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Metacognitive accuracy is understood as the congruency of subjective evaluation and objectively measured learning performance. With reference to the "cue utilisation framework" and the "embedded-processes model of working memory," we proposed that prompts impact attentional processes during learning. Through guided prompting, learners place their attention on specific information during the learning process. We assumed that the information will be taken into account when comprehension judgments are formed. Subsequently, metacognitive accuracy will be altered. Based on the results of this online study with pre-service biology teachers, we can neither confirm nor reject our main hypothesis and assume small effects of prompting on metacognitive accuracy if there are any. Learning performance and judgment of comprehension were not found to be impacted by the use of resource- and deficit-oriented prompting. Other measurements of self-evaluation (i.e. satisfaction with learning outcome and prediction about prolonged comprehension) were not influenced through prompting. The study provides merely tentative evidence for altered metacognitive accuracy and effects on information processing through prompting. Results are discussed in light of online learning settings in which the effectiveness of prompt implementation might have been restricted compared to a classroom environment. We provide recommendations for the use of prompts in learning settings with the aim to facilitate their effectiveness, so that both resource-oriented and deficit-oriented prompts can contribute to metacognitive skill development if they are applied appropriately.

In this retrospective case series on neovascular age-related macular degeneration (nAMD), we aimed to improve Choroidal Neovascularization (CNV) visualization in Optical Coherence Tomography Angiography (OCTA) scans by addressing segmentation errors. Out of 198 eyes, 73 OCTA scans required manual segmentation correction. We compared uncorrected scans to those with minimal (2 corrections), moderate (10 corrections), and detailed (50 corrections) efforts targeting falsely segmented Bruch's Membrane (BM). Results showed that 55% of corrected OCTAs exhibited improved quality after manual correction. Notably, minimal correction (2 scans) already led to significant improvements, with additional corrections (10 or 50) not further enhancing expert grading. Reduced background noise and improved CNV identification were observed, with the most substantial improvement after two corrections compared to baseline uncorrected images. In conclusion, our approach of correcting segmentation errors effectively enhances image quality in OCTA scans of nAMD. This study demonstrates the efficacy of the method, with 55% of resegmented OCTA images exhibiting enhanced quality, leading to a notable increase in the proportion of high-quality images from 63 to 83%.

Variation in inflectional morphology across languages raises questions about the factors affecting their learnability. This study explores the effects of two suggested factors: the implicative structure of the paradigm and the distribution of forms within it, and how they interact to affect the learnability of the system. Our results from a human behavioral study and artificial neural network simulations suggest that these factors influence learning, though type frequency may only serve as a proxy for the effects of token frequency.

Infants develop the ability to anticipate action goals during their first year, as shown by anticipatory gaze behavior. As they grow older, this is first evident for most familiar actions and agents, e.g., human hands performing a reaching action; later also for unusual agents (e.g., mechanical claws). We argue that this ability emerges as infants attempt to segment the world they observe into events—to infer the currently unfolding events and to predict their consequences for minimizing anticipated uncertainty. We propose a computational model that explains this development from a functional, algorithmic perspective, CAPRI² (Cognitive Action PRediction And Inference in Infants). Our model integrates proposals about the development of object files, event files, and physical reasoning abilities into a learning and probabilistic planning-as-inference framework. While observing goal-directed, or arbitrary, interactions between two objects (i.e., potential agent and patient), CAPRI²’s active inference processes infer both maximally consistent event interpretations and motor actions (here, eye fixations), where the latter are executed in the service of further minimizing current and anticipated uncertainties. As a result, CAPRI² models typical developmental patterns of infants’ anticipatory gaze behavior in an emergent manner. Inparticular, to successfully model the emergent developmental pattern, our model suggests that infants activate object event files, implicitly reason about object interactions in an event-oriented manner, infer consistent interpretations of their observations, and control their gaze shifts to minimize anticipated uncertainty. We propose that these mechanisms, as reflected in our model, may constitute fundamental building blocks for developing goal-predictive capacities in infants.

Abstract Background At a global scale, the SARS-CoV-2 virus did not remain in its initial genotype for a long period of time, with the first global reports of variants of concern (VOCs) in late 2020. Subsequently, genome sequencing has become an indispensable tool for characterizing the ongoing pandemic, particularly for typing SARS-CoV-2 samples obtained from patients or environmental surveillance. For such SARS-CoV-2 typing, various in vitro and in silico workflows exist, yet to date, no systematic cross-platform validation has been reported. Results In this work, we present the first comprehensive cross-platform evaluation and validation of in silico SARS-CoV-2 typing workflows. The evaluation relies on a dataset of 54 patient-derived samples sequenced with several different in vitro approaches on all relevant state-of-the-art sequencing platforms. Moreover, we present UnCoVar, a robust, production-grade reproducible SARS-CoV-2 typing workflow that outperforms all other tested approaches in terms of precision and recall. Conclusions In many ways, the SARS-CoV-2 pandemic has accelerated the development of techniques and analytical approaches. We believe that this can serve as a blueprint for dealing with future pandemics. Accordingly, UnCoVar is easily generalizable towards other viral pathogens and future pandemics. The fully automated workflow assembles virus genomes from patient samples, identifies existing lineages, and provides high-resolution insights into individual mutations. UnCoVar includes extensive quality control and automatically generates interactive visual reports. UnCoVar is implemented as a Snakemake workflow. The open-source code is available under a BSD 2-clause license at github.com/IKIM-Essen/uncovar.

Abstract In this retrospective case series on neovascular age-related macular degeneration (nAMD), we aimed to improve Choroidal Neovascularization (CNV) visualization in Optical Coherence Tomography Angiography (OCTA) scans by addressing segmentation errors. Out of 198 eyes, 73 OCTA scans required manual segmentation correction. We compared uncorrected scans to those with minimal (2 corrections), moderate (10 corrections), and detailed (50 corrections) efforts targeting falsely segmented Bruch’s Membrane (BM). Results showed that 55% of corrected OCTAs exhibited improved quality after manual correction. Notably, minimal correction (2 scans) already led to significant improvements, with additional corrections (10 or 50) not further enhancing expert grading. Reduced background noise and improved CNV identification were observed, with the most substantial improvement after two corrections compared to baseline uncorrected images. In conclusion, our approach of correcting segmentation errors effectively enhances image quality in OCTA scans of nAMD. This study demonstrates the efficacy of the method, with 55% of resegmented OCTA images exhibiting enhanced quality, leading to a notable increase in the proportion of high-quality images from 63 to 83%.

Abstract Background The advancement of sequencing technologies results in the rapid release of hundreds of new genome assemblies a year providing unprecedented resources for the study of genome evolution. Within this context, the significance of in-depth analyses of repetitive elements, transposable elements (TEs) in particular, is increasingly recognized in understanding genome evolution. Despite the plethora of available bioinformatic tools for identifying and annotating TEs, the phylogenetic distance of the target species from a curated and classified database of repetitive element sequences constrains any automated annotation effort. Moreover, manual curation of raw repeat libraries is deemed essential due to the frequent incompleteness of automatically generated consensus sequences. Results Here, we present an example of a crowd-sourcing effort aimed at curating and annotating TE libraries of two non-model species built around a collaborative, peer-reviewed teaching process. Manual curation and classification are time-consuming processes that offer limited short-term academic rewards and are typically confined to a few research groups where methods are taught through hands-on experience. Crowd-sourcing efforts could therefore offer a significant opportunity to bridge the gap between learning the methods of curation effectively and empowering the scientific community with high-quality, reusable repeat libraries. Conclusions The collaborative manual curation of TEs from two tardigrade species, for which there were no TE libraries available, resulted in the successful characterization of hundreds of new and diverse TEs in a reasonable time frame. Our crowd-sourcing setting can be used as a teaching reference guide for similar projects: A hidden treasure awaits discovery within non-model organisms.

We study the effect of magnification in the Dark Energy Survey Year 3 analysis of galaxy clustering and galaxy-galaxy lensing, using two different lens samples: a sample of luminous red galaxies, redMaGiC, and a sample with a redshift-dependent magnitude limit, MagLim. We account for the effect of magnification on both the flux and size selection of galaxies, accounting for systematic effects using the Balrog image simulations. We estimate the impact of magnification on the galaxy clustering and galaxy-galaxy lensing cosmology analysis, finding it to be a significant systematic for the MagLim sample. We show cosmological constraints from the galaxy clustering autocorrelation and galaxy-galaxy lensing signal with different magnifications priors, finding broad consistency in cosmological parameters in ΛCDM and wCDM. However, when magnification bias amplitude is allowed to be free, we find the two-point correlation functions prefer a different amplitude to the fiducial input derived from the image simulations. We validate the magnification analysis by comparing the cross-clustering between lens bins with the prediction from the baseline analysis, which uses only the autocorrelation of the lens bins, indicating that systematics other than magnification may be the cause of the discrepancy. We show that adding the cross-clustering between lens redshift bins to the fit significantly improves the constraints on lens magnification parameters and allows uninformative priors to be used on magnification coefficients, without any loss of constraining power or prior volume concerns.

Abstract Background The efficacy of oncolytic viruses (OV) in cancer treatment depends on their ability to successfully infect and destroy tumor cells. However, patients’ tumors vary, and in the case of individual insensitivity to an OV, therapeutic efficacy is limited. Here, we present a protocol for rapid generation of tumor cell-specific adapted oncolytic coxsackievirus B3 (CVB3) with enhanced oncolytic potential and a satisfactory safety profile. This is achieved by combining directed viral evolution (DVE) with genetic modification of the viral genome and the use of a microRNA-dependent regulatory tool. Methods The oncolytic CVB3 variant PD-H was adapted to the refractory colorectal carcinoma cell line Colo320 through serial passaging. XTT assays and virus plaque assays were used to determine virus cytotoxicity and virus replication in vitro. Recombinant PD-H variants were generated through virus mutagenesis. Apoptosis was detected by Western blots, Caspase 3/7 assays, and DAPI staining. The therapeutic efficacy and safety of the adapted recombinant OV PD-SK-375TS were assessed in vivo using a subcutaneous Colo320 xenograft mouse model. Results PD-H was adapted to the colorectal cancer cell line Colo320 within 10 passages. Sequencing of passage 10 virus P-10 revealed a heterogenous virus population with five nucleotide mutations resulting in amino acid substitutions. The genotypically homogeneous OV PD-SK was generated by inserting the five detected mutations of P-10 into the genome of PD-H. PD-SK showed significantly stronger replication and cytotoxicity than PD-H in Colo320 cells, but not in other colorectal carcinoma cell lines. Increase of apoptosis induction was detected as key mechanisms of Colo320 cell-specific adaptation of PD-SK. For in vivo safety PD-SK was engineered with target sites of the miR-375 (miR-375TS) to exclude virus replication in normal tissues. PD-SK-375TS, unlike the PD-H-375TS not adapted homolog suppressed the growth of subcutaneous Colo320 tumors in nude mice without causing any side effects. Conclusion Taken together, here we present an optimized protocol for the rapid generation of tumor cell-specific adapted oncolytic CVB3 based on the oncolytic CVB3 strain PD-H. The protocol is promising for the generation of personalized OV for tumor therapy and has the potential to be applied to other OV.

Abstract Established methods of age estimation are based on correlating defined maturation stages of bony structures with tables representing the observed range of biological ages in the majority of cases. In this retrospective monocentric study in southwestern Germany, common age estimation methodology was assessed in n = 198 subjects at the age of 25 or younger by analyzing the influence of age, quadratic age, biological sex and age-sex interaction on the ossification stages of the medial epiphysis fugue. Three readers (ICC ≥ 0.81 for left/right side) evaluated routine care computed tomography images of the clavicle with a slice thickness of 1 mm. By using least square regression analyses, to determine the real biological age a quadratic function was determined corrected for the age estimated by established methods and sex (R2 = 0.6 each side), reducing the mean absolute error and root mean squared error in the age estimation of women (2.57 and 3.19) and men (2.57 and 3.47) to 1.54 and 1.82 for women, and 1.54 and 2.25 for men. In women, the medial clavicle epiphysis seem to fuse faster, which was particularly observable from approximately 18 years of age. Before that age, the estimation method was relatively close to the ideal correlation between assessed and real age. To conclude, the presented new method enables more precise age estimation in individuals and facilitates the determination and quantification of additional variables, quantifying their influence on the maturation of the medial clavicle epiphysis based on the established ossification stages.

Abstract Background Recent exercise intervention studies have shown promising results in improving quality of life (QoL) and physical function (PF) in diverse chronic disease and advanced cancer patients. However, the effects of structured exercise in palliative care patients, having different therapeutic needs, lower life expectancies and PFs remain unknown. This study primarily aimed to assess the feasibility of an exercise intervention with follow-up by analysing recruitment numbers, screening procedures, acceptability, preferences, and safety of the exercise intervention as well as retention in follow-up. Our secondary aims related to changes in QoL and PF. Methods This study comprised of a one-arm design without a control group. Over 6 months, every in-hospital palliative care unit (PCU) patient was screened for eligibility. Eligible patients were asked to participate in a 2-week exercise intervention consisting of resistance training and/or endurance training with moderate or high intensity based on personal preferences and a 4-week follow-up. Before and after the exercise intervention, QoL and PF were assessed and a qualitative interview after the intervention addressed expectations and experiences of the exercise intervention. For follow-up, patients were provided with information on independent training and after 1 and 4 weeks a QoL assessment and qualitative interview were conducted. Results Of 124 patients screened, 10 completed the intervention with an adherence rate of (80 ± 25%), of which 6 patients completed follow-up. Endurance training was the most performed training type and only a few minor adverse events occurred in certain or likely connection to the exercise intervention. While physical QoL and PF measured by arm curl strength and time up and go performance improved, mental QoL and the other PF tests remained unchanged. Conclusion Despite the challenges that were faced in our screening and testing process, that are specific to the palliative patient population with their unique therapeutic requirements and varying mental-/ physical capabilities, we discovered the 2-week exercise intervention to be feasible, safe, and well tolerated by palliative care patients. Moreover, it seems that short-term improvements in QoL and PF are possible. Further full scale studies are required to confirm our findings. Trial registration The study was retrospectively registered on 25.01.2022 in the German Clinical Trials Register (DRKS00027861)

Betrachtet man die öffentliche Diskussion um das Thema «Medienabhängigkeit», wird diese vor allem von suchtmedizinischer Seite bestimmt. Dies trifft ebenfalls auf das Phänomen der exzessiven Computerspielnutzung zu. Um einer Pathologisierung entgegenzuwirken, erachten wir es als erkenntnisreich, sich den existierenden Positionen zum Phänomen zu widmen und insbesondere mögliche medienpädagogische Perspektiven zu skizzieren. Mit dem Begriff der «problematischen Medienabhängigkeit» definieren wir einen Arbeitsbegriff entlang einer kritisch-optimistischen anstatt einer kulturpessimistischen Sicht. Die theoretischen Überlegungen zur Notwendigkeit eines solchen Perspektivwechsels werden anhand einer empirischen Untersuchung zur exzessiven Computerspielnutzung verdeutlicht. In den mittels theoretischen Kodierens nach der Grounded Theory ausgewerteten Interviews mit betroffenen Computerspielnutzer:innen zeigt sich, dass die Medienangebote selbst nicht als Ursache, sondern als Lösungsstrategien einer problematischen Medienabhängigkeit zu betrachten sind. Die Vorteile dieses Perspektivwechsels für die medienpädagogische Forschung und Arbeit werden in den abschliessenden Implikationen für die Praxis zusammengefasst.

Adipose tissue-derived non-esterified saturated long-chain fatty acid palmitate (PA) decisively contributes to β-cell demise in type 2 diabetes mellitus in part through the excessive generation of hydrogen peroxide (H2O2). The endoplasmic reticulum (ER) as the primary site of oxidative protein folding could represent a significant source of H2O2. Both ER-oxidoreductin-1 (ERO-1) isoenzymes, ERO-1α and ERO-1β, catalyse oxidative protein folding within the ER, generating equimolar amounts of H2O2 for every disulphide bond formed. However, whether ERO-1-derived H2O2 constitutes a potential source of cytotoxic luminal H2O2 under lipotoxic conditions is still unknown. Here, we demonstrate that both ERO-1 isoforms are expressed in pancreatic β-cells, but interestingly, PA only significantly induces ERO-1α. Its specific deletion significantly attenuates PA-mediated oxidative ER stress and subsequent β-cell death by decreasing PA-mediated ER-luminal and mitochondrial H2O2 accumulation, by counteracting the dysregulation of ER Ca2+ homeostasis, and by mitigating the reduction of mitochondrial membrane potential and lowered ATP content. Moreover, ablation of ERO-1α alleviated PA-induced hyperoxidation of the ER redox milieu. Importantly, ablation of ERO-1α did not affect the insulin secretory capacity, the unfolded protein response, or ER redox homeostasis under steady-state conditions. The involvement of ERO-1α-derived H2O2 in PA-mediated β-cell lipotoxicity was corroborated by the overexpression of a redox-active ERO-1α underscoring the proapoptotic activity of ERO-1α in pancreatic β-cells. Overall, our findings highlight the critical role of ERO-1α-derived H2O2 in lipotoxic ER stress and β-cell failure.

Objective: In 2009, Palliative care was incorporated into the medical curriculum as Cross-Sectional Subject 13 (QB13) by means of the revision of the Medical Licensing Regulations for Physicians. The aim of this study was to determine the strengths and deficits of QB13 student education for palliative care in clinical practice in a multi-centre setting and to identify potential for improvement.Methods: Online questionnaires filled out by medical students during their Practical Year (PY) and resident physicians from the university hospitals in Aachen, Düsseldorf, and Cologne were descriptively analyzed using SPSS; free-text responses were categorized and quantified. Semi-structured interviews with the resident physicians (using a mixed-methods design) were analyzed through content analysis. Emerging categories were quantified.Results: Analysis of 130 fully completed questionnaires and 23 interviews revealed that participants particularly benefited from patient- and practice-oriented small-group sessions for their clinical work. Despite some university-specific differences, the PY students identified a need for training in end-of-life-care, while resident physicians saw a need for training primarily in dealing with patients and their relatives. They also reported deficits in transferability. Conclusion: QB13 should be organised in cross-university curricula and provide sufficient resources for practical-oriented small-group teaching. Based on the "unit of care", besides caring for palliative patients, dealing with patients’ families should also be an education focus. To improve transferability into clinical practice, students should be actively involved in the care of palliative patients.

Abstract Synthesizing intermetallic phases containing noble metals often poses a challenge as the melting points of noble metals often exceed the boiling point of bismuth (1560 °C). Reactions in the solid state generally circumvent this issue but are extremely time consuming. A convenient method to overcome these obstacles is the co‐reduction of metal salts in polyols, which can be performed within hours at moderate temperatures and even allows access to metastable phases. However, little attention has been paid to the formation mechanisms of intermetallic particles in polyol reductions. Identifying crucial reaction parameters and finding patterns are key factors to enable targeted syntheses and product design. Here, we chose metastable γ‐BiPd as an example to investigate the formation mechanism from mixtures of metal salts in ethylene glycol and to determine critical factors for phase formation. The reaction was also monitored by in situ X‐ray diffraction using synchrotron radiation. Products, intermediates and solutions were characterized by (in situ) X‐ray diffraction, electron microscopy, and UV‐Vis spectroscopy. In the first step of the reaction, elemental palladium precipitates. Increasing temperature induces the reduction of bismuth cations and the subsequent rapid incorporation of bismuth into the palladium cores, yielding the γ‐BiPd phase.