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Isocitrate Dehydrogenase-1 (IDH1) is commonly mutated in lower-grade diffuse gliomas. The IDH1R132H mutation is an important diagnostic tool for tumor diagnosis and prognosis; however, its role in glioma development, and its impact on response to therapy, is not fully understood. We developed a murine model of proneural IDH1R132H-mutated glioma that shows elevated production of 2-hydroxyglutarate (2-HG) and increased trimethylation of lysine residue K27 on histone H3 (H3K27me3) compared to IDH1 wild-type tumors. We found that using Tazemetostat to inhibit the methyltransferase for H3K27, Enhancer of Zeste 2 (EZH2), reduced H3K27me3 levels and increased acetylation on H3K27. We also found that, although the histone deacetylase inhibitor (HDACi) Panobinostat was less cytotoxic in IDH1R132H-mutated cells (either isolated from murine glioma or oligodendrocyte progenitor cells infected in vitro with a retrovirus expressing IDH1R132H) compared to IDH1-wild-type cells, combination treatment with Tazemetostat is synergistic in both mutant and wild-type models. These findings indicate a novel therapeutic strategy for IDH1-mutated gliomas that targets the specific epigenetic alteration in these tumors.

Introduction: This study explores the shift toward predictive maintenance through real-time data analytics to minimize machine downtime and improve machinery insights in industrial environments. Predictive maintenance aims to enable proactive interventions by predicting failures, enhancing operational efficiency. Methods: The research was conducted in three stages. First, BA Glass equipment was sensorized using OPC Router and PowerStudio SCADA to facilitate real-time data extraction. A predictive maintenance algorithm was then developed in Python to analyze sensor data, predict failures, and trigger alarms. Finally, various forecasting models, including Linear and Polynomial Regression, Simple and Double Exponential Smoothing, ARIMA, and Prophet, were evaluated using a combination of blocked cross-validation and rolling window methodologies. The algorithm calculated performance metrics such as MSE, RMSE, and MAE for different parameter configurations and training sizes. Results: A comparative analysis between wired and wireless sensors concluded that wireless sensors, although more expensive, were more practical and interchangeable in the factory setting. The results from the evaluation of prediction models showed that the Double Exponential Smoothing (DES) model with an additive damped trend and linear models performed best for datasets with daily seasonality and gradual oscillations. For datasets with stable trends and higher frequency oscillations, ARIMA and Prophet models proved to be more accurate. Discussion: These findings suggest that the choice of sensors and prediction models can significantly impact the effectiveness of predictive maintenance systems. Wireless sensors offer long-term benefits in terms of flexibility and practicality, while the DES model and ARIMA/Prophet models are optimal depending on the dataset characteristics. This research highlights the value of real-time data analytics and predictive models in industrial environments for reducing downtime and improving decision-making. [ABSTRACT FROM AUTHOR]

Background: The myelin sheath ensures efficient nerve impulse transmission along the axons. Remyelination is a spontaneous process that restores axonal insulation, promoting neuroprotection and recovery after myelin damage. There is an urgent need for new pharmacological approaches to remyelination and to improve the most effective molecules. Some glucocorticoids (GC) were identified through phenotypical screens for their promyelinating properties. These GC compounds share the ability to bind the Smoothened (Smo) receptor of the Hedgehog (Hh) pathway. Gaining a deeper insight into how they modulate Smo receptor activity could guide structure-based studies to leverage the GCs' potent promyelinating activity for a more targeted approach to remyelination. Methods: Here we focused on clarifying the mechanism of action of Budesonide, a GC known to bind the Smo cysteine-rich domain (CRD) and prevent Smo translocation to the cilium in fibroblasts. Our study employed a combination of cellular, biochemical and molecular dynamics approaches. Results: We show that treating oligodendroglial cells with Budesonide promotes myelination of synthetic axons and reduces Smo CRD conformational flexibility. This inhibits the Smo-mediated canonical signaling while activating the Liver Kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) pathway, leading to Myelin basic protein (MBP) expression. Discussion: These insights pave the way for pharmacological targeting of Smo CRD to enhance oligodendrocyte precursor cells (OPCs) differentiation and improve remyelination. [ABSTRACT FROM AUTHOR]

Myelinating oligodendrocytes arise from the stepwise differentiation of oligodendrocyte progenitor cells (OPCs). Approximately 5% of all adult brain cells are OPCs. Why would a mature brain need such a large number of OPCs? New myelination is possibly required for higher‐order functions such as cognition and learning. Additionally, this pool of OPCs represents a source of new oligodendrocytes to replace those lost during injury, inflammation, or in diseases such as multiple sclerosis (MS). How OPCs are instructed to differentiate into oligodendrocytes is poorly understood, and for reasons presently unclear, resident pools of OPCs are progressively less utilized in MS. The complement component 1, q subcomponent‐like (C1QL) protein family has been studied for their functions at neuron–neuron synapses, but we show that OPCs express C1ql1. We created OPC‐specific conditional knockout mice and show that C1QL1 deficiency reduces the differentiation of OPCs into oligodendrocytes and reduces myelin production during both development and recovery from cuprizone‐induced demyelination. In vivo over‐expression of C1QL1 causes the opposite phenotype: increased oligodendrocyte density and myelination during recovery from demyelination. We further used primary cultured OPCs to show that C1QL1 levels can bidirectionally regulate the extent of OPC differentiation in vitro. Our results suggest that C1QL1 may initiate a previously unrecognized signaling pathway to promote differentiation of OPCs into oligodendrocytes. This study has relevance for possible novel therapies for demyelinating diseases and may illuminate a previously undescribed mechanism to regulate the function of myelination in cognition and learning. [ABSTRACT FROM AUTHOR]

CSF1R-related disorder (CSF1R-RD) is a neurodegenerative condition that predominantly affects white matter due to genetic alterations in the CSF1R gene, which is expressed by microglia. We studied an elderly man with a hereditary, progressive dementing disorder of unclear etiology. Standard genetic testing for leukodystrophy and other neurodegenerative conditions was negative. Brain autopsy revealed classic features of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), including confluent white matter degeneration with axonal spheroids and pigmented glial cells in the affected white matter, consistent with CSF1R-RD. Subsequent long-read sequencing identified a novel deletion in CSF1R that was not detectable with short-read exome sequencing. To gain insight into potential mechanisms underlying white matter degeneration in CSF1R-RD, we studied multiple brain regions exhibiting varying degrees of white matter pathology. We found decreased CSF1R transcript and protein across brain regions, including intact white matter. Single nuclear RNA sequencing (snRNAseq) identified two disease-associated microglial cell states: lipid-laden microglia (expressing GPNMB, ATG7, LGALS1, LGALS3) and inflammatory microglia (expressing IL2RA, ATP2C1, FCGBP, VSIR, SESN3), along with a small population of CD44+ peripheral monocyte-derived macrophages exhibiting migratory and phagocytic signatures. GPNMB+ lipid-laden microglia with ameboid morphology represented the end-stage disease microglia state. Disease-associated oligodendrocytes exhibited cell stress signatures and dysregulated apoptosis-related genes. Disease-associated oligodendrocyte precursor cells (OPCs) displayed a failure in their differentiation into mature myelin-forming oligodendrocytes, as evidenced by upregulated LRP1, PDGFRA, SOX5, NFIA, and downregulated NKX2-2, NKX6.2, SOX4, SOX8, TCF7L2, YY1, ZNF488. Overall, our findings highlight microglia–oligodendroglia crosstalk in demyelination, with CSF1R dysfunction promoting phagocytic and inflammatory microglia states, an arrest in OPC differentiation, and oligodendrocyte depletion. [ABSTRACT FROM AUTHOR]

Background and Purpose: ApTOLL is an aptamer selected to antagonize toll‐like receptor 4 (TLR4), a relevant actor for innate immunity involved in inflammatory responses in multiple sclerosis (MS) and other diseases. The currently available therapeutic arsenal to treat MS is composed of immunomodulators but, to date, there are no (re)myelinating drugs available in clinics. In our present study, we studied the effect of ApTOLL on different animal models of MS. Experimental Approach: The experimental autoimmune encephalomyelitis (EAE) model was used to evaluate the effect of ApTOLL on reducing the inflammatory component. A more direct effect on oligodendroglia was studied with the cuprizone model and purified primary cultures of murine and human oligodendrocyte precursor cells (OPCs) isolated through magnetic‐activated cell sorting (MACS) from samples of brain cortex. Also, we tested these effects in an ex vivo model of organotypic cultures demyelinated with lysolecithin (LPC). Key Results: ApTOLL treatment positively impacted the clinical symptomatology of mice in the EAE and cuprizone models, which was associated with better preservation plus restoration of myelin and oligodendrocytes in the demyelinated lesions of animals. Restoration was corroborated on purified cultures of rodent and human OPCs. Conclusion and Implications: Our findings reveal a new therapeutic approach for the treatment of inflammatory and demyelinating diseases such as MS. The molecular nature of the aptamer exerts not only an anti‐inflammatory effect but also neuroprotective and remyelinating effects. The excellent safety profile demonstrated by ApTOLL in animals and humans opens the door to future clinical trials in MS patients. [ABSTRACT FROM AUTHOR]

Since the advanced Integrated Circuit (IC) manufacturing process has reached the 14 nm technology node and beyond, the pattern size of integrated circuits has become much smaller than the theoretical minimum resolution of lithography. In order to further extend the performance of immersion lithography, the industry introduces Multiple Patterning Technology (MPT) and Negative Tone Development (NTD) lithography technology. MPT and NTD lithography have greatly improved the process window of immersion lithography, enabling ArF immersion lithography to extend to 7 nm or even 5 nm technology nodes and below. However, MPT still has limited ability to improve the process window for some special patterns. For example，for the poly gate process in Front End of Line (FEOL) or the metal routing process in Back End of Line (BEOL), IC design often uses a special kind of patterns, such as the bi-line or tri-line structures. Due to the fact that some type of the bi-line/tri-line structures have a semi-dense pattern on each side, the process window of these patterns are relatively narrow, making them difficult to manufacture. This paper focuses on the patterning technology scheme of bi-line/tri-line structures in IC design under the diffraction limit of 193 nm immersion lithography. This paper explores the solution for bi-line/tri-line patterns through mask split strategy and NTD lithography process simulation with a physical model, including illumination conditions, Optical Proximity Correction (OPC) methods, and photoresist process parameter design. This study provides a reference scheme for subsequent NTD process development and patterning technology, as well as a reference idea for IC design methods.

In people with multiple sclerosis (MS), newborn and surviving oligodendrocytes (OLs) can contribute to remyelination, however, current therapies are unable to enhance or sustain endogenous repair. Low intensity repetitive transcranial magnetic stimulation (LI-rTMS), delivered as an intermittent theta burst stimulation (iTBS), increases the survival and maturation of newborn OLs in the healthy adult mouse cortex, but it is unclear whether LI-rTMS can promote remyelination. To examine this possibility, we fluorescently labelled oligodendrocyte progenitor cells (OPCs; Pdgfrα-CreER transgenic mice) or mature OLs (Plp-CreER transgenic mice) in the adult mouse brain and traced the fate of each cell population over time. Daily sessions of iTBS (600 pulses; 120 mT), delivered during cuprizone (CPZ) feeding, did not alter new or pre-existing OL survival but increased the number of myelin internodes elaborated by new OLs in the primary motor cortex (M1). This resulted in each new M1 OL producing ~ 471 µm more myelin. When LI-rTMS was delivered after CPZ withdrawal (during remyelination), it significantly increased the length of the internodes elaborated by new M1 and callosal OLs, increased the number of surviving OLs that supported internodes in the corpus callosum (CC), and increased the proportion of axons that were myelinated. The ability of LI-rTMS to modify cortical neuronal activity and the behaviour of new and surviving OLs, suggests that it may be a suitable adjunct intervention to enhance remyelination in people with MS. [ABSTRACT FROM AUTHOR]

With the breakthrough of cellulose pretreatment and enzyme hydrolysis technology, fermentation has become one of the main limiting factors for process enhancement. Current fermentation techniques are still dominated by the old-fashioned batch mode production with the lag and stationary phase demanding considerable operational time. This handicaps production efficiency and economic viability. In addition, a downtime between two batches is requested for harvesting, cleaning and sterilization, which reduces the overall productivity and increases human labor. Continuous culturing in chemostat, on the other hand, can enhance production and reduce labor (e.g. eliminating downtime intervals, and prior-fermentation steps like shake-flask culture, inoculation and subculture). However, ethanol content might be diluted, making downstream distillation and purification difficult and costly. This study endeavors to explore possible unsteady-state operation/control strategies to improve process performance. Starting from a simplified model of ethanol fermentation, stability analysis of the semi-continuous fermentation process is performed and the instability conditions of the system under ethanol inhibition is conducted. Based on the optimal periodic control (OPC) theory, the optimal criteria for switch production by periodic operations are explored, and the benefit of periodic dilution rate in the chemostat model in terms of averaged conversion rate is discussed. The results show that for the classical chemostat model with a Monod growth function, the performance of the averaged conversion rate can be improved under certain conditions, thus providing theoretical support for the study of self-cyclic fermentation. [ABSTRACT FROM AUTHOR]

For the first time, this paper explores the role of hydration kinetics on microcrack development in cement mortars using the μ-CT technique with a resolution of 2.2 µm. Three binders were tested: fine-grained ordinary Portland cement (OPC) with Blaine fineness of 391 m2/kg, coarse-grained OPC made from the same clinker with Blaine fineness of 273 m2/kg, and H-cement as a representative of the alkali-activated binder. It was found that most microcracks have a width in the range of 5–10 µm, increasing their occurrence with the progress of sealed hydration. While H-cement and coarse-grained OPC showed a comparable number of microcracks, fine-grained OPC exhibited more than twice the number of microcracks. In this sense, high hydration kinetics induce more microcracks, promoting later coalescence into visible cracks and disintegration of concrete at the end. Therefore, durable concrete with minimum microcracks should be derived from slow hydration kinetics or alkali-activation processes. [ABSTRACT FROM AUTHOR]

This study examines cement and ceramic waste (CW) for the sub-base layer of roads. This innovative method can do away with the risks associated with improper disposal of industrial waste. To achieve this objective, several proportions of cement and CW were used, ranging from 1.5 to 2% and 5% to 15%, respectively. The aim of the work was to examine the influences of CW and ordinary Portland cement (OPC) on the unconfined compressive strength (UCS), permeability, consolidation, and microstructures of untreated and treated soil of road sub-base layer. The Guelph permeameter, UCS, permeability, and onedimensional consolidation were among the laboratory and in-situ tests that were examined; the microstructures were characterised using SEM, infrared (IR), and mercury intrusion porosimetry (MIP). The findings indicated that the high permeability of the natural soil caused harm to our road soon after construction. Applying 5 to 15% CW reduced permeability by approximately 100% and settlement by around 43%. Furthermore, under wet and immersed conditions, mixing CW and OPC with soil raised UCS by approximately 182% and 20 times, respectively. This study demonstrated that by enhancing the geotechnical properties of soil, CW and OPC combined with it could be used as a road sub-base layer material. [ABSTRACT FROM AUTHOR]

This Perspectives paper advances understanding of coaching in pediatric rehabilitation. We compare three coaching approaches designed for pediatric rehabilitation: Coping with and Caring for Infants with Special Needs (COPCA), Occupational Performance Coaching (OPC), and Solution-Focused Coaching in Pediatric Rehabilitation (SFC-peds). Our objectives are to contrast the theory underpinning the approaches, discuss the evidence for outcomes and hypothesized mechanisms of change, consider the necessary mindsets of effective coaches, and propose directions for research and practice. The coaching approaches have different theoretical bases and are designed for specific contexts, yet are similar in their mechanisms of change and intended outcomes. There is growing evidence of important effects of coaching on coachees' goal achievement, empowerment, and capacity building. Studies indicate that stakeholders value coaching, and provide a preliminary understanding of the mechanisms, including engagement and self-efficacy, by which coaching approaches support clients' self-directed and sustained change. Open, curious, and client-centered practitioner mindsets are fundamental to effective coaching. Coaching is a distinctive group of relational, goal-oriented, and evidence-based approaches that support goal achievement and empowerment. These approaches reflect and advance an ongoing paradigm shift in pediatric rehabilitation—a movement from therapist-as-expert approaches to those that build empowerment and capacity. Coaching is a distinctive group of theory-based approaches that support clients' goal achievement and empowerment, and build capacity Coaching practitioners are collaborative facilitators who assist clients and families with their own discovery of solutions that fit their everyday contexts The evidence suggests that coaching triggers engagement and self-efficacy, which are the mechanisms by which changes in longer-term outcomes occur Open, curious, and client/family-centered practitioner mindsets are fundamental to effective coaching [ABSTRACT FROM AUTHOR]

HPV16 is responsible for approximately 60% and 90% of global HPV–induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A–D). Our understanding of HPV16 variants mostly derives from epidemiological studies on cervical cancer (CC) in which HPV16 B, C, and D lineages (previously named "non-European" variants) were mainly associated with high-grade cervical lesions and cancer. Although a predominance of HPV16 lineage A (previously named "European variants") has been observed in head and neck squamous cell carcinoma (HNSCC), epidemiological and in vitro biological studies are still limited for this tumor site. Next Generation Sequencing (NGS) of the entire HPV genome has deepened our knowledge of the prevalence and distribution of HPV variants in CC and HNSCC. Research on cervical cancer has shown that certain HPV16 sublineages, such as D2, D3, A3, and A4, are associated with an increased risk of cervical cancer, and sublineages A4, D2, and D3 are linked to a higher risk of developing adenocarcinomas. Additionally, lineage C and sublineages D2 or D3 of HPV16 show an elevated risk of developing premalignant cervical lesions. However, it is still crucial to conduct large-scale studies on HPV16 variants in different HPV–related tumor sites to deeply evaluate their association with disease development and outcomes. This review discusses the current knowledge and updates on HPV16 phylogenetic variants distribution in HPV–driven anogenital and head and neck cancers. [ABSTRACT FROM AUTHOR]

White matter injuries (WMIs) are the leading cause of neurologic impairment in infants born premature. There are no treatment options available. The most common forms of WMIs in infants occur prior to the onset of normal myelination, making its pathophysiology distinctive, thus requiring a tailored approach to treatment. Neonates present a unique opportunity to repair WMIs due to a transient abundance of neural stem/progenitor cells (NSPCs) present in the germinal matrix with oligodendrogenic potential. We identified an endogenous oxysterol, 20-αHydroxycholesterol (20HC), in human maternal breast milk that induces oligodendrogenesis through a sonic hedgehog (shh), Gli-dependent mechanism. Following WMI in neonatal mice, injection of 20HC induced subventricular zone-derived oligodendrogenesis and improved myelination in the periventricular white matter, resulting in improved motor outcomes. Targeting the oligodendrogenic potential of postnatal NSPCs in neonates with WMIs may be further developed into a novel approach to mitigate this devastating complication of preterm birth.

This study examines cement and ceramic waste (CW) for the sub-base layer of roads. This innovative method can do away with the risks associated with improper disposal of industrial waste. To achieve this objective, several proportions of cement and CW were used, ranging from 1.5 to 2% and 5% to 15%, respectively. The aim of the work was to examine the influences of CW and ordinary Portland cement (OPC) on the unconfined compressive strength (UCS), permeability, consolidation, and microstructures of untreated and treated soil of road sub-base layer. The Guelph permeameter, UCS, permeability, and one- dimensional consolidation were among the laboratory and in-situ tests that were examined; the microstructures were characterised using SEM, infrared (IR), and mercury intrusion porosimetry (MIP). The findings indicated that the high permeability of the natural soil caused harm to our road soon after construction. Applying 5 to 15% CW reduced permeability by approximately 100% and settlement by around 43%. Furthermore, under wet and immersed conditions, mixing CW and OPC with soil raised UCS by approximately 182% and 20 times, respectively. This study demonstrated that by enhancing the geotechnical properties of soil, CW and OPC combined with it could be used as a road sub-base layer material.

IntroductionThis study explores the shift toward predictive maintenance through real-time data analytics to minimize machine downtime and improve machinery insights in industrial environments. Predictive maintenance aims to enable proactive interventions by predicting failures, enhancing operational efficiency.MethodsThe research was conducted in three stages. First, BA Glass equipment was sensorized using OPC Router and PowerStudio SCADA to facilitate real-time data extraction. A predictive maintenance algorithm was then developed in Python to analyze sensor data, predict failures, and trigger alarms. Finally, various forecasting models, including Linear and Polynomial Regression, Simple and Double Exponential Smoothing, ARIMA, and Prophet, were evaluated using a combination of blocked cross-validation and rolling window methodologies. The algorithm calculated performance metrics such as MSE, RMSE, and MAE for different parameter configurations and training sizes.ResultsA comparative analysis between wired and wireless sensors concluded that wireless sensors, although more expensive, were more practical and interchangeable in the factory setting. The results from the evaluation of prediction models showed that the Double Exponential Smoothing (DES) model with an additive damped trend and linear models performed best for datasets with daily seasonality and gradual oscillations. For datasets with stable trends and higher frequency oscillations, ARIMA and Prophet models proved to be more accurate.DiscussionThese findings suggest that the choice of sensors and prediction models can significantly impact the effectiveness of predictive maintenance systems. Wireless sensors offer long-term benefits in terms of flexibility and practicality, while the DES model and ARIMA/Prophet models are optimal depending on the dataset characteristics. This research highlights the value of real-time data analytics and predictive models in industrial environments for reducing downtime and improving decision-making.

France is Europe's leading producer of flaxseed. This seed is rich in omega-3, energy, and protein for animals, but it also contains anti-nutritional factors such as mucilage. Thus, mucilage must be removed and could be used as a bio-admixture in cementitious materials development, reducing the environmental impact of cementitious materials. This study aims to valorize the usage of flaxseed mucilage (FM) in ordinary Portland cement. FM caused macroscopic and microscopic changes in the materials studied. The higher the concentration, the greater the changes were. The admixed samples showed an exponentially concentration-dependent delay in setting. FM degradation products induced by the cementitious conditions accentuated the delay. However, this delay in setting did not affect the hydrates' growth in the material. In fact, FM showed a "delay accelerator" behavior, meaning that once hydration began, it was accelerated as compared to a reference. Macroscopically, FM induced significant flocculation, increasing material porosity and carbonation. Consequently, bulk density and thermal conductivity were reduced. At the highest amount of FM admixture (0.75% w/w), FM allowed bridge formation between Ca(OH)2 crystals, which can improve the mechanical properties of mortars. Because FM is highly hygroscopic, it has the capability to absorb water and subsequently release it gradually and under controlled conditions into the cement matrix. Therefore, regulation of water diffusion from the mucilage may induce the self-healing properties responsible for mechanical properties similar to that of the reference in the medium to long term. [ABSTRACT FROM AUTHOR]

Demyelination is typically followed by a remyelination process through mature oligodendrocytes (OLs) differentiated from precursor cells (OPCs) recruited into the lesioned areas, however, this event usually results in uncompleted myelination. Potentiation of the remyelination process is an important target for designing effective therapeutic strategies against white matter loss. Here, it was evaluated the remyelinating effect of different β-carbolines that present differential allosteric modulation on the GABAA receptor expressed in OLs. For this, we used a focalized demyelination model in the inferior cerebellar peduncle (i.c.p.) of rats (DRICP model), in which, demyelination by ethidium bromide (0.05%) stereotaxic injection was confirmed histologically by staining with Black-Gold II (BGII) and toluidine blue. In addition, a longitudinal analysis with diffusion-weighted magnetic resonance imaging (dMRI) was made by computing fractional anisotropy (FA), apparent diffusion coefficient (ADC) and diffusivity parameters to infer i.c.p. microstructural changes. First, dMRI analysis revealed FA decreases together with ADC and radial diffusivity (RD) increases after demyelination, which correlates with histological BGII observations. Then, we evaluated the effect produced by three allosteric GABAA receptor modulators, the N-butyl-β-carboline-3-carboxylate (β-CCB), ethyl 9H-pyrido [3,4-b]indole-3-carboxylate (β-CCE), and 4-ethyl-6,7-dimethoxy-9H-pyrido [3,4-b]indole-3-carboxylic acid methyl ester (DMCM). The results indicated that daily systemic β-CCB (1 mg/Kg) or β-CCE (1 mg/Kg) administration for 2 weeks, but not DMCM (0.35 mg/Kg), in lesioned animals increased FA and decreased ADC or RD, suggesting myelination improvement. This was supported by BGII staining analysis that showed a recovery of myelin content. Also, it was quantified by immunohistochemistry both NG2+ and CC1+ cellular population in the different experimental sceneries. Data indicated that either β-CCB or β-CCE, but not DMCM, produced an increase in the population of CC1+ cells in the lesioned area. Finally, it was also calculated the g-ratio of myelinated axons and observed a similar value in those lesioned animals treated with β-CCB or β-CCE compared to controls. Thus, using the DRICP model, it was observed that either β-CCB or β-CCE, positive modulators of the GABAA receptor in OLs, had a potent promyelinating effect. [ABSTRACT FROM AUTHOR]

Aerosols, as well as suspended particulate matter, impact atmospheric pollution, the climate, and human health, directly or indirectly. Particle size, chemical composition, and other aerosol characteristics are determinant factors for atmospheric pollution dynamics and more. In the last decade, low-cost devices have been widely used in instrumentation to measure aerosols. However, they present some issues, such as the problem of discriminating whether the aerosol is composed of liquid particles or solid. This issue could lead to errors in the estimation of mass concentration in monitoring environments where there is fog. In this study, we investigate the use of an optical particle counter (OPC) coupled to a quartz crystal microbalance with an integrated microheater (H-QCM) to enhance measurement performances. The H-QCM was used not only to measure the collected mass on its surface but also, by using the integrated microheater, it was able to heat the collected mass by performing heating cycles. In particular, we tested the developed system with aerosolized saline solutions of sodium chloride (NaCl), with three decreasing concentrations of salt and three electronic cigarette solutions (e-liquid), with different concentrations of propylene glycol and glycerin mixtures. The results showed that the OPC coherently counted the salt dilution effects, and the H-QCM output confirmed the presence of liquid and solid particles in the aerosols. In the case of e-liquid aerosols, the OPC counted the particles, and the HQCM output highlighted that in the aerosol, there were no solid particles but a liquid phase only. These findings contribute to the refinement of aerosol measurement methodologies by low-cost sensors, fostering a more comprehensive understanding. [ABSTRACT FROM AUTHOR]

Oligodendrocyte progenitor cells (OPCs) were regarded for years solely for their regenerative role; however, their immune‐modulatory roles have gained much attention recently, particularly in the context of multiple sclerosis (MS). Despite extensive studies on OPCs, there are limited data elucidating the interactions between their intrinsic regenerative and immune functions, as well as their relationship with the inflamed central nervous system (CNS) environment, a key factor in MS pathology. We examined the effects of pro‐inflammatory cytokines, represented by interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α, as well as anti‐inflammatory cytokines, represented by interleukin (IL)‐4 and IL‐10, on OPC differentiation and immune characteristics. Using primary cultures, enzyme‐linked immunosorbent assay and immunofluorescence stainings, we assessed differentiation capacity, phagocytic activity, major histocompatibility complex (MHC)‐II expression, and cytokine secretion. We observed that the anti‐inflammatory milieu (IL4 and IL10) reduced both OPC differentiation and immune functions. Conversely, exposure to TNF‐α led to intact differentiation, increased phagocytic activity, high levels of MHC‐II expression, and cytokines secretion. Those effects were attributed to signalling via TNF‐receptor‐2 and counteracted the detrimental effects of IFN‐γ on OPC differentiation. Our findings suggest that a pro‐regenerative, permissive inflammatory environment is needed for OPCs to execute both regenerative and immune‐modulatory functions. [ABSTRACT FROM AUTHOR]

Preclinical studies of pro-remyelinating therapies for multiple sclerosis tend to neglect the effect of the disease-relevant inflammatory milieu. Interferon-gamma (IFN-γ) is known to suppress oligodendrocyte progenitor cell (OPC) differentiation and induce a recently described immune OPC (iOPC) phenotype characterized by expression of major histocompatibility complex (MHC) molecules. We tested the effects of cladribine (CDB), dimethylfumarate (DMF), and interferon-beta (IFN-β), existing anti-inflammatory therapies for MS, on the IFN-γ-induced iOPC formation and OPC differentiation block. In line with previous reports, we demonstrate that IFN-β and DMF inhibit OPC proliferation, while CDB had no effect. None of the drugs exhibited cytotoxic effects at the physiological concentrations tested in vitro. In a differentiation assay, none of the drugs were able to promote differentiation, under inflammatory or basal conditions. To study drug effects on iOPCs, we monitored MHC expression in vitro with live cell imaging using cells isolated from MHC reporter mice. IFN-β suppressed induction of MHC class II, and DMF led to suppression of both class I and II. CDB had no effect on MHC induction. We conclude that promoting proliferation and differentiation and suppressing iOPC induction under inflammatory conditions may require separate therapeutic strategies and must be balanced for maximal repair. Our in vitro MHC screening assay can be leveraged across cell types to test the effects of drug candidates and disease-related stimuli.

ABSTRACT The incidence rate of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is increasing in countries with high human development index. HPV cell-free DNA (cfDNA) isolated from 3 to 4 mL blood plasma has been successfully used for therapy surveillance. A highly discussed application of HPV-cfDNA is early detection of HPV-OPC. This requires sensitive and specific cfDNA detection as cfDNA levels can be very low. To study the predictive power of pre-diagnostic HPV-cfDNA, archived samples from epidemiological cohorts with limited plasma volume are an important source. To establish a cfDNA detection workflow for low plasma volumes, we compared cfDNA purification methods [MagNA Pure 96 (MP96) and QIAamp ccfDNA/RNA] and digital PCR systems (Biorad QX200 and QIAGEN QIAcuity One). Final assay validation included 65 low-volume plasma samples from oropharyngeal cancer (OPC) patients with defined HPV status stored for 2–9 years. MP96 yielded a 28% higher cfDNA isolation efficiency in comparison to QIAamp. Both digital PCR systems showed comparable analytical sensitivity (6–17 copies for HPV16 and HPV33), but QIAcuity detected both types in the same assay. In the validation set, the assay had 80% sensitivity (n = 28/35) for HPV16 and HPV33 and a specificity of 97% (n = 29/30). In samples with ≥750 µL plasma, the sensitivity was 85% (n = 17/20), while in samples with

Human papillomavirus (HPV) is the most common sexually transmitted disease. Certain strains have the potential to cause malignancy in multiple anatomical sites if not cleared by the immune system. In most infected people, HPV is cleared within two years. However, HPV may persist in susceptible individuals with certain risk factors, eventually leading to malignancy. New evidence suggests that over 75% of all oropharyngeal cancers (OPC) are directly attributable to HPV. It is estimated that prophylactic HPV vaccination alone may take at least 25 years to have a significant impact on reducing the incidence of OPC. The temporal link between detection of oral HPV, persistence of the infection and the subsequent development of OPC have been well established. Moreover, men have threefold higher risk than women for acquiring HPV-OPC. This comprehensive review focuses on OPC development in men, highlighting the risk factors associated with malignant transformation of HPV-OPC. Current evidence is insufficient to determine whether early identification of at-risk demographics, screening, and prompt diagnosis result in improved outcomes. Hitherto, the effectiveness of an oral HPV screening program in this regard has not been investigated. Nevertheless, the potential to emulate the success of the cervical screening program remains a very real possibility.

Background: To retrospectively access outcome, adverse events and prognostic factors in oropharyngeal carcinoma (OPC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: Ninety-eight OPC patients were treated between 2000 and 2015. Thirty-three patients received definitive and 65 adjuvant radiotherapy. Seventy-one percent had simultaneous chemotherapy. Patients were systematically followed up (mean 114 months, range 19-197 months). Statistical analysis used Kaplan-Meier method, Cox regression analysis, and log-rank test. Adverse events were classified according to common toxicity criteria version (CTCAE) 4.03. Results: The 1-, 5-, and 10-year overall survival rates in the adjuvant vs. definitive cohort were 90.8% vs. 66.7%, 67.4% vs. 33.1%, and 57.7% vs. 16.5%. Survival in the adjuvant cohort was significantly longer than in the definitive cohort (P < 0.00005). Patients <65 years had a significantly longer survival than older patients. Locoregional tumor control rates after 1-, 5-, and 10 years in the adjuvant vs. definitive cohort were 90.2% vs. 66.7%, 82.2% vs 45.4%, and 72.1% vs. 30.3%. Locoregional tumor control in the adjuvant cohort was significantly longer than in the definite cohort (P < 0.005). Distant metastases were diagnosed in 20.4% of all patients. Most patients had mild CTCAE grade 1 and 2 adverse events and mild late adverse events including xerostomia, dysphagia, and lymphedema. Conclusion: Intensity-modulated radiotherapy for OPC is an important part of the treatment algorithm alone and in particular after surgery while the additional benefits of chemotherapy might be age dependent. Despite advanced tumor stages, nearly half of our patients were alive in the long term. The majority of patients had relatively mild chronic adverse events. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate the occupational variation in incidence of oropharyngeal cancer (OPC). Methods: We calculated standardized incidence ratios (SIRs) of OPC in occupational categories in the Nordic countries relative to the entire national populations. The data covered 6155 OPC cases. Results: Among men high risk of OPC was observed, among else, in waiters (SIR 6.28, 95% CI 4.68–8.26), beverage workers (SIR 3.00, 95% CI 1.72–4.88), and artistic workers (SIR 2.97, 95% CI 2.31–3.76). Among women high risk of OPC was observed in waiters (SIR 2.02, 95% CI 1.41–2.81) and packers (SIR 1.73, 95% CI 1.07–2.64). The lowest SIRs were observed in female gardeners (SIR 0.27, 95% CI 0.12–0.51) and male farmers (SIR 0.30, 95% CI 0.25–0.35). Conclusion: The 20-fold variation in incidence of OPC between occupations needs further investigation in studies with detailed information on occupational and non-occupational risk factors. [ABSTRACT FROM AUTHOR]

This review paper scrutinizes the staging of dense wavelength division multiplexing soliton system in return to zero and non-return to zero format. In-line optical phase conjugator (OPC) is used to depreciate the power of four wave mixing (FWM). Destructive interference between both the halves of in-line OPC plummets the FWM power sturdily. This paper concludes with the indication that return-to-zero with OPC gives out better performance with FWM suppression. [ABSTRACT FROM AUTHOR]

This article discusses a variety of more recent alternatives to Portland cement (OPC) that can lower energy consumption and greenhouse gas emissions. Some of these new binders can be made utilizing fuels and low-grade industrial waste. Only after thorough examination of various physico-mechanical, microstructural, and durability properties can the practical viability of these alternative binders be substantiated.In this review paper seven important alternative cementitious binder systems i.e. Supplemental cementitious in place of OPC in some cases, Industrial By-Products, Alternative cements, Concrete Made Using Garbage as Aggregate, Carbona table Calcium Silicate Cement, Cements With a Calcium Hydro silicate Base, Eggshell waste for sustainable construction materials are discussed. It was deduced that all of the more recent cementitious binders could be created utilizing industrial wastes such as low-grade limestone or clay, fly ash, and slags. This would result in the achievement of the desired physico-mechanical and durability properties, as well as a decrease in cost and energy consumption of between 20 and 58 percent. In addition, the creation of the aforementioned alternative binder results in a reduction of greenhouse gases that is anywhere from 15–55%. [ABSTRACT FROM AUTHOR]

The control of rheological properties is gaining in importance to meet the special requirements for cementitious materials in novel technologies such as 3D‐printing. A deeper understanding of the underlying mechanisms of cement hydration is necessary to customize the mix design to the specific application. The hydration of OPC is mainly characterized by the silicate and aluminate reaction. The aluminate reaction is especially relevant for the early rheological development, whereas the formation of C‐S‐H (silicate reaction) is responsible for the later hardening of the hydrating paste. A hydration control agent is used to delay the initial aluminate reaction to a defined point in time. When no additional mixing occurs during this period of rapid ettringite precipitation, the cement paste stiffens to a solid cement stone. However, when the sample is mixed during this period, the workability of the paste is retained. The rheological changes can be correlated directly to the magnitude of ettringite formation. Additionally, the compressive strength and pore size distribution of all systems (reference, HCA, HCA with additional mixing) are investigated to analyze the long‐term properties. These results predict future customized mix designs in various application fields. [ABSTRACT FROM AUTHOR]

Marine clays are normally characterized by high compressibility and low shear strength, which contribute to many geotechnical problems and, at times, necessitate the need to adopt stabilization with calcium-based stabilizers. However, calcium-based stabilization, when adopted on clays rich with sulfates, causes sulfate heaving, which impacts the strength of the soil. As a result of this heaving, severe damage has occurred to transportation infrastructure such as highways, runways, tunnels, canals, etc. Numerous pavement failures attributed to sulfate-induced heave in cement-treated sulfate-bearing clay subgrades have been documented by researchers worldwide. In this study, an attempt was made to prevent the sulfate attack in cement-treated clay by introducing barium hydroxide and sulphate resisting cement. Unconfined compressive strength, CBR, liquid limit and free swell index tests were conducted on treated clay samples to determine the effect of sulfates in cement-treated sulfate-bearing clays for prolonged curing periods. On the basis of the results obtained, the incorporation of barium hydroxide produced a high CBR value of 70% and a strength gain of 551 kPa in treated clay samples, indicating the effectiveness of barium hydroxide in mitigating the adverse effects of high sulfate content in soil. It was also determined that the sulphate-resistant cement was sufficient to lessen the impact of 0.5% sulfate content in soil, but it was unable to mitigate the impacts of 4% sulfate, resulting in a significant reduction in strength of 34%. [ABSTRACT FROM AUTHOR]

Demyelination is typically followed by a remyelination process through mature oligodendrocytes (OLs) differentiated from precursor cells (OPCs) recruited into the lesioned areas, however, this event usually results in uncompleted myelination. Potentiation of the remyelination process is an important target for designing effective therapeutic strategies against white matter loss. Here, it was evaluated the remyelinating effect of different β-carbolines that present differential allosteric modulation on the GABAA receptor expressed in OLs. For this, we used a focalized demyelination model in the inferior cerebellar peduncle (i.c.p.) of rats (DRICP model), in which, demyelination by ethidium bromide (0.05%) stereotaxic injection was confirmed histologically by staining with Black-Gold II (BGII) and toluidine blue. In addition, a longitudinal analysis with diffusion-weighted magnetic resonance imaging (dMRI) was made by computing fractional anisotropy (FA), apparent diffusion coefficient (ADC) and diffusivity parameters to infer i.c.p. microstructural changes. First, dMRI analysis revealed FA decreases together with ADC and radial diffusivity (RD) increases after demyelination, which correlates with histological BGII observations. Then, we evaluated the effect produced by three allosteric GABAA receptor modulators, the N-butyl-β-carboline-3-carboxylate (β-CCB), ethyl 9H-pyrido [3,4-b]indole-3-carboxylate (β-CCE), and 4-ethyl-6,7-dimethoxy-9H-pyrido [3,4-b]indole-3-carboxylic acid methyl ester (DMCM). The results indicated that daily systemic β-CCB (1 mg/Kg) or β-CCE (1 mg/Kg) administration for 2 weeks, but not DMCM (0.35 mg/Kg), in lesioned animals increased FA and decreased ADC or RD, suggesting myelination improvement. This was supported by BGII staining analysis that showed a recovery of myelin content. Also, it was quantified by immunohistochemistry both NG2+ and CC1+ cellular population in the different experimental sceneries. Data indicated that either β-CCB or β-CCE, but not DMCM, produced an increase in the population of CC1+ cells in the lesioned area. Finally, it was also calculated the g-ratio of myelinated axons and observed a similar value in those lesioned animals treated with β-CCB or β-CCE compared to controls. Thus, using the DRICP model, it was observed that either β-CCB or β-CCE, positive modulators of the GABAA receptor in OLs, had a potent promyelinating effect.

HPV16 is responsible for approximately 60% and 90% of global HPV–induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A–D). Our understanding of HPV16 variants mostly derives from epidemiological studies on cervical cancer (CC) in which HPV16 B, C, and D lineages (previously named “non-European” variants) were mainly associated with high-grade cervical lesions and cancer. Although a predominance of HPV16 lineage A (previously named “European variants”) has been observed in head and neck squamous cell carcinoma (HNSCC), epidemiological and in vitro biological studies are still limited for this tumor site. Next Generation Sequencing (NGS) of the entire HPV genome has deepened our knowledge of the prevalence and distribution of HPV variants in CC and HNSCC. Research on cervical cancer has shown that certain HPV16 sublineages, such as D2, D3, A3, and A4, are associated with an increased risk of cervical cancer, and sublineages A4, D2, and D3 are linked to a higher risk of developing adenocarcinomas. Additionally, lineage C and sublineages D2 or D3 of HPV16 show an elevated risk of developing premalignant cervical lesions. However, it is still crucial to conduct large-scale studies on HPV16 variants in different HPV–related tumor sites to deeply evaluate their association with disease development and outcomes. This review discusses the current knowledge and updates on HPV16 phylogenetic variants distribution in HPV–driven anogenital and head and neck cancers.

Oligodendrocyte (OL) maturation arrest in human white matter injury contributes significantly to the failure of endogenous remyelination in multiple sclerosis (MS) and newborn brain injuries such as hypoxic ischemic encephalopathy (HIE) that cause cerebral palsy. In this study, we identify an oligodendroglial-intrinsic factor that controls OL maturation specifically in the setting of injury. We find a requirement for the ring finger protein Rnf43 not in normal development but in neonatal hypoxic injury and remyelination in the adult mammalian CNS. Rnf43, but not the related Znrf3, is potently activated by Wnt signaling in OL progenitor cells (OPCs) and marks activated OPCs in human MS and HIE. Rnf43 is required in an injury-specific context, and it promotes OPC differentiation through negative regulation of Wnt signal strength in OPCs at the level of Fzd1 receptor presentation on the cell surface. Inhibition of Fzd1 using UM206 promotes remyelination following ex vivo and in vivo demyelinating injury.