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    External proficiency testing exercises: challenges and opportunities

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    Heavy Metal Stabilization of DNA Origami Nanostructures

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    DNA origami is a powerful tool to fold 3-dimensional DNA structures with nanometer precision. Its usage, however, is limited as high ionic strength, temperatures below ∼60 °C, and pH values between 5 and 10 are required to ensure the structural integrity of DNA origami nanostructures. Here, we demonstrate a simple and effective method to stabilize DNA origami nanostructures against harsh buffer conditions using [PdCl4]2–. It provided the stabilization of different DNA origami nanostructures against mechanical compression, temperatures up to 100 °C, double-distilled water, and pH values between 4 and 12. Additionally, DNA origami superstructures and bound cargos are stabilized with yields of up to 98%. To demonstrate the general applicability of our approach, we employed our protocol with a Pd metallization procedure at elevated temperatures. In the future, we think that our method opens up new possibilities for applications of DNA origami nanostructures beyond their usual reaction conditions

    Intraoperative Extravascular Ultrasound in the Identification of Flow-Limiting Dissections after Balloon Angioplasty in the Femoropopliteal Segment

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    Background: The BIO REACT study is designed to investigate the incremental value of Extravascular UltraSound (EVUS) added to conventional angiography, compared to conventional angiography only for the identification of Flow-Limiting Dissections (FLD) and to evaluate the safety and efficacy of the REsponse Adapted Combination Therapy (REACT) for the treatment of femoropopliteal lesions. Methods: The primary endpoints were the specificity and sensitivity of EVUS added to angiography for the detection of FLD. Secondary endpoints were primary patency of the REACT therapy within 12 months, fCD-TLR, freedom from MAE, major target limb amputations (mTLA) and survival rates within 24 months. Results: A total of 150 patients were included. EVUS added to angiography had an overall sensitivity of 29% and specificity of 93% for the detection of FLD. There was no PSVR cut-off offering a clinically acceptable trade-off between meaningful sensitivity and specificity values for the detection of FLD. At 12 months, treatment with the REACT resulted in primary patency and fCD-TLR of 81.6% and 94.3%, respectively. In addition, freedom from MAE was 94.3% at 12 months. At 24 months, the survival rate was 94.0%. No mTLA was reported up to the 24-month follow-up. Conclusions: The addition of DUS to angiography showed limited value for detecting FLD in femoropopliteal artery disease

    Intrauterine Growth Restriction: Need to Improve Diagnostic Accuracy and Evidence for a Key Role of Oxidative Stress in Neonatal and Long-Term Sequelae

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    Intrauterine growth restriction (IUGR) and being small for gestational age (SGA) are two distinct conditions with different implications for short- and long-term child development. SGA is present if the estimated fetal or birth weight is below the tenth percentile. IUGR can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnion, lack of growth in the interval, estimated weight below the third percentile) and can also be present in fetuses and neonates with weights above the tenth percentile. There is a need to differentiate between IUGR and SGA whenever possible, as IUGR in particular is associated with greater perinatal morbidity, prematurity and mortality, as well as an increased risk for diseases in later life. Recognizing fetuses and newborns being “at risk” in order to monitor them accordingly and deliver them in good time, as well as to provide adequate follow up care to ameliorate adverse sequelae is still challenging. This review article discusses approaches to differentiate IUGR from SGA and further increase diagnostic accuracy. Since adverse prenatal influences increase but individually optimized further child development decreases the risk of later diseases, we also discuss the need for interdisciplinary follow-up strategies during childhood. Moreover, we present current concepts of pathophysiology, with a focus on oxidative stress and consecutive inflammatory and metabolic changes as key molecular mechanisms of adverse sequelae, and look at future scientific opportunities and challenges. Most importantly, awareness needs to be raised that pre- and postnatal care of IUGR neonates should be regarded as a continuum

    Optimization of sample preparation and data evaluation techniques for X-ray fluorescence prediction of soil texture, pH, and cation exchange capacity of loess soils

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    Use of X-ray fluorescence (XRF) spectrometry for estimation of soil texture, pH, and cation exchange capacity (CEC) is desirable given the time-consuming nature of traditional methods. Recent studies have shown promising results; however, fur- ther investigation is required to determine the effects of sample preparation and data evaluation techniques on accuracy. Our objective was to compare (I) a sim- ple but well-founded approach, combining measurement of powder samples and modeling with elemental contents as predictors in stepwise multiple linear regres- sions (MLR), with alternative approaches including (II) use of partial least squares regression (PLSR), (III) sample preparation as a pressed pellet, and (IV) spectral intensities as predictors (20 kV, 40 kV, and concatenated 20 + 40 kV). A total of 395 loess soils from three arable fields were used with a fivefold random training-testing approach and a hold-one-site-out training-testing approach. With random partition- ing, clay, silt, and sand accuracy with approach I was excellent (ratio of performance to interquartile distance in validation (RPIQv) = 8.5–12.9), while pH and CEC esti- mations were satisfactory to excellent (RPIQv = 2.0–2.5 and 2.2–3.3, respectively). Differences between MLR and PLSR were negligible. Increases in accuracy with pellet samples were 1%–13% of RPIQv for 20 kV intensities, but effects were incon- sistent for other predictors. The optimal predictor varied by property, and differences ranged from 3% to 13% of RPIQv. Improvements to accuracy from Approach I to the best alternative were largest for texture (10%–15%) but may be superfluous given the excellent accuracy across all approaches. Although the leave-one-site-out train- ing resulted in variable performance, inclusion of soils from the target site in training assured reliable accuracy

    Shape or size matters? Towards standard reporting of tensile testing parameters for human soft tissues: systematic review and finite element analysis

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    Material properties of soft-tissue samples are often derived through uniaxial tensile testing. For engineering materials, testing parameters (e.g., sample geometries and clamping conditions) are described by international standards; for biological tissues, such standards do not exist. To investigate what testing parameters have been reported for tensile testing of human soft-tissue samples, a systematic review of the literature was performed using PRISMA guidelines. Soft tissues are described as anisotropic and/or hyperelastic. Thus, we explored how the retrieved parameters compared against standards for engineering materials of similar characteristics. All research articles published in English, with an Abstract, and before 1 January 2023 were retrieved from databases of PubMed, Web of Science, and BASE. After screening of articles based on search terms and exclusion criteria, a total 1,096 articles were assessed for eligibility, from which 361 studies were retrieved and included in this review. We found that a non-tapered shape is most common (209 of 361), followed by a tapered sample shape (92 of 361). However, clamping conditions varied and were underreported (156 of 361). As a preliminary attempt to explore how the retrieved parameters might influence the stress distribution under tensile loading, a pilot study was performed using finite element analysis (FEA) and constitutive modeling for a clamped sample of little or no fiber dispersion. The preliminary FE simulation results might suggest the hypothesis that different sample geometries could have a profound influence on the stress-distribution under tensile loading. However, no conclusions can be drawn from these simulations, and future studies should involve exploring different sample geometries under different computational models and sample parameters (such as fiber dispersion and clamping effects). Taken together, reporting and choice of testing parameters remain as challenges, and as such, recommendations towards standard reporting of uniaxial tensile testing parameters for human soft tissues are proposed

    Parents’ Perceptions Regarding Their Children’s Medications and Expert-Assessed Drug-Related Problems in Pediatric Patients with Inborn Errors of Metabolism

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    We aimed to explore parents’ perceptions of their children’s medication use for inborn errors of metabolism (IEM), including the importance of medication intake, potential complications, and concerns about adverse drug reactions (ADR). Additionally, we aimed to determine expert-assessed clinically relevant drug-related problems, particularly those attributable to IEM. We interviewed 108 parents of 119 pediatric patients with IEM using a questionnaire relating to their perceptions regarding their children’s IEM medication. In affected siblings, a questionnaire was used for each child. We performed medication analyses to evaluate the patient’s complete medication regimen for clinically relevant drug-related problems, including medication for conditions other than IEM. It was very important to the parents of 85% of the patients to use IEM medication exactly as prescribed. The parents of 41% of patients perceived complications in their children’s use of IEM medication. The parents of 47% of patients reported fears concerning ADR because of IEM medication. Parents observed ADR in 27% of patients because of IEM medication. In 44% of patients, medication for conditions other than IEM was inadequate because of drug-related problems not associated with the IEM; a safe alternative existed in 21% of patients. In summary, almost half of the parents of patients with IEM reported complications with their child’s IEM medication intake and fears of ADR. Medication analyses showed that drug-related problems occurred regardless of IEM, emphasizing the general need to prescribe and dispense adequate, child-appropriate medication to minimize clinically relevant drug-related problems in pediatric patients

    Patient perspective on living with mild hemophilia in Germany: results from a nationwide survey

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    The disease burden and bleeding risk of patients with mild hemophilia may be underestimated. Their health-related quality of life (QoL) may be negatively impacted by insufficient treatment and bleed-related joint damage connected to a potentially delayed diagnosis

    Subdiffraction Distance Measurement of Dipolar Emitting Qubit Pairs

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    In this work, we present a possibility to measure the distance between two color centers far below the diffraction limit of light in the optical wavelength range using a confocal fluorescence microscope. For this purpose, we show how the process of fabricating nitrogen-vacancy (NV)-based qubits in diamond by ion implantation with lithography masks is carried out. These masks contain small holes down to 80 nm in diameter in which the qubits are formed. A method to systematically identify the spots with exactly two qubits, the photons of which are polarized perpendicular to each other, is introduced. Further, an optical polarization dependent photoluminescene measurement principle is shown to determine the projected color center distances in several spots between 16 and 95 nm. It is thus possible to precisely determine the positions and distances of two quantum bits with a standard deviation of less than 10 nm for most measurements. This will enable a simple, systematic procedure for finding suitable qubit systems for quantum applications

    The association between boredom and creativity in educational contexts: A scoping review on research approaches and empirical findings

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    Assumptions around the association between boredom and creativity are contentious. Although studies suggest positive effects of boredom, it is also considered a negative predictor of creativity. Researchers also assume that creativity reduces boredom, but boredom can also occur during creative tasks. In this review, we identify and systematise the empirical evidence available to date on the association between creativity and boredom in educational contexts. The string-guided electronic search yielded 2849 publications. Nineteen publications based on 27 empirical studies met the inclusion criteria. Two reviewers extracted definitions, theories, methods, operationalisations, measurement instruments, and outcomes from the studies using a coding scheme. We identified a range of different theoretical and methodological approaches. The largest cache of empirical evidence was obtained from experimental and quasi-experimental studies (five positive associations, four negative, two contradictory, and three insignificant results). Correlation studies identified three negative, one contradictory, and seven insignificant correlations between boredom and creativity. In addition, two studies with exploratory, statistically not relevant results contributed to the body of research. The results from the identified and evaluated studies argue both for and against the sensitivity of creative processes in relation to boredom—but a clear causal, positive or negative effect of boredom on creativity is not currently supported by the empirical evidence available. Previous research has also not yet demonstrated an apparent effect of creative states or traits on academic boredom. Future research should aim to explore under what circumstances different relationships between boredom and creativity can be observed and reliably replicated

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