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Computational Thinking (CT) is crucial for the advancement of the STEM field, where there continues to be a lack of female representation. Teaching and learning (T/L) of CT should incorporate didactic strategies that aim to eliminate gender biases and integrate girls/women into this context. In response to the question, "What didactic strategies have been implemented in the T/L of CT in primary and secondary education?". A systematic review was conducted following a PRISMA protocol specifically designed for this review. The study analysed Didactic Strategies (DS) and examined whether they incorporated the so-called "minimum actions" (MA) proposed in this article as a strategy to integrate females into CT. The findings revealed a limited number of studies that implemented these actions. In conclusion, there is an urgent need to continue developing DS that incorporate these MA to effectively integrate girls and women into CT, allowing them to play a central role in its advancement and development.

BACKGROUND:Intestinal metaplasia (IM) is a precursor lesion that precedes gastric cancer (GC). There are two IM histological subtypes, complete (CIM) and incomplete (IIM), the latter having higher progression rates to GC. This study was aimed at analysing gene expression and molecular processes involved in the progression from normal mucosa to IM, and also from IM subtypes to GC. METHODOLOGY:We used expression data to compare the transcriptome of healthy gastric mucosa to that of IM not progressing to GC, and the transcriptome of IM subtypes that had progressed to GC to those that did not progress. Some deregulated genes were validated and pathway analyses were performed. RESULTS:Comparison of IM subtypes that had progressed to GC with those that did not progress showed smaller differences in the expression profiles than the comparison of IM that did not progress with healthy mucosa. New transcripts identified in IM not progressing to GC included TRIM, TMEM, homeobox and transporter genes and SNORD116. Comparison to normal mucosa identified non tumoral Warburg effect and melatonin degradation as previously unreported processes involved in IM. Overexpressed antigen processing is common to both IM-subtypes progressing to GC, but IIM showed more over-expressed oncogenic genes and molecular processes than CIM. CONCLUSIONS:There are greater differences in gene expression and molecular processes involved in the progression from normal healthy mucosa to IM than from IM to gastric cancer. While antigen processing is common in both IM-subtypes progressing to GC, more oncogenic processes are observed in the progression of IIM.

BackgroundWaist circumference (WC) is a simple and reliable measure of fat distribution that may add to the prediction of type 2 diabetes (T2D), but previous studies have been too small to reliably quantify the relative and absolute risk of future diabetes by WC at different levels of body mass index (BMI).Methods and findingsThe prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident T2D cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. We used Prentice-weighted Cox regression and random effects meta-analysis methods to estimate hazard ratios for T2D. Kaplan-Meier estimates of the cumulative incidence of T2D were calculated. BMI and WC were each independently associated with T2D, with WC being a stronger risk factor in women than in men. Risk increased across groups defined by BMI and WC; compared to low normal weight individuals (BMI 18.5-22.4 kg/m(2)) with a low WC (102/88 cm). Among the large group of overweight individuals, WC measurement was highly informative and facilitated the identification of a subgroup of overweight people with high WC whose 10-y T2D cumulative incidence (men, 70 per 1,000 person-years; women, 44 per 1,000 person-years) was comparable to that of the obese group (50-103 per 1,000 person-years in men and 28-74 per 1,000 person-years in women).ConclusionsWC is independently and strongly associated with T2D, particularly in women, and should be more widely measured for risk stratification. If targeted measurement is necessary for reasons of resource scarcity, measuring WC in overweight individuals may be an effective strategy, since it identifies a high-risk subgroup of individuals who could benefit from individualised preventive action.

Summary: We present a detailed protocol for sequencing full-length mRNA isoforms using the Oxford nanopore long-read sequencing technology. We describe steps for poly(A) RNA isolation, library preparation, and cDNA size selection. We then detail procedures for sequencing and processing and a computational framework to identify exon couplings and assign mRNA 5′ ends and 3′ ends to each other. Our approach enables the identification of links between transcription initiation and co-transcriptional RNA processing events.For complete details on the use and execution of this protocol, please refer to Alfonso-Gonzalez et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract FUS is an RNA-binding protein involved in familiar forms of ALS and FTLD that also assembles into fibrillar cytoplasmic aggregates in some neurodegenerative diseases without genetic causes. The self-adhesive prion-like domain in FUS generates reversible condensates via the liquid–liquid phase separation process (LLPS) whose maturation can lead to the formation of insoluble fibrillar aggregates in vitro, consistent with the appearance of cytoplasmic inclusions in ageing neurons. Using a single-molecule imaging approach, we reveal that FUS can assemble into nanofibrils at concentrations in the nanomolar range. These results suggest that the formation of fibrillar aggregates of FUS could occur in the cytoplasm at low concentrations of FUS, below the critical ones required to trigger the liquid-like condensate formation. Such nanofibrils may serve as seeds for the formation of pathological inclusions. Interestingly, the fibrillation of FUS at low concentrations is inhibited by its binding to mRNA or after the phosphorylation of its prion-like domain, in agreement with previous models.

Summary: Studies have reported increased intestinal permeability in multiple sclerosis (MS) patients and its mouse model experimental autoimmune encephalomyelitis (EAE). However, the mechanisms driving increased intestinal permeability that in turn exacerbate neuroinflammation during EAE remain unclear. Here we showed that vancomycin preserved the integrity of the intestinal barrier, while also suppressing gut trypsin activity, enhancing the relative abundance of specific Lactobacilli and ameliorating disease during EAE. Furthermore, Lactobacilli enriched in the gut of vancomycin-treated EAE mice at day 3 post immunization negatively correlated with gut trypsin activity and EAE severity. In untreated EAE mice, we observed increased intestinal permeability and increased intestinal protease activated receptor 2 (PAR2) expression at day 3 post immunization. Prior studies have shown that trypsin increases intestinal permeability by activating PAR2. Our results suggest that the interaction between intestinal PAR2 and trypsin may be a key modulator of intestinal permeability and disease severity during EAE.

DC microgrids (DCMGs), typically envisioned with high bandwidth communications, may well expand their application range by considering additional autonomous control strategies, especially to increase resiliency in contingency situation. These strategies are based on the droop control methods, enabling voltage regulation and proportional load sharing based only on local measurements. Control challenges arise when coordinating the output of multiple DCMGs, each composed of several distributed energy resources through bus-to-bus transactional converters. This paper proposes an autonomous control strategy for transactional converters when multiple DCMGs are connected through a common bus. This control strategy seeks to match the external bus voltage with the internal bus voltage, balancing power. Three case scenarios are considered: standalone operation of each DCMG, excess generation on one DCMG, and generation deficit in one DCMG. Results using Sandia National Laboratories’ Secure Scalable Microgrid Simulink library, and models developed in MATLAB are compared. These results demonstrated that the proposed control strategy supported the advantage of seamless operation with and without local generation-load mismatches and expanded the range of autonomous operation between DCMGs.

Abstract Here, we present the first two Swedish cases of Conserved Oligomeric Golgi complex subunit 6‐congenital disorders of glycosylation (COG6‐CDG). Their clinical symptoms include intellectual disability, Attention Deficit/Hyperactivity Disorder (ADHD), delayed brain myelinization, progressive microcephaly, joint laxity, hyperkeratosis, frequent infections, and enamel hypoplasia. In one family, compound heterozygous variants in COG6 were identified, where one (c.785A>G; p.Tyr262Cys) has previously been described in patients of Moroccan descent, whereas the other (c.238G>A; p.Glu80Lys) is undescribed. On the other hand, a previously undescribed homozygous duplication (c.1793_1795dup) was deemed the cause of the disease. To confirm the pathogenicity of the variants, we treated patient and control fibroblasts with the ER‐Golgi transport inhibitor Brefeldin‐A and show that patient cells manifest a significantly slower anterograde and retrograde ER‐Golgi transport.

Despite multiple recent field studies, herpetological species diversity of the Romblon Island Group in the central Philippines—particularly Sibuyan Island—has remained underestimated. Recently, we investigated the diversity of the herpetofauna of Mount Guiting-Guiting Natural Park, based on an elevational transect (10–1557 m a.s.l.). Our surveys resulted in a total of 47 species of amphibians and reptiles, including 14 new island records and one atypical occurrence of a snake species recorded for the first time from a high elevation (939 m a.s.l). These new records constitute a notable increase (21%) in Sibuyan’s herpetological species diversity as compared to surveys from a decade ago. We also provide updates of the taxonomy and identification of species endemic to this island (e.g., members of the genera Platymantis Günther, 1858, Brachymeles Duméril & Gibron, 1839, and Pseudogekko Taylor, 1922), and discuss the importance of continued surveys and field-derived data to inform conservation status assessments of Sibuyan’s unique assemblage of amphibians and reptiles.

Summary: The microenvironment plays an essential role in tumor development and metastatic progression. Here, we describe a simple and rapid protocol to generate tumors in mice using colon cancer cell lines or tumoroids in the correct microenvironment, colonic mucosa. We also detail steps for monitoring the growth of the primary tumor in real time using colonoscopy or in vivo imaging system, as well as monitoring metastasis development. Finally, we describe tissue collection and sample preparation for subsequent immunohistochemistry analysis. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive neoplasm with very poor patient survival outcomes despite available treatments. There is an urgent need for new potential treatment options and novel biomarkers for these patients. Delta-like canonical Notch ligand 3 (DLL3) interacts with the Notch receptor and causes inhibition of Notch signaling, which confers a survival advantage to PDAC cells. Thus, DLL3 expression could affect cell survival, and its inhibition could increase a patient’s survival. To test this hypothesis, a survival analysis was conducted using the progression-free and overall survival from two independent datasets of PDAC patients, with one using mRNA z-score levels and the other using the Hscore protein expression level; both were carried out using a log-rank test and plotted using Kaplan–Meier curves. DLL3 at the mRNA expression level showed an association between high mRNA expression and both a longer progression-free survival (PFS) and overall survival (OS) of patients. Then, we designed a retrospective study with resected PDAC samples. Our primary objective with this dataset was to assess the relationship between PFS and OS and DLL3 protein expression. The secondary assessment was to provide a rationale for the use of anti-DLL3-based treatments in combination with immunotherapy that is supported by the link between DLL3 and other factors that are involved in immune checkpoints. The survival analyses revealed a protective effect of high DLL3 protein expression levels in both PFS and OS. Interestingly, high DLL3 protein expression levels were significantly correlated with PD-L1/2 and negatively correlated with NOTCH1. Therefore, DLL3 could be considered a biomarker for better prognosis in resectable PDAC patients as well as a therapeutic biomarker for immunotherapy response. These facts set a rationale for testing anti-DLL3-based treatments either alone or combined with immunotherapy or other NOTCH1 inhibitors.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating tumor type where a very high proportion of people diagnosed end up dying from cancer. Surgical resection is an option for only about 20% of patients, where the 5-year survival increase ranges from 10 to 25%. In addition to surgical resection, there are adjuvant chemotherapy schemes, such as FOLFIRINOX (a mix of Irinotecan, oxaliplatin, 5-Fluorouraci and leucovorin) or gemcitabine-based treatment. These last two drugs have been compared in the NAPOLI-3 clinical trial, and the NALIRIFOX arm was found to have a higher overall survival (OS) (11.1 months vs. 9.2 months). Despite these exciting improvements, PDAC still has no effective treatment. An interesting approach would be to drive ferroptosis in PDAC cells. A non-apoptotic reactive oxygen species (ROS)-dependent cell death, ferroptosis was first described by Dixon et al. in 2012. ROS are constantly produced in the tumor cell due to high cell metabolism, which is even higher when exposed to chemotherapy. Tumor cells have detoxifying mechanisms, such as Mn-SOD or the GSH-GPX system. However, when a threshold of ROS is exceeded in the tumor cell, the cell’s antioxidant systems are overwhelmed, resulting in lipid peroxidation and, ultimately, ferroptosis. In this review, we point out ferroptosis as an approach to consider in PDAC and propose that altering the cellular ROS balance by combining oxidizing agents or with inhibitors of the main cellular detoxifiers triggers ferroptosis in PDAC.

A food traceability system (FTS) can record information about processes along a production chain to determine their safety and quality. Under the Internet of Things (IoT) concept, the communication technologies that support FTSs act as platforms for mass access to information with limited security. However, the integrity of the collected data is not immune to security attacks. This paper proposes a point-to-point information transmission path with no edges or access boundaries (no intermediaries) to transmit data with integrity. This route is possible thanks to the architectural articulation of a hardware device (sensor BIoTS) at the perception layer, with the Blockchain architecture at the application layer. This pairing makes an ecosystem with the ability to trace and certify in parallel the products, the supply chain processes, and the data recorded in it possible. The design of the security testing ecosystem is based on the theoretical and technical principles of cybersecurity. It is executed through mathematical models that define the probability of attacks’ success against the transmitted data’s integrity. The security tests performed allow for establishing that this BIoTS information transmission route is unlikely to suffer from transmission vulnerabilities and that it is not prone to security attacks against integrity. This work paves the way toward fully integrating Blockchain technology in dedicated IoT architectures.

Field experiments in the last decade documented discrimination in several social domains: labour, housing, education, transportation, and sports. Previous research shows that when asking to join a training with an amateur soccer club, people with foreign-sounding names are significantly less likely to receive a positive response than those with native-sounding names. This result differs in magnitude but is traceable across 23 European countries, including Switzerland (Gomez-Gonzalez et al., 2021; Nesseler et al., 2019). The findings redirect attention from self-segregation to collective exclusion mechanisms when analyzing the ethnic participation gap in amateur sports. The negative implications are magnified as research identifies sport participation as key in promoting social integration among minority group members. Experimental economics also show that field experiments can play a crucial role in developing effective policies to combat discrimination in the future decade. Previous research demonstrates the importance of intervention studies to test the effectiveness of the policies, as not all have the intended results. Dur et al. (2022) analyze the effectiveness of a low-cost intervention to reduce discrimination among amateur soccer clubs in Norway. A correspondence test is preceded by an anti-discrimination intervention in collaboration with the Norwegian Football Federation (NFF). The intervention is based on an information campaign sent via email to a random selection of amateur soccer clubs, which do not modify their behavior as expected. The experimental design of an intervention makes it possible to estimate the causal effect of a low-cost policy against discrimination in the field. In this research, I design an intervention to reduce the ethnic response gap among amateur soccer clubs in Switzerland, where more than 1,000 amateur clubs would be subject to an intervention. I explore the features of the information campaign: message, sender, and channel, and potential collaborations with sports governing bodies to increase the impact of such policy. References Dur, R., Gomez-Gonzalez, C., & Nesseler, C. (2022). How to reduce discrimination? Evidence from a field experiment in amateur soccer. Journal of Ethnic and Migration Studies, 49(1), 175-191. https://doi.org/10.1080/1369183X.2022.2071688 Gomez-Gonzalez, C., Nesseler, C., & Dietl, H. M. (2021). Mapping discrimination in Europe through a field experiment in amateur sport. Humanities and Social Sciences Communications, 8, Article 95. https://doi.org/10.1057/s41599-021-00773-2 Nesseler, C., Gomez-Gonzalez, C., & Dietl, H. (2019). What’s in a name? Measuring access to social activities with a field experiment. Palgrave Communications, 5, Article 160. https://doi.org/10.1057/s41599-019-0372-0

RNA-protein interactions (RPIs) are promising targets for developing new molecules of therapeutic interest. Nevertheless, challenges arise from the lack of methods and feedback between computational and experimental techniques during the drug discovery process. Here, we tackle these challenges by developing a drug screening approach that integrates chemical, structural and cellular data from both advanced computational techniques and a method to score RPIs in cells for the development of small RPI inhibitors; and we demonstrate its robustness by targeting Y-box binding protein 1 (YB-1), a messenger RNA-binding protein involved in cancer progression and resistance to chemotherapy. This approach led to the identification of 22 hits validated by molecular dynamics (MD) simulations and nuclear magnetic resonance (NMR) spectroscopy of which 11 were found to significantly interfere with the binding of messenger RNA (mRNA) to YB-1 in cells. One of our leads is an FDA-approved poly(ADP-ribose) polymerase 1 (PARP-1) inhibitor. This work shows the potential of our integrative approach and paves the way for the rational development of RPI inhibitors.

ABSTRACTInflammatory Bowel Disease (IBD) is a chronic immune-mediated inflammatory disease of the gastrointestinal tract that is a growing public burden. Gut microbes and their interactions with hosts play a crucial role in disease pathogenesis and progression. These interactions are complex, spanning multiple physiological systems and data types, making comprehensive disease assessment difficult, and often overwhelming single-omic capabilities. Stool-based multi-omics is a promising approach for characterizing host-gut microbiome interactions using deep integration of technologies such as 16S rRNA sequencing, shotgun metagenomics, meta-transcriptomics, metabolomics, and metaproteomics. The wealth of information generated through multi-omic studies is poised to usher in advancements in IBD research and precision medicine. This review highlights historical and recent findings from stool-based muti-omic studies that have contributed to unraveling IBD’s complexity. Finally, we discuss common pitfalls, issues, and limitations, and how future pipelines should address them to standardize multi-omics in IBD research and beyond.