Genomic and Epigenetic Changes Drive Aberrant Skeletal Muscle Differentiation in Rhabdomyosarcoma

Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children and adolescents, represents an aberrant form of skeletal muscle differentiation. Both skeletal muscle development, as well as regeneration of adult skeletal muscle are governed by members of the myogenic family of regulatory transcription factors (MRFs), which are deployed in a highly controlled, multi-step, bidirectional process. Many aspects of this complex process are deregulated in RMS and contribute to tumorigenesis. Interconnected loops of super-enhancers, called core regulatory circuitries (CRCs), define aberrant muscle differentiation in RMS cells. The transcriptional regulation of MRF expression/activity takes a central role in the CRCs active in skeletal muscle and RMS. In PAX3::FOXO1 fusion-positive (PF+) RMS, CRCs maintain expression of the disease-driving fusion oncogene. Recent single-cell studies have revealed hierarchically organized subsets of cells within the RMS cell pool, which recapitulate developmental myogenesis and appear to drive malignancy. There is a large interest in exploiting the causes of aberrant muscle development in RMS to allow for terminal differentiation as a therapeutic strategy, for example, by interrupting MEK/ERK signaling or by interfering with the epigenetic machinery controlling CRCs. In this review, we provide an overview of the genetic and epigenetic framework of abnormal muscle differentiation in RMS, as it provides insights into fundamental mechanisms of RMS malignancy, its remarkable phenotypic diversity and, ultimately, opportunities for therapeutic intervention

Negative correlation of single-cell PAX3:FOXO1 expression with tumorigenicity in rhabdomyosarcoma

Rhabdomyosarcomas (RMS) are phenotypically and functionally heterogeneous. Both primary human RMS cultures and low-passage Myf6Cre,Pax3:Foxo1,p53 mouse RMS cell lines, which express the fusion oncoprotein Pax3:Foxo1 and lack the tumor suppressor Tp53 (Myf6Cre,Pax3:Foxo1,p53), exhibit marked heterogeneity in PAX3:FOXO1 (P3F) expression at the single cell level. In mouse RMS cells, P3F expression is directed by the Pax3 promoter and coupled to eYFP. YFPlow/P3Flow mouse RMS cells included 87% G0/G1 cells and reorganized their actin cytoskeleton to produce a cellular phenotype characterized by more efficient adhesion and migration. This translated into higher tumor-propagating cell frequencies of YFPlow/P3Flow compared with YFPhigh/P3Fhigh cells. Both YFPlow/P3Flow and YFPhigh/P3Fhigh cells gave rise to mixed clones in vitro, consistent with fluctuations in P3F expression over time. Exposure to the anti-tropomyosin compound TR100 disrupted the cytoskeleton and reversed enhanced migration and adhesion of YFPlow/P3Flow RMS cells. Heterogeneous expression of PAX3:FOXO1 at the single cell level may provide a critical advantage during tumor progression

Investigation on Thermally Evaporated Aluminium Contact Layers for Perovskite Solar Cell Applications

Perovskite solar cells (PSCs) have gained wide interest due to their high device efficiency of up to 22.1%. Perovskite solar cells are comprised of five main layers: fluorine-doped tin oxide (FTO) glass, titanium dioxide (TiO2) electron transport layer (ETL), perovskite active layer, Spiro-OMeTAD hole transport layer (HTL), and a metal contact layer. The metal contact layer plays a significant role in collecting and transporting the generated current and hence governs the performance of the device. Aluminium (Al) is more cost-efficient than the commonly used silver (Ag) or gold (Au) contact layers in perovskite solar cells. The aim of this work is to investigate the influence of different thicknesses and surface morphologies on the electrical properties of the Al thin film contact layers for perovskite solar cell applications. The Al contact layers were deposited using a thermal evaporator with varying Al wire source lengths at constant deposition duration and pressure. The deposited films were characterised for thickness, morphology, and electrical properties using a stylus profilometer, an atomic force microscope, and a four-point probe, respectively. Results showed that thicker Al films have larger particle sizes as compared to the thinner films, demonstrating a more continuous film morphology. Resistivity and conductivity show a variance with different film thickness. Based on literature, higher conductivity and larger particle sizes of the metal contact layers can improve charge transportation, which contributes to the performance of the perovskite solar cell

Electrochromic Properties of Sol-Gel Deposited Electrochromic TiO2 Thin Films

Electrochromic (EC) smart windows are a type of glass window that can change from transparent to darker colour shades when a small voltage is applied. Titanium dioxide (TiO2) can be utilised as an EC material for EC smart windows. Although the TiO2 sol-gel spin-coating method is commonly used, the effect of the number of TiO2 layers was not reported. Thus, this paper investigates the effect of the number of TiO2layers. The increasing number of TiO2film layers demonstrated a noticeable increase in the thin films ‘anodic and cathodic diffusion coefficient, particularly with 11 TiO2layers. Additionally, the colouration and bleaching time was revealed to have a low correlation as the number of layers increased. Nonetheless, the lower number of TiO2layers resulted in lower colouring transmittance. Comparatively, the colouration efficiency for all films did not exhibit any significant change. Hence this study on the effect of the TiO2layering technique can open a new pathway in understanding the EC properties of TiO2-based EC devices

Pre-heating Temperature Effect on Electrochromic Properties of TiO2 Thin Films

Smart windows represent a promising technology that enables the selective transmission of light and heat, and electrochromism technology is gaining interest in smart window applications. Electrochromic (EC) smart windows are the preferred choice for outdoor applications due to their ability to withstand high temperatures. Particularly, Tungsten Trioxide (WO3) is commonly used as an electrochromic layer in EC devices. Although Titanium Dioxide (TiO2) is a less expensive EC material compatible with optoelectronics applications (including solar cells), it has received little research attention. In the course of this study, the sol-gel spin coating method was utilised to deposit a thin film of TiO2 onto Indium Tin Oxide (ITO). This technique was chosen for its simplicity, affordability, and ease of coating thin films. The pre-heating temperature demonstrated a critical role in sol-gel fabrication, particularly in electrochromic applications. As the impact of the pre-heating temperature remains poorly understood, this study effectively investigated the effect of various pre-heating temperatures on the performance of TiO2-based electrochromic thin films. Moreover, this study effectively analysed the structural, optical, and EC properties of the TiO2 thin films pre-heated at different temperature

Rapid post-annealing effect on the TiO2-based electrochromic films

The electrochromic (EC) window is a promising energy-saving smart window that can vary between three states: transparent, translucent, and opaque by applying low voltages. One of the potential EC materials is known as titanium dioxide (TiO2) due to its unique chemical and physical properties. Conventional post-annealing has been commonly employed for phase transition in EC thin films, but it suffers from drawbacks such as long treatment time and high energy consumption. Hence, in this study, TiO2 thin films were deposited on indium-doped tin oxide (ITO) and fluoride-doped tin oxide (FTO) glass substrates using a sol-gel spin coating technique, followed by a rapid post-annealing interval of 5 min at temperatures ranging from 300 to 450 °C. The optical, morphological, structural, and EC properties of TiO2 thin films were investigated. The measurement depicted that rapid post-annealing was a cost-effective and time-saving method for realising high-quality TiO2 EC thin films. Hence, this approach reduces the overall fabrication time and minimises energy consumption, rendering it an environmentally friendly process. The successful deployment of TiO2 in EC applications paves the way for integrating EC and photovoltaic technologies in energy-saving window glass applications, considering TiO2 is a crucial element in photovoltaic devices

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)