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Projecting the global evolution of glaciers is crucial to quantify future sea-level rise and changes in glacier-fed rivers. Recent intercomparison efforts have shown that a large part of the uncertainties in the projected glacier evolution is driven by the glacier model itself and by the data used for initial conditions and calibration. Here, we quantify the effect that mass balance observations, one of the most crucial data sources used in glacier modelling, have on glacier projections. For this, we model the 21st century global glacier evolution under Coupled Model Intercomparison Phase 6 project (CMIP6) climate scenarios with the Global Glacier Evolution Model (GloGEM) calibrated to match glacier-specific mass balance observations, as opposed to relying on regional mass balance observations. We find that the differences in modelled 21st century glacier changes can be large at the scale of individual glaciers (up to several tens of percent), but tend to average out at regional to global scales (a few percent at most). Our study thus indicates that the added value of relying on glacier-specific observations is at the subregional and local scale, which will increasingly allow projecting the glacier-specific evolution and local impacts for every individual glacier on Earth. To increase the ensemble of models that project global glacier evolution under CMIP6 scenarios, simulations are also performed with the Open Global Glacier Model (OGGM). We project the 2015–2100 global glacier loss to vary between 25 ± 15 % (GloGEM) and 29 ± 14 % (OGGM) under SSP1-2.6 to 46 ± 26 % and 54 ± 29 % under SSP5-8.5 (ensemble median, with 95 % confidence interval; calibration with glacier-specific observations). Despite some differences at the regional scale and a slightly more pronounced sensitivity to changing climatic conditions, our results agree well with the recent projections by Rounce et al. (2023), thereby projecting, for any emission scenario, a higher 21st century mass loss than the current community estimate from the second phase of the Glacier Model Intercomparison Project (GlacierMIP2).

Biological patterning events that occur early in development establish proper tissue morphogenesis. Identifying the mechanisms that guide these patterning events is necessary in order to understand the molecular drivers of development and disease and to build tissues in vitro. In this study, we use an in vitro model of gastrulation to study the role of tight junctions and apical/basolateral polarity in modulating bone morphogenic protein-4 (BMP4) signaling and gastrulation-associated patterning in colonies of human pluripotent stem cells (hPSCs). Disrupting tight junctions via knockdown (KD) of the scaffolding tight junction protein-1 (TJP1, also known as ZO1) allows BMP4 to robustly and ubiquitously activate pSMAD1/5 signaling over time, resulting in loss of the patterning phenotype and marked differentiation bias of pluripotent stem cells to primordial germ cell-like cells (PGCLCs). These findings give important insights into how signaling events are regulated and lead to spatial emergence of diverse cell types in vitro.

Mariaelena Malvasi,1 Sabrina Compagno,1 Alessandro Segnalini,1 Vito Maurizio Malvasi,2 Fernanda Pacella,3 Paolo Turchetti,4 Elena Pacella1 1Department of Sense Organs, Faculty of Medicine and Dentistry, Sapienza University of Rome, Rome, Italy; 2Department of Odontostomatological and Maxillo-Facial Sciences, Sapienza University of Rome, Rome, Italy; 3Department of Ophthalmology, Carlo Poma Hospital, Mantua, Italy; 4National Institute for Health, Migration and Poverty (INMP/NIHMP), Rome, ItalyCorrespondence: Elena Pacella, Department of Sense Organs, University Sapienza, Rome, Policlinico Umberto I, Viale, del Policlinico 155, Rome, 00161, Italy, Email elena.pacella@uniroma1.itBackground: The success of fixation training using microperimetric biofeedback (MP-3 MBFT) in the realm of visual rehabilitation for patients with central vision loss caused by macular pathologies is well established. This study aimed to assess the effectiveness and safety of visual rehabilitation with microperimetric biofeedback in consolidating the benefits obtained, with the goal of reducing the need for repeated intravitreal injections (IVT). Specifically, the focus is on the eyes of patients with central vision loss treated with slow-release corticosteroid IVT following retinal venous thrombosis (RVO), aiming to enhance and maintain postoperative efficacy.Methods: This retrospective review involved the examination of 44 eyes affected by macular edema due to RVO associated with central vision loss. Patients were divided into two groups, with only one undergoing ten sessions of 10-minute visual rehabilitation with a microperimeter (MP-3 MBFT) after IVT over a period of 20 weeks.Results: All the treated patients demonstrated good tolerance to the procedure, with no reported complications. A comparison of best-corrected visual acuity (BCVA), retinal sensitivity recorded with a microperimeter, and pre-IVT fixation stability revealed statistically significant improvements at the end of the first month after IVT. However, the treatment group continued to exhibit superior and more enduring results at four months post-IV.Conclusion: The synergistic use of MP-3 MBFT rehabilitation after IVT with slow-release corticosteroids has proven particularly effective in improving BCVA and long-term fixation stability. This led to a significant reduction in the number of required IVTs, with no related adverse events. The authors argue that biofeedback utilization represents a noninvasive therapeutic option devoid of contraindications and easy to implement and that it positively contributes to the overall patient experience regarding quality of life in advanced stages of macular diseases.Keywords: microperimetric biofeedback, visual rehabilitation, macular edema, intravitreal corticosteroid, retinal vein occlusion

Mycobacterium senegalense is a Non-Tuberculous Mycobacterium (NTM) belonging to the M. fortuitum group, often associated with veterinary diseases, such as bovine farcy. However, it can also cause human infections and appears to be involved in Catheter-Associated Infections in immunocompromised patients. Here, we report the first Italian isolation of a strain of M. senegalense from a 16-year-old oncological female patient being treated at Fondazione IRCCS Policlinico San Matteo Pavia (Italy). Following pain at the Port-a-Cath site, a pus culture was collected and the positivity for the M. fortuitum group revealed the NTM infection. Antimicrobial susceptibility tests were performed and interpreted according to the available CLSI breakpoints. This information allowed us to implement the correct antibiotic therapy that, together with the device removal, led to the patient’s recovery. Finally, due to the increasing number of isolations, the possible presence of NTM infections in prosthetic devices should be among the primary diagnostic questions in a clinical setting.

This paper deals with a major challenge linked to the collection of audiovisual documents within television and web archives. Looking for repeated sequences within a corpus of thousands of videos, we faced the fact that the footage we were looking for reveals itself to be reachable only as ghost data. In fact, any audiovisual sequence reused within different contexts exists conceptually as the repetition of one single visual unit, but from the point of view of the metadata tagging its occurrences, each item is a distinct document. Like a ghost, the shot is there, scattered among different places, but the metadata cannot point us to the visual form repeated, despite its evidence to the human viewer. When facing large amounts of data, to relate a visual unit to its occurrences, data analysis techniques are needed. We describe our procedures of collection and annotation, and the solutions combining qualitive work and a computer-aided approach to face this main challenge, within the research project Crossing Borders Archives (CROBORA).

A wide range of platinum(0)-η2-(E)-1,2-ditosylethene complexes bearing isocyanide, phosphine and N-heterocyclic carbene ancillary ligands have been prepared with high yields and selectivity. All the novel products underwent thorough characterization using spectroscopic techniques, including NMR and FT-IR analyses. Additionally, for some compounds, the solid-state structures were elucidated through X-ray diffractometry. The synthesized complexes were successively evaluated for their potential as anticancer agents against two ovarian cancer cell lines (A2780 and A2780cis) and one breast cancer cell line (MDA-MB-231). The majority of the compounds displayed promising cytotoxicity within the micromolar range against A2780 and MDA-MB-231 cells, with IC50 values comparable to or even surpassing those of cisplatin. However, only a subset of compounds was cytotoxic against cisplatin-resistant cancer cells (A2780cis). Furthermore, the assessment of antiproliferative activity on MRC-5 normal cells revealed certain compounds to exhibit in vitro selectivity. Notably, complexes 3d, 6a and 6b showed low cytotoxicity towards normal cells (IC50 > 100 µM) while concurrently displaying potent cytotoxicity against cancer cells.

The Toffoli gate is the essential ingredient for reversible computing, an energy-efficient classical computational paradigm that evades the energy dissipation resulting from Landauer's principle. In this paper, we analyze different setups to realize a magnetic implementation of the Toffoli gate using three interacting classical spins, each one embodying one of the three bits needed for the Toffoli gate. In our scheme, different control-spin configurations produce an effective field capable of conditionally flipping the target spin. We study what the experimental requirements are for the realization of our scheme, focusing on the degree of local control, the ability to dynamically switch the spin-spin interactions, and the required single-spin anisotropies to make the classical spin stable, showing that these are compatible with current technology.

Abstract Background Gangliogliomas are brain tumors associated with drug-resistant focal epilepsy. In most cases, seizures improve after surgical treatment. It is still not concluded to what extent the lesion itself or the perilesional area contributes to the epileptogenicity. Case presentation In the case presented in this report, the patient, a 24-year-old Caucasian male, developed a refractory status epilepticus after a surgical attempt to remove a cerebral ganglioglioma. The postoperative magnetic resonance imaging revealed that the lesion was intact, and that inadvertently only the perilesional area and adjacent cortex had been resected. The patient underwent a new surgical procedure where the ganglioglioma was removed, and the status epilepticus cessated. Conclusions This clinical case suggests that the lesion itself plays an important role in seizure generation and propagation, and notably, that the surrounding cortex by an inhibitory action can act as a gate to seizure spread.

More than 10,000 locations in High-Mountain Asia are identified as likely to host ice-dammed lakes, responsible for most of the glacier outburst floods in High-Mountain Asia, using a combination of a digital elevation model and a glacier model.

Mycobacterium senegalense is a Non-Tuberculous Mycobacterium (NTM) belonging to the M. fortuitum group, often associated with veterinary diseases, such as bovine farcy. However, it can also cause human infections and appears to be involved in Catheter-Associated Infections in immunocompromised patients. Here, we report the first Italian isolation of a strain of M. senegalense from a 16-year-old oncological female patient being treated at Fondazione IRCCS Policlinico San Matteo Pavia (Italy). Following pain at the Port-a-Cath site, a pus culture was collected and the positivity for the M. fortuitum group revealed the NTM infection. Antimicrobial susceptibility tests were performed and interpreted according to the available CLSI breakpoints. This information allowed us to implement the correct antibiotic therapy that, together with the device removal, led to the patient's recovery. Finally, due to the increasing number of isolations, the possible presence of NTM infections in prosthetic devices should be among the primary diagnostic questions in a clinical setting. [ABSTRACT FROM AUTHOR]

Currently, about 12 %–13 % of High Mountain Asia’s glacier area is debris-covered, which alters its surface mass balance. However, in regional-scale modelling approaches, debris-covered glaciers are typically treated as clean-ice glaciers, leading to a bias when modelling their future evolution. Here, we present a new approach for modelling debris area and thickness evolution, applicable from single glaciers to the global scale. We derive a parameterization and implement it as a module into the Global Glacier Evolution Model (GloGEMflow), a combined mass-balance ice-flow model. The module is initialized with both glacier-specific observations of the debris' spatial distribution and estimates of debris thickness. These data sets account for the fact that debris can either enhance or reduce surface melt depending on thickness. Our model approach also enables representing the spatiotemporal evolution of debris extent and thickness. We calibrate and evaluate the module on a selected subset of glaciers and apply GloGEMflow using different climate scenarios to project the future evolution of all glaciers in High Mountain Asia until 2100. Explicitly accounting for debris cover has only a minor effect on the projected mass loss, which is in line with previous projections. Despite this small effect, we argue that the improved process representation is of added value when aiming at capturing intra-glacier scales, i.e. spatial mass-balance distribution. Depending on the climate scenario, the mean debris-cover fraction is expected to increase, while mean debris thickness is projected to show only minor changes, although large local thickening is expected. To isolate the influence of explicitly accounting for supraglacial debris cover, we re-compute glacier evolution without the debris-cover module. We show that glacier geometry, area, volume, and flow velocity evolve differently, especially at the level of individual glaciers. This highlights the importance of accounting for debris cover and its spatiotemporal evolution when projecting future glacier changes.

IntroductionInclusive physical activity games at school can be useful for teachers dealing with students with disabilities. The use of inclusive strategies and games can be directly linked to teachers’ self-efficacy and familiarity with the inclusive strategies, while it could be indirectly influenced by their attitude toward inclusion and, in a smaller part, by social desirability in their response. Moreover, teachers’ responses could be different among the different school grades. Therefore, the aim of the current study is to investigate the role of attitude toward inclusion, social desirability, self-efficacy, and familiarity in the use of physical activity games at school in teachers from all school grades.MethodsA sample of 1,583 schoolteachers was asked to fill out a questionnaire about their perceptions of governmental measures, self-efficacy, familiarity with inclusive strategies through physical activity, and two standardized questionnaires assessing attitudes toward inclusion and social desirability.ResultsTeachers from primary school reported lower scores in attitude toward inclusion total score and dimensions, namely impact on teacher, impact on the environment, impact on the other children, and impact on the student with disability. Moreover, the path analysis model showed that the attitude toward inclusion indirectly influenced the use of inclusive strategy and had a small direct effect on familiarity with inclusive strategies and self-efficacy. Social desirability slightly influenced both familiarity and self-efficacy but not the use of inclusive strategies. Familiarity and self-efficacy had a direct effect on the use of inclusive physical activity games.DiscussionThe results of the current study suggest that being familiar with and having a high self-efficacy in implementing inclusive strategies are well related to the use of inclusive strategies at school. In addition, more attention should be given to kindergarten and primary school teachers, who reported lower scores in the attitude toward inclusion and higher scores in social desirability.

Galectins play relevant roles in tumor development, progression and metastasis. Accordingly, galectins are certainly enticing targets for medical intervention in cancer. To date, however, clinical trials based on galectin inhibitors reported inconclusive results. This review summarizes the galectin inhibitors currently being evaluated and discusses some of the biological challenges that need to be addressed to improve these strategies for the benefit of cancer patients.

Background and Objectives: In patients with multiple sclerosis (MS), a decrease in muscle strength can lead to limitations in pulmonary functions, potentially causing respiratory complications. To address these challenges, the lung volume recruitment (LVR) maneuver has emerged as a potential intervention. This study sought to evaluate the impact of a four-week LVR protocol on respiratory function in secondary progressive MS patients. Materials and Methods: In a quasi-randomized pre/post-controlled trial, 24 patients with secondary progressive MS were recruited. Participants aged 20–70 years with an EDSS score of 2 to 9 were alternately allocated to intervention (n = 12) or control groups (n = 12). The intervention group underwent a 4-week respiratory rehabilitation training focused on LVR, using a standardized cough machine treatment protocol twice daily. The control group received no respiratory intervention. Outcomes measured included forced vital capacity (FVC), maximal insufflation capacity (MIC), and peak cough flow (PCF), using turbine spirometry and other associated equipment. All measurements were taken at baseline (T0) and after 4 weeks (T1) by a blinded assessor. Results: For the intervention group, the mean difference pre/post-treatment in MIC (mL) was 0.45 (SD 1.13) (p = 0.02), and in MIC (%), it was 0.13 (SD 0.24) (p = 0.03). Compared to the control group (n = 10), the between-group mean difference for MIC (mL) was 0.54 (p = 0.02), and for MIC (%), it was 0.15 (p = 0.02). Conclusions: The short-term daily LVR protocol notably improved passive lung capacity, despite minimal changes in active lung capacity or cough force. The LVR maneuver offers promise for enhancing respiratory function, especially passive lung capacity, in secondary progressive MS patients. Further research should explore optimal treatment durations and frequencies for more extensive respiratory gains.