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.

Background/Objectives: Different approaches are required in treating patients with multiple pulmonary lesions. A multistage procedure may increase the risk of complications and patient discomfort. This study provides an initial experience with single-stage management of multiple lung lesions using percutaneous ablation with thoracoscopic resection in a hybrid operating room (HOR). Methods: We retrospectively evaluated patients who underwent combined ablation and resection in a HOR between May 2022 and July 2024. All patients received a single anesthesia via endotracheal tube intubation. Clinical data, operative findings, and pathological characteristics of the lung nodules were recorded. Results: A total of 23 patients were enrolled in this study. Twenty patients underwent unilateral procedures, and the other three patients underwent bilateral procedures. Ablations were performed before lung resection in 22 patients; only one patient underwent surgery first. The median global operating room time was 227.0 min. The median total radiation dose (dose area product) was 14076 μGym2. The median hospital postoperative length of stay was 2 days. Conclusion: The single-stage procedure of percutaneous ablation with thoracoscopic resection under general anesthesia in a HOR is feasible and safe. This procedure is an alternative method for managing multiple pulmonary lesions.

Introduction: Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are susceptible to viral infections, including varicella-zoster virus (VZV) reactivation due to both disease-related and treatment-induced immunosuppression. The recombinant adjuvanted herpes zoster vaccine (RZV) has shown high efficacy in immunocompetent adults, but immunogenicity data in CLL and MM patients is limited. This study evaluates the immunogenicity and safety of RZV in this population. Methods: Patients with CLL and MM vaccinated with RZV (administered in two doses at least one month apart) were included in the study. Pre- and post-vaccination anti-VZV IgM and IgG antibody levels were measured to assess immunogenicity, and adverse events (AEs) were captured for safety evaluation. Results: Seventy-eight patients received both vaccine doses, and 71 had post-vaccination samples. Most of the patients were IgM seronegative and IgG seropositive before vaccination. Pre-vaccination IgG levels were higher in CLL compared to MM patients (p=0.001), while post-vaccination IgG levels significantly increased in both CLL (p<0.0001) and MM (p<0.0001) patients. In actively treated CLL patients, the pre-vaccination IgG levels were significantly lower than in not actively treated patients (p=0.002). Post-vaccination IgG levels were lower in MM patients receiving antiviral prophylaxis concurrently with the vaccination (p=0.013). AEs were reported in 49.4% after the first dose and 48.7% after the second dose, mostly mild (local or low-grade systemic). One case of immune thrombocytopenia was noted. Conclusion: RZV demonstrated strong immunogenicity and acceptable safety in CLL and MM patients, significantly boosting IgG levels, even in actively treated or heavily pretreated patients.

Contextualising the narrative on energy efficiency as the first fuel in the clean energy transition, the energy efficiency first principle (EE1) was introduced in EU energy and climate policy with Energy Union communication in 2015 and made nonbinding with the EU Governance Regulation in 2018. In 2023, the EU legislators made EE1 legally binding to apply in policy, planning and investment decisions exceeding 100 million euros each and 175 million euros in the transport sector across all sectors that affect the energy system. By applying the multiple streams framework, this article analyses the role of policy entrepreneurs in the policy process and politics of making EE1 binding through qualitative text analysis of policy documents, position papers and reports from EU negotiations. The analysis shows how nonprofit and nongovernmental organisations such as the Regulatory Assistance Project, the European Climate Foundation and the Energy Efficiency Financial Institutions Group, as well as the European Commission and the rotating Council Presidency, were critical policy entrepreneurs for coupling the problem, policy and politics streams. The coupling was performed once a policy window was opened by the Paris Agreement on climate change, the entering office of the Ursula von der Leyen European Commission in late 2019, immediately presenting the European Grean Deal as the EU’s climate action plan and green growth strategy, and the energy crisis in Europe following Russia’s second war on Ukraine, leading the Commission to present the REPowerEU Plan and the EU Save Energy Strategy. This paper provides better knowledge of the policy processes and politics related to EE1, contextualising and concretising the concept of energy efficiency as the first fuel into binding law.

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.

Ingestion of corrosive agents is a well-known cause of extensive and severe gastrointestinal tract injury. Acids can result in significant acute complications throughout the gastrointestinal system. Herein, we present a case of total gastrointestinal necrosis after a patient ingested a large amount of concentrated hydrochloric acid. Of note, the patient developed an intestinal fistula six days following ingestion, requiring surgical intervention. This case underscores the potential for delayed gastrointestinal necrosis with high-volume and concentrated hydrochloric acid ingestion. Early CT evaluationto and multi-organ protectionis are crucial for such patients. For patients with no signs of perforation, multidisciplinary physicians should comprehensively evaluate the necessity of surgical exploration. In such cases, comprehensive treatment strategies can significantly improve outcomes. The purpose of this case report is to highlight the complexities and challenges in managing severe hydrochloric acid ingestion, to discuss the multidisciplinary approach required for such cases, and to contribute to the existing literature by providing detailed insights into the clinical presentation, treatment, and outcomes of a rare and severe instance of concentrated HCl ingestion.

It has been more than a century since Erlang published his paper in 1909. The classical queueing system for the M/D/c queue has been investigated by many authors. The key is to find the roots of an equation using explicit or numerical methods. We present an alternate form of explicit solution(s) of this/these root(s) using the Lambert-W function in this paper. In addition, the unsaturated probabilities of the number of customers in the system is derived explicitly in terms of this/these root(s). Finally, the mean number of customers in the system and the mean queueing delay are obtained from these probabilities. The exact queueing delay formula for the M/D/c queue is expressed in closed-form in terms of the root(s). Numerical results show that they are in excellent agreement with the numerical results published by Seelen, Tijms and Van Hoorn.

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.

The development of transport infrastructure is a key element of economic growth, social connectivity, and sustainable development. Many countries have historically underinvested in transport infrastructure, necessitating more efficient strategic planning in transport infrastructure investment projects implementation. This article addresses the selecting and scheduling of transport infrastructure projects, specifically within the context of drawing available resources from pre-allocated funds within a multi-annual budget investment program. The current decision-making process is largely based on expert judgment, lacking quantitative decision support methods. The authors propose a genetic algorithm as a decision-support tool that frames the problem as an NP-hard 0-1 multiple knapsack problem. The proposed genetic algorithm is unique for its matrix-encoded chromosomes, specially designed genetic operators, and a customized repair operator, which is implemented to address the large number of invalid chromosomes generated during the GA computation. The goal is to maximize the impact of allocated funds over a seven-year programming period, while respecting constraints specified by the funding authorities. In computational experiments, proposed GA is compared to an exact solution and is proved to be efficient in terms of quality of obtained solutions and computational time, highlighting its potential for enhancing strategic decision-making in transport infrastructure development.

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

Background/Objectives: Multiple sclerosis (MS) is a chronic neurological disorder characterized by various clinical presentations and manifestations that include biopsychosocial impediments. This study has three interrelated goals relevant to biopsychosocial functioning. The first is to compare cognitive, neuropsychological, and affective functioning and quality of life between patients with MS (PwMS) and a control group. The second is to examine whether cognitive and neuropsychological performance is affected by gender, and the third is to examine whether variation in QoL hinges on cognitive neuropsychological performance. Methods: This multicenter study was carried out among clinically stable PwMS under follow-up in two tertiary care units in urban Oman. Healthy controls, matched for age and sex, were also recruited as a comparison group. Data were collected using cognitive batteries sensitive to current reasoning ability and conventional neuropsychological batteries designed to measure verbal learning, visual-spatial ability, and processing speed. The affective range (anxiety and depressive symptoms) and quality of life (QoL) were also assessed. Results: The PwMS group scored lower on current reasoning ability, verbal learning, visual-spatial ability, and processing speed compared with the control group. The incidence of anxiety was higher in the PwMS group but there was no statistically significant difference in depressive symptoms. No significant differences were found in cognitive variables between the two sexes, except in visual-spatial ability, where women outperformed men. PwMS with low QoL scored lower on the attention and concentration indices than those with adequate QoL. According to QoL, no significant differences were observed in reasoning, verbal learning, and visual-spatial ability. Conclusions: The present sentinel study suggests that the Omani cohort with MS tends to have lower indices of current reasoning ability, visual and spatial memory and cognitive speed compared to control subjects. Gender differences are minimal, except for visual-spatial abilities where women outperform men. Quality of life significantly affects cognitive functioning. In general, the biopsychosocial impediment appears to be significant, indicating the need for comprehensive evaluation and care in the management of MS.

In this paper, we investigate a class of hierarchical variational inequalities (HVIPs, i.e., strongly monotone variational inequality problems defined on the solution set of multiple-set split common fixed point problems) with quasi-pseudocontractive mappings in real Hilbert spaces, which special cases can be found in many important engineering practical applications such as image recognizing, signal processing and machine learning. In order to solve HVIPs of potential application value, inspired by the primal-dual algorithm, we propose a novel accelerated cyclic iterative algorithm that combines the inertial method with a correction term and a self-adaptive step-size technique. Our approach eliminates the need for prior knowledge of the bounded linear operator norm. Under appropriate assumptions, we establish strong convergence of the algorithm. Finally, we apply our novel iterative approximation to solve multiple-set split feasibility problems and verify the effectiveness of the proposed iterative algorithm through numerical results.

Introduction: Multiple sclerosis (MS) is a long-term inflammatory disease that affects the central nervous system due to an abnormal immune response. Hormonal and enzyme changes in these patients can influence the progression and prognosis of the disease. In this research, the levels of cortisol, adrenocorticotropic hormone (ACTH), melatonin, and lactate dehydrogenase (LDH) in the blood of MS patients were studied.Methods: This study involved 50 MS patients and 50 healthy individuals. The levels of ACTH, melatonin, and cortisol in the blood were measured using specific ELISA kits. The data obtained were then analyzed statistically using SPSS software.Results: The findings revealed a significant increase in the levels of cortisol and LDH in MS patients (P<0.05), while the levels of melatonin and ACTH showed a significant decrease (P<0.05). The elevated cortisol levels may be attributed to chronic stress and inflammation associated with MS. An increase in LDH levels can indicate tissue damage caused by myelin destruction. On the other hand, decreased melatonin levels may lead to sleep disturbances and increased stress in these patients, while decreased ACTH levels may be linked to disruptions in the hypothalamic-pituitary-adrenal (HPA) axis. Conclusion: The hormonal and enzyme changes observed in MS patients illustrate the wide-ranging impact of the disease on various body systems. The increase in cortisol and LDH as well as the decrease in melatonin and ACTH could serve as useful biomarkers for predicting disease progression and managing the condition. These findings align with previous studies and contribute to a deeper understanding of the pathological mechanisms of MS.

This study focuses on the design, installation, and performance evaluation of a photovoltaic farm situated in Tulcea County, Romania, connected to a 20 kV distribution network. The farm, with a peak capacity of approximately 2800 kWp, benefits from Romania’s favorable climate conditions and supportive renewable energy policies. The analysis encompasses both the photovoltaic panel array and the electrical energy evacuation system. The substation at the park is equipped with technology that adheres to European standards and incorporates advanced features typical of modern electricity distribution networks. The assessment includes an evaluation of the park’s operational efficiency, with detailed calculations of the performance ratio and various power losses attributed to factors like temperature fluctuations, fouling, inverter efficiency, grid-related challenges, and availability issues. The farm contributes around 3620 MWh of electricity to the grid annually, demonstrating the effectiveness of photovoltaic installations in promoting sustainable energy solutions within regional energy networks.

As the smallest member of the fullerene family, C20 is yet to be discovered in planetary nebulae. In this work, we present a quantum chemical study via density functional theory (DFT) on the ionization tolerance of this molecule in the space environment. Considering that the ionization and excitation phenomena play key roles in alerting the lifetime of a molecule, we examined both ground and excited electronic states potential energy surfaces (PES) of C20 and its cations C20q+. Our theoretical results indicate that the C20 cage tolerates a positive charge as high as 13+ via characterizing local minimum geometries on both mentioned electronic states. We also explored theoretically and systematically, scenarios in which the electronic structure of neutral C20 is excited to very high spin multiplicity (beyond triplet state) and local minimum molecular geometries with cage structure are well characterized. We anticipate that such structural resistance to excitation and ionization deliver a prolonged lifetime necessary for the spectroscopic detection of this interesting molecule and its cations in space and potentially in planetary nebulea (PN).

Different polyurethanes (PUs) were synthesized with polycarbonate polyols of molecular weights 500, 1000 and 2000 Da. Their self-healing abilities at 20 °C were tested and their structural, thermal, and mechanical properties were analyzed. The PUs made with polycarbonates of molecular weights 500 (YC500) and 1000 Da (YC1000) exhibited self-healing at 20 °C and the self-healing time of YC1000 was the shortest. The high mobility of the short polymeric chains, the absence of crystallinity and the low degree of micro-phase separation favored self-healing at 20 °C in YC500. However, the presence of tack and the existence of allophanate species and urethane-carbonate and urea-carbonate hydrogen bonds disfavored self-healing. Consequently, the self-healing time at 20 °C of YC500 was longer than expected. On the other hand, YC1000 exhibited an “equilibrium” between the urethane-carbonate and urea-carbonate hydrogen bonds and carbonate-carbonate interactions among the soft segments, so a particular structural order was produced which was associated to its fastest self-healing at 20 °C. The PU made with the polycarbonate of molecular weight 2000 Da did not exhibit self-healing at 20 °C because its significant micro-phase separation and the presence of semi-crystalline soft domains.

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

The blood-brain barrier (BBB) acts as a structural and functional barrier for brain homeostasis. This review highlights the pathological contribution of BBB dysfunction to neuroimmunological diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS). The transmigration of massive lymphocytes across the BBB caused by the activation of cell adhesion molecules is involved in the early phase of MS, and dysfunction of the cortical BBB is associated with the atrophy of gray matter in the late phase of MS. In the onset of NMOSD, increased permeability of the BBB causes the entry of circulating AQP4 autoantibodies into the central nervous system (CNS). Recent reports have shown the importance of glucose-regulated protein (GRP) autoantibodies as BBB-reactive autoantibodies in NMOSD, inducing antibody-mediated BBB dysfunction. BBB breakdown has also been observed in MOGAD, NPSLE, and AE with anti-NMDAR antibodies. Our recent report demonstrated the presence of GRP78 autoantibodies in patients with MOGAD and the molecular mechanism responsible for GRP78 autoantibody-mediated BBB impairment. Disruption of the BBB may explain the symptoms in the brain and cerebellum in the development of PNS, as it induces the entry of pathogenic autoantibodies or lymphocytes into the CNS by autoimmunity against tumors in the periphery. GRP78 autoantibodies were detected in paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome and were associated with cerebellar ataxia with anti-P/Q type voltage-gated calcium channel antibodies. This review reports that therapies affecting the BBB that are currently available for disease-modifying therapies for neuroimmunological diseases have the potential to prevent BBB damage.

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: 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.

This comprehensive study looks at how operational conditions affect the performance of a novel seven-channel titania ceramic ultrafiltration membrane for the treatment of produced water. A Full factorial design experiment (23) was conducted to study the effect of the cross-flow operating factors on the membrane permeate flux decline and the overall permeate volume. Eleven experimental runs were performed for three important process operating variables: Transmembrane Pressure (TMP), Crossflow Velocity (CFV), and Filtration Time (FT). Steady final membrane fluxes and permeate volumes were recorded for each experimental run. Under the optimized conditions (1.5 bar, 1 m/s, and 2 hours), the membrane performance index demonstrated an oil rejection rate of 99%, a flux of 297 liters/m2·hr (LMH), a 38% overall initial flux decline, and a total permeate volume of 8.14 L. The regression models used for the steady-state membrane permeate flux decline and overall permeate volume led to the highest goodness of fit to the experimental data with a correlation coefficient of 0.999. A Multiple Linear Regression method and an Artificial Neural Network approach were also employed to model the experimental membrane permeate flux decline and analyze the impact of the operating conditions on membrane performance. The predictions of the Gaussian regression and the Levenberg-Marquardt backpropagation method were validated with a determination coefficient of 99 % and a mean square error of 0.07.

Digital solutions in the field of restorative neurology offer significant assistance, enabling patients to engage in rehabilitation activities remotely. This research introduces ReMoVES, an Internet of Medical Things (IoMT) system delivering telemedicine services specifically tailored for Multiple Sclerosis rehabilitation, within the overarching framework of the STORMS project. The ReMoVES platform facilitates the provision of a rehabilitative exercise protocol, seamlessly integrated into the Individual Rehabilitation Project, curated by a multidimensional medical team operating remotely. This manuscript delves into the second phase of the study, elucidating the technology employed, the outcomes achieved, and the practical, professional, and academic implications. The STORMS initiative, as the genesis of digital telerehabilitation solutions, aims to enhance the quality of life for Multiple Sclerosis patients.

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

Background: Inflammatory demyelination and impaired recovery processes result in permanent neurodegeneration and neurological disability in patients with multiple sclerosis (MS). In terms of smoldering MS, chronic neuroinflammation develops in the early period of the disease and leads to confirmed disability accumulation. There is a great need to identify biomarkers of neuro-degeneration and disease progression. Methods: We evaluated the concentrations of the param-eters of brain injury (NF-H, GPAF, S100B, UCHL1) in the cerebrospinal fluid (CSF) and the se-lected interleukins (ILs) in serum of 123 relapsing-remitting MS (RRMS) and 88 progressive MS (PMS) patients. Results: The levels of GFAP, S100B and UCHL were higher in the PMS group compared to RRMS as opposed to the levels of NF-H. We observed a positive correlation be-tween the selected pro-inflammatory cytokines and the parameters of brain injury. The Ex-panded Disability Status Scale score (EDSS) increased with GFA and NF-H levels and correlated with the selected ILs. The concentrations of S100B, UCHL1 and NF-H reflected the duration of MS symptoms. Conclusions: The levels of brain injury parameters in the CSF and the selected serum ILs in MS patients seem to be promising biomarkers to determine neurodegeneration and neuroinflammation in smoldering MS. Further studies are warranted in this respect.

The symptoms of multiple sclerosis (MS) are determined by the location of demyelinating lesions in the white matter of the brain and spinal cord. Currently, magnetic resonance imaging (MRI) is the most common tool for diagnosing MS, understanding the course of the disease, and analyzing the effects of treatments. However, undesirable components may appear during the generation of MRI, such as noise or intensity variations. Mathematical morphology (MM) is a powerful image analysis technique that helps to filter the image and extract relevant structures. Granulometry is an image measurement tool of MM that determines the size distribution of objects in an image without explicitly segmenting each object. While, several methods have been proposed for the automatic segmentation of MS lesions in MRI, in some cases only simple data preprocessing, such as image resizing to standardize the input dimensions, has been performed before the algorithm training. Therefore, this paper proposes an MRI preprocessing algorithm performing elementary morphological transformations in brain images of MS patients and healthy individuals to delete undesirable components and extract the relevant structures such as MS lesions. Also, the algorithm computes the granulometry in MRI to describe the size qualities of lesions and trains two artificial neural networks (ANN) to predict MS diagnosis. The computing of differences in granulometry measurements of an image with MS lesions and a reference image (without lesions) can determine the size characterization of the lesions. Then, the ANNs were evaluated with the validation set and the performance results (test accuracy = 0.9753, and cross-entropy loss = 0.0247) show the proposed algorithm can support the decision of specialists for diagnosing MS and estimating the disease progress, based on granulometry values.

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.

The use of chimeric antigen receptors (CAR-T cells) for the treatment of patients with malignant haematological diseases has become a well-established application, for conditions such as refractory or relapsed B cell acute lymphoblastic leukaemia (B-ALL), B cell lymphomas (BCL), and multiple myeloma (MM). Nearly 35,000 patients have received autologous CAR-T cells for the treatment of these conditions only in the USA. Since their approval by the Food and Drug Administration (FDA) in 2017, over 1200 clinical trials have been initiated globally and there are at least 10 different CAR-T cells with approval by different regulatory agencies around the globe. In the USA the Food and Drug Administration (FDA) has approved 6 commercial CAR-T cells that are widely distributed worldwide. At the time of this writing, several clinical trials have been performed in patients with solid tumours such as glioblastoma, renal and pancreatic cancer, as well as in patients with autoimmune conditions such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SS). There are also several studies showing the potential benefit of CAR-T cells for other non-malignant diseases such as asthma and even fungal infections. In this review, without pretending to cover all the current areas of treatments with CAR-T cells, we offer a brief summary of some of the most relevant aspects of the use of CAR-T cells for some of these conditions.

Global attention to climate change has surged since the advent of the Paris Agreement, intensifying the importance of measuring and managing carbon productivity indicators on a national level. Nevertheless, concerns persist regarding the reliability of such measurements because of inherent discrepancies in implementing and operating national-level carbon productivity indicators, coupled with their inherent uncertainty. This study proposes a multiple regression model to address these issues aimed at refining national-level carbon productivity indicators metrics, accounting for factors such as the gross domestic product and total greenhouse gas emissions by sectors. The objective was to offer insights into enhancing and effectively utilizing current indicators, enabling a more nuanced interpretation of the variation in the carbon productivity indicators across diverse industrial landscapes. This study showed that adjustments of the carbon productivity metrics reflect disparities in emissions across industrial structures, with countries characterized by high emissions from non-service industries showing improving trends. In addition, this paper proposes an auxiliary indicator estimating method for carbon productivity, emphasizing its utility in interpreting productivity indicators within the context of varying industrial compositions across OECD countries. This study underscores the inadequacies of the current national productivity estimating method, pinpointing areas requiring refinement. Specifically, the method for estimating the auxiliary indicator for carbon productivity guarantees enhanced rationality when integrated with current methodologies. Moreover, by elucidating the nuances of industrial structures, this study advocates for more sophisticated approaches to interpreting and managing the productivity indicators tailored to each unique economic landscape of each country. Nevertheless, the limitations stemming from data availability underscore the need for further research, particularly in refining the national-level carbon resource productivity indicators analyses and exploring the thematic productivity variations in greater depth. By addressing these gaps, future studies will contribute to a more comprehensive understanding of national-level carbon resource productivity indicators dynamics and reveal targeted strategies for sustainable development.

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

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

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.

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.

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.

Magnetic resonance (MR) image acquisitions are usually time-consuming, limiting utilization in neuroimaging. For multiple sclerosis (MS) patients, MR imaging plays a major role in drug therapy decision-making. The purpose of this study was to evaluate whether an ultrafast, T2-weighted (T2w), deep-learning-enhanced (DL), echo-planar-imaging-based (EPI) fluid-attenuated inversion recovery (FLAIR) sequence (FLAIRUF) that has been targeting neurological emergencies so far might even be an option to detect MS lesions of the brain compared to conventional FLAIR sequences. Therefore, 17 MS patients were enrolled prospectively in this exploratory study. Standard MR protocols and ultrafast acquisitions were conducted at 3 tesla (T), including three-dimensional (3D)-FLAIR, turbo/fast spin echo (TSE)-FLAIR, and FLAIRUF. Inflammatory lesions were grouped by size and location. Lesion conspicuity and image quality were rated on an ordinal five-point Likert scale, and lesion detection rates were calculated. Statistical analyses were performed to compare results. Altogether, 568 different lesions were found. Data indicated no significant differences in lesion detection (sensitivity and positive predictive value [PPV]) between FLAIRUF and axially reconstructed 3D-FLAIR (lesion size ≥ 3 mm × ≥ 2 mm) and no differences in sensitivity between FLAIRUF and TSE-FLAIR (lesion size ≥ 3 mm total). Lesion conspicuity in FLAIRUF was similar in all brain regions except for superior conspicuity in the occipital lobe and inferior conspicuity in central brain regions. Further findings include location-dependent limitations of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as artifacts such as spatial distortions in FLAIRUF. In conclusion, FLAIRUF could potentially be an expedient alternative to conventional methods for brain imaging in MS patients since the acquisition can be performed in a fraction of time while maintaining good image quality.

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

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.

Asparagus shoots are worldwide consumed, although most of such species have a restricted range, and several taxa still remain unstudied. In this work, a total of four taxa from different locations were scrutinized and compared with cultivated A. officinalis. All shoots were screened for saponins by LC-MS, and in vitro antiproliferative activities against the HT-29 colorectal cancer cell line (by MTT assay). The total saponins (TS) contained in the crude extracts ranged from 710.0 (A. officinalis) to 1258.6 mg/100 g dw (A. acutifolius). It stands out the richness of compounds detected in this work: a total of 47 saponins have been detected and quantified in the edible parts (shoots) of 5 taxa of Asparagus. The structure of all the saponins found present skeletons of the furostane and spirostane type. In turn, the structures with a furostane skeleton are divided into unsaturated and dioxygenated, both in the 20-22 position. The sum of dioscin and derivatives varied largely along the studied taxa. It reached the following percentages of TS: 27.11 (A. officinalis), 18.96 (A. aphyllus), 5.37 (A. acutifolius), and 0.59 (A. albus), while in A. horridus such compound remains undetected. Aspachiosde A, D, and M varied largely among samples, while a total of seven aspaspirostanosides were characterized in the analyzed species. Hierarchical cluster analysis of the saponin profiles clearly separated the various taxa and demonstrated that the taxonomic position is more important than the place from which the samples were acquired. Thus, saponin profiles have chemotaxonomic significance in Asparagus taxa. The MTT assay showed dose- and time-dependent inhibitory effects of several saponins extracts on HT-29 cancer cells, standing out the cell growth inhibition exercised by A. albus and A. acutifolius (GI50 of 125 and 175 µg/mL). This work constitutes a whole approach to evaluate the saponins from shoots of different Asparagus taxa and provide arguments for use them as functional foods.

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.

Due to advances in power electronics technology and the evolution of automation devices, the number of electrical devices that are sensitive to power quality is rapidly increasing, and for this reason, users are increasing their demand for high quality. To meet power quality demands, many power conversion devices are used, including dynamic voltage restorers (DVRs). DVRs are rec-ognized as devices that can effectively manage problems such as voltage segment, swells, and harmonics. DVR control requires many samples for harmonic compensation, which has the dis-advantage of being complicated to implement due to fast digital signal processing computation and the application of the cyclic discrete Fourier transform. In this paper, a high-precision DVR system configuration is proposed that compensates for harmonics using a periodically equivalent time-interval sampling technique and a novel circular structured memory filter. The proposed circular structured multi-pointer memory filter is an effective filter algorithm for high-precision input voltage measurement because it can remove noise and compensate for the delay of the phase angle of the filter in voltage measurement. A simulation and DVR prototype system was built, and the feasibility and effectiveness of the phase angle multi-filter voltage detection method and the compensation method were verified by experiments.

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

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

The cDNA sequences of the common gonadotrophic hormone α-subunit (ag-GTHα) and 13 of the specific follicle-stimulating hormone β-subunit (ag-FSHβ) of the giant Amazonian fish Ara-14 paima gigas, have been previously isolated by our research group. A synthesis of ag-FSH in HEK293 15 cells and its purification and preliminary characterization were also carried out. In the present work, 16 ag-FSH was obtained and purified from the same host cells and an extensive physical chemical 17 characterization was performed via RP-HPLC, HPSEC and MALDI-TOF-MS. Ag-FSH, when com-18 pared to human FSH (hFSH), showed a higher hydrophobicity by RP-HPLC and a higher molecular 19 mass (MM) via HPSEC. The same higher MM was also confirmed via MALDI-TOF-MS: 35,353 Da 20 for ag-FSH against 31,969 Da for hFSH. Its immunological activity was also confirmed via an hFSH 21 ELISA, in comparison with the highly purified pituitary preparation of hFSH-AFP7298A, from the 22 National Hormone and Pituitary Program (NHPP-USA). Finally, an in-vitro bioassay, based on the 23 stimulated release of 11-ketotestosterone (11-KT) from immature A. gigas testis, quantified its bio-24 logical activity in comparison with human chorionic gonadotropin (hCG) and with the WHO Inter-25 national Standard of recombinant hFSH (NIBSC-08/282) This suggests that injections of ag-FSH in 26 A. gigas and ag-FSH cDNA Gene Therapy applications should improve the reproductive functions 27 of this threatened species.

Multiple myeloma (MM) is a common type of cancer that unfortunately leads to a significant number of deaths each year. The majority of the reported MM cases are detected in the advanced stages, posing significant challenges for treatment. Additionally, all MM patients eventually develop resistance or experience relapse, therefore advances in treatment are needed. However, developing new anti-cancer drugs, especially for MM, requires significant financial investment and a lengthy development process. The study of drug repurposing involves exploring the potential of existing drugs for new therapeutic uses. This can significantly reduce both time and costs, which is typically a major concern for MM patients. The utilization of pre-existing non-cancer drugs for various myeloma treatments presents a highly efficient and cost-effective strategy, considering their prior preclinical and clinical development. The drugs have shown promising potential in targeting key pathways associated with MM progression and resistance. Thalidomide exemplifies the success that can be achieved through this strategy. This review delves into the current trends, the challenges faced by conventional therapies for MM, and the importance of repurposing drugs for MM. This review highlights a noncomprehensive list of conventional therapies that have potentially significant anti-myeloma properties and anti-neoplastic effects. Additionally, we offer valuable insights into the resources that can help streamline and accelerate drug repurposing efforts in the field of MM.

In this paper, we propose a method to find all efficient solutions of an interval multiple objective linear programming (IMOLP) problem with interval coefficients in the objective functions, the constraint matrix and the right-hand side vector. The set of all efficient solutions of an IMOLP problem can completely supply information to the decision makers in finding their most preferred solutions but, up to now, not all efficient solutions of an IMOLP problem can be found by known methods. A numerical example is given to illustrate the working of the proposed method.

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.

In the context of evolving perceptions of sexuality, particularly within the realm of health and disability, this study investigates the impact of multiple sclerosis (MS) on female sexual function and quality of life. A quantitative study involving 130 female MS patients aged 35 to 50 was conducted, employing measures such as The Female Sexual Function Index (FSFI), The Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19), and The Fatigue Severity Scale (FSS). Results indicate a significant association between greater sexual dysfunction and poorer quality of sex life, alongside the correlation of increased fatigue with diminished sexual satisfaction. Factors such as education level, time of diagnosis, and treatment regimen also influenced outcomes. Findings underscore the importance of supportive interventions, including counseling, to enhance the quality of sex life for women with disabilities, particularly those with MS.

In response to the burgeoning global demand for premium agricultural products, particularly within the competitive nut market, this paper introduces an innovative methodology aimed at enhancing the grading process for almonds and their shells. Leveraging state-of-the-art Deep Convolutional Neural Networks (CNNs), specifically the AlmondNet-20 architecture, our study achieves exceptional accuracy exceeding 99%, facilitated by the utilization of a 20-layer CNN model. To bolster robustness in differentiating between almonds and shells, data augmentation techniques are employed, ensuring the reliability and accuracy of our classification system. Our model, meticulously trained over 1000 epochs, demonstrates remarkable performance, boasting an accuracy rate of 99% alongside a minimal loss function of 0.0567. Rigorous evaluation through test datasets further validates the efficacy of our approach, revealing impeccable precision, recall, and F1-score metrics for almond detection. Beyond its technical prowess, this advanced classification system offers tangible benefits to both industry experts and non-specialists alike, ensuring globally reliable almond classification. The application of deep learning algorithms, as showcased in our study, not only enhances grading accuracy but also presents opportunities for product patents, thereby contributing to the economic value of our nation. Through the adoption of cutting-edge technologies such as the AlmondNet-20 model, we pave the way for future advancements in agricultural product classification, ultimately enriching global trade and economic prosperity.

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

The DNA Damage Response (DDR) network and the mitogen-activated protein kinase (MAPK) signaling pathway are crucial mechanisms for the survival of all living beings. An accumulating body of evidence suggests that there is a crosstalk between these two systems, thus favoring the appropriate functioning of multi-cellular organisms. On the other hand, aberrations within these mechanisms are thought to play a vital role in the onset and progression of several diseases, including cancer, as well as in the emergence of drug resistance. Here, we provide an overview of the current knowledge regarding alterations in the DDR machinery and the MAPK signaling pathway, as well as abnormalities in the DDR-MAPK functional crosstalk in multiple myeloma, the second most common hematologic malignancy. We also present the latest advances in the development of anti-myeloma drugs targeting crucial DDR- and MAPK-associated molecular components. These data could potentially be exploited to discover new therapeutic targets and effective biomarkers, as well as for the design of novel clinical trials. Interestingly, they might provide a new approach to increase the efficacy of anti-myeloma therapy by combining drugs targeting the DDR network and the MAPK signaling pathway.

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

This paper deals with the problem of determining the optimal capacity of Concentrated Solar Power (CSP) plants, especially in the context of hybrid solar power plants. This work presents an innovative analytical approach to optimize the capacity of concentrated solar plants. The proposed method is based on the use of additional non-dimensional parameters, in particular the design factor and the solar multiple factor. The paper presents a mathematical optimization model that focuses on the capacity of concentrated solar power plants where thermal storage plays a key role in the energy source. The analytical approach provides a more complete understanding of the design process for hybrid power plants. In addition, the use of additional factors and the combination of the proposed method with existing numerical methods allows for a more refined optimization, which allows for a more accurate selection of the capacity for specific geographical conditions. Importantly, the proposed method significantly increases the speed of computation compared to traditional numerical methods. Finally, the authors present the results of the analysis of the proposed system of equations for calculating the levelized cost of electricity (LCOE) for hybrid solar power plants. The nonlinearity of the LCOE on the main calculation parameters is shown.

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.

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

This study presents a detailed computational investigation aimed at identifying and evaluating potential small organic molecular scaffolds as inhibitors targeting the Pks13 protein, a critical enzyme in tuberculosis (TB) drug discovery. Our approach integrates multiple computational techniques, including quantitative structure-activity relationship (QSAR) modelling, compound library generation, molecular docking, biological activity prediction, re-evaluation of screened compounds, molecular dynamics (MD) analysis, and binding free energy estimation using the MM-GBSA approach. We developed a robust QSAR model using multiple linear regression (MLR) techniques, specifically tailored to predict the minimum inhibitory concentration (MIC) values of potential anti-TB agents. This model demonstrated excellent predictive performance, validated through rigorous internal and external validation procedures. Through molecular docking simulations, we identified five promising inhibitors Ethyl (R,Z)-2-(2-((2-chlorobenzyl) oxy)benzylidene)-5-(4-chlorophenyl)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo [3,2-a] pyrimidine-6-carboxylate (PKD1), (7R,9aR)-7-(2-hydroxyphenyl)-4-(2-methoxyphenyl)-3-methyl-7,8,9,9a-tetrahydroisoxazolo[5,4-b]quinolin-5(6H)-one (PKD2), (7-(4-methoxy phenyl)-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-5-yl)(4-(3-(trifluoromethyl)phenyl) piperazin-1-yl)methanone (PKD3), (8S,10S)-10-(((2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyl tetrahydro-2H-pyran-2-yl)oxy)-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-7,8,9,10-tetra-hydrotetracene-5,12-dione (PKD4), 3-(3,4-dimethylphenyl)-5-((2-(4-fluorophenyl)-2-oxoethyl) thio)-6-phenyl-2-thioxo-2,3,5,7a-tetrahydrothiazolo[4,5-d]pyrimidin-7(6H)-one (PKD5)with high binding affinities, prioritizing them based on their binding energies. These selected compounds were further assessed for their biological activity predictions, guiding the selection of candidates for experimental validation. Subsequent re-evaluation using absolute binding free energy estimation and MD simulations provided insights into the stability and dynamics of the protein-ligand complexes over time. Our findings highlighted the potential of identified compounds as stable binders within the Pks13-TE domain binding pocket, underscoring their viability as drug candidates. Additionally, binding free energy analysis using MM-GBSA reaffirmed the strong affinity of the proposed compounds towards Pks13. Our integrated computational approach offers a systematic and detailed framework for the identification and characterization of potential Pks13 inhibitors with specific relevance to TB drug discovery.

Over the past decade and a half, dynamic functional imaging has revolutionized the neuroimaging field. Since 2009, it has revealed low dimensional brain connectivity measures, has identified potential common human spatial connectivity states, has tracked the transition patterns of these states, and has demonstrated meaningful alterations in these transition and spatial patterns in neurological disorders, psychiatric disorders, and over the course of development. Recently, researchers have begun to analyze this data from the perspective of dynamic system and information theory in the hopes of understanding how these dynamics support less easily quantified processes, such as information processing, cortical hierarchy, and consciousness. Consciousness, in particular, appears to be strongly linked to entropy production in the brain. Little attention has been paid to the effects of psychiatric disease on entropy production in the human brain, however. Even disorders characterized by substantial changes in conscious experience have not been widely analyzed from this perspective. We begin to rectify this by examining the complexity of subject trajectories in state space through the lens of information theory. Specifically, we identify a basis for the dynamic functional connectivity state space and track subject trajectories through this space over the course of the scan. The dynamic complexity of these trajectories is assessed along each dimension of the proposed basis space. Using these estimates, we demonstrate that schizophrenia patients display substantially simpler trajectories than demographically matched healthy controls, and that this drop in complexity concentrates along specific dimensions. We also demonstrate that entropy generation in at least one of these dimensions is linked to cognitive performance. Overall, results suggest great value in applying dynamic systems theory to problems of neuroimaging and reveal a substantial drop in the complexity of schizophrenia patients’ brain function.

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.

Background/Purpose: Multimorbidity of malaria, anaemia, and malnutrition (MAMM) is a condition in which an individual cohabits with two or more of these health outcomes and is becoming an emergent public health concern in sub-Saharan African countries. The independent associations of a child’s demographic variables and socioeconomic disparities with a child’s health outcomes have been established in literature. However, the effects of the intersection of these factors on MAMM, while accounting for other covariates have not been studied. Therefore, this study aimed to determine how children’s sex, age and socioeconomic status interact to explain the variations in MAMM among children aged 6-59 months in Nigeria. Methods: Data from the 2018 Nigeria Demographic and Health Survey and the 2018 National Human Development Report (NHDR) were used. The study includes weighted samples of 10,184 children aged 6-59 months in Nigeria. A three-level multilevel mixed effect ordinal logistic regression model such that individual characteristics at level 1 are nested in communities at level 2 and nested in states at level 3 was used. Subsequently, predictive probability charts and average adjusted probability tables were used to interpret the intersectional effects. Five models were created in this scenario. Model 1 is the interaction between the child's sex and wealth status; model 2, child's sex and age; model 3 is between child's age and wealth status; model 4 has the three 2-way interactions of child's sex, age, and household wealth status, and model 5 includes model 4 and the 3-way interactions between a child's sex, age, and wealth quintiles. Results: The prevalence of children with ‘none of the three diseases’ outcomes was 17.3% (1767/10,184), while, 34.4% (3499/10,184) had ‘only one of the diseases’, and 48.3% (4,918/10,184) cohabit with ‘two or more’ of MAMM. However, in the multivariate analyses, model 3 was the best fit compared with other models, so, that the two-way interaction effects of a child's age and wealth status are significant predictors in the model. Children aged 36-47 months living in the poorest households have the probability of 0.11, 0.18, and 0.32 of contracting MAMM above the probability of children of the same age and live in the middle, more prosperous and richest households, respectively, while all other covariates are held constant. Thus, the variation in MAMM over a child's age differs depending on the household wealth quintile. In other words, as the children grow older, variations in MAMM become more evident between the rich and the poor household. Conclusion: Therefore, it is recommended that policies that are geared toward economic redistribution will help bridged the disparities observed in multiple diseases among children aged 6-59 months in Nigeria

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.

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

MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in mul-tiple myeloma (MM) pathogenesis by regulating gene expression. This study evalu-ated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide/dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both corre-lated with the depth of response and mir-16 with sustained response to LD treatment. The ratios of both miR-16 and miR-21 expression levels (prior to LD treat-ment/diagnosis) below 2 predicted a shorter time to response (P = 0.027) and a longer time to next treatment (P = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels corre-lated with disease variables and treatment outcomes.

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

Multiple sclerosis is an autoinflammatory condition that results in damage of myelinated neurons in affected patients. While disease-modifying treatments have been successful in slowing the progression of relapsing remittent disease, most patients still progress to secondary progressive disease that is largely unresponsive to disease-modifying treatments. Similarly, there is currently no effective treatment for patients with primary progressive MS. Innate and adaptive immune cells in the CNS play a critical role in initiating an autoimmune attack and in maintaining the chronic inflammation that drives disease progression. In this review, we will focus on recent insights into the role of T cells with regulatory function in suppressing the progression of MS, and, more importantly, in promoting the remyelination and repair of MS lesions in the CNS. We will discuss the exciting opportunity to genetically reprogram regulatory T cells to achieve immune suppression and enhance repair locally at sites of tissue damage, while retaining a fully competent immune system outside the CNS. In the future, reprogramed regulatory T cells with defined specificity and function may provide life medicines that can persist in patients and achieve lasting disease suppression after one cycle of treatment.

Multiple myeloma (MM) accounts for about 10 to 15% of all diagnosed hematologic malignancies and about 1-2% of all cancer cases. Approximately 80-90% of MM patients develop bone disease and the changes rarely regress. It is only possible to stop or slow their progression. A major role in bone destruction in MM is attributed to the Wnt signaling pathway, and its action can be modified by various types of interventions including training and diet. Therefore, the aim of this project was to evaluate the effects of a Nordic Walking (NW) training cycle and intermittent fasting (IF) on the levels of selected bone turnover markers associated with the Wnt pathway in patients with MM. Results from 35 patients divided into training (NW and IF NW) and non-training (IF and control) groups were included in the analysis. A 6-week training cycle involving 60-minute workouts 3 times a week was conducted. Body mass and composition and the levels of: vitamin D, calcium and phosphorus, beta2-microglobulin and albumin were examined before and after completion of training cycle. Markers of bone turnover were also determined: sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), osteoprotegrin (OPG), osteopontin (OPN) and Tartrate-resistant acid phos-phatase 5b (TRACP 5b). There was no negative effect of IF or combined training and fasting on the nutritional status of the patients (the level of albumines was unchanged). Both training groups showed an increase in serum concentrations of the active metabolite of vitamin D (IF NW and NW: p=0.001 and p=0.022, re-spectively). The change in the concentration of this vitamin negatively correlated with the con-centration of TRACP 5b (r=-0.413, p=0.014). Evaluating the concentrations of markers related to bone turnover, a reduction in the concentrations of SOST (time: p=0.026, time vs. group: p=0.033) and TRACP 5b (time: p

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

Naturally fermented dairy products are an important component of the human diet. They are a valuable source of nutrients as well as vitamins and minerals. Their importance as a source of probiotic bacterial strains should not be overlooked. A number of studies highlights the positive effects of species of the Lactobacillacea on the intestinal microbiota, the overall homeostasis of the body, as well as a complementary treatment for some diseases. However, data on the effects on intestinal epithelial cells of postmetabolites released by bacteria are incomplete. This is likely due to the fact that these effects are species and strain specific. In the present study, we investigated the effects of postmetabolites produced by a pre-selected candidate probiotic strain Limosilactobacillus fermentum on HT-29 intestinal epithelial cells. Our data showed a pronounced proliferative effect, evaluated by flow cytometry, quantification of cell population, and determination of mitotic index. This was accompanied by stabilization of the cell monolayer, measured by increase of TEER (trans epithelial electric resistance) and reorganization of actin filaments. The data obtained are a clear indication of the positive effects, that the products secreted by L. fermentum strain 53 have on the intestinal epithelial cells.

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

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

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.

Background: Several studies recently confirmed the emergence of resistance to antimalarial drugs in sub-Saharan Africa. Multiple first-line treatment (MFT) is one of the measures envisaged to respond to the emergence and spread of this resistance. The aim of this study was to identify perceived advantages and disadvantages of several MFT deployment strategies and to better understand potential implementation drivers and barriers. Methods: A qualitative survey was conducted in seven sub-Saharan countries amongst key opinion-leaders, national decision-makers, and end users. A total of 200 individual interviews were conducted and findings were analyzed following a thematic inductive approach. Results: From a policy perspective, the new MFT intervention would require endorsement at the global, national, and regional levels to ensure its inclusion in guidelines. Funding of the MFT intervention could be a bottleneck due to costs associated with additional training of healthcare workers, adaptation of drug delivery mechanisms, and higher costs of drugs. Concerning the MFT deployment strategies, a slight preference for the segmentation strategy was expressed over the rotation and geographic approaches, due to the perception that a segmentation approach is already in place at country level. Conclusions: The findings highlighted the need for a collective approach to MFT deployment through the engagement of stakeholders at all levels of malaria management.

German noise action plans aim to reduce negative health outcomes from noise exposure and identify quiet areas free of noise pollution. Quiet area identification in German noise action plans is based primarily on noise mapping and spatial analysis and not empirical or qualitative data about acoustic environments, thus leaving a gap in the understanding of the quality of formally recognized quiet areas in noise action plans. This work presents a comparative empirical case study in Dortmund, Germany, with the aim to describe the diurnal dB(A) and biophonic properties of quiet areas versus noise 'hot spots'. Sound observations were collected (n=282,764) in five different natural or recreational land use patch types larger than four acres within 33 proposed quiet areas in Dortmund (n=70) and 23 noise hot spots between April 27^th, 2022 and March 2^nd, 2023. We find that quiet areas are on average more than 20 dB(A) quieter than noise hot spots almost every hour of the day. Forests, managed tree stands, cemeteries, and agriculture diel patterns are dominated by dawn dusk chorus in spring and summer, whereas sport and recreation as well as noise hot spots are dominated by traffic and human noise. A novel composite biophony mapping procedure is presented that finds distinct temporal distribution of biophony in forested and agriculture peri-urban locations positively associated with patch size, distance away from LDEN > 55, proximity to water, and the number of vegetation layers in the plant community. Anthrophony distribution dominates urban land uses in all hours of the day, but expands during day and evening and contracts at night and in dusk hours. The procedures presented here illustrate how qualitative information regarding quiet areas can be integrated into German noise action planning.

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.

: 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%.

In the modern power grid, characterized by the increased penetration of power electronics and extensive utilization of renewable energy, inverters-based power plants play a pivotal role as the principal interface of renewable energy sources (RESs) and the grid. Considering the stability characteristics of grid-following (GFL) inverters when the grid is relatively weak, the application of grid-forming (GFM) controls becomes imperative to enhance the stability of the entire power plant. Thus, there is an urgent need for suitable and effective models to study the interaction and stability of the paralleled inverters employing GFL and GFM controls. Thus, the small-signal modeling with full-order state space model and eigenvalues analysis is presented in this paper. First, the small-signal state-space model of the individual GFL and GFM inverters is obtained considering the control loop, interaction, reference frame, transmissions, and time delays. Then, the models of the individual inverter are extended to the hybrid inverters to study the effects of the GFM inverters on the small- signal stability of the entire system. And, the impacts of the inertia and damping are analyzed by the eigenvalues of the state-transition matrix. Case comprising three parallel GFL inverters and two GFL inverters with one GFM inverter, respectively, are studied to examine the effectiveness and accuracy of the model. Finally, the stability margin obtained from the eigenvalue analysis of the entire system is verified by time-domain simulations.

Statistical denoising techniques have been well studied, however many challenges still remain. This 9 article focuses on determining the least necessary number of significant samples in a statistical pop-10 ulation sampling, while minimizing the impact on the statistical detection of the fiber Bragg grating 11 (FBG) power spectra. This is achieved by using Bayesian decision making, small population statis-12 tics while excluding false detection. First, we investigate the impact of two-sided sliding window 13 technique applied near the cell under the test. The window size varies from 8 to 60 samples. The 14 considered maximum size of population sampling is connected with the number of wavelength 15 samples within the bandwidth of the symmetrical FBG power spectra peaks. Regarding the sym-16 metry of FBG power spectra peaks and the possible reduction of computational demands, we inves-17 tigate the impact of a one-sided sliding window. This enables to achieve less processing latency for 18 real time applications thus brings benefits to FBG-based fiber optical sensing. Both, two- and one-19 sided small population sampling techniques are then experimentally verified. Detection results are 20 analyzed in depth via calculating detection thresholds by using the small size window sliding along-21 side the waveband. From results achieved, it was found that the normality three-sigma rule does 22 not need to be followed while using the small population sampling. Experimental demonstrations 23 and analyses showed that the proposed concept of denoising and statistical threshold detection 24 based on the sliding window does not depend on the prior knowledge of probability distribution 25 functions of the FBG power spectra peaks level and background noise. We have also found that the 26 thresholds’ adaptability mainly depends on the statistical numerical characteristics of the above ad-27 ditive mixture of the FBG power spectra peaks signals and background noise.

This study investigates the long-term stability of the Suomi National Polar-orbiting Partnership (S-NPP) Visible Infrared Imaging Radiometer Suite (VIIRS) moderate-resolution Thermal Emissive Bands (M TEBs; M12 – M16) covering a period from February 2012 to August 2020. It also assesses inter-sensor consistency of the VIIRS M TEBs among three satellites-S-NPP, NOAA-20, and NOAA-21 over eight months spanning from March 18 to November 30, 2023. The field of interesting is limited to the ocean surface between 60°S and 60°N, specifically under clear-sky conditions. Taking radiative transfer modeling (RTM) as the transfer reference, we employed the Community Radiative Transfer Model (CRTM) to simulate VIIRS TEB brightness temperature (BTs), incorporating European Centre for Medium-range Weather Forecasts (ECMWF) reanalysis data as inputs. Our results reveal two key findings. Firstly, the reprocessed S-NPP VIIRS TEBs exhibit a robust long-term stability, as demonstrated through analyses of the observation minus background BT differences (O-B ∆BTs) between VIIRS measurements (O) and CRTM simulations (B). The drifts of the O-B BT differences are consistently less than 0.105 K/Decade across all S-NPP VIIRS M TEB bands. Notably, observations from VIIRS M14 and M16 stand out with drifts well within 0.04 K/Decade, reinforcing their exceptional reliability for climate change studies. Secondly, excellent inter-sensor consistency among these three VIIRS instruments is confirmed through the double-difference analysis method (O-O). This method relies on the O-B BT differences obtained from daily data. The mean inter-VIIRS O-O BT differences remain within 0.08 K for all M TEBs, except for M13. Even in the case of M13, the O-O BT differences between NOAA-21 and NOAA-20/S-NPP have values of 0.312 K and 0.234 K, respectively, which are comparable to the 0.2 K difference between some TEBs among VIIRS and MODIS. These disparities are primarily attributed to the significant differences in the Spectral Response Function (SRF) of NOAA-21 compared to NOAA-20 and S-NPP. Our study confirms the RTM-based TEB quality evaluation method’s versatility and effectiveness in assessing long-term sensor stability and inter-sensor consistency. The double-difference approach effectively mitigates uncertainties and biases inherent to CRTM simulations, establishing itself a robust mechanism for assessing inter-sensor consistency. In addition, we’ve observed that, except for M13, M12 always exhibits larger spatial variations of O-O BT differences with greater uncertainties compared to the other M TEBs. The influence of solar contribution through sea surface reflection on the Top of Atmosphere (TOA) radiance measurements during daytime in M12 should not be underestimated.

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.

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.

Seeds from several Ribes taxa were surveyed for phenolic compounds and in vitro antiproliferative activity against HT-29 colorectal cancer cells. Total phenolic compounds were analysed through the Folin-Ciocalteu procedure, while phenolic profiles were analysed by LC coupled to a single mass spectrometer Orbitrap using an electrospray interface (ESI). Antitumor effects were established using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Total phenolics ranged from 11.4 in R. alpinum to 94.8 mg of caffeic acid equivalents (CAE)/g in R. nigrum 'Koksa'. Concerning phenolic compounds, four were hydroxylated benzoic acids, four cinnamic acid derivatives, eight flavonoids, and nine flavonoid glycosides. The growth inhibition against HT-29 cancer cells was exercised much better by R. nigrum 'Koksa' and Ribes 'Erkeeni' (GI50 37 and 42 µg/ml). All Ribes extracts, except R. nigrum 'Hara katarlik', showed higher activity than that of R. rubrum (GI50 at 72 h: 99 µg/ml). Interestingly, the highly bioactive extract from Ribes 'Erkeeni' contains all detected phenolics, while R. nigrum 'Koksa' lacks only populnin. Therefore, the high bioactivity found for such extracts could be due to a synergy due to all detected compounds. This work constitutes a comprehensive action for expanding knowledge on the phenolic profiles and antitumor activity of GLA-rich Ribes seeds.

Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the development of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, the review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

This study focuses on the potential medicinal properties of Campsis radicans L. extracts and its aim is to investigate the antioxidant and antiproliferative effects of these extracts on the human colon adenocarcinoma cell line (HT-29). Cytotoxic activity in the HT-29 cell line was evaluated, and the 3-dimensional structures of phenolic compounds were obtained using the GC-MS method. Docking simulations were performed with AutoDock Vina, targeting proteins that are crucial in the apoptotic pathway (Bax, Bcl-2, and Caspase-3). Drug similarities and ADMET estimates of the phenolic compounds were obtained from databases. The highest antioxidant activity of Campsis radicans L. plant was observed in ethanol and water extracts, with notable inhibition capacities. While the total phenolic content was highest in ethanol, water, and ether extracts respectively the total flavonoid content was highest in ethanol, then ether, and water extracts. Certain elements were undetectable in mineral determination, and others exceeded the toxic doses for plants. The water extract exhibited dose-dependent cytotoxic activity in the HT-29 cell line, with an IC50 value of 4.47 mg/mL. Molecular docking results revealed the binding of phenolic molecules to the active sites of apoptotic pathway proteins. The findings suggest that Campsis radicans L. plant possesses cytotoxic properties, significant phenolic and flavonoid content, and a high antioxidant capacity. These properties make it a potential candidate for treatment use, emphasizing its potential therapeutic value in the HT-29 cell line. Further research and exploration on the identified phenolic compounds could contribute to the development of novel therapeutic agents.

Commuting is a vital travel channel for college students throughout their higher education career; nevertheless, excessive commute time negatively impacts students’ school satisfaction, academic achievement, health, and quality of life. Meanwhile, few studies have explored students’ commute time, covering a large population and scope. Therefore, this study analyzes the dwelling type that influences college and graduate students’ school commute times in the Seoul Metropolitan Area, using data from the 2016 Household Travel Diary Survey. This study uses spatial data on housing development to classify five dwelling types (i.e., new town, housing site development, Seoul, Incheon, and Gyeonggi-do). A multiple linear regression model empirically analyses students’ household and personal characteristics. The results reveal that dwelling type significantly affects students’ commute time. Specifically, Students living in Seoul have a shorter commute to school than those living in new towns. Socioeconomic characteristics have less effect on college and graduate students' school commute time. This study discusses the problem of excessive commuting of college and graduate students in new towns.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

The performance of the presurgical test (preSurg) for temporal lobe epilepsy (TLE) was evaluated via video-electroencephalography (VEEG), electroencephalography (EEG), 99mTc-HmPAO single-photon emission tomography (SPECT) and 1.5 T magnetic resonance imaging (MRI) in a group of 112 men (37.0 ± 1.1 years) and 106 women (39.7 ± 1.1 years) operated on for TLE. The epileptic zone (EZ) was adequately identified to determine whether the patient reached an Engel I grade (EI) at least one year postop. Accuracy was evaluated by the coefficient α, ranging from 3 (when result = EZ) to 2 (result in the same hemisphere as the EZ), 1 (noninformative result) or 0 (EZ in the contralateral hemisphere). The simplicity of diagnosis was defined as the number of preSurg surgeries needed to identify the EZ. EI was obtained in 85.8% of patients even though 42.2% of patients had noninformative MRI results. For preSurg α was (mean ± SEM) = VEEG (2.83 ± 0.04) &gt; MRI (2.14 ± 0.08) &gt; EEG (1.87 ± 0.09) &gt; SPECT (1.71 ± 0.09). The accuracy (combination of sensitivity and specificity) was calculated as follows: VEEG (0.797) &gt; MRI (0.518) &gt; EEG (0.446) &gt; SPECT (0.360). The likelihood positive ratio was greater, and the likelihood negative ratio was lower for VEEG. The most relevant factor for the regression model was VEEG (3.106) &gt; MRI (2.558) &gt; EEG (1.905), and the factors were not significantly related to SPECT. EZs in EI patients with low simplicity were identified mainly by VEEG. A very good postoperative outcome can be obtained even in TLE patients with no lesions on MRI. The VEEG is the most reliable preSurg test and may be the only reliable test for patients with very low simplicity (i.e., difficult).single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

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

Building energy demand impacts a myriad of interconnected economic, societal, and environmental aspects. As a result, Buildings Energy Models (BEM) play an important role in the process of urban design and planning. While previous studies have investigated the effects of building interventions on energy efficiency, their applicability may be limited due to the BEM’s high computational complexity. This limits their ability to systematically study important aspects of energy demand on a large scale. The development of Machine Learning Models (MLM) allows to design the required detailed analysis and solutions, while reducing the computational burden, making MLM attractive for urban designers. The capability of MLM to generalize well for multiple contexts (in our case, multiple buildings) is a crucial contributor to their applicability. However, the validation process in a wider context is often overlooked, therefore its generalization capabilities are not quantified. In this paper, we present a framework to train and validate a surrogate model derived from a physics-based BEM. Our method employs a Multiple Linear Regression model to predict Energy Use Intensity (EUI) for office buildings in Singapore using 36 input parameters (covariates), based on a training dataset of 23,000 samples. Model validation is performed by comparing the results of the Surrogate Model (SM) to a widely used BEM for a sample of 120 buildings. Our results indicate that the SM has an accuracy of NRMSE of 13%, NMBE of −3.56%, and R2 of 0.92, which suggests it can effectively and accurately predict building EUI. We also conduct a sensitivity analysis, which indicates that the parameters associated with internal loads and internal space usage are the most influential. Additionally, we present a reduced order model trained with only the 11 most influential parameters, which exhibits negligible loss in accuracy compared to the full SM while providing reduced complexity. Finally, we demonstrate an application of our SM to evaluate energy efficiency under uncertainty scenarios. The analytically derived results indicate a potential reduction of EUI of offices in Singapore from 227kWh/m2 to 99kWh/m2 by altering the building parameters that were identified as most influential.

Safety limits application has always been a traditional approach to ensure the safe operation of electro-mechanical systems within many industries including automated vehicles, robotics, aerospace, traditional automotive, railways, manufacturing, etc. In all of these applications, control and safety limits are usually hard-coded into the production firmware and are fixed throughout the entire product life cycle. Currently, due to the evolving needs of automated systems like automated vehicles and robots, this traditional approach does not address all the use cases and scenarios to ensure safe operation. Especially for data-driven machine learning applications that constantly evolve and learn over time, it is important to be able to adjust the safety limits application strategy to be more flexible and adaptable based on different Operational Design Domains (ODDs) and scenarios. Our ITSC conference paper ~\cite{4} introduced the concept of a new safety limits application strategy called the Dynamic Control Limits Application (DCLA) strategy that supports the flexible application of diverse limits profiles based on the parameters involved within the dynamic scenario at different layers of the Autonomy software stack.This paper extends the DCLA strategy to derive the complete methodology for safety limits application based on ODD elements, scenario identification and scenario classification using Decision Making Engines. It leverages the layered architecture introduced in the ITSC conference paper to implement the Decision Making (DM) algorithms. Another important extension is the use of cloud infrastructure that is based on the Vehicle-to-Infrastructure (V2I) technology to store the scenarios and the limits mapping to serve as a ground truth and/or a backup mechanism in case of errors or failures associated with the main Decision Making (DM) Engine. There is also a focus on providing a more comprehensive list of scenarios and a custom built experimental dataset to cover the maximum ODD elements, and multiple tables of safety limits to be chosen from, which eventually helps in creating different safety limits application profiles. These distinct safety limits application profiles are based on the scenario parameters that are perceived by the system upon which the Decision Making algorithms are applied or trained. This systematic approach can be used within the industry for any of the future automated vehicles and systems until Level 5 Autonomy.

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

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.

In the evolving landscape of vibration analysis, the integration of machine learning technologies for semi-automated analytical processes presents challenges in establishing clear cause-and-effect relationships in decision-making formulas. This research addresses this gap by exploring analytical diagnosis through residual signals, enabling the identification of anomalies and underperformance in machinery. Vibration signature analysis, focusing on distinctive vibration patterns, proves instrumental in detecting bearing defects and optimizing maintenance for enhanced operational efficiency and safety. Mathematical modeling, particularly worst-case analysis, provides a structured framework for decision-making under uncertainty. The research employs descriptive methods to analyze bearing wear data, transforming it into quantitative data for multiple regression equations. The derived equations reveal the dominance of harmonics in determining bearing wear stages, with PeakVue and overall vibration further indicating damage progression. The findings emphasize the significance of harmonic detection and high-frequency vibration analysis in predicting bearing health, offering a comprehensive approach to enhance machinery reliability. The study concludes with practical recommendations for bearing damage diagnosis based on the developed mathematical models, providing valuable insights for predictive maintenance strategies.

The overwhelming evidence supports the assertion that the climate is undergoing change. Understanding the perception of locals of the magnitude of climate change and its influence on non-timber forest products (NTFPs) challenge at a global scale. Although studies on climate change, value addition, and the multiple uses of NTFPs and their impact on local livelihoods have been conducted, locals' perceptions of these factors have not been fully explored. This study aims to assess various social factors, including education, gender, and religion, and their influence on locals' perceptions of the abovementioned factors. The research focused on five regions where NTFPs are prevalent in Ghana (Western North, Bono, Ahafo, Ashanti, and Eastern regions). To investigate the impact of social factors on local perceptions of climate change, value addition, and the multiple values of NTFPs within rural communities, a total of 732 interviews with a team of interviewers across these five regions in Ghana were carried out. We applied a logistic regression model to assess the social factors and their influencing locals’ perceptions of the mentioned variables. It was revealed that age, gender, education, and occupation did not significantly influence locals' perceptions of climate change. However, religion was found to influence locals' perceptions of climate change. Furthermore, the results demonstrated that gender (P<0.000328) and education (P<0.00426) strongly influenced locals' perceptions of value addition to NTFPs. In contrast, religion and constraints (related to time, finance, and skills) did not significantly influence locals' perceptions. Additionally, it was observed that gender (0.00132), education (0.00692), and religion (8.12e-05) significantly influenced how locals perceive and use NTFPs. In conclusion, this study provides valuable insights into the intricate interplay among local perceptions, climate change, value addition, multiple uses of NTFPs, and the capacity of NTFPs to enhance the well-being of forest fringe communities. These findings underscore the importance of comprehensive, tailor-made interventions that consider local perspectives and adhere to sustainable approaches, with the aim of optimising the positive impacts of NTFPs in poverty alleviation and overall community development.

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.

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

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

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

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.

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.