six checks were evaluated under managed drought and well-watered conditions at Ikenne for two seasons between 2021 and 2023. A 14*14-lattice design was used for the field evaluations under both research conditions. Drought stress was achieved by the complete withdrawal of irrigation water 25 days after planting. Results revealed significant differences among the hybrids under drought and well-watered conditions. Grain yield, ears per plant, and plant aspect under managed drought were correlated to the same traits under well-watered conditions suggesting that the expression of these traits is governed by common genetic factors. Twenty-nine hybrids were identified as top-performing drought-tolerant hybrids by the multiple trait base index and multiple-trait genotype–ideotype distance index. Of the selected outstanding 29 hybrids, 34% were derived from crosses involving the tester TZEEIOR 197, demonstrating the outstanding genetic potential of this inbred line. Further analysis of the 29 selected hybrids revealed TZEEIOR 509 × TZEEIOR 197 as the hybrid that combined the most drought-tolerant adaptive traits. However, the hybrids TZEEIOR 526 × TZEEIOR 97, TZEEIOR 384 × TZEEIOR 30, TZEEIOR 515 × TZEEIOR 249, TZEEIOR 510 × TZEEIOR 197, TZEEIOR 479 × TZEEIOR 197, and TZEEIOR 458 × TZEEIOR 197 were identified as the most stable hybrids across drought and well-watered conditions. These hybrids should be extensively tested in multi-location trials for deployment and commercialization in SSA.

This paper investigates the reconfigurable intelligent surface (RIS)-aided uplink multicell massive multiple-input multiple-output (mMIMO) communication system with transceiver hardware impairments (THWIs), and the practical and feasible two-timescale scheme is used to design the phase shifts of RIS. We consider the Rician channel model and use maximal-ratio combining (MRC) technology to process the received signal at BS. The expression of the uplink achievable rate is derived and analyzed. Besides, genetic algorithm (GA) is used to optimize the phase shifts of RIS to maximize the data rate. Finally, the accuracy of the derived results is verified. The simulation results show that appropriately increasing the number of RIS’s reflecting elements can compensate for the performance loss caused by inter-cell interference and THWIs, and reduce the demand for the number of BS antennas, which can significantly reduce the hardware costs at the BS.

Multiple Myeloma (MM) is a malignant plasma cell disorder characterized by the accumulation of abnormal plasma cells in the bone marrow. Mesenchymal stem cells (MSCs) and reticulated platelets (RPs) have been implicated in the pathogenesis of MM. This narrative review aims to explore the role of MSCs and RPs in the pathophysiology of MM, particularly their clinical use as possible variables of prognostic value in this hematologic neoplasia. The interaction between MSCs and MM cells within the bone marrow microenvironment supports MM cell survival, proliferation, and drug resistance. MSCs contribute to the development and maintenance of MM through the secretion of various factors, including cytokines, chemokines, and growth factors. Moreover, RPs, young and highly reactive platelets, have been implicated in promoting angiogenesis, tumor growth, and metastasis in MM. Several studies show that cells such as MSCs and platelets participate actively in the biology of the disease. Still, in clinical practice, they are not considered part of evaluating affected patients. In this review, we explore the possibility of including the evaluation of MSC and PRs in the clinical practice of patients with MM as part of the strategies to improve the follow-up of this disease.

The statistical technique, the multiple regression model, is employed to analyze the relationship between the dependent variable and several independent variables. The multicollinearity problem is one of the assumptions in the multiple regression model that occurred in the relationship among independent variables. The ordinal least square is the standard method to evaluate parameters in the regression model, but the multicollinearity problem affects the unstable estimator. The Liu regression is proposed to approximate the Liu estimators based on the Liu parameter to overcome multicollinearity. For this paper, we have proposed the modified Liu parameter to estimate the biasing parameter in scaling options to compare the ordinal least square estimator with two modified Liu parameters and six standard Liu parameters. The performance of the modified Liu parameter is considered with the generating independent variables from the multivariate normal distribution in the Toeplitz correlation pattern as the multicollinearity data, where the dependent variable is obtained from the independent variable multiplied with a coefficient of regression and with the error from the normal distribution. The mean absolute percentage error is computed as an evaluation criterion of estimation. For application, the Hepatitis C patients dataset is a real dataset to investigate the benefit of the modified Liu parameter. Through the simulation and real dataset, it can be seen from the results that the modified Liu parameter outperforms the other Liu parameters and the ordinal least square estimator. It can recommend the user for estimating parameters by using the modified Liu parameter when the independent variable exits the multicollinearity problem.

: Controlling the distribution of water and wastewater between industrial processes is very vital in rationalizing water and preserving the environment. In this paper, a mathematical technique is proposed to optimize water-wastewater networks; a nonlinear program is introduced to minimize the consumption of freshwater, and consequently, the flowrate of the wastewater dis-charge will be also minimized. A general mathematical model, able to handle industrial plants containing up to eight sources and eight sinks, is developed using LINGO optimization software to facilitate dealing with complex case studies. The introduced model can handle single contam-inant networks as well as multiple contaminants cases. The optimal water network is synthe-sized through two steps; the first step is to introduce the case study data to the developed mathematical model. The second step considers using the optimal solution produced after run-ning the developed LINGO model as feed data for a pre-designed Excel sheet able to deal with these results and simultaneously draw the optimal water-wastewater network. The proposed mathematical model is applied to two case studies; The first case study includes actual data from four fertilizer plants located in Egypt; the water resources and requirements are simultaneously integrated to obtain a sensible cutting in both freshwater consumption (lowered by 52.2%) and wastewater discharge (zero wastewater discharge). The second case study is for a Brazilian pet-rochemical plant; the obtained results showed noticeable reductions in freshwater consumption for the second case study by 12.3 % while the reduction percentage of wastewater discharge is 4.5%.

Cognitive impairment affects 34-65% of People with Multiple Sclerosis (PwMS), significantly impacting their quality of life. Clinicians routinely address cognitive deficits with in-clinic neuro-behavioural interventions, but accessibility issues exist. Telerehabilitation is a promising solution that utilises digital tools for home-based cognitive remediation. This narrative review assessed the feasibility and efficacy of cognitive telerehabilitation in PwMS, identifying 13 relevant studies. Regarding the feasibility of cognitive telerehabilitation, evidence shows adherence rates are generally good, although, surprisingly, not all studies reported a measure of compliance with the cognitive training explored. Considering the efficacy of different rehabilitative techniques on cognitive performance of PwMS, findings are generally inconsistent, with only one study reporting consistently positive results. A range of methodological limitations are reported as potential factors contributing to the variability of results. Overcoming some of these issues will be key. Upcoming research is necessary to determine optimal intervention approaches, long-term effects of rehabilitation, and how to best integrate the use of telerehabilitation into routine clinical practice. By exploiting digital tools in the best way and addressing methodological concerns, home-based rehabilitation holds the potential for improving cognitive functions and enhancing the quality of life in PwMS.

In the discussion on environmental policies, the notion of eco-efficiency is often used. Eco-efficiency is defined as the delivery of products and services with competitive values, while reducing the ecological impacts and satisfying human needs. In an environment of great competitiveness in which the companies operate, the improvements in the productive process is one of the differentiating factors for guaranteeing a strong competition. Also it is essential rationalizing energy consumption and natural resources. For this it is necessary to understand the main operations and dynamics of the company. This work presents an empirical study of a Portuguese company in the industrial sector. The problematic here presented is based on the company’s growing concern to reduce the amount of scrap produced. From the literature research that was performed, a strong dependence relation between the different variables in the extrusion process was found. The main objective of this work is to model the aluminium extrusion process, with the aim of minimizing the production of scrap. For this several variables involved in the process are taking into account. Using statistical techniques, in particular multiple linear regressions, it was possible to identify the importance of the variables under study for the scrap production.

Multiple imputation with chained equations (MICE) is a widespread approach to account for missing data in empirical research. Combining MICE with bootstrapping, that is, repeatedly resampling with replacement from the data to estimate variances and confidence intervals of statistics of interest, is not straightforward. The current document provides an overview of how to use bootstrapping with imputed data in Stata. Two main approaches (impute first and then bootstrap or vice-versa) are discussed and shortly compared. Code is provided for Stata.

Telemonitoring and telerehabilitation have shown promise in delivering individualized healthcare remotely. We introduce STASISM, a Sensor-Based Telerehabilitation and Telemonitoring System, in this work. This platform has been created to facilitate individualized telerehabilitation and telemonitoring for those who need rehabilitation or ongoing monitoring. To gather and analyze pertinent and validated physiological, kinematic, and environmental data, the system combines a variety of sensors and data analytic methodologies. The platform facilitates customized rehabilitation activities based on individual needs, allows for remote monitoring of patients' progress, and offers real-time feedback. To protect the security of patient data and to safeguard patient privacy, STASISM also provides secure data transmission and storage. The platform has the potential to significantly improve the accessibility and efficacy of telerehabilitation and telemonitoring programs, enhancing patients' quality of life and allowing healthcare professionals to provide individualized care outside of traditional clinical settings/

Multiple sclerosis (MS) is a chronic and demyelinating disease with an autoimmune origin, in which inflammation and demyelination lead to neurodegeneration and progressive disability. The treatment target is slowing down the disease course and mitigating the symptoms. Approximately 30 to 50% of patients do not respond optimally to Disease Modifying Therapies (DMTs), in which therapeutic response may be influenced by genetic factors such as genetic variants. Therefore, our study aimed to investigate the association of HLA DRB1*0403 genetic variant and therapeutic response to DMTs in MS. We included 105 patients with MS diagnosis. No evidence of disease activity based on the absence of clinical relapse, disability progression or radiological activity (NEDA-3), was used to classify therapeutic response. Patients were classified as follows: a) control: patients who achieved NEDA-3 b) case: patients who did not achieve NEDA-3. DNA was extracted from peripheral blood leukocytes. HLA DRB1*0403 genetic variant was analyzed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. NEDA-3 was achieved in 86.7% of MS patients treated with DMTs. Genotype frequencies were: GG 50.5%, GA 34.3% and AA 15.2%. No differences were observed in the genetic variant AA between patients who achieved NEDA-3 versus patients who did not achieve NEDA-3 (48.7% vs. 43.1%, p=0.6). We concluded that in Mexican patients with MS, HLA DRB1*0403 was not associated with therapeutic response to DMTs.

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

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

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

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

Introduction: This study aimed to validate the psychometric properties of the German eHealth Impact Questionnaire (eHIQ-G), which is divided into two independently administered and scored parts. Methods: 162 people with MS browsed one of two possible websites containing information on MS and completed an online survey. Internal consistency was assessed by Cronbach’s alpha and structural validity by Confirmatory Factor Analysis. Construct validity was examined by assessing correlations with the eHealth Literacy Questionnaire and the General Self-Efficacy Scale. Moreover, the mean difference of the eHIQ-G score between the two websites was investigated. Results: Cronbach’s alpha for the eHIQ-G subscales ranged from .833 to .885. The eHIQ-G part 1 achieved acceptable levels of goodness-of-fit indices, whereas the fit for the eHIQ-G part 2 was poor and likewise for the alternative modified models. The correlations with the reference instruments were 0.08 – 0.62 and as expected. Older age was related with lower eHIQ-G part 1 score, whereas no significant effect was found for education. Although not significant, the website ‘AMSEL’ reached higher mean scores on eHIQ part 2. Conclusion: The eHIQ-G has good internal consistency, and sufficient structural and construct validity. It will facilitate the measurement of the impact of websites providing health information.

Background and Aim: Multiple sclerosis (MS) is known as an autoimmune disease and a chronic inflammatory condition, inducing a wide variety of mood affective disorders, including depression and feelings of hopelessness in many aspects of patients’ quality of life (QoL). In view of the positive side effects of spirituality and spiritual care on finding appropriate strategies for further adaptation, this study aimed to determine the impact of group spiritual care (GSC) on levels of hope in patients suffering from MS. Materials and Methods: This clinical trial was conducted on a total number of 96 patients with MS, referring to the National Multiple Sclerosis Society (NMSS) in the city of Zahedan, Iran. Following sample selection via the convenience sampling technique, the patients meeting the inclusion criteria were randomized into two groups, i.e., intervention and control. The data collection tools for this purpose included a demographic information form and the Adult Hope Scale (AHS, Snyder et al. 1991), completed by the subjects at the pre- and post-intervention stages. As well, the intervention group received five sessions of GSC during three weeks but the control group members only talked over daily issues along with their mental health problems. The data were also analyzed using the SPSS Statistics software (ver. 14). Results: The Kruskal-Wallis test results revealed that the GSC intervention could have a significant positive effect on raising hope in the patients with MS (p<0.001). Moreover, a significant growth was observed in the scores of hope dimensions including agency and pathway (p<0.001). Conclusion: GSC can effectively boost levels of hope in patients suffering from MS in all dimensions. Therefore, it is recommended to utilize this type of care in order to nurture hope in such individuals.

Background: Rituximab is a monoclonal antibody widely used in the treatment of inflammatory and autoimmune disorders. Despite reports of its effectiveness in the treatment of demyelinating diseases of central nervous system (DDCNS), it is not yet approved for use in these disorders. The aim of this study was to investigate the effectiveness and safety of low dose rituximab in three different subgroups of DDCNS including relapsing-remitting multiple sclerosis (RRMS), secondary-progressive multiple sclerosis (SPMS) and neuromyelitis-optica-spectrum disorders (NMOSD).Methods: In a prospective cohort study, we monitored expanded-disability-status-scale (EDSS), relapses (new attacks) and serum-IgG levels to assess effectiveness and drug-adverse-events for safety in patients with RRMS, SPMS and NMOSD. These patients were candidates to receive rituximab according to our common practice protocol. We switched patients to rituximab if there was poor response to first line therapies. We follow a low dose protocol in our center (500 mg twice, two weeks apart, repeating every six months) and these patients treated in a 4-year period were assessed retrospectively for evaluation of our protocol’s safety and effectiveness. Results: 99 patients (42 RRMS, 43 SPMS and 14 NMOSD) received rituximab for a range of 12 to 40 months period. New attacks occurred in 8 RRMS (19%), 10 SPMS (23%) and 1 NMOSD (7%) patients. EDSS decreased in RRMS and NMOSD cases. Serum-IgG levels decremented in SPMS and NMOSD patients. Drug-adverse-events happened in two cases.Conclusion: In this study, low dose rituximab showed substantial effectiveness in preventing disease progression with a considerably good safety profile.

According to the French Agency for Food, Environmental and Occupational Health & Safety, electromagnetic hypersensitivity affects more than 3 million people in France, and headaches are a very frequent cause of complaint in electrohypersensitive patients, to the point of dominating the clinical picture. These headaches share characteristics with migraine pathology, and clinical improvement with anti-migraine therapy has led us to consider that the headache in the electrohypersensitive patient may be a variant of the migraine disease mediated by the TRPA1 receptor, which if confirmed, would offer effective therapeutic possibilities to relieve the electrohypersensitive patient.

Multiple Sclerosis (MS) has a well established link with Epstein-Barr virus (EBV) and a growing association with human endogenous retroviruses (HERVs). In this review, we described how these two pieces may interact in MS pathogenesis

Tuberculosis (TB) is an infectious-contagious disease caused by M. tuberculosis (Koch’s bacillus). About one-quarter of the world’s population is infected with that bacillus and at risk of developing TB disease. Latent tuberculosis corresponds to people who have been infected by TB bacteria but are not (yet) ill. The most vulnerable population to TB activation includes HIV infected, drug abuse and autoimmune disease patients. Multiple Sclerosis (MS) is a chronic and autoimmune neurological disease caused by lymphocytic infiltration. Its prevalence worldwide is 22.2 million cases of MS. There is a relation between TB and MS: due to immunomodulation or immunosuppression treatment of MS (reactivation of latent infection), or due to the intense inflammatory response before the infection of the bacillus (increased susceptibility to the development of autoimmune diseases). Screening for TB includes complete patient history, physical exam, chest radiography, and Tuberculin Skin Test or IGRA (Interferon Gamma Release Assay). This investigation is suggested when MS drugs (immunomodulatory and immunosuppressant medications) are prescribed. If a patient has positive results, the treatment for MS should not be delayed for the finishing TB treatment. In this paper, considering the high prevalence of tuberculosis, we recommend that TB screening should be also done at the moment of Multiple Sclerosis diagnosis.

STAT3 is an oncoprotein which has been shown to contribute to drug resistance in multiple myeloma (MM). Nonetheless, the clinical utility of STAT3 inhibitors in treating MM has been limited, partly related to some of their pharmacologic properties. To overcome these challenges, our group had previously packaged STAT3 inhibitors using a novel formulation of nanoparticles (NP) and found encouraging results. In this study, we aimed to further improve the pharmacologic properties of these NP by decorating them with monoclonal anti-CD38 antibodies. NP loaded with S3I-1757 (a STAT3 inhibitor), labeled as S3I-NP, were generated. S3I-NP decorated with anti-CD38 (labeled as CD38-S3I-NP) were found to have a similar nanoparticular size, drug encapsulation and loading as S3I-NP. The release of S3I-1757 at 24 hours was also similar between the two formulations. Using Cy5.5 labeling of the NP, we found that the decoration of anti-CD38 on these NP significantly increased the cellular uptake by two MM cell lines (p<0.001). Accordingly, CD38-S3I-NP showed a significantly lower inhibitory concentration at 50% (IC50) compared to S3I-NP in two IL6-stimulated MM cell lines (p<0.001). In a xenograft mouse model, CD38-S3I-NP significantly reduced the tumor size by 4 folds compared to S3I-NP on day 12 after drug administration (p=0.006). The efficacy of CD38-S3I-NP in suppressing STAT3 phosphorylation in the xenografts was confirmed by using immunocytochemistry and western blot analysis. In conclusion, our study suggests that the decoration of anti-CD38 on NP loaded with STAT3 inhibitors can further improve their therapeutic effects against MM.

Multiple sclerosis is an autoimmune disorder where both T cells and B cells are implicated in pathology. However, it remains unclear how these two distinct populations cooperate to drive disease. There is ample evidence from studies in both MS patients and mouse models that Th17, B cells, and follicular T helper (TFH) cells contribute to disease. This review article describes the literature that identifies mechanisms by which Th17, TFH, and B cells cooperatively drive disease activity in MS and EAE. The curation of this literature has identified that CNS-infiltrating TFH cells act with TH17 cell to contribute to an inflammatory B cell response in neuroinflammation. This demonstrates that TFH cells and their products are promising targets for therapies in MS.

The role of pregnancy in multiple sclerosis (MS) is of importance because many patients with MS are young women in the childbearing age who require information to inform their reproductive decisions. Pregnancy is now well-known to be associated with fewer relapses of MS and reduced activity of autoimmune encephalomyelitis (EAE). However, in women with multiple sclerosis, this benefit is not always sufficient to protect against a rebound of disease activity if disease modulating therapy is ceased for pregnancy. There is reason to be concerned that use of assisted reproductive therapies can be associated with relapses of MS. It is thought that the beneficial effects of pregnancy are due to the pregnancy-associated changes in the maternal immune system. There is some evidence of this in human studies and studies of EAE. There is also evidence that having been pregnant leads to better long-term outcome of MS. The mechanism for this is not fully understood but it could result from epigenetic changes resulting from pregnancy or parenthood. Further studies of the mechanisms of the beneficial effects of pregnancy could provide information that might be used to produce new therapies.

An increased risk of multiple sclerosis (MS) had been found when individuals had consumed large amounts of processed meat and sausages at young age (Lauer, 2014). Furthermore it was found in many studies that MS patients had acquired a number of common childhood infections at higher ages than controls. Therefore, MS patients from an epidemiological long-term investigation in Germany and different hospital controls, were evaluated for a statistical interaction of these two factors. 324 MS patients and 242 hospital controls were inquired. The study focussed on age 0 - 16. Subjects were tested for additive interaction by multiple linear regression analysis (Knol et al., 2007). There was an additive interaction of the age at any common childhood infection with the consumption of scalded sausages (regression estimate = 0.1370; standard error = 0.0603; p = 0.0239). In contrast, no such interaction could be shown for: animal fats; smoked meat (e.g. ham and bacon); and cold - smoked German salami. Thus there was a synergy of the intake of scalded sausages (e.g. frankfurters, bolognas, etc.) and age at common childhood infections, for the later risk of MS.

This paper presents a new approach to suppress interference between neighbouring radiating elements resulting from surface wave currents. The proposed technique will enable the realization of low-profile implementation of highly dense antenna configuration necessary in SAR and MIMO communication systems. Unlike other conventional techniques of mutual coupling suppression where decoupling slab is located between the radiating antennas the proposed technique is simpler and only requires embedding linear slots near the periphery of the patch. Attributes of this technique are (i) significant improvement in the maximum isolation between the adjacent antennas by 26.7 dB in X-band, & >15 dB in Ku and K-bands; (ii) reduction in edge-to-edge gap between antennas to 10 mm (0.37λ); and (iii) improvement in gain by >40% over certain angular directions, which varies between 4.5 dBi to 8.2 dBi. The proposed technique is simple to implement at low-cost.

Dimethyl fumarate (DMF) and diroximel fumarate (DRF) are two treatments used in multiple sclerosis (MS), that have been shown to be effective in controlling MS patients. DRF was intro-duced in 2019, with the aim of decreasing the gastrointestinal side effects caused by DMF. Few real-life studies verify the data provided in the clinical trials. Methods: A retrospective descriptive study was conducted in MS patients at the Hospital Universitario Torrecárdenas under treatment with DRF and DMF. Demographic, clinical, and analytical variables were studied and compared between groups. Results: 60 patients were recruited, 30 with each treatment, observing similar baseline characteristics. Fewer gastrointestinal (GI) effects were observed in the DRF group, while more infections were detected in the DMF group. We recorded lower levels in the DRF group, with 4 moderate-severe lymphopenia in the DRF group vs. none in the DMF group. In addition, we observed a decrease in lymphocytes after the change from DMF to DRF in patients with a change. Conclusions: Our real-life analysis of patients treated with DMF or DRF supports studies’ findings of decreased GI side effects with DRF vs. DMF, without decreasing efficacy. However, our data show greater reduction in lymphocytes in patients with DRF compared to DMF, so more studies are necessary.

Microglial cells are highly specialized central nervous system (CNS) cells that can promote the inflammation and neurodegeneration seen in Multiple Sclerosis (MS). MS is a neurodegenerative autoimmune disease characterized by inflammation, demyelination, and axonal degeneration. In MS patients, demyelination is associated with activated microglia. Endothelin-1 (ET-1) is a potent vasoconstrictor that induces severe and prolonged cerebral vasoconstriction and inflammation. However, the mechanism of how ET-1 activates a proinflammatory response in the CNS is unknown. To investigate ET-1’s role in microglia activation, HMC3 cells were treated with ET-1 in the presence or absence of endothelin receptor B antagonist, BQ788. TNFα and IL-6 levels were measured using ELISA. Nitric Oxide (NO) production was measured using Griess Reagent. Reactive oxygen species (ROS) production was measured using the MUSE Oxidative Stress kit. ET-1 increases TNFα levels by 56% (p= 0.0003) and IL-6 levels by 86% (p= 0.0111) in HMC3 cells, and it was decreased to basal levels in the presence of BQ788. NO and ROS production is induced by ET-1 (p&lt;0.05), and treatment with BQ788 was able to decrease them. ET-1 increases STAT-1 activation by 3.5 folds compared to control (p &lt;0.0001) in microglia cells. Moreover, to study ET-1 levels in MS, we used C57BL/6 mice brains with or without induced experimental autoimmune encephalomyelitis (EAE). The brain ET-1 levels were measured by qPCR and ELISA. We found that the ET-1 gene and protein were upregulated by 1.5 folds (p= 0.0199) in EAE mice compared to the control. These data suggest that in vitro administration of ET-1-activated microglia significantly increased inflammatory cytokine levels and NO and ROS formation. This novel mechanism of microglial cell activation will provide key information to understand MS pathogenesis.

Background: To evaluate the effectiveness of Defocus Incorporated Multiple Segments (DIMS) in slowing myopia progression in pediatric patients as a function of age. Methods: This was a non-randomized experimenter-masked retrospective controlled observational study of European individuals aged 6 -16 years with progressive myopia but no ocular pathology. We retrospectively reviewed the charts of the participants allocated to receive DIMS spectacles (Hoya® MiyoSmart®) or single vision spectacle lenses (control group). Cycloplegic spherical equivalent (SE) and axial length (AL), were measured at baseline and at 36 month follow up. The results were stratified by age into four groups: patients that wore DIMS spectacles oldest or youngest than 10 years of age (respectively, group A, 20 patients mean age 13.6±2.2 and group C, 20 patients mean age 9.0±1.2) and age-matched control groups (group B, 18 patients mean age 13.2±2.5 and group D, 22 patients mean age 8.5±0.9). Results: At 36 months, SE and AL increase resulted significantly reduced in groups A and C, respectively compared to groups B and D (p<0.05). Linear regression analysis showed a significant correlation (P<0.05) between patient age and myopia progression for SE in groups A and C, but only in group A also for AL. Groups B and D did not show any significant correlation (P>0.05). Conclusion: DIMS spectacles seem to slow myopia increase in pediatric patients, however their effectiveness results greatest in children oldest than 10 years of age. Morover our findings suggest that AL may be the more reliable parameter for evaluating myopia progression.

Introduction. Anesthesia is widely used in various fields of dentistry to reduce patient discomfort when the treatment would be painful. The dentist may need to infiltrate the anesthetic into multiple locations and this is usually done with the same needle which passes through the soft tissues several times to distribute the anesthetic solution over a larger area. The present study aims to evaluate, through a morphological analysis under a scanning electron microscope (SEM), how the beveled tip of a 30G needle, used to inject anesthetic several times into different areas of the vestibular mucosa, changes. Materials and methods. 30G needles with two different brands were tested, in vivo used for a variable number of sequential injections from 1 to 6 on 192 patients. The specimens were analyzed under SEM observation to evaluate any deformations induced by contact with the vestibular soft tissues. Results. The amount of deformation, measured along the axis parallel to the needle, was proportional to the number of injections. The protrusion of deformations, measured on an axis perpendicular to the needle, were maximum on the needles used 3 times. For the needles used 4,5 and 6 injections, no further increase in deformations was noted. Conclusion. From the data it seems that the tested needles are not produced to withstand multiple injections consequently after the first injection on soft tissues, they undergo a deformation which could increase the risk of injury to the mucosa itself or to nerves and vessels with which they come into contact. It would be advisable to use the single needle for a reduced number of injections.

For the first time to optimize the creation of new neuroprotective agents based on bioflavonoids, we applied information technologies - docking analysis to calculate the binding of candidate molecules to the pharmacological target protein transthyretin, as well as the program of virtual screening of NO scavengers. As a result of this approach, the substance catechin was isolated from candidate molecules - quercetin, catechin, Epicatechin gallate, Epicatechin, Procyanidin B1, Procyanidin B2, Procyanidin B3, Catechin-3-gallate according to docking analysis. As a result of virtual screening, catechin was identified as a potential NO scavenger (55.15% prediction). The results of the prediction were confirmed by in vitro experiments. Course administration of catechin to animals with experimental multiple sclerosis (MS) against the background of methylprednisolone administration completely eliminated lethal cases, reduced the number of diseased animals by 20%, as well as prevented the development of severe neurological symptoms by 20% (compared to the methylprednisolone group) and by 60% compared to the control group. Course administration of catechin with methylprednisolone leads to decrease of neurodegradation markers in the cytosol of rats with EAE: NSE by 37%, and S-100 - by 54.8%. The combined administration of methylprednisolone significantly exceeds the combination of methylprednisolone with the reference drug mexidol by the degree of NSE reduction. The obtained results indicate a significant neuroprotective effect of ocular combinations of methylprednisolone and catechin. The above-mentioned confirms the correctness of bioflavonoid selection with the help of virtual screening program.

Objective: Daratumumab (Dara) is the first-in-class human-specific anti-CD38 mAb approved for treating multiple myeloma (MM). However, DARA-induced depletion of CD38high natural killer (NK) cells results in crippled antibody-dependent cellular cytotoxicity (ADCC), which limits its clinical detection and prediction for Dara efficacy. Therefore, we aimed to explore new NK subsets that could predict Dara efficacy and the underlying mechanism in Dara development. Methods: Multicolour spectral flow cytometry monitored changes in the immune cells of 13 paired RRMM patients. We used machine learning-driven clustering, FlowSOM (Flow Self-Organizing Maps), and dimensional reduction with tSNE (t-distributed Stochastic Neighbour Embedding) to identify unique cell populations pre- and posttreatment. Then, in vitro, fratricide and proliferation assays were performed to explore the function of new NK subsets against MM under Dara treatment. Results: The NK cells were divided into 25 subsets, among which we found that the percentages of KIR-NKP46+ NK cells decreased in paired RRMM patients compared to healthy controls but increased significantly post-Dara treatment. The fold change in KIR-NKP46+ after one dose of Dara treatment can predict whether the best response could be achieved within one month (ROC=0.86, p=0.011). Further in vitro experiments showed that KIR-NKP46+ NK cells are superior to KIR+ NK cells, cooperatively acting with daratumumab to sustainably eradicate MM cells. Meanwhile, apoptosis was significantly decreased, and the proliferation ability was relatively increased post-Dara treatment. Conclusion: In conclusion, the fold change in KIR-NKP46+ NK cell subsets after one dose of Dara treatment can predict the outcome of the curative effect, indicating a putative role of KIR-NKP46+ subsets against MM cells. The mechanism attributed to a relative expansion of the subset due to decreased apoptosis and increased proliferation ability.

Patients with Multiple Myeloma have an increased susceptibility to severe infections due to several various factors, especially the high tumor burden. The use of the anti-CD38 monoclonal antibodies-based therapies has changed the frequency and epidemiology of infections. We report herein the safety profile of the pivotal clinical trials conducted with anti-CD38 mAbs (daratumumab and isatuximab) and anti-SLAMF7 mAbs (elotuzumab) that led to the approval of regimens employed today in NDMM and RRMM patients.

Gender has been a rarely addressed aspect in digital game-based learning (DGBL). Likewise, mixed results have been presented regarding the effects according to gender and the conditions that generate these effects. The present work studies the effects of a drill-and-practice mathe-matical game on primary students. The study focused on an analysis by gender, measuring learning performance, and motivation in the practice activity. Also, two instructional mechanics were considered regarding the question answering, a multiple-try (MTF) and a single-try (STF) condition, to search for possible differences. A total of 81 students from 4 courses and 2 schools participated in the experiment. The study's main findings were that: (a) the girls outperformed boys in terms of students' learning gains, (b) girls presented lower levels of competence and autonomy than boys, (c) in the MTF, girls presented lower levels of autonomy but no differences in competence contrasted to boys, (d) in the STF, girls presented lower levels of competence but no differences in autonomy against boys, and (e) no differences existed in interest, effort and value among gender overall o per instructional condition. This study enhances the knowledge of gender differences under diverse instructional settings, in particular providing insights into possible differences by gender when varying the number of attempts provided to students.

As the adoption of renewable energy sources grows, ensuring a stable power balance across various time frames has become a central challenge for modern power systems. In line with the "dual carbon" objectives and the seamless integration of renewable energy sources, harnessing the advantages of various energy storage resources and coordinating the operation of long-term and short-term storage have become pivotal directions for future energy storage deployment. To address the complexities arising from the coupling of different time scales in optimizing energy storage capacity, this paper proposes a method for energy storage planning that accounts for power imbalance risks across multiple time scales. Initially, the Seasonal and Trend decomposition using the Loess (STL) decomposition method is utilized to temporally decouple actual operational data. Subsequently, power balance computations are performed based on the obtained data at various time scales to optimize the allocation of different types of energy storage capacities and assess the associated imbalance risks. Finally, the effectiveness of the proposed approach is validated through hourly applications using real-world data from a province in China over recent years.

23-Hydroxy ursolic acid (23-OH UA) is a potent atheroprotective and anti-obesogenic phytochemical, with anti-inflammatory and inflammation resolving properties. In this study, we examined whether dietary 23-OH UA protects mice against the acute onset and progression of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Female C57BL/6 mice were fed either a defined low-calorie maintenance diet (MD) or an MD supplemented with 0.2 % wgt/wgt 23-OH UA for 5 weeks prior to actively inducing EAE and during the 30 days post-immunization. We observed no difference in the onset of EAE between both groups of mice, but ataxia and EAE disease severity were suppressed by 52% and 48%, respectively, and disease incidence was reduced by over 49% in mice that received 23-OH UA in their diet. Furthermore, disease-associated weight loss was strikingly ameliorated in 23-OH UA-fed mice. ELISPOT analysis showed no significant differences in frequencies of T cells producing IL-17 or IFN- between 23-OH UA fed mice and control mice, suggesting that 23-OH UA does not appear to regulate peripheral T-cell responses. In summary, our findings demonstrate that dietary 23-OH UA may represent an effective oral adjunct therapy for the prevention and treatment of relapsing-remitting MS.

Steroid hormones have diverse roles in pregnancy; some, such as progesterone and its metabolites, help stabilise pregnancy and can very likely influence the stability of pregnancy and the onset of labour. Changes and disorders in steroidogenesis may be involved in several pregnancy pathologies, such as premature delivery, preeclampsia, and intrahepatic cholestasis. To date, only a few studies have performed steroid analysis in multiple pregnancies. However, these studies offered a limited analysis of the steroidome in children and mothers with multiple pregnancies. Our team and a team from the Department of Steroids and Proteofactors of the Institute of Endocrinology in Prague investigated multiple pregnancies regarding the biosynthesis, transport, and effects of steroids. We recruited two groups of patients: pregnant women with multiple pregnancies as the study group and singleton pregnancies as the control group. Blood samples were drawn from the participants and analysed. Information about the mother, foetus, delivery, and newborn was extracted from medical records. The data were then analysed. The gestational age of twin pregnancies during delivery ranged from 35+3 to 39+3 weeks, while it was 38+1 to 41+1 weeks for the controls. Our findings provide answers to questions regarding the steroidome in multiple pregnancies.

Background. The purpose of the study was to evaluate the intensity and frequency of low back pain (LBP) in people with multiple sclerosis (PwMS) and the patient's knowledge of physiotherapeutic methods of combating. Methods. In this study, patients with confirmed multiple sclerosis were selected. The study was carried out using an original survey questionnaire and a numerical pain intensity scale (Visual Analogue Scale). PwMS were divided into 3 age groups: 18-30 years, 31-50 years, and over 50 years. Results. Ninety PwMS (68 women and 22 men) aged 18 to 60 years were included in the study. The mean duration of the disease was 9.5±4.9 years, and the mean EDSS was 3.5±1.6. Most of the patients had a relapse-remitting form. 68.9% of PwMS felt lower back pain (n = 62). The relationship tested was statistically significant (p=0.0000012), and the strength of the relationship was high (rc=0.695). The average level of low back pain among PwMS was 4.7 out of 10 on the VAS scale. The prevalence of LBP was higher in female patients (p<0.001), with a secondary progressive form (p<0.001) and with a longer duration of the disease (p=0.023). The most widely used methods of LBP therapy were kinesitherapy and manual therapy. Conclusions. LBP is common in multiple sclerosis. A female sex, a secondary progressive form of MS, and a longer duration of the disease increased the risk of LBP. It is important to implement properly planned physiotherapy activities and educate patients on how to combat LBP.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. According to recent studies, cellular senescence caused by telomere shortening may contribute to the development of MS. Aim of the study: to determine the associations of TEP1 rs1760904, rs1713418, TERC rs12696304, rs35073794 gene polymorphisms with the occurrence of MS. Methods: The study included 200 patients with MS and 230 healthy controls. Genotyping of TEP1 rs1760904, rs1713418 and TERC rs12696304, rs35073794 was performed using RT-PCR. Statistical analysis of the obtained data was performed using the program "IBM SPSS Statistics 29.0". Haplotype analysis was performed using the online program "SNPStats". Results: The TERC rs12696304 G allele of this SNP is associated with a 1.4-fold lower odds of developing MS (p=0.035). TERC rs35073794 is associated with an approximately 2.4-fold reduced odds of MS occurrence in the codominant, dominant, overdominant, and additive models (p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). Haplotype analysis shows that the rs1760904-G - rs1713418-A haplotype is statistically significantly associated with a 1.75-fold increased odds of developing MS (p=0.006). The rs12696304-C - rs35073794-A haplotype is statistically significantly associated with a 2-fold decreased odds of developing MS (p=0.008). In addition, the rs12696304-G - rs35073794-A haplotype was found to be statistically significantly associated with a 5.3-fold decreased odds of developing MS (p&lt;0.001). Conclusion: Current evidence may suggest a protective role of TERC SNP in the occurrence of MS, while TEP1 has the opposite effect.

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

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

Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remote organ damage after trauma remain obscure. HMGB1 and inflammatory mediators were analyzed in plasma from 54 combat casualties, collected on admission to a military hospital in Iraq, and at 8 and 24 hours after admission. Forty-five (83%) of these patients had traumatic brain injury (TBI). Nine healthy volunteers were enrolled as controls. HMGB1 plasma levels were significantly increased in the first 8 hours after admission, and were found to be associated with systemic inflammatory responses, injury severity score, and presence of TBI. These data provided the rationale for designing experiments in rats subjected to blast injury and hemorrhage, to explore the effect of HMGB1 inhibition by CX-01. Animals were cannulated, then recovered for 5-7 days before blast injury in a shock tube and volume-controlled hemorrhage. Blast injury and hemorrhage induced an early increase in HMGB1 plasma levels that coincided with severity of tissue damage and mortality. CX-01 inhibited systemic HMGB1 release, decreased local and systemic inflammatory responses, significantly reduced tissue and organ damage, and tended to increase survival. These data suggest that CX-01 has potential as an adjuvant treatment for traumatic hemorrhage.

We investigated the response of the Manila clam Venerupis philippinarum to possible temperature and salinity changes in a holding facility. First, clams were exposed to four temperatures for 15 days. Valve closure and survival of clams exposed to seawater at 18℃ were higher than that of those exposed to seawater at 24℃. Second, clams were exposed to six salinities for 15 days. Survival of clams exposed to two salinity fluctuation conditions (24–30 and 27–24 psu) was lower than that of clams exposed to constant 30 psu conditions. Valve closures of clams exposed to constant low salinity conditions (24 psu) and two salinity fluctuation conditions (24–30 and 27–24 psu) were higher than of those exposed to constant 30 psu conditions. Lastly, clams were exposed to two different temperatures and three different salinities conditions for 8 days. Valve closure and survival decreased significantly under the combination of 24℃ and 18 psu. These results suggest that an increase in temperature or a wider range of salinity fluctuations are detrimental to the survival of the Manila clam. The synergistic effect of temperature and salinity stressors may decrease the survival period of clams compared to the effect of a single stressor.

Despite recent advances in immune-modulatory drugs, pharmacological therapies have been proven ineffective in severe presentations of multiple sclerosis (MS), including secondary progressive MS. At present, therapeutic interventions' performance is primarily focused on ameliorating symptoms to improve the patient's quality of life. Among complementary treatments, nutrition has been considered a decisive factor to control symptoms and enhance the wellness of MS patients. Although no special diets are associated with MS, the impact of diet and dietary supplements on the course of progressive forms of the disease have been studied during the last years. Fatigue is among the most common and disabling symptoms reported by MS patients. Fatigue has been defined in the Multiple Sclerosis Council for Clinical Practice Guidelines (MSCCPG, 1998) as a "subjective lack of physical and/or mental energy that the individual perceives as an interference with habitual and desired activities". This study aimed to compare the psychometric functioning of the "Fatigue Severity Scale" (FSS) and the "Modified Fatigue Impact Scale" (MFIS) in our sample of people with MS. Specifically, during chronic treatment, the change in these two parameters with two vitamin-rich dietary supplements (Citozym® and Ergozym®) was evaluated. The impact of these nutritional supplements revealed differences in antioxidant and anti-inflammatory parameters between treatment groups with subsequent improvement in fatigue. In conclusion, the results obtained have confirmed the effectiveness of complementary nutritional therapies, evaluated essentially based on hematological biomarkers, through which it is possible to act on disability to improve the quality of life of MS patients.

Complex models have received significant interest in recent years and are being increasingly used to explain the stochastic phenomenon with upward and downward fluctuation such as the stock market. Different from existing semi-variance methods in traditional integer dimension construction for two variables, this paper proposes a simplified multi-factorized fractional dimension derivation with the exact Excel tool algorithm involving the fractional center moment extension to covariance, which is a complex parameter average that is a multi-factorized extension to Pearson covariance. By examining the peaks and troughs of gold price averages, the proposed algorithm provides more insight into revealing underlying stock market trends to see who is the financial market leader during good economic times. The calculation results demonstrate that the complex covariance is able to distinguish subtle differences among stock market performances and gold prices for the same field that the two variable covariance may overlook. We take the London, Tokyo, Shanghai, Toronto and Nasdaq as the representative examples.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The interferons (IFNs) were discovered in 1957, and recombinant IFN-β-1b was approved by the US Food and Drug Administration as the first disease-modifying therapy (DMT) for MS in 1993. Since that time, clinical trials and real-world observational studies have demonstrated the effectiveness of IFN therapies. The pivotal intramuscular IFN-β-1a phase 3 trial was the first to demonstrate that a DMT could reduce accumulation of sustained disability in MS. Patient adherence to treatment is higher with intramuscular IFN-β-1a, given once weekly, than with subcutaneous formulations requiring multiple injections per week. Moreover, subcutaneous IFN-β-1a is associated with an increased incidence of injection site reactions and neutralizing antibodies compared with intramuscular administration. In recent years, revisions to MS diagnostic criteria have improved clinicians’ ability to identify patients with MS and have promoted the use of magnetic resonance imaging (MRI) for diagnosis and monitoring. MRI studies show that treatment with IFN-β-1a, relative to placebo, reduces T2 and gadolinium-enhancing lesions and gray matter atrophy. Since the approval of intramuscular IFN-β-1a, several high-efficacy therapies have been approved for MS, though the benefit of these high-efficacy therapies should be balanced against the increased risk of serious adverse events. For some subpopulations of patients, including pregnant women, the safety profile of IFN-β formulations may provide a particular benefit. In addition, the antiviral properties of IFNs may indicate therapeutic opportunities for IFN-β in the treatment of viral infections such as COVID-19.

Abstract: Long noncoding RNAs (lncRNAs) are deregulated in human cancers and are associated with disease progression. Plasmacytoma Variant Translocation 1 (PVT1), an lncRNA, is located adjacent to MYC, linked to multiple myeloma (MM). PVT1 is expressed in MM and is associated with carcinogenesis, however, its role and regulation machinery remain uncertain. We examined PVT1/MYC expression through real time PCR in plasma cells purified from 59 MGUS and 140 MM patients. MM cell lines KMS11, KMS12PE, OPM2, and RPMI8226 were treated with JQ1, a MYC superenhancer inhibitor, or MYC inhibitor 10058-F4. The expression levels of PVT1 and MYC were significantly higher in MM than in MGUS (p &lt; 0.0001), and showed positive correlation with disease progression (r = 0.394, p &lt; 0.0001). JQ1 inhibited cell proliferation and decreased the expression levels of MYC and PVT1. However, 10054-F4 did not alter the expression level of PVT1. The positive correlation between MYC and PVT1 in patients, synchronous downregulation of MYC and PVT1 by JQ1, and no effect of MYC inhibitor on PVT1 expression suggest that the expression of these two genes is coregulated by a superenhancer. Cooperative effects between these two genes may contribute to MM pathogenesis and progression.

Risk attitudes are relevant factors affecting the production and investment decisions at farm level. They are key factors that are related to farmers’ attitudes towards environment and climate change. Several methodological approaches are available to measure the level of stated risk of an economic agent. The Multiple Price List (MPL) method is one of the methods that is gaining relevance. In this study we apply the MPL and relate the risk outcomes with farmers’ characteristics and their perception towards environment and climate change. Data was collected using a face to face survey carried out for a group of 370 agricultural producers of the irrigation district located in northwest of Mexico. Results showed an average risk of about 0.32, locating the agricultural producers of the region in a group with risk aversion, according to the MPL scale. The heterogeneity analysis showed that the socioeconomic factors and the perceptions towards climate change are related to the farmers´ stated risk level. Farmers who are young women with propensity to use public support to invest were shown to be greater risk lovers. Farmers in the region have perceived climate change to a greater extent like floods, hail, diseases and pests, and changing vegetation.

Two sufi women take part in activities related to sufism and create an attraction point in the secular side in Turkey.The most striking point is that both women do not wear headscarves although they are muslim women. This article attempts to show how sufi women Cemalnur Sargut and Hayatnur Artıran have idealized a Muslim woman's identity, the work they are doing to achieve this ideal, their attidue toward Rebublic values, and the effects of these attidues on their followers. This article was created from my doctoral thesis and based on Qualitative research which has been established on the basis of 2-year long participant observation and data obtained from in-depth and focus interviews. 31 women and 20 men were interviewed in depth and focus interviews.The main conclusions of my qualitative research are that the influence of theese sufi women is related with process of modernization by accelerating the establishment of the republic in Turkey. It seems that a perception has established concerning that “public apparency’’ of woman will disappear if the “apparency of body’’ disappears and the woman will return to its role which had relapsed into silence for centuries. Besides not using the headscarf, religious conversation have been created by theese sufi women in the balance of religion, philosophy and science and the fact that they are conducting their works under secular institutions such as foundations and associations have also been observed to have a very important effect on seculer side.

Conyza canadensis is a species invading large agricultural areas throughout the world, mainly to its ability to evolve herbicide resistance. Specifically, in Hungary, extensive areas have been infested by this species due to the difficulty in controlling it with glyphosate. To corroborate this fact as resistance and not as an incorrect herbicide application, eight suspicious glyphosate-resistant C. canadensis populations from different Hungarian regions were studied. In dose-response assays with glyphosate, the LD50 and GR50 values indicated that populations 1 to 5 were resistant to this herbicide (H-5 population the most resistant). Besides, the shikimic acid accumulation tests corroborated the results observed in the dose-response assays. 11 alternative herbicides from 6 different mode of action (MOA) were applied at field doses as control alternatives on populations H-5 and H-6 (both in the same regions). The H-5 population showed an unexpected resistance to flazasulfuron (ALS-inhibitor). The ALS enzyme activity studies indicated that the I50 for H-5 was 63.3 fold higher compared to its correspondent susceptible population (H-6). Therefore, the H-5 population exhibited multiple-resistance to flazasulfuron and glyphosate, being the first case reported in Europe for this two MOA. For that reason, the other herbicides with different MOA have to be tested here.

Malignant cells cultured in three-dimensional (3D) models have been found to be phenotypically and biochemically different from their counterparts cultured conventionally. Since most of these studies employed solid tumor types, how 3D culture affects multiple myeloma (MM) cells is not well understood. Here, we compared MM cells (U266 and RPMI8226) in a 3D culture model with those in conventional culture. While the conventionally cultured cells were present in single cells or small clusters, MM-3D cells grew in large spheroids. We discovered that STAT3 was the pathway that was more activated in 3D in both cell lines. The active form of STAT3 (phospho-STAT3 or pSTAT3), which was absent in MM cells cultured conventionally, became detectable after 1-2 days in 3D culture. This elevated pSTAT3 level was dependent on the 3D environment, since it disappeared after transferring to conventional culture. STAT3 inhibition using a pharmacological agent, Stattic, significantly decreased the cell viability of MM cells and sensitized them to bortezomib in 3D culture. Using an oligonucleotide array, we found that 3D culture significantly increased the expression of several known STAT3 downstream genes implicated in oncogenesis. Since most primary MM tumors are naturally STAT3-active, studies of MM in 3D culture can generate results that are more representative of the disease.

The role of natural factors mainly solar eleven-year cycle variability, and volcanic eruptions on two major modes of climate variability the North Atlantic Oscillation (NAO) and El Niño Southern Oscillation (ENSO) are studied for around last 150 years period. The NAO is the primary factor to regulate Central England Temperature (CET) during winter throughout the period, though NAO is impacted differently by other factors in various time periods. Solar variability indicates a strong positive influence on NAO during 1978-1997, though suggests opposite in earlier period. Solar NAO lag relationship is also shown sensitive to the chosen times of reference and thus points towards the previously proposed mechanism/ relationship related to the sun and NAO. The ENSO is influenced strongly by solar variability and volcanic eruptions in certain periods. This study observes a strong negative association between the sun and ENSO before the 1950s, which is even opposite during the second half of 20th century. The period 1978-1997, when two strong eruptions coincided with active years of strong solar cycles, the ENSO, and volcano suggested a stronger association, and we discussed the important role played by ENSO. That period showed warming in central tropical Pacific while cooling in the North Atlantic with reference to the later period (1999-2017) and also from chosen earlier period. Here we show that the mean atmospheric state is important for understanding the connection between solar variability, the NAO and ENSO and associated mechanism. It presents a critical analysis to improve knowledge about major modes of variability and their role in climate. We also discussed the importance of detecting the robust signal of natural variability, mainly the sun.

A novel configuration for a super-wide impedance planar antenna is presented based on a 2 × 2 microstrip patch antenna (MPA). The antenna comprises a symmetrical arrangement of four-square patches that are interconnected to each other with cross-shaped high impedance microstrip lines. The antenna array is exciting through a single feedline connected to one of the patches. The proposed antenna array configuration overcomes the main drawback of conventional MPA of narrow bandwidth that is typically <5%. The antenna exhibits a super-wide frequency bandwidth from 20 GHz to 120 GHz for S₁₁<−15 dB, which corresponds to a fractional bandwidth of 142.85%. The antenna’s performance of bandwidth, impedance match, and radiation gain were enhanced by etching slots on the patches. The slotted microstrip patch essentially acts like a left-handed capacitance to exhibit metamaterial properties over a given frequency range. With the inclusion of the slot the maximum radiation gain and efficiency of the MPA have increased to 15.11 dBi and 85.79% at 80 GHz, which show an improvement of 2.58 dBi and 12.54%, respectively. The dimension of each patch antenna is 30 × 30 mm². The results show that the proposed MPA is useful for various communications existing and emerging systems such as ultra-wideband (UWB) communications, RFID systems, massive multiple-output multiple-input (MIMO) for 5G, and radar systems.

In this paper, spatial pulse position modulation (SPPM) is used as a case study to investigate the performance of the optical spatial modulation (SM) technique in outdoor atmospheric turbulence (AT). A closed-form expression for the upper bound on the asymptotic symbol error rate (SER) of SPPM in AT is derived and validated by closely-matching simulation results. The error performance is evaluated in weak to strong AT conditions. As the AT strength increases from the weak to strong, the channel fading coefficients become more dispersed and differentiable. Thus, a better error performance is observed under moderate-to-strong AT compared to weak AT. The performance in weak AT can be improved by applying unequal power allocation to make FSO links more distinguishable at the receiver. Receive diversity is considered to mitigate irradiance fluctuation and improve the robustness of the system to turbulence-induced channel fading. The diversity order is computed as half of the number of detectors. Performance comparisons, in terms of energy and spectral efficiencies, are drawn between the SPPM scheme and conventional MIMO schemes such as repetition coding and spatial multiplexing.

Finding out an available car parking space has been one of the most crucial problems for the crowded cities, which causes such issues as traffic congestions, air pollutions, and stressful drivers. To mitigate the issues here, smart car parking management system (SPMS) solutions can be used which digitalise the parking processes and maximise the drivers’ productiveness. However, the existing SPMS solutions are either domain-specific or address the applications of particular techniques and technologies. None of the solutions in the literature propose any generic approach that can be re-used for the analysis and design of any SPMSs. In this paper, we propose a reference architecture (RA) for the SPMS product family. Performing comprehensive domain analysis, we provide a feature model of the common and varying features for SPMSs. We designed 4 architectural viewpoints, which are context, module, component&amp;connector, and allocation. Each viewpoint addresses a different concern and proposes a generic solution that can be re-used for any specific SPMSs. To validate our RA design, we used the commercial 4Park SPMS application and specified its architecture using our RA viewpoints. We strongly believe that our RA design for SPMSs can be useful for the SPMS domain who develop SPMS solutions.

Background/Objectives: Monoclonal antibodies (mAbs) have revolutionized multiple myeloma (MM) treatment. However, post-marketing data on their neuropsychiatric safety is limited. This study aimed to evaluate neuropsychiatric adverse events (AEs) related to mAbs used for MM through a retrospective pharmacovigilance analysis using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database. Methods: Individual case safety reports (ICSRs) from 2015 to 2023 with at least one neuropsy-chiatric AE and one of the MM-approved mAbs as the suspect drug (i.e., daratumumab, elo-tuzumab, isatuximab, belantamab mafodotin, teclistamab, elranatamab, and talquentamab) were analyzed using descriptive and disproportionality approaches. Results: Unknown signals of disproportionate reporting (SDR) included cerebral infarction for daratumumab (n = 45; reporting odds ratio (ROR) = 2.39, 95% confidence interval (CI) = 1.79-3.21; information component (IC) = 1.54, IC025-IC075 = 1.05-1.9), elotuzumab (25; 7.61, 5.13-11.28; 3.03, 2.37-3.51), and isatuximab (10; 2.56, 1.38-4.76; 1.67, 0.59-2.4); mental status changes for daratumumab (40; 2.66, 1.95-3.63; 1.67, 1.14-2.04) and belantamab mafodotin (10; 4.23, 2.28-7.88; 2.3, 1.22-3.03); altered state of consciousness for daratumumab (32; 1.97, 1.39-2.78; 1.32, 0.73-1.74) and belantamab mafodotin (6; 2.35, 1.05-5.23; 1.6, 0.19-2.52); Guil-lain-Barre syndrome (GBS) for daratumumab (23; 6.42, 4.26-9.69; 2.81, 2.11-3.3), isatuximab (8; 10.72, 5.35-21.48; 3.57, 2.35-4.37), and elotuzumab (3; 4.74, 1.53-14.7; 2.59, 0.52-3.8); and orthos-tatic intolerance for daratumumab (10; 12.54, 6.71-23.43; 3.75, 2.67-4.48) and elontuzumab (4; 28.31, 10.58-75.73; 5 , 3.24-6.08). Conclusions: Our analysis highlighted several previously unacknowledged SDRs for MM-approved mAbs. Given the complex and not entirely understood etiology of some neuropsy-chiatric AEs, including GBS, further investigations are necessary.

In order to quickly develop a multi ship collaborative collision avoidance plan in multi ship encounter scenarios, a multi ship collision avoidance decision model is proposed in accordance with the requirements of the International Maritime Collision Avoidance Regulations, taking into account the collision avoidance operations in multi ship encounter scenarios. Firstly, the collision risk between ships is determined by the closest encounter distance (DCPA) and closest encounter time (TCPA). Secondly, a decision objective function is established based on rules, degree of ship deviation, and ship risk. Finally, the prediction mechanism is used to calculate the minimum value of the objective function and complete the collision avoidance decision. The simulation results show that in the scenario of multiple ship encounters, the collision avoidance model can achieve safe collision avoidance with a smaller steering frequency and a shorter col-lision avoidance time. The proposed multi ship collision avoidance model can provide reference for collision avoidance decision-making in multi ship encounter scenarios, which helps to im-prove the collision avoidance efficiency in multi ship collision avoidance

Acute coronary syndrome (ACS) is a life-threatening condition that requires a prompt diagnosis and therapeutic intervention. Although serum troponin T and creatinine kinase-MB (CK-MB) are established biomarkers for ACS, it may take several hours to reach diagnostic values for ACS. In this study, we attempted to explore novel biomarkers for ACS with higher sensitivity than that of troponin T and CK-MB. The metabolomic profiles of 18 patients with ACS upon hospital arrival and those of the age-matched control (HC) group consisted of 24 healthy volunteers were analyzed using liquid chromatography-time-of-flight mass spectrometry. Volcano plots showed 24 metabolites whose concentrations differed significantly between the ACS and HC groups. Using these data, we developed a multiple logistic regression model for the ACS diagnosis, in which lysine, isocitrate, and tryptophan were selected as minimum-independent metabolites. The area under the receiver operating characteristic curve value for discriminating ACS from HC was 1.00 (95% confidence interval [CI]: 1.00-1.00). In contrast, those for troponin T and CK-MB were 0.917 (95% confidence interval [CI]: 0.812-1.00) and 0.988 (95% CI: 0.966-1.00), respectively. This study showed the potential of combining three plasma metabolites to discriminate ACS from HC with a higher sensitivity than that of troponin T and CK-MB.

An increased demand for natural products nowadays most specifically probiotics (PRO) is evident since it comes in conjunction with beneficial health effects for the consumers. In this regard, it is well known that encapsulation could affect positively the PRO's viability throughout food manufacturing and long-term storage. This paper aims to analyze and review various multilayer strategies for encapsulation of PRO. Double-layer encapsulation of PRO by electro-hydrodynamic atomization or electrospray technology has been reported along with layer-by-layer assembly and water-in-oil-in-water (W1/O/W2) double emulsions to produce multilayer PRO-loaded carriers. Finally, their applications in food products are presented. The resistance (cover material) and viability of (PRO) to mechanical damage, during gastrointestinal transit and shelf life of these trapping systems are also described. The PRO encapsulation in double and multiple-layer coatings combined with other technologies can be examined to increase the opportunities for new functional products with amended functionalities opening a novel horizon in food technology.

Objective: The goal of this review is to provide a succinct, yet comprehensive, guide to the an-tepartum management of multiple gestations. Methods: This narrative review on twins and multiple gestation provides a concise guide for providers with this ever-growing patient population. PubMED was utilized for literature search. Each reference was evaluated and graded for quality of evidence by US Preventative Services Task Force and Cochrane Review guidelines. Screening, surveillance, and management strategies are delineated succinctly and organized by type of multiple gestation being managed from the lowest risk dichorionic twin pair to the increasingly escalating risks of twins and higher order multiples sharing a placenta and/or amniotic sac. Results: The incidence of twin pregnancies has grown over the past several years, due in large part to delayed reproductive timing and surge in assisted reproductive technologies. Twin pregnancies are associated with higher morbidity for both gravidas and offspring, warranting evidence-based approach in counseling and management. Conclusions: We note the important differences among multiples in chorionicity and amnionicity, in the importance of close surveillance and early delivery. Graded clinical pearls and evi-dence-based recommendations are presented to guide obstetric providers.

Balo’s concentric sclerosis is a rare disease and a subtype of multiple sclerosis. A 38-year-old male patient presented to the hospital with the complaint of numbness in the left-sided upper and lower limb, slurring of speech and left-sided headache for 15 days. Further investigation was done and in ECG ‘Delta wave’ was identified along with tachycardia. Diagnosis of Wolff Parkinson White syndrome was made. The patient’s MRI Brain has shown a non-enhancing intra-axial altered signal intensity lesion at the callose-septal interface adjacent to both lateral ventricles, which was identified as Balo’s concentric sclerosis.

The flow field around a straight chain of multiple slip spherical particles rotating steadily in an incompressible Newtonian fluid about their line of centers is analyzed at low Reynolds numbers. The particles may vary in radius, slip coefficient, and angular velocity, and they are permitted to be unevenly spaced. Through the use of a boundary collocation method, the Stokes equation governing the fluid flow is solved semi-analytically. The interaction effects among the particles are found to be noteworthy under appropriate conditions. For the rotation of two spheres, our collocation results for their hydrodynamic torques are in good agreement with the analytical asymptotic solution in the literature obtained by using a method of twin multipole expansions. For the rotation of three spheres, the particle interaction effect indicates that the existence of the third particle can influence the torques exerted on the other two particles noticeably. The interaction effect is stronger on the smaller or less slippery particles than on the larger or more slippery ones. Torque results for the rotation of chains of many particles visibly show the shielding effect among the particles.

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

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

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

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

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

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

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

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

Obesity has become a rising global health problem affecting adults’ quality of life. The objective of this study was to describe the prevalence of obesity in Indonesian adults based on the cluster of islands. The study was also aimed to identify the risk factors of obesity in each island cluster. This study analysed secondary data of Indonesian Basic Health Research 2018. Our data for analysis comprised 688,638 adults (>=15 years) randomly selected using proportionate to population size throughout Indonesia. We included 20 variables for sociodemographic and obesity-related risk factors for analysis. Obese status was defined using Body Mass Index (BMI) >= 27.5 kg/m2. Our current study defined seven major islands cluster as the unit analysis consisting of 34 provinces in Indonesia. Descriptive analysis was conducted to determine the characteristics of the population and to calculate the prevalence of obesity within provinces in each of the island’s clusters. Multivariate logistic regression analyses to calculate odds ratios (ORs) was performed using R version 3.6.3. The study results showed that all island clusters had at least one province with an obesity prevalence of more than 20%. Six out of twenty variables, comprising four diet factors (consumption of sweet food, high-salt food, meat food, and carbonated drinks) and two other factors (mental health disorders and smoking behaviour), varied across the island clusters. In conclusion, there was a variation of obesity prevalence of the provinces within and between island clusters. Variation of risk factors raised in each cluster island suggested the government rethink and reframe the intervention to address obesity.

This paper will discuss the application of statistic modeling to interpret a health system crisis in Sri Lanka due to COVID- 19.A strong focus on the preventive approach and the contact tracing with the utilization of available resources in a rational manner describes Sri Lanka’s response towards COVID- 19 prevention and mitigation. The early contact tracing, preemptive quarantining, isolation, and treatment were implemented as a concerted effort. This approach, proven efficient during the early phase of the pandemic, was sustainable when there was a rapid increase in the COVID- 19 patients since July 2021, exceeding the health system capacity.The country’s COVID- 19 situation during the period from 01st of August 2021 to 31st of October 2021 was taken into consideration. Variables used for analysis were; total number of cases, recovered cases, comorbid and O₂ dependent patients, ICU patients, and deaths. The regression model was applied to analyze the data by using the EViews 12 (x64) software application.The correlation coefficients of all the independent variables under consideration implies that they have a strong positive relationship with the number of deaths occurred during the said period. According to the computed multiple linear regression model, the number of positive cases and O₂ dependents have a positive relationship with the dependent variable. Further, the Durbin- Watson stat value of the model and multicollinearity test reflect that it is free from serial correlation thereby the model is fit. From the perspective of epidemiological control, these findings highlight the importance of keeping the number of cases within the limits of health system capacity.

Despite extensively investigating the impact of social media on fashion products’ marketing, little evidence is available on how the platforms influence sales prediction. Focusing on Lolita fashion, this study investigates the impact of social media marketing on the sales volume prediction of fashion products. Essentially, we analyzed marketing data, including comments, likes, and shares from the Weibo social platform, to forecast future sales, examine how to enhance profit performance, and make production decisions. Using a quantitative approach, we tested three different prediction models, including multiple regression, decision tree, and XGBoost. The results revealed that increasing comments and decreasing the number of likes could significantly improve the sales volumes of Lolita products. In contrast, shares exerted a less significant impact on sales. Regarding prediction models, XGBoost was found to be the best method. In the fashion industry, social media is a useful tool for forecasting market trend. A limitation of this study is that only one social media platform was used to extract data, which might limit the generalization of the findings.

In this paper we deal with the resolution of a fuzzy multiobjective programming problem using the level sets optimization. We compare it to other optimization strategies studied until now and we propose an algorithm to identify possible Pareto efficient optimal solutions.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by varying degrees of demyelination of uncertain etiology, and is associated with specific environmental and genetic factors. Upon recognition of CNS antigens, the immune cells initiate an inflammatory process which leads to destruction and deterioration of the neurons. Innate immune cells such as macrophages, dendritic cells and natural killer cells are known to play critical roles in the pathogenesis of MS. Also, the activation of peripheral CD4+ T cells by CNS antigens leads to their extravasation into the CNS causing damages that exacerbates the disease. This could be accompanied by dysregulation of T regulatory cells and other cell types functions. Experimental autoimmune encephalomyelitis (EAE) is a mouse model used to study the pathophysiology of MS disease. In this review, we highlight the roles of innate and adaptive immune players in the pathogenesis of MS and EAE.

Paper-based microfluidic analysis devices (μPADs) have attracted attention as a cost-effective platform for point-of-care testing (POCT), food safety, and environmental monitoring. Recently, three-dimensional (3D)-μPADs have been developed to improve the performance of μPADs. For accurate diagnosis of diseases, however, 3D-μPADs need to be developed to simultaneously detect multiple biomarkers. Here, we report a 3D-μPADs platform for the detection of multiple biomarkers that can be analyzed and diagnosed with a smartphone. The 3D-μPADs were fabricated using a 3D digital light processing printer and consisted of a sample reservoir (300 µL) connected to 24 detection zones (of 4 mm in diameter) through 8 microchannels (of 2 mm in width). With the smartphone application, eight different biomarkers related to various diseases were detectable in concentrations ranging from normal to abnormal conditions: glucose (0–20 mmol/L), cholesterol (0–10 mmol/L), albumin (0–7 g/dL), alkaline phosphatase (0–800 U/L), creatinine (0–500 µmol/L), aspartate aminotransferase (0–800 U/L), alanine aminotransferase (0–1000 U/L), and urea nitrogen (0–7.2 mmol/L). These results suggest that 3D-µPADs can be used as a POCT platform for simultaneous detection of multiple biomarkers.

Introduction: Multiple sclerosis (MS) is a demyelinating, chronic, inflammatory and autoimmune disease of the central nervous system (CNS) with axonal degeneration, presenting a progressive and variable course. MS patients usually have complications, such as bladder dysfunction, presence of urinary symptoms and Urinary Tract infection (UTI), which is one of the three most common non-neurological complications in MS patients. Objective: Analyze the most diverse aspects of UTI in MS patients, focusing on risk factors, prevalence, hospitalization and mortality rates of UTIs in this group. Methods: A non-systematic review of articles published on PubMed in the last 10 years with the search terms "Urinary Tract Infection" AND "Multiple Sclerosis". Discussion: MS patients have a high UTI prevalence, mainly due to the occurrence of urinary disorders in these patients. The most common symptoms of UTI in MS patients are urinary urgency, polyuria, nocturia, urinary retention, and incontinence. Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the most found organisms and treatment is based on antibiotic therapy. Moreover, UTIs can precipitate outbreaks, worsen the disease, causing more damage and a severe neurological condition deterioration. Therefore, UTIs in this group are associated with a high hospitalizations rate and a high mortality rate. Conclusion: UTI represents a great risk and concern in MS patients. The high prevalence, hospitalization rate and mortality rate of UTI in MS is worrying, such as the cause-consequence relationship between UTIs and the use of corticosteroids in outbreaks. Therefore, it is important to be aware of a UTI in this group to make early diagnoses, adequate management, and new infections prevention. Thus, further studies are needed to thoroughly analyze each nuance of this important comorbidity for MS patients.

World Health Organization (WHO) provides the guideline for managing the Particulate Matter (PM) level because when the PM level is higher, it threats the human health. For managing PM level, the procedure for measuring PM value is needed firstly. We use Tapered Element Oscillating Microbalance (TEOM)-based PM measuring sensors because it shows higher cost-effectiveness than Beta Attenuation Monitor (BAM)-based sensor. However, TEOM-based sensor has higher probability of malfunctioning than BAM-based sensor. In this paper, we call the overall malfunction as an anomaly, and we aim to detect anomalies for the maintenance of PM measuring sensors. We propose a novel architecture for solving the above aim that named as Hypothesis Pruning Generative Adversarial Network (HP-GAN). We experimentally compare the several anomaly detection architectures to certify ours performing better.