Rearranged during transfection (RET) lung cancer - Update on targeted therapies

The enhanced comprehension of the molecular pathways underpinning oncogenesis in non-small cell lung cancer (NSCLC) has led to the advancement of personalized treatment for individuals with actionable mutations using targeted therapies. The rearranged during transfection (RET) proto-oncogene, is critical in the embryonic development of various tissues, including renal, neural, and neuroendocrine tissue. RET fusions have been observed in approximately 1–2% of NSCLC cases. Targeted therapies for NSCLC with RET alterations have progressed significantly over the past decade. While multikinase inhibitors (MKIs) faced limitations in efficacy and tolerability, the introduction of selective RET inhibitors (SRIs) such as selpercatininb and pralsetinib has transformed patient outcomes, resulting in deep and durable responses. Ongoing clinical trials are exploring their potential benefits in the neoadjuvant and adjuvant setting. Early phase clinical trials endeavor to demonstrate next-generation selective RET inhibitors can effectively overcome SRI resistance mechanisms, offer improved safety profiles, and enhance patient outcomes.</p

Integrating muscle energetics into biomechanical models to understand variance in the cost of movement

In this Review, we explore the state of the art of biomechanical models for estimating energy consumption during terrestrial locomotion. We consider different mechanical models that provide a solid framework to understand movement energetics from the perspective of force and work requirements. Whilst such models are highly informative, they lack specificity for predicting absolute metabolic rates across a range of species or variations in movement patterns. Muscles consume energy when they activate to generate tension, as well as when they shorten to generate positive work. Phenomenological muscle models incorporating steady-state parameters have been developed and are able to reproduce how muscle fibre energy consumption changes under different contractile conditions; however, such models are difficult to validate when scaled up to whole muscle. This is, in part, owing to limited availability of data that relate muscle dynamics to energetic rates during contraction of large mammalian muscles. Furthermore, factors including the compliance of tendinous tissue, dynamic shape changes and motor unit recruitment can alter the dynamics of muscle contractile tissue and potentially improve muscle efficiency under some locomotion conditions. Despite the many challenges, energetic cost estimates derived from musculoskeletal models that simulate muscle function required to generate movement have been shown to reasonably predict changes in human metabolic rates under different movement conditions. However, accurate predictions of absolute metabolic rate are still elusive. We suggest that conceptual models may be adapted based on our understanding of muscle energetics to better predict the variance in movement energetics both within and between terrestrial species.</p

Embeddables: Designing Physical-Digital Manipulatives for Young Children

Introducing digital literacy to young children develops foundational skills in problem-solving and supports their cognitive development, including critical thinking. However, physical manipulatives for digital literacy are not always designed for early-year environments or specifically for young children. Physical manipulatives can offer developmentally appropriate tools to introduce foundational digital literacy through dynamic system knowledge before children become developmentally ready for more formalised coding activities. This paper presents an initial study in a preschool environment with children (ages 3 – 5 years) using novel physical manipulatives, Embeddables (Fig. 1), in child-led free and guided play activities in a preschool. From our initial analysis of the types of activities the children engaged in, we identify how, firstly, children used the proximal relations to undertake experimental understanding of the devices, which secondly led to using the proximal relationships in their social play, further supported by the scale and feedback of the toys

Wobblies: Designing Intentional Playthings with Young Children

This paper analyses a novel tangible technology in early childhood environments as a boundary object. Objects in early childhood environments often share space between adults’ and children's objectives. By considering these objects as boundary objects, designers are led to explore how children appropriate objects for playful learning activities beyond adult objectives. This paper discusses Wobblies (see Figure 1), a novel technology probe, to interrogate how a socially-motivated design with conditional and positional interactive behaviour was understandable to children, and how they appropriated the probe in playful activities. We deployed the probe in a rural Australian preschool in a free-play environment. Initial observational findings show that the children understood the procedure of the interactions and moved from exploring to constructive play activities

Criminology

Queer Criminology is an emerging field of study focused on advancing the state of knowledge on the intersections of sexuality, gender diversity, and criminal justice. This entry provides an introduction this field, charting its emergence within criminology and canvassing its key empirical and theoretical contributions and innovations. The entry also explores the theoretical and conceptual debates within Queer Criminology, specifically concerning the role and influence of Queer Theory in the field

双轴应变对单层Janus过渡金属硫族化合物热输运和热电性能的影响 [Influence of biaxial strain effects on thermal transport and thermoelectric performance of Janus transition metal dichalcogenide monolayers]

Janus transition metal dichalcogenide monolayers, characterized by antisymmetric crystal structures and unique physical properties, show great potential applications in micro/nano-electronic devices and thermoelectrics. In this work, the strain-tuned phonon thermal transport and thermoelectric performance of six Janus transition metal dichalcogenide monolayers are systematically investigated by first-principles calculations. This study focuses on monolayers of PtSSe and PtTeSe with a 1T-phase crystal structure, as well as monolayers of MoSSe, MoTeSe, WSSe, and WTeSe with a 1H-phase crystal structure. For all these monolayers, first-principles calculations are performed using the open-source software Quantum ESPRESSO. The lattice thermal conductivity is obtained based on lattice dynamics and iterative solutions of the Boltzmann transport equation. The thermal conductivities of PtSSe, MoSSe, and WSSe monolayers are generally higher than those of PtTeSe, MoTeSe, and WTeSe. Acoustic phonons are responsible for the majority of thermal transport, contributing over 95%. Under unstrained conditions, monolayer PtSSe demonstrates a superior thermal conductivity of 104 W·m –1·K –1, making it advantageous for thermal management applications in electronic devices. Under tensile strain, the thermal conductivities of PtSSe, MoSSe, and WSSe monolayers exhibit a monotonic decrease trend; however, for PtTeSe, MoTeSe, and WTeSe monolayers, their thermal conductivities initially show an increase trend, followed by a subsequent decrease trend. Under a 10% tensile strain, the thermal conductivities of these six Janus monolayers all demonstrate a reduction exceeding 60%. Furthermore, this work provides a comprehensive analysis of the influences of strain on specific heat capacity, phonon group velocity, and phonon lifetime. The phonon mode-level analysis and cross-calculated thermal conductivity (with specific heat capacity, phonon group velocity, and phonon lifetime replaced by values under different strain conditions) reveal that phonon lifetime is the dominant factor governing thermal conductivity under strain. For electrical transport properties, calculations are performed using the Boltzmann transport equation based on deformation potential theory. At room temperature, the thermoelectric figure of merit (ZT) for PtTeSe is 0.91 without strain, which can be improved to 1.31 under 10% tensile strain. The ZT value reaches as high as 3.96 for p-type PtTeSe and 2.38 for n-type PtTeSe at 700 K, indicating that the PtTeSe monolayer is a highly promising thermoelectric material. Strain-induced enhancement in the thermoelectric performance of PtTeSe is facilitated by reducing lattice thermal conductivity and reconfigurating the band structure. This work demonstrates that strain engineering is an effective strategy for adjusting the thermal transport and thermoelectric properties of Janus transition metal dichalcogenide monolayers.</p

Arousal burden is highest in supine sleeping position and during light sleep

Study Objectives: Arousal burden (AB) is defined as the cumulative duration of arousals during sleep divided by the total sleep time. However, in-depth analysis of AB related to sleep characteristics is lacking. Based on previous studies addressing the arousal index, we hypothesized that the AB would peak in the supine sleeping position and during non-rapid eye movement stage 1 and show high variability between scorers. Methods: Nine expert scorers analyzed polysomnography recordings of 50 participants, the majority with an increased risk for obstructive sleep apnea. AB was calculated in different sleeping positions and sleep stages. A generalized estimating equation was used to test the association between AB and sleeping positions, sleep stages, and scorers. The correlation between AB and arousal index was tested with Spearman’s rank-order correlation. Results: AB significantly differed between sleeping positions (P < .001). The median AB in the supine sleeping position was 47–62% higher than in the left and right positions. The AB significantly differed between the sleep stages (P < .001); the median AB was more than 200% higher during non-rapid eye movement stage 1 than during other sleep stages. In addition, the AB differed significantly between scorers (P < .001) and correlated strongly with arousal index (r = .935, P < .001). Conclusions: AB depends on the sleeping position, sleep stage, and scorer, as hypothesized. AB behaved similarly to the arousal index, but the high variability in the ABs between scorers indicates a potential limitation caused by subjective manual scoring. Thus, the development of more accurate techniques for scoring arousals is required before AB can be reliably used.</p

Carbon Emissions of Railways: An Overview

Reducing greenhouse gas (GHG) emissions from transport is critical to global sustainable development efforts. Large-scale railways have the potential to reduce GHG emissions significantly throughout their life cycle, thus considered an effective solution. However, a comprehensive evaluation on the research landscape of railway carbon emissions (RCEs) is still missing in the current body of knowledge. This study conducted an extensive review of 15,881 articles from the Web of Science and Scopus databases, selecting 197 publications from 1999 to September 2024 for analysis. Using CiteSpace for keyword co-occurrence and clustering analysis, preliminary research themes were identified. This was followed by a detailed literature review using content analysis to examine research trends and themes deeply. The findings indicate a growing interest in RCEs research, especially after 2015, with most coming from China (82 articles) and the United States (23 articles). Seven research themes for RCEs were identified, with measurement methods (49 articles), impact on carbon emissions (39 articles), and mitigation measures (69 articles) as leading ones. Various measurement methods, including life cycle assessment, emission coefficient method, input-output model, and field monitoring method, are utilized, however, challenges related to activity data and emission factors hinder measurement accuracy. Railways influence carbon emissions through transport substitution, industrial structure upgrading, and technological innovation, with spatial spillovers and regional heterogeneity, however, inconsistencies arise regarding the directionality of this impact, whether positive or negative, and the underlying mechanism remains inadequately illustrated. Mitigation measures include policy level, technological innovation, and project management, nonetheless, each specific measure requires further empirical investigation and should be integrated to form a comprehensive governance. Additionally, more attention should be given to research in developing countries. This review provides the first comprehensive analysis of RCEs, highlighting key areas for future research and policy development, and offering valuable insights for researchers and practitioners.</p

The Palgrave Handbook of Mental Health Practice in Sub-Saharan Africa

The focus of this handbook is to highlight the key issues in addressing the challenges and opportunities to promote mental health is Sub-Saharan Africa. A unique feature of this work is the privileging of African voices in expressing the strengths, vulnerabilities, and unique approaches which have been found within the Sub-Saharan context. The handbook is broken into three sections. The first introduces the handbook and the general issues and concepts discussed. The second describes diverse community outreach and mental health interventions applied by the contributors in diverse Sub-Saharan Africa countries and contexts and addressing a range of mental health topics. The third focuses on systemic issues that affect mental health service delivery, with recommendations provided. Opportunities for creating new models for sharing practices and disseminating knowledge generated by Sub-Saharan African practitioners for their culture and contexts are discussed

In vitro and in vivo degradation studies of a dual medical-grade scaffold design for guided soft tissue regeneration

Biodegradable scaffolds with tailored mechanical and structural properties are essential for scaffold-guided soft tissue regeneration (SGSTR). SGSTR requires scaffolds with controllable degradation and erosion characteristics to maintain mechanical and structural integrity and strength for at least four to six months. Additionally, these scaffolds must allow for porosity expansion to create space for the growing tissue and exhibit increased mechanical compliance to match the properties of the newly formed tissue. Although progress has been made in this area, previous studies have yet to fully explore these aspects using biodegradable polymers that are synthesized and 3D printed into filaments classified as medical-grade. In this study, we optimized scaffold design based on the properties of biodegradable materials and employed digital-assisted 3D printing to adjust the degradation pathway of dual-material scaffolds dynamically, thereby modulating mechanical and structural changes. Two medical-grade 3D printing filaments were utilized: Dioxaprene® (DIO), which has a degradation rate of approximately six months, and Caproprene™ (CAP), which has a degradation rate of about 36 months. The scaffolds were 3D printed with these materials to create the desired architecture. An in vitro degradation study showed the increasing pore size and compliance (>90% increase) of the scaffold architecture via the breakdown of DIO. Meanwhile, the slow-degrading CAP maintained long-term mechanical and structural integrity. Furthermore, over six months of subcutaneous implantation in rats, the dual material showed an approximately two-fold increase in mechanical compliance and free volume expansion, with the pore size increasing from 1 mm to 2 mm to accommodate the growing tissue. The scaffold remained structurally intact and provided mechanical support for the newly formed tissue. Histological and immunohistochemical analyses indicated good in vivo biocompatibility, tissue guidance, and the formation of organized soft tissue architecture, supported by an extensive network of blood vessels. </p