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Many symbionts are sexually transmitted and impact their host's development, ecology, and evolution. While the significance of symbionts that cause sexually transmitted diseases (STDs) is relatively well understood, the prevalence and potential significance of the sexual transmission of mutualists remain elusive. Here, we study the effects of sexually transmitted mutualist nematodes on their dung beetle hosts. Symbiotic Diplogastrellus monhysteroides nematodes are present on the genitalia of male and female Onthophagus beetles and are horizontally transmitted during mating and vertically passed on to offspring during oviposition. A previous study indicates that the presence of nematodes benefits larval development and life history in a single host species, Onthophagus taurus. However, Diplogastrellus nematodes can be found in association with a variety of beetle species. Here, we replicate these previous experiments, assess whether the beneficial effects extend to other host species, and test whether nematode-mediated effects differ between male and female host beetles. Rearing three relatively distantly related dung beetle species with and without nematodes, we find that the presence of nematodes benefits body size, but not development time or survival across all three species. Likewise, we found no difference in the benefit of nematodes to male compared to female beetles. These findings highlight the role of sexually transmitted mutualists in the evolution and ecology of dung beetles.

Many organisms actively manipulate the environment in ways that feed back on their own development, a process referred to as developmental niche construction. Yet, the role that constructed biotic and abiotic environments play in shaping phenotypic variation and its evolution is insufficiently understood. Here, we assess whether environmental modifications made by developing dung beetles impact the environment-sensitive expression of secondary sexual traits. Gazelle dung beetles both physically modify their ontogenetic environment and structure their biotic interactions through the vertical inheritance of microbial symbionts. By experimentally eliminating (i) physical environmental modifications and (ii) the vertical inheritance of microbes, we assess the degree to which (sym)biotic and physical environmental modifications shape the exaggeration of several traits varying in their degree and direction of sexual dimorphism. We expected the experimental reduction of a larva's ability to shape its environment to affect trait size and scaling, especially for traits that are sexually dimorphic and environmentally plastic. We find that compromised developmental niche construction indeed shapes sexual dimorphism in overall body size and the absolute sizes of male-limited exaggerated head horns, the strongly sexually dimorphic fore tibia length and width, as well as the weakly dimorphic elytron length and width. This suggests that environmental modifications affect sex-specific phenotypic variation in functional traits. However, most of these effects can be attributed to nutrition-dependent plasticity in size and non-isometric trait scaling rather than body-size-independent effects on the developmental regulation of trait size. Our findings suggest that the reciprocal relationship between developing organisms, their symbionts, and their environment can have considerable impacts on sexual dimorphism and functional morphology.

Volatile organic compounds (VOCs) and volatile inorganic compounds (VICs) provide critical information across many scientific fields including atmospheric chemistry and soil and biological processes. Chemical ionization (CI) mass spectrometry has become a powerful tool for tracking these chemically complex and temporally variable compounds in a variety of laboratory and field environments. It is particularly powerful with time-of-flight mass spectrometers, which can measure hundreds of compounds in a fraction of a second and have enabled entirely new branches of VOC and/or VIC research in atmospheric and biological chemistry. To accurately describe each step of these chemical, physical, and biological processes, measurements across the entire range of gaseous products is crucial. Recently, chemically comprehensive gas-phase measurements have been performed using many CI mass spectrometers deployed in parallel, each utilizing a different ionization method to cover a broad range of compounds. Here we introduce the recently developed Vocus AIM (adduct ionization mechanism) ion–molecule reactor (IMR), which samples trace vapors in air and ionizes them via chemical ionization at medium pressures. The Vocus AIM supports the use of many different reagent ions of positive and negative polarity and is largely independent of changes in the sample humidity. Within the present study, we present the performance and explore the capabilities of the Vocus AIM using various chemical ionization schemes, including chloride (Cl−), bromide (Br−), iodide (I−), nitrate (NO3-), benzene cations (C6H6+), acetone dimers ((C3H6O)2H+), and ammonium (NH4+) reagent ions, primarily in laboratory and flow tube experiments. We report the technical characteristics and operational principles, and compare its performance in terms of time response, humidity dependence, and sensitivity to that of previous chemical ionization approaches. This work demonstrates the benefits of the Vocus AIM reactor, which provides a versatile platform to characterize VOCs and VICs in real time at trace concentrations.

Abstract Purpose The implementation of artificial intelligence (AI) in health care is gaining popularity. Many publications describe powerful AI-enabled algorithms. Yet there’s only scarce evidence for measurable value in terms of patient outcomes, clinical decision-making or socio-economic impact. Our aim was to investigate the significance of AI in the emergency treatment of wrist trauma patients. Method Two groups of physicians were confronted with twenty realistic cases of wrist trauma patients and had to find the correct diagnosis and provide a treatment recommendation. One group was assisted by an AI-enabled application which detects and localizes distal radius fractures (DRF) with near-to-perfect precision while the other group had no help. Primary outcome measurement was diagnostic accuracy. Secondary outcome measurements were required time, number of added CT scans and senior consultations, correctness of the treatment, subjective and objective stress levels. Results The AI-supported group was able to make a diagnosis without support (no additional CT, no senior consultation) in significantly more of the cases than the control group (75% vs. 52%, p = 0.003). The AI-enhanced group detected DRF with superior sensitivity (1.00 vs. 0.96, p = 0.06) and specificity (0.99 vs. 0.93, p = 0.17), used significantly less additional CT scans to reach the correct diagnosis (14% vs. 28%, p = 0.02) and was subjectively significantly less stressed (p = 0.05). Conclusion The results indicate that physicians can diagnose wrist trauma more accurately and faster when aided by an AI-tool that lessens the need for extra diagnostic procedures. The AI-tool also seems to lower physicians' stress levels while examining cases. We anticipate that these benefits will be amplified in larger studies as skepticism towards the new technology diminishes.

Nutrition-dependent growth of sexual traits is a major contributor to phenotypic diversity, and a large body of research documents insulin signalling as a major regulator of nutritional plasticity. However, findings across studies raise the possibility that the role of individual components within the insulin signalling pathway diverges in function among traits and taxa. Here, we use RNAi-mediated transcript depletion in the gazelle dung beetle to investigate the functions of forkhead box O (Foxo) and two paralogs of the insulin receptor (InR1 and InR2) in shaping nutritional plasticity in polyphenic male head horns, exaggerated fore legs, and weakly nutrition-responsive genitalia. Our functional genetic manipulations led to three main findings: FoxoRNAi reduced the length of exaggerated head horns in large males, while neither InR1 nor InR2 knock-downs resulted in measurable horn phenotypes. These results are similar to those documented previously for another dung beetle (Onthophagus taurus), but in stark contrast to findings in rhinoceros beetles. Secondly, knockdown of Foxo, InR1, and InR2 led to an increase in the intercept or slope of the scaling relationship of genitalia size. These findings are in contrast even to results documented previously for O. taurus. Lastly, while FoxoRNAi reduces male forelegs in D. gazella and O. taurus, the effects of InR1 and InR2 knockdowns diverged across dung beetle species. Our results add to the growing body of literature indicating that despite insulin signalling's conserved role as a regulator of nutritional plasticity, the functions of its components may diversify among traits and species, potentially fuelling the evolution of scaling relationships.

Abstract Background The incidence of fragility fractures of the pelvis is rising. Whereas the treatment for FFP type I, III, and IV is clear, the optimal treatment for FFP type II remains a topic of discussion. Traditionally these fractures have been treated conservatively. However, there is a shift toward early surgical stabilization with percutaneous screw fixation to reduce pain and promote mobility in an already frail patient population. High-quality evidence, however, is lacking. Therefore, a randomized clinical trial was designed to compare conservative management to early percutaneous screw fixation in patients with type II fragility fractures. Methods This is a monocenter randomized controlled trial. All patients with a FFP type II are screened for inclusion. After obtaining informed consent, patients are randomized between conservative management and surgical stabilization. Conservative management consists of early mobilization under guidance of physiotherapy and analgesics. Patients randomized for surgical treatment are operated on within 72 h using percutaneous screw fixation. The primary endpoint is mobility measured by the DEMMI score. Secondary endpoints are other dimensions of mobility, pain levels, quality of life, mortality, and morbidity. The total follow-up is 1 year. The required sample size is 68. Discussion The present study aims to give certainty on the potential benefit of surgical treatment. Current literature on this topic remains unclear. According to the volume of FFP at the study hospital, we assume that the number of patients needed for this study is gathered within 2 years. Trial registration ClinicalTrials.gov NCT04744350. Registered on February 8, 2021.

Abstract Background Technology-based assessments using 2D virtual reality (VR) environments and goal-directed instrumented tasks can deliver digital health metrics describing upper limb sensorimotor function that are expected to provide sensitive endpoints for clinical studies. Open questions remain about the influence of the VR environment and task complexity on such metrics and their clinimetric properties. Methods We aim to investigate the influence of VR and task complexity on the clinimetric properties of digital health metrics describing upper limb function. We relied on the Virtual Peg Insertion Test (VPIT), a haptic VR-based assessment with a virtual manipulation task. To evaluate the influence of VR and task complexity, we designed two novel tasks derived from the VPIT, the VPIT-2H (VR environment with reduced task complexity) and the PPIT (physical task with reduced task complexity). These were administered in an observational longitudinal study with 27 able-bodied participants and 31 participants with multiple sclerosis (pwMS, VPIT and PPIT only) and the value of kinematic and kinetic metrics, their clinimetric properties, and the usability of the assessment tasks were compared. Results Intra-participant variability strongly increased with increasing task complexity (coefficient of variation + 56%) and was higher in the VR compared to the physical environment (+ 27%). Surprisingly, this did not translate into significant differences in the metrics’ measurement error and test–retest reliability across task conditions (p > 0.05). Responsiveness to longitudinal changes in pwMS was even significantly higher (effect size + 0.35, p

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

Abstract Introduction Courier delivery has become a popular antiretroviral therapy (ART) distribution method in some HIV care settings, yet data on ART courier delivery and how it relates to ART outcomes are scarce. We studied the differences in viral suppression rates between individuals from a South African private sector HIV programme receiving ART by courier delivery and those receiving ART through traditional retail dispensing. Methods Individuals aged 15 years or older who were actively enrolled in the Aid for AIDS programme between January 2011 and July 2022 were eligible for the analysis. The outcome of interest was viral suppression defined as a viral load (VL)

Background Accumulating evidence suggests that cardiac findings after stroke are an important, yet understudied, manifestation of brain–heart interactions. Our aim was to investigate and compare cardiac findings after different cerebrovascular events (acute ischemic stroke, transient ischemic attack, and hemorrhagic stroke). Methods and Results There were 7113 patients screened who were treated between December 2013 and December 2020 at the University Hospital Zurich for ischemic stroke, transient ischemic attack, and hemorrhagic stroke. Seven hundred twenty‐one patients without evidence of previous cardiac disease or presumed cardioembolic origin of their cerebrovascular disease and with at least 1 cardiac checkup were included. Clinical reports from the year following disease onset were screened for new cardiac findings, which were categorized as arrhythmia/electrocardiographic changes, myocardial alterations, valvular abnormalities, and coronary perfusion insufficiency. Differences in proportions of findings among groups were analyzed using the Pearson χ2 test or Fisher exact test. ECG changes were observed in 81.7% (n=474) of patients with ischemic stroke, 71.4% (n=70) of patients with transient ischemic attack, and 55.8% (n=24) of patients with hemorrhagic stroke (P

Pancreatic ductal adenocarcinoma (PDAC) poses a significant threat due to its tendency to evade early detection, frequent metastasis, and the subsequent challenges in devising effective treatments. Processes that govern epithelial-mesenchymal transition (EMT) in PDAC hold promise for advancing novel therapeutic strategies. SAMD1 (SAM domain-containing protein 1) is a CpG island-binding protein that plays a pivotal role in the repression of its target genes. Here, we revealed that SAMD1 acts as a repressor of genes associated with EMT. Upon deletion of SAMD1 in PDAC cells, we observed significantly increased migration rates. SAMD1 exerts its effects by binding to specific genomic targets, including CDH2, encoding N-cadherin, which emerged as a driver of enhanced migration upon SAMD1 knockout. Furthermore, we discovered the FBXO11-containing E3 ubiquitin ligase complex as an interactor and negative regulator of SAMD1, which inhibits SAMD1 chromatin-binding genome-wide. High FBXO11 expression in PDAC is associated with poor prognosis and increased expression of EMT-related genes, underlining an antagonistic relationship between SAMD1 and FBXO11. In summary, our findings provide insights into the regulation of EMT-related genes in PDAC, shedding light on the intricate role of SAMD1 and its interplay with FBXO11 in this cancer type.

Key message Evolving societal demands and accelerated ecological dynamics due to global change are rapidly altering forest ecosystems and their services. This has prompted the need for advancing forest inventorying and monitoring initatives to expand their scope, improve data collection, foster scientific understanding, and better inform policy responses. Here, we discuss the collaborative processes followed to develop an Advanced Inventorying and Monitoring (AIM) system for Swiss forests. Further, we provide the key messages that emerged from this process which can be of interest to those involved in similar processes at the national/international level.

BackgroundPrevious studies have observed that haemoglobin concentrations can be affected by type of blood collection, analysis methods and device, and that near-in-time population-based surveys report substantially different anaemia prevalence. We investigated whether differences in mean haemoglobin or prevalence of anaemia between near-in-time surveys of the same population were associated with differences in type of blood collection or analytic approach to haemoglobin measurement.MethodsWe systematically identified pairs of population-based surveys that measured haemoglobin in the same population of women of reproductive age (WRA) or preschool-aged children (PSC). Surveys were matched on geographic coverage, urban/rural place of residence, inclusion of pregnant women, time of data collection (within 18 months), and, to the extent feasible, age range. Differences in anaemia prevalence were presented graphically. Random-effects meta-analysis and meta-regression of difference in mean haemoglobin were carried out, with subgroups defined by comparison of type of blood collection and analytic approach within each survey pair.ResultsWe included 23 survey pairs from 17 countries for PSC and 17 survey pairs from 11 countries for WRA. Meta-regression indicates that surveys measuring haemoglobin with HemoCue® Hb 301 found higher haemoglobin concentrations than near-in-time surveys using HemoCue® Hb 201+ in non-pregnant women ((NPW); 5.8 g/L (95% confidence interval (CI) = 3.2-8.3) mean difference, n = 5 pairs) and PSC (4.3 g/L (1.4-7.2), n = 6). Surveys collecting venous blood found higher haemoglobin concentrations than near-in-time surveys collecting capillary blood in PSC (3.8 g/L (0.8-6.7), n = 8), but not NPW (0.4 g/L (-1.9-2.8), n = 9).ConclusionsBecause this study is observational, differences in haemoglobin concentrations in near-in-time surveys may be caused by other factors associated with choice of analytic approach or type of blood collected. The source or sources of differences should be clarified to improve use of surveys to prioritize and evaluate public health programs.RegistrationPROSPERO CRD42022296553.

Early-life adversity (ELA) and recent stress experiences are relevant explanatory factors in the understanding of health differences across the life span. However, their particular role in explaining the vast health heterogeneity in older adulthood has yet to be defined. To address this gap, this study examined (a) the health of older individuals with differing levels of ELA and recent stressful experiences; and (b) the type (i.e., linear, curvilinear) of the expected stress-health relationships. Longitudinal quantitative data were collected on health, ELA, and stressful life experiences of the previous 21 months in N = 216 participants ( M age = 69.8 years, 45.8% female). Findings support linear (rather than curvilinear) stress-health relationships for ELA and recent stress with physical and mental health. Furthermore, ELA significantly moderated the relationship between recent stress and physical illnesses. As the detrimental health impact of ELA can still be detected in older adulthood, ELA may be critical for understanding later life health heterogeneity.

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

ABSTRACTDuring the SARS-CoV-2 pandemic, many countries directed substantial resources toward genomic surveillance to detect and track viral variants. There is a debate over how much sequencing effort is necessary in national surveillance programs for SARS-CoV-2 and future pandemic threats. We aimed to investigate the effect of reduced sequencing on surveillance outcomes in a large genomic data set from Switzerland, comprising more than 143k sequences. We employed a uniform downsampling strategy using 100 iterations each to investigate the effects of fewer available sequences on the surveillance outcomes: (i) first detection of variants of concern (VOCs), (ii) speed of introduction of VOCs, (iii) diversity of lineages, (iv) first cluster detection of VOCs, (v) density of active clusters, and (vi) geographic spread of clusters. The impact of downsampling on VOC detection is disparate for the three VOC lineages, but many outcomes including introduction and cluster detection could be recapitulated even with only 35% of the original sequencing effort. The effect on the observed speed of introduction and first detection of clusters was more sensitive to reduced sequencing effort for some VOCs, in particular Omicron and Delta, respectively. A genomic surveillance program needs a balance between societal benefits and costs. While the overall national dynamics of the pandemic could be recapitulated by a reduced sequencing effort, the effect is strongly lineage-dependent—something that is unknown at the time of sequencing—and comes at the cost of accuracy, in particular for tracking the emergence of potential VOCs.IMPORTANCESwitzerland had one of the most comprehensive genomic surveillance systems during the COVID-19 pandemic. Such programs need to strike a balance between societal benefits and program costs. Our study aims to answer the question: How would surveillance outcomes have changed had we sequenced less? We find that some outcomes but also certain viral lineages are more affected than others by sequencing less. However, sequencing to around a third of the original effort still captured many important outcomes for the variants of concern such as their first detection but affected more strongly other measures like the detection of first transmission clusters for some lineages. Our work highlights the importance of setting predefined targets for a national genomic surveillance program based on which sequencing effort should be determined. Additionally, the use of a centralized surveillance platform facilitates aggregating data on a national level for rapid public health responses as well as post-analyses.

Literature has widely explored the learning processes with information and communication technology (ICT) in later life, mostly focusing on the individual learner rather than materialities--such as smartphones, notepads, and handouts. The aim of this paper is to introduce a socio-material perspective by focusing on the question: What role do materialities play in digital learning processes in later life? This paper draws upon a situation analysis of data from a qualitative multi-perspective study. Researchers conducted participatory observations of five ICT courses for older adults in Austria and semi-structured interviews with seven trainers and nine older participants (61-81 years). By identifying three social worlds (digital devices, education, and participants' everyday lives), the findings show how ICT-learning processes are embedded in the everyday lives of older adults and include not only digital, but also everyday materialities, such as pens, paper and books. These material convoys of digital learning in later life are vital in facilitating successful technology appropriation in later life.

BackgroundIn the presence of inflammation, the serum or plasma ferritin concentration ("ferritin" hereafter) transiently increases, confounding its interpretation as an iron status marker. The extent to which adiposity-related inflammation may influence ferritin interpretation is uncertain.ObjectivesWe describe relationships between weight status, inflammation, and ferritin among nonpregnant women of reproductive age (WRA; 15-49 years) and preschool-age children (PSC; 6-59 months) with normal weight to overweight or obesity (OWOB) in differing geographic settings.MethodsCross-sectional data were separately analyzed from 18 surveys (WRA) and 25 surveys (PSC) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project, excluding observations with underweight, wasting, pregnancy, or malaria. Relationships were assessed between BMI (in WRA) or BMI-for-age z-score (BAZ; in PSC), inflammatory biomarkers of C-reactive protein (CRP) and/or α-1-acid glycoprotein (AGP), ferritin by linear regression, and potential mediation by CRP and/or AGP in relationships between BMI or BAZ and ferritin with structural equation modeling. Regression and mediation models accounted for complex survey designs. Results were grouped by World Bank income classifications.ResultsIn 5 of 6 surveys among WRA from upper-middle and high-income countries, ferritin was significantly positively associated with BMI, and this relationship was partially (or fully, in the United States) mediated by CRP and/or AGP. Mediation was present in 4 of 12 surveys for WRA in low- and lower-middle income countries. Among PSC, ferritin was positively associated with CRP and/or AGP in all surveys, but there were no significant CRP- or AGP-mediated relationships between ferritin and BAZ, except a negative relationship in the Philippines.ConclusionsWhere having OWOB is common among WRA, measurements of inflammatory biomarkers and their uses in interpreting ferritin may improve iron status assessments. While these relationships were inconsistent among PSC, inflammation was common and should be measured to interpret iron status. Included Kenyan trial data are registered at clinicaltrials.gov as NCT01088958.

Integrated Motor Drives (IMDs) are gaining popularity in industrial Variable Speed Drive (VSD) applications, thanks to their more compact realization and simpler installation. However, mission profiles of, e.g., servo applications, demand overload torques of two to three times the nominal value during several seconds, which is thermally challenging for the power electronics. Accordingly, high efficiency and power density of the inverter are of paramount importance for motor integration. Multi-Level Flying Capacitor inverters (ML-FCis) benefit from a reduced output filter volume and improved switching and on-state performance of low-voltage devices for increasing number of levels $N$ , whereas the PCB overhead and gate drive volume increases. In this paper, the most power dense solution between a seven-level (7L) FCi with Si semiconductors and a three-level (3L) FCi with GaN semiconductors is evaluated. Thereby, a straightforward design procedure allows to dimension both FCis for 99% efficiency at nominal operation, while providing a high short-term overload torque (three times the nominal torque) also for low inverter output frequencies. Due to its slightly higher power density and greatly reduced complexity, a phase module of the 3L GaN FCi is realized as an IMD hardware demonstrator. A transient thermal model is employed to specify the feasible overload operating range, considering the limited heat spreading in the baseplate and parameter variations, e.g., from manufacturing tolerances. The experimental analysis of the demonstrator verifies an efficiency of 98.94% and the practically required overload capability.

The rapid development of digital technologies and their increasing application in many areas of everyday life challenge all citizens to continuously learn digital skills. This also applies to older adults, among whom digital literacy is on average less well-developed than among younger adults. This article investigates why retired older adults participate in opportunities to learn digital skills. Multiple case design with both qualitative and quantitative methods was used to include the views of older adults from Austria, Finland, and Germany. The results of this interdisciplinary study indicated individual, social and technical reasons for their participation in digital skills training. Practical implications and recommendations for future studies are suggested.

Abstract The ecological and genetic changes that underlie the evolution of host–microbe interactions remain elusive, primarily due to challenges in disentangling the variables that alter microbiome composition. To understand the impact of host habitat, host genetics, and evolutionary history on microbial community structure, we examined gut microbiomes of river‐ and three cave‐adapted morphotypes of the Mexican tetra, Astyanax mexicanus, in their natural environments and under controlled laboratory conditions. Field‐collected samples were dominated by very few taxa and showed considerable interindividual variation. We found that lab‐reared fish exhibited increased microbiome richness and distinct composition compared to their wild counterparts, underscoring the significant influence of habitat. Most notably, however, we found that morphotypes reared on the same diet throughout life developed distinct microbiomes suggesting that genetic loci resulting from cavefish evolution shape microbiome composition. We observed stable differences in Fusobacteriota abundance between morphotypes and demonstrated that this could be used as a trait for quantitative trait loci mapping to uncover the genetic basis of microbial community structure.

Objectives In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial.Design This is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial.Setting 10 Swiss paediatric hospitals (secondary and tertiary care) participated.Participants Paediatric patients hospitalised with PIMS-TS.Interventions All patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event.Results Of 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like).Conclusion The masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future.Trial registration numbers SNCTP000004720 and NCT 04826588.

Abstract Many symbionts are sexually transmitted and impact their host's development, ecology, and evolution. While the significance of symbionts that cause sexually transmitted diseases (STDs) is relatively well understood, the prevalence and potential significance of the sexual transmission of mutualists remain elusive. Here, we study the effects of sexually transmitted mutualist nematodes on their dung beetle hosts. Symbiotic Diplogastrellus monhysteroides nematodes are present on the genitalia of male and female Onthophagus beetles and are horizontally transmitted during mating and vertically passed on to offspring during oviposition. A previous study indicates that the presence of nematodes benefits larval development and life history in a single host species, Onthophagus taurus. However, Diplogastrellus nematodes can be found in association with a variety of beetle species. Here, we replicate these previous experiments, assess whether the beneficial effects extend to other host species, and test whether nematode‐mediated effects differ between male and female host beetles. Rearing three relatively distantly related dung beetle species with and without nematodes, we find that the presence of nematodes benefits body size, but not development time or survival across all three species. Likewise, we found no difference in the benefit of nematodes to male compared to female beetles. These findings highlight the role of sexually transmitted mutualists in the evolution and ecology of dung beetles.

AIMS OF THE STUDY: The Eversense® CGM System is the first and only continuous glucose monitoring system (CGMS) that uses a fully subcutaneous implanted sensor. This study aimed to evaluate effectiveness, safety and patient-reported outcomes in patients using the Eversense® CGM System in a realistic clinical setting, assessed at a single Swiss diabetes centre (Luzerner Kantonsspital) with prolonged follow-up. METHODS: This was a prospective and retrospective observational study that included patients with type 1 diabetes mellitus in whom at least one Eversense® glucose sensor was implanted between 2017 and 2022. The primary endpoint was the change in HbA1c levels from the baseline (before implantation of the sensor) to 6 ± 2 and 12 ± 2 months and the last follow-up (newest available value) after implantation. The secondary outcome measures were the number of premature sensor breakdowns, adverse events related to the implantation procedure (infection, bleeding, difficulties with implantation or explantation) and patient-related outcomes (assessed with a questionnaire). RESULTS: A total of 33 patients participated in this study. The median follow-up time was 50 (IQR 22.3–58.5) months. In total, 178 sensor implantations were performed. Valid HbA1c results were available for 26 participants. Compared to the baseline values, HbA1c levels at 6 and 12 months and the last follow-up changed by –0.25%, –0.45 and –0.2 (p = 0.278, 0.308 and 0.296, respectively). We recorded 16 (9%) premature sensor breakdowns, all occurring between 2019 and 2020. Apart from one late-onset infection and four complicated sensor removals, no major complications were assessed. The results of the questionnaire showed a subjective improvement in hypoglycaemia rates, a better perception of hypoglycaemia and the impression of better diabetes management. Common issues with the device reported by the patients were technical errors (connection problems) and problems with the removal procedure. CONCLUSIONS: The use of the Eversense® CGM System resulted in changes in HbA1c of between –0.2% and –0.45%. The rate of premature sensor breakdown was low. Major complications following sensor implantation or removal were absent, apart from one case of infection and four cases of complicated removal. Patient-reported outcomes with the Eversense® CGM System showed a subjective positive impact on hypoglycaemia rates, greater confidence in managing hypoglycaemia and diabetes in general, and easy handling of the transmitter and mobile app. Technical issues must be considered but are nowadays, with the use of the newest sensor generation, very rare.