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Although lexical diversity is often used as a measure of productive proficiency (e.g., as an aspect of lexical complexity) in SLA studies involving oral tasks, relatively little research has been conducted to support the reliability and/or validity of these indices in spoken contexts. Furthermore, SLA researchers commonly use indices of lexical diversity such as Root TTR (Guiraud's index) and D (vocd-D and HD-D) that have been preliminarily shown to lack reliability in spoken L2 contexts and/or have been consistently shown to lack reliability in written L2 contexts. In this study, we empirically evaluate lexical diversity indices with respect to two aspects of reliability (text-length independence and across-task stability) and one aspect of validity (relationship with proficiency scores). The results indicated that neither Root TTR nor D is reliable across different text lengths. However, support for the reliability and validity of optimized versions of MATTR and MTLD was found.

The devastating floods that swept through the Ahr valley in July 2021 left indelible marks on the region's landscape and communities. Beyond the visible damage, experience from other events suggests an increase in mental health issues among those affected. However, there is a lack of data and understanding regarding the impact of flooding on mental health in Germany. Therefore, this study aims to determine how much the flooding in 2021 affected the population's mental wellbeing. For this purpose, a household-level survey (n=516) was conducted in the district of Ahrweiler, Rhineland-Palatinate – Germany's most-affected region – 1 year after the flood event, specifically in June and July 2022. The survey employed a short epidemiological screening scale to assess the prevalence of individuals showing indications of post-traumatic stress disorder (PTSD). Using binary logistic regression analyses, we identify risk and protective factors that may have played a role in the development of PTSD to find intervention points for supporting those affected. Our findings indicate significant mental health issues 1 year after the flood event, with 28.2 % of respondents showing indications of PTSD. Furthermore, this study has uncovered essential risk factors for developing indications of PTSD after flooding: female gender, being seriously injured or becoming sick during the event, and feeling left alone to cope with flood impacts. The study emphasizes that severe flooding, such as the 2021 flood, results in new health-related needs that demand attention. As a result, care methods should be adapted to tackle the prevalence and risk factors connected with PTSD in the affected population, e.g., by providing targeted aftercare for individuals who were injured or became sick during the flood event.

Abstract Anastomotic leakage (AL) is a potentially life-threatening complication following colorectal cancer (CRC) resection. In this study, we aimed to unravel longitudinal changes in microbial structure before, during, and after surgery and to determine if microbial alterations may be predictive for risk assessment between sufficient anastomotic healing (AS) and AL prior surgery. We analysed the microbiota of 134 colon mucosal biopsies with 16S rRNA V1-V2 gene sequencing. Samples were collected from three location sites before, during, and after surgery, and patients received antibiotics after the initial collection and during surgery. The microbial structure showed dynamic surgery-related changes at different time points. Overall bacterial diversity and the abundance of some genera such as Faecalibacterium or Alistipes decreased over time, while the genera Enterococcus and Escherichia_Shigella increased. The distribution of taxa between AS and AL revealed significant differences in the abundance of genera such as Prevotella, Faecalibacterium and Phocaeicola. In addition to Phocaeicola, Ruminococcus2 and Blautia showed significant differences in abundance between preoperative sample types. ROC analysis of the predictive value of these genera for AL revealed an AUC of 0.802 (p = 0.0013). In summary, microbial composition was associated with postoperative outcomes, and the abundance of certain genera may be predictive of postoperative complications.

Microplastic pollution from everyday plastic items has increased tremendously worldwide. Pyrolysis gas chromatography coupled to mass spectrometry (Py-GC/MS) has been widely investigated for the qualitative and quantitative analysis of microplastics in environmental samples. However, there are several pitfalls to consider when developing an appropriate protocol for their analysis. This study aimed at the development of an in-house database of primary (single) polymers, binary (two) polymers and tertiary (three) polymer mixtures. In this context the potential occurrence of gas phase reactions during pyrolysis of binary and tertiary polymers were investigated. Further, different diluters were tested for the accurate preparation of calibration standards for quantification purposes.Seven different polymers were included in this study, which were chosen due to their prevalence in daily plastic appliances. For each single polymer specific peaks could be identified and recommendation for quantifier analytes given. The analysis of binary polymer mixtures revealed gas phase reactions for PET with PVC, PVC with MDI-PU and PE with PVC. For these binary polymers, several different novel pyrolysis products, specific for the according binary polymer mixture, could be identified. These results confirmed that especially PVC exhibits strong interactions during co-pyrolysis with ester- and ether-based polymers. Similar results were obtained for tertiary polymers.For accurate preparation of calibration standards different diluters (silica, deactivated silica, calcium carbonate, THF and HFIP) were tested. It was observed that deactivated silica had only an influence on the pyrolysis of PET. Whereas, dilution with silica affected PA-6/66, PE, PET and MDI-PU. Only PVC was not influenced by dilution with silica.In conclusion, our results highlight the necessity of an international standard of reference material as well as a standardized analytical protocol for the analysis and quantification of polymers in environmental samples. It is crucial to use diluters suitable for the specific polymer, to exclude potential interactions of diluters with the polymer. The present work has to be seen as a foundation, but future work is needed to adequately address the quantification of polymers in environmental samples.

Abstract Background Vascular anomalies caused by somatic (postzygotic) variants are clinically and genetically heterogeneous diseases with overlapping or distinct entities. The genetic knowledge in this field is rapidly growing, and genetic testing is now part of the diagnostic workup alongside the clinical, radiological and histopathological data. Nonetheless, access to genetic testing is still limited, and there is significant heterogeneity across the approaches used by the diagnostic laboratories, with direct consequences on test sensitivity and accuracy. The clinical utility of genetic testing is expected to increase progressively with improved theragnostics, which will be based on information about the efficacy and safety of the emerging drugs and future molecules. The aim of this study was to make recommendations for optimising and guiding the diagnostic genetic testing for somatic variants in patients with vascular malformations. Results Physicians and lab specialists from 11 multidisciplinary European centres for vascular anomalies reviewed the genes identified to date as being involved in non-hereditary vascular malformations, evaluated gene–disease associations, and made recommendations about the technical aspects for identification of low-level mosaicism and variant interpretation. A core list of 24 genes were selected based on the current practices in the participating laboratories, the ISSVA classification and the literature. In total 45 gene–phenotype associations were evaluated: 16 were considered definitive, 16 strong, 3 moderate, 7 limited and 3 with no evidence. Conclusions This work provides a detailed evidence-based view of the gene–disease associations in the field of vascular malformations caused by somatic variants. Knowing both the gene–phenotype relationships and the strength of the associations greatly help laboratories in data interpretation and eventually in the clinical diagnosis. This study reflects the state of knowledge as of mid-2023 and will be regularly updated on the VASCERN-VASCA website (VASCERN-VASCA, https://vascern.eu/groupe/vascular-anomalies/ ).

Summary: Purpose: Until now, the Hospitalization Rate (HR) served as an indicator (among others) for the COVID-19 associated healthcare burden. To ensure that the HR accomplishes its full potential, hospitalizations caused by COVID-19 (primary cases) and hospitalizations of patients with incidental positive SARS-CoV-2 test results (incidental cases) must be differentiated. The aim of this study was to synthesize the existing evidence on differentiation criteria between hospitalizations of primary cases and incidental cases. Methods: An online survey of the members of the German Network University Medicine (NUM) was conducted. Additionally, senior clinicians with expertise in COVID-19 care were invited for qualitative, semi-structured interviews. Furthermore, a rapid literature review was undertaken on publications between 03/2020 and 12/2022. Results: In the online survey (n=30, response rate 56%), pneumonia and acute upper respiratory tract infections were the most indicative diagnoses for a primary case. In contrast, malignant neoplasms and acute myocardial infarctions were most likely to be associated with incidental cases. According to the experts (n=6), the diagnosis, ward, and type of admission (emergency or elective), low oxygen saturation, need for supplemental oxygen, and initiation of COVID-19 therapy point to a primary case. The literature review found that respiratory syndromes and symptoms, oxygen support, and elevated levels of inflammatory markers were associated with primary cases. Conclusion: There are parameters for the differentiation of primary from incidental cases to improve the objective of the HR. Ultimately, an updated HR has the potential to serve as a more accurate indicator of the COVID-19 associated healthcare burden.

Abstract Mosquitoes (Culicidae) represent the main vector insects globally, and they also inhabit many of the terrestrial and aquatic habitats of the world. DNA barcoding and metabarcoding are now widely used in both research and routine practices involving mosquitoes. However, these methodologies rely on information available in databases consisting of barcode sequences representing taxonomically identified voucher specimens. In this study, we assess the availability of public data for mosquitoes in the main online databases, focusing specifically on the two most widely used DNA barcoding markers in Culicidae: COI and ITS2. In addition, we test hypotheses on possible factors affecting species coverage (i.e., the percentage of species covered in the online databases) for COI in different countries and the occurrence of the DNA barcode gap for COI. Our findings showed differences in the data publicly available in the repositories, with a taxonomic or species coverage of 28.4–30.11% for COI in BOLD + GenBank, and 12.32% for ITS2 in GenBank. Afrotropical, Australian and Oriental biogeographic regions had the lowest coverages, while Nearctic, Palearctic and Oceanian had the highest. The Neotropical region had an intermediate coverage. In general, countries with a higher diversity of mosquitoes and higher numbers of medically important species had lower coverage. Moreover, countries with a higher number of endemic species tended to have a higher coverage. Although our DNA barcode gap analyses suggested that the species boundaries need to be revised in half of the mosquito species available in the databases, additional data must be gathered to confirm these results and to allow explaining the occurrence of the DNA barcode gap. We hope this study can help guide regional species inventories of mosquitoes and the completion of a publicly available reference library of DNA barcodes for all mosquito species.

Generating large labeled datasets is a common barrier in machine learning efforts, with frequent challenges in both labeling and creating useful models for these datasets. We introduce a new approach to the automatic text labeling and semantic textual similarity tasks, which utilizes an encoder layer that is fine-tuned using triplet loss. This approach, contrastive meta-learning (CML), is specifically designed to create a naturally separable embedding space, based on minimal a priori examples. We find that through the use of CML, we are able to perform up to state-of-the-art performance on similar few-shot learning automatic labeling methodologies. For the semantic textual similarity task, CML creates a close approximation to a model trained with the full dataset, with as little as 8 training examples, whereas other common approaches require outside datasets.

The study determines the frequency–temperature dependence of the conductivity of a moist solid insulation component of power transformers, impregnated with the innovative bio-oil NYTRO® BIO 300X, manufactured from plant-based raw materials. The research was conducted for six moisture levels ranging from 0.6% to 5% by weight, within a frequency range from 10−4 Hz to 5 · 103 Hz and measurement temperatures from 20 °C to 70 °C, with a 10 °C step. The conduction model for both DC and AC, based on the quantum mechanical phenomenon of electron tunneling between water nanodroplets, was used to analyze the obtained results. It was determined that the frequency dependence of the conductivity of pressboard-bio-oil-moisture composites is influenced by two factors as follows: the activation energy of conductivity and the activation energy of relaxation time. For each moisture content, 16 values of the activation energy of the relaxation time and 16 values of the activation energy of conductivity were determined. It was found that the values of activation energy of conductivity and relaxation time are equal and independent of moisture content, frequency, and temperature. Based on 192 residual activation energy values, the mean generalized activation energy value for the relaxation time and conductivity was calculated with high precision, resulting in ΔE ≈ (1.02627 ± 0.01606) eV. The uncertainty of its determination was only ±1.6%. This indicates that electron tunneling from the first nanodroplet to the second, causing AC conductivity, and their return from the second nanodroplet to the first, determining the relaxation time, occur between the same energy states belonging to the water nanodroplets located in the pressboard impregnated with bio-oil. For each moisture content, the curves obtained for different measurement temperatures were recalculated to a reference temperature of 20 °C using the generalized activation energy. It was found that the shifted curves obtained for different temperatures perfectly overlap. Increased moisture content shifts the recalculated curves toward higher conductivity values. It was established that for all moisture contents in the lowest frequency range, conductivity is constant (DC conductivity). A further increase in frequency causes a rapid rise in conductivity. The increasing period can be divided into two stages. The first stage occurs up to about 100 Hz–101 Hz, depending on the moisture content. In the second stage, the rate of conductivity increase is higher, and its value depends on moisture content. The lower the moisture content, the faster the conductivity increases. Recalculation using the generalized activation energy eliminated the effect of temperature on the curves. It was found that the shapes of the recalculated curves and their position relative to the coordinates depend only on the moisture content in the composite. The equality of the activation energy of the relaxation time and conductivity established in the study, as well as their independence from frequency and moisture content in the pressboard impregnated with NYTRO® BIO 300X bio-oil, allows for recalculating the curves of electrical parameters determined at any operating temperatures of the transformer to a reference temperature, for example, 20 °C. Comparing the curve obtained for the transformer, recalculated to the reference temperature, with reference curves determined by us in the laboratory for different moisture contents, will allow for the precise determination of the moisture content of the solid insulation component impregnated with NYTRO® BIO 300X bio-oil. This will contribute to the early detection of approaching critical moisture content, threatening catastrophic transformer failure.

Background: This study examined the cognitive, behavioral, and affective mechanisms underlying the efficacy of Applied Relaxation (AR) in reducing psychopathological symptoms. AR is a cognitive-behavioral technique that allows for rapid relaxation at the first sign of stress or tension in daily life. Methods: A randomized controlled trial was conducted in 277 adults (18–55 years) with elevated symptoms of depression, anxiety, or stress but without a 12-month DSM-5 mental disorder at study entry. Participants were randomized to an intervention group receiving AR training (10 weeks, N = 139) and an assessment-only control group (N = 138). Mental health outcomes (depressive, anxiety, and stress symptoms) and potential cognitive (self-efficacy, perceived control), behavioral (coping behaviors) and affective (positive and negative affect) mediators of the intervention efficacy were assessed at baseline and post-assessment in both groups. Results: Structural equation models indicated that baseline to post reductions in psychopathological symptoms due to AR partially passed through less avoidance-oriented and less other dysfunctional coping (proportion of total effect mediated; ratio of indirect to total effect: resignation: 55.0%, rumination: 27.9%, escape: 27.4%, aggression: 21.3%), less negative affect (46.3%), more positive affect (41.8%), lower external control beliefs (14.5%), and higher self-efficacy (13.3%). Conclusions: Our results suggest that improvements in cognitive, behavioral, and affective mediator variables partially explain the intervention efficacy of AR in improving mental health. Trial registration and data statement: The study protocol has been pre-registered on ClinicalTrials.gov (NCT03311529). The study protocol, minimum dataset, and analysis codes are available at OpARA - Open Access Repository and Archive. Supplementary materials (e.g., the course manual and additional training materials) are available on request from the last author (katja.beesdo-baum@tu-dresden.de).

RASopathies are a group of genetic disorders caused by mutations in genes encoding components and regulators of the RAS/MAPK signaling pathway, resulting in overactivation of signaling. RASopathy patients exhibit distinctive facial features, cardiopathies, growth and skeletal abnormalities, and varying degrees of neurocognitive impairments including neurodevelopmental delay, intellectual disabilities, or attention deficits. At present, it is unclear how RASopathy mutations cause neurocognitive impairment and what their neuron-specific cellular and network phenotypes are. Here, we investigated the effect of RASopathy mutations on the establishment and functional maturation of neuronal networks. We isolated cortical neurons from RASopathy mouse models, cultured them on multielectrode arrays and performed longitudinal recordings of spontaneous activity in developing networks as well as recordings of evoked responses in mature neurons. To facilitate the analysis of large and complex data sets resulting from long-term multielectrode recordings, we developed MATLAB-based tools for data processing, analysis, and statistical evaluation. Longitudinal analysis of spontaneous network activity revealed a convergent developmental phenotype in neurons carrying the gain-of-function Noonan syndrome-related mutations Ptpn11D61Y and KrasV14l. The phenotype was more pronounced at the earlier time points and faded out over time, suggesting the emergence of compensatory mechanisms during network maturation. Nevertheless, persistent differences in excitatory/inhibitory balance and network excitability were observed in mature networks. This study improves the understanding of the complex relationship between genetic mutations and clinical manifestations in RASopathies by adding insights into functional network processes as an additional piece of the puzzle.

Background We aimed to correlate alterations in the rat sarcoma virus (RAS)/mitogen‐activated protein kinase pathway in vascular anomalies to the clinical phenotype for improved patient and treatment stratification. Methods and Results This retrospective multicenter cohort study included 29 patients with extracranial vascular anomalies containing mosaic pathogenic variants (PVs) in genes of the RAS/mitogen‐activated protein kinase pathway. Tissue samples were collected during invasive treatment or clinically indicated biopsies. PVs were detected by the targeted sequencing of panels of genes known to be associated with vascular anomalies, performed using DNA from affected tissue. Subgroup analyses were performed according to the affected genes with regard to phenotypic characteristics in a descriptive manner. Twenty‐five vascular malformations, 3 vascular tumors, and 1 patient with both a vascular malformation and vascular tumor presented the following distribution of PVs in genes: Kirsten rat sarcoma viral oncogene (n=10), neuroblastoma ras viral oncogene homolog (n=1), Harvey rat sarcoma viral oncogene homolog (n=5), V‐Raf murine sarcoma viral oncogene homolog B (n=8), and mitogen‐activated protein kinase kinase 1 (n=5). Patients with RAS PVs had advanced disease stages according to the Schobinger classification (stage 3–4: RAS, 9/13 versus non‐RAS, 3/11) and more frequent progression after treatment (RAS, 10/13 versus non‐RAS, 2/11). Lesions with Kirsten rat sarcoma viral oncogene PVs infiltrated more tissue layers compared with the other PVs including other RAS PVs (multiple tissue layers: Kirsten rat sarcoma viral oncogene, 8/10 versus other PVs, 6/19). Conclusions This comparison of patients with various PVs in genes of the RAS/MAPK pathway provides potential associations with certain morphological and clinical phenotypes. RAS variants were associated with more aggressive phenotypes, generating preliminary data and hypothesis for future larger studies.

RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the National Institutes of Health. A history of RASopathy gene discovery, identification of new disease genes, and the latest research, both at the bench and in the clinic, were discussed.

Different approaches analyze the strength of a natural language argument in different ways. This paper contrasts the dialectical, structural, probabilistic (or Bayesian), computational, and empirical approaches by exemplarily applying them to a single argumentative text (Epicureans on Squandering Life; Aikin & Talisse, 2019). Rather than pitching these approaches against one another, our main goal is to show the room for fruitful interaction. Our focus is on a dialectical analysis of the squandering argument as an argumentative response that voids an interlocutor’s right to assertion. This analysis addresses the pragmatic dimensions of arguing and implies an argument structure that is consistent with empirical evidence of perceived argument strength. Results show that the squandering argument can be evaluated as a (non-fallacious) ad hominem argument, which however is not necessarily stronger than possible arguments attacking it.

The Lucena 1 cell line, derived from the human chronic myeloid leukemia cell line K562 under selective pressure of vincristine supplementation, exhibits multidrug resistance (MDR). This study aims to explore and elucidate the underlying mechanisms driving MDR in the Lucena 1 cell line. A proteomic analysis comparing K562 and Lucena 1 revealed qualitative differences, with a focus on the ATP-dependent efflux pump, Translocase ABCB1, a key contributor to drug resistance. Tubulin analysis identified two unique isoforms, Tubulin beta 8B and alpha chain-like 3, exclusive to Lucena 1, potentially influencing resistance mechanisms. Additionally, the association of Rap1A and Krit1 in cytoskeletal regulation and the presence of STAT1, linked to the urea cycle and tumor development, offered insights into Lucena 1’s distinctive biology. The increased expression of carbonic anhydrase I suggested a role in pH regulation. The discovery of COP9, a tumor suppressor targeting p53, further highlighted the Lucena 1 complex molecular landscape. This study offers new insights into the MDR phenotype and its multifactorial consequences in cellular pathways. Thus, unraveling the mechanisms of MDR holds promise for innovating cancer models and antitumor targeted strategies, since inhibiting the P-glycoprotein (P-gp)/ABCB1 protein is not always an effective approach given the associated treatment toxicity.