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Purpose: This individual participant data meta-analysis (IPD-MA) assesses exercise effects on self-reported cognitive functioning (CF) and investigates whether effects differ by patient-, intervention-, and exercise-related characteristics. Methods: IPD from 16 exercise RCTs, including 1987 patients across multiple types of non-metastatic cancer, was pooled. A one-stage IPD-MA using linear mixed-effect models was performed to assess exercise effects on self-reported CF (z-score) and to identify whether the effect was moderated by sociodemographic, clinical, intervention- and exercise-related characteristics, or fatigue, depression, anxiety, and self-reported CF levels at start of the intervention (i.e., baseline). Models were adjusted for baseline CF and included a random intercept at study level to account for clustering of patients within studies. A sensitivity analysis was performed in patients who reported cognitive problems at baseline. Results: Minimal significant beneficial exercise effects on self-reported CF (β=−0.09 [−0.16; −0.02]) were observed, with slightly larger effects when the intervention was delivered post-treatment (n=745, β=−0.13 [−0.24; −0.02]), and no significant effect during cancer treatment (n=1,162, β=−0.08 [−0.18; 0.02]). Larger effects were observed in interventions of 12 weeks or shorter (β=−0.14 [−0.25; −0.04]) or 24 weeks or longer (β=−0.18 [−0.32; −0.02]), whereas no effects were observed in interventions of 12–24 weeks (β=0.01 [−0.13; 0.15]). Exercise interventions were most beneficial when provided to patients without anxiety symptoms (β=−0.10 [−0.19; −0.02]) or after completion of treatment in patients with cognitive problems (β=−0.19 [−0.31; −0.06]). No other significant moderators were identified. Conclusions: This cross-cancer IPD meta-analysis observed small beneficial exercise effects on self-reported CF when the intervention was delivered post-treatment, especially in patients who reported cognitive problems at baseline. Implications for Cancer Survivors: This study provides some evidence to support the prescription of exercise to improve cognitive functioning. Sufficiently powered trials are warranted to make more definitive recommendations and include these in the exercise guidelines for cancer survivors. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) increases the long-term risk of neurodegenerative diseases, including Alzheimer's disease (AD). Here, we demonstrate that protein variant pathology generated in brain tissue of an experimental TBI mouse model is similar to protein variant pathology observed during early stages of AD, and that subacute accumulation of AD associated variants of amyloid beta (Aβ) and tau in the TBI mouse model correlated with behavioral deficits. Male C57BL/6 mice were subjected to midline fluid percussion injury or to sham injury, after which sensorimotor function (rotarod, neurological severity score), cognitive deficit (novel object recognition), and affective deficits (elevated plus maze, forced swim task) were assessed post-injury (DPI). Protein pathology at 7, 14, and 28 DPI was measured in multiple brain regions using an immunostain panel of reagents selectively targeting different neurodegenerative disease-related variants of Aβ, tau, TDP-43, and alpha-synuclein. Overall, TBI resulted in sensorimotor deficits and accumulation of AD-related protein variant pathology near the impact site, both of which returned to sham levels by 14 DPI. Individual mice, however, showed persistent behavioral deficits and/or accumulation of toxic protein variants at 28 DPI. Behavioral outcomes of each mouse were correlated with levels of seven different protein variants in ten brain regions at specific DPI. Out of 21 significant correlations between protein variant levels and behavioral deficits, 18 were with variants of Aβ or tau. Correlations at 28 DPI were all between a single Aβ or tau variant, both of which are strongly associated with human AD cases. These data provide a direct mechanistic link between protein pathology resulting from TBI and the hallmarks of AD. [ABSTRACT FROM AUTHOR]

Objectives: This study analyzed the human maxilla to support the development of mean-value-based cutting guide systems for maxillary reconstruction, bridging the gap between freehand techniques and virtual surgical planning (VSP). Materials and methods: This retrospective cohort study used routine CT scans. DICOM data enabled 3D modelling and the maxilla was divided into four regions: paranasal (R1), facial maxillary sinus wall (R2), zygomatic bone (R3) and alveolar process (R4). Surface comparisons were made with a reference skull. Statistical analyses assessed anatomical variations, focusing on mean distance (Dmean), area of valid distance (AVD), integrated distance (ID) and integrated absolute distance (IAD). The study addressed hemimaxillectomy defects for two-segmental reconstructions using seven defined bilateral points to determine segmental distances and angles. Results: Data from 50 patients showed R2 as the most homogeneous and R4 as the most heterogeneous region. Significant age and gender differences were found in R3 and R4, with younger patients and females having more outliers. Cluster analysis indicated that males had R1 and R3 positioned anterior to the reference skull. The mean angle for segmental reconstruction was 131.24° ± 1.29°, with anterior segment length of 30.71 ± 0.57 mm and posterior length of 28.15 ± 0.86 mm. Conclusions: Anatomical analysis supported the development of semistandardized segmental resection approaches. Although gender and anatomical differences were noted, they did not significantly impact the feasibility of mean-value-based cutting-guide systems. Clinical relevance: This study provides essential anatomical data for creating cost-effective and efficient reconstruction options for maxillary defects, potentially improving surgical outcomes and expanding reconstructive possibilities beyond current techniques. [ABSTRACT FROM AUTHOR]

For nearly two decades, augmented reality (AR) has found diverse applications in education, particularly in science education, where its efficacy has been supported by relevant theories and many empirical studies. However, previous studies have revealed the following research deficit: While AR technology appears to influence learning-related variables, at the time of this study only few research on the use of AR glasses in physics, a discipline for which this technology seems particularly promising in the context of laboratory experiments, has been found. Thus, the present study uses an experimental comparison group design to investigate the question of how the use of AR glasses in a physics laboratory experiment (compared to in a learning setting without AR) influences students' motivation to learn, their cognitive load during the learning process and their learning achievement. The study (sample size N = 75) investigated the impact of AR glasses in a physics laboratory experiment on optical polarization. Results align with prior research, indicating heightened motivation among learners using AR applications. However, the absence of a significant difference in cognitive load between AR and non-AR learners was unexpected. Despite expectations based on spatial contiguity, learners with AR showed no advantage in learning achievement, challenging existing meta-analyses in physics education. These findings suggest a need to shift focus from surface features, like specific AR technology, to the content design of AR applications. Future studies should analyze the deep structure of AR applications, identifying features conducive to learning. [ABSTRACT FROM AUTHOR]

Background: The multicentre randomised SPARC trial evaluated the efficacy of a nurse-led sexual rehabilitation intervention on sexual functioning, distress, dilator use, and vaginal symptoms after radiotherapy for gynaecological cancers. Methods: Eligible women were randomised to the rehabilitation intervention or care-as-usual. Four intervention sessions were scheduled over 12 months, with concurrent validated questionnaires and clinical assessments. Primary outcome was the Female Sexual Function Index (FSFI). A generalised-mixed-effects model compared groups over time. Results: In total, 229 women were included (n = 112 intervention; n = 117 care-as-usual). No differences in FSFI total scores were found between groups at any timepoint (P = 0.37), with 12-month scores of 22.57 (intervention) versus 21.76 (care-as-usual). The intervention did not significantly improve dilator use, reduce sexual distress or vaginal symptoms compared to care-as-usual. At 12 months, both groups had minimal physician-reported vaginal stenosis; 70% of women were sexually active and reported no or mild vaginal symptoms. After radiotherapy and brachytherapy, 85% (intervention) versus 75% (care-as-usual) of participants reported dilation twice weekly. Discussion: Sexual rehabilitation for women treated with combined (chemo)radiotherapy and brachytherapy improved before and during the SPARC trial, which likely contributed to comparable study groups. Best practice involves a sexual rehabilitation appointment 1 month post-radiotherapy, including patient information, with dilator guidance, preferably by a trained nurse, and follow-up during the first year after treatment. Clinical trial registration: NCT03611517. [ABSTRACT FROM AUTHOR]

Left atrial (LA) physiology and hemodynamics are intimately connected to cardiac and lung function in health and disease. This study examined the relationship between MRI-based left atrial (LA) size and function with MRI-based lung volume and pulmonary function testing (PFT) parameters in the population-based KORA study cohort of 400 participants without overt cardiovascular disease. MRI quantification assessed LA size/function in sequences with and without ECG synchronization, alongside lung volume. Regression analysis explored the relationship of LA with MRI lung volume and PFT parameters. Among 378 participants (average age 56.3 ± 9.2 years; 42.3% women), non-gated LA size averaged 16.8 cm2, while maximal and minimal LA size from gated measurements were 19.6 cm2 and 11.9 cm2 respectively. The average MRI-derived lung volume was 4.0 L, with PFT showing a total lung capacity of 6.2 L, residual lung volume of 2.1 L, and forced vital capacity of 4.1 L. Multivariate regression analysis, adjusted for age, gender, and cardiovascular risk factors, revealed an inverse association between maximum LA size, non-gated LA, and LA area fraction with lung volume (ß = − 0.03, p = 0.006; ß = − 0.03, p = 0.021; ß = − 0.01, p = 0.012), with no significant association with PFT parameters. This suggests that MRI-based assessment may offer greater sensitivity in detecting subclinical LA impairment than PFT. [ABSTRACT FROM AUTHOR]

Background: The occurrence of visual hallucinations in visually impaired people without mental impairment is known as Charles Bonnet Syndrome (CBS). To date, the prevalence of CBS has been reported with high variance. The present study aims at evaluating the prevalence of CBS among low-vision patients. Methods: From March 2018 to February 2022, 194 patients with a visual acuity ≥ 0.5 logMAR approached the low vision section of the Eye Clinic Sulzbach. Of these, 50 patients were found eligible, agreed to participate in the study and were screened for CBS. The course of the disease, its phenomenology and characteristics, the circumstance of onset, the ability to manipulate and resolve the hallucinations, and the psychosocial aspects of CBS were investigated. Results: 26% of patients with low vision suffered from CBS. Women did not suffer from CBS significantly more often than men. Often, insight into the unreality of the images is not achieved immediately. Patterns or so-called "simple" hallucinations occurred just as frequently as other types of images such as people, body parts or faces. The most frequent images were animals. Visual hallucinations, lasting only for seconds in most cases, occurred more frequently during the day and in bright surroundings. All patients experienced the hallucinations exclusively with their eyes open. The hallucinations generally did not move with the eyes. Many sufferers did neither communicate about their hallucinations nor consult any physician. Conclusions: CBS among low-vision patients is common. Its prevalence constitutes clinical relevance. Future management of CBS may benefit from encouraging patients to share their experiences and consult a physician. [ABSTRACT FROM AUTHOR]

This study examined the influence of eHealth literacy on Chinese individuals' attitudes towards post-COVID-19 vaccination and explored methods to address obstacles related to eHealth literacy that could affect their comprehension and willingness to get vaccinated. In 2022, a web-based cross-sectional survey was conducted to assess the vaccination-related knowledge, attitudes and intentions of 950 participants. Vaccination knowledge was established by employing validated measures and conducting a Mokken scale analysis. Causal-directed acyclic graphs were used to illustrate the current comprehension of the correlation between eHealth literacy and the desire to receive vaccinations. This study utilised causal mediation and multiple linear regression analysis to determine the relationships between eHealth literacy, vaccination knowledge, vaccination willingness and subjective health status. The primary finding of this study was that an individual's comprehension of vaccination was a robust indicator of their inclination to receive vaccination. Moreover, eHealth literacy has an indirect effect on the propensity to get vaccinated by enhancing one's understanding of vaccines. This study emphasises the significant role of eHealth literacy in enhancing vaccination awareness and willingness, particularly among Chinese adults with poorer health in the post-COVID-19 period. The results affirm the efficacy of employing eHealth technologies to bolster immunisation initiatives, amplify vaccine consciousness, and promote compliance. Moreover, this study emphasises the significance of additional research to assess and record the function of eHealth literacy in immunisation practices. [ABSTRACT FROM AUTHOR]

The North Temperate Lakes Long-Term Ecological Research (NTL-LTER) program has been extensively used to improve understanding of how aquatic ecosystems respond to environmental stressors, climate fluctuations, and human activities. Here, we report on the metagenomes of samples collected between 2000 and 2019 from Lake Mendota, a freshwater eutrophic lake within the NTL-LTER site. We utilized the distributed metagenome assembler MetaHipMer to coassemble over 10 terabases (Tbp) of data from 471 individual Illumina-sequenced metagenomes. A total of 95,523,664 contigs were assembled and binned to generate 1,894 non-redundant metagenome-assembled genomes (MAGs) with ≥50% completeness and ≤10% contamination. Phylogenomic analysis revealed that the MAGs were nearly exclusively bacterial, dominated by Pseudomonadota (Proteobacteria, N = 623) and Bacteroidota (N = 321). Nine eukaryotic MAGs were identified by eukCC with six assigned to the phylum Chlorophyta. Additionally, 6,350 high-quality viral sequences were identified by geNomad with the majority classified in the phylum Uroviricota. This expansive coassembled metagenomic dataset provides an unprecedented foundation to advance understanding of microbial communities in freshwater ecosystems and explore temporal ecosystem dynamics. [ABSTRACT FROM AUTHOR]

The impact of ustekinumab (UST) on mucosal- and fistula healing and extraintestinal manifestations (EIM) in Crohn's disease (CD) were not fully elucidated in the registration trials. In this prospective, multicenter study (EudraCT number: 2017-005151-83) we evaluated the German label real-world-effectiveness of UST to achieve the primary endpoint of combined clinical and endoscopic response at week 52 and several secondary endpoints. Of 79 screened we enrolled 52 patients (female n = 28, bionaïve n = 13, biologic n = 39). At week 52 (per protocol analysis), 52% (n = 13/25) of patients achieved the primary endpoint [50% (n = 3/6) in the bionaïve, 45.5% (n = 5/11) biologic, 62.5% (n = 5/8) multiple biologics cohorts, respectively with age as independent predictor [OR 95% CI 0.933 (0.873, 0.998) p = 0.043], 60% (n = 15/25) achieved endoscopic response [50% (n = 3/6) in the bionaïve, 54.5% (n = 6/11) biologic, 75% (n = 6/8) multiple biologics cohorts, respectively], 36% (n = 9/25) achieved endoscopic remission [50% (n = 3/6) in the bionaïve, 27.3% (n = 3/11) biologic, 37.5% (n = 3/8) multiple biologics cohorts, respectively], 48% (n = 12/25) achieved mucosal healing [50% (n = 3/6) in the bionaïve, 36.4% (n = 4/11) biologic, 62.5% (n = 5/8) multiple biologics cohorts, respectively]. All achieved a fistula response and 33.3% (n = 1/3) in the multiple biologics group fistula remission at week 52. EIM decreased (week 0 28.2% vs. week 52 8%). CRP, FCP, PRO-2, EQ-5D-5L improved throughout. 36 patients (69.2%) experienced ≥ 1 treatment emergent adverse event, in 8 (15.4%) cases rated as severe and in 5 (9.6%) leading to UST discontinuation, but no very severe events or deaths. The effectiveness of UST was better than in the registration trials. [ABSTRACT FROM AUTHOR]

This study aimed to examine psychometric properties of the Adherence to Refills and Medications Scale (ARMS) in people with gout. We conducted exploratory factor analysis (EFA) and tested internal consistency (ordinal and Cronbach's alpha coefficients) and agreement (intraclass correlation coefficient (2,1)) in ARMS scores across three timepoints (baseline, 6, and 12 months) in 487 people with gout. The Kruskal–Wallis test, Spearman's rank, Kendall's tau-b correlations, and logistic regression were used to examine the criterion-related validity of the ARMS and factors associated with the ARMS. EFA suggested a one-factor structure, explaining 43.2% of total variance. High internal consistency (ordinal alpha = 0.902 at baseline) and moderate agreement in ARMS scores over time (ICCs > 0.5; p < 0.001) were observed. Lower ARMS scores (indicating better adherence) predicted achieving target serum urate (OR, 0.89; 95% CI, 0.83–0.95; p < 0.001), but not urate-lowering therapy (ULT) adherence (Proportion of Days Covered (PDC) ≥ 80%) (OR, 0.93; 95% CI, 0.81–1.05; p = 0.261). Negative correlations between ARMS and PDC were not statistically significant (Kendall's tau-b, r = − 0.126, p = 0.078; Spearman's rho = − 0.173, p < 0.073). Differences in median ARMS scores (IQR) of 16 (14–20), 13 (12–15), and 17.5 (15–21) in three groups of participants who reported (1) not taking ULT, (2) taking ULT and adherent, and (3) taking ULT but not adherent, respectively, were statistically significant (p < 0.001). Age was the only patient factor independently associated with optimal adherence (ARMS score = 12) (OR, 1.91; 95% CI, 1.50–2.43; p < 0.001). The ARMS is a reliable and valid measure of medication adherence behaviours in people with gout, justifying its use in gout medication adherence research. Key Points • Valid, practical, and efficient methods of measuring adherence to medications are needed in people with gout. • Commonly used medication adherence questionnaires have limited validity or have not been validated in people with gout. • The Adherence to Refills and Medications Scale (ARMS) has been proven valid and practical in many chronic illnesses but has not been validated in people with gout. • We showed the ARMS is valid and reliable for use in people with gout. [ABSTRACT FROM AUTHOR]

After in vitro fertilization with a single embryo, the parents learned about being pregnant with twins in the 10th week with various indications that an embryonic mix-up could have taken place. The affected couple thus expressed the urgent desire for a clarification of parenthood considering an abortion. However, the prenatal test results would not have been available until the 14/15th week of pregnancy. Legally, then, severe physical or mental distress of the pregnant woman must be claimed by physicians to justify an abortion after the twelfth week. However, a lack of genetic relatedness could lead to serious psychological distress for the parents, making a pregnancy termination possible even after the twelfth week, which is discussed in this case study alongside the interdisciplinary team's ethical, legal, and medical considerations. For the invasive relationship testing, cultivated chorionic villi samples (CVS) from both unborn and saliva samples from the putative parents were genetically analyzed using classical short tandem repeats (STR) analysis. The perfect match of both CVS profiles suggested the occurrence of an unusual late twin shaft, for which, fortunately, parenthood could be confirmed. To our knowledge, this is the first report on a prenatal investigation of a suspected embryo mix-up after assisted reproductive technology (ART), in which parenthood should be fixed. We want to draw attention to this unthinkable scenario, which may increase in the future with ART-induced rising multiple pregnancies. [ABSTRACT FROM AUTHOR]

This study investigated the anti-inflammatory effect of hydrophilic and lipophilic extracts from juçara fruits (Euterpe edulis Martius) through measurement of nitric oxide (NOx) and cytokines (IL-12p70, TNF-α, INF-γ, MCP-1, IL-6, and IL-10). J774 macrophages were stimulated with lipopolysaccharides (1 µg/mL) and treated with various concentrations (1–100 µg/mL) of juçara fruits extracts from crude extracts, and hexane, dichloromethane, ethyl acetate, and butanol fractions. Potential relationships between the phenolic composition of the extracts determined by LC-ESI-MS/MS and their anti-inflammatory capacity were also evaluated. Hexane and dichloromethane fractions inhibited NOx and IL-12p70 while increased IL-10. Hexane fractions also decreased IL-6 and IFN-γ production. Hexane and dichloromethane fractions showed a higher number of phenolic compounds (32 and 34, respectively) than the other extracts tested and were also the only ones that presented benzoic acid and pinocembrin. These results suggest juçara fruits compounds as potential anti-inflammatory agents, especially those of a more apolar nature. [ABSTRACT FROM AUTHOR]

Key message: Stem rust resistance was mainly based on a few, already known resistance genes; for yellow rust resistance there was a combination of designated genes and minor QTLs. Yellow rust (YR) caused by Puccinia striiformis f. sp. tritici (Pst) and stem rust (SR) caused by Puccinia graminis f. sp. tritici (Pgt) are among the most damaging wheat diseases. Although, yellow rust has occurred regularly in Europe since the advent of the Warrior race in 2011, damaging stem rust epidemics are still unusual. We analyzed the resistance of seven segregating populations at the adult growth stage with the parents being selected for YR and SR resistances across three to six environments (location–year combinations) following inoculation with defined Pst and Pgt races. In total, 600 progenies were phenotyped and 563 were genotyped with a 25k SNP array. For SR resistance, three major resistance genes (Sr24, Sr31, Sr38/Yr17) were detected in different combinations. Additional QTLs provided much smaller effects except for a gene on chromosome 4B that explained much of the genetic variance. For YR resistance, ten loci with highly varying percentages of explained genetic variance (pG, 6–99%) were mapped. Our results imply that introgression of new SR resistances will be necessary for breeding future rust resistant cultivars, whereas YR resistance can be achieved by genomic selection of many of the detected QTLs. [ABSTRACT FROM AUTHOR]

The assessment of skin changes in the context of possible child abuse is an important task in forensic medicine. This requires knowledge of pigmentation variants and pigmentation disorders such as congenital dermal melanocytosis, which includes Mongolian spots. Particularly in the case of atypical localization and dark pigmented skin, the differentiation from hematomas can be challenging. A case of two Nigerian siblings with extensive and atypically localized Mongolian spots is reported. The 1.5-year-old girl showed Mongolian spots on her back and the right side of her trunk. The 8-year-old boy showed Mongolian spots only on the back of his thighs. The authors are not aware of any case in which so called Mongolian spots were present exclusively on the back of the thighs and this case is all the more noteworthy as the back of the thigh is a common localization of blunt force trauma. [ABSTRACT FROM AUTHOR]

The hemodynamics in Fontan patients with single ventricles rely on favorable flow and energetics, especially in the absence of a subpulmonary ventricle. Age-related changes in energetics for extracardiac and lateral tunnel Fontan procedures are not well understood. Vorticity (VOR) and viscous dissipation rate (VDR) are two descriptors that can provide insights into flow dynamics and dissipative areas in Fontan pathways, potentially contributing to power loss. This study examined power loss and its correlation with spatio-temporal flow descriptors (vorticity and VDR). Data from 414 Fontan patients were used to establish a relationship between the superior vena cava (SVC) to inferior vena cava (IVC) flow ratio and age. Computational flow modeling was conducted for both extracardiac conduits (ECC, n = 16) and lateral tunnels (LT, n = 25) at different caval inflow ratios of 2, 1, and 0.5 that corresponded with ages 3, 8, and 15+. In both cohorts, vorticity and VDR correlated well with PL, but ECC cohort exhibited a slightly stronger correlation for PL-VOR (>0.83) and PL-VDR (>0.89) than that for LT cohort (>0.76 and > 0.77, respectively) at all ages. Our data also suggested that absolute and indexed PL increase (p < 0.02) non-linearly as caval inflow changes with age and are highly patient-specific. Comparison of indexed power loss between our ECC and LT cohort showed that while ECC had a slightly higher median PL for all 3 caval inflow ratio examined (3.3, 8.3, 15.3) as opposed to (2.7, 7.6, 14.8), these differences were statistically non-significant. Lastly, there was a consistent rise in pressure gradient across the TCPC with age-related increase in IVC flows for both ECC and LT Fontan patient cohort. Our study provided hemodynamic insights into Fontan energetics and how they are impacted by age-dependent change in caval inflow. This workflow may help assess the long-term sustainability of the Fontan circulation and inform the design of more efficient Fontan conduits. [ABSTRACT FROM AUTHOR]

Purpose: Penile cancer is a rare entity and has a good prognosis in localized stage. Delayed surgical treatment of lymphatic disease is associated with poor overall survival but conventional imaging cannot detect occult lymph node metastasis sufficiently. Imaging cancer related fibroblasts has shown promising results as non-invasive staging tool in various tumor entities but has not yet been evaluated in penile cancer. Methods: In this single-center pilot study, patients planned for surgical treatment for penile cancer underwent preoperatively [68Ga]Ga-FAPI-46 PET/CT. Post-operative histopathology was compared to [68Ga]Ga-FAPI-46 PET/CT results. Results: From January 2022 to June 2022, a total number 11 patients with histopathologically proven penile cancer underwent surgery and received [68Ga]Ga-FAPI-46 PET/CT prior therapy. 8 primary tumor sites and 4 lymph node regions were analyzed. FAPI uptake was increased on primary tumor site (SUVmax 16.2 (9.1 – 25.8)). Histopathological proven lymph node regions showed highly increased FAPI uptakes (SUVmax 17.9 (16.4 – 23.5) on [68Ga]Ga-FAPI-46 PET/CT. Conclusion: In this first pilot cohort, there were no false-positive FAPI uptake which might allow the detection of occult lymph node metastasis by [68Ga]Ga-FAPI-46 PET/CT and might consequently lead to omitting lymph node regions during surgery that had no increased FAPI uptake pre-operatively. [ABSTRACT FROM AUTHOR]

Aims: To establish reference values and clinically relevant determinants for measures of heart rate variability (HRV) and to assess their relevance for clinical outcome prediction in individuals with heart failure. Methods: Data from the MyoVasc study (NCT04064450; N = 3289), a prospective cohort on chronic heart failure with a highly standardized, 5 h examination, and Holter ECG recording were investigated. HRV markers were selected using a systematic literature screen and a data-driven approach. Reference values were determined from a healthy subsample. Clinical determinants of HRV were investigated via multivariable linear regression analyses, while their relationship with mortality was investigated by multivariable Cox regression analyses. Results: Holter ECG recordings were available for analysis in 1001 study participants (mean age 64.5 ± 10.5 years; female sex 35.4%). While the most frequently reported HRV markers in literature were from time and frequency domains, the data-driven approach revealed predominantly non-linear HRV measures. Age, sex, dyslipidemia, family history of myocardial infarction or stroke, peripheral artery disease, and heart failure were strongly related to HRV in multivariable models. In a follow-up period of 6.5 years, acceleration capacity [HRperSD 1.53 (95% CI 1.21/1.93), p = 0.0004], deceleration capacity [HRperSD: 0.70 (95% CI 0.55/0.88), p = 0.002], and time lag [HRperSD 1.22 (95% CI 1.03/1.44), p = 0.018] were the strongest predictors of all-cause mortality in individuals with heart failure independently of cardiovascular risk factors, comorbidities, and medication. Conclusion: HRV markers are associated with the cardiovascular clinical profile and are strong and independent predictors of survival in heart failure. This underscores clinical relevance and interventional potential for individuals with heart failure. ClinicalTrials.gov identifier: NCT04064450. [ABSTRACT FROM AUTHOR]

Context: Radical nephroureterectomy (RNU) with bladder cuff resection is the standard treatment in patients with high-risk upper tract urothelial cancer (UTUC). However, it is unclear which specific surgical technique may lead to improve oncological outcomes in term of intravesical recurrence (IVR) in patients with UTUC. Objective: To evaluate the efficacy of surgical techniques and approaches of RNU in reducing IVR in UTUC patients. Evidence Acquisition: Three databases were queried in January 2024 for studies analyzing UTUC patients who underwent RNU. The primary outcome of interest was the rate of IVR among various types of surgical techniques and approaches of RNU. Evidence Synthesis: Thirty-one studies, comprising 1 randomized controlled trial and 1 prospective study, were included for a systematic review and meta-analysis. The rate of IVR was significantly lower in RNU patients who had an early ligation (EL) of the ureter compared to those who did not (HR: 0.64, 95% CI: 0.44–0.94, p = 0.02). Laparoscopic RNU significantly increased the IVR compared to open RNU (HR: 1.28, 95% CI: 1.06–1.54, p < 0.001). Intravesical bladder cuff removal significantly reduced the IVR compared to both extravesical and transurethral bladder cuff removal (HR: 0.65, 95% CI: 0.51–0.83, p = 0.02 and HR: 1.64, 95% CI: 1.15–2.34, p = 0.006, respectively). Conclusions: EL of the affected upper tract system, ureteral management, open RNU, and intravesical bladder cuff removal seem to yield the lowest IVR rate in patients with UTUC. Well-designed prospective studies are needed to conclusively elucidate the optimal surgical technique in the setting of single post-operative intravesical chemotherapy. [ABSTRACT FROM AUTHOR]

Our prototype system designed for clinical data acquisition and recording of studies is a novel electronic data capture (EDC) software for simple and lightweight data capture in clinical research. Existing software tools are either costly or suffer from very limited features. To overcome these shortcomings, we designed an EDC software together with a mobile client. We aimed at making it easy to set-up, modifiable, scalable and thereby facilitating research. We wrote the software in R using a modular approach and implemented existing data standards along with a meta data driven interface and database structure. The prototype is an adaptable open-source software, which can be installed locally or in the cloud without advanced IT-knowledge. A mobile web interface and progressive web app for mobile use and desktop computers is added. We show the software's capability, by demonstrating four clinical studies with over 1600 participants and 679 variables per participant. We delineate a simple deployment approach for a server-installation and indicate further use-cases. The software is available under the MIT open-source license. Conclusively the software is versatile, easily deployable, highly modifiable, and extremely scalable for clinical studies. As an open-source R-software it is accessible, open to community-driven development and improvement in the future. [ABSTRACT FROM AUTHOR]

Purpose: We explored the associations between socioeconomic status, as evaluated by the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index (SVI), and characteristics of open globe injury (OGI) in a Level I trauma center during the COVID-19 pandemic. Methods: Retrospective review of electronic medical records of patients who underwent OGI evaluation and repair at Harborview Medical Center between March/2017 and March/2021. Demographic data and patient characteristics were recorded. The SVI was obtained based on the patient's home address. Patients were grouped into the "historical" (pre-COVID) cohort, including dates from March 2017 – March 2020, and the "COVID" cohort, including dates from March 2020 – March 2021. Results: 318 patients (77.4% male) were included. Average ± S.D. age (years) and SVI scores were 44.7 ± 22.7 and 0.413 ± 0.195, respectively. SVI scores were significantly higher (more vulnerable) during the COVID-19 pandemic compared to years prior (p = 0.017), however when compared to scores for the same patients prior to the pandemic, no difference was found (p = 0.609). There was no significant difference between intentional and non-intentional trauma, work-related injuries, OGI type, presence of endophthalmitis, or ocular trauma score (p ≥ 0.293). Still, significantly fewer motor vehicle-associated (MVA) OGIs occurred during the pandemic (p = 0.041). Conclusions: Patients with OGI during the COVID-19 pandemic had higher SVI scores, however when considering the overall effect of the pandemic, our findings are likely reflective of the societal changes at large. There was no identifiable impact on the mechanisms or characteristics of ocular injuries, except for fewer MVA injuries. [ABSTRACT FROM AUTHOR]

Recent years have witnessed signs of increasing political instability in democratic countries as well as growing alienation from civic institutions and processes among citizens, especially among young people. Within the context of civic and citizenship education, it is important to review such phenomena and study their extent among young people as well as the factors that have the potential of promoting different forms of citizenship engagement. Using data from the International Civic and Citizenship Education Study (ICCS) 2016 and 2009, this article provides insights into the expectations of young people to actively engage as citizens in the future and what influences these expectations, with a primary focus on the role of civic knowledge and trust in civic institutions. Results from ICCS 2009 and 2016 show that while large majorities among young people expected to vote in elections, only relatively few found it likely to be more actively involved in political action. Except for engagement in illegal protest, young people's expected participation in general appeared to be positively related to trust. However, associations with civic knowledge were more differentiated. Trust and civic knowledge tended to have negative correlations in countries with higher levels of perceived corruption, while a different association became apparent in democracies with more transparent institutions. Civic knowledge was consistently positively related to anticipated voting while it was negatively related to expected illegal protest. More knowledgeable students were also less inclined to consider active (conventional) forms of political participation in the future. [ABSTRACT FROM AUTHOR]

Peste des petits ruminants virus (PPRV) is a multi-host pathogen with sheep and goats as main hosts. To investigate the role of cattle in the epidemiology of PPR, we simulated conditions similar to East African zero-grazing husbandry practices in a series of trials with local Zebu cattle (Bos taurus indicus) co-housed with goats (Capra aegagrus hircus). Furthermore, we developed a mathematical model to assess the impact of PPRV-transmission from cattle to goats. Of the 32 cattle intranasally infected with the locally endemic lineage IV strain PPRV/Ethiopia/Habru/2014 none transmitted PPRV to 32 co-housed goats. However, these cattle or cattle co-housed with PPRV-infected goats seroconverted. The results confirm previous studies that cattle currently play a negligible role in PPRV-transmission and small ruminant vaccination is sufficient for eradication. However, the possible emergence of PPRV strains more virulent for cattle may impact eradication. Therefore, continued monitoring of PPRV circulation and evolution is recommended. Field trials and modeling in East Africa suggest zebu cattle, often co-housed with goats under zero-grazing conditions, show no evidence of transmitting PPRV to goats, supporting the strategy of focusing vaccination on small ruminants for PPR eradication in mixed-species systems. [ABSTRACT FROM AUTHOR]

The right ventricle (RV) differs developmentally, anatomically and functionally from the left ventricle (LV). Therefore, characteristics of LV adaptation to chronic pressure overload cannot easily be extrapolated to the RV. Mitochondrial abnormalities are considered a crucial contributor in heart failure (HF), but have never been compared directly between RV and LV tissues and cardiomyocytes. To identify ventricle-specific mitochondrial molecular and functional signatures, we established rat models with two slowly developing disease stages (compensated and decompensated) in response to pulmonary artery banding (PAB) or ascending aortic banding (AOB). Genome-wide transcriptomic and proteomic analyses were used to identify differentially expressed mitochondrial genes and proteins and were accompanied by a detailed characterization of mitochondrial function and morphology. Two clearly distinguishable disease stages, which culminated in a comparable systolic impairment of the respective ventricle, were observed. Mitochondrial respiration was similarly impaired at the decompensated stage, while respiratory chain activity or mitochondrial biogenesis were more severely deteriorated in the failing LV. Bioinformatics analyses of the RNA-seq. and proteomic data sets identified specifically deregulated mitochondrial components and pathways. Although the top regulated mitochondrial genes and proteins differed between the RV and LV, the overall changes in tissue and cardiomyocyte gene expression were highly similar. In conclusion, mitochondrial dysfuntion contributes to disease progression in right and left heart failure. Ventricle-specific differences in mitochondrial gene and protein expression are mostly related to the extent of observed changes, suggesting that despite developmental, anatomical and functional differences mitochondrial adaptations to chronic pressure overload are comparable in both ventricles. [ABSTRACT FROM AUTHOR]

Background: Although cavitating ultrasonic aspirators are commonly used in neurosurgical procedures, the suitability of ultrasonic aspirator-derived tumor material for diagnostic procedures is still controversial. Here, we explore the feasibility of using ultrasonic aspirator-resected tumor tissue to classify otherwise discarded sample material by fast DNA methylation-based analysis using low pass nanopore whole genome sequencing. Methods: Ultrasonic aspirator-derived specimens from pediatric patients undergoing brain tumor resection were subjected to low-pass nanopore whole genome sequencing. DNA methylation-based classification using a neural network classifier and copy number variation analysis were performed. Tumor purity was estimated from copy number profiles. Results were compared to microarray (EPIC)-based routine neuropathological histomorphological and molecular evaluation. Results: 19 samples with confirmed neuropathological diagnosis were evaluated. All samples were successfully sequenced and passed quality control for further analysis. DNA and sequencing characteristics from ultrasonic aspirator-derived specimens were comparable to routinely processed tumor tissue. Classification of both methods was concordant regarding methylation class in 17/19 (89%) cases. Application of a platform-specific threshold for nanopore-based classification ensured a specificity of 100%, whereas sensitivity was 79%. Copy number variation profiles were generated for all cases and matched EPIC results in 18/19 (95%) samples, even allowing the identification of diagnostically or therapeutically relevant genomic alterations. Conclusion: Methylation-based classification of pediatric CNS tumors based on ultrasonic aspirator-reduced and otherwise discarded tissue is feasible using time- and cost-efficient nanopore sequencing. [ABSTRACT FROM AUTHOR]

Purpose: Immunosuppression is a well-established risk factor for primary central nervous system lymphomas (PCNSLs), which present in this context distinct radiological characteristics. Our aim was to describe the radiological evolution of treated PCNSL in immunocompromised patients and suggest adapted MRI response criteria. Methods: We conducted a multicenter retrospective study of patients from the French LOC, K-Virogref and CANCERVIH network databases and enrolled adult immunocompromised patients with newly diagnosed PCNSL. Results: We evaluated the baseline, intermediate, end-of-treatment and follow-up MRI data of 31 patients (9 living with HIV, 16 with solid organ transplantation and 6 with an autoimmune disease under chronic immunosuppressive therapy). At baseline, 23/30 (77%) patients had necrotic lesions with ring enhancement and 28% of the lesions were hemorrhagic. At the end of the first-line treatment, 12/28 (43%) patients could not be classified according to the IPCG criteria. Thirteen of 28 (46%) patients still harbored contrast enhancement, and 11/28 (39%) patients had persistent large necrotic lesions with a median diameter of 15 mm. These aspects were not associated with a pejorative outcome and progressively diminished during follow-up. Six patients relapsed; however, we failed to identify any neuroimaging risk factors on the end-of-treatment MRI. Conclusion: In immunocompromised patients, PCNSLs often harbor alarming features on end-of-treatment MRI, with persistent contrast-enhanced lesions frequently observed. However, these aspects seemed to be related to the necrotic and hemorrhagic nature of the lesions and were not predictive of a pejorative outcome. Specific response criteria for this population are thereby proposed. [ABSTRACT FROM AUTHOR]

Purpose: The receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL) have been shown to promote proliferation of the breast and breast carcinogenesis. The objective of this analysis was to investigate whether tumor-specific RANK and RANKL expression in patients with primary breast cancer is associated with high percentage mammographic density (PMD), which is a known breast cancer risk factor. Methods: Immunohistochemical staining of RANK and RANKL was performed in tissue microarrays (TMAs) from primary breast cancer samples of the Bavarian Breast Cancer Cases and Controls (BBCC) study. For RANK and RANKL expression, histochemical scores (H scores) with a cut-off value of > 0 vs 0 were established. PMD was measured in the contralateral, non-diseased breast. Linear regression models with PMD as outcome were calculated using common predictors of PMD (age at breast cancer diagnosis, body mass index (BMI) and parity) and RANK and RANKL H scores. Additionally, Spearman rank correlations (ρ) between PMD and RANK and RANKL H score were performed. Results: In the final cohort of 412 patients, breast cancer-specific RANK and RANKL expression was not associated with PMD (P = 0.68). There was no correlation between PMD and RANK H score (Spearman's ρ = 0.01, P = 0.87) or RANKL H score (Spearman's ρ = 0.04, P = 0.41). RANK expression was highest in triple-negative tumors, followed by HER2-positive, luminal B-like and luminal A-like tumors, while no subtype-specific expression of RANKL was found. Conclusion: Results do not provide evidence for an association of RANK and RANKL expression in primary breast cancer with PMD. [ABSTRACT FROM AUTHOR]

This paper presents a numerical framework for the analysis of quantum devices based on the Von Neumann (VN) equation, which involves the concept of the Tight-Binding Method (TBM). The model is based on the application of the Tight-Binding Hamiltonian within Quantum Liouville Type Equations and has the advantage that the atomic structure of the materials used is taken into account. Furthermore, the influence of a Complex Absorbing Potential (CAP) as a complementary boundary condition and its essential contribution to the system stability with respect to the eigenvalue spectrum is discussed. [ABSTRACT FROM AUTHOR]

The simulation of nanodevices is computationally inefficient with current algorithms. The discontinuous Galerkin approach has been demonstrated in the field of computational fluid dynamics to deliver high order accuracy and efficiency due to its reliance on matrix–vector multiplications. Previously, the discontinuous Galerkin approach was successfully used in conjunction with the finite volume technique to solve the Liouville–von Neumann equation in center-mass coordinates and thus simulate nanodevices. To exploit its full potential regarding high-performance computing, this work aims to substitute the aforementioned finite volume technique with the discontinuous Galerkin method. To arrive at the said formalism, a finite element method is implemented as an intermediate step. [ABSTRACT FROM AUTHOR]

Purpose: To propose a paradigm change for the validation procedures of medication adherence questionnaires. Methods: A total of 121 validation procedures of unique questionnaires for medication adherence were analyzed. Results: "Construct validity" and "internal consistency" were most often assessed, and test results varied largely. A more in-depth analysis indicated that the assessment of medication non-adherence included distinct but related constructs, such as the extent to which doses are missed, and the attempt to identify different facets of medication-taking behavior. Consequently, each construct requires a different measurement approach with different psychometric tests for establishing its validity and reliability. Conclusion: Results show that assessing the validity and reliability of adherence questionnaires with standard procedures including statistical tests is inconclusive. Refinement of the constructs of non-adherence is needed in pharmacy and medical practice. We suggest a distinction between the (i) extent of missed doses over the past 2 weeks, (ii) modifiable reasons for non-adherence behavior, and (iii) unmodifiable factors of non-adherence. Validation procedures and corresponding statistical methods should be selected according to the specific single constructs. [ABSTRACT FROM AUTHOR]

Copyright of Die Unfallchirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures. Broad and targeted lipidomic analyzes of primary macrophages and comparative lipid profiling of atheroma identified a broad impact of LDAH on esterified sterols, including natural liver X receptor (LXR) sterol ligands. Transcriptomic analyzes coupled with rescue experiments show that LDAH modulates the expression of prototypical LXR targets and leads macrophages to a less inflammatory phenotype with a profibrotic gene signature. These studies underscore the role of LDs as reservoirs and metabolic hubs of bioactive lipids, and suggest that LDAH favorably modulates macrophage activation and protects against atherosclerosis via lipolytic mobilization of regulatory sterols. The mechanisms and consequences of bioactive lipids release from lipid droplets remain poorly understood. Here the authors link a lipid droplet enzyme to mobilization of esters of regulatory sterols in foam cells and protection against atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Cognitive reserve (CR) is considered a protective factor for cognitive function and may explain interindividual differences of cognitive performance given similar levels of neurodegeneration, e.g., in Alzheimer´s disease. Recent evidence suggests that CR is also relevant in Parkinson's disease (PD). Objective: We aimed to explore the role of life-stage specific CR for overall cognition and specific cognitive domains cross-sectionally and longitudinally in PD. Methods: The cross-sectional analysis with data from the DEMPARK/LANDSCAPE study included 81 individuals without cognitive impairment (PD-N) and 87 individuals with mild cognitive impairment (PD-MCI). Longitudinal data covered 4 years with over 500 observations. CR was operationalized with the Lifetime of Experiences Questionnaire (LEQ), capturing the complexity of lifestyle activities across distinct life-stages. Cognition was assessed using a comprehensive neuropsychological test battery. Results: Higher LEQ scores, particularly from mid- and late-life, were observed in PD-N compared to PD-MCI [F(1,153) = 4.609, p =.033, ηp2 = 0.029]. They were significantly associated with better cognitive performance (0.200 ≤ β ≤ 0.292). Longitudinally, linear mixed effect models (0.236 ≤ marginal R2 ≤ 0.441) revealed that LEQ scores were positively related to cognitive performance independent of time. However, the decline in overall cognition and memory over time was slightly more pronounced with higher LEQ scores. Conclusions: This study emphasizes the association between complex lifestyle activities and cognition in PD. Data indicate that while CR might be related to a delay of cognitive decline, individuals with high CR may experience a more pronounced drop in overall cognition and memory. Future studies will have to replicate these findings, particularly regarding domain-specific effects and considering reverse causal mechanisms. [ABSTRACT FROM AUTHOR]

Identifying and characterizing mobile genetic elements in sequencing data is essential for understanding their diversity, ecology, biotechnological applications and impact on public health. Here we introduce geNomad, a classification and annotation framework that combines information from gene content and a deep neural network to identify sequences of plasmids and viruses. geNomad uses a dataset of more than 200,000 marker protein profiles to provide functional gene annotation and taxonomic assignment of viral genomes. Using a conditional random field model, geNomad also detects proviruses integrated into host genomes with high precision. In benchmarks, geNomad achieved high classification performance for diverse plasmids and viruses (Matthews correlation coefficient of 77.8% and 95.3%, respectively), substantially outperforming other tools. Leveraging geNomad's speed and scalability, we processed over 2.7 trillion base pairs of sequencing data, leading to the discovery of millions of viruses and plasmids that are available through the IMG/VR and IMG/PR databases. geNomad is available at https://portal.nersc.gov/genomad. geNomad identifies mobile genetic elements in sequencing data. [ABSTRACT FROM AUTHOR]

Primary medication non-adherence describes the situation when a first prescription for a new medication is never filled. Primary non-adherence is an important, yet understudied aspect of reduced effectiveness of pharmacotherapy. This review summarizes the frequency, impact, reasons, predictors, and interventions regarding primary non-adherence to cardiovascular/cardiometabolic drugs. The current literature reveals a high prevalence of primary non-adherence. The individual risk of primary non-adherence is determined on multiple factors, e.g., primary non-adherence of lipid-lowering drugs is higher compared to antihypertensive medications. However, the overall rate of primary non-adherence is > 10%. Additionally, this review identifies specific areas for research to better understand why patients forgo evidence-based beneficial pharmacotherapy and to explore targeted interventions. At the same time, measures to reduce primary non-adherence—once proven to be effective—may represent an important new opportunity to reduce cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Copyright of Österreichische Wasser- und Abfallwirtschaft is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Desensitisation of the mu-opioid receptor (MOR) is proposed to underlie the initiation of opioid analgesic tolerance and previous work has shown that agonist-induced phosphorylation of the MOR C-tail contributes to this desensitisation. Moreover, phosphorylation is important for β-arrestin recruitment to the receptor, and ligands of different efficacies induce distinct phosphorylation barcodes. The C-tail 370TREHPSTANT379 motif harbours Ser/Thr residues important for these regulatory functions. 375Ser is the primary phosphorylation site of a ligand-dependent, hierarchical, and sequential process, whereby flanking 370Thr, 376Thr and 379Thr get subsequently and rapidly phosphorylated. Here we used GRK KO cells, phosphosite specific antibodies and site-directed mutagenesis to evaluate the contribution of the different GRK subfamilies to ligand-induced phosphorylation barcodes and β-arrestin2 recruitment. We show that both GRK2/3 and GRK5/6 subfamilies promote phosphorylation of 370Thr and 375Ser. Importantly, only GRK2/3 induce phosphorylation of 376Thr and 379Thr, and we identify these residues as key sites to promote robust β-arrestin recruitment to the MOR. These data provide insight into the mechanisms of MOR regulation and suggest that the cellular complement of GRK subfamilies plays an important role in determining the tissue responses of opioid agonists. CRISPR/Cas9 knock-out of GRKs combined with mutagenesis and phospho-specific antibodies reveal the sites of the mu-opioid receptor that underlie the differences in regulation of this receptor by morphine and fentanyl. [ABSTRACT FROM AUTHOR]

Invasive species are one of the main reasons for the decline in global biodiversity. When it comes to the management of invasive species, stakeholders who are directly involved with this issue play a particularly important role, as they are directly engaged in management and can also influence the public's perception. This study therefore investigates how different stakeholder groups in Germany perceive invasive species. In total, more than 2200 people were surveyed, belonging to nine different stakeholder groups that are in contact with invasive species (hunters and members in hunting associations, farmers, members of environmental and conservation organizations, members in allotment garden clubs, animal welfare supporters, divers, employees in zoological gardens, administrative employees in the regulatory authority, speleologists). It was found that the number of invasive animal and plant species in Germany was roughly correctly estimated in all groups, but the economic damage caused by invasive species was substantially underestimated. When invasive species were mentioned, mainly conspicuous mammals or plants were listed (e.g. Procyon lotor or Impatiens glandulifera). In all surveyed groups, there was a notable level of interest in invasive species, and they were commonly regarded as environmental issues. While these results offer valuable insights into stakeholders' perspectives on invasive species, they also highlight the need for improvement. In particular, there is a need for greater education of stakeholders about inconspicuous invasive species, the spread of invasive species and the damage caused by them. [ABSTRACT FROM AUTHOR]

To prevent ordinary people from being harmed by natural language processing (NLP) technology, finding ways to measure the extent to which a language model is biased (e.g., regarding gender) has become an active area of research. One popular class of NLP bias measures are bias benchmark datasets—collections of test items that are meant to assess a language model's preference for stereotypical versus non-stereotypical language. In this paper, we argue that such bias benchmarks should be assessed with models from the psychometric framework of item response theory (IRT). Specifically, we tie an introduction to basic IRT concepts and models with a discussion of how they could be relevant to the evaluation, interpretation and improvement of bias benchmark datasets. Regarding evaluation, IRT provides us with methodological tools for assessing the quality of both individual test items (e.g., the extent to which an item can differentiate highly biased from less biased language models) as well as benchmarks as a whole (e.g., the extent to which the benchmark allows us to assess not only severe but also subtle levels of model bias). Through such diagnostic tools, the quality of benchmark datasets could be improved, for example by deleting or reworking poorly performing items. Finally, in regards to interpretation, we argue that IRT models' estimates for language model bias are conceptually superior to traditional accuracy-based evaluation metrics, as the former take into account more information than just whether or not a language model provided a biased response. [ABSTRACT FROM AUTHOR]

Amber captures a snapshot of life and death from millions of years in the past. Here, the fate of three fossil Darwin wasps in Baltic amber is virtually dissected with the help of micro-CT scanning, to better understand the taphonomic processes that affected their preservation. The states of the fossils range from nearly perfect preservation, including remains of internal organs, to empty casts that were strongly affected by decomposition. We describe the three specimens as new taxa, Osparvis aurorae gen. et sp. nov., Grana harveydenti gen. et sp. nov. and Xorides? romeo sp. nov. Based on the taphonomic and morphological interpretations, we conclude that two specimens were trapped alive, and the third ended up in resin post-mortem. The morphology and classification of the specimens provide clues regarding their ecology, and we discuss their likely hosts and parasitation modes. Taken together, our three wasp fossils showcase how an integrative analysis of amber taphonomy, taxonomic association and morphology can shed light onto past biodiversity and offer valuable insights for interpreting their evolutionary history. [ABSTRACT FROM AUTHOR]

Religious attachment has been identified as an important correlate of civic participation, civic engagement, and civil participation among adults. This study investigates two aspects of relationships between religiosity and intended political engagement among lower secondary school students in 2009 and 2016. One aspect is the extent to which religious attachment is associated with an endorsement of the influence of religion in society. This can be viewed as the converse of secularity which asks for the separation of social and political institutions from religion. A second aspect investigated is the extent to which religious attachment is associated with expected adult electoral participation and expected adult active political participation after controlling for the effects of other characteristics. While the results from this study show no strong or consistent relationships between religious background and expected political participation among lower-secondary students, findings suggest that young people's endorsement of religious influence in society depends strongly on their religious background and in turn shows associations with expected active political participation. [ABSTRACT FROM AUTHOR]

Mucus stasis is a pathologic hallmark of muco-obstructive diseases, including cystic fibrosis (CF). Mucins, the principal component of mucus, are extensively modified with hydroxyl (O)-linked glycans, which are largely terminated by sialic acid. Sialic acid is a negatively charged monosaccharide and contributes to the biochemical/biophysical properties of mucins. Reports suggest that mucin sialylation may be altered in CF; however, the consequences of reduced sialylation on mucus clearance have not been fully determined. Here, we investigated the consequences of reduced sialylation on the charge state and conformation of the most prominent airway mucin, MUC5B, and defined the functional consequences of reduced sialylation on mucociliary transport (MCT). Reduced sialylation contributed to a lower charged MUC5B form and decreased polymer expansion. The inhibition of total mucin sialylation de novo impaired MCT in primary human bronchial epithelial cells and rat airways, and specific α-2,3 sialylation blockade was sufficient to recapitulate these findings. Finally, we show that ST3 beta-galactoside alpha-2,3-sialyltransferase (ST3Gal1) expression is downregulated in CF and partially restored by correcting CFTR via Elexacaftor/Tezacaftor/Ivacaftor treatment. Overall, this study demonstrates the importance of mucin sialylation in mucus clearance and identifies decreased sialylation by ST3Gal1 as a possible therapeutic target in CF and potentially other muco-obstructive diseases. [ABSTRACT FROM AUTHOR]

Androgen insensitivity syndrome (AIS) is a difference of sex development (DSD) characterized by different degrees of undervirilization in individuals with a 46,XY karyotype despite normal to high gonadal testosterone production. Classically, AIS is explained by hemizygous mutations in the X-chromosomal androgen receptor (AR) gene. Nevertheless, the majority of individuals with clinically diagnosed AIS do not carry an AR gene mutation. Here, we present a patient with a 46,XY karyotype, born with undervirilized genitalia, age-appropriate testosterone levels and no uterus, characteristic for AIS. Diagnostic whole exome sequencing (WES) showed a maternally inherited LINE1 (L1) retrotransposon insertion in the 5′ untranslated region (5′UTR) of the AR gene. Long-read nanopore sequencing confirmed this as an insertion of a truncated L1 element of ≈ 2.7 kb and showed an increased DNA methylation at the L1 insertion site in patient-derived genital skin fibroblasts (GSFs) compared to healthy controls. The insertion coincided with reduced AR transcript and protein levels in patient-derived GSFs confirming the clinical diagnosis AIS. Our results underline the relevance of retrotransposons in human disease, and expand the growing list of human diseases associated with them. [ABSTRACT FROM AUTHOR]

Harmful algae blooms are a rare phenomenon in rivers but seem to increase with climate change and river regulation. To understand the controlling factors of cyanobacteria blooms that occurred between 2017 and 2020 over long stretches (> 250 km) of the regulated Moselle River in Western Europe, we measured physico-chemical and biological variables and compared those with a long-term dataset (1997–2016). Cyanobacteria (Microcystis) dominated the phytoplankton community in the late summers of 2017–2020 (cyano-period) with up to 110 µg Chlorophyll-a/L, but had not been observed in the river in the previous 20 years. From June to September, the average discharge in the Moselle was reduced to 69–76% and water temperature was 0.9–1.8 °C higher compared to the reference period. Nitrogen (N), phosphorus (P) and silica (Si) declined since 1997, albeit total nutrient concentrations remained above limiting conditions in the study period. Cyanobacterial blooms correlated best with low discharge, high water temperature and low nitrate. We conclude that the recent cyanobacteria blooms have been caused by dry and warm weather resulting in low flow conditions and warm water temperature in the regulated Moselle. Under current climate projections, the Moselle may serve as an example for the future of regulated temperate rivers. [ABSTRACT FROM AUTHOR]

The interferometric control of dissipation in a two-port system is a fruitful concept enabling the enhancement or cancellation of the input amplitudes as a function of their relative phases. Here, beyond the canonical configuration of Coherent Perfect Absorption (CPA), we apply this concept to two simultaneously excited strongly-coupled nanoscale electromechanical resonators submitted to independently controlled phase-shifted excitations. Both subsystems are read simultaneously by optical means allowing us to completely reconstruct the signature of coherent annihilation or amplification on both quadrature. We evidence that the mechanical modes amplitude can be enhanced or inhibited with respect to the case of single port excitation while phase experiences strong variations with the excitation imbalance and phase difference. Meanwhile, phase singularities with opposite topological charges are observed for mechanical normal modes. Close to the phase singularity, we demonstrate that the input of a weak phase modulation induces a large, pure phase modulation of the normal mode. These experimental demonstrations are fully modelled via the mechanical dynamical equations of our system. The interferometric control may open avenues for low-power amplitude controlled phase modulation schemes and vice-versa for potential switches and logical gates. Coherent perfect absorption allows to entirely dissipate the energy impinging on both single and multimode systems, but it typically does not allow for a control of the phase quadratures. Here, the authors implement coherent interferometric control of the phase quadratures in two strongly-coupled electromechanical nanoresonators. [ABSTRACT FROM AUTHOR]

The present study examines for the first time the emission patterns and olfactory signatures of 9 complete human corpses of different stages of decomposition. Air sampling was performed inside the body bags with solid sorbents and analysed by coupled gas chromatography-mass spectrometry after thermal desorption (TD-GC-MS). Furthermore, odour-related substances were detected by gas chromatography-olfactometry (GC-O). Sulfurous compounds (mainly dimethyl di- and trisulfide) were identified as most important to the odour perception. Around 350 individual organic substances were detected by TD-GC-MS, notably sulfurous and nitrogenous substances as well as branched alkanes, aldehydes, ketones, alcohols, carboxylic acids, carboxylic acid esters and ethers. A range of terpenes was detected for the first time in a characteristic emission pattern over all decomposition stages. Concentrations of the substances varied greatly, and no correlation between the emission patterns, the stage of decomposition and the cause of death could be found. While previous studies often analysed pig cadavers or only parts of human tissue, the present study shows the importance of analysing complete human corpses over a range of decomposition stages. Moreover, it is shown that using body bags as a kind of "emission test chamber" is a very promising approach, also because it is a realistic application considering the usual transport and store of a body before autopsy. [ABSTRACT FROM AUTHOR]

Objectives: Fixed orthodontic appliances may increase the risk for caries and white spot lesions. The aim of this retrospective study was to determine the long-term associations between both in orthodontic patients. Materials and methods: 103 patients aged 36.6 ± 6.5 years whose fixed appliance orthodontic treatment had finished at least 15 years ago were included. Current clinical data and photographs (T3), panoramic x-ray and photographs from before treatment (T0), after debonding (T1) and at 2-year follow-up (T2) were available. Parameters of interest were dentine caries, “Missing/Filled Teeth” (MFT), “White Spot Lesion” (WSL) index and “Periodontal Screening and Recording” index (PSR; T3 only). Results: At T0, 30.4% had no caries experience decreasing to 25.6%, 22.4% and 6.8% at T1, T2 and T3 resp. The median MFT (95% CI) at T0, T1, T2 and T3 was 2 (1;3), 3 (2;4), 3 (2;4) and 7 (6;9) resp. increasing significantly at each time point (p < 0.001 each); 30.1% had WSL at debonding. Patients with caries experience at T0 had a 2.4-fold increased risk of WSL at debonding. Dentine caries, caries experience and WSL at T1 were significantly associated with incident caries at T2, but not at T3. PSR at T3 had a significant association with previous caries incidence and WSL. Conclusions: Caries experience prior to orthodontic treatment may constitute a risk indicator for WSL, and caries experience and WSL at its end for caries incidence in the near term. Clinical Relevance: Present caries and WSL may help identifying orthodontic patients with special need for prevention and counselling. [ABSTRACT FROM AUTHOR]

Shape optimization methods have been proven useful for identifying interfaces in models governed by partial differential equations. Here we consider a class of shape optimization problems constrained by nonlocal equations which involve interface–dependent kernels. We derive a novel shape derivative associated to the nonlocal system model and solve the problem by established numerical techniques. The code for obtaining the results in this paper is published at (https://github.com/schustermatthias/nlshape). [ABSTRACT FROM AUTHOR]