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Background: We aim to provide up-to-date real-world evidence on the persistence, adherence, healthcare resource utilization, and costs of multiple sclerosis (MS) by comparing ocrelizumab to other disease-modifying treatments (DMTs) and within different DMT sequences. Methods: We included 3371 people with MS who first received or switched DMT prescriptions from January 2018 to December 2022; they were identified through hospital discharge records, drug prescriptions, and exemption codes from the Campania Region (South Italy). We calculated persistence (time from the first prescription to discontinuation or switching to another DMT), adherence (proportion of days covered (PDC)), DMT costs, and MS hospital admissions and related costs. Results: The most frequently prescribed DMT was dimethyl fumarate (n = 815; age 38.90 ± 11.91 years; 69.5% females), followed by ocrelizumab (n = 682; age 46.46 ± 11.29 years; 56.3%); 28.8% of the patients treated with ocrelizumab were naïve to DMTs. Using ocrelizumab as a statistical reference, the risk of discontinuation was higher for other highly active (HR = 6.32; 95%CI = 3.16, 12.63; p < 0.01) and low-/medium-efficacy DMTs (HR = 10.10; 95%CI = 5.10, 19.77; p < 0.01); adherence was lower for other highly active DMTs (Coeff = −0.07; 95%CI = −0.10, −0.04; p < 0.01) and low-/medium-efficacy DMTs (Coeff = −0.16; 95%CI = −0.19, −0.14; p < 0.01). monthly DMT costs were higher for other highly active DMTs (Coeff = 77.45; 95%CI = 29.36, 125.53; p < 0.01) but lower for low-/medium-efficacy DMTs (Coeff = −772.31; 95%CI = −816.95, −727.66; p < 0.01). The hospital admissions and related costs of MS were similar between ocrelizumab, other highly active DMTs, and other low-/medium-efficacy DMTs, and with ocrelizumab as the first-line DMT after other highly active DMTs and after low-/medium-efficacy DMTs, which was possibly due to the low number of observations. Conclusions: From 2018 to 2022, ocrelizumab was among the most frequently prescribed DMTs, with 28.8% prescriptions to incident MS patients, confirming its relevance in clinical practice. Ocrelizumab was associated with the highest persistence and adherence, pointing towards its favorable benefit–risk profile. The costs of ocrelizumab were lower than those of other highly active DMTs.

Abstract Whilst the importance of fungal primary biological aerosol particles (PBAPs) has been recognised, few studies have empirically assessed how land-use patterns influence them. Here, we show the impacts of different land-use patterns on fungal PBAPs within the Brazilian Atlantic Forest biodiversity hotspot. Spanning a distance of ca. 600 km within this biome, we collected fungal bioaerosols in the following land-use patterns: a 25-year-old coffee plantation, a 2.5-year-old Eucalyptus plantation, a 3-months-old maize crop, a 2-year-old and another 7-year-old native forest reforestation area, and a native forest fragment. Using the portable Burkard air sampler, a total of 14 morphotype-species were found. Cladosporium sp. comprised as much as about 95% of all fungal spores collected, being present in all samples (frequency of 100%). Forest systems had as much as 5-to-19-fold more fungal spores in the air than maize crops. Sampling height and time (morning vs. afternoon) did not influence fungal concentration and number of species. In addition, using data derived from an eddy covariance tower in the Eucalyptus site, we estimated the emission rate to be 6649 spores m−2 s−1. Our study confirms that land-use patterns affect fungal PBAPs, and that replacing large areas of native Atlantic Forest by monospecific stands, a homogenisation of airborne fungi is occurring, with unknown consequences for climate regulation.

Study purpose. At the end of the twentieth century, the development of highly reliable and painless non-invasive transcranial brain stimulation techniques and devices has aroused great scientific and clinical interest in numerous fields. In neuroscience, since the introduction of innovative and non-invasive devices such as the brain stimulator, the investigation of cortical processes and their neural basis has played a fundamental role. Furthermore, neuroscientists are attracted to therapeutic applications for the treatment of food craving. This narrative review is aimed to explain the growing and constant interest of neuroscientific experimentation in the field of non-invasive transcranial stimulation. Material and methods. After an introduction explaining the historical evolution of NIBS, we will try to provide an overview of the two stimulation techniques (TMS and tDCS); we will describe the different types of stimulation that can be performed using these techniques, the excitatory/inhibitory effects, and the various mechanisms of action at the level of brain activity. Results. We will also provide some elucidations regarding the implications of the facilitative/inhibitory effects, and how these stimulation methods can be used to advance knowledge of the neurofunctional organization of the brain. Conclusion. The results of the study showed the effect of brain neuromodulation on sports and nutrition.

Abstract Three-dimensional motion analysis represents a quantitative approach to assess spatio-temporal and kinematic changes in health and disease. However, these parameters provide only segmental information, discarding minor changes of complex whole body kinematics characterizing physiological and/or pathological conditions. We aimed to assess how levodopa intake affects the whole body, analyzing the kinematic interactions during gait in Parkinson’s disease (PD) through network theory which assess the relationships between elements of a system. To this end, we analysed gait data of 23 people with PD applying network theory to the acceleration kinematic data of 21 markers placed on participants’ body landmarks. We obtained a matrix of kinematic interactions (i.e., the kinectome) for each participant, before and after the levodopa intake, we performed a topological analysis to evaluate the large-scale interactions among body elements, and a multilinear regression analysis to verify whether the kinectome’s topology could predict the clinical variations induced by levodopa. We found that, following levodopa intake, patients with PD showed less trunk and head synchronization (p-head = 0.048; p-7th cervical vertebrae = 0.032; p-10th thoracic vertebrae = 0.006) and an improved upper-lower limbs synchronization (elbows right, p = 0.002; left, p = 0.005), (wrists right, p = 0.003; left, p = 0.002; knees right, p = 0.003; left, p = 0.039) proportional to the UPDRS-III scores. These results may be attributable to the reduction of rigidity, following pharmacological treatment.

This study evaluates the effectiveness of iron-modified biochar (Fe-BC) in fixed-bed heterogeneous Fenton processes for levofloxacin (LFX) removal, a widely-used fluoroquinolone antibiotic. The objective is to optimize parameters such as pH, oxidants (H2O2 and S2O82−), and biochar forms (functionalized and raw) using factorial analysis of mixed data (FAMD) and response surface methodology (RSM). These optimizations identified the ideal conditions for maximal LFX removal. The most effective removal with Fe-BC occurred at 2.5 mM H2O2 and pH 7.5, while the optimal S2O82− conditions were 1.6 mM at pH 2.8. Both Fe-BC and raw biochar (RBC) showed the highest adsorption at pH 5.8. In adsorption-only, RBC and Fe-BC reduced LFX to 530 μg/L and 335 μg/L, respectively, in 60 min. The oxidation process further decreased LFX levels to between 8.9 μg/L and 0.1 μg/L using S2O82− and H2O2, respectively. The research expanded upon a kinetic model, incorporating the calculation of kinetic constants for both adsorption and oxidation processes, to deepen our understanding of the intricate degradation dynamics at play. Identifying by-products was crucial in elucidating degradation pathways. These findings are vital for environmental remediation, demonstrating the efficiency of Fe-BC in removing harmful antibiotics from water. This research highlights the potential of modified biochar in environmental clean-up, especially for water contaminated with antibiotics. The results emphasize the importance of optimizing treatment conditions for effective antibiotic removal, contributing valuable insights to the field of environmental remediation.

Landfills play a key role as greenhouse gas (GHGs) emitters, and urgently need assessment and management plans development to swiftly reduce their climate impact. In this context, accurate emission measurements from landfills under different climate and management would reduce the uncertainty in emission accounting. In this study, more than one year of long-term high-frequency data of CO2 and CH4 fluxes were collected in two Italian landfills (Giugliano and Case Passerini) with contrasting management (gas recovery VS no management) using eddy covariance (EC), with the aim to i) investigate the relation between climate drivers and CO2 and CH4 fluxes at different time intervals and ii) to assess the overall GHG balances including the biogas extraction and energy recovery components. Results indicated a higher net atmospheric CO2 source (5.7 ± 5.3 g m2 d−1) at Giugliano compared to Case Passerini (2.4 ± 4.9 g m2 d−1) as well as one order of magnitude higher atmospheric CH4 fluxes (6.0 ± 5.7 g m2 d−1 and 0.7 ± 0.6 g m2 d−1 respectively). Statistical analysis highlighted that fluxes were mainly driven by thermal variables, followed by water availability, with their relative importance changing according to the time-interval considered. The rate of change in barometric pressure (dP/dt) influenced CH4 patterns and magnitude in the classes ranging from −1.25 to +1.25 Pa h−1, with reduction when dP/dt > 0 and increase when dP/dt

The impact of technology on human life is significant, touching various aspects such as communication, economy, education, medicine, industry, and even ecosystems [...]

A pre-deployment calibration and a field validation of two low-cost (LC) stations equipped with O3 and NO2 metal oxide sensors were addressed. Pre-deployment calibration was performed after developing and implementing a comprehensive calibration framework including several supervised learning models, such as univariate linear and non-linear algorithms, and multiple linear and non-linear algorithms. Univariate linear models included linear and robust regression, while univariate non-linear models included a support vector machine, random forest, and gradient boosting. Multiple models consisted of both parametric and non-parametric algorithms. Internal temperature, relative humidity, and gaseous interference compounds proved to be the most suitable predictors for multiple models, as they helped effectively mitigate the impact of environmental conditions and pollutant cross-sensitivity on sensor accuracy. A feature analysis, implementing dominance analysis, feature permutations, and the SHapley Additive exPlanations method, was also performed to provide further insight into the role played by each individual predictor and its impact on sensor performances. This study demonstrated that while multiple random forest (MRF) returned a higher accuracy than multiple linear regression (MLR), it did not accurately represent physical models beyond the pre-deployment calibration dataset, so a linear approach may overall be a more suitable solution. Furthermore, as well as being less computationally demanding and generally more suitable for non-experts, parametric models such as MLR have a defined equation that also includes a few parameters, which allows easy adjustments for possible changes over time. Thus, drift correction or periodic automatable recalibration operations can be easily scheduled, which is particularly relevant for NO2 and O3 metal oxide sensors. As demonstrated in this study, they performed well with the same linear model form but required unique parameter values due to intersensor variability.

Background: Neurofibromatosis type 1 (NF1) is a genetic disorder that affects multiple systems in the body, often leading to physical disfigurements and a wide range of clinical symptoms. This study aims to investigate the relationship between NF1 severity and visibility and the quality of life (QoL) in children. Methods: The Pediatric Quality of Life Inventory (PedsQL) and a modified version of the Ablon scale were used to assess QoL and NF1 severity and visibility, respectively. Self-reported and parent-reported QoL scores were compared, and the associations between NF1 severity/visibility and QoL were explored. Results: Thirty-eight pediatric NF1 patients and their parents were enrolled. QoL scores did not differ significantly between patient self-reports and parent reports. However, correlational analyses revealed that higher NF1 severity was associated with lower physical QoL in patients, and greater NF1 visibility was linked to lower physical and social QoL. For parents, higher NF1 severity correlated with lower school functioning, whereas NF1 visibility did not show a significant correlation with QoL. Conclusion: The severity and visibility of NF1 have distinct impacts on various aspects of QoL in children, highlighting the need for tailored interventions that address both physical and psychological challenges. These findings underscore the importance of comprehensive care approaches in managing NF1 in pediatric populations.

Do homestays benefit host communities, perpetuate neocolonial relationships, or both? While the St. Lawrence Kenya-Semester Program (KSP) has centered homestays as an essential component of experiential learning and community engagement since 1972, this article flips the script and places homestay families at the center of knowledge production on study abroad. Drawn from 15 years of homestay experiences in Nyeri and Kericho counties, we situate this program as an important case study to analyze host community perceptions of the benefits and challenges of homestays for rural agricultural Kenyan communities and the implications this has for study abroad assessment and community engagement.

Lowland meadows represent aboveground and belowground biodiversity reservoirs in intensive agricultural areas, improving water retention and filtration, ensuring forage production, contrasting erosion and contributing to soil fertility and carbon sequestration. Besides such major ecosystem services, the presence of functionally different plant species improves forage quality, nutritional value and productivity, also limiting the establishment of weeds and alien species. Here, we tested the effectiveness of a commercial seed mixture in restoring a lowland mixed meadow in the presence or absence of inoculation with arbuscular mycorrhizal (AM) fungi and biostimulation of symbiosis development with the addition of short chain chito-oligosaccharides (CO). Plant community composition, phenology and productivity were regularly monitored alongside AM colonization in control, inoculated and CO-treated inoculated plots. Our analyses revealed that the CO treatment accelerated symbiosis development significantly increasing root colonization by AM fungi. Moreover, the combination of AM fungal inoculation and CO treatment improved plant species evenness and productivity with more balanced composition in forage species. Altogether, our study presented a successful and scalable strategy for the reintroduction of mixed meadows as valuable sources of forage biomass; demonstrated the positive impact of CO treatment on AM development in an agronomic context, extending previous observations developed under controlled laboratory conditions and leading the way to the application in sustainable agricultural practices.

Multiwavelength polarimetry and radio observations of Swift J1727.8–1613 at the beginning of its recent 2023 outburst suggested the presence of a bright compact jet aligned in the north–south direction, which could not be confirmed without high-angular-resolution images. Using the Very Long Baseline Array and the Long Baseline Array, we imaged Swift J1727.8–1613 during the hard/hard-intermediate state, revealing a bright core and a large, two-sided, asymmetrical, resolved jet. The jet extends in the north–south direction, at a position angle of −0.60° ± 0.07° east of north. At 8.4 GHz, the entire resolved jet structure is $\sim 110(d/2.7\,\mathrm{kpc})/\sin i$ au long, with the southern approaching jet extending $\sim 80(d/2.7\,\mathrm{kpc})/\sin i$ au from the core, where d is the distance to the source and i is the inclination of the jet axis to the line of sight. These images reveal the most resolved continuous X-ray binary jet, and possibly the most physically extended continuous X-ray binary jet ever observed. Based on the brightness ratio of the approaching and receding jets, we put a lower limit on the intrinsic jet speed of β ≥ 0.27 and an upper limit on the jet inclination of i ≤ 74°. In our first observation we also detected a rapidly fading discrete jet knot 66.89 ± 0.04 mas south of the core, with a proper motion of 0.66 ± 0.05 mas hr ^−1 , which we interpret as the result of a downstream internal shock or a jet–interstellar medium interaction, as opposed to a transient relativistic jet launched at the beginning of the outburst.

Fast X-ray Transients (FXTs) are extragalactic bursts of soft X-rays first identified ≳10 yr ago. Since then, nearly 40 events have been discovered, although almost all of these have been recovered from archival Chandra and XMM-Newton data. To date, optical sky surveys and follow-up searches have not revealed any multiwavelength counterparts. The Einstein Probe, launched in 2024 January, has started surveying the sky in the soft X-ray regime (0.5–4 keV) and will rapidly increase the sample of FXTs discovered in real time. Here we report the first discovery of both an optical and radio counterpart to a distant FXT, the fourth source publicly released by the Einstein Probe. We discovered a fast-fading optical transient within the 3′ localization radius of EP 240315a with the all-sky optical survey ATLAS, and our follow-up Gemini spectrum provides a redshift, z = 4.859 ± 0.002. Furthermore, we uncovered a radio counterpart in the S band (3.0 GHz) with the MeerKAT radio interferometer. The optical (rest-frame UV) and radio luminosities indicate that the FXT most likely originates from either a long gamma-ray burst or a relativistic tidal disruption event. This may be a fortuitous early mission detection by the Einstein Probe or may signpost a mode of discovery for high-redshift, high-energy transients through soft X-ray surveys, combined with locating multiwavelength counterparts.

Despite advancements in therapeutic strategies, the development of drug resistance and metastasis remains a serious concern for the efficacy of chemotherapy against colorectal cancer (CRC). We have previously demonstrated that low expression of ribosomal protein uL3 positively correlates with chemoresistance in CRC patients. Here, we demonstrated that the loss of uL3 increased the metastatic capacity of CRC cells in chick embryos. Metabolomic analysis revealed large perturbations in amino acid and glutathione metabolism in resistant uL3-silenced CRC cells, indicating that uL3 silencing dramatically triggered redox metabolic reprogramming. RNA-Seq data revealed a notable dysregulation of 108 genes related to ferroptosis in CRC patients. Solute Carrier Family 7 Member 11 (SLC7A11) is one of the most dysregulated genes; its mRNA stability is negatively regulated by uL3, and its expression is inversely correlated with uL3 levels. Inhibition of SLC7A11 with erastin impaired resistant uL3-silenced CRC cell survival by inducing ferroptosis. Of interest, the combined treatment erastin plus uL3 enhanced the chemotherapeutic sensitivity of uL3-silenced CRC cells to erastin. The antimetastatic potential of the combined strategy was evaluated in chick embryos. Overall, our study sheds light on uL3-mediated chemoresistance and provides evidence of a novel therapeutic approach, erastin plus uL3, to induce ferroptosis, establishing individualized therapy by examining p53, uL3 and SLC7A11 profiles in tumors.

(1) Background: Although MRI is a well-established tool in Multiple Sclerosis (MS) diagnosis and management, neuroradiological reports often lack standardization and/or quantitative information, with possible consequences in clinical care. The aim of this study was to evaluate the impact of information provided by neuroradiological reports and different reporting systems on the clinical management of MS patients. (2) Methods: An online questionnaire was proposed to neurologists working in Italian tertiary care level MS centers. Questions assessed the impact of different MRI-derived biomarkers on clinical choices, the preferred way of receiving radiological information, and the neurologists’ opinions about different reporting systems and the use of automated software in clinical practice. (3) Results: The online survey was completed by 62 neurologists. New/enlarging (100%) lesions, the global T2w/FLAIR lesion load (96.8%), and contrast-enhancing (95.2%) lesions were considered the most important biomarkers for therapeutic decision, while new/enlarging lesions (98.4%), global T2w/FLAIR lesion load (96.8%), and cerebral atrophy (90.3%) were relevant to prognostic evaluations. Almost all participants (98.4%) considered software for medical imaging quantification helpful in clinical management, mostly in relation to prognostic evaluations. (4) Conclusions: These data highlight the impact of providing accurate and reliable data in neuroradiological reports. The use of software for medical imaging quantification in MS can be helpful to standardize radiological reports and to provide useful clinical information to neurologists.