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Objective: Speculation about the effects of COVID-19, especially on youth social development, has been mixed. This study aimed to examine change in loneliness and belongingness into the first month of stay-at-home orders (January through April 2020). Participants: College students (N = 73, mean age = 19.03 years, SD = 1.44 years) enrolled in a life-span development course. Methods: Participants completed online surveys at the beginning and the end of the semester assessing change in well-being. Results: Results revealed that loneliness scores significantly decreased, and belongingness scores significantly increased from Time 1 to Time 2. Among those who experienced increased belongingness, loneliness significantly decreased while there was not a significant change in loneliness among those who decreased in belongingness. Conclusions: These findings suggest that increasing belongingness should be a focus when trying to combat loneliness, especially in young adults experiencing a dramatic life event during a critical time for social development.

Abstract Lacustrine methane emissions are strongly mitigated by aerobic methane-oxidizing bacteria (MOB) that are typically most active at the oxic-anoxic interface. Although oxygen is required by the MOB for the first step of methane oxidation, their occurrence in anoxic lake waters has raised the possibility that they are capable of oxidizing methane further anaerobically. Here, we investigate the activity and growth of MOB in Lake Zug, a permanently stratified freshwater lake. The rates of anaerobic methane oxidation in the anoxic hypolimnion reached up to 0.2 µM d−1. Single-cell nanoSIMS measurements, together with metagenomic and metatranscriptomic analyses, linked the measured rates to MOB of the order Methylococcales. Interestingly, their methane assimilation activity was similar under hypoxic and anoxic conditions. Our data suggest that these MOB use fermentation-based methanotrophy as well as denitrification under anoxic conditions, thus offering an explanation for their widespread presence in anoxic habitats such as stratified water columns. Thus, the methane sink capacity of anoxic basins may have been underestimated by not accounting for the anaerobic MOB activity.

Large earthquakes can contribute to mountain growth by building topography but also contribute to mass removal from mountain ranges through widespread mass wasting. On annual to decadal or centennial timescales, large earthquakes also have the potential to significantly alter fluvial sediment dynamics if a significant volume of the sediment generated reaches the fluvial network. In this contribution, we focus on the Melamchi–Indrawati and Bhote Koshi rivers in central Nepal, which have both experienced widespread landsliding associated with the 2015 Gorkha (Nepal) earthquake. Using a time series of high-resolution satellite imagery, we have mapped exposed sediment along the rivers from 2012–2021 to identify zones of active channel deposition and document changes over time. Counter to expectations, we show negligible increases in coarse-sediment accumulation along both river corridors since the Gorkha earthquake. However, an extremely high-concentration flow event on 15 June 2021 caused an approximately 4-fold increase in exposed sediment along a 30 km reach of the channel with up to 12 m of channel aggradation in the Melamchi–Indrawati rivers; this event was localised and did not impact the neighbouring Bhote Koshi catchment. Based on published reports, new helicopter-based photography, and satellite data, we demonstrate that this event was sourced from a localised rainfall event between 4500 and 4800 m and that a significant fraction of the sediment was supplied from sources that were unrelated to the landslides generated by the Gorkha earthquake.

Introduction Incidence rates in anterior cruciate ligament (ACL) injuries, which are linked to multiple factors, are higher in females than males (Sutton & Bullock, 2013). However, the main contributors to the difference in risk are biomechanical factors such as increased knee valgus (KV), knee internal rotation (KIR), or decreased hip flexion (HF; Seyedahmadi et al., 2022). Returning back to sports after an injury requires extensive rehabilitation as well as training of dual-task situations in order to be physically and cognitively prepared. Exergaming represents a dual task including a cognitive and a motor component and may be used as training modality during rehabilitation. It is known that performing a dual-task leads to altered landing movement patterns in healthy athletes (Dai et al., 2018). Before an exergame for rehabilitation after ACL injury can be implemented and tailored to the specific needs of female and male athletes, the movement patterns of males and females need to be understood. Therefore, the aim of this study was to identify biomechanical differences between males and females when performing a high-intensive exergame. Methods Using 3D-motion capture (Vicon) kinematics were measured in 18 healthy athletes (9 male, 9 female) during a 25-min exergame (Sphery Racer, ExerCube). The exergame included nine different exercises of which 8 were used for analysis. The exercises were separated into neutral (squat, jump, burpee) and side-specific exercises (low-touch, mid-touch, high-touch, punch, lunge). For analysis, the maximal KV, maximal KIR, and the minimal HF were extracted during 10-30° knee flexion. These maximal values were then compared between the sexes, the exercises, and both legs with a linear mixed model, for each the neutral and the side-specific exercises. Results A main effect of sex was only found for side-specific exercises in KIR (F(1, 16) = 6.1, p = .02) with females exhibiting higher values. For KV and HF in side-specific exercises as well as all variables in neutral exercises, no significant main effect for sex was found. However, there was a main effect of exercise in KV; KIR, and HF in neutral (p < .001) as well as in side-specific exercises (p < .001). Discussion/Conclusion Differences in KIR between males and females primarily exist during touches and punches. Therefore, exergames should incorporate this fact to counteract increased risk for knee injuries in females. References Dai, B., Cook, R. F., Meyer, E. A., Sciascia, Y., Hinshaw, T. J., Wang, C., & Zhu, Q. (2018). The effect of a secondary cognitive task on landing mechanics and jump performance. Sports Biomechanics, 17(2), 192–205. https://doi.org/10.1080/14763141.2016.1265579 Seyedahmadi, M., Minoonejad, H., Karimizadeh Ardakani, M., Heidari, Z., Bayattork, M., & Akbari, H. (2022). What are gender differences in lower limb muscle activity during jump-landing tasks? A systematic review and meta-analysis. BMC Sports Science, Medicine & Rehabilitation, 14(1), Article 77. https://doi.org/10.1186/s13102-022-00469-3 Sutton, K. M., & Bullock, J. M. (2013). Anterior cruciate ligament rupture: Differences between males and females. The Journal of the American Academy of Orthopaedic Surgeons, 21(1), 41–50. https://doi.org/10.5435/jaaos-21-01-41

Introduction Exergaming - physically active gaming - offers great potential for rehabilitation after knee injuries in sports, as it combines physical and cognitive challenges. However, before its use in sports rehabilitation can be recommended as safe and reliable, it is necessary to assess the biomechanics associated with knee injuries - an abducted, internally rotated knee at 10-30° of flexion (Koga et al., 2010). The aim of this study was to compare knee valgus (KV) during 10-30° knee flexion between healthy individuals without previous knee injuries and patients undergoing rehabilitation after knee injuries in three exercises of a high-intensive, immersive exergame (ExerCube). Methods The kinematics of 18 healthy subjects (25.2 ± 3.3 years, 9 female) and 6 patients (25.0 ± 5.9 years, 2 female) were recorded using marker-based movement analysis (Vicon) during 25 minutes of exergame training (Sphery Racer, ExerCube). The average maximum KV angle during 10-30° knee flexion was compared between healthy subjects and patients in the squat, jump, and burpee for the right leg using a linear mixed model. Results The average maximal KV in the squat was 4.3° for healthy subjects and 4.8° for patients. In the jump, an average maximal KV of 5.9° (healthy subjects) and 6.8° (patients) was found. With an average of 6.9° in the maximal KV of healthy subjects and 8.6° in patients, the burpee showed the highest KV of all exercises. A significant main effect was found for exercise (F(2, 45) = 57.03, p < .001), but not for the difference between groups (F(1, 22) = 0.45, p = 0.51). Discussion/Conclusion There are no significant differences in KV between healthy participants and patients undergoing rehabilitation after knee injuries. This indicates that the pre-injury movement pattern was restored in the patients, and it can be assumed that the studied exercises during exergaming are safe for use in this stage of rehabilitation. References Koga, H., Nakamae, A., Shima, Y., Iwasa, J., Myklebust, G., Engebretsen, L., Bahr, R., & Krosshaug, T. (2010). Mechanisms for noncontact anterior cruciate ligament injuries: Knee joint kinematics in 10 injury situations from female team handball and basketball. The American Journal of Sports Medicine, 38(11), 2218–2225. https://doi.org/10.1177/0363546510373570

Objectives: Ketamine exerts rapid antidepressant effects by enhancing neuroplasticity, particularly in the amygdala and hippocampus-regions involved in fear processing and learning. While the role of ketamine's dissociative effects in its antidepressant response is debated, anxiety experienced during infusion has been negatively correlated with treatment outcomes. Methods: In this single-blind, placebo-controlled study, a subset of 17 healthy volunteers (6 males, 23.12 ± 1.9 years) received intravenously a placebo in the first and 0.5 mg/kg racemic ketamine in the second session. Anxiety-related experiences were assessed by the 5D-ASC score obtained post-infusion, structural magnetic resonance imaging scans were acquired 4 h post-infusion. An anxiety-score was obtained from the 5D-ASC. Relation between post-placebo amygdala volume, hippocampal volume, and its subfields with the anxiety-score were assessed using linear regression models. Results: Results showed a statistically significant negative relation between hippocampal head volume and the anxiety score (β = -0.733, p = 0.006), with trending negative association for each subfield's head and the score. Conclusion: These findings suggest that anxiety-related experiences during ketamine infusion may be mediated by the hippocampus, with smaller hippocampal volumes leading to more anxiety-related experiences. Thus, hippocampal subfield volumes may be used as a predictor for anxiety-related events during ketamine use and might predict treatment outcome in future approaches.

Background: This monocentric randomized controlled pilot trial investigates the impact of virtual reality (VR) hypnosedation on perioperative anxiety, pain, patient satisfaction, and medication usage during port implantation under local anesthesia., Methods: A total of 120 patients undergoing elective port implantation between January 2022 and August 2023 were enrolled and randomized in a 1:1 ratio to either a VR hypnosedation group or a control group. The VR group used a commercially available VR headset with the HypnoVR application, providing various environments, musical backgrounds, and a guiding voice, while the control group underwent the procedure without VR. Patients with ASA > 3, chronic pain, cognitive issues, and contraindications against VR use were excluded. The main outcomes measured were perioperative pain and anxiety scores, with secondary outcomes including perioperative medication usage. Due to the nature of the interventions, blinding of patients and physicians was not feasible. Statistical analysis was primarily descriptive and exploratory, focusing on estimating effect sizes for future trials., Results: The study found no significant differences in immediate postoperative pain with 1.43 ± 1.63 vs. 1.6 ± 2.05 (p = 0.62) or anxiety scores 30.65 ± 9.13 vs. 31.78 ± 13.34 (p = 0.60) between the no VR and VR group, respectively. Additionally, there was a trend to less usage of certain medications, particularly remifentanil (mean dose of 200 mg vs. 100 mg (p = 0.12)) and novaminsulfon (mean dose of 1250 mg vs. 900 mg (p = 0.26)) in the VR group vs. no VR group, respectively. However, these differences were not statistically significant and therefore no definitive conclusions can be drawn regarding medication usage based on this data., Conclusion: While VR hypnosedation did not significantly reduce perioperative pain or anxiety in this pilot trial, the observed trends in reduced medication usage suggest potential benefits. These findings warrant further investigation in larger, confirmatory trials to better understand the role of VR in enhancing patient comfort and potentially reducing reliance on pharmacological interventions during surgical procedures., Trial Registration: German Clinical Trials Register: DRKS00028508; registration date 15 March 2022; Universal Trial Number: U1111-1275-4995., (© 2024. The Author(s).)

Background : The diagnosis and follow-up of cardiac involvement in Fabry disease constitutes an important challenge for clinicians caring for affected patients. Combining cardiac imaging with laboratory biomarkers appears most appropriate for longitudinal monitoring. Therefore, we examined the use of NT-proBNP and its association with imaging findings in patients with Fabry disease. Methods : We analysed cardiac MRI and echocardiography data, as well as laboratory results, from a single-centre prospective registry. Results : Repetitive follow-ups of 38 patients with Fabry disease, of whom 18 presented with left ventricular hypertrophy (LVH), revealed a correlation of NT-proBNP with left ventricular (LV) interventricular septal thickness, LV maximum wall thickness, LV and right ventricular (RV) mass index and trabecular mass in patients with LVH. Patients without LVH did not exhibit any tangible association between NT-proBNP and the mentioned parameters. Conversely, we could not detect an association of NT-proBNP with impairment of LV or RV ejection fraction or diastolic volume. Conclusions : NT-proBNP plays a pivotal role as a biomarker for cardiac involvement in patients with Fabry disease. Interestingly, in this specific population with mostly preserved ejection fraction, it seems to reflect ventricular hypertrophy rather than ventricular dysfunction or dilatation. While strong associations were found in hypertrophic patients, NT-proBNP's prognostic value appears limited in non- or pre-hypertrophic stages.

Fabry disease (FD) constitutes a rare, X-linked lysosomal storage disorder affecting multiple organ systems, most notably heart, kidneys, and the central nervous system. Neurofilament light chains (NfL) have emerged as a prime candidate for a body fluid biomarker reflecting neuro-axonal injury. We aimed to evaluate its addition to the diagnostic and monitoring armamentarium in FD. Serum NfL concentrations (sNfL) were measured in 50 people with FD (PwFD) and 30 healthy control subjects (HC) using the Simoa© technology, followed by calculation of Z-scores adjusted for age and body mass index. In addition, clinical disease severity in PwFD was measured using the FOS-MSSI (Fabry outcome study - Mainz severity score index), which comprises clinical and paraclinical parameters. PwFD show elevated sNfL Z-scores compared to HC (PwFD: 1.12 [SD 1.5], HC: 0.01 [SD 1.2], p < 0.001). In PwFD, males showed higher sNfL Z-scores than females (1.75 [SD 1.5] vs. 0.73 [SD 1.4]). Importantly, sNfL Z-scores were increased in PwFD with ischemic white matter lesions of the CNS (1.5, SD 2.2 vs. 0.5, SD 2.9, p = 0.03). In our small cohort, sNfL Z-scores correlated fairly with FOS-MSSI (Kendall's-Tau [τ] = 0.25, p = 0.01), and, interestingly with serum creatinine (τ = 0.28, p = 0.005) and estimated glomerular filtration rate (eGFR, τ =-0.28, p = 0.005). Based on these exploratory results, sNfL might provide value as a biomarker of neuroaxonal damage in FD, possibly reflecting cerebrovascular injury. Additionally, the correlation of sNfL with renal function warrants further investigation., (© 2024. The Author(s).)

Purpose: In this study, the objectification of the subjective perception of loudness was investigated using electroencephalography (EEG). In particular, the emergence of objective markers in the domain of the acoustic discomfort threshold was examined., Methods: A cohort of 27 adults with normal hearing, aged between 18 and 30, participated in the study. The participants were presented with 500 ms long noise stimuli via in-ear headphones. The acoustic signals were presented with sound levels of [55, 65, 75, 85, 95 dB]. After each stimulus, the subjects provided their subjective assessment of the perceived loudness using a colored scale on a touchscreen. EEG signals were recorded, and afterward, event-related potentials (ERPs) locked to sound onset were analyzed., Results: Our findings reveal a linear dependency between the N100 component and both the sound level and the subjective loudness categorization of the sound. Additionally, the data demonstrated a nonlinear relationship between the P300 potential and the sound level as well as for the subjective loudness rating. The P300 potential was elicited exclusively when the stimuli had been subjectively rated as "very loud" or "too loud"., Conclusion: The findings of the present study suggest the possibility of the identification of the subjective uncomfortable loudness level by objective neural parameters., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Combined [ 18 F]FDG PET-cardiac MRI imaging (PET/CMR) is a useful tool to assess myocardial viability and cardiac function in patients with acute myocardial infarction (AMI). Here, we evaluated the prognostic value of PET/CMR in a porcine closed-chest reperfused AMI (rAMI) model. Late gadolinium enhancement by PET/CMR imaging displayed tracer uptake defect at the infarction site by 3 days after the rAMI in the majority of the animals (group Match, n = 28). Increased [ 18 F]FDG uptake at the infarcted area (metabolism/contractility mismatch) with reduced tracer uptake in the remote viable myocardium (group Mismatch, n = 12) 3 days after rAMI was observed in the animals with larger infarct size and worse left ventricular ejection fraction (LVEF) (34 ± 8.7 vs 42.0 ± 5.2%), with lower LVEF also at the 1-month follow-up (35.8 ± 9.5 vs 43.0 ± 6.3%). Transcriptome analyses by bulk and single-nuclei RNA sequencing of the infarcted myocardium and border zones (n = 3 of each group, and 3 sham-operated controls) revealed a strong inflammatory response with infiltration of monocytes and macrophages in the infarcted and border areas in Mismatch animals. Our data indicate a high prognostic relevance of combined PET/MRI in the subacute phase of rAMI for subsequent impairment of heart function and underline the adverse effects of an excessive activation of the innate immune system in the initial phase after rAMI., (© 2024. The Author(s).)

Rationale: Approximately 80% of patients with non-familial pulmonary arterial hypertension (PAH) lack identifiable pathogenic genetic variants. While most genetic studies of PAH have focused on predicted loss-of-function variants, recent approaches have identified ultra-rare missense variants associated with the disease. FOXF1 encodes a highly conserved transcription factor, essential for angiogenesis and vasculogenesis in human and mouse lungs., Objectives: We identified a rare FOXF1 missense coding variant in two unrelated probands with PAH. FOXF1 is an evolutionarily conserved transcription factor required for lung vascular development and vascular integrity. Our aims were to determine the frequency of FOXF1 variants in larger PAH cohorts compared to the general population, study FOXF1 expression in explanted lung tissue from PAH patients versus control (failed-donor) lungs, and define potential downstream targets linked to PAH development., Methods: Three independent, international, multicenter cohorts were analyzed to evaluate the frequency of FOXF1 rare variants. Various composite prediction models assessed the deleteriousness of individual variants. Bulk RNA sequencing datasets from human explanted lung tissues were compared to failed-donor controls to determine FOXF1 expression. Bioinformatic tools identified putative FOXF1 binding targets, which were orthogonally validated using mouse ChIP-seq datasets., Measurements and Main Results: Seven novel or ultra-rare missense coding variants were identified across three patient cohorts in different regions of the FOXF1 gene, including the DNA binding domain. FOXF1 expression was dysregulated in PAH lungs, correlating with disease severity. Histological analysis showed heterogeneous FOXF1 expression, with the lowest levels in phenotypically abnormal endothelial cells within complex vascular lesions in PAH samples. A hybrid bioinformatic approach identified FOXF1 downstream targets potentially involved in PAH pathogenesis, including BMPR2 ., Conclusions: Large genomic and transcriptomic datasets suggest that decreased FOXF1 expression or predicted dysfunction is associated with PAH.

Introduction: Major urological tumor surgery entails a severe risk of unexpected adverse events, persistent functional deterioration, and death in older patients. The Erlangen Index (EI) geriatric assessment tool has previously been shown to predict incomplete functional recovery following major urological tumor surgery in an elderly patient collective. We prospectively evaluated assessment tools including EI in a multicenter setting., Materials and Methods: A total of 340 patients over the age of 65 were assessed prospectively before and after cystectomy, prostatectomy, or renal tumor surgery at three academic centers in Germany and Austria. Endpoints were long-term functional deterioration (Activities of daily living (ADL) measured by Barthel-Index) at day 30 and day 180, and mortality at day 180., Results: In this study 58 (17.0 %) patients underwent cystectomy, 140 (41.2 %) prostatectomy and 142 (41.8 %) a kidney tumor operation. Mean age was 74.8 years. ADL impairment as a measure of incomplete recovery at day 30 and 180 after surgery were recorded in 47.6 % and 37.4 % of cases, respectively. The EI showed good sensitivity for mortality at day 180 (reference cohort: 85 %, validation center 1: 100 %, validation center 2: 50 %) and for ADL impairment at day 180 (reference cohort 75.4 %, validation center 1 72.3 %, validation center 2 83.3 %)., Conclusion: Elderly patients with a poor performance status have a high risk of persistent functional deterioration. Data from this multicenter external validation trial confirms the EI as an accurate and reliable tool to identify patients with high risk of mortality or persistent postoperative functional impairment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

EBV-positive primary nodal T-cell/NK cell lymphoma (TNKL) is a rare diagnosis with a poor prognosis. No relationship with follicular lymphoma (FL), classic Hodgkin lymphoma (cHL), or other non-Hodgkin lymphomas is established. We describe a case of Epstein-Barr virus (EBV)-positive cHL and EBV-positive primary nodal TNKL in the background of an antecedent FL, with all 3 subtypes identified in a single lymph node biopsy from an immunocompetent patient. Intensive frontline therapy achieved only a temporary response, with subsequent rapid progression associated with hemophagocytic lymphohistiocytosis (HLH). We discuss the relationship of the three lymphoma subtypes and the potential roles of EBV and immune dysregulation as contributing factors to this previously undescribed composite lymphoma., Competing Interests: The authors declare that they have are no conflicts of interest., (Copyright © 2024 Suravi Raychaudhuri et al.)

Background: Heart transplantation with donation after circulatory death and ex-situ heart perfusion offers excellent outcomes and increased transplantation rates. However, improved graft evaluation techniques are required to ensure effective utilization of grafts. Therefore, we investigated circulating factors, both in-situ and ex-situ, as potential biomarkers for cardiac graft quality., Methods: Circulatory death was simulated in anesthetized male pigs with warm ischemic durations of 0, 10, 20, or 30 minutes. Hearts were explanted and underwent ex-situ perfusion for 3 hours in an unloaded mode, followed by left ventricular loading for 1 hour, to evaluate cardiac recovery (outcomes). Multiple donor blood and ex-situ perfusate samples were used for biomarker evaluation with either standard biochemical techniques or nuclear magnetic resonance spectroscopy., Results: Circulating adrenaline, both in the donor and at 10 minutes ex-situ heart perfusion, negatively correlated with cardiac recovery (p < 0.05 for all). We identified several new potential biomarkers for cardiac graft quality that can be measured rapidly and simultaneously with nuclear magnetic resonance spectroscopy. At multiple timepoints during unloaded ex-situ heart perfusion, perfusate levels of acetone, betaine, creatine, creatinine, fumarate, hypoxanthine, lactate, pyruvate and succinate (p < 0.05 for all) significantly correlated with outcomes; the optimal timepoint being 60 minutes., Conclusions: In heart donation after circulatory death, circulating adrenaline levels are valuable for cardiac graft evaluation. Nuclear magnetic resonance spectroscopy is of particular interest, as it measures multiple metabolites in a short timeframe. Improved biomarkers may allow more precision and therefore better support clinical decisions about transplantation suitability., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives/hypothesis: The respiratory process is important in vocal training and in professional singing, the airflow is highly important. It is hypothesized that subglottal resonances are important to the singing voice in high performance singing., Study Design: Single subject, prospective., Method: A professional soprano singer shaped her vocal tract to form the vowels [a], [e], [i], [o], and [u] at the pitch d4. We measured phonated vowels and the vocal tract impedance spectra with a deterministic noise supplied by an iPhone buzzer in the range of 200 to 4,000 Hz at closed glottis, during exhalation and during inhalation while maintaining the shape of the vocal tract., Results: Measurements of the phonated vowels before and after the different glottal adjustments were highly reproducible. Vocal tract resonances and the ones resulting during respiration are reported. The impedance spectra show vowel dependent resonances with closed and open glottis. The formants of the vocal spectra are explained by including both, the vocal tract, and the subglottal resonances., Conclusion: The findings indicate that subglottal resonances influence the first formant as well as the singers's formant cluster in high-performance singing. The instrumental setup used for the impedance measurement allows a simple and lightweight procedure for a measurement of vocal tract and subglottal resonances., (Copyright © 2022 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: The goal of the study was to determine the short- and long-term outcome of health-related quality of life (HRQoL) in adults implanted with a Vibrant Soundbridge (VSB)., Methods: Twenty-one adults (8 females, 13 males; mean age at implantation: 57 ±10 years) who received a unilateral VSB for combined or conductive hearing loss, were administered two questionnaires: the Nijmegen Cochlear Implant Questionnaire (NCIQ) as a measure of hearing-specific HRQoL, and the Health Utility Index 3 (HUI 3) as a measure of generic HRQoL. The questionnaires were administered before implantation and three, six, 12 and 24 months after processor activation., Results: The NCIQ total score raised significantly from 62 points before implantation to 76 points at three months after processor activation (p < 0.005). Thereafter, no significant increases occurred anymore. The HUI 3 multi-attribute score (MAUS) increased from 0.59 before implantation to 0.70 at three months and at six months after processor activation and then declined slightly to 0.68 at 24 months after processor activation. Similar values were observed with the HUI 3 single-attribute score (SAUS) of Hearing. The increases of the HUI 3 scores were not statistically significant, but all pre-post-implantation differences were clinically relevant., Discussion: VSB recipients experienced a quick improvement of their HRQoL. After just three months of device use, a significant improvement of hearing-specific HRQoL and a clinically relevant improvement of generic HRQoL were seen. After three months, no essential changes of HRQoL occurred in our sample, suggesting that the achieved level of HRQoL may remain stable in the long term., (© 2024. The Author(s).)

The excellent versatility of 5-axis computer numerical control (CNC) micromilling has led to its application for prototyping NMR microcoils tailored to mass-limited samples (reducing development time and cost). However, vibrations during 5-axis milling can hinder the creation of complex 3D volume microcoils (i.e., solenoids and saddle coils). To address these limitations, a high-resolution NSCNC ELARA 4-axis milling machine was developed with the extra precision required for making complex 3D volume microcoils. Upon investigating the performance of resonators made with various copper-coated dielectrics, resonators with poly(methyl methacrylate) (PMMA) provided the best SNR/line shape. Thus, complex 1.7 mm microcoil designs were machined from Cu-coated PMMA. A milled 6.4 mm solenoid also provided 6.6× the total carbon signal for a 13 C-labeled broccoli seed compared to a commercial inverse 5 mm NMR probe (demonstrating potential for larger coil designs). However, the manufacture of coils <1.7 mm with copper-coated PMMA rods was challenging as ∼0.5 mm of remaining PMMA was needed to retain their structural integrity. To manufacture smaller microcoils, both a solenoid and saddle coil (both with 1 mm O.D., 0.1 mm thick walls) were etched from Cu-coated glass capillaries using a UV picosecond laser that was mounted onto an NSCNC 5-axis MiRA7L. Both resonators showed excellent signal and identified a wide range of metabolites in a 13 C-labeled algae extract, while the solenoid was further tested on two copepod egg sacs (∼4 μg of total sample). In summary, the flexibility to prototype complex microcoils in-house allows laboratories to tailor microcoils to specific mass-limited samples while avoiding the costs of cleanrooms.

Aquaculture is expected to play a vital role in solving the challenge of sustainably providing the growing world population with healthy and nutritious food. Pathogen outbreaks are a major risk for the sector, so early detection and a timely response are crucial. This can be enabled by monitoring the pathogen levels in aquaculture facilities. This paper describes a photonic biosensing platform based on silicon nitride waveguide technology with integrated active components, which could be used for such applications. Compared to the state of the art, the current system presents improvements in terms of miniaturization of the Photonic Integrated Circuit (PIC) and the development of wafer-level processes for hybrid integration of active components and for material-selective chemical and biological surface modification. Furthermore, scalable processes for integrating the PIC in a microfluidic cartridge were developed, as well as a prototype desktop readout instrument. Three bacterial aquaculture pathogens ( Aeromonas salmonicida , Vagococcus salmoninarum , and Yersinia ruckeri ) were selected for assay development. DNA biomarkers were identified, corresponding primer-probe sets designed, and qPCR assays developed. The biomarker for Aeromonas was also detected using the hybrid PIC platform. This is the first successful demonstration of biosensing on the hybrid PIC platform.

Purpose: To evaluate the diagnostic performance (DP) of the high-resolution contrast computed tomography (HR-contrast-CT) based Neck-Persistency-Net in distinguishing vital from non-vital persistent cervical lymph nodes (pcLNs) in patients with advanced head and neck squamous cell carcinoma (HNSCC) following primary concurrent chemoradiotherapy (CRT) with [18F]-fluorodeoxyglucose positron emission tomography and high-resolution contrast-enhanced computed tomography ([18F]FDG-PET-CT). Furthermore, the Neck-Persistency-Net's potential to justify omitting post-CRT neck dissection (ND) without risking treatment delays or preventing unnecessary surgery was explored., Methods: All HNSCC patients undergoing primary CRT followed by post-CRT-ND for pcLNs recorded in the institutional HNSCC registry were analyzed. The Neck-Persistency-Net DP was explored for three scenarios: balanced performance (BalPerf), optimized sensitivity (OptSens), and optimized specificity (OptSpec). Histopathology of post-CRT-ND served as a reference., Results: Among 68 included patients, 11 were female and 32 had vital pcLNs. The Neck-Persistency-Net demonstrated good DP with an area under the curve of 0.82. For BalPerf, both sensitivity and specificity were 78%; for OptSens (90%), specificity was 62%; for OptSpec (95%), sensitivity was 54%. Limiting post-CRT-ND to negative results would have delayed treatment in 27%, 40%, and 7% for BalPerf, OptSens and OptSpec, respectively, versus 23% for [18F]FDG-PET-CT. Conversely, restricting post-CRT-ND to positive results would have prevented unnecessary post-CRT-ND in 78%, 60%, and 95% for BalPerf, OptSens and OptSpec, respectively, versus 55% for [18F]FDG-PET-CT., Conclusion: The DP of the Neck-Persistency-Net was comparable to [18F]-FDG-PET-CT. Depending on the chosen decision boundary, the potential to justify the omission of post-CRT-ND without risking treatment delays in false negative findings or reliably prevent unnecessary surgery in false positive findings outperforms the [18F]-FDG-PET-CT., (© 2024. The Author(s).)

Competing Interests: The authors declare that they have no conflict of interest.

Background: During donation after circulatory death (DCD), cardiac grafts are exposed to potentially damaging conditions that can impact their quality and post-transplantation outcomes. In a clinical DCD setting, patients have closed chests in most cases, while many experimental models have used open-chest conditions. We therefore aimed to investigate and characterize differences in open- vs. closed-chest porcine models., Methods: Withdrawal of life-sustaining therapy (WLST) was simulated in anesthetized juvenile male pigs by stopping mechanical ventilation following the administration of a neuromuscular block. Functional warm ischemic time (fWIT) was defined to start when systolic arterial pressure was <50 mmHg. Hemodynamic changes and blood chemistry were analyzed. Two experimental groups were compared: (i) an open-chest group with sternotomy prior to WLST and (ii) a closed-chest group with sternotomy after fWIT., Results: Hemodynamic changes during the progression from WLST to fWIT were initiated by a rapid decline in blood oxygen saturation and a subsequent cardiovascular hyperdynamic (HD) period characterized by temporary elevations in heart rates and arterial pressures in both groups. Subsequently, heart rate and systolic arterial pressure decreased until fWIT was reached. Pigs in the open-chest group displayed a more rapid transition to the HD phase after WLST, with peak heart rate and peak rate-pressure product occurring significantly earlier. Furthermore, the HD phase duration tended to be shorter and less intense (lower peak rate-pressure product) in the open-chest group than in the closed-chest group., Discussion: Progression from WLST to fWIT was more rapid, and the hemodynamic changes tended to be less pronounced in the open-chest group than in the closed-chest group. Our findings support clear differences between open- and closed-chest models of DCD. Therefore, recommendations for clinical DCD protocols based on findings in open-chest models must be interpreted with care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Hubacher, Egle, Graf, Arnold, Segiser, Sanz, Casoni, Garcia Casalta, Nettelbeck, Mihalj, Siepe, Kadner and Longnus.)

Purpose: Even though workflow analysis in the operating room has come a long way, current systems are still limited to research. In the quest for a robust, universal setup, hardly any attention has been given to the dimension of audio despite its numerous advantages, such as low costs, location, and sight independence, or little required processing power., Methodology: We present an approach for audio-based event detection that solely relies on two microphones capturing the sound in the operating room. Therefore, a new data set was created with over 63 h of audio recorded and annotated at the University Hospital rechts der Isar. Sound files were labeled, preprocessed, augmented, and subsequently converted to log-mel-spectrograms that served as a visual input for an event classification using pretrained convolutional neural networks., Results: Comparing multiple architectures, we were able to show that even lightweight models, such as MobileNet, can already provide promising results. Data augmentation additionally improved the classification of 11 defined classes, including inter alia different types of coagulation, operating table movements as well as an idle class. With the newly created audio data set, an overall accuracy of 90%, a precision of 91% and a F1-score of 91% were achieved, demonstrating the feasibility of an audio-based event recognition in the operating room., Conclusion: With this first proof of concept, we demonstrated that audio events can serve as a meaningful source of information that goes beyond spoken language and can easily be integrated into future workflow recognition pipelines using computational inexpensive architectures., (© 2024. The Author(s).)

Uterine diseases are main indications for antibiotic use in dairy cows. To test a non-antibiotic treatment option, we compared the effect of an intrauterine cephapirin (Metricure®; cefapirin benzathin 500 mg per dosis; CEPH) with an intrauterine applied herbal product (25 ml of EucaComp® PlantaVet containing alcoholic extracts of Calendula officinalis L., Mellissa officinalis L., Origanum majorana L. and Eucalyptus globulus Labill. (EUC)) on the clinical cure of endometritis. Examinations of 816 cows between 21 and 35 days after calving were performed and cases of clinical endometritis (n = 169) were included. Diagnosis based on a scoring system for vaginal discharge. Study animals were randomly assigned to one of two treatment groups and treated immediately. After excluding animals with incomplete datasets, 136 cows (EUC: n = 61; CEPH: n = 75) remained for the final analysis. In total, 64% (EUC: 61%, CEPH: 67%) of analysed endometritis cases were considered as clinically cured 14 ± 2 days after the first treatment, 15% stayed uncured after the application of a maximum of two consecutive treatments, leading to an overall clinical cure rate of 85% (EUC: 82%, CEPH: 88%). No statistically difference in clinical cure rates could be observed between both treatment groups nor 14 ± 2 days after the first treatment (p = 0.956) neither regarding the overall cure rate (p = 0.923). In conclusion, the clinical cure of dairy cows' endometritis after the intrauterine application of the herbal product was non-inferior to the intrauterine application of the antibiotic cephapirin. These results could contribute to reduce the antimicrobial use in the daily veterinary routine treatment of endometritis., Competing Interests: Declaration of competing interest The study was funded by SaluVet GmbH. The funding institution was neither involved in data collection nor in data analysis. Two authors are staff of SaluVet GmbH., (Copyright © 2023. Published by Elsevier Ltd.)

The number of tracheotomized patients with dysphagia and their need for treatment are continuously increasing in clinical and community settings. The revised version of the directive on home care and community-based intensive care of the Federal Joint Committee (G-BA) requires that tracheotomized patients are regularly evaluated with the aim of identifying and promoting the therapeutic potential after hospital discharge. Dysphagia treatment plays a crucial role as without improvement of severe dysphagia there is practically no possibility for decannulation. Tracheotomized patients with dysphagia are treated by speech and language therapists (SLT); however, the contents of tracheostomy management (TM) are not obligatory in the speech and language therapeutic training curricula, so that there is a need for further education and treatment standards must be secured. Therefore, the German Interdisciplinary Society for Dysphagia (DGD) in cooperation with the participating German medical and therapeutic societies developed a postgraduate curriculum for TM. This should serve as the basis for contents in TM and qualification of therapists within the framework of the delegation of medical services. The goals of the TM curriculum are the definition of theoretical and practical contents of TM, the qualification to perform TM according to current standards of care and quality assurance. The curriculum defines two qualification levels (user and trainer), entry requirements, curricular contents, examination and qualification criteria as well as transitional regulations for SLTs already experienced in TM., (© 2024. The Author(s).)

A light-driven dual and ternary catalytic aza-Wacker protocol for the construction of 3-pyrrolines by partially disulfide-assisted selenium-π-acid multicatalysis is reported. A structurally diverse array of sulfonamides possessing homopolar mono-, di- and trisubstituted olefinic double bonds is selectively converted to the corresponding 3-pyrrolines in up to 95 % isolated yield and with good functional group tolerance. Advanced electrochemical mechanistic investigations of the protocol suggest a dual role of the disulfide co-catalyst. On the one hand, the disulfide serves as an electron hole shuttle between the excited photoredox catalyst and the selenium co-catalyst. On the other hand, the sulfur species engages in the final, product releasing step of the catalytic cycle by accelerating the β-elimination of the selenium moiety, which was found in many cases to lead to considerably improved product yields., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Due to the drastically rising coronavirus disease (COVID-19) incidence since March 2020, social life was shut down across the globe, and most opera houses were closed. As a result, there are limited data on SARS-CoV-2 infections among artists. The Bavarian State Opera has been reopened in September 2020. This study aimed to identify the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among employees in the Bavarian State Opera. In addition, the various hygiene strategies for the work groups within the institution are described. During the study period from September 1, 2020 to July 31, 2021, 10,061 nasopharyngeal swabs were obtained from 1,460 artistic staff members in a rolling system. During the entire study period, 61 individuals tested positive for SARS-CoV-2. None of the patients had a severe disease course. Compared to the seven-day-incidence per 100,000 German inhabitants, the estimated corresponding incidence among employees was lower at 37 weeks and higher or equal at 9 weeks. Among the infected individuals, 58.3% were symptomatic, 23.3% were presymptomatic, and 18.3% were asymptomatic. Forty-five percent of employees reported that they had been infected in their private environment, 41.7% suspected that their colleagues were the main contact, and 13.3% were unsure about the origin of their infection. Twenty-four diseased employees were ballet dancers, eight from the orchestra, seven from the administration, seven from the choir singers, six from the costume department, 10 from technical support, and one guest solo singer. In the 2020/2021 theater season, increased SARS-CoV-2 infections and large disease outbreaks were avoided at the Bavarian State Opera. Hygiene strategies, that existed since the beginning, was specifically designed for various work areas in the opera. Regular, mandatory PCR testing and follow-up of positive cases with the issuance of quarantine were performed. Using this disease management approach, artistic work at and reopening of the Bavarian State Opera was feasible with a well-controlled risk., Competing Interests: DECLARATIONS OF INTEREST COI: Funded by the BMBF via the Network University Medicine (NUM), project B-FAST to UP and GS CDS reports grants, personal fees and non-financial support from Braun Melsungen, grants, personal fees and non-financial support from Braun Melsungen, grants, personal fees and non-financial support from Gilead Sciences, grants and personal fees from Janssen-Cilag, personal fees from Eli Lilly, personal fees from Formycon, other from Apeiron, grants and personal fees from MSD, grants from Cepheid, personal fees from GSK, personal fees from Molecular partners, other from Eli Lilly, during the conduct of the study; personal fees from AbbVie, personal fees from MSD, grants and personal fees from ViiV Healthcare, outside the submitted work. AMC reports research support, clinical study grants, fees for advisory boards speaker honoraria and other via Technical University Munich (TUM) from ALK-Abello, Allergopharma, ASIT Biotech, AstraZeneca, Bencard/Allergen Therapeutics, European Institute of Technology (EIT Health), German Federal Ministry of Education and Research, GSK, Immunotek, LETI, Lofarma, Novartis, Regeneron Pharmaceuticals Inc., Roche, Sanofi Genzyme, Zeller outside the submitted work. UP reports grants from ALiOS and VirBio, and personal fees from AbbVie, Arbutus, Gilead, GSK, Johnson & Johnson, Roche, Sobi, and Vaccitech, outside the study. UP is co-founder and shareholder of SCG Cell BW reports grants from: Astra Zeneca, Novartis, Cassella Med, Repha Pharma, fees for advisory boards speaker honoraria: MSD, BMS, ROCHE, Astra Zeneca,personal fees from: MSD, BMS, ROCHE, Astra Zeneca, Sanofi, Novartis outside the submitted work SG reports Pharma fees for advisory boards speaker honoraria: Biogen, from outside the submitted work., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac donation after circulatory death is a promising option to increase graft availability. Graft preservation with 30 minutes of hypothermic oxygenated perfusion (HOPE) before normothermic machine perfusion may improve cardiac recovery as compared with cold static storage, the current clinical standard. We investigated the role of preserved nitric oxide synthase activity during HOPE on its beneficial effects., Methods and Results: Using a rat model of donation after circulatory death, hearts underwent in situ ischemia (21 minutes), were explanted for a cold storage period (30 minutes), and then reperfused under normothermic conditions (60 minutes) with left ventricular loading. Three cold storage conditions were compared: cold static storage, HOPE, and HOPE with Nω-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor). To evaluate potential confounding effects of high coronary flow during early reperfusion in HOPE hearts, bradykinin was administered to normalize coronary flow to HOPE levels in 2 additional groups (cold static storage and HOPE with Nω-nitro-L-arginine methyl ester). Cardiac recovery was significantly improved in HOPE versus cold static storage hearts, as determined by cardiac output, left ventricular work, contraction and relaxation rates, and coronary flow ( P <0.05). Furthermore, HOPE attenuated postreperfusion calcium overload. Strikingly, the addition of Nω-nitro-L-arginine methyl ester during HOPE largely abolished its beneficial effects, even when early reperfusion coronary flow was normalized to HOPE levels., Conclusions: HOPE provides superior preservation of ventricular and vascular function compared with the current clinical standard. Importantly, HOPE's beneficial effects require preservation of nitric oxide synthase activity during the cold storage. Therefore, the application of HOPE before normothermic machine perfusion is a promising approach to optimize graft recovery in donation after circulatory death cardiac grafts.

To attract and retain a more diverse workforce, organizations embrace diversity initiatives, expressed in diversity statements on their websites. While the explicit content of diversity statements influences attitudes towards organizations, much less is known about the effect of subtle cues such as emotions. In three pre-registered studies, we tested the effect of positive emotionality in diversity statements on attitudes towards organizations. Study 1 focused on the degree to which 600 European organizations employed emotionality in their diversity statements, finding that although their statements differed in the level of emotionality, on average, organizations avoided highly emotional words. Study 2 (N = 220 UK participants) tested the effect of original diversity statements on readers' attitudes towards an organization, demonstrating that the level of emotionality in the existing statements did not influence positive attitudes towards the organization. In Study 3 (N = 815 UK participants), we thus modified the diversity statements so that they contained high levels of positive emotionality that triggered more positive emotions and resulted in more positive attitudes towards an organization. Taken together, highly emotional words (e.g. passionate; happy; wholeheartedly) are key in diversity statements if organizations wish to increase their attractiveness among potential employees., (© 2023 British Psychological Society.)

Conditions to which the cardiac graft is exposed during transplantation with donation after circulatory death (DCD) can trigger the recruitment of macrophages that are either unpolarized (M0) or pro-inflammatory (M1) as well as the release of extracellular vesicles (EV). We aimed to characterize the effects of M0 and M1 macrophage-derived EV administration on post-ischaemic functional recovery and glucose metabolism using an isolated rat heart model of DCD. Isolated rat hearts were subjected to 20 min aerobic perfusion, followed by 27 min global, warm ischaemia or continued aerobic perfusion and 60 min reperfusion with or without intravascular administration of EV. Four experimental groups were compared: (1) no ischaemia, no EV; (2) ischaemia, no EV; (3) ischaemia with M0-macrophage-dervied EV; (4) ischaemia with M1-macrophage-derived EV. Post-ischaemic ventricular and metabolic recovery were evaluated. During reperfusion, ventricular function was decreased in untreated ischaemic and M1-EV hearts, but not in M0-EV hearts, compared to non-ischaemic hearts (p < 0.05). In parallel with the reduced functional recovery in M1-EV versus M0-EV ischaemic hearts, rates of glycolysis from exogenous glucose and oxidative metabolism tended to be lower, while rates of glycogenolysis and lactate release tended to be higher. EV from M0- and M1-macrophages differentially affect post-ischaemic cardiac recovery, potentially by altering glucose metabolism in a rat model of DCD. Targeted EV therapy may be a useful approach for modulating cardiac energy metabolism and optimizing graft quality in the setting of DCD., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Purpose of Review: This review aims to outline some consequences that maternal history of trauma with and without related psychopathology, such as posttraumatic stress symptoms (PTSS), can have on their children's development and functioning. It then addresses mechanisms through which intergenerational transmission of interpersonal violence (IPV) and related psychopathology may occur., Recent Findings: Findings include the effects of maternal IPV experience and related psychopathology on child social-emotional and biologically-based outcomes. This includes increased developmental disturbances and child psychopathology, as well as physiological factors. Secondly, the review focuses on psychobiological mechanisms by which maternal experience of IPV and related psychopathology likely trigger intergenerational effects. Maternal IPV and related psychopathology can have a negative impact on several areas of their child's life including development, interactive behavior, psychopathology, and physiology. This transmission may partially be due to fetal and perinatal processes, genetic and epigenetic effects, and interactions with their parents., (© 2024. The Author(s).)

Background: Gout is the most common cause of inflammatory arthritis worldwide, particularly in Pacific regions. We aimed to establish the prevalence of gout and hyperuricaemia in French Polynesia, their associations with dietary habits, their comorbidities, the prevalence of the HLA-B*58:01 allele, and current management of the disease., Methods: The Ma'i u'u survey was epidemiological, prospective, cross-sectional, and gout-focused and included a random sample of adults from the general adult population of French Polynesia. It was conducted and data were collected between April 13 and Aug 16, 2021. Participants were randomly selected to represent the general adult population of French Polynesia on the basis of housing data collected during the 2017 territorial census. Each selected household was visited by a research nurse from the Ma'i u'u survey who collected data via guided, 1-h interviews with participants. In each household, the participant was the individual older than 18 years with the closest upcoming birthday. To estimate the frequency of HLA-B*58:01, we estimated HLA-B haplotypes on individuals who had whole-genome sequencing to approximately 5× average coverage (mid-pass sequencing). A subset of individuals who self-reported Polynesian ancestry and not European, Chinese, or other ancestry were used to estimate Polynesian-ancestry specific allele frequencies. Bivariate associations were reported for weighted participants; effect sizes were estimated through the odds ratio (OR) of the association calculated on the basis of a logistic model fitted with weighted observations., Findings: Among the random sample of 2000 households, 896 participants were included, 140 individuals declined, and 964 households could not be contacted. 22 participants could not be weighted due to missing data, so the final weighted analysis included 874 participants (449 [51·4%] were female and 425 [48·6%] were male) representing the 196 630 adults living in French Polynesia. The estimated prevalence of gout was 14·5% (95% CI 9·9-19·2), representing 28 561 French Polynesian adults, that is 25·5% (18·2-32·8) of male individuals and 3·5% (1·0-6·0) of female individuals. The prevalence of hyperuricaemia was estimated at 71·6% (66·7-76·6), representing 128 687 French Polynesian adults. In multivariable analysis, age (OR 1·5, 95% CI 1·2-1·8 per year), male sex (10·3, 1·8-60·7), serum urate (1·6, 1·3-2·0 per 1 mg/dL), uraturia (0·8, 0·8-0·8 per 100 mg/L), type 2 diabetes (2·1, 1·4-3·1), BMI more than 30 kg/m 2 (1·1, 1·0-1·2 per unit), and percentage of visceral fat (1·7, 1·1-2·7 per 1% increase) were associated with gout. There were seven heterozygous HLA-B*58:01 carriers in the full cohort of 833 individuals (seven [0·4%] of 1666 total alleles) and two heterozygous carriers in a subset of 696 individuals of Polynesian ancestry (two [0·1%])., Interpretation: French Polynesia has an estimated high prevalence of gout and hyperuricaemia, with gout affecting almost 15% of adults. Territorial measures that focus on increasing access to effective urate-lowering therapies are warranted to control this major public health problem., Funding: Variant Bio, the French Polynesian Health Administration, Lille Catholic University Hospitals, French Society of Rheumatology, and Novartis., Competing Interests: Declaration of interests TP receives honorary fees from Novartis and a research grant (DREAMER grant) for the conduct of this study and consulting fees from Horizon Pharmaceuticals. KAW, SLvB, SEC, A-KE, and LY-A are employees and stock owners of Variant Bio. LY-A is a stock owner of GlaxoSmithKline. ND has received consulting fees, speaker fees, or grants from AstraZeneca, Novartis, Dyve Biosciences, Horizon, Selecta, Arthrosi, JW Pharmaceutical, PK Med, LG Chem, Al-Jazeera Pharmaceutical Industries, PTC Therapeutics, Protalix, Unlocked Labs, and Hikma. TM has research contracts from Variant Bio. TB has received consulting fees from Novartis. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Quantitative susceptibility mapping (QSM) has attracted considerable interest for tissue characterization (e.g., iron and calcium accumulation, myelination, venous vasculature) in the human brain and relies on extensive data processing of gradient-echo MRI phase images. While deep learning-based field-to-susceptibility inversion has shown great potential, the acquisition parameters applied in clinical settings such as image resolution or image orientation with respect to the magnetic field have not been fully accounted for. Furthermore, the lack of comprehensive training data covering a wide range of acquisition parameters further limits the current QSM deep learning approaches. Here, we propose the integration of a priori information of imaging parameters into convolutional neural networks with our approach, adaptive convolution, that learns the mapping between the additional presented information (acquisition parameters) and the changes in the phase images associated with these varying acquisition parameters. By associating a-priori information with the network parameters itself, the optimal set of convolution weights is selected based on data-specific attributes, leading to generalizability towards changes in acquisition parameters. Moreover, we demonstrate the feasibility of pre-training on synthetic data and transfer learning to clinical brain data to achieve substantial improvements in the computation of susceptibility maps. The adaptive convolution 3D U-Net demonstrated generalizability in acquisition parameters on synthetic and in-vivo data and outperformed models lacking adaptive convolution or transfer learning. Further experiments demonstrate the impact of the side information on the adaptive model and assessed susceptibility map computation on simulated pathologic data sets and measured phase data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Graf, Wohlgemuth and Deistung.)

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions., (© 2024. The Author(s).)

Purpose of Review: Management of stone disease in pregnancy poses a challenge for all healthcare professionals involved in their care. During pregnancy, there is an increase in the incidence of urolithiasis. Major technological and procedural advances have been seen in the last decade for endoscopic management of urolithiasis. The purpose of this review is to provide a comprehensive workup of available literature on use of ureteroscopy for stone treatment during pregnancy., Recent Findings: We identified 268 articles on screening, of which 28 were included in the final review. Overall adverse event rates were low, with no severe complications reported in the included studies. On multivariate analysis, the only significant correlation was an inverse relationship between calculated caseload and adverse obstetric events. No further correlation could be found between caseload, operation technique and adverse event rates. Data quality was low among the included studies., Summary: While ureteroscopy is a relatively safe and effective option for active stone treatment during pregnancy, they should be performed in experienced endourology centres in conjunction with obstetric teams., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

High-throughput transcriptomics is of increasing fundamental biological and clinical interest. The generation of molecular data from large collections of samples, such as biobanks and drug libraries, is boosting the development of new biomarkers and treatments. Focusing on gene expression, the transcriptomic market exploits the benefits of next-generation sequencing (NGS), leveraging RNA sequencing (RNA-seq) as standard for measuring genome-wide gene expression in biological samples. The cumbersome sample preparation, including RNA extraction, conversion to cDNA and amplification, prevents high-throughput translation of RNA-seq technologies. Bulk RNA barcoding and sequencing (BRB-seq) addresses this limitation by enabling sample preparation in multi-well plate format. Sample multiplexing combined with early pooling into a single tube reduces reagents consumption and manual steps. Enabling simultaneous pooling of all samples from the multi-well plate into one tube, our technology relies on smart labware: a pooling lid comprising fluidic features and small pins to transport the liquid, adapted to standard 96-well plates. Operated with standard fluidic tubes and pump, the system enables over 90% recovery of liquid in a single step in less than a minute. Large scale manufacturing of the lid is demonstrated with the transition from a milled polycarbonate/steel prototype into an injection molded polystyrene lid. The pooling lid demonstrated its value in supporting high-throughput barcode-based sequencing by pooling 96 different DNA barcodes directly from a standard 96-well plate, followed by processing within the single sample pool. This new pooling technology shows great potential to address medium throughput needs in the BRB-seq workflow, thereby addressing the challenge of large-scale and cost-efficient sample preparation for RNA-seq., (© 2024. The Author(s).)

The emergence of COVID-19 dramatically changed social behavior across societies and contexts. Here we study whether social norms also changed. Specifically, we study this question for cultural tightness (the degree to which societies generally have strong norms), specific social norms (e.g. stealing, hand washing), and norms about enforcement, using survey data from 30,431 respondents in 43 countries recorded before and in the early stages following the emergence of COVID-19. Using variation in disease intensity, we shed light on the mechanisms predicting changes in social norm measures. We find evidence that, after the emergence of the COVID-19 pandemic, hand washing norms increased while tightness and punishing frequency slightly decreased but observe no evidence for a robust change in most other norms. Thus, at least in the short term, our findings suggest that cultures are largely stable to pandemic threats except in those norms, hand washing in this case, that are perceived to be directly relevant to dealing with the collective threat., (© 2024. The Author(s).)

Background: Few methicillin-resistant Staphylococcus aureus (MRSA) from the early years of its global emergence have been sequenced. Knowledge about evolutionary factors promoting the success of specific MRSA multi-locus sequence types (MLSTs) remains scarce. We aimed to characterize a legacy MRSA collection isolated from 1965 to 1987 and compare it against publicly available international and local genomes., Methods: We accessed 451 historic (1965-1987) MRSA isolates stored in the Culture Collection of Switzerland, mostly collected from the Zurich region. We determined phenotypic antimicrobial resistance (AMR) and performed whole genome sequencing (WGS) using Illumina short-read sequencing on all isolates and long-read sequencing on a selection with Oxford Nanopore Technology. For context, we included 103 publicly available international assemblies from 1960 to 1992 and sequenced 1207 modern Swiss MRSA isolates from 2007 to 2022. We analyzed the core genome (cg)MLST and predicted SCCmec cassette types, AMR, and virulence genes., Results: Among the 451 historic Swiss MRSA isolates, we found 17 sequence types (STs) of which 11 have been previously described. Two STs were novel combinations of known loci and six isolates carried previously unsubmitted MLST alleles, representing five new STs (ST7843, ST7844, ST7837, ST7839, and ST7842). Most isolates (83% 376/451) represented ST247-MRSA-I isolated in the 1960s, followed by ST7844 (6% 25/451), a novel single locus variant (SLV) of ST239. Analysis by cgMLST indicated that isolates belonging to ST7844-MRSA-III cluster within the diversity of ST239-MRSA-III. Early MRSA were predominantly from clonal complex (CC)8. From 1980 to the end of the twentieth century, we observed that CC22 and CC5 as well as CC8 were present, both locally and internationally., Conclusions: The combined analysis of 1761 historic and contemporary MRSA isolates across more than 50 years uncovered novel STs and allowed us a glimpse into the lineage flux between Swiss-German and international MRSA across time., (© 2024. The Author(s).)

Objectives: Very little is known on the efficacy and safety of drugs for the management of chronic calcium pyrophosphate (CPP) crystal inflammatory arthritis. The objectives of this work were to describe the drugs used in the management of chronic CPP crystal inflammatory arthritis in expert European centres, and to examine treatment retention., Methods: This was a retrospective cohort study. Charts from patients with a diagnosis of persistent inflammatory and/or recurrent acute CPP crystal arthritis were reviewed in seven European centres. Baseline characteristics were collected, and visits at months 3, 6, 12 and 24 included an assessment of treatment response and safety., Results: One hundred and ninety-four treatments were initiated in 129 patients. Colchicine (used first-line in n = 73/86), methotrexate (used first-line in n = 14/36), anakinra (n = 27) and tocilizumab (n = 25) were the most prescribed treatments, while long-term corticosteroids, hydroxychloroquine, canakinumab and sarilumab were used occasionally. The 24-month on-drug retention was higher for tocilizumab (40%) than anakinra (18.5%) (P < 0.05), while the difference between colchicine (29.1%) and methotrexate (44.4%) was not statistically significant (P = 0.10). Adverse events led to 14.1% of colchicine discontinuations (100% of diarrhoea), 4.3% for methotrexate, 31.8% for anakinra and 20% for tocilizumab; all other discontinuations were related to insufficient response or losses to follow-up. Efficacy outcomes did not differ significantly between treatments throughout follow-up., Conclusion: Daily colchicine is the first-line therapy used in chronic CPP crystal inflammatory arthritis, which is considered efficient in a third to half of cases. Second-line treatments include methotrexate and tocilizumab, which have higher retention than anakinra., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Hypoxic reprogramming of vasculature relies on genetic, epigenetic, and metabolic circuitry, but the control points are unknown. In pulmonary arterial hypertension (PAH), a disease driven by hypoxia inducible factor (HIF)-dependent vascular dysfunction, HIF-2α promoted expression of neighboring genes, long noncoding RNA (lncRNA) histone lysine N -methyltransferase 2E-antisense 1 ( KMT2E-AS1 ) and histone lysine N-methyltransferase 2E ( KMT2E ). KMT2E-AS1 stabilized KMT2E protein to increase epigenetic histone 3 lysine 4 trimethylation (H3K4me3), driving HIF-2α-dependent metabolic and pathogenic endothelial activity. This lncRNA axis also increased HIF-2α expression across epigenetic, transcriptional, and posttranscriptional contexts, thus promoting a positive feedback loop to further augment HIF-2α activity. We identified a genetic association between rs73184087, a single-nucleotide variant (SNV) within a KMT2E intron, and disease risk in PAH discovery and replication patient cohorts and in a global meta-analysis. This SNV displayed allele (G)-specific association with HIF-2α, engaged in long-range chromatin interactions, and induced the lncRNA-KMT2E tandem in hypoxic (G/G) cells. In vivo, KMT2E-AS1 deficiency protected against PAH in mice, as did pharmacologic inhibition of histone methylation in rats. Conversely, forced lncRNA expression promoted more severe PH. Thus, the KMT2E-AS1 /KMT2E pair orchestrates across convergent multi-ome landscapes to mediate HIF-2α pathobiology and represents a key clinical target in pulmonary hypertension.

The human microbiome has emerged as a rich source of diverse and bioactive natural products, harboring immense potential for therapeutic applications. To facilitate systematic exploration and analysis of its biosynthetic landscape, we present ABC-HuMi: the Atlas of Biosynthetic Gene Clusters (BGCs) in the Human Microbiome. ABC-HuMi integrates data from major human microbiome sequence databases and provides an expansive repository of BGCs compared to the limited coverage offered by existing resources. Employing state-of-the-art BGC prediction and analysis tools, our database ensures accurate annotation and enhanced prediction capabilities. ABC-HuMi empowers researchers with advanced browsing, filtering, and search functionality, enabling efficient exploration of the resource. At present, ABC-HuMi boasts a catalog of 19 218 representative BGCs derived from the human gut, oral, skin, respiratory and urogenital systems. By capturing the intricate biosynthetic potential across diverse human body sites, our database fosters profound insights into the molecular repertoire encoded within the human microbiome and offers a comprehensive resource for the discovery and characterization of novel bioactive compounds. The database is freely accessible at https://www.ccb.uni-saarland.de/abc&#95;humi/., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)