Search

Larvae of lacewings (Neuroptera) are known to be fierce predators today. Most characteristic are their prominent piercing-sucking stylets, which are used for venom injection and sucking out the fluids of the prey. Among lacewing larvae, aphidlions (larvae of the groups Chrysopidae and Hemerobiidae, green and brown lacewings) are today highly specialised to feed on aphids and evolved strategies to not be detected and attacked by, e.g., aphid-protecting ants. Fossil relatives of modern aphidlions seem to have also employed other strategies. For the species Pedanoptera arachnophila from about 100-million-year-old Kachin amber, Myanmar, an interaction of its larvae with spiders has been assumed. We present here new specimens resembling these larvae, including one piece of Cretaceous Kachin amber with a syn-inclusion of an aphidlion-like larva and an immature planthopper, indicating planthoppers as potential prey of the group about 100 million years ago. The morphology of the lacewing larva, with a trapezoid head capsule (in dorsal view), simple, toothless stylets, very elongate legs, and a spindle-shaped trunk, indicates that it is conspecific or at least closely related to P. arachnophila. We reconstruct the possible ontogenetic sequence of Pedanoptera arachnophila and discuss its ecology. [ABSTRACT FROM AUTHOR]

Childhood obesity poses a significant public health challenge, yet the molecular intricacies underlying its pathobiology remain elusive. Leveraging extensive multi-omics profiling (methylome, miRNome, transcriptome, proteins and metabolites) and a rich phenotypic characterization across two parts of Europe within the population-based Human Early Life Exposome project, we unravel the molecular landscape of childhood obesity and associated metabolic dysfunction. Our integrative analysis uncovers three clusters of children defined by specific multi-omics profiles, one of which characterized not only by higher adiposity but also by a high degree of metabolic complications. This high-risk cluster exhibits a complex interplay across many biological pathways, predominantly underscored by inflammation-related cascades. Further, by incorporating comprehensive information from the environmental risk-scape of the critical pregnancy period, we identify pre-pregnancy body mass index and environmental pollutants like perfluorooctanoate and mercury as important determinants of the high-risk cluster. Overall, our work helps to identify potential risk factors for prevention and intervention strategies early in the life course aimed at mitigating obesity and its long-term health consequences. Obesity encompasses numerous interconnected pathological mechanisms. Here, the authors show that integrating multi-omics data uncovers distinct molecular profiles and prenatal factors linked to childhood obesity and metabolic dysfunction, providing insights for early prevention and intervention strategies. [ABSTRACT FROM AUTHOR]

Including routine client feedback can increase the effectiveness of mental health interventions for children, especially when implemented as intended. Rate of implementation, or dose, of such feedback interventions has been shown to moderate results in some studies. Variation in implementation and use of client feedback may also contribute to the mixed results observed within the feedback literature. This study evaluates dose-response associations of client feedback using a novel Measurement Feedback System (MFS) within an indicated group intervention. The primary aim was to determine whether the rate of MFS implementation predicts symptom reduction in anxiety and depression among school-aged children. The secondary aim was to assess whether the rate of MFS implementation influences children's satisfaction with the group intervention or their dropout rates. Data were collected via a randomized factorial study (clinicaltrials.gov NCT04263558) across 58 primary schools in Norway. Children aged 8 to 12 years (N = 701) participated in a group-based, transdiagnostic intervention targeting elevated symptoms of anxiety or depression. Half of the child groups also received the feedback intervention using the MittEcho MFS. Group leaders (N = 83), recruited locally, facilitated the interventions. The MFS dose was measured using the Implementation Index, which combines the use of MFS by both children and providers (group leaders) into a single dose variable. Results showed no significant additional effect of dose of MFS on change in depression or anxiety scores, on user satisfaction with the intervention or on intervention dropout. The discussion addresses potential reasons for these non-significant findings and implications for MFS implementation in preventive, group-based interventions in school settings. [ABSTRACT FROM AUTHOR]

Introduction: SARS-CoV-2 antibodies in the cerebrospinal fluid (CSF) of COVID-19 patients possibly reflect blood-cerebrospinal fluid barrier (BCB) disruption due to systemic inflammation. However, some studies indicate that CSF antibodies signal a neurotropic infection. Currently, larger studies are needed to clarify this, and it is unknown if CSF antibodies appear solely after infection or also after COVID-19 vaccination. Therefore, we aimed to investigate the CSF dynamics of SARS-CoV-2 antibodies in a multicenter study of COVID-19 patients and vaccinated controls. Methods: A cohort study of Danish and Norwegian COVID-19 patients and controls investigated with a lumbar puncture (April 2020–December 2022). Serum and CSF were analysed locally for routine investigations, and centrally at Statens Serum Institut (Danish governmental public health institute) for SARS-CoV-2 IgG antibodies against the spike protein using the Euroimmun (quantitative) and Wantai (qualitative) assays. Primary outcome was the quantity of CSF SARS-CoV-2 antibodies post-COVID versus post-vaccination. Secondary outcomes included regression models examining the relationship between CSF antibodies and serum levels, albumin ratio, CSF pleocytosis, COVID-19 severity, and temporal antibody dynamics. Results: We included 124 individuals (Mean [SD] age 47.2 [16.6]; 59.7% males surviving COVID-19 and controls. Of these, 86 had paired CSF-serum testing. Antibody-index calculations did not support a SARS-CoV-2 brain infection. Multi-variate regression revealed that CSF SARS-CoV-2 antibodies were most strongly influenced by serum antibody levels and BCB permeability, as measured by increasing albumin ratio. CSF antibody levels displayed a dose–response relationship (p < 0.0001) influenced by preceding vaccinations or infections. CSF antibody levels (median [IQR]) were highest among those both previously infected and vaccinated, 100.0 [25.0–174.0], and those vaccinated without prior infection, 85.0 [12.0–142.0], and lowest among previously infected individuals without preceding vaccination, 5.9 [2.7–55.1], (p = 0.003). SARS-CoV-2 antibodies in CSF were also detected via qualitative assays in the COVID-19 (46.8%) and vaccinated (78.6%) groups, p = 0.03. Conclusion: SARS-CoV-2 antibodies detected in CSF can be derived following both infection and vaccination for COVID-19. CSF antibody levels increase in a dose–response relationship with the number of prior infections and vaccinations and are most strongly influenced by serum antibody levels and BCB permeability. These findings stress the importance of carefully interpreting CSF antibody results when assessing neurological complications following infections not categorized as neurotropic. [ABSTRACT FROM AUTHOR]

Aroma compositions are usually complex mixtures of odor-active compounds exhibiting diverse molecular structures. Due to chemical interactions of these compounds in the olfactory system, assessing or even predicting the olfactory quality of such mixtures is a difficult task, not only for statistical models, but even for trained assessors. Here, we combine fast automated analytical assessment tools with human sensory data of 11 experienced panelists and machine learning algorithms. Using 16 previously analyzed whisky samples (American or Scotch origin), we apply the linear classifier OWSum to distinguish the samples based on their detected molecules and to gain insights into the key molecular structure characteristics and odor descriptors for sample type. Moreover, we use OWSum and a Convolutional Neural Network (CNN) architecture to classify the five most relevant odor attributes of each sample and predict their sensory scores with promising accuracies (up to F1: 0.71, MCC: 0.68, ROCAUC: 0.78). The predictions outperform the inter-panelist agreement and thus demonstrate previously impossible data-driven sensory assessment in mixtures. Aroma compositions are usually complex mixtures of odor-active compounds exhibiting diverse molecular structures, and assessing or predicting the olfactory qualities of such mixtures is challenging. Here, fast automated analytical assessment tools are combined with the human sensory data of 11 experienced panelists and machine learning algorithms, enabling samples to be distinguished and classified based on their detected molecules, and gaining insights into key molecular structure characteristics and odor descriptors. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) permeates all fields of life, which resulted in new challenges in requirements engineering for artificial intelligence (RE4AI), e.g., the difficulty in specifying and validating requirements for AI or considering new quality requirements due to emerging ethical implications. It is currently unclear if existing RE methods are sufficient or if new ones are needed to address these challenges. Therefore, our goal is to provide a comprehensive overview of RE4AI to researchers and practitioners. What has been achieved so far, i.e., what practices are available, and what research gaps and challenges still need to be addressed? To achieve this, we conducted a systematic mapping study combining query string search and extensive snowballing. The extracted data was aggregated, and results were synthesized using thematic analysis. Our selection process led to the inclusion of 126 primary studies. Existing RE4AI research focuses mainly on requirements analysis and elicitation, with most practices applied in these areas. Furthermore, we identified requirements specification, explainability, and the gap between machine learning engineers and end-users as the most prevalent challenges, along with a few others. Additionally, we proposed seven potential research directions to address these challenges. Practitioners can use our results to identify and select suitable RE methods for working on their AI-based systems, while researchers can build on the identified gaps and research directions to push the field forward. [ABSTRACT FROM AUTHOR]

Introduction: According to the United Nations Convention on the Rights of the Child, adolescents' involvement in their healthcare is a fundamental right, and self-engagement in mental health treatment is vital for realizing their potential within person-centered care (PCC). Research exists that highlights barriers to involving adolescents in their care decisions. However, research on adolescents' own voices about self-engagement in mental health treatment has been scarce. This scoping review aimed to examine and summarize current knowledge on adolescents' voices regarding self-engagement in mental health treatment. Method: The review followed the scoping methodology of Arksey and O'Malley from 2005, updated by Levac and colleagues in 2010, involving five stages: (1) identifying the research question, (2) identifying relevant studies, (3) study selection, (4) charting the data, and (5) collating, summarizing and reporting the results. Results: Nineteen studies were included. The following themes on adolescents' voices regarding self-engagement in mental health treatment were identified: (1) the therapeutic alliance, (2) the need for active engagement in treatment, (3) different experiences due to time of data collection, (4) treatment context and healthcare system, and (5) adolescent-caregiver interaction. Conclusion: Adolescents' understanding of self-engagement was multilevel and comprehensive, including individual, contextual and relational factors. A strong therapeutic alliance with healthcare providers, and a need to be actively engaged in treatment were highlighted. To succeed in strengthening PCC in mental healthcare for adolescents, health professionals must take this complex understanding into consideration, as treatment without adolescents' self-engagement may worsen their clinical outcomes. Future research should explore specific PCC interventions and incorporate diverse methodologies in various clinical contexts. Additionally, insights from healthcare providers and caregivers on self-engagement in mental health treatment will complement these findings. [ABSTRACT FROM AUTHOR]

Objectives: Radical prostatectomy (RP) is a common intervention in patients with localized prostate cancer (PCa), with nerve-sparing RP recommended to reduce adverse effects on patient quality of life. Accurate pre-operative detection of extraprostatic extension (EPE) remains challenging, often leading to the application of suboptimal treatment. The aim of this study was to enhance pre-operative EPE detection through multimodal data integration using explainable machine learning (ML). Methods: Patients with newly diagnosed PCa who underwent [68Ga]Ga-PSMA-11 PET/MRI and subsequent RP were recruited retrospectively from two time ranges for training, cross-validation, and independent validation. The presence of EPE was measured from post-surgical histopathology and predicted using ML and pre-operative parameters, including PET/MRI-derived features, blood-based markers, histology-derived parameters, and demographic parameters. ML models were subsequently compared with conventional PET/MRI-based image readings. Results: The study involved 107 patients, 59 (55%) of whom were affected by EPE according to postoperative findings for the initial training and cross-validation. The ML models demonstrated superior diagnostic performance over conventional PET/MRI image readings, with the explainable boosting machine model achieving an AUC of 0.88 (95% CI 0.87–0.89) during cross-validation and an AUC of 0.88 (95% CI 0.75–0.97) during independent validation. The ML approach integrating invasive features demonstrated better predictive capabilities for EPE compared to visual clinical read-outs (Cross-validation AUC 0.88 versus 0.71, p = 0.02). Conclusion: ML based on routinely acquired clinical data can significantly improve the pre-operative detection of EPE in PCa patients, potentially enabling more accurate clinical staging and decision-making, thereby improving patient outcomes. Critical relevance statement: This study demonstrates that integrating multimodal data with machine learning significantly improves the pre-operative detection of extraprostatic extension in prostate cancer patients, outperforming conventional imaging methods and potentially leading to more accurate clinical staging and better treatment decisions. Key Points: Extraprostatic extension is an important indicator guiding treatment approaches. Current assessment of extraprostatic extension is difficult and lacks accuracy. Machine learning improves detection of extraprostatic extension using PSMA-PET/MRI and histopathology. [ABSTRACT FROM AUTHOR]

Representatives of Schizomida, known as short-tailed whip scorpions, are an understudied group within Megoperculata. They are found subterraneanly in tropical and sub-tropical regions. They lack eyes, have superior mobility, and possess a flagellum which is relevant to their mating, but in general little is known about their general biology. Fossil representatives of Schizomida from a variety of time periods are available for study. Using 23 fossil specimens (14 of which are described here for the first time) and 86 extant individuals from the literature, changes in both body size and flagella shape in Schizomida were compared over time. Measurements of prosoma length and leg length were used as a proxy for body size, and a comparative size analysis was carried out. Individuals from the Cretaceous period were found to be significantly smaller than extant individuals, contrary to our expectations. For flagellum shape, images were used to create reconstructions, which were then analysed using an elliptic Fourier analysis followed by a principal component analysis. The morphological diversity of the male flagellum shape was found to have decreased between the Cretaceous and modern fauna. We discuss potential explanations for our findings, although a greater understanding of the general biology of Schizomida is required to properly interpret our results. [ABSTRACT FROM AUTHOR]

Beetle larvae show high diversity in forms and ecological roles. Beetle larvae are often roughly categorised into certain larval types, for example: campodeiform, onisciform, scarabeiform, or elateriform. Larvae of the latter type are virtually absent from the fossil record. Here, we report three amber pieces from Cretaceous Kachin amber, Myanmar (about 100 million years old) that together include nine elateriform beetle larvae. One of the amber pieces has a single specimen included. The specimen is interpreted as a larva of Elateridae, the group of click beetles, possibly of the ingroup Elaterinae; yet accessible details are limited. Eight specimens within the other two amber pieces show certain similarities with larvae of Elateridae, but show significant differences in the trunk end, which bears two lobes armed with hooks in these fossils. This very specific structure is well known in modern larvae of Ptilodactylidae (toed-winged beetles). Therefore, the fossils are interpreted as larvae of Ptilodactylidae. Both types of here reported elateriform larvae represent the first fossil record of larvae of their respective groups. It is well known that larval morphology does not evolve in concert with adult morphology, and a modern-type morphology of the one may precede that of the other. Hence, the new fossils are important indicators of the appearance of the modern larval morphologies of their respective lineages. We also briefly discuss the fossil record of larvae of Elateriformia (of which Elateridae and Ptilodactylidae are ingroups) in general. [ABSTRACT FROM AUTHOR]

Following implementation of a national prevention program against iodine deficiency-related disorders in 1993 in Germany, the prevalence of thyroid disorders declined, but aggregated drug dispensation data suggested a recent increase in thyroid hormone use. We aimed to systematically investigate trends in the use of thyroid diagnostic and treatment measures between 2008 and 2019 in Germany. Using the GePaRD database (claims data from ~ 20% of the German population), we determined the annual age-specific and age-standardized prevalence of the use of thyroid diagnostics (thyroid-stimulating hormone (TSH) measurement, thyroid ultrasound, scintiscan, biopsy) and treatment (medication, surgery, radioiodine therapy) from 2008 to 2019 stratified by sex. Between 2008 and 2019, the age-standardized prevalence of TSH measurement increased by 44% in males (from 165 to 238 per 1,000 persons) and by 31% in females (from 134 to 176 per 1,000). The prevalence of thyroid ultrasound use showed no clear time trend, while there was a decrease in the prevalence of scintiscan use (males/females: decrease by 42/43%) and biopsy (males/females: decrease by 42/34%). The prevalence of levothyroxine use increased by ~ 31% both in males (from 36 to 47 per 1,000) and females (from 134 to 175 per 1,000), while the prevalence of thionamide use, iodine use, thyroidectomy, and radioiodine therapy decreased. Our study suggests a continued decline in the prevalence of clinically significant thyroid disorders between 2008 and 2019. The substantial increase in the prevalence of TSH measurement and levothyroxine use during this time period might indicate overuse of diagnostics and overtreatment, warranting further investigation. [ABSTRACT FROM AUTHOR]

Aims: We aimed to describe treatment of lung cancer patients in Germany based on health claims data, focusing particularly on differences by age. Materials and methods: Using the German Pharmacoepidemiological Research Database (GePaRD, ~ 20% of the German population) we identified lung cancer patients diagnosed in 2015–2018 based on a previously developed algorithm and followed them until death, end of continuous insurance or end of 2020. We described initial treatment patterns after diagnosis and survival, stratified among others by age. Results: We included 42,629 incident lung cancer patients (58% male). Surgery within three months after diagnosis was performed in 36%, 31%, 29% and 18% of patients aged < 50, 50–69, 70–79 and ≥ 80, respectively. Among patients without surgery, systemic therapy was administered in 77%, 72%, 54% and 25% of patients aged < 50, 50–69, 70–79 and ≥ 80, respectively. Monoclonal antibodies were administered in 15–30% of patients across age groups, and 4% to 15% received protein kinase inhibitors. Overall, 21% of patients remained untreated. In the age groups < 50, 50–69, 70–79 and ≥ 80, this proportions was 9%, 12%, 22% and 48%, respectively. Conclusion: In conclusion, our study provides a comprehensive overview of the therapy of lung cancer patients in Germany and quantitatively demonstrates the considerable differences between age groups. In terms of clinical cancer registration, the results are useful to estimate the completeness of data for the different types of treatment. [ABSTRACT FROM AUTHOR]

Although research has investigated the association between pathological gaming and academic performance in adolescence, the complexity of the relationship has not been thoroughly examined. This short longitudinal study aimed to investigate the interactions between pathological gaming, academic self-efficacy, academic initiative, and academic performance in an adolescent sample, focusing on sex differences. The participants (N = 2853; 50.1% boys) were students in the second and third years of upper secondary school. Their grade point average (GPA) at graduation the same year was obtained. The moderated mediation structural equation model results showed that academic self-efficacy, directly and indirectly through academic initiative, impacted later GPA. There was no direct effect of pathological gaming on academic initiative or GPA. However, academic self-efficacy moderated the impact of pathological gaming on GPA for boys. In other words, boys with increased pathological gaming tended to achieve poorer grades in school if they experienced a strong academic self-efficacy. This study contributes to the understanding of the complex interplay between sex, pathological gaming, academic self-efficacy, academic initiative, and academic performance. We suggest that future research examines confidence or other relevant factors as explanatory mechanisms in the relationships between pathological gaming, academic self-efficacy, and GPA, particularly in male samples. [ABSTRACT FROM AUTHOR]

Background: Patient-derived tumour organoids (PDOs) are highly advanced in vitro models for disease modelling, yet they lack vascularisation. To overcome this shortcoming, organoids can be inoculated onto the chorioallantoic membrane (CAM); the highly vascularised, not innervated extraembryonic membrane of fertilised chicken eggs. Therefore, we aimed to (1) establish a CAM patient-derived xenograft (PDX) model based on PDOs generated from the liver metastasis of a colorectal cancer (CRC) patient and (2) to evaluate the translational pipeline (patient – in vitro PDOs – in vivo CAM-PDX) regarding morphology, histopathology, expression of C-X-C chemokine receptor type 4 (CXCR4), and radiotracer uptake patterns. Results: The main liver metastasis of the CRC patient exhibited high 2-[18F]FDG uptake and moderate and focal [68Ga]Ga-Pentixafor accumulation in the peripheral part of the metastasis. Inoculation of PDOs derived from this region onto the CAM resulted in large, highly viable, and extensively vascularised xenografts, as demonstrated immunohistochemically and confirmed by high 2-[18F]FDG uptake. The xenografts showed striking histomorphological similarity to the patient's liver metastasis. The moderate expression of CXCR4 was maintained in ovo and was concordant with the expression levels of the patient's sample and in vitro PDOs. Following in vitro re-culturing of CAM-PDXs, growth, and [68Ga]Ga-Pentixafor uptake were unaltered compared to PDOs before transplantation onto the CAM. Although [68Ga]Ga-Pentixafor was taken up into CAM-PDXs, the uptake in the baseline and blocking group were comparable and there was only a trend towards blocking. Conclusions: We successfully established an in vivo CAM-PDX model based on CRC PDOs. The histomorphological features and target protein expression of the original patient's tissue were mirrored in the in vitro PDOs, and particularly in the in vivo CAM-PDXs. The [68Ga]Ga-Pentixafor uptake patterns were comparable between in vitro, in ovo and clinical data and 2-[18F]FDG was avidly taken up in the patient's liver metastasis and CAM-PDXs. We thus propose the CAM-PDX model as an alternative in vivo model with promising translational value for CRC patients. [ABSTRACT FROM AUTHOR]

Background: Current risk stratification tools for prostate cancer patients under active surveillance (AS) may inadequately identify those needing treatment. We investigated DNA ploidy and PTEN as potential biomarkers to predict aggressive disease in AS patients. Methods: We assessed DNA ploidy by image cytometry and PTEN protein expression by immunohistochemistry in 3197 tumour-containing tissue blocks from 558 patients followed in AS at a Norwegian local hospital. The primary endpoint was treatment, with treatment failure (biochemical recurrence or initiation of salvage therapy) as the secondary endpoint. Results: The combined DNA ploidy and PTEN (DPP) status at diagnosis was associated with treatment-free survival in univariable- and multivariable analysis, with a HR for DPP-aberrant vs. DPP-normal tumours of 2.12 (p < 0.0001) and 1.94 (p < 0.0001), respectively. Integration of DNA ploidy and PTEN status with the Cancer of the Prostate Risk Assessment (CAPRA) score improved risk stratification (c-index difference = 0.025; p = 0.0033). Among the treated patients, those with DPP-aberrant tumours exhibited a significantly higher likelihood of treatment failure (HR 2.01; p = 0.027). Conclusions: DNA ploidy and PTEN could serve as additional biomarkers to identify AS patients at increased risk of developing aggressive disease, enabling earlier intervention for nearly 50% of the patients that will eventually receive treatment with current protocol. [ABSTRACT FROM AUTHOR]

Centipedes are predatory representatives of the group Myriapoda and important components of the soil and leaf-litter fauna. The first pair of trunk appendages is modified into venom-injecting maxillipeds in all centipedes. The number of trunk appendage pairs varies between the different groups of centipedes, from 15 pairs as apparently ancestral (plesiomorphic) condition, up to 191 pairs. The last pair of trunk legs can be used for different tasks in centipedes, e.g. mechano-sensation, defense, or stridulation. Many morphological details are also known from fossil centipedes, but especially the oldest fossils are often fragmentary and the fossil record in general is rather scarce. Especially the late appearance of lithobiomorphans in Cenozoic ambers is notable, though some not formally described lithobiomorph-like specimens from Cretaceous amber from Myanmar have been published. We present here a new specimen from Cretaceous Kachin amber, Myanmar with a lithobiomorph-type of morphology, Lithopendra anjafliessae gen. et sp. nov. The very large ultimate leg appears to have been used for defence and is, in relative proportions, larger than in any known lithobiomorphan, only comparable to that in scolopendromorphans. With this, the specimen presents a mixture of characters, which are in the modern fauna only known from two different centipede groups. We discuss the implications of this new fossil, also concerning events of convergence in this lineage. [ABSTRACT FROM AUTHOR]

Purpose: To improve reproducibility and predictive performance of PET radiomic features in multicentric studies by cycle-consistent generative adversarial network (GAN) harmonization approaches. Methods: GAN-harmonization was developed to harmonize whole-body PET scans to perform image style and texture translation between different centers and scanners. GAN-harmonization was evaluated by application to two retrospectively collected open datasets and different tasks. First, GAN-harmonization was performed on a dual-center lung cancer cohort (127 female, 138 male) where the reproducibility of radiomic features in healthy liver tissue was evaluated. Second, GAN-harmonization was applied to a head and neck cancer cohort (43 female, 154 male) acquired from three centers. Here, the clinical impact of GAN-harmonization was analyzed by predicting the development of distant metastases using a logistic regression model incorporating first-order statistics and texture features from baseline 18F-FDG PET before and after harmonization. Results: Image quality remained high (structural similarity: left kidney ≥ 0.800, right kidney ≥ 0.806, liver ≥ 0.780, lung ≥ 0.838, spleen ≥ 0.793, whole-body ≥ 0.832) after image harmonization across all utilized datasets. Using GAN-harmonization, inter-site reproducibility of radiomic features in healthy liver tissue increased at least by ≥ 5 ± 14% (first-order), ≥ 16 ± 7% (GLCM), ≥ 19 ± 5% (GLRLM), ≥ 16 ± 8% (GLSZM), ≥ 17 ± 6% (GLDM), and ≥ 23 ± 14% (NGTDM). In the head and neck cancer cohort, the outcome prediction improved from AUC 0.68 (95% CI 0.66–0.71) to AUC 0.73 (0.71–0.75) by application of GAN-harmonization. Conclusions: GANs are capable of performing image harmonization and increase reproducibility and predictive performance of radiomic features derived from different centers and scanners. [ABSTRACT FROM AUTHOR]

Background: Circulating-tumor DNA (ctDNA) and prostate-specific membrane antigen (PSMA) ligand positron-emission tomography (PET) enable minimal-invasive prostate cancer (PCa) detection and survival prognostication. The present study aims to compare their tumor discovery abilities and prognostic values. Methods: One hundred thirty men with confirmed PCa (70.5 ± 8.0 years) who underwent [68Ga]Ga-PSMA-11 PET/CT (184.8 ± 19.7 MBq) imaging and plasma sample collection (March 2019–August 2021) were included. Plasma-extracted cell-free DNA was subjected to whole-genome-based ctDNA analysis. PSMA-positive tumor lesions were delineated and their quantitative parameters extracted. ctDNA and PSMA PET/CT discovery rates were compared, and the prognostic value for overall survival (OS) was evaluated. Results: PSMA PET discovery rates according to castration status and PSA ranges did differ significantly (P = 0.013, P < 0.001), while ctDNA discovery rates did not (P = 0.311, P = 0.123). ctDNA discovery rates differed between localized and metastatic disease (P = 0.013). Correlations between ctDNA concentrations and PSMA-positive tumor volume (PSMA-TV) were significant in all (r = 0.42, P < 0.001) and castration-resistant (r = 0.65, P < 0.001), however not in hormone-sensitive patients (r = 0.15, P = 0.249). PSMA-TV and ctDNA levels were associated with survival outcomes in the Logrank (P < 0.0001, P < 0.0001) and multivariate Cox regression analysis (P = 0.0023, P < 0.0001). Conclusion: These findings suggest that PSMA PET imaging outperforms ctDNA analysis in detecting prostate cancer across the whole spectrum of disease, while both modalities are independently highly prognostic for survival outcomes. [ABSTRACT FROM AUTHOR]

We present a novel semi-analytical method for parton evolution. It is based on constructing a family of analytic functions spanning x-space which is closed under the considered evolution equation. Using these functions as a basis, the original integro-differential evolution equation transforms into a system of coupled ordinary differential equations, which can be solved numerically by restriction to a suitably chosen finite subsystem. The evolved distributions are obtained as analytic functions in x with numerically obtained coefficients, providing insight into the analytic behavior of the evolved parton distributions. As a proof-of-principle, we apply our method to the leading order non-singlet and singlet DGLAP equation. Comparing our results to traditional Mellin-space methods, we find good agreement. The method is implemented in the code POMPOM in Mathematica as well as in Python. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist [177Lu]Lu-satoreotide tetraxetan in patients with advanced neuroendocrine tumours (NETs). Methods: This study was part of a phase I/II trial of [177Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three planned cycles (median activity/cycle: 4.5 GBq), in 40 patients with progressive NETs. Organ absorbed doses were monitored at each cycle using patient-specific dosimetry; the cumulative absorbed-dose limits were set at 23.0 Gy for the kidneys and 1.5 Gy for bone marrow. Absorbed dose coefficients (ADCs) were calculated using both patient-specific and model-based dosimetry for some patients. Results: In all evaluated organs, maximum [177Lu]Lu-satoreotide tetraxetan uptake was observed at the first imaging timepoint (4 h after injection), followed by an exponential decrease. Kidneys were the main route of elimination, with a cumulative excretion of 57–66% within 48 h following the first treatment cycle. At the first treatment cycle, [177Lu]Lu-satoreotide tetraxetan showed a median terminal blood half-life of 127 h and median ADCs of [177Lu]Lu-satoreotide tetraxetan were 5.0 Gy/GBq in tumours, 0.1 Gy/GBq in the bone marrow, 0.9 Gy/GBq in kidneys, 0.2 Gy/GBq in the liver and 0.8 Gy/GBq in the spleen. Using image-based dosimetry, the bone marrow and kidneys received median cumulative absorbed doses of 1.1 and 10.8 Gy, respectively, after three cycles. Conclusion: [177Lu]Lu-satoreotide tetraxetan showed a favourable dosimetry profile, with high and prolonged tumour uptake, supporting its acceptable safety profile and promising efficacy. Trial registration: NCT02592707. Registered October 30, 2015. [ABSTRACT FROM AUTHOR]

This article examines the implementation, participation rates, and potential determinants of participation in the digital addiction prevention program "ready4life." A two-arm cluster-randomized trial recruited German vocational students via class-based strategies. Intervention group received 16 weeks of in-app coaching; the control group received health behavior information, with coaching offered after 12 months. Potential determinants of participation were analyzed based on class and individual characteristics. Out of 525 contacted schools, 35 participated, enrolling 376 classes. Implementation during the pandemic required flexible adjustments, with 49.7% of introductions conducted in person, 43.1% digitally via online streaming, and 7.2% received a video link via email. Despite challenges, 72.3% of the vocational students downloaded the app, and 46.7% gave informed consent. Participation rates were highest among (associate) professionals, vocational grammar school classes, classes introduced by females, younger individuals, members of the project team, and classes introduced face-to-face. Female gender, lower social competencies, lifetime cannabis use, higher problematic internet use, and higher perceived stress were associated with higher individual participation. The study highlights the importance of proactive outreach and personalized interventions for addiction prevention programs in vocational schools. While reached students aligned with the aims of the app, tailored recruitment strategies could enhance engagement among under-represented groups. The trial was registered in the German Clinical Trials Register (DRKS): DRKS00022328; registration date 09.10.2020. [ABSTRACT FROM AUTHOR]

Transient receptor potential (TRP) ion channels are involved in the surveillance or regulation of the acid-base balance. Here, we demonstrate that weak carbonic acids, including acetic acid, lactic acid, and CO2 activate and sensitize TRPV2 through a mechanism requiring permeation through the cell membrane. TRPV2 channels in cell-free inside-out patches maintain weak acid-sensitivity, but protons applied on either side of the membrane do not induce channel activation or sensitization. The involvement of proton modulation sites for weak acid-sensitivity was supported by the identification of titratable extracellular (Glu495, Glu561) and intracellular (His521) residues on a cryo-EM structure of rat TRPV2 (rTRPV2) treated with acetic acid. Molecular dynamics simulations as well as patch clamp experiments on mutant rTRPV2 constructs confirmed that these residues are critical for weak acid-sensitivity. We also demonstrate that the pore residue Glu609 dictates an inhibition of weak acid-induced currents by extracellular calcium. Finally, TRPV2-expression in HEK293 cells is associated with an increased weak acid-induced cytotoxicity. Together, our data provide new insights into weak acids as endogenous modulators of TRPV2. Synopsis: The transient receptor potential vanilloid 2 (TRPV2) ion channel controls important physiological and pathophysiological processes, but its regulation by acid species remains unclear. Here, combined structure-function work uncovers activation of rat TRPV2 by endogenous weak acids and offers a detailed characterization of its membrane permeation-dependent acid sensitivity. Weak, but not strong acids activate and sensitize TRPV2. Membrane permeability of weak acids is required for TRPV2 activation. Positively charged S4-S5 linker residue His521 controls TRPV2 weak acid-sensitivity. Extracellular calcium inhibits weak acid-induced TRPV2 activation. Weak acetic acids are endogenous agonists of rat TRPV2 acting via permeation through the cell membrane. [ABSTRACT FROM AUTHOR]

Objective: To determine the preferred ankle, knee, and elbow arthrography injection techniques for Society of Skeletal Radiology (SSR) members and whether more recently described techniques are gaining acceptance. We also sought to determine whether the concept of knowledge translation might explain differences between the preferred technique, year of fellowship graduation, and year the newer technique was described. Materials and methods: A 29-question survey was created in Qualtrics and submitted to current SSR members to determine if they perform knee, elbow, and ankle arthrography, and if so, the year of fellowship completion and preferred approaches. Survey respondents indicated the starting and ending needle tip positions for three knee, two elbow, and three ankle arthrography approaches using grids placed over provided frontal and lateral radiographs. Results: Two hundred seventy-four SSR members (mean post-fellowship 13 years; range 0–38) completed the survey and performed fluoroscopic-guided knee (93%), elbow (95%), and ankle (75%) arthrography. Preferred approaches included the following: knee lateral subpatellar (43%), anterior (40%); elbow radiocapitellar (74%); ankle anterior/peritendon (70%), lateral mortise (24%). Preference of newer technique was related to fellowship graduation year and publication year for the ankle mortise (26% before, 42% after; p = 0.03) and posterior trans-triceps elbow articles (19% before, 33% after; p < 0.01). The anterior knee approach preference increased from 11% in 2008 to 40% (p ≤ 0.001). Conclusion: Nearly twice as many SSR members who graduated after the posterior trans-triceps and ankle mortise techniques were published prefer them for performing arthrography, possibly due to knowledge translation. The preference of the anterior knee arthrography approach has increased nearly fourfold since 2008. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Stress urinary incontinence (SUI) is defined as involuntary leakage of urine on physical effort and is prevalent among power- and weightlifters. However, there is scant knowledge on treatment options for this population. The aim of this pilot study was to evaluate the potential outcomes and feasibility of a pelvic floor muscle training (PFMT) program on SUI in nulliparous female power- and weightlifters. Methods: This was a case-series study, including one weightlifter and two powerlifters aged 21–32 years. The participants conducted 12 weeks of PFMT at home, with weekly follow-up by a physiotherapist. Change in total score of the International Consensus of Incontinence Questionnaire Urinary Incontinence Short Form (ICIQ-UI-SF) was the primary outcome. Secondary outcome was perceived change assessed by the Patient Global Impression of Improvement (PGI-I) Scale and impact on sport participation. PFM strength, endurance, and resting pressure was measured using vaginal manometry. Feasibility was evaluated as adherence to training and self-efficacy (Self Efficacy Scale for Practicing Pelvic Floor Exercises). Results: One athlete reduced their ICIQ-UI-SF score and experienced improvement in symptoms. One athlete reported no change, and one reported a worsening of symptoms. All three participants improved PFM strength and endurance, completed the testing, and 12 weeks of PFMT, but adherence varied between 40 and 80%. Participants reported a lack of time and energy and forgetting to perform the exercises, as reasons for low adherence. Conclusion: There were varying effects of a 12-week PFMT program on SUI in three strength athletes. The results can create the basis for a future randomized controlled trial. [ABSTRACT FROM AUTHOR]

Mg/Ca is an independent proxy in paleoceanography to reconstruct past seawater temperature. Femtosecond Laser Ablation Inductively Coupled Plasma Mass Spectrometry (fs-LA-ICP-MS) was employed to determine the Mg/Ca composition of tests (shells) of the planktic foraminifer species Globigerinoides ruber albus (white chromotype) and G. ruber ruber (red/pink chromotype) sampled alive from the temperate to subtropical eastern North Atlantic with the research sailing yacht Eugen Seibold. Mg/Ca data are compared to (i) the measured in-situ temperature of ambient seawater, (ii) average mixed layer temperature, and (iii) sea surface temperature (SST). The pooled mean chamber Mg/Ca from each plankton tow site exhibits a positive relationship with SST. Two chamber-specific calibrations are derived, which are consistent with previous calibration equations for comparable paleo-archives. The results confirm fs-LA-ICP-MS as reliable method for determining Mg/Ca in G. ruber, and both the penultimate and antepenultimate chambers of adult specimens may provide comprehensible Mg/Ca temperatures of the surface ocean. [ABSTRACT FROM AUTHOR]

Convergent evolution is a common phenomenon, independently leading to similar morphologies in different evolutionary lineages. Often similar functional demands drive convergent evolution. One example is the independent evolution of grasping structures in different lineages of Euarthropoda, though the exact morphology of these grasping structures varies significantly. In this study, we investigated grasping apparatuses with two movable counteracting structures as well as some related structures, exemplified by the stylets (compound structures of mouthparts) of aphidlion-like larvae (part of Neuroptera or lacewings) and the cerci of immature earwigs (Dermaptera). For the stylets of aphidlion-like larvae, studies have pointed to a significant loss in morphological diversity in the last 100 million years. We used quantitative morphology to evaluate if a similar process has also occurred in the cerci of earwigs. The cerci of extant immature earwigs exhibit two distinct types of morphologies in the modern fauna: elongated cerci divided into several ringlets with a feeler-type function, and pincer-like stout cerci. In some fossil immature earwigs, however, the cerci are generally elongated but undivided and roughly occupy the morphospace between those of the two modern cerci types; hence this fossil cerci morphology appears to have been lost. To some extent, a comparable loss is also found in certain lacewing larvae. Outgroup comparisons suggest that the morphologies no longer present today are in fact not ancestral, but instead specialised, hence their loss is possibly resulting from disruptive evolution in earwigs as well as lacewings. We discuss the possible functions of these specialised grasping structures. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine geographic and socioeconomic variation in curative treatment and choice of treatment modality among elderly prostate cancer (PCa) patients. Methods: This register-based cohort study included all Norwegian men ≥ 70 years when diagnosed with non-metastatic, high-risk PCa in 2011–2020 (n = 10 807). Individual data were obtained from the Cancer Registry of Norway, the Norwegian Prostate Cancer Registry, and Statistics Norway. Multilevel logistic regression analysis was used to model variation across hospital referral areas (HRAs), incorporating clinical, demographic and socioeconomic factors. Results: Overall, 5186 (48%) patients received curative treatment (radical prostatectomy (RP) (n = 1560) or radiotherapy (n = 3626)). Geographic variation was found for both curative treatment (odds ratio 0.39–2.19) and choice of treatment modality (odds ratio 0.10–2.45). Odds of curative treatment increased with increasing income and education, and decreased for patients living alone, and with increasing age and frailty. Patients with higher income had higher odds of receiving RP compared to radiotherapy. Conclusions: This study showed geographic and socioeconomic variation in treatment of elderly patients with non-metastatic, high-risk PCa, both in relation to overall curative treatment and choice of treatment modality. Further research is needed to explore clinical practices, the shared decision process and how socioeconomic factors influence the treatment of elderly patients with high-risk PCa. [ABSTRACT FROM AUTHOR]

Background: The use of 3D planning to guide corrective osteotomies of the lower extremity is increasing in clinical practice. The use of computer-tomography (CT) data acquired in supine position neglects the weight-bearing (WB) state and the gold standard in 3D planning involves the manual adaption of the surgical plan after considering the WB state in long-leg radiographs (LLR). However, this process is subjective and dependent on the surgeons experience. A more standardized and automated method could reduce variability and decrease costs. Purpose: The aim of the study was (1) to compare three different three-dimensional (3D) planning modalities for medial open-wedge high tibial osteotomy (MOWHTO) and (2) to describe the current practice of adapting NWB CT data after considering the WB state in LLR. The purpose of this study is to validate a new, standardized approach to include the WB state into the 3D planning and to compare this method against the current gold standard of 3D planning. Our hypothesis is that the correction is comparable to the gold standard, but shows less variability due compared to the more subjective hybrid approach. Methods: Three surgical planning modalities were retrospectively analyzed in 43 legs scheduled for MOWHTO between 2015 and 2019. The planning modalities included: (1) 3D hybrid (3D non-weight-bearing (NWB) CT models after manual adaption of the opening angle considering the WB state in LLR, (2) 3D NWB (3D NWB CT models) and (3) 3D WB (2D/3D registration of 3D NWB CT models onto LLR to simulate the WB state). The pre- and postoperative hip-knee-ankle angle (HKA) and the planned opening angle (°) were assessed and differences among modalities reported. The relationship between the reported differences and BMI, preoperative HKA (LLR), medial meniscus extrusion, Outerbridge osteoarthritis grade and joint line convergence angle (JLCA) was analyzed. Results: The mean (std) planned opening angle of 3D hybrid did not differ between 3D hybrid and 3D WB (0.4 ± 2.1°) (n.s.) but was higher in 3D hybrid compared to 3D NWB (1.1° ± 1.1°) (p = 0.039). 3D WB demonstrated increased preoperative varus deformity compared to 3D NWB: 6.7 ± 3.8° vs. 5.6 ± 2.7° (p = 0.029). Patients with an increased varus deformity in 3D WB compared to 3D NWB (> 2 °) demonstrated more extensive varus alignment in LLR (p = 0.009) and a higher JLCA (p = 0.013). Conclusion: Small intermodal differences between the current practice of the reported 3D hybrid planning modality and a 3D WB approach using a 2D/3D registration algorithm were reported. In contrast, neglecting the WB state underestimates preoperative varus deformity and results in a smaller planned opening angle. This leads to potential under correction in MOWHTO, especially in patients with extensive varus deformities or JLCA. Clinical Relevance: Incorporating the WB state in 3D planning modalities has the potential to increase accuracy and lead to a more consistent and reliable planning in MOWHTO. The inclusion of the WB state in automatized surgical planning algorithms has the potential to reduce costs and time in the future. [ABSTRACT FROM AUTHOR]

Purpose: Many studies on cancer patients investigate the impact of treatment on health-related quality of life (QoL). Typically, QoL is measured longitudinally, at baseline and at predefined timepoints thereafter. The question is whether, at a given timepoint, patients who return their questionnaire (available cases, AC) have a different QoL than those who do not return their questionnaire (non-AC). Methods: We employed augmented inverse probability weighting (AIPW) to estimate the average QoL of non-AC in two studies on advanced-stage cancer patients. The AIPW estimator assumed data to be missing at random (MAR) and used machine learning (ML)-based methods to estimate answering probabilities of individuals at given timepoints as well as their reported QoL, as a function of auxiliary variables. These auxiliary variables were selected by medical oncologists based on domain expertise. We aggregated results both by timepoint and by time until death and compared AIPW estimates to the AC averages. Additionally, we used a pattern mixture model (PMM) to check sensitivity of our AIPW estimates against violation of the MAR assumption. Results: Our study included 1927 patients with advanced pancreatic and 797 patients with advanced breast cancer. The AIPW estimate for average QoL of non-AC was below the average QoL of AC when aggregated by timepoint. The difference vanished when aggregated by time until death. PMM estimates were below AIPW estimates. Conclusions: Our results indicate that non-AC have a lower average QoL than AC. However, estimates for QoL of non-AC are subject to unverifiable assumptions about the missingness mechanism. [ABSTRACT FROM AUTHOR]

Purpose: Gracilis muscle flaps are useful to cover defects of the hand. However, there are currently no studies describing outcome measurements after covering soft tissue defects using free flaps in the hand. Aim: To analyze mid-term results of gracilis muscle flap coverage for defects on the hand, with regard to functional and esthetic integrity. Methods: 16 patients aged 44.3 (range 20–70) years were re-examined after a mean follow-up of 23.6 (range 2–77) months. Mean defect size was 124 (range 52–300) cm2 located palmar (n = 9), dorsal (n = 6), or radial (n = 1). All flaps were performed as microvascular muscle flaps, covered by split thickness skin graft. Results: Flaps survived in 15 patients. 6 patients required reoperations. Reasons for revisions were venous anastomosis failure with total flap loss (n = 1) requiring a second gracilis muscle flap; necrosis at the tip of the flap (n = 1) with renewed split thickness skin cover. A surplus of the flap (n = 2) required flap thinning and scar corrections were performed in 2 patients. Mean grip strength was 25% (range 33.3–96.4%) compared to the contralateral side and mean patient-reported satisfaction 1.4 (range 1–3) (1 = excellent; 4 = poor). Conclusions: Gracilis muscle flaps showed a survival rate of 94%. Patients showed good clinical outcomes with acceptable wrist movements and grip strength as well as high reported satisfaction rates. Compared to fasciocutaneous free flaps, pliability and thinness especially on the palmar aspect of the hand are advantageous. Hence, covering large defects of the hand with a gracilis muscle flap can be a very satisfactory procedure. Level of evidence: IV observational. [ABSTRACT FROM AUTHOR]

Introduction: Non-dissociative carpal instability (CIND) may lead to severe functional impairment. Destabilisation of the scapho-trapezial-trapezoidal (STT) ligament complex seems to result in a CIND. Materials and methods: In one group with eight cadaver arms, distal scaphoid pole was resected with the adjacent ligaments. In the other eight cadavers, hemitrapeziectomy was performed followed by total trapeziectomy. CT scans were performed in different wrist positions, and the changed positions of the scaphoid, lunate and capitate were measured in comparison to non-operated wrists. Results: Mainly in clenched fist position, dissociation between proximal and distal row can be determined after total trapeziectomy and resection of distal scaphoid pole. Capitate rotates dorsally up to 24°, the scaphoid up to 17° and the lunate up to 7° compared to the non-operated wrists. Resection of the distal scaphoid pole results in dorsal rotation of capitate and scaphoid of about 14° and the lunate 8°. Relative scapholunate and capitolunate angle increased significantly after total trapeziectomy, especially in clenched fist position. After scaphoid pole resection, significant SL and CL angles changes could be seen in almost every wrist position. Conclusion: Destabilisation of the STT ligament complex by total trapeziectomy or distal scaphoid pole resection results in dissociation of the proximal and distal carpal row without instability within the proximal or distal row, corresponding to a CIND. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Eocene amber is an important window into the past about 35 million years ago. The large quantities of resin produced by this forest of the past, resulting in amber, triggered the idea of a forest under stress. Recent findings of higher abundances of hoverfly larvae in Eocene amber, in the modern fauna often associated with wood-borer larvae, provided a hint that wood-borer larvae may have contributed to this stress. Yet, so far only few such larvae have been reported. We have compiled a dozen additional wood-borer larvae in amber, including a giant one of at least 35 mm length in Rovno amber. Heavily damaged fossils furthermore indicate that larger larvae of this type were prone to oxidation and that, at least some, enigmatic tube-like tunnels in larger amber pieces may represent remains of large wood-borer larvae. This find strongly indicates that wood-borer larvae were not rare, but common in the Eocene amber forest, which is compatible with the high abundances of hoverfly larvae and further supports the idea of a forest under stress. Whether the possible higher abundances of wood-borer larvae were the cause of the stress or a symptom of an already stressed forest remains so far unclear. [ABSTRACT FROM AUTHOR]

Despite the large number of species in the group Coleoptera (beetles), it is usually relatively easy to identify an adult beetle as such due to certain common characteristics. Among beetle larvae, however, there is a larger variability of body organisation. In some lineages, specialised larval morphologies are carried on into the adult phase by heterochrony, more exactly paedomorphosis. Such evolutionary events resulted in larviform females, as they occur in some extant representatives of Lycidae (net-winged beetles) and Lampyridae (fireflies). However, such larviform individuals, larvae or paedomorphic females, have been very rarely described in the fossil record until now and were restricted to Cenozoic ambers. Here, we report fossil larviform representatives, resembling larvae of the groups Lampyridae and Lycidae in certain aspects, from 100-million-year-old Myanmar amber. We furthermore discuss the morphological similarities and differences of the three new specimens in relation to extant larviform representatives of the groups and possible relationships of the new fossils. [ABSTRACT FROM AUTHOR]

Electric vehicles (EVs) are expected to be vital in transitioning to a low-carbon energy system. However, integrating EVs into the power grid poses significant challenges for grid operators and energy suppliers, especially regarding the uncertainty and variability of EV charging demand. Accurate forecasting of EV charging demand is essential for optimal power system integration, yet previous studies have often only considered point predictions that are inadequate for risk assessment. Therefore, this paper compares different probabilistic forecasting models for the short-term prediction of EV charging demand at various aggregation levels, using a large and novel dataset of over 350,000 charging processes at more than 500 locations across Germany. The performance of both machine learning and deep learning methods is evaluated against a naïve benchmark model, and the impact of data availability on the forecasting models is investigated. Further, the paper examines the effects of forecast accuracy on energy procurement, which has so far received minor attention in the literature. The results show that machine learning methods such as Ada Boosting and Random Forest yield robust results with a normalized root mean square error of 0.42 and 0.41 and a mean absolute scaled error of 0.36 and 0.34 at the highest aggregation level. Furthermore, the results show the influence of different site compositions on the forecast quality and how many charging points are likely to yield a robust forecast. Energy and fleet managers can use the described method to reliably predict the required energy quantities for fleets of sufficient size and procure them at low risk. [ABSTRACT FROM AUTHOR]

Background: Reliable RT-qPCR results are dependent on appropriate normalisation. Oocyte maturation studies can be challenging in this respect, as the stage of development can distinctively affect reference gene transcript abundance. The aim of this study was to validate the use of reference genes in oocyte in vitro maturation RT-qPCR studies, and thereafter, examine the abundance of transcripts supporting histone modification during oocyte and early embryo development in oocytes of contrasting quality. Methods and results: Total RNA from oocytes from prepubertal gilts and sows was extracted either directly succeeding follicle aspiration or after 44 h in vitro maturation, followed by RT-qPCR. The stability of YWHAG, HPRT1, ACTB, GAPDH, HMBS and PFKP, was analysed by NormFinder and further cross-validated by assessing results generated following application of different combinations of potential reference genes for normalisation of the RT-qPCR data. Combining ACTB and PFKP generated high stability according to NormFinder and concordant results. Applying this normalisation, gilt derived oocytes displayed significantly higher abundance than oocytes from sows of almost all the epigenetic-related transcripts studied (HDAC2, SIRT1, SALL4, KDM1A, KDM1B, KDM5A), both before and after maturation. Conclusions: This study identified the combined use of ACTB and PFKP as the optimal normalisation for porcine oocyte RT-qPCR data. In oocytes collected from prepubertal gilts, transcription did not appear to be silenced at the time of aspiration, and accumulation of transcripts supporting histone modification facilitating proper fertilization and further embryo development seemed delayed. The results imply the epigenetic-related transcripts may have potential as markers of oocyte quality. [ABSTRACT FROM AUTHOR]

We are demonstrating new relationships among the Hawking temperature, the Cosmic Microwave Background (CMB) temperature, and the Planck scale. When understood deeply, these are in line with recent advancements in cosmological quantization and its connection to the Planck scale. This is also completely consistent with a recently published method for quantizing Einstein’s general theory of relativity. [ABSTRACT FROM AUTHOR]

Introduction: Sufficiently high analytical quality of blood glucose monitoring systems (BGMS) is a prerequisite for efficient diabetes therapy. In this study we assessed system accuracy, measurement repeatability, intermediate measurement precision, user performance, and the influence of hematocrit on two CE-marked blood glucose monitoring systems. For one BGMS, measurement accuracy using venous samples was additionally investigated. Methods: Study procedures were based on the International Organization of Standardization (ISO) 15197:2013/EN ISO 15197:2015 ("ISO 15197"). User performance included data from 100 subjects who used one test strip lot, whereas for all other analyses three different reagent system lots were used. For system accuracy assessment, 100 capillary samples were measured in duplicate with each of three reagent system lots per system, resulting in 600 results per system. Results: CareSens S Fit and CareSens H Beat both fulfilled the ISO 15197 accuracy criteria with 97.5–100% of each test strip lot's results falling within ± 15 mg/dL or ± 15% of the results of the comparison method and 100% of results in consensus error grid (CEG) zone A for all three lots. User performance evaluation revealed sufficient accuracy in the hands of lay users although some handling errors were documented by study staff. Assessment of measurement repeatability and intermediate measurement precision is given by standard deviation (SD) (glucose levels < 100 mg/dL) and by coefficient of variation (CV) (glucose concentrations ≥ 100 mg/dL). SD was ≤ 4.1 mg/dL and CV ≤ 4.2% for measurement repeatability and SD was ≤ 2.2 mg/dL and CV ≤ 2.6% for intermediate measurement precision. In case of hematocrit influence, both BGMS complied with all three tested lots with the defined criteria. Conclusion: Both BGMS analyzed in this study fulfilled the required accuracy criteria of ISO 15197. They showed high precision, good performance in the hands of lay users, and the influence of hematocrit was acceptable in the labeled range. [ABSTRACT FROM AUTHOR]

Purpose: Vascularized lymph node transfer (VLNT) entails the autologous relocation of lymph nodes to a lymphedematous region of the body, whereas lymphaticovenous anastomosis (LVA) creates a direct bypass between the lymphatic and venous system. Both techniques are meant to lastingly bolster the local lymphatic drainage capacity. This study compared safety and effectiveness of VLNT and LVA in patients with chronic breast cancer related lymphedema (BCRL). Methods: A retrospective cohort study was conducted using data from our encrypted database composed of patients with chronic BCRL who were treated with either VLNT or LVA and had a minimum follow-up of two years. Patient-specific variables analyzed included pre- and postoperative arm circumferences, lymphedema stages and postoperative complications. Results: A total of 105 patients met the inclusion criteria, of which 96 patients demonstrated a complete follow-up period of two years. The VLNT group displayed larger preoperative circumferential measurements, evident in both in the isolated examination of the affected arm, as well as when adjusted for the contralateral unaffected arm. Significant reduction in arm volume was achieved by both groups. However, VLNT demonstrated superior relative reduction rates than LVA, neutralizing any significant arm size disparities after 24 months. Surgery duration was slightly longer for VLNT than LVA. Postoperative complications, predominantly minor, were exclusively observed in the VLNT group. Conclusions: Both VLNT and LVA offer significant improvement for patients suffering from chronic BCRL. VLNT shows an even greater potential for improvement in more severe cases of BCRL, but involves a higher risk for (mostly minor) complications. [ABSTRACT FROM AUTHOR]

Little is known about exposure determinants of acrylamide (AA), a genotoxic food-processing contaminant, in Europe. We assessed determinants of AA exposure, measured by urinary mercapturic acids of AA (AAMA) and glycidamide (GAMA), its main metabolite, in 3157 children/adolescents and 1297 adults in the European Human Biomonitoring Initiative. Harmonized individual-level questionnaires data and quality assured measurements of AAMA and GAMA (urine collection: 2014–2021), the short-term validated biomarkers of AA exposure, were obtained from four studies (Italy, France, Germany, and Norway) in children/adolescents (age range: 3–18 years) and six studies (Portugal, Spain, France, Germany, Luxembourg, and Iceland) in adults (age range: 20–45 years). Multivariable-adjusted pooled quantile regressions were employed to assess median differences (β coefficients) with 95% confidence intervals (95% CI) in AAMA and GAMA (µg/g creatinine) in relation to exposure determinants. Southern European studies had higher AAMA than Northern studies. In children/adolescents, we observed significant lower AA associated with high socioeconomic status (AAMA:β = − 9.1 µg/g creatinine, 95% CI − 15.8, − 2.4; GAMA: β = − 3.4 µg/g creatinine, 95% CI − 4.7, − 2.2), living in rural areas (AAMA:β = − 4.7 µg/g creatinine, 95% CI − 8.6, − 0.8; GAMA:β = − 1.1 µg/g creatinine, 95% CI − 1.9, − 0.4) and increasing age (AAMA:β = − 1.9 µg/g creatinine, 95% CI − 2.4, − 1.4; GAMA:β = − 0.7 µg/g creatinine, 95% CI − 0.8, − 0.6). In adults, higher AAMA was also associated with high consumption of fried potatoes whereas lower AAMA was associated with higher body-mass-index. Based on this large-scale study, several potential determinants of AA exposure were identified in children/adolescents and adults in European countries. [ABSTRACT FROM AUTHOR]

Purpose: We present the results of an open-label, phase I/II study evaluating the safety and efficacy of the novel somatostatin receptor (SSTR) antagonist [177Lu]Lu-satoreotide tetraxetan in 40 patients with previously treated, progressive neuroendocrine tumours (NETs), in which dosimetry was used to guide maximum administered activity. Methods: This study was conducted in two parts. Part A consisted of 15 patients who completed three cycles of [177Lu]Lu-satoreotide tetraxetan at a fixed administered activity and peptide amount per cycle (4.5 GBq/300 µg). Part B, which included 25 patients who received one to five cycles of [177Lu]Lu-satoreotide tetraxetan, evaluated different administered activities (4.5 or 6.0 GBq/cycle) and peptide amounts (300, 700, or 1300 μg/cycle), limited to a cumulative absorbed radiation dose of 23 Gy to the kidneys and 1.5 Gy to the bone marrow. Results: Median cumulative administered activity of [177Lu]Lu-satoreotide tetraxetan was 13.0 GBq over three cycles (13.1 GBq in part A and 12.9 GBq in part B). Overall, 17 (42.5%) patients experienced grade ≥ 3 treatment‑related adverse events; the most common were lymphopenia, thrombocytopenia, and neutropenia. No grade 3/4 nephrotoxicity was observed. Two patients developed myeloid neoplasms considered treatment related by the investigator. Disease control rate for part A and part B was 94.7% (95% confidence interval [CI]: 82.3–99.4), and overall response rate was 21.1% (95% CI: 9.6–37.3). Conclusion: [177Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three cycles, has an acceptable safety profile with a promising clinical response in patients with progressive, SSTR-positive NETs. A 5-year long-term follow-up study is ongoing. Trial registration: ClinicalTrials.gov, NCT02592707. Registered October 30, 2015. [ABSTRACT FROM AUTHOR]

Loss of biodiversity and especially insect decline are widely recognised in modern ecosystems. This decline has an enormous impact due to the crucial ecological roles of insects as well as their economic relevance. For comparison, the fossil record can provide important insights on past biodiversity losses. One group of insects, for which a significant decline over the last 100 million years has often been postulated, but not demonstrated quantitatively, is Neuroptera (lacewings). Many adult lacewings are pollinators, while the larvae are mostly predators, which becomes very obvious from their prominent stylet-like mouthparts. We investigated the fossil record of larvae of all neuropteran lineages as well as a large share of extant neuropteran larvae. Based on these, we performed an outline analysis of the head with stylets. This analysis provides a quantitative frame for recognising the decline of lacewings since the Cretaceous, indicating also a severe loss of ecological roles. [ABSTRACT FROM AUTHOR]

Lacewings (Neuroptera) have predatory larvae with highly specialised mouthparts. Larvae of many groups within Neuroptera are well represented as fossils preserved in ambers; however, larvae of some groups are less often reported in the literature. Here we report such a rare case, a larva of the group Hemerobiidae, an aphidlion, preserved in a piece of Eocene Baltic amber (about 40 million years old). It is preserved together with three possible prey items, wingless aphids, most likely representatives of Germaraphis (or at least closely related to this group). The aphidlion can be identified based on the morphology of the antennae, simple curved and toothless stylets, well developed labial palps, and the absence of other mouth-part structures such as a protruding labrum or maxillary palps. A long, club-shaped distal element of the labial palps identifies the specimen as a larva of Hemerobiidae. The aphids can be identified based on their very long, beak-like mouth parts. This find is, to our knowledge, the first example of a lacewing larva preserved together with its potential prey. We briefly discuss other cases in which fossils preserved in amber allow us to reconstruct aspects of behaviour and interactions of fossil lacewing larvae. [ABSTRACT FROM AUTHOR]

We report a new and unusual beetle larva preserved in ca. 100 million-year-old Kachin amber. Larvae of many modern lineages of beetles are associated with wood, breaking it into smaller pieces or directly digesting it. With such a lifestyle, beetle larvae are important for carbon cycling. We can assume that this is not only the case in modern ecosystems, but was similar in the past. Yet, wood-associated beetle larvae seem so far rare in Kachin amber despite its otherwise rich record of many different ecotypes. Only recently, solid-wood-boring larvae and those living in decaying wood have been reported from this amber deposit. Larvae of the group Eucnemidae, false click beetles, which are also wood-associated, have so far been only known from sedimentary rock deposits. Here we report the first larva of a false click beetle preserved in amber. The fossil larva combines features of different modern lineages of Eucnemidae in a unique morphology that is not known in the modern fauna. The fossil adds to the growing number of wood-associated holometabolan larvae in Kachin amber and with this contributes to a more complete view on this now extinct community and ecosystem. [ABSTRACT FROM AUTHOR]

Raphidioptera, the group of snakeflies, is a rather species-poor in-group of Holometabola. Yet, fossils of snakeflies indicate that the group was more diverse in the past. Here we compare the morphological diversity of snakefly larvae over time. Snakefly larvae are well represented in Cretaceous and Eocene ambers facilitating such a comparison. We used measurements of discrete dimensions as a basis for comparison. This reveals a larger diversity of snakefly larvae in the Cretaceous, especially in relation to head shapes and morphology of the antennae, which were much more variable. In particular, some Cretaceous larvae possessed greatly elongated head capsules and uniquely long and prominent antennae, unparalleled among modern forms. Already by the Eocene, snakefly larvae were less variable than those of the Cretaceous, although some still possessed longer antennae than modern-day larvae. The loss of morphological diversity supports the already well-established loss of taxonomic diversity in the group across time. Quite likely, this also indicates a loss of ecological diversity. These results are comparable to losses in different lineages of the closely related group Neuroptera. [ABSTRACT FROM AUTHOR]

In the context of gravitational objects with spherical symmetry, we derive a solution to Einstein’s field equations using two methods leading to the same result. The first is based on a stress-energy tensor that takes into account both the electric field energy of the charge and the gravitational field energy of the mass. The second is based on the mass-energy equivalence and has more general validity. We show that the metric falls within the Weyl class of metrics, representing a static and axisymmetric solution to Einstein’s field equations. The metric, which has a form similar to that of Reisser-Nordström, is used for predictions in strong fields and possibly shows better agreement with observation in high z quasars. [ABSTRACT FROM AUTHOR]

Background and Objective: Acitretin has long-lasting teratogenic properties. Therefore, pregnancies must be avoided during and within 3 years after acitretin treatment. We aimed to describe (i) acitretin use in women of childbearing age in Germany, (ii) the occurrence of acitretin-exposed pregnancies, and (iii) malformations among children exposed in utero. Methods: Using 2004–2019 data from the German Pharmacoepidemiological Research Database (GePaRD—claims data from ~ 20% of the German population), we determined annual age-standardized prevalence of acitretin use among girls and women aged 13–49 years. In longitudinal analyses, we estimated the number of exposed pregnancies by assessing whether the exposure window assigned to the last dispensation before pregnancy (days covered by dispensation plus 3 years) overlapped the onset of pregnancy or whether there was a dispensation in the first eight weeks of pregnancy. Data of live-born children with in utero exposure to acitretin were reviewed to assess the presence of congenital malformations. Results: The age-standardized prevalence of acitretin use per 1000 girls and women was 0.04 in 2019. We identified 35 acitretin-exposed pregnancies; 94.3% of these pregnancies were classified as exposed because they occurred within 3 years after stopping acitretin treatment. Among 18 live-born children linked to their mother, four children (22.2%) had congenital malformations (three children with a major malformation). Conclusions: We observed 35 acitretin-exposed pregnancies mainly because treatment ended too late before pregnancy. Approximately one in five children born from these pregnancies had malformations, highlighting the importance of drawing more attention to the long-lasting teratogenicity of this drug. [ABSTRACT FROM AUTHOR]

The evaluation of aroma properties of beverages, both analytically as well as with human sensory studies, is a challenging task and most often related to time- and cost-intensive analyses. Whisky is a spirit offering a wide variety of aroma impressions caused by a complex mixture of aroma active compounds. In the present study, methods for the efficient evaluation of aroma characteristics are evaluated for 16 whisky samples of different origins (Scotch and American). Rate all that apply (RATA) was applied as a rapid method for the sensory evaluation of whiskies. Sensory evaluation of the samples led to the determination of eight significant aroma attributes: caramel-/cream caramel-/toffee-like, vanilla-like, (canned) peach-like, phenolic, smoky, fruity, flowery and (fermented) apple-/cider-like. Chemical analysis was conducted by stir bar sorptive extraction (SBSE) coupled to gas chromatography-mass spectrometry in combination with an in-house data processing tool for semi-automated analyte detection. Through chemical analysis of the whisky samples and automated compound detection, we report over 200 mostly aroma-active volatiles. To test both approaches for their potential for sample classification, a simple classification problem (Scotch vs. American) was applied. Linear discriminant analysis (LDA) indicates both that sensory evaluation by RATA (97.86%) and the applied analytical procedure (96.94%) are suitable for the distinction between the two whisky types. In both approaches, potential markers were determined for the classification. These investigations build a solid foundation for the implementation of a versatile platform facilitating rapid and efficient aroma evaluation in various foodstuffs and beverages. [ABSTRACT FROM AUTHOR]

Data quality (DQ) issues consume a significant part of many companies' administrative and operational costs. To reduce such costs, companies often engage in master data management (MDM) initiatives to improve their DQ. MDM is, however, not a silver bullet that solves all data quality issues, but typically there are trade-offs between different data management strategies. Such trade-offs have not received much attention in the academic literature, and conceptualizations of the strategies for implementing MDM are sparse. Thus, with the aim of conceptualizing MDM strategies and understanding their consequences, this paper conducts a longitudinal case study at a large international hearing healthcare company in which an MDM initiative was implemented. The analysis identifies consequences of centralized and decentralized MDM approaches, on which basis four distinct strategies for data management are defined. [ABSTRACT FROM AUTHOR]

Background: Since the first face transplant procedure was performed in 2005, hundreds of publications have been published on the topic. In this bibliometric analysis we identify the key influential studies, based on citation power, in the field of face transplantation and summarize their content and characteristics. Methods: The Clarivate Analytics' Web of Science database was searched for the topic "face transplantation." We applied no limitations on publication date, language, or article length. The top 100 publications accruing the most citations were identified and information on title, year, journal, first and corresponding author, institution, country of corresponding author, methodology, and topic focus were extracted. Results: Of the top 100, most papers were published in 2011 (n = 11), with the publication years ranging between 2002 and 2019. Eight themes were identified, including ethics and psychology and post-operative outcomes. The most common theme was post-operative outcomes. Most publications had a clinical focus (n = 67), with only 11 being basic science. The country with the highest number of publications was the USA (n = 68), pooling a total of 3509 citations. The department with the highest number of publications was the Department of Plastic Surgery of Cleveland Clinic (n = 22). Conclusion: This analysis outlines the most influential publications in the field of face transplantation, providing a novel perspective on the field. These 100 publications reflect the progression of the field and outline significant advances in face transplantation. The analysis summarizes the trends occurring in the field and can help guide future academic research. Level of evidence: Not ratable. [ABSTRACT FROM AUTHOR]