Provocation Through Narratives: New Speculative Design Tools for Human-Non-Human Collaborations

In a complex and changing world, design is called to act to nurture and provoke critical reflections regarding wicked, complex, and interconnected issues, becoming a sensemaking agent that, exploiting its speculative methods, uses narratives as an inquiry tool, as a co-design tool, and as a provocative tool. Through the presentation and analysis of a provotype designed by the authors, the research aims to define new speculative tools for human-non-human collaborations and highlight how design narratives may be involved within more-than-human discourses

N6-Methyladenosine (m6A): A Promising New Molecular Target in Acute Myeloid Leukemia

Recent studies have uncovered an important role for RNA modifications in gene expression regulation, which led to the birth of the epitranscriptomics field. It is now acknowledged that RNA modifiers play a crucial role in the control of differentiation of stem and progenitor cells and that changes in their levels are a relevant feature of different types of cancer. To date, among more than 160 different RNA chemical modifications, the more relevant in cancer biology is the reversible and dynamic N6-methylation of adenosine, yielding N6-methyladenosine (m6A). m6A is the more abundant internal modification in mRNA, regulating the expression of the latter at different levels, from maturation to translation. Here, we will describe the emerging role of m6A modification in acute myeloid leukemia (AML), which, among first, has demonstrated how mis-regulation of the m6A modifying system can contribute to the development and progression of cancer. Moreover, we will discuss how AML is paving the way to the development of new therapeutic options based on the inhibition of m6A deposition

La simulazione medica nel futuro: un tentativo di visioning The health simulation in the future: an attempt of visioning

La pratica clinica è un componente indispensabile dell’apprendimento e del mantenimento delle competenze in molte delle discipline sanitarie e la simulazione offre l’opportunità di praticare in maniera sicura ed efficace senza rischi per il paziente. La simulazione nella didattica medica si è già ampiamente evoluta rispetto alle sue fasi iniziali. L’introduzione dei simulatori di pazienti umani, intorno alla fine del XX secolo, rappresenta una tappa fondamentale nella scienza dell’educazione in sanità. Fino ad oggi l’attenzione degli sviluppatori si è concentrata da un lato sulla capacità dei simulatori di dare feedback verosimili e coerenti con il comportamento del paziente e con la fisiologia umana e dall’altro sull’interazione fra simulatore e utilizzatore. Le emergenti tecnologie nel campo della percezione sensoriale apporteranno miglioramenti significativi sia nella formazione in simulazione che nella gestione della simulazione stessa. Basandosi sull’analisi delle tecnologie attualmente disponibili e in via di sviluppo, questo scritto vuole essere uno sforzo di visioning sul futuro delle tecniche di simulazione. Nano-sensori e nano-attuatori, usati nella realtà aumentata/virtuale/ mista, permetteranno sia la concettualizzazione di sistemi capaci di aumentare il livello di realismo e di immersione sensoriale ma anche di mappare i movimenti e le azioni al fine di generare protocolli univoci di intervento. Proiettandoci in un ipotetico 2025, la simulazione medica sarà un’esperienza democratica, largamente accessibile, dinamica e immersiva a 360°, grazie alle tecniche di implementazione neuro-percettive.Practice is a key component of skills learning and maintenance in many health disciplines and simulation offers the opportunity to practice in a safe and effective manner improving patient safety. Simulation for healthcare training has already evolved through its initial historical phases. The introduction of human patient simulator toward the end of the 20th century was a milestone in health sciences education. To date the attention of developers has been paid to the capability of the simulator to give feedback, consistent with patient behavior and physiologic response, and the interaction between simulator and users. The emerging technologies in the field of sensorial perception will bring improvements both in education and in management of the simulation. Grounding on the analysis of current and under-development technology, the manuscript is an attempt of visioning simulation-based training in health education in a coming future. Nano-sensors and nano-actuators, used in augmented/virtual/mixed reality, will allow the conceptualization of systems increasing the level of realism and the sensorial immersion, and the mapping of movements and action in order to generate univocal protocols of intervention. Projecting ourselves in 2025, medical simulation will be a democratic, largely accessible, dynamic and 360° sensorial experience, thanks to techniques of neuro-perceptive implementation

"Electro-clinical Syndromes" with onset in Paediatric Age. the highlights of the clinical-EEG, genetic and therapeutic advances

The genetic causes underlying epilepsy remain largely unknown, and the impact of available genetic data on the nosology of epilepsy is still limited. Thus, at present, classification of epileptic disorders should be mainly based on electroclinical features. Electro-clinical syndrome is a term used to identify a group of clinical entities showing a cluster of electro-clinical characteristics, with signs and symptoms that together define a distinctive, recognizable, clinical disorder. These often become the focus of treatment trials as well as of genetic, neuropsychological, and neuroimaging investigations. They are distinctive disorders identifiable on the basis of a typical age onset, specific EEG characteristics, seizure types, and often other features which, when taken together, permit a specific diagnosis which, in turn, often has implications for treatment, management, and prognosis. Each electro-clinical syndrome can be classified according to age at onset, cognitive and developmental antecedents and consequences, motor and sensory examinations, EEG features, provoking or triggering factors, and patterns of seizure occurrence with respect to sleep. Therefore, according to the age at onset, here we review the more frequently observed paediatric electro-clinical syndrome from their clinical-EEG, genetic and therapeutic point of views

METTL3 regulates WTAP protein homeostasis

The Wilms tumor 1 (WT1)-associated protein (WTAP) is upregulated in many tumors, including, acute myeloid leukemia (AML), where it plays an oncogenic role by interacting with different proteins involved in RNA processing and cell proliferation. In addition, WTAP is also a regulator of the nuclear complex required for the deposition of N6-methyladenosine (m6A) into mRNAs, containing the METTL3 methyltransferase. However, it is not clear if WTAP may have m6A-independent regulatory functions that might contribute to its oncogenic role. Here, we show that both knockdown and overexpression of METTL3 protein results in WTAP protein upregulation, indicating that METTL3 levels are critical for WTAP protein homeostasis. However, we show that WTAP upregulation is not sufficient to promote cell proliferation in the absence of a functional METTL3. Therein, these data indicate that the reported oncogenic function of WTAP is strictly connected to a functional m6A methylation complex

A STUDY ON THE SKILLS GAP ANALYSIS IN THE JORDANIAN TOURISM SECTOR

According to the national development plans, the Jordanian tourism sector needs to be updated in order to meet international qualitative standards. To achieve this goal, one of the expected actions to be undertaken is the definition and the implementation of innovative professional profiles that should be integrated within the whole supply chain, and the updating of the related study plans. In order to address this demand, the research aimed to produce a skills gap analysis of the Jordanian tourism, hospitality, and heritage education system, which should highlight sets of innovative and underdeveloped skills for the tackled sectors, and the relative academic paths. The research also aimed to understand the actual offering of the Jordanian education system and to compare it with the requirements of the labor market. Although different plans have been developed, their implementation is still not fully exploited to achieve the desired transformation of the reference sector. By exploiting mixed research techniques, both quantitative and qualitative, it has been possible to understand the actual offeri ng of the Jordanian education system and to compare it with the requirements of the labor market: these activities represent the needed basis to produce the demanded skills gap analysis, which is also part of this contribution

Transition product design. A framework proposal for a holistic approach to systemic design

The Transition Design (TD) discipline is based on a design framework and methodology that prioritises social and environmental well-being and the goals of local resilience and radical changes in socio-technical contexts. Terry Irwin (2019) sees two aspects of TD as fundamental: the idea that entire societies will face a transition to sustainable futures and the realisation that this will entail changes at the systemic level. As part of the ongoing disciplinary debate, this contribution investigates the potential of new design drivers, such as territorial value and local resilience, linked to specific case studies that can be seen as best practices. The result is a theoretical framework of eight guidelines that aims to answer some of the TD process’s problems and model the requirements that can then be replicated

ADAR1 is a new target of METTL3 and plays a pro-oncogenic role in glioblastoma by an editing-independent mechanism

Background: N6-methyladenosine (m6A) and adenosine-to-inosine (A-to-I) RNA editing are two of the most abundant RNA modification events affecting adenosines in mammals. Both these RNA modifications determine mRNA fate and play a pivotal role in tumor development and progression. Results: Here, we show that METTL3, upregulated in glioblastoma, methylates ADAR1 mRNA and increases its protein level leading to a pro-tumorigenic mechanism connecting METTL3, YTHDF1, and ADAR1. We show that ADAR1 plays a cancer-promoting role independently of its deaminase activity by binding CDK2 mRNA, underlining the importance of ADARs as essential RNA-binding proteins for cell homeostasis as well as cancer progression. Additionally, we show that ADAR1 knockdown is sufficient to strongly inhibit glioblastoma growth in vivo. Conclusions: Hence, our findings underscore METTL3/ADAR1 axis as a novel crucial pathway in cancer progression that connects m6A and A-to-I editing post-transcriptional events

Combined Experimental and Numerical Investigation of the ECN Spray G under Different Engine-Like Conditions

A detailed understanding of Gasoline Direct Injection (GDI) techniques applied to spark-ignition (SI) engines is necessary as they allow for many technical advantages such as increased power output, higher fuel efficiency and better cold start performances. Within this context, the extensive validation of multi-dimensional models against experimental data is a fundamental task in order to achieve an accurate reproduction of the physical phenomena characterizing the injected fuel spray. In this work, simulations of different Engine Combustion Network (ECN) Spray G conditions were performed with the Lib-ICE code, which is based on the open source OpenFOAM technology, by using a RANS Eulerian-Lagrangian approach to model the ambient gas-fuel spray interaction. Foremost, the main scope of the activity was to identify the most accurate numerical set-up in terms of atomization ad secondary break-up models, thanks to a validation of the computed results against experimental data available for the ECN Spray G baseline condition. Specifically, attention was focused on spray penetration along with an analysis of spray morphology and effects of plume-to-plume interaction. Afterwards, the reference set-up was tested and validated under different operating conditions, characterized by detailed experimental measurements specifically provided for this work. In particular, Mie scattering and Schlieren techniques allowed the quasi-simultaneous acquisition of both vapor and liquid penetrations, while a customized image-processing procedure, developed in Matlab environment, was used for the outline of the spray contours of both fuel phases to measure the parameters characterizing the jet development. A robust reference numerical set-up was identified, capable to reproduce with good accuracy the injection process of a multi-hole GDI spray under the wide range of tested operating conditions

MALAT1-dependent hsa_circ_0076611 regulates translation rate in triple-negative breast cancer

Vascular Endothelial Growth Factor A (VEGFA) is the most commonly expressed angiogenic growth factor in solid tumors and is generated as multiple isoforms through alternative mRNA splicing. Here, we show that lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and ID4 (inhibitor of DNA-binding 4) protein, previously referred to as regulators of linear isoforms of VEGFA, induce back-splicing of VEGFA exon 7, producing circular RNA circ_0076611. Circ_0076611 is detectable in triple-negative breast cancer (TNBC) cells and tissues, in exosomes released from TNBC cells and in the serum of breast cancer patients. Circ_0076611 interacts with a variety of proliferation-related transcripts, included MYC and VEGFA mRNAs, and increases cell proliferation and migration of TNBC cells. Mechanistically, circ_0076611 favors the expression of its target mRNAs by facilitating their interaction with components of the translation initiation machinery. These results add further complexity to the multiple VEGFA isoforms expressed in cancer cells and highlight the relevance of post-transcriptional regulation of VEGFA expression in TNBC cells