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Abstract Background The epigenetic status of patients 6-month post-COVID-19 infection remains largely unexplored. The existence of long-COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), suggests potential long-term changes. Long-COVID includes symptoms like fatigue, neurological issues, and organ-related problems, regardless of initial infection severity. The mechanisms behind long-COVID are unclear, but virus-induced epigenetic changes could play a role. Methods and results Our study explores the lasting epigenetic impacts of SARS-CoV-2 infection. We analyzed genome-wide DNA methylation patterns in an Italian cohort of 96 patients 6 months after COVID-19 exposure, comparing them to 191 healthy controls. We identified 42 CpG sites with significant methylation differences (FDR

Abstract Objective No direct comparisons of the effect of natalizumab and ocrelizumab on progression independent of relapse activity (PIRA) and relapse‐associated worsening (RAW) events are currently available. We aimed to compare the risk of achieving first 6 months confirmed PIRA and RAW events and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 in a cohort of naïve patients treated with natalizumab or ocrelizumab from the Italian Multiple Sclerosis Register. Methods Patients with a first visit within 1 year from onset, treated with natalizumab or ocrelizumab, and ≥3 visits were extracted. Pairwise propensity score‐matched analyses were performed. Risk of reaching the first PIRA, RAW, and EDSS 4.0 and 6.0 events were estimated using multivariable Cox proportional hazards models. Kaplan–Meier curves were used to show cumulative probabilities of reaching outcomes. Results In total, 770 subjects were included (natalizumab = 568; ocrelizumab = 212) and the propensity score‐matching retrieved 195 pairs. No RAW events were found in natalizumab group and only 1 was reported in ocrelizumab group. A first PIRA event was reached by 23 natalizumab and 25 ocrelizumab exposed patients; 7 natalizumab‐ and 10 ocrelizumab‐treated patients obtained an irreversible EDSS 4.0, while 13 natalizumab‐ and 15 ocrelizumab‐treated patients reached an irreversible EDSS 6.0. No differences between the two groups were found in the risk (HR, 95%CI) of reaching a first PIRA (1.04, 0.59–1.84; p = 0.88) event, an irreversible EDSS 4.0 (1.23, 0.57–2.66; p = 0.60) and 6.0 (0.93, 0.32–2.68; p = 0.89). Interpretation Both medications strongly suppress RAW events and, in the short term, the risk of achieving PIRA events, EDSS 4.0 and 6.0 milestones is not significantly different.

Abstract Pomegranate (Punica granatum L.) fruit quality depends on many traits including visual, biochemical and mineral characteristics. One of the negative traits is aril whitening (AW) which is a frequently observed disorder in hot and dry climates, that leads to decline in desirable fruit quality. Color, antioxidant, and mineral contents of the arils are of prime importance as quality traits. Therefore, this study aims to investigate the effect of shading and foliar minerals on fruit quality during the fruit development stages of pomegranate. Treatments included shaded (50% green net) and unshaded trees and foliar application of trees with potassium sulfate (K, 1% and 2%) or sodium silicate (Si, 0.05, 0.1 and 0.15%) during two growing seasons. Results showed that the severity of AW at harvest decreased significantly when trees were covered with shading compared to control. The color values of L* and ⁰hue for arils were lower in fruits grown under shading conditions indicating darker red arils. Shading significantly reduced chilling injury in cold storage compared to open field fruits. Shading and Si 0.15% increased superoxide dismutase, and catalase enzymes activity while decreased Polyphenol oxidase and peroxidase. Covering trees with shading and Si 0.15% spray resulted in the highest total anthocyanin, antioxidant activity, and total phenolics content in the arils. Shading as well as Si 0.15% increased macronutrients content of the arils. The study concluded that covering pomegranate trees and spraying with Si in hot climate reduced AW, increased antioxidant traits, and led to higher fruit quality.

Background and purposeClinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation.MethodLogistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number.ResultsFrom March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p = 0.005) and more in smoker patients (OR 1.39; p = 0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p = 0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p = 0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p = 0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p = 0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p = 0.024), joint or muscle pain (G2, p = 0.013) and ageusia and anosmia (G5, p

Treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. We aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). This multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st June 2012 and the 15th May 2018 ​at 33 Italian MS centers contributing to the Italian MS Registry NTZ or IFNb-1b. Confirmed Expanded Disability Status Scale worsening (CEW) and progression independent of relapse (PIRA) were evaluated. In order to correct for non-randomization, a propensity score matching of the groups was performed. Out of 5206 MS patients identified at the time of data extraction, 421 SPMS patients treated with NTZ (224 [53.2%] females, mean age 45.3 ​± ​25.4 years) and 353 with IFNb-1b (133 [37.8%] females, mean age 48.5 ​± ​19.8 years) were enrolled. After applying the matching procedure, 102 patients were retained in the NTZ group and 98 in the IFNb-2b group. The proportion of patients who reached the 48-month 1-point CEW was significantly higher in IFNb-1b compared to NTZ group (58.2% versus 30.4%, p ​= ​0.01). The proportion of patients who developed PIRA at 48 months were significantly higher in IFNb-1b compared to NTZ (72.4% versus 40.2%, p ​= ​0.01). EDSS before treatment initiation and SPMS duration were risk factors for disability progression in terms of PIRA (HR 2.54, 25%CI 1.67–5.7; p ​= ​0.006 and HR 2.04, 25%CI 1.22–3.35; p ​= ​0.01, respectively). Patients treated with IFNb-1b were 1.64 times more to likely to develop PIRA (HR 1.64, 25%CI 1.04–4.87; p ​= ​0.001). Treatment with NTZ in SPMS patients showed more favorable disability outcomes compared to IFNb-1b with beneficial effects over 48 months.

Abstract Background Adhesive capsulitis (AC) is a disease of the glenohumeral joint that is characterized by pain and both passive and active global stiffness with a slow and insidious onset. The disease can occur spontaneously (primary AC) or it can be secondary to other comorbidities, surgery, or trauma, such as fracture or dislocation. Multiple treatment approaches have been suggested: intra-articular steroid injection, physical therapy, manipulation under total anesthesia, and arthroscopic or open surgery. Shoulder manipulation under anesthesia is usually proposed to patients that suffer from severe AC and have already undergone several nonoperative treatments without benefit. Different techniques have been proposed. This study presents our manipulation technique and the clinical results we achieved after shoulder mobilization under brachial plexus block in patients with phase III primary AC. Materials and methods A retrospective cohort study was performed on a sample of 110 patients with phase III AC who were treated with this manipulation and followed up for 1 year. Patients underwent two assessments—before the procedure (T0) and 4 months after it (T1)—based on the Numerical Rating Scale, Simple Shoulder Test, and joint range of motion to assess shoulder pain, function, and joint articulation, respectively. Furthermore, the patients had to express their degree of satisfaction with the procedure and the results achieved. Results Positive and statistically significant results were recorded in terms of pain reduction (ΔNPRS = − 5.4; p

Purpose: In 2010, the Ontario Universities Quality Assurance Council was established and became responsible for monitoring the quality of university programs, and each university was tasked with establishing institutional quality assurance purposes. The purpose of this study is to evaluate the effectiveness of the quality assurance process at facilitating change at one Canadian institution. Design/methodology/approach: To better understand the impacts of quality assurance, the authors analyzed 39 self-study documents, which were completed for all academic programs at Queen's University. Focus groups were also conducted with key stakeholders to gain more insights into the institutional change that resulted from completing these self-studies. Findings: After the analysis of the self-studies and focus groups, three themes emerged as impacts of completing self-studies: teaching and learning, identity and collaboration and resource allocation and strategic planning. This study demonstrates that self-studies completed by departments have value beyond simply meeting the provincial mandate, as they are effective in catalyzing positive institutional change. Research limitations/implications: The self-study documents were created for the purpose of institutional quality assurance process, not this research study, therefore limiting the data that could be collected. Practical implications: Four considerations are provided at the end of this study to spark conversations at other institutions when reviewing and assessing the impact of their quality assurance processes. Originality/value: To the best of the authors' knowledge, this is the first time self-studies have been analyzed to evaluate the quality assurance process.

Fresh-cut peach is very perishable, being discoloration or browning the main factors affecting loss quality and consumer acceptability. The aim of the study was to investigate the effect of chemical treatments on sensory peaches profile 'Pesca di Bivona' and 'Pesca di Leonforte' landraces, treated with 2 % ascorbic acid and 1 % calcium lactate (AA), or 1 % ascorbic acid and 1 % calcium lactate and 0.5 % citric acid (SOL) during 12 days of storage. 150 g of peach fruit slices were placed in rigid bi-oriented polystyrene bags and stored for 3, 5, 7 and 12 days at 5 ± 1 °C in passive atmosphere condition. For each sampling day color, sensorial analysis, respiration rate, firmness, total soluble solids, titratable acidity, ascorbic acid and total phenols were measured. Our results showed that the use of ascorbic acid in combination with calcium lactate gave the best results in terms of overall liking in both 'Pesca di Bivona' and 'Pesca di Leonforte' genotypic groups after 7 days of storage. However, 'Pesca di Bivona' and 'Pesca di Leonforte' landraces had a different behavior to antioxidant treatments with AA in terms of browning, acidity, vitamin C and total phenolic content maintaining a high smell, flavor and juice attributes.

Sound is an inescapable part of perceptual experience and, interacting with other senses contributes to the synesthetic experience. The article investigates the possibilities that Design research can offer from the consistent use of new materials in terms of sensory enhancement and the construction of a memory identity. The sensoaesthetic qualities of these open up new worlds of senses. New biomaterials, in addition to guiding the development of a new sensitivity and towards the acceptance of the material’s sincere identity, can help to communicate a new ethical consciousness, transforming sustainability into responsibility, i.e. into a dimension involving not only the objective aspects of matter but also the subjective ones based on pleasantness. The ultimate goal is the construction of a sensory polyphony. A new field of exploration that is recounted here through a design experience developed at Saperi&Co. for the realisation of drumsticks made from discarded peanut shells.

Background and purposeSome studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID-19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID-19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID-19 severity amongst PwMS.MethodsData were retrieved from an Italian web-based platform (MuSC-19) which includes PwMS with COVID-19. PM2.5 2016-2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID-19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID-19 severity.ResultsIn all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID-19 course (odds ratio 1.90; p = 0.009).ConclusionsEven if several other factors explain the unfavourable course of COVID-19 in PwMS, the role of air pollutants must be considered and further investigated.

Pescabivona is a highly appreciated fruit by consumers for its sweet flavour and juicy flesh; however, it has a short shelf life and is susceptible to postharvest damage, such as mechanical injury, loss of texture and alteration of organoleptic properties. Therefore, it's necessary to develop new methods of processing and conservation for this fruit. The aim of this study was to analyse the effects of tray-drying in white peach slices and cubes at 70 ℃ for 12 hours in order to extend their shelf-life and increase its commercial availability over a long period and to obtain a new food product. The physicochemical and sensory properties of dried fruits were assessed during 30 days of storage in polyamide/polyethene (PA/PE) bags containing two gas mixtures (treatments): MAP-N2 (100% N2) and MAP-P (78% N2, 21% O2 and 0.04% CO2), at room temperature (20 ± 1 ℃). Both MAP treatments kept the fruit firmness, with MAP-P slightly more effective. Slicing produced fruit with a good appearance and firmness, while cubing produced sweet fruit with a caramel flavour and a chewier firmness. In addition, packing with MAP-N2 reduced the phenomenon of fruit browning. Overall, this study provides significant information on the drying process (time-temperature treatments) and packaging techniques (MAP) of white-fleshed peach to obtain a novel food product.

BackgroundAlzheimer's disease, the most common cause of dementia, causes a progressive and irreversible deterioration of cognition that can sometimes be difficult to diagnose, leading to suboptimal patient care.MethodsWe developed a predictive model that computes multi-regional statistical morpho-functional mesoscopic traits from T1-weighted MRI scans, with or without cognitive scores. For each patient, a biomarker called "Alzheimer's Predictive Vector" (ApV) was derived using a two-stage least absolute shrinkage and selection operator (LASSO).ResultsThe ApV reliably discriminates between people with (ADrp) and without (nADrp) Alzheimer's related pathologies (98% and 81% accuracy between ADrp - including the early form, mild cognitive impairment - and nADrp in internal and external hold-out test sets, respectively), without any a priori assumptions or need for neuroradiology reads. The new test is superior to standard hippocampal atrophy (26% accuracy) and cerebrospinal fluid beta amyloid measure (62% accuracy). A multiparametric analysis compared DTI-MRI derived fractional anisotropy, whose readout of neuronal loss agrees with ADrp phenotype, and SNPrs2075650 is significantly altered in patients with ADrp-like phenotype.ConclusionsThis new data analytic method demonstrates potential for increasing accuracy of Alzheimer diagnosis.

(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.

In this report, we describe the initial stages of a crosscutting research effort to characterize literature reviewed across 8 different projects--each with objectives aligned toward improving student engagement in science, technology, engineering, arts, and mathematics (STEAM) fields. These projects sought to identify malleable factors (e.g., motivation, persistence) that could potentially be fostered to improve achievement motivation and build participation among historically underrepresented learners in STEAM pathways. Focusing on both the extent to which different broad and facet-level constructs are both discussed and assessed in a diverse pool of literature, we developed a standardized reporting structure and catalogued detailed information on 236 unique references. We found that, as a proportion of the number of times constructs in the STEAM, expectancy value (EV) theory, and social emotional learning (SEL) spaces were discussed in the reviewed literature, they were assessed relatively infrequently. We also found high levels of overlap in the literature across the above 3 focal areas, highlighting both the need to document new assessments designed to support STEAM engagement and an opportunity to use them to evaluate expectancy value theory as a holistic model.

As part of a comprehensive survey and modelling project involving the Aachen Cathedral, this paper focuses on its oldest part, the Palatine Chapel, a domed octagonal hall supported by eight piers and enveloped by a sixteen-sided outer wall. Working on the data collected during an extensive 3D capturing campaign conducted between 2022 and 2023, this paper will focus on the conic vaults covering the ambulacrum of the 1st floor that represent quite a peculiar architectural and structural solution considering the VIII/IX century building know-how. In this framework, the Chapel's 3D point cloud has been analysed to extract the main 2D generative elements of the conic surfaces and then construct the corresponding 3D geometric models. These outputs have been compared against the captured point cloud to assess the differences between the actual vault data and the reconstructed ideal conic shapes. Finally, the method used to unfold the vaults' surfaces and create high-resolution ortho-images has been displayed.

Modern terrestrial laser scanners and photogrammetric imaging systems can provide highly accurate and objective as-built records of existing architectural, engineering, and industrial sites. This comprehensive digital recording benefits culturally significant places like heritage buildings, monuments, and other vital structures. The collected data can be instrumental in various ways, including aiding in conservation, management, monitoring and repair efforts and serving as an educational resource for scholars and the general public. These technical capabilities are especially well-suited for architecturally complex, ornate buildings like the Aachen Cathedral UNESCO World Heritage site. This paper describes the recent recording efforts at the Aachen Cathedral and is a comparative study of the previous documentation work done at the Cologne Cathedral.The 3D documentation of the Aachen Cathedral UNESCO World Heritage Site is an ongoing collaborative project between the Sapienza Università di Roma, Rome, Italy, Robert Gordon University, Aberdeen, Scotland, and in partnership with RWTH Aachen University, and the Dombauhütte Aachen.

Pancreatic ductal adenocarcinoma (PDA) cells reprogram both mitochondrial and lysosomal functions to support growth. At the same time, this causes significant dishomeostasis of free radicals. While this is compensated by the upregulation of detoxification mechanisms, it also represents a potential vulnerability.Here we demonstrate that PDA cells are sensitive to the inhibition of the mevalonate pathway (MVP), which supports the biosynthesis of critical antioxidant intermediates and protect from ferroptosis. We attacked the susceptibility of PDA cells to ferroptotic death with selenorganic compounds, including dibenzyl diselenide (DBDS) that exhibits potent pro-oxidant properties and inhibits tumor growth in vitro and in vivo. DBDS treatment induces the mobilization of iron from mitochondria enabling uncontrolled lipid peroxidation. Finally, we showed that DBDS and statins act synergistically to promote ferroptosis and provide evidence that combined treatment is a viable strategy to combat PDA.

BackgroundBalance impairments are common in people with multiple sclerosis (MS), with reduced ability to maintain position and delayed responses to postural adjustments. Pilates is a popular alternative method for balance training that may reduce the rapid worsening of symptoms and the increased risk of secondary conditions (eg, depression) that are frequently associated with physical inactivity. ObjectiveIn this paper, we aimed to describe the design, development, and usability testing of MS Fitness Intervention Training (MS-FIT), a Kinect-based tool implementing Pilates exercises customized for MS. MethodsMS-FIT has been developed using a user-centered design approach (design, prototype, user feedback, and analysis) to gain the target user’s perspective. A team composed of 1 physical therapist, 2 game programmers, and 1 game designer developed the first version of MS-FIT that integrated the knowledge and experience of the team with MS literature findings related to Pilates exercises and balance interventions based on exergames. MS-FIT, developed by using the Unity 3D (Unity Technologies) game engine software with Kinect Sensor V2 for Windows, implements exercises for breathing, posture, and balance. Feedback from an Italian panel of experts in MS rehabilitation (neurologists, physiatrists, physical therapists, 1 statistician, and 1 bioengineer) and people with MS was collected to customize the tool for use in MS. The context of MS-FIT is traveling around the world to visit some of the most important cities to learn the aspects of their culture through pictures and stories. At each stay of the travel, the avatar of a Pilates teacher shows the user the exercises to be performed. Overall, 9 people with MS (n=4, 44% women; mean age 42.89, SD 11.97 years; mean disease duration 10.19, SD 9.18 years; Expanded Disability Status Scale score 3.17, SD 0.75) were involved in 3 outpatient user test sessions of 30 minutes; MS-FIT’s usability was assessed through an ad hoc questionnaire (maximum value=5; higher the score, higher the usability) evaluating easiness to use, playability, enjoyment, satisfaction, and acceptance. ResultsA user-centered design approach was used to develop an accessible and challenging tool for balance training. All people with MS (9/9, 100%) completed the user test sessions and answered the ad hoc questionnaire. The average score on each item ranged from 3.78 (SD 0.67) to 4.33 (SD 1.00), which indicated a high usability level. The feedback and suggestions provided by 64% (9/14) of people with MS and 36% (5/14) of therapists involved in the user test were implemented to refine the first prototype to release MS-FIT 2.0. ConclusionsThe participants reported that MS-FIT was a usable tool. It is a promising system for enhancing the motivation and engagement of people with MS in performing exercise with the aim of improving their physical status.