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Composites of textile fabrics and 3D-printed layers have been investigated thoroughly during the last decade. Usually, material extrusion such as the fused deposition modeling (FDM) technique is used to build such composites, revealing challenges in preparing form-locking connections between both materials due to the highly viscous polymer melt, which can hardly be pressed into textile fabrics. Resins used for 3D printing by vat photopolymerization, i.e., for stereolithography (SLA), are less viscous and can thus penetrate deeper into textile fabrics; however, fixing a textile on the printing bed that is fully dipped into the resin is more complicated. Here, we present one possible solution to easily fix textile fabrics for SLA printing with consumer printers according to the digital light processing (DLP) sub-method. Also, we show the results of a study of the mechanical properties of the resulting textile/polymer composites, as revealed by three-point bending tests.

Abstract While better management of loco-regional prostate cancer (PC) has greatly improved survival, advanced PC remains a major cause of cancer deaths. Identification of novel targetable pathways that contribute to tumor progression in PC could open new therapeutic options. The di-ganglioside GD2 is a target of FDA-approved antibody therapies in neuroblastoma, but the role of GD2 in PC is unexplored. Here, we show that GD2 is expressed in a small subpopulation of PC cells in a subset of patients and a higher proportion of metastatic tumors. Variable levels of cell surface GD2 expression were seen on many PC cell lines, and the expression was highly upregulated by experimental induction of lineage progression or enzalutamide resistance in CRPC cell models. GD2high cell fraction was enriched upon growth of PC cells as tumorspheres and GD2high fraction was enriched in tumorsphere-forming ability. CRISPR-Cas9 knockout (KO) of the rate-limiting GD2 biosynthetic enzyme GD3 Synthase (GD3S) in GD2high CRPC cell models markedly impaired the in vitro oncogenic traits and growth as bone-implanted xenograft tumors and reduced the cancer stem cell and epithelial-mesenchymal transition marker expression. Our results support the potential role of GD3S and its product GD2 in promoting PC tumorigenesis by maintaining cancer stem cells and suggest the potential for GD2 targeting in advanced PC.

Mercury (Hg) methylation genes (hgcAB) mediate the formation of the toxic methylmercury and have been identified from diverse environments, including freshwater and marine ecosystems, Arctic permafrost, forest and paddy soils, coal-ash amended sediments, chlor-alkali plants discharges and geothermal springs. Here we present the first attempt at a standardized protocol for the detection, identification and quantification of hgc genes from metagenomes. Our Hg-cycling microorganisms in aquatic and terrestrial ecosystems (Hg-MATE) database, a catalogue of hgc genes, provides the most accurate information to date on the taxonomic identity and functional/metabolic attributes of microorganisms responsible for Hg methylation in the environment. Furthermore, we introduce marky-coco, a ready-to-use bioinformatic pipeline based on de novo single-metagenome assembly, for easy and accurate characterization of hgc genes from environmental samples. We compared the recovery of hgc genes from environmental metagenomes using the marky-coco pipeline with an approach based on coassembly of multiple metagenomes. Our data show similar efficiency in both approaches for most environments except those with high diversity (i.e., paddy soils) for which a coassembly approach was preferred. Finally, we discuss the definition of true hgc genes and methods to normalize hgc gene counts from metagenomes.

Possibilities to perform 3D printing directly on textile fabrics have been investigated intensively during the last decade. Usually, fused deposition modeling (FDM) printing with often inexpensive 3D printers is applied in these experiments. Several studies revealed the influence of textile fabrics, FDM polymers and printing parameters, indicating that not all combinations of fabrics and printing materials are suitable for this task. Recently, first approaches to use stereolithography (SLA) or PolyJet Modeling (PJM) directly on textile fabrics have been reported. Here, the first comparison of the adhesion forces reached by FDM and SLA printing on different woven fabrics is shown, revealing significantly better adhesion for SLA printing.

Este texto tem por objetivo refletir sobre as imagens da arte utilizadas em contexto escolar, especialmente nas aulas de Artes Visuais, e sobre seu papel na propagação do racismo ou, na contramão desse, em atuação na luta antirracista. Para tanto, inicia-se a reflexão a partir da obra "A Redenção de Cam" (1895), de Modesto Brocos y Gómez, pintura pertencente ao acervo do Museu Nacional de Belas Artes (MNBA) e símbolo da tese do branqueamento no Brasil. São referenciais para a problematização dessa imagem os estudos de Lotierzo (2013; 2017), acerca do racismo na pintura brasileira entre 1850-1940; a ideia de olhar opositor/oposicional, de bell hooks (2019); e o conceito de imagens de controle, de Patrícia Hill Collins (2019). Ao final, são apresentadas produções das artistas Aline Motta, Renata Sampaio e Renata Felinto dos Santos, como imagens que podem provocar modos de se compreenderem as relações raciais no Brasil e, talvez, contribuir para o exercício de uma docência mais reflexiva e comprometida com a luta antirracista no que se refere ao trabalho com imagens da arte na escola.

The accuracy of reaction theories used to extract properties of exotic nuclei from scattering experiments is often unknown or not quantified, but of utmost importance when, e.g., constraining the equation of state of asymmetric nuclear matter from observables as the neutron-skin thickness. In order to test the Glauber multiple-scattering model, the total interaction cross section of Image 1 on carbon targets was measured at initial beam energies of 400, 550, 650, 800, and 1000 MeV/nucleon. The measurements were performed during the first experiment of the newly constructed R3B (Reaction with Relativistic Radioactive Beams) experiment after the start of FAIR Phase-0 at the GSI/FAIR facility with beam energies of 400, 550, 650, 800, and 1000 MeV/nucleon. The combination of the large-acceptance dipole magnet GLAD and a newly designed and highly efficient Time-of-Flight detector enabled a precise transmission measurement with several target thicknesses for each initial beam energy with an experimental uncertainty of ±0.4%. A comparison with the Glauber model revealed a discrepancy of around 3.1% at higher beam energies, which will serve as a crucial baseline for the model-dependent uncertainty in future fragmentation experiments.

BackgroundThe World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes.Methods and findingsA stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations.ConclusionsIn this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pregnancy in different populations, with different screening strategies and clinical management guidelines, to optimise women's and children's health in the short and long term.Trial registrationThe trial is registered with ISRCTN (41918550).

Abstract De novo synthesis of the pyrimidine, cytidine triphosphate (CTP), is crucial for DNA/RNA metabolism and depends on the CTP synthetases, CTPS1 and −2. Partial CTPS1 deficiency in humans has previously been shown to lead to immunodeficiency, with impaired expansion of T and B cells. Here, we examine the effects of conditional and inducible inactivation of Ctps1 and/or Ctps2 on mouse embryonic development and immunity. We report that deletion of Ctps1, but not Ctps2, is embryonic-lethal. Tissue and cells with high proliferation and renewal rates, such as intestinal epithelium, erythroid and thymic lineages, activated B and T lymphocytes, and memory T cells strongly rely on CTPS1 for their maintenance and growth. However, both CTPS1 and CTPS2 are required for T cell proliferation following TCR stimulation. Deletion of Ctps1 in T cells or treatment with a CTPS1 inhibitor rescued Foxp3-deficient mice from fatal systemic autoimmunity and reduced the severity of experimental autoimmune encephalomyelitis. These findings support that CTPS1 may represent a target for immune suppression.

Abstract Background New 3D technologies for superficial soft tissue changes, especially in plastic and reconstructive surgical procedures, can improve the planning and documentation of facial surgeries. The purpose of this study was to compare and determine the applicability and feasibility of three different 3D-photography systems in clinical practice imaging the nose. Methods A total of 16 healthy non-operated noses were included in this prospective study. A plaster model of each nose was produced, digitized, and converted to a .stl mesh (= ground truth model). Three-dimensional images of each nose were then taken using Artec Space Spider (gold standard), Planmeca ProFace®, and the Bellus3D Dental Pro application. All resulting .stl files were aligned to the ground truth model using MeshLab software, and the root mean square error (RMSE), mean surface distance (MSD), and Hausdorff distance (HD) were calculated. Results The Artec Space Spider 3D-photography system showed significantly better results compared to the two other systems in regard to RMSE, MSD, and HD (each p

Nanofiber mats with a high surface-to-volume ratio can be prepared by electrospinning. The Porosity is sometimes reported to be tunable by blending different materials, e.g., water-soluble poly(ethylene oxide) (PEO) with not water-soluble poly(acrylonitrile) (PAN). Here, nanofiber mats were electrospun from different PAN:PEO ratios, using a wire-based electrospinning machine “Nanospider Lab”. Investigations of the as-spun nanofiber mats as well as of membranes after washing off the water-soluble PEO by scanning electron microscopy (SEM) revealed severe differences in the nanofiber mat morphologies, such as varying fiber diameters and especially non-fibrous areas in the carbonized nanofiber mats, depending on the amount of PEO in the nanofiber mat as well as the molecular weight of the PEO. Similarly, the ratio and molecular weight of PEO influenced the results of stabilization and carbonization. This paper discusses the possibility of tailoring nanofiber porosity for the potential use of PAN nanofiber mats in tissue engineering, filtration, and other applications.

Summary: Receptor tyrosine kinases (RTKs) control stem cell maintenance vs. differentiation decisions. Casitas B-lineage lymphoma (CBL) family ubiquitin ligases are negative regulators of RTKs, but their stem cell regulatory roles remain unclear. Here, we show that Lgr5+ intestinal stem cell (ISC)-specific inducible Cbl-knockout (KO) on a Cblb null mouse background (iDKO) induced rapid loss of the Lgr5Hi ISCs with transient expansion of the Lgr5Lo transit-amplifying population. LacZ-based lineage tracing revealed increased ISC commitment toward enterocyte and goblet cell fate at the expense of Paneth cells. Functionally, Cbl/Cblb iDKO impaired the recovery from radiation-induced intestinal epithelial injury. In vitro, Cbl/Cblb iDKO led to inability to maintain intestinal organoids. Single-cell RNA sequencing in organoids identified Akt-mTOR (mammalian target of rapamycin) pathway hyperactivation upon iDKO, and pharmacological Akt-mTOR axis inhibition rescued the iDKO defects. Our results demonstrate a requirement for Cbl/Cblb in the maintenance of ISCs by fine-tuning the Akt-mTOR axis to balance stem cell maintenance vs. commitment to differentiation.

ObjectiveTo document the recovery of vascular services in Europe following the first COVID-19 pandemic peak.MethodsAn online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March - May 2020, "period 1"), and then again between May and June ("period 2") and June and July 2020 ("period 3"). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume.ResultsThe impact of the pandemic continued to be felt well after countries' first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence.ConclusionCentres reported a broad return of services approaching pre-pandemic "normal" by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries.

Relaxed Si1−xGex layers on Si(001) serve as virtual substrates for strained Si or Ge layers. However, plastically relaxed layers inevitably contain misfit and threading dislocations, negatively affecting devices. Deposition of a SiGe layer on the backside of the substrate introduces a dislocation reservoir at the wafer edge that can reduce the threading dislocation density (TDD) of Si0.98Ge0.02/Si layers, as these preexisting dislocations start gliding toward the wafer center upon reaching the critical thickness. Here, we show that this low-strain system can be used effectively to study dislocation glide kinetics. In agreement with the literature, dislocation glide is a thermally activated process with an activation energy of 2.12–2.16 eV. Near the critical thickness, relaxation is sluggish and inefficient due to the linear dependence of the glide velocity on excess stress. At lower growth rates, dislocations from the edge reservoir are activated in a lower density due to the increase in the critical thickness through partial strain relaxation by already activated dislocations. Contrary to common models, here, the lowest possible growth rate is not essential for minimizing the TDD. Instead, a careful balance between low and high growth rates is beneficial. Overcoming the initial sluggish and inefficient relaxation phase is critical while also avoiding accumulation of strain energy, and, therefore, the activation of dislocation sources. Only in a later stage of buffer growth, the growth rate should be reduced to a minimum. With this method, the TDD of strain relaxed Si0.84Ge0.16 layers is reduced to 7 × 104 cm−2. [ABSTRACT FROM AUTHOR]

In the context of developing a machine to automatically crochet fabrics, a suitable design tool tailored to the new technology and enabling its application is crucial. The paper offers first insights into the prototype of the crochet machine and presents the approach of such a design tool implemented in Python for creating, modeling and generating the machine instructions. With a graphical user interface (GUI), a flat crocheted fabric can be designed by arranging international crochet symbols for slip stitch (SL), single crochet (SC) and half double crochet (HDC). Built-in error checking mechanisms, following the rules of crochet and the machine’s constraints, will aid inexperienced crocheters in this process. Based on the resulting computer representation as an array containing short strings for the respective stitches, a topology-based 3D model at the meso scale is automatically created as a preview of the designed crocheted fabric. Also, machine instructions to automatically crochet the fabric with the crochet machine prototype are generated by mapping the computer representation of the stitches to macros of G-code and appending them in a valid order. The straightforward design tool shows the capabilities of the crochet machine and is extensible for further enhancements. Through modeling, the structure of the machine-crocheted fabrics is presented for the first time. In comparison to manually crocheted fabrics, the machine-crocheted ones exhibit a technical front and back, since stitches are formed by the machine only from one side.

Abstract HELLS/LSH (Helicase, Lymphoid Specific) is a SNF2-like chromatin remodelling protein involved in DNA methylation. Its loss-of-function in humans causes humoral immunodeficiency, called ICF4 syndrome (Immunodeficiency, Centromeric Instability, Facial anomalies). Here we show by our newly generated B-cell-specific Hells conditional knockout mouse model that HELLS plays a pivotal role in T-dependent B-cell responses. HELLS deficiency induces accelerated decay of germinal center (GC) B cells and impairs the generation of high affinity memory B cells and circulating antibodies. Mutant GC B cells undergo dramatic DNA hypomethylation and massive de-repression of evolutionary recent retrotransposons, which surprisingly does not directly affect their survival. Instead, they prematurely upregulate either memory B cell markers or the transcription factor ATF4, which is driving an mTORC1-dependent metabolic program typical of plasma cells. Treatment of wild type mice with a DNMT1-specific inhibitor phenocopies the accelerated kinetics, thus pointing towards DNA-methylation maintenance by HELLS being a crucial mechanism to fine-tune the GC transcriptional program and enable long-lasting humoral immunity.

Abstract Background Tumour hypoxia is a negative predictive and prognostic biomarker in colorectal cancer typically assessed by invasive sampling methods, which suffer from many shortcomings. This retrospective proof-of-principle study explores the potential of MRI-derived imaging markers in predicting tumour hypoxia non-invasively in patients with colorectal liver metastases (CLM). Methods A single-centre cohort of 146 CLMs from 112 patients were segmented on preoperative T2-weighted (T2W) images and diffusion-weighted imaging (DWI). HIF-1 alpha immunohistochemical staining index (high/low) was used as a reference standard. Radiomic features were extracted, and machine learning approaches were implemented to predict the degree of histopathological tumour hypoxia. Results Radiomic signatures from DWI b200 (AUC = 0.79, 95% CI 0.61–0.93, p = 0.002) and ADC (AUC = 0.72, 95% CI 0.50–0.90, p = 0.019) were significantly predictive of tumour hypoxia. Morphological T2W TE75 (AUC = 0.64, 95% CI 0.42–0.82, p = 0.092) and functional DWI b0 (AUC = 0.66, 95% CI 0.46–0.84, p = 0.069) and b800 (AUC = 0.64, 95% CI 0.44–0.82, p = 0.071) images also provided predictive information. T2W TE300 (AUC = 0.57, 95% CI 0.33–0.78, p = 0.312) and b = 10 (AUC = 0.53, 95% CI 0.33–0.74, p = 0.415) images were not predictive of tumour hypoxia. Conclusions T2W and DWI sequences encode information predictive of tumour hypoxia. Prospective multicentre studies could help develop and validate robust non-invasive hypoxia-detection algorithms. Critical relevance statement Hypoxia is a negative prognostic biomarker in colorectal cancer. Hypoxia is usually assessed by invasive sampling methods. This proof-of-principle retrospective study explores the role of AI-based MRI-derived imaging biomarkers in non-invasively predicting tumour hypoxia in patients with colorectal liver metastases (CLM). Graphical Abstract

Abstract Overexpression of the EPS15 Homology Domain containing 1 (EHD1) protein has been linked to tumorigenesis but whether its core function as a regulator of intracellular traffic of cell surface receptors plays a role in oncogenesis remains unknown. We establish that EHD1 is overexpressed in Ewing sarcoma (EWS), with high EHD1 mRNA expression specifying shorter patient survival. ShRNA-knockdown and CRISPR-knockout with mouse Ehd1 rescue established a requirement of EHD1 for tumorigenesis and metastasis. RTK antibody arrays identified IGF-1R as a target of EHD1 regulation in EWS. Mechanistically, we demonstrate a requirement of EHD1 for endocytic recycling and Golgi to plasma membrane traffic of IGF-1R to maintain its surface expression and downstream signaling. Conversely, EHD1 overexpression-dependent exaggerated oncogenic traits require IGF-1R expression and kinase activity. Our findings define the RTK traffic regulation as a proximal mechanism of EHD1 overexpression-dependent oncogenesis that impinges on IGF-1R in EWS, supporting the potential of IGF-1R and EHD1 co-targeting.

BackgroundThe Network University Medicine projects are an important part of the German COVID-19 research infrastructure. They comprise 2 subprojects: COVID-19 Data Exchange (CODEX) and Coordination on Mobile Pandemic Apps Best Practice and Solution Sharing (COMPASS). CODEX provides a centralized and secure data storage platform for research data, whereas in COMPASS, expert panels were gathered to develop a reference app framework for capturing patient-reported outcomes (PROs) that can be used by any researcher. ObjectiveOur study aims to integrate the data collected with the COMPASS reference app framework into the central CODEX platform, so that they can be used by secondary researchers. Although both projects used the Fast Healthcare Interoperability Resources (FHIR) standard, it was not used in a way that data could be shared directly. Given the short time frame and the parallel developments within the CODEX platform, a pragmatic and robust solution for an interface component was required. MethodsWe have developed a means to facilitate and promote the use of the German Corona Consensus (GECCO) data set, a core data set for COVID-19 research in Germany. In this way, we ensured semantic interoperability for the app-collected PRO data with the COMPASS app. We also developed an interface component to sustain syntactic interoperability. ResultsThe use of different FHIR types by the COMPASS reference app framework (the general-purpose FHIR Questionnaire) and the CODEX platform (eg, Patient, Condition, and Observation) was found to be the most significant obstacle. Therefore, we developed an interface component that realigns the Questionnaire items with the corresponding items in the GECCO data set and provides the correct resources for the CODEX platform. We extended the existing COMPASS questionnaire editor with an import function for GECCO items, which also tags them for the interface component. This ensures syntactic interoperability and eases the reuse of the GECCO data set for researchers. ConclusionsThis paper shows how PRO data, which are collected across various studies conducted by different researchers, can be captured in a research-compatible way. This means that the data can be shared with a central research infrastructure and be reused by other researchers to gain more insights about COVID-19 and its sequelae.