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We provide an overview of the status of Monte-Carlo event generators for high-energy particle physics. Guided by the experimental needs and requirements, we highlight areas of active development, and opportunities for future improvements. Particular emphasis is given to physics models and algorithms that are employed across a variety of experiments. These common themes in event generator development lead to a more comprehensive understanding of physics at the highest energies and intensities, and allow models to be tested against a wealth of data that have been accumulated over the past decades. A cohesive approach to event generator development will allow these models to be further improved and systematic uncertainties to be reduced, directly contributing to future experimental success. Event generators are part of a much larger ecosystem of computational tools. They typically involve a number of unknown model parameters that must be tuned to experimental data, while maintaining the integrity of the underlying physics models. Making both these data, and the analyses with which they have been obtained accessible to future users is an essential aspect of open science and data preservation. It ensures the consistency of physics models across a variety of experiments.

Background: Gross motor function impairments and manual dexterity deficits are frequently observed in children and adolescents with Cerebral Palsy (CP), having a major impact on their activity level and autonomy. Improving manual dexterity and activity level of patients with CP is often the focus of rehabilitation. Novel and adjuvant treatment methods that could support the standard training also in chronic conditions are a research priority. The transcutaneous Vagus Nerve Stimulation (tVNS) is a non-invasive brain stimulation technique, which provides a bottom-up stimulation of subcortical and cortical brain structures, enhancing brain GABA and Noradrenaline levels. This technique may play a pivotal role in brain plasticity, which has not been tested in CP patients before., Methods: 44 children and adolescents with CP will be involved, treated in pairs in a randomized, double-blind, pre-post test study. The two groups will undergo the Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) for 2 consecutive weeks, with 3 h daily sessions for 5 days per week, for an overall time interval of 30 h; the training will be combined with the application for 75 min/day of active or sham tVNS, in separate, randomly allocated groups. The primary outcome measure will include the scores at the Assisting Hand Assessment and Box and Block Test, and at an ad-hoc visuomotor task evaluating manual visuomotor control. Secondary outcomes will include the scores at the Children's Hand Experience Questionnaire, Canadian Occupational Performance Measure, Melbourne Assessment of Unilateral Upper Limb Function, Gross Motor Function Measure, Vineland, Pediatric quality of life inventory. The evaluation points will include pre (T0), post (T1) and 3-month follow up (T2) assessments. Safety and tolerability will also be assessed., Results: The results of this trial will assess whether tVNS can effectively boost the effects of an intensive two-week bimanual training, in improving manual dexterity in children and adolescents with cerebral palsy, ensuring safety and tolerability throughout the intervention period. Clinical trial registration : ClinicalTrials.gov, NCT06372028., Competing Interests: The authors declare that the research will be conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Oldrati, Gasparroni, Michelutti, Ciricugno, Borgatti, Orcesi, Fazzi, Morandi, Galli, Piccinini, Maghini, Arioli, Cattaneo, Urgesi and Finisguerra.)

Purpose: Deep brain stimulation (DBS) of nucleus ventralis intermedius thalami (Vim) is a validated technique for the treatment of essential tremor (ET) in adults. Conversely, its use for post traumatic tremor (PTT) and in paediatric patients is still debated. We evaluated the efficacy of Vim-DBS for lesional tremor in three paediatric patients with drug-resistant post-traumatic unilateral tremor., Methods: We retrospectively collected data regarding three patients with unilateral tremor due to severe head injury, with no MRI evidence of basal ganglia lesions. The three patients underwent stereotactic frame-based robot-assisted DBS of Vim contralateral to the tremor side., Results: Mean follow-up was 48 months (range: 36-60 months). Tremor was reduced in all patients with a better control of voluntary movements and improvement of functional status (mean FIM scale improvement + 7 points). No surgical complications occurred., Conclusion: Unilateral contralateral DBS of Vim could be efficacious in post-traumatic tremor, even in paediatric patients and should be offered in PTT drug-resistant patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Plants continuously face various environmental stressors throughout their lifetime. To be able to grow and adapt in different environments, they developed specialized tissues that allowed them to maintain a protected yet interconnected body. These tissues undergo specific primary and secondary cell wall modifications that are essential to ensure normal plant growth, adaptation and successful land colonization. The composition of cell walls can vary among different plant species, organs and tissues. The ability to remodel their cell walls is fundamental for plants to be able to cope with multiple biotic and abiotic stressors. A better understanding of the changes taking place in plant cell walls may help identify and develop new strategies as well as tools to enhance plants' survival under environmental stresses or prevent pathogen attack. Since the invention of microscopy, numerous imaging techniques have been developed to determine the composition and dynamics of plant cell walls during normal growth and in response to environmental stimuli. In this review, we discuss the main advances in imaging plant cell walls, with a particular focus on fluorescent stains for different cell wall components and their compatibility with tissue clearing techniques. Lay Description: Plants are continuously subjected to various environmental stresses during their lifespan. They evolved specialized tissues that thrive in different environments, enabling them to maintain a protected yet interconnected body. Such tissues undergo distinct primary and secondary cell wall alterations essential to normal plant growth, their adaptability and successful land colonization. Cell wall composition may differ among various plant species, organs and even tissues. To deal with various biotic and abiotic stresses, plants must have the capacity to remodel their cell walls. Gaining insight into changes that take place in plant cell walls will help identify and create novel tools and strategies to improve plants' ability to withstand environmental challenges. Multiple imaging techniques have been developed since the introduction of microscopy to analyse the composition and dynamics of plant cell walls during growth and in response to environmental changes. Advancements in plant tissue cleaning procedures and their compatibility with cell wall stains have significantly enhanced our ability to perform high-resolution cell wall imaging. At the same time, several factors influence the effectiveness of cleaning and staining plant specimens, as well as the time necessary for the process, including the specimen's size, thickness, tissue complexity and the presence of autofluorescence. In this review, we will discuss the major advances in imaging plant cell walls, with a particular emphasis on fluorescent stains for diverse cell wall components and their compatibility with tissue clearing techniques. We hope that this review will assist readers in selecting the most appropriate stain or combination of stains to highlight specific cell wall components of interest., (© 2024 The Authors. Journal of Microscopy published by John Wiley & Sons Ltd on behalf of Royal Microscopical Society.)

Alcohol dehydrogenases (ADHs) are a group of zinc-binding enzymes belonging to the medium-length dehydrogenase/reductase (MDR) protein superfamily. In plants, these enzymes fulfill important functions involving the reduction of toxic aldehydes to the corresponding alcohols (as well as catalyzing the reverse reaction, i.e., alcohol oxidation; ADH1) and the reduction of nitrosoglutathione (GSNO; ADH2/GSNOR). We investigated and compared the structural and biochemical properties of ADH1 and GSNOR from Arabidopsis thaliana. We expressed and purified ADH1 and GSNOR and determined two new structures, NADH-ADH1 and apo-GSNOR, thus completing the structural landscape of Arabidopsis ADHs in both apo- and holo-forms. A structural comparison of these Arabidopsis ADHs revealed a high sequence conservation (59% identity) and a similar fold. In contrast, a striking dissimilarity was observed in the catalytic cavity supporting substrate specificity and accommodation. Consistently, ADH1 and GSNOR showed strict specificity for their substrates (ethanol and GSNO, respectively), although both enzymes had the ability to oxidize long-chain alcohols, with ADH1 performing better than GSNOR. Both enzymes contain a high number of cysteines (12 and 15 out of 379 residues for ADH1 and GSNOR, respectively) and showed a significant and similar responsivity to thiol-oxidizing agents, indicating that redox modifications may constitute a mechanism for controlling enzyme activity under both optimal growth and stress conditions., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Cerebral palsy poses challenges in walking, necessitating ankle foot orthoses (AFOs) for stability. Gait analysis, particularly on slopes, is crucial for effective AFO assessment. The study aimed to compare the performance of commercially available AFOs with a new sports-specific AFO in children with hemiplegic cerebral palsy and to assess the effects of varying slopes on gait. Eighteen participants, aged 6-11, with hemiplegia, underwent gait analysis using GRAIL technology. Two AFO types were tested on slopes (uphill +10 deg, downhill -5 deg, level-ground). Kinematic, kinetic, and spatiotemporal parameters were analyzed. The new AFO contributed to significant changes in ankle dorsi-plantar-flexion, foot progression, and trunk and hip rotation during downhill walking. Additionally, the new AFO had varied effects on spatiotemporal gait parameters, with an increased stride length during downhill walking. Slope variations significantly influenced the kinematics and kinetics. This study provides valuable insights into AFO effectiveness and the impact of slopes on gait in hemiplegic cerebral palsy. The findings underscore the need for personalized interventions, considering environmental factors, and enhancing clinical and research approaches for improving mobility in cerebral palsy.

Objective: To review methods for aquatic exercise monitoring using wearables., Data Sources: Database search of PubMed, IEEEXplore, Scopus and Web of Science based on keywords, considering articles from the year 2000. The last search was performed on 26 October 2022., Review Methods: Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocol, eligible articles on water exercises were selected and summarized. Further screening process concentrated on studies exploiting wearable devices, organized according to demographics, purpose, protocols, outcomes and methods. A custom critical appraisal questionnaire was applied., Results: Out of the 1062 articles identified, 572 were considered eligible and subjected to preliminary synthesis. The final review focused on 27 articles featuring wearable devices applied to aquatic exercises. Four studies were disregarded as they applied wearable devices to determine daily physical activity or for sleep monitoring after training. Summary tables of 23 studies exploiting wearable devices for underwater motion analysis are provided, specifying the investigated parameters, major outcomes and study quality. This review identified four research gaps: (a) the absence of clinical protocols for underwater motion studies, (b) a deficit of whole-body studies, (c) the lack of longitudinal studies monitored via wearable devices and (d) the reliance of underwater studies on measurement and assessment methods developed for land-based investigations., Conclusions: This review emphasizes the need for both technological and methodological improvements for underwater motion analysis studies using wearables. We advocate for longitudinal clinical investigations with wearables to substantiate water exercise as an addition or replacement for land-based physical activity.

N-terminal cysteine oxidases (NCOs) use molecular oxygen to oxidise the amino-terminal cysteine of specific proteins, thereby initiating the proteolytic N-degron pathway. To expand the characterisation of the plant family of NCOs (plant cysteine oxidases [PCOs]), we performed a phylogenetic analysis across different taxa in terms of sequence similarity and transcriptional regulation. Based on this survey, we propose a distinction of PCOs into two main groups. A-type PCOs are conserved across all plant species and are generally unaffected at the messenger RNA level by oxygen availability. Instead, B-type PCOs appeared in spermatophytes to acquire transcriptional regulation in response to hypoxia. The inactivation of two A-type PCOs in Arabidopsis thaliana, PCO4 and PCO5, is sufficient to activate the anaerobic response in young seedlings, whereas the additional removal of B-type PCOs leads to a stronger induction of anaerobic genes and impairs plant growth and development. Our results show that both PCO types are required to regulate the anaerobic response in angiosperms. Therefore, while it is possible to distinguish two clades within the PCO family, we conclude that they all contribute to restrain the anaerobic transcriptional programme in normoxic conditions and together generate a molecular switch to toggle the hypoxic response., (© 2022 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.)

Running is an essential activity for children with cerebral palsy (CP). This study aims to characterize the locomotor pattern of running in hemiplegic children with new generation ankle foot orthosis (AFOs) conceived to foster intense motor activities such as running. A group of 18 children with spastic hemiplegia was recruited. A biomechanical multivariable comparison was made between barefoot and with AFO running trials. The focus was devoted to bilateral sagittal plane hip, knee, ankle kinematics and kinetics, and three-dimensional ground reaction forces. Wearing the orthoses, the children were found to reduce cadence and the duration of the stance phase as well as increase the step and stride length. The new AFO resulted in significant changes in kinematics of affected ankle both at initial contact 0-3% GC ( p < 0.017) and during the entire swing phase 31-100%GC ( p < 0.001) being the ankle more dorsiflexed with AFO compared to barefoot condition. Ankle power was found to differ significantly both in absorption and generation 5-10%GC ( p < 0.001); 21-27%GC ( p < 0.001) with a reduction in both cases when the AFO was worn. No statistical differences were recorded in the GRF components, in the affected ankle torque and hip and knee kinematics and kinetics.

Renewable natural resources are strategic for reducing greenhouse gas emissions and the human footprint. The renewability of these resources is a crucial aspect that should be evaluated in utilization of scenario planning. The renewability of geothermal resources is strictly related to the physical and geological processes that favor water circulation and heating. In the Veneto region (NE Italy), thermal waters of the Euganean Geothermal System are the most profitable regional geothermal resource, and its renewability assessment entails the evaluation of fluid and heat recharge, regional and local geological settings, and physical processes controlling system development. This renewability assessment is aimed at defining both the importance of such components and the resource amount that can be exploited without compromising its future preservation. In the second part of the twentieth century, the Euganean thermal resource was threatened by severe overexploitation that caused a sharp decrease in the potentiometric level of the thermal aquifers. Consequently, regulation for their exploitation is required. In this work, the renewability of the Euganean Geothermal System was assessed using the results from numerical simulations of fluid flow and heat transport. The simulations were based on a detailed hydrogeological reconstruction that reproduced major regional geological heterogeneities through a 3D unstructured mesh, while a heterogeneous permeability field was used to reproduce the local fracturing of the thermal aquifers. The model results highlight the role played by the resolved structural elements, in particular the subsurface high-angle faults of the exploitation field, and by the anomalous regional crustal heat flow affecting the central Veneto region., (© 2021. The Author(s).)

Synthetic biology approaches to engineer light-responsive systems are widely used, but their applications in plants are still limited due to the interference with endogenous photoreceptors and the intrinsic requirement of light for photosynthesis. Cyanobacteria possess a family of soluble carotenoid-associated proteins named orange carotenoid proteins (OCPs) that, when activated by blue-green light, undergo a reversible conformational change that enables the photoprotection mechanism that occurs on the phycobilisome. Exploiting this system, we developed a chloroplast-localized synthetic photoswitch based on a protein complementation assay where two nanoluciferase fragments were fused to separate polypeptides corresponding to the OCP2 domains. Since Arabidopsis (Arabidopsis thaliana) does not possess the prosthetic group needed for the assembly of the OCP2 complex, we first implemented the carotenoid biosynthetic pathway with a bacterial β-carotene ketolase enzyme (crtW) to generate keto-carotenoid-producing plants. The photoswitch was tested and characterized in Arabidopsis protoplasts and stably transformed plants with experiments aimed to uncover its regulation by a range of light intensities, wavelengths, and its conversion dynamics. Finally, we applied the OCP-based photoswitch to control transcriptional responses in chloroplasts in response to green light illumination by fusing the two OCP fragments with the plastidial SIGMA FACTOR 2 and bacteriophage T4 anti-sigma factor AsiA. This pioneering study establishes the basis for future implementation of plastid optogenetics to regulate organelle responses upon exposure to specific light spectra., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

The effects of robotic-assisted gait training on upper and lower body strategy during gait in diplegic children with Cerebral Palsy (CP) were quantified using summary parameters (Upper Body Profile Score (UBPS) and Gait Profile Score (GPS)). Firstly, the upper body strategy during gait was assessed in 73 children with CP and 15 healthy children (Control Group: CG): patients with CP exhibited higher values of most of the summary parameters of the upper body position than the CG. Then, the effects of a robotic-assisted gait training in a sub-group of 35 children by means of UBPS were evaluated. After robotic-assisted gait training program, no significant differences as for the summary parameters (UBPS and GPS). However, considering the specific variables scores, significant improvements are displayed as for the upper body parameter on the sagittal plane (Upper Body Ant/Pst index) and the lower limbs, in particular pelvis (Pelvic Ant/Pst and Pelvic Int/Ext indices) and as for walking velocity. A sort of reorganization of full-body kinematics, especially at upper body and proximal level (pelvis) seems to appear, with a new gait approach, characterised by a better strategy of the upper body associated with a significant improvement of the pelvis movement.