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The paper presents a report that discusses the experience of participation of the authors in the EduHack, an online course designed to train university teachers in the use of digital techniques and learning strategies. This study highlights two issues of great interest in pandemic times. The first one is the structure and the organization of the EduHack course with some suggestions related to its improvement; the second one is Drag&Fly, the project idea of an e-learning web platform developed by the authors during the collaborative part of the course. The experience of participation to EduHack course has been analyzed by authors using concepts and categories of analysis widespread in the pragmatic theoretical tradition, enhancing the possibility of changing the teachers' approach to the design and the implementation of a higher education e-learning course.

Modern cloud/edge architectures need to orchestrate multiple layers of heterogeneous computing nodes, including pervasive sensors/actuators, distributed edge/fog nodes, centralized data centers, and quantum devices. The optimal assignment and scheduling of computation on the different nodes is a very difficult problem, with NP-hard complexity. In this article, we explore the possibility of solving this problem with variational quantum algorithms, which can become a viable alternative to classical algorithms in the near future. In particular, we compare the performance, in terms of success probability, of two algorithms, i.e., quantum approximate optimization algorithm and variational quantum eigensolver (VQE). The simulation experiments, performed for a set of simple problems, show that the VQE algorithm ensures better performance when it is equipped with appropriate circuit ansatzes that are able to restrict the search space. Moreover, experiments executed on real quantum hardware show that the execution time, when increasing the size of the problem, grows much more slowly than the trend obtained with classical computation, which is known to be exponential.

Ion channelopathies result from impaired ion channel protein function, due to mutations affecting ion transport across cell membranes. Over 40 diseases, including neuropathy, pain, migraine, epilepsy, and ataxia, are associated with ion channelopathies, impacting electrically excitable tissues and significantly affecting skeletal muscle. Gene mutations affecting transmembrane ionic flow are strongly linked to skeletal muscle disorders, particularly myopathies, disrupting muscle excitability and contraction. Electromyography (EMG) analysis performed on a patient who complained of weakness and fatigue revealed the presence of primary muscular damage, suggesting an early-stage myopathy. Whole exome sequencing (WES) did not detect potentially causative variants in known myopathy-associated genes but revealed a novel homozygous deletion of the P2RX6 gene likely disrupting protein function. The P2RX6 gene, predominantly expressed in skeletal muscle, is an ATP-gated ion channel receptor belonging to the purinergic receptors (P2RX) family. In addition, STRING pathways suggested a correlation with more proteins having a plausible role in myopathy. No previous studies have reported the implication of this gene in myopathy. Further studies are needed on patients with a defective ion channel pathway, and the use of in vitro functional assays in suppressing P2RX6 gene expression will be required to validate its functional role.

In the energy production and transportation industries, numerous metallic structures may be subjected to at least several billions of cycles, i.e. loaded in the very high cycle fatigue domain (VHCF). Therefore, to design structures in the VHCF domain, a reliable methodology is necessary. One useful quantity to characterize plastic activity at the microscopic scale and fatigue damage evolution is the mechanical work supplied to a material. However, the estimation of this mechanical work in a metal during ultrasonic fatigue tests remains challenging. This paper aims to present an innovative methodology to quantify this. An experimental procedure was developed to estimate the mechanical work from stress and total strain evolution measurements during one loading cycle with a time accuracy of about 50 ns. This was achieved by conducting time-resolved X-ray diffraction coupled to strain gauge measurements at a synchrotron facility working in pulsed mode (single-bunch mode).

Abstract Background The introduction of biological drugs has led to great expectations and growing optimism in the possibility that this new therapeutic strategy could favourably change the natural history of Inflammatory Bowel Disease (IBD) and, in particular, that it could lead to a significant reduction in surgery in the short and long term. This study aims to assess the impact of biological versus conventional therapy on surgery-free survival time (from the diagnosis to the first bowel resection) and on the overall risk of surgery in patients with Crohn’s disease (CD) who were never with the surgical option. Methods This is a retrospective, double-arm study including CD patients treated with either biological or conventional therapy (mesalamine, immunomodulators, antibiotics, or steroids). All CD patients admitted at the GI Unit of the S. Salvatore Hospital (L’Aquila. Italy) and treated with biological therapy since 1998 were included in the biological arm. Data concerning the CD patients receiving a conventional therapy were retrospectively collected from our database. These patients were divided into a pre-1998 and post-1998 group. Our primary outcome was the evaluation of the surgery-free survival since CD diagnosis to the first bowel resection. Surgery-free time and event incidence rates were calculated and compared among all groups, both in the original population and in the propensity-matched population. Results Two hundred three CD patients (49 biological, 93 conventional post-1998, 61 conventional pre-1998) were included in the study. Kaplan-Meier survivorship estimate shows that patients in the biological arm had a longer surgery-free survival compared to those in the conventional arm (p = 0.03). However, after propensity matching analysis, conducted on 143 patients, no significant difference was found in surgery-free survival (p = 0.3). A sub-group analysis showed shorter surgery-free survival in patients on conventional therapy in the pre-biologic era only (p = 0.02; Hazard Ratio 2.9; CI 1.01–8.54) while no significant difference was found between the biologic and conventional post-biologic groups (p = 0.15; Hazard Ratio 2.1; CI 0.69–6.44). Conclusion This study shows that the introduction of biological therapy has only a slight impact on the eventual occurrence of surgery in CD patients over a long observation period. Nevertheless, biological therapy appears to delay the first intestinal resection.

The production of beer, a beverage of global cultural and industrial importance, has a significant impact on the environment due to the use of natural resources and the emissions generated during the various stages of the production process. Therefore, this article examines the sustainability of beer production through a review of literature articles that have used Life Cycle Assessment (LCA) to assess its environmental impacts. A systematic literature review was conducted by selecting peer-reviewed articles published between 2001 and July 2024 using databases such as Scopus and Google Scholar. The search included studies analyzing different stages of the beer life cycle, from raw material production to packaging and distribution, using specific keywords related to LCA and brewing. The results showed that energy use and packaging are the two critical aspects identified in the review, which represent a significant part of the environmental footprint. However, it is important to note that the available studies on the subject are few and heterogeneous and they use different methodologies, impact categories, and functional units, which complicates the comparison and synthesis of results, limiting the ability to draw definitive conclusions. Recommendations were made to improve sustainability, including the adoption of more efficient technologies, the use of recycled materials for packaging, and the implementation of sustainable agricultural practices. These strategies could aim to significantly reduce the overall environmental impact of beer production.

Background: Thirty years ago, the first attempt by Saliba and colleagues was made to reduce the negative effects (hypercarbia) of exogenous surfactant (ES) by slowing its administration. Sixteen years later, we observed the first less invasive surfactant administration (LISA) attempt by Kribs and colleagues. Many studies, since that time, have tried to minimize the invasiveness of ES and subsequent cerebral blood flow perturbations through studies using near-infrared spectroscopy (NIRS). We sought to address this medical challenge by identifying a less problematic modality of ES administration by delivering multiple aliquots of ES instead of a single one, as typically performed. The aim of this study was to test the hypothesis that a different way of administering ES using more aliquots could be a safe alternative that should be assessed in further studies. Methods: Patients between 26 + 0 and 35 + 6 weeks of gestational age (GA) requiring ES administration were enrolled (April 2023–February 2024). Differently fractioned doses were delivered according to an arbitrary standard dosage (0.3 mL per aliquot in babies < 29 weeks; 0.6 mL in babies ≥ 29 weeks), while NIRS and transcutaneous CO2 (tCO2) monitoring were always performed. ES’s effectiveness was assessed based on the reduction in the Oxygen Saturation Index (OSI) after administration. Persistent desaturation, bradycardia, and airway obstruction were defined as adverse effects and used to evaluate safety during ES administration, as well as variability in NIRS-rSO2 values and tCO2. Results: Twenty-four patients were enrolled with a median GA of 29 weeks (IQR 4.5) and BW of 1223 ± 560 g. In addition, 50% of the cohort received fewer than three aliquots, whereas the other 50% received more than three. Monitoring was started before the procedure and continued 30′ after the last ES aliquot administration. The variability in NIRS-SpO2 values was significantly higher in the group (p = 0.007) with a lower number of aliquots administered. Similarly, increased NIRS-rSO2 values (p = 0.003) and increased tCO2 levels (p = 0.005) were observed in infants who underwent an ES split after the administration of a low number of aliquots. Conclusions: Our data obtained from the group with > 3 fractionated doses of ES seem to justify the preparation of a more robust study, as the combination of reduced NIRS variability and reduced tCO2 maximum levels is consistent with more stable cerebral blood flow during the challenging time of ES administration.

The essential oil and the aqueous and ethanolic extracts obtained from the aerial parts of Pelargonium graveolens cultivated in Morocco were studied for their antioxidant and insecticidal activity against rice weevils (Sitophylus oryzae). The total phenolic content of the extracts was determined by a spectrophotometric method and the phenolic compounds were extensively characterized by HPLC-PDA/ESI-MS. To evaluate antioxidant potential, three in vitro assays were used. In the DPPH test, the ethanolic extract was the most active, followed by the aqueous extract and the essential oil. In the reducing power assay, excellent activity was highlighted for both extracts, while in the Fe2+ chelating activity assay, weak activity was observed for both the essential oil and the ethanolic extract and no activity for the aqueous extract. Concerning insecticide activity, the toxicity of the essential oil and the extracts was tested against rice weevils; the lethal concentrations LC50 and LC99 were determined, as well as the lethal time required for the death of 50% (LT50) and 99% (LT99) of the weevils. The essential oil had the highest activity; 100% mortality of S. oryzae was observed around 5, 9, and 8 days for the essential oil and the aqueous and ethanolic extracts, respectively.

This paper explores school principals' and teachers' views of the Italian teachers' appraisal system and related indicators. In particular, the research aimed at examining the opinions of school principals and teachers regarding the domains to be considered for teacher appraisal purposes. An investigation involving 37 school principals and 868 in service teachers, from three Italian regions, is presented. The data was collected through a questionnaire and statistically analysed. Findings suggest operationalising new data sources -- specifically students and parent, - is beneficial to evaluate teacher quality as a construct in data- based professional learning communities. They show different positioning: teachers seem to be really inclined to be evaluated, especially by students and parents, while school principals still seem very cautious in entrusting the teachers' appraisal to an external point of view. This paper adds to the existing research showing the perspective of a new teachers' appraisal, inspired by multi-faceted models based on multiple points of view (students, parents, not only principals) and not reduced to simplistic solutions of an accounting type. Furthermore, the study answers the call for research into teachers' appraisal as part of the professional learning actions and in view of more integrated professional leadership.

In this perspective, we present our experience developing and conducting two pragmatic clinical trials investigating physical therapist-led telehealth strategies for persons with chronic low back pain. Both trials, the BeatPain Utah and AIM-Back trials, are part of pragmatic clinical trial collaboratories and are being conducted with persons from communities that experience pain management disparities. Practice guidelines recommend nonpharmacologic care, and advise against opioid therapy, for the primary care management of persons with chronic low back pain. Gaps between these recommendations and actual practice patterns are pervasive, particularly for persons from racial or ethnic minoritized communities, those with fewer economic resources, and those living in rural areas including Veterans. Access barriers to evidence-based nonpharmacologic care, which is often provided by physical therapists, have contributed to these evidence-practice gaps. Telehealth delivery has created new opportunities to overcome access barriers for nonpharmacologic pain care. As a relatively new delivery mode however, telehealth delivery of physical therapy comes with additional challenges related to technology, intervention adaptations and cultural competence. The purpose of this article is to describe the challenges encountered when implementing telehealth physical therapy programs for persons with chronic low back pain in historically underserved communities. We also discuss strategies developed to overcome barriers in an effort to improve access to telehealth physical therapy and reduce pain management disparities. Inclusion of diverse and under-represented communities in pragmatic clinical trials is a critical consideration for improving disparities, but the unique circumstances present in these communities must be considered when developing implementation strategies.

Retomando o famoso prólogo ao livro Diferença e Repetição, no qual Gilles Deleuze pontua se aproximar o tempo no qual não seria possível escrever um livro de filosofia como outrora, procuraremos pensar a evocação deleuziana da necessidade de adotarmos um novo tom e novas regras para o exercício filosófico. Acreditamos que retomar esse apelo do filósofo nos lançaria no coração da concepção deleuziana e deleuzo-guattariana da filosofia como um exercício de experimentação. A fim de perseguir quais tons e regras estariam no horizonte do filósofo francês, buscaremos nos aprofundar nas analogias experimentadas por Deleuze em seu prólogo, ao sugerir que um tratado filosófico deveria soar tanto como uma espécie de romance policial quanto como uma ficção científica. Esse excurso, defendemos, não apenas nos auxiliaria na compreensão deleuziana e deleuzo-guattariana da filosofia como experimentação, como também possibilitaria rascunhar algumas pistas sobre o papel da história da filosofia no coração dessa concepção outra apresentada por Deleuze.

Cancer immunotherapy has made impressive advances in improving the outcome of patients affected by malignant diseases. Nonetheless, some limitations still need to be tackled to more efficiently and safely treat patients, in particular for those affected by solid tumors. One of the limitations is related to the immunosuppressive tumor microenvironment (TME), which impairs anti-tumor immunity. Efforts to identify targets able to turn the TME into a milieu more auspicious to current immuno-oncotherapy is a real challenge due to the high redundancy of the mechanisms involved. However, the insulin-like growth factor 1 receptor (IGF1R), an attractive drug target for cancer therapy, is emerging as an important immunomodulator and regulator of key immune cell functions. Here, after briefly summarizing the IGF1R signaling pathway in cancer, we review its role in regulating immune cells function and activity, and discuss IGF1R as a promising target to improve anti-cancer immunotherapy.

Patients reaching the emergency department (ED) with symptoms of acute ischemic stroke (AIS) may be affected by a stroke mimics (SMs). A prompt clinical diagnosis could avoid unnecessary thrombolysis. We evaluated a new and rapid approach, the Santa Maria Nuova-Stroke Mimic (SMN-SM) scale, to improve a prompt clinical diagnosis. 340 consecutive patients admitted to the ED with suspected AIS were evaluated. The final diagnosis was: AIS in 267 (78,5%) and SMs in 73 (21,5%) patients. Multivariate logistical analysis showed that the following features – lack of facial paralysis, dizziness, migraine, seizure disorders, blood pressure

Background: The endometrium remains a difficult tissue for the analysis of microbiota, mainly due to the low bacterial presence and the sampling procedures. Among its pathologies, endometrial cancer has not yet been completely investigated for its relationship with microbiota composition. In this work, we report on possible correlations between endometrial microbiota dysbiosis and endometrial cancer. Methods: Women with endometrial cancer at various stages of tumor progression were enrolled together with women with a benign polymyomatous uterus as the control. Analyses were performed using biopsies collected at two specific endometrial sites during the surgery. This study adopted two approaches: the absolute quantification of the bacterial load, using droplet digital PCR (ddPCR), and the analysis of the bacterial composition, using a deep metabarcoding NGS procedure. Results: ddPCR provided the first-ever assessment of the absolute quantification of bacterial DNA in the endometrium, confirming a generally low microbial abundance. Metabarcoding analysis revealed a different microbiota distribution in the two endometrial sites, regardless of pathology, accompanied by an overall higher prevalence of pathogenic bacterial genera in cancerous tissues. Conclusions: These results pave the way for future studies aimed at identifying potential biomarkers and gaining a deeper understanding of the role of bacteria associated with tumors.

As of 2035, the European Union has ratified the obligation to register only zero-emission cars, including ultra-low-emission vehicles (ULEVs). In this context, electric mobility fits in, which, however, presents the critical issue of the over-exploitation of critical raw materials (CRMs). An interesting solution to reduce this burden could be the so-called second life, in which batteries that are no longer able to guarantee high performance in vehicles are used for other applications that do not require high performance, such as so-called stationary systems, effectively avoiding new over-exploitation of resources. In this study, therefore, the environmental impacts of second-life lithium iron phosphate (LiFePO4) batteries are verified using a life cycle perspective, taking a second life project as a case study. The results show how, through the second life, GWP could be reduced by −5.06 × 101 kg CO2 eq/kWh, TEC by −3.79 × 100 kg 1.4 DCB eq/kWh, HNCT by −3.46 × 100 kg 1.4 DCB eq/kWh, −3.88 × 100 m2a crop eq/kWh, and −1.12 × 101 kg oil eq/kWh. It is further shown how second life is potentially preferable to other forms of recycling, such as hydrometallurgical and pyrometallurgical recycling, as it shows lower environmental impacts in all impact categories, with environmental benefits of, for example, −1.19 × 101 kg CO2 eq/kWh (compared to hydrometallurgical recycling) and −1.50 × 101 kg CO2 eq/kWh (pyrometallurgical recycling), −3.33 × 102 kg 1.4 DCB eq/kWh (hydrometallurgical), and −3.26 × 102 kg 1.4 DCB eq/kWh (pyrometallurgical), or −3.71 × 100 kg oil eq/kWh (hydrometallurgical) and −4.56 × 100 kg oil eq/kWh (pyrometallurgical). By extending the service life of spent batteries, it may therefore be possible to extract additional value while minimizing emissions and the over-exploitation of resources.

IntroductionDelayed discharge represents the difficulty in proceeding with discharge of patients who do not have any further benefit from prolonged stay. A quota of this problem is related to organizational issues. In the Lazio region in Italy, a macro service re-organization in on the way, with a network of hospital and territorial centers engaged in structuring in- and out- of hospital patient pathways, with a special focus on intermediate care structures. Purpose of this study is to quantify the burden of delayed discharge on a single hospital structure, in order to estimate costs and occurrence of potential resource misplacement.Material and methodsObservational Retrospective study conducted at the Santo Spirito Hospital in Rome, Italy. Observation period ranged from 1/09/2022, when the local database was instituted, to 1/03/2023 (6 months). Data from admissions records was anonymously collected. Data linkage with administrative local hospital database was performed in order to identify the date a discharge request was fired for each admission. Surgical discharges and Intensive Care Unit (ICU) discharges were excluded from this study. A Poisson hierarchical regression model was employed to investigate for the role of ward, Severity of Disease (SoD) and Risk of Mortality (RoM) on elongation of discharge time.Results1222 medical ward admissions were recorded in the timeframe. 16% of them were considered as subject to potentially elongated stay, and a mean Delay in discharge of 6.3 days (SD 7.9) was observed.Discussion and conclusionsDelayed discharge may cause a "bottleneck" in admissions and result in overcrowded Emergency Department, overall poor performance, and increase in overall costs. A consisted proportion of available beds can get inappropriately occupied, and this inflates both direct and indirect costs. Clinical conditions on admission are not a good predictor of delay in discharge, and the root causes of this phenomenon likely lie in organizational issues (on structure\system level) and social issues (on patient's level).

Introduction Fast and accurate diagnosis of acute stroke is crucial to timely initiate reperfusion therapies. Conventional high-field (HF) MRI yields the highest accuracy in discriminating early ischaemia from haemorrhages and mimics. Rapid access to HF-MRI is often limited by contraindications or unavailability. Low-field (LF) MRI (

Background and aimsEpidemiology of atherosclerotic cardiovascular disease might be different in patients with polygenic hypercholesterolemia plus high levels (≥30 mg/dl) of Lp(a) (H-Lpa) than in those with polygenic hypercholesterolemia alone (H-LDL). We compared the incidence of peripheral artery disease (PAD), coronary artery disease (CAD), and cerebrovascular disease (CVD) in patients with H-Lpa and in those with H-LDL.MethodsRetrospective analysis of demographics, risk factors, vascular events, therapy, and lipid profile in outpatient clinical data. Inclusion criteria was adult age, diagnosis of polygenic hypercholesterolemia, and both indication and availability for Lp(a) measurement.ResultsMedical records of 258 patients with H-Lpa and 290 H-LDL were reviewed for occurrence of vascular events. The median duration of follow-up was 10 years (IQR 3–16). In spite of a similar reduction of LDL cholesterol, vascular events occurred more frequently, and approximately 7 years earlier (P = 0.024) in patients with H-Lpa than in H-LDL (HR 1.96 1.21–3.17, P = 0.006). The difference was around 10 years for acute events (TIA, Stroke, acute coronary events) and one year for chronic ones (P = 0.023 and 0.525, respectively). Occurrence of acute CAD was higher in H-Lpa men (HR 3.1, 95% CI 1.2–7.9, P = 0.007) while, among women, PAD was observed exclusively in H-Lpa subjects with smoking habits (P = 0.009).ConclusionsPatients with high Lp(a) levels suffer from a larger and earlier burden of the disease compared to those with polygenic hypercholesterolemia alone. These patients are at higher risk of CAD if they are men, and of PAD if they are women.