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Abstract This proof-of-concept study explores quantitative imaging of articular cartilage using photon-counting detector computed tomography (PCD-CT) with a dual-contrast agent approach, comparing it to clinical dual-energy CT (DECT). The diffusion of cationic iodinated CA4 + and non-ionic gadolinium-based gadoteridol contrast agents into ex vivo bovine medial tibial plateau cartilage was tracked over 72 h. Continuous maps of the contrast agents’ diffusion were created, and correlations with biomechanical indentation parameters (equilibrium and instantaneous moduli, and relaxation time constants) were examined at 28 specific locations. Cartilage at each location was analyzed as full-thickness to ensure a fair comparison, and calibration-based material decomposition was employed for concentration estimation. Both DECT and PCD-CT exhibit strong correlations between CA4 + content and biomechanical parameters, with PCD-CT showing superior significance, especially at later time points. DECT lacks significant correlations with gadoteridol-related parameters, while PCD-CT identifies noteworthy correlations between gadoteridol diffusion and biomechanical parameters. In summary, the experimental PCD-CT setup demonstrates superior accuracy and sensitivity in concentration estimation, suggesting its potential as a more effective tool for quantitatively assessing articular cartilage condition compared to a conventional clinical DECT scanner.

Abstract Benthic organisms typically possess a planktonic propagule stage in the form of larvae or spores, which enables them to spread over large distances before settlement, and promotes tight pelago-benthic coupling. However, factors driving dispersal and epibenthos recruitment in shallow hard-bottom Arctic communities are poorly known. We therefore conducted a year-round in situ colonization experiment in Isfjorden (Svalbard), and found out that variation in early-stage epibenthic assemblages was explained by the combination of: abiotic (45.9%) and biotic variables (23.9%), and their interactions (30.2%). The upward-facing experimental plates were dominated by coralline algae, and this is the first study showing that at high latitudes coralline algae Lithothamnion sp. settle in high numbers on available substrates during the polar night in winter. The downward-facing plates, which had much less exposure to light, contained more diverse organisms, with a predominance of polychaetas and bryozoans. However, in summer, the barnacle Semibalanus balanoides outcompeted all the other recruits, as a result of massive occurrence of meroplanktonic Cirripedia larvae, triggered by the phytoplankton bloom. In conclusion, the rate and success of epibenthic settlements were dependent mostly on light availability and temperature, suggesting that larval settlement will be impacted by global warming with some taxa benefitting, while others losing.

Abstract Force-driven cellular interactions are crucial for cancer cell invasion but remain underexplored in vascular abnormalities. Cerebral cavernous malformations (CCM), a vascular abnormality characterized by leaky vessels, involves CCM mutant cells recruiting wild-type endothelial cells to form and expand mosaic lesions. The mechanisms behind this recruitment remain poorly understood. Here, we use an in-vitro model of angiogenic invasion with traction force microscopy to reveal that hyper-angiogenic Ccm2-silenced endothelial cells enhance angiogenic invasion of neighboring wild-type cells through force and extracellular matrix-guided mechanisms. We demonstrate that mechanically hyperactive CCM2-silenced tips guide wild-type cells by transmitting pulling forces and by creating paths in the matrix, in a ROCKs-dependent manner. This is associated with reinforcement of β1 integrin and actin cytoskeleton in wild-type cells. Further, wild-type cells are reprogrammed into stalk cells and activate matrisome and DNA replication programs, thereby initiating proliferation. Our findings reveal how CCM2 mutants hijack wild-type cell functions to fuel lesion growth, providing insight into the etiology of vascular malformations. By integrating biophysical and molecular techniques, we offer tools for studying cell mechanics in tissue heterogeneity and disease progression.

Abstract In this paper, we present a comprehensive case study of a laser-based powder bed fusion-manufactured optimized filtrate nozzle, focusing on environmental impacts and benefits. The scope of the study covers the raw material production, part manufacturing and use phases. We compare the results for similar components manufactured by conventional, mainly material-removing manufacturing technologies. Primary data, measured from processes, are utilized for life cycle assessment calculations, which are completed with database data when necessary. The results show that by exploiting the design freedom of additive manufacturing, it is possible to achieve positive environmental benefits, namely, a 40% reduction in the carbon footprint during the use phase, although the manufacturing phase per se requires a similar amount or even more resources than the conventional manufacturing route. In addition to environmental benefits, we present here some other potential benefits for using optimized, additively manufactured parts.

Abstract Tropical montane forest ecosystems are pivotal for sustaining biodiversity and essential terrestrial ecosystem services, including the provision of high-quality fresh water. Nonetheless, the impact of montane deforestation and climate change on the capacity of forests to deliver ecosystem services is yet to be fully understood. In this study, we offer observational evidence demonstrating the response of air temperature and cloud base height to deforestation in African montane forests over the last two decades. Our findings reveal that approximately 18% (7.4 ± 0.5 million hectares) of Africa’s montane forests were lost between 2003 and 2022. This deforestation has led to a notable increase in maximum air temperature (1.37 ± 0.58 °C) and cloud base height (236 ± 87 metres), surpassing shifts attributed solely to climate change. Our results call for urgent attention to montane deforestation, as it poses serious threats to biodiversity, water supply, and ecosystem services in the tropics.

Abstract Sea-ice microalgae are a key source of energy and nutrient supply to polar marine food webs, particularly during spring, prior to open-water phytoplankton blooms. The nutritional quality of microalgae as a food source depends on their biomolecular (lipid:protein:carbohydrate) composition. In this study, we used synchrotron-based Fourier transform infra-red microspectroscopy (s-FTIR) to measure the biomolecular content of a dominant sea-ice taxa, Nitzschia frigida, from natural land-fast ice communities throughout the Arctic spring season. Repeated sampling over six weeks from an inner (relatively stable) and an outer (relatively dynamic) fjord site revealed high intra-specific variability in biomolecular content, elucidating the plasticity of N. frigida to adjust to the dynamic sea ice and water conditions. Environmental triggers indicating the end of productivity in the ice and onset of ice melt, including nitrogen limitation and increased water temperature, drove an increase in lipid and fatty acids stores, and a decline in protein and carbohydrate content. In the context of climate change and the predicted Atlantification of the Arctic, dynamic mixing and abrupt warmer water advection could truncate these important end-of-season environmental shifts, causing the algae to be released from the ice prior to adequate lipid storage, influencing carbon transfer through the polar marine system.

Abstract Synovial Sarcomas (SS) are characterized by the presence of the SS18::SSX fusion gene, which protein product induce chromatin changes through remodeling of the BAF complex. To elucidate the genomic events that drive phenotypic diversity in SS, we performed RNA and targeted DNA sequencing on 91 tumors from 55 patients. Our results were verified by proteomic analysis, public gene expression cohorts and single‐cell RNA sequencing. Transcriptome profiling identified three distinct SS subtypes resembling the known histological subtypes: SS subtype I and was characterized by hyperproliferation, evasion of immune detection and a poor prognosis. SS subtype II and was dominated by a vascular‐stromal component and had a significantly better outcome. SS Subtype III was characterized by biphasic differentiation, increased genomic complexity and immune suppression mediated by checkpoint inhibition, and poor prognosis despite good responses to neoadjuvant therapy. Chromosomal abnormalities were an independent significant risk factor for metastasis. KRT8 was identified as a key component for epithelial differentiation in biphasic tumors, potentially controlled by OVOL1 regulation. Our findings explain the histological grounds for SS classification and indicate that a significantly larger proportion of patients have high risk tumors (corresponding to SS subtype I) than previously believed.

Abstract Fair allocation of funding in multi-centre clinical studies is challenging. Models commonly used in Germany - the case fees (“fixed-rate model”, FRM) and up-front staffing and consumables (“up-front allocation model”, UFAM) lack transparency and fail to suitably accommodate variations in centre performance. We developed a performance-based reimbursement model (PBRM) with automated calculation of conducted activities and applied it to the cohorts of the National Pandemic Cohort Network (NAPKON) within the Network of University Medicine (NUM). The study protocol activities, which were derived from data management systems, underwent validation through standardized quality checks by multiple stakeholders. The PBRM output (first funding period) was compared among centres and cohorts, and the cost-efficiency of the models was evaluated. Cases per centre varied from one to 164. The mean case reimbursement differed among the cohorts (1173.21€ [95% CI 645.68–1700.73] to 3863.43€ [95% CI 1468.89–6257.96]) and centres and mostly fell short of the expected amount. Model comparisons revealed higher cost-efficiency of the PBRM compared to FRM and UFAM, especially for low recruitment outliers. In conclusion, we have developed a reimbursement model that is transparent, accurate, and flexible. In multi-centre collaborations where heterogeneity between centres is expected, a PBRM could be used as a model to address performance discrepancies. Trial registration: https://clinicaltrials.gov/ct2/show/NCT04768998 ; https://clinicaltrials.gov/ct2/show/NCT04747366 ; https://clinicaltrials.gov/ct2/show/NCT04679584 .

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

Abstract Tools for predicting COVID-19 outcomes enable personalized healthcare, potentially easing the disease burden. This collaborative study by 15 institutions across Europe aimed to develop a machine learning model for predicting the risk of in-hospital mortality post-SARS-CoV-2 infection. Blood samples and clinical data from 1286 COVID-19 patients collected from 2020 to 2023 across four cohorts in Europe and Canada were analyzed, with 2906 long non-coding RNAs profiled using targeted sequencing. From a discovery cohort combining three European cohorts and 804 patients, age and the long non-coding RNA LEF1-AS1 were identified as predictive features, yielding an AUC of 0.83 (95% CI 0.82–0.84) and a balanced accuracy of 0.78 (95% CI 0.77–0.79) with a feedforward neural network classifier. Validation in an independent Canadian cohort of 482 patients showed consistent performance. Cox regression analysis indicated that higher levels of LEF1-AS1 correlated with reduced mortality risk (age-adjusted hazard ratio 0.54, 95% CI 0.40–0.74). Quantitative PCR validated LEF1-AS1’s adaptability to be measured in hospital settings. Here, we demonstrate a promising predictive model for enhancing COVID-19 patient management.

Abstract Although metabolic reprogramming within tumor cells and tumor microenvironment (TME) is well described in breast cancer, little is known about how the interplay of immune state and cancer metabolism evolves during treatment. Here, we characterize the immunometabolic profiles of tumor tissue samples longitudinally collected from individuals with breast cancer before, during and after neoadjuvant chemotherapy (NAC) using proteomics, genomics and histopathology. We show that the pre-, on-treatment and dynamic changes of the immune state, tumor metabolic proteins and tumor cell gene expression profiling-based metabolic phenotype are associated with treatment response. Single-cell/nucleus RNA sequencing revealed distinct tumor and immune cell states in metabolism between cold and hot tumors. Potential drivers of NAC based on above analyses were validated in vitro. In summary, the study shows that the interaction of tumor-intrinsic metabolic states and TME is associated with treatment outcome, supporting the concept of targeting tumor metabolism for immunoregulation.

Abstract Awareness is vital for cancer prevention. US studies show a strong link between web searches and cancer incidence. In Europe, the relationship remains unclear. This study characterizes regional and temporal relationships between cancer incidence and web searches and investigates the content of searches related to breast, cervical, colorectal, lung, prostate, and testicular cancer, brain tumors, and melanoma in Germany (July 2018–December 2019). Aggregate data from Google Ads Keyword Planner and national cancer registry data were analyzed. Spearman’s correlation coefficient (r S ) examined associations between cancer incidence and web search, repeated measures correlation (r rm ) assessed time trends and searches were qualitatively categorized. The frequency of malignancy-related web searches correlated with cancer incidence (r S = 0.88, P = 0.007), e.g., breast cancer had more queries than the lower-incidence cervical cancer. Seasonally, incidence and searches followed similar patterns, peaking in spring and fall, except for melanoma. Correlations between entity incidence and searches (0.037 ≤ r rm ≤ 0.208) varied regionally. Keywords mainly focused on diagnosis, symptoms, and general information, with variations between entities. In Germany, web searches correlated with regional and seasonal incidence, revealing differences between North/East and South/West. These insights may help improve prevention strategies by identifying regional needs and assessing impact of awareness campaigns.

Abstract Fluorescence molecular imaging plays a vital role in image‐guided surgery. In this context, the urokinase plasminogen activator receptor (uPAR) is an interesting biomarker enabling the detection and delineation of various tumor types due to its elevated expression on both tumor cells and the tumor microenvironment. In this study, anti‐uPAR Nanobodies (Nbs) are generated through llama immunization with human and murine uPAR protein. Extensive in vitro characterization and in vivo testing with radiolabeled variants are conducted to assess their pharmacokinetics and select lead compounds. Subsequently, the selected Nbs are converted into fluorescent agents, and their application for fluorescence‐guided surgery is evaluated in various subcutaneous and orthotopic tumor models. The study yields a panel of high‐affinity anti‐uPAR Nbs, showing specific binding across multiple types of cancer cells in vitro and in vivo. Lead fluorescently‐labeled compounds exhibit high tumor uptake with high contrast at 1 h after intravenous injection across all assessed uPAR‐expressing tumor models, outperforming a non‐targeting control Nb. Additionally, rapid and accurate tumor localization and demarcation are demonstrated in an orthotopic human glioma model. Utilizing these Nbs can potentially enhance the precision of surgical tumor resection and, consequently, improve survival rates in the clinic.

Abstract Despite attractive cost‐effectiveness, scalability, and superior stability, carbon‐based printable perovskite solar cells (CPSCs) still face moisture‐induced degradation that limits their lifespan and commercial potential. Here, the moisture‐preventing mechanisms of thin nanostructured super‐repellent coating (advancing contact angle >167° and contact angle hysteresis 7°) integrated into CPSCs are investigated for different moisture forms (falling water droplets vs water vapor vs condensed water droplets). It is shown that unencapsulated super‐repellent CPSCs have superior performance under continuous droplet impact for 12 h (rain falling experiments) compared to unencapsulated pristine (uncoated) CPSCs that degrade within seconds. Contrary to falling water droplets, where super‐repellent coating serves as a shield, water vapor is found to physisorb through porous super‐repellent coating (room temperature and relative humidity, RH 65% and 85%) that increase the CPSCs performance for 21% during ≈43 d similarly to pristine CPSCs. It is further shown that water condensation forms within or below the super‐repellent coating (40 °C and RH 85%), followed by chemisorption and degradation of CPSCs. Because different forms of water have distinct effects on CPSC, it is suggested that future standard tests for repellent CPSCs should include rain falling and condensate formation tests. The findings will thus inspire the development of super‐repellent coatings for moisture prevention.

Abstract Open water transposition channels in hot and arid regions, like those in the São Francisco River Integration Project (PISF) in Brazil, suffer significant water losses through evaporation. This paper proposes covering these channels with photovoltaic (PV) panels to reduce evaporation while simultaneously generating clean energy. The research aims to quantify water savings and energy generation potential across all channel lengths and assess whether the generated solar power can substitute grid electricity for powering the transposition pumps during peak hours, thereby enhancing energy efficiency. This study analyzed the state-of-the-art of PV generation and calculated their solar potential. Identified the specific characteristics of PISF channels and watercourses considering the regional geography, meteorology, irradiation, and social peculiarities. And, finally, assessed the feasibility of covering the watercourses with solar panels. The results reveal that covering all current PISF channels with PV panels could save up to 25,000 cubic meters of water per day, significantly contributing to water security and improving the quality of life for the local population. Additionally, the project could generate 1200 gigawatt-hours of electricity annually, meeting the energy demands of the transposition pumps during peak hours and promoting energy efficiency within the project. This research paves the way for utilizing PV technology to address water scarcity challenges and enhance the sustainability of water infrastructure projects in arid regions worldwide.

Abstract Conditions experienced by an individual during migration have the potential to shape migratory tactic and in turn fitness. For large birds, environmental conditions encountered during migration have been linked with survival and subsequent reproductive output, but this is less known for smaller birds, hindering our understanding of mechanisms driving population change. By combining breeding and tracking data from 62 pied flycatchers (Ficedula hypoleuca) representing two breeding populations collected over 2016-2020, we determine how variation in migration phenology and tactic among individuals affects subsequent breeding. Departure date from West African non-breeding areas to European breeding grounds was highly variable among individuals and had a strong influence on migration tactic. Early departing individuals had longer spring migrations which included longer staging duration yet arrived at breeding sites and initiated breeding earlier than later departing individuals. Individuals with longer duration spring migrations and early arrival at breeding sites had larger clutches, and for males higher fledging success. We suggest that for pied flycatchers, individual carry-over effects may act through departure phenology from West Africa, and the associated spring migration duration, to influence reproduction. While our results confirm that departure date from non-breeding areas can be associated with breeding success in migratory passerines, we identify spring staging duration as a key component of this process.

Abstract Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI −1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = −0.482; 95% CI,−0.813, −0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.

Abstract X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.

Abstract COVID-19 is characterised by systemic immunological perturbations in the human body, which can lead to multi-organ damage. Many of these processes are considered to be mediated by the blood. Therefore, to better understand the systemic host response to SARS-CoV-2 infection, we performed systematic analyses of the circulating, soluble proteins in the blood through global proteomics by mass-spectrometry (MS) proteomics. Here, we show that a large part of the soluble blood proteome is altered in COVID-19, among them elevated levels of interferon-induced and proteasomal proteins. Some proteins that have alternating levels in human cells after a SARS-CoV-2 infection in vitro and in different organs of COVID-19 patients are deregulated in the blood, suggesting shared infection-related changes.The availability of different public proteomic resources on soluble blood proteome alterations leaves uncertainty about the change of a given protein during COVID-19. Hence, we performed a systematic review and meta-analysis of MS global proteomics studies of soluble blood proteomes, including up to 1706 individuals (1039 COVID-19 patients), to provide concluding estimates for the alteration of 1517 soluble blood proteins in COVID-19. Finally, based on the meta-analysis we developed CoViMAPP, an open-access resource for effect sizes of alterations and diagnostic potential of soluble blood proteins in COVID-19, which is publicly available for the research, clinical, and academic community.

Foundation species that modify their habitat can facilitate other species, including other foundation species. Most studies focus solely on a single foundation species, overlooking such facilitation cascades. In this study, we investigated the interactions between the two coastal foundation species Mytilus edulis (blue mussel) and Lanice conchilega (sand mason worm). We investigated whether these species engage in facilitative interactions or if their association simply reflects a shared ecological niche on the soft-sediment intertidal flats of the Dutch Wadden Sea. To do so, we performed species distribution modeling, manipulative field experiments, and field surveys. We found a positive association between both foundation species, with a 2.45 times higher occurrence of both species compared to a random distribution. In addition, these species partially occupied the same ecological niche. We demonstrated that L. conchilega provided settlement substrate for M. edulis spat, increasing densities by 400 times compared to bare plots. Furthermore, M. edulis reefs facilitated L. conchilega occurrence in the wake of the reef. Biogenic reef development revealed that this interspecific facilitation resulted in spatial habitat heterogeneity. Therefore, we conclude that interspecific facilitation can significantly enhance the occurrence of these two important intertidal foundation species. Acknowledgment of such complex facilitation interactions has an untapped potential for improving the success of restoration and conservation programs.

Abstract Immunoglobulin A (IgA) is acknowledged to play a role in the defence of the mucosal barrier by coating microorganisms. Surprisingly, IgA-deficient humans exhibit few infection-related complications, raising the question if the more specific IgG may help IgM in compensating for the lack of IgA. Here we employ a cohort of IgA-deficient humans, each paired with IgA-sufficient household members, to investigate multi-Ig bacterial coating. In IgA-deficient humans, IgM alone, and together with IgG, recapitulate coating of most bacterial families, despite an overall 3.6-fold lower Ig-coating. Bacterial IgG coating is dominated by IgG1 and IgG4. Single-IgG2 bacterial coating is sparse and linked to enhanced Escherichia coli load and TNF-α. Although single-IgG2 coating is 1.6-fold more prevalent in IgA deficiency than in healthy controls, it is 2-fold less prevalent than in inflammatory bowel disease. Altogether we demonstrate that IgG assists IgM in coating of most bacterial families in the absence of IgA and identify single-IgG2 bacterial coating as an inflammatory marker.

Abstract Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. As the available therapeutic options show a lack of efficacy, novel therapeutic strategies are urgently needed. Given its T-cell infiltration, we hypothesized that MPM is a suitable target for therapeutic cancer vaccination. To date, research on mesothelioma has focused on the identification of molecular signatures to better classify and characterize the disease, and little is known about therapeutic targets that engage cytotoxic (CD8+) T cells. In this study we investigate the immunopeptidomic antigen-presented landscape of MPM in both murine (AB12 cell line) and human cell lines (H28, MSTO-211H, H2452, and JL1), as well as in patients’ primary tumors. Applying state-of-the-art immuno-affinity purification methodologies, we identify MHC I-restricted peptides presented on the surface of malignant cells. We characterize in vitro the immunogenicity profile of the eluted peptides using T cells from human healthy donors and cancer patients. Furthermore, we use the most promising peptides to formulate an oncolytic virus-based precision immunotherapy (PeptiCRAd) and test its efficacy in a mouse model of mesothelioma in female mice. Overall, we demonstrate that the use of immunopeptidomic analysis in combination with oncolytic immunotherapy represents a feasible and effective strategy to tackle untreatable tumors.

Abstract The Arctic environment is transforming rapidly due to climate change. Aerosols’ abundance and physicochemical characteristics play a crucial, yet uncertain, role in these changes due to their influence on the surface energy budget through direct interaction with solar radiation and indirectly via cloud formation. Importantly, Arctic aerosol properties are also changing in response to climate change. Despite their importance, year-round measurements of their characteristics are sparse in the Arctic and often confined to lower latitudes at Arctic land-based stations and/or short high-latitude summertime campaigns. Here, we present unique aerosol microphysics and chemical composition datasets collected during the year-long Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition, in the central Arctic. These datasets, which include aerosol particle number concentrations, size distributions, cloud condensation nuclei concentrations, fluorescent aerosol concentrations and properties, and aerosol bulk chemical composition (black carbon, sulfate, nitrate, ammonium, chloride, and organics) will serve to improve our understanding of high-Arctic aerosol processes, with relevance towards improved modelling of the future Arctic (and global) climate.

Citizen science covers initiatives from crowdsourcing, distributed intelligence, and participatory science, to extreme citizen science. Terminological overlap, varied project aims, and cultural differences in the fields of research have, however, led to discord regarding how impactful citizen science projects can be. Here, we showcase a mobile application–based citizen science campaign (in Finnish: Muuttolintujen kevät), an automated bird sound classifier of Finnish birds. Over a single season (2023), the method attracted 140,000 participants who uploaded close to three million recordings containing six million bird observations. We report the spatial and temporal distribution of the observations collected, characterize the user behaviour, and discuss reliability of the user-based validations of the AI-powered species identifications. To circumvent data quality problems that characterize many citizen science projects, our approach stores the raw audio in a centralized repository, enabling rigorous validation and re-analysis. Mobile application-based citizen science initiatives can be harnessed to probe the state of our environment almost in real time and potentially guide conservation acts in the future.

The authors would like to make the following corrections to their published paper [...]

Accurate livestock counts are essential for effective pastureland management. High spatial resolution remote sensing, coupled with deep learning, has shown promising results in livestock detection. However, challenges persist, particularly when the targets are small and in a heterogeneous environment, such as those in African rangelands. This study evaluated nine state-of-the-art object detection models, four variants each from YOLOv5 and YOLOv8, and Faster R-CNN, for detecting cattle in 10 cm resolution aerial RGB imagery in Kenya. The experiment involved 1039 images with 9641 labels for training from sites with varying land cover characteristics. The trained models were evaluated on 277 images and 2642 labels in the test dataset, and their performance was compared using Precision, Recall, and Average Precision (AP0.5–0.95). The results indicated that reduced spatial resolution, dense shrub cover, and shadows diminish the model’s ability to distinguish cattle from the background. The YOLOv8m architecture achieved the best AP0.5–0.95 accuracy of 39.6% with Precision and Recall of 91.0% and 83.4%, respectively. Despite its superior performance, YOLOv8m had the highest counting error of −8%. By contrast, YOLOv5m with AP0.5–0.95 of 39.3% attained the most accurate cattle count with RMSE of 1.3 and R2 of 0.98 for variable cattle herd densities. These results highlight that a model with high AP0.5–0.95 detection accuracy may struggle with counting cattle accurately. Nevertheless, these findings suggest the potential to upscale aerial-imagery-trained object detection models to satellite imagery for conducting cattle censuses over large areas. In addition, accurate cattle counts will support sustainable pastureland management by ensuring stock numbers do not exceed the forage available for grazing, thereby mitigating overgrazing.

Abstract Since February 2022, the full-scale war in Ukraine has been strongly affecting society and economy in Ukraine and beyond. Satellite observations are crucial tools to objectively monitor and assess the impacts of the war. We combine satellite-based tropospheric nitrogen dioxide (NO2) and carbon dioxide (CO2) observations to detect and characterize changes in human activities, as both are linked to fossil fuel combustion processes. We show significantly reduced NO2 levels over the major Ukrainian cities, power plants and industrial areas: the NO2 concentrations in the second quarter of 2022 were 15–46% lower than the same quarter during the reference period 2018–2021, which is well below the typical year-to-year variability (5–15%). In the Ukrainian capital Kyiv, the NO2 tropospheric column monthly average in April 2022 was almost 60% smaller than 2019 and 2021, and about 40% smaller than 2020 (the period mostly affected by the COVID-19 restrictions). Such a decrease is consistent with the essential reduction in population and corresponding emissions from the transport and commercial/residential sectors over the major Ukrainian cities. The NO2 reductions observed in the industrial regions of eastern Ukraine reflect the decline in the Ukrainian industrial production during the war (40–50% lower than in 2021), especially from the metallurgic and chemical industry, which also led to a decrease in power demand and corresponding electricity production by thermal power plants (which was 35% lower in 2022 compared to 2021). Satellite observations of land properties and thermal anomalies indicate an anomalous distribution of fire detections along the front line, which are attributable to shelling or other intentional fires, rather than the typical homogeneously distributed fires related to crop harvesting. The results provide timely insights into the impacts of the ongoing war on the Ukrainian society and illustrate how the synergic use of satellite observations from multiple platforms can be useful in monitoring significant societal changes. Satellite-based observations can mitigate the lack of monitoring capability during war and conflicts and enable the fast assessment of sudden changes in air pollutants and other relevant parameters.

Health care education is facing common challenges of the education sector, such as ageing staff, time pressures, digitalization, and the COVID-19 pandemic. This study is part of a larger participatory international action research titled Developing Occupational Well-Being of Health Care Teachers in Estonia, 2021â2023. The objective of the study is to describe and evaluate health care teachersâ occupational well-being at the pretest phase of the action research project, as well as to describe the occupational well-being development plan and related development activities at Tallinn Health Care College. The data were collected from health care teachers by an electronical survey (n = 46, response rate 46%). The quantitative data were analysed by statistical methods and qualitative data by deductive-inductive analysis. In general, the teachers were satisfied with their physical environment. Many considered their work important, and they were also satisfied with working time arrangements. Based on the pretest results, an occupational well-being development plan was created. Improving communication and ergonomics were established as the main objectives in the development strategy. These improvement activities will be part of the collegeâs new development plan. Various activities have been planned to promote occupational well-being. These activities have already begun as seminars on communication, bullying, and ergonomics in the workplace and home office. The information can be utilized to develop long-term occupational well-being at Tallinn Health Care College. The results and good practices can enhance decision-making and education at local, regional, national, and international levels.

Abstract Prediction, prevention and treatment of virus infections require understanding of cell-to-cell variability that leads to heterogenous disease outcomes, but the source of this heterogeneity has yet to be clarified. To study the multimodal response of single human cells to herpes simplex virus type 1 (HSV-1) infection, we mapped high-dimensional viral and cellular state spaces throughout the infection using multiplexed imaging and quantitative single-cell measurements of viral and cellular mRNAs and proteins. Here we show that the high-dimensional cellular state scape can predict heterogenous infections, and cells move through the cellular state landscape according to infection progression. Spatial information reveals that infection changes the cellular state of both infected cells and of their neighbors. The multiplexed imaging of HSV-1-induced cellular modifications links infection progression to changes in signaling responses, transcriptional activity, and processing bodies. Our data show that multiplexed quantification of responses at the single-cell level, across thousands of cells helps predict infections and identify new targets for antivirals.

Abstract The year of 2020 was profoundly marked by a global pandemic caused by a strain of coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19). To control disease spread, a key strategy adopted by many countries was the regular testing of individuals for infection. This led to the rapid development of diagnostic testing technologies. In Norway, within a week, our group developed a test kit to quickly isolate viral RNA and safely detect SARS-CoV-2 infection with sensitivity comparable to available kits. Herein, the procedure employed for the detection of SARS-CoV-2 in swab samples from patients using the NTNU-COVID-19 test kit is described in detail. This procedure, based on NAxtra magnetic nanoparticles and an optimized nucleic acid extraction procedure, is robust, reliable, and straightforward, providing high-quality nucleic acids within 14 min. The NAxtra protocol is adaptable and was further validated for extraction of DNA and RNA from other types of viruses. A comparison of the protocol on different liquid handling systems is also presented. Due to the simplicity and low cost of this method, implementation of this technology to diagnose virus infections on a clinical setting would benefit health care systems, promoting sustainability.

BackgroundFemale sex workers (FSWs) are at high risk for HIV infection and face unique barriers to receiving and adhering to testing and treatment. Early viral suppression and consistent viral load testing are critical to optimizing health and reducing transmission in this population. However, the factors associated with testing and successful viral suppression among FSWs are poorly understood, especially in Sub-Saharan Africa. Our study aimed to examine factors, including social, demographic, and clinical characteristics, associated with viral load testing and suppression among female sex workers initiating antiretroviral therapy in Nigeria.MethodsIn this retrospective study, we analyzed routine programmatic data from FSWs enrolled in the National HIV Key Populations (KP) program in Nigeria. We included FSWs who were newly diagnosed with HIV and registered between January 2016 and January 2022. Primary outcomes of interest were a), receiving a viral load test at any point after treatment initiation and b), viral suppression (FindingsOut of 34,976 FSWs, 97.1% (n = 33,945) received at least one viral load test, with 94.5% (n = 32,092) indicating viral suppression. The odds of receiving at least one viral load test were higher for those who entered treatment in more recent years, those with formal education and those with advanced HIV stages at baseline (adjusted odds ratios [aOR]: 1.17 [1.14-1.19] for those who entered treatment in 2020 vs. 2016; 1.02 [1.01-1.03] for post-secondary vs. no education; and 1.05 [1.01-1.10] for WHO clinical stage 3/4 vs. stage 1 respectively). The odds of successful viral suppression were higher for those who entered treatment in more recent years, but lower for those with advanced HIV stages at baseline (aOR: 1.13 [1.09-1.18] for 2022 vs. 2016; and 0.92 [0.87-0.98] for WHO clinical stage 3/4 vs. stage 1 respectively).ConclusionsThe study underscored the relevance of timely diagnosis and ART initiation for optimal outcomes among HIV-positive FSWs in Nigeria. We also observed significant improvements in the likelihood of early viral load testing and suppression over the study period, reflecting advancements in the KP program. Further research should clarify factors driving these trends to further strengthen the HIV care pipeline for female sex workers.

A variety of costly research-grade imaging devices are available for the detection of spectroscopic features. Here we present an affordable, open-source and versatile device, suitable for a range of applications. We provide the files to print the imaging chamber with commonly available 3D printers and instructions to assemble it with easily available hardware. The imager is suitable for rapid sample screening in research, as well as for educational purposes. We provide details and results for an already proven set-up which suits the needs of a research group and students interested in UV-induced near-infrared fluorescence detection of microbial colonies grown on Petri dishes. The fluorescence signal confirms the presence of bacteriochlorophyll a in aerobic anoxygenic phototrophic bacteria (AAPB). The imager allows for the rapid detection and subsequent isolation of AAPB colonies on Petri dishes with diverse environmental samples. To this date, 15 devices have been build and more than 7000 Petri dishes have been analyzed for AAPB, leading to over 1000 new AAPB isolates. Parts can be modified depending on needs and budget. The latest version with automated switches and double band pass filters costs around 350€ in materials and resolves bacterial colonies with diameters of 0.5 mm and larger. The low cost and modular build allow for the integration in high school classes to educate students on light properties, fluorescence and microbiology. Computer-aided design of 3D-printed parts and programming of the employed Raspberry Pi computer could be incorporated in computer sciences classes. Students have been also inspired to do agar art with microbes. The device is currently used in seven different high schools in Finland. Additionally, a science education network of Finnish universities has incorporated it in its program for high school students. Video guides have been produced to facilitate easy operation and accessibility of the device.

BackgroundResilience is a process of drawing on internal or external strengths to regain, sustain or improve adaptive outcomes despite adversity. Using a child resilience measure co-designed with Aboriginal and Torres Strait Islander communities, we investigate: 1) children's personal, family, school and community strengths; 2) gender differences; and 3) associations between resilience and wellbeing.Methods1132 parent/caregivers of children aged 5-12 years were recruited to the Childhood Resilience Study, including through the Aboriginal Families Study. The Aboriginal Families Study is a population-based cohort of 344 mothers of an Aboriginal and/or Torres Strait Islander child. This paper focuses on the wave 2 survey data on child resilience at age 5-9 years (n = 231). Resilience was assessed with the Child Resilience Questionnaire-parent/caregiver report (CRQ-P/C), categorised into tertiles of low, moderate and high scores. Child emotional/behavioural wellbeing and mental health competence was assessed with the parent-report Strengths and Difficulties Questionnaire. All Tobit regression models adjusted for child age.OutcomesAboriginal and Torres Strait Islander girls had higher resilience scores compared to boys (Adj.β = 0·9, 95%CI 0·9-1·4), with higher School Engagement, Friends and Connectedness to language scale scores. Resilience scores were strongly associated with wellbeing and high mental health competence. A higher proportion of girls with low resilience scores had positive wellbeing than did boys (73.3% versus 49.0%). High resilience scores were associated with lower SDQ total difficulties score after adjusting for child age, gender, maternal age and education and family location (major city, regional, remote) (Adj.β = -3.4, 95%CI -5.1, -1.7). Compared to the Childhood Resilience Study sample, Aboriginal Families Study children had higher mean CRQ-P/C scores in the personal and family domains.InterpretationHigh family strengths can support Aboriginal and Torres Strait Islander children at both an individual and cultural level. Boys may benefit from added scaffolding by schools, family and communities to support their social and academic connectedness.

Monogenic diabetes is characterized as a group of diseases caused by rare variants in single genes. Like for other rare diseases, multiple genes have been linked to monogenic diabetes with different measures of pathogenicity, but the information on the genes and variants is not unified among different resources, making it challenging to process them informatically. We have developed an automated pipeline for collecting and harmonizing data on genetic variants linked to monogenic diabetes. Furthermore, we have translated variant genetic sequences into protein sequences accounting for all protein isoforms and their variants. This allows researchers to consolidate information on variant genes and proteins linked to monogenic diabetes and facilitates their study using proteomics or structural biology. Our open and flexible implementation using Jupyter notebooks enables tailoring and modifying the pipeline and its application to other rare diseases.

In this exploratory study, we investigate the influence of several semantic-pragmatic and syntactic factors on prosodic prominence production in German, namely referential and lexical newness/givenness, grammatical role, and position of a referential target word within a sentence. Especially in terms of the probabilistic distribution of accent status (nuclear, prenuclear, deaccentuation) we find evidence for an additive influence of the discourse-related and syntactic cues, with lexical newness and initial sentence position showing the strongest boosting effects on a target word's prosodic prominence. The relative strength of the initial position is found in nearly all prosodic factors investigated, both discrete (such as the choice of accent type) and gradient (e.g., scaling of the Tonal Center of Gravity and intensity). Nevertheless, the differentiation of prominence relations is information-structurally less important in the beginning of an utterance than near the end: The prominence of the final object relative to the surrounding elements, especially the verbal component, is decisive for the interpretation of the sentence. Thus, it seems that a speaker adjusts locally important prominence relations (object vs. verb in sentence-final position) in addition to a more global, rhythmically determined distribution of prosodic prominences across an utterance.

Abstract This study examined whether active commuting to school in childhood and adolescence predicted active commuting to work and overall physical activity (PA) in adulthood. Participants from the Young Finns Study (N = 2436) were aged 9–18 years in 1980 and followed up until 2018/2020. Their commuting modes to school were assessed with a self-reported questionnaire in 1980. Adulthood PA was assessed through self-reports regarding commuting modes to work (2001–2018), leisure-time physical activity (LTPA) (2001–2018), and objectively measured daily steps (2007–2018/2020). Associations between childhood commuting and adulthood PA were evaluated using regression analyses and multilevel models. Demographic, socioeconomic and environmental covariates were adjusted for in the analyses. Active commuting to school in childhood contributed favourably to LTPA in 2001 (B = .38, p

Abstract Success in long-term weight management depends partly on psychological and behavioral aspects. Understanding the links between psychological factors and eating behavior tendencies is needed to develop more effective weight management methods. This population-based cross-sectional study examined whether eating self-efficacy (ESE) is associated with cognitive restraint (CR), uncontrolled eating (UE), emotional eating (EE), and binge eating (BE). The hypothesis was that individuals with low ESE have more unfavorable eating behavior tendencies than individuals with high ESE. Participants were classified as low ESE and high ESE by the Weight-Related Self-Efficacy questionnaire (WEL) median cut-off point. Eating behavior tendencies were assessed with Three Factor Eating Questionnaire R-18 and Binge Eating Scale, and additionally, by the number of difficulties in weight management. The difficulties were low CR, high UE, high EE, and moderate or severe BE. Five hundred and thirty-two volunteers with overweight and obesity were included in the study. Participants with low ESE had lower CR (p

Abstract Accumulating evidence suggests mitochondria as key modulators of normal and premature aging, yet whether primary oxidative phosphorylation (OXPHOS) deficiency can cause progeroid disease remains unclear. Here, we show that mice with severe isolated respiratory complex III (CIII) deficiency display nuclear DNA damage, cell cycle arrest, aberrant mitoses, and cellular senescence in the affected organs such as liver and kidney, and a systemic phenotype resembling juvenile-onset progeroid syndromes. Mechanistically, CIII deficiency triggers presymptomatic cancer-like c-MYC upregulation followed by excessive anabolic metabolism and illicit cell proliferation against lack of energy and biosynthetic precursors. Transgenic alternative oxidase dampens mitochondrial integrated stress response and the c-MYC induction, suppresses the illicit proliferation, and prevents juvenile lethality despite that canonical OXPHOS-linked functions remain uncorrected. Inhibition of c-MYC with the dominant-negative Omomyc protein relieves the DNA damage in CIII-deficient hepatocytes in vivo. Our results connect primary OXPHOS deficiency to genomic instability and progeroid pathogenesis and suggest that targeting c-MYC and aberrant cell proliferation may be therapeutic in mitochondrial diseases.

Abstract The subjective indicator of health self-rated health (SRH) and the chronic inflammation biomarker soluble urokinase plasminogen activator receptor (suPAR) are both robust predictors of healthcare use and mortality. However, the possible relationship between SRH and suPAR in the assessment of hospitalization and mortality risk is unknown. We used data from the Danish population-based Inter99 cohort to examine the association between SRH and suPAR and test their individual and combined associations with 2-year risk of acute hospitalization and 5- and 15-year mortality. SRH and serum suPAR levels were measured in 5490 participants (median age 45.1 years, 48.7% men). Poorer SRH was associated with elevated suPAR. In unadjusted analyses, SRH and suPAR were individually associated with higher risks of acute hospitalization and mortality, and both measures remained independently associated with higher risks of hospitalization and 15-year mortality after mutual adjustments. The association of suPAR with mortality was stronger in poorer SRH categories, and when combined, SRH and suPAR could identify different groups of individuals with increased risk of acute hospitalization and mortality. Both SRH and suPAR were independently associated with risk of acute hospitalization and mortality, and different combinations of the two measures could identify different groups of individuals at increased risk.

Most of the annual 10 million cancer-related deaths are caused by metastatic disease. Survival rates for cancer are strongly dependent on the type of cancer and its stage at detection. Early detection remains a challenge due to the lack of reliable biomarkers and cost-efficient screening methods. Phage biosensors can offer a solution for early detection using non-invasive liquid biopsies. Here, we report the first results of the bifunctional phage biosensor to detect metastatic urological cancers from urine. A dye-sensitized phage library was used to select metastasis-related phage binders. After selection rounds, the most promising phage candidate was used to classify metastatic cancer from controls. Additionally, we applied one chemical sensor (phenoxazine non-fluorescent dye) to classify cancer from urine. A statistical significance (p = 0.0002) was observed between metastatic and non-metastatic cancer, with sensitivity of 70% and specificity of 79%. Furthermore, the chemical sensor demonstrated significance in detecting cancer (p < 0.0001) with a sensitivity of 71% and a specificity of 75%. Our data suggest a new promising field for urine biomarker research, and further evaluation with prospectively collected samples is ongoing. In conclusion, we report, for the first time, the potential of a chemical- and phage-based biosensor method to detect metastatic cancer using urine.

Cold seeps release methane (CH4) from the seafloor to the water column, which fuels microbially mediated aerobic methane oxidation (MOx). Methane-oxidising bacteria (MOB) utilise excess methane, and the MOB biomass serves as a carbon source in the food web. Yet, it remains unclear if and how MOx modifies the composition of dissolved organic matter (DOM) in cold seeps. We investigated MOx rates, DOM compositions and the microbial community during ex-situ incubations of seawater collected from a cold seep site at Norskebanken (north of the Svalbard archipelago) in the Arctic Ocean. Samples were incubated with and without methane amendments. Samples amended with methane (∼1 µM final concentration) showed elevated rates of MOx in both seep and non-seep incubations. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) analyses showed that the number of DOM formulas (i.e., molecular diversity) increased by up to 39% in these incubations. In contrast, the number of formulas decreased by 20% in samples not amended with methane, both from non-seep and seep locations. DOM composition was thus altered towards a more diverse and heterogeneous composition along with elevated methanotrophic activity in methane-amended conditions. In addition to microbial DOM production, abating microbial diversity indicates that elevated DOM diversity was potentially related to grazing pressure on bacteria. The diversity of DOM constituents, therefore, likely increased with the variety of decaying cells contributing to DOM production. Furthermore, based on a principal coordinate analysis, we show that the final DOM composition of non-seep samples amended with methane became more resemblant to that of seep samples. This suggests that methane intrusions will affect water column DOM dynamics similarly, irrespective of the water column’s methane history.

Sea ice algae have a broad salinity tolerance but can experience stress during rapid decreases in salinity that occur with seasonal ice melt and during ice sample melt. This study investigated the impact of salinity on the photophysiological responses of bottom-ice algal communities from two Svalbard fjords (Tempelfjorden and Van Mijenfjorden). To further investigate the impact of salinity alone, and particularly to rapid freshening, the responses of a lab-cultured ice algal community from Van Mijenfjorden were assessed. Photophysiological responses were mainly determined via 14C-based incubations which provided photosynthesis-irradiance curves. Main findings showed that i) the bottom-ice algal community in Tempelfjorden was characterized by lower photosynthetic efficiency and chlorophyll a biomass than the Van Mijenfjorden communities, and ii) a lab-cultured ice algal community from Van Mijenfjorden dominated by pennate diatoms had significantly lower photosynthetic efficiency, maximum photosynthesis and photoacclimation index after a decrease in salinity from 33 to 10. The lower photosynthetic efficiency and chlorophyll a biomass at Tempelfjorden may be attributed to the almost two-fold lower bulk-ice salinity in Tempelfjorden compared to Van Mijenfjorden, which was likely associated with freshwater inputs from the tidewater glacier Tunabreen during sea ice formation. Other factors such as under-ice light intensities, brine volume fraction and brine nutrient concentrations likely also contributed to variability in ice algal response. Furthermore, experimental results indicated that the cultured Van Mijenfjorden community was negatively impacted by a rapid (within 4 to 24 h) reduction in salinity from 33 to 10. We further documented a significant start of recovery of these algae after 168 h. From this work, we surmise that decreases in surface water salinity, for example arising from the intensifying freshening of fjord waters, may only cause temporary changes in ice algal photoacclimation state and thus in chlorophyll a biomass. Further, this study also supports the need for salinity buffered melt of sea ice samples to reduce artificial bias in biological measurements.

Abstract Despite the fact that the effect of sex on the occurrence of cancers has been studied extensively, it remains unclear whether sex modifies familial aggregation of cancers. We explored sex-specific familial aggregation of cancers in a large population-based historical cohort study. We combined cancer and population registry data, inferring familial relationships from birth municipality-surname-sex (MNS) combinations. Our data consisted of 391,529 incident primary cancers in 377,210 individuals with 319,872 different MNS combinations. Cumulative sex-specific numbers of cancers were compared to expected cumulative incidence. Familial cancer risks were similar between the sexes in our population-wide analysis. Families with concordant cancer in both sexes exhibited similar sex-specific cancer risks. However, some families had exceptionally high sex-specific cumulative cancer incidence. We identified six families with exceptionally strong aggregation in males: three families with thyroid cancer (ratio between observed and expected incidence 184.6; 95% credible interval (95% CI) 33.1–1012.7, 173.4 (95% CI 65.4–374.3), and 161.4 (95% CI 29.6–785.7), one with stomach (ratio 14.4 (95% CI 6.9–37.2)), colon (ratio 15.5 (95% CI 5.7–56.3)) cancers and one with chronic lymphocytic leukaemia (ratio 33.5 (95% CI 17.2–207.6)). Our results imply that familial aggregation of cancers shows no sex-specific preference. However, the atypical sex-specific aggregation of stomach cancer, colon cancer, thyroid cancer and chronic lymphocytic leukaemia in certain families is difficult to fully explain with present knowledge of possible causes, and could yield useful knowledge if explored further.

Abstract Respiratory brain pulsations pertaining to intra-axial hydrodynamic solute transport are markedly altered in focal epilepsy. We used optical flow analysis of ultra-fast functional magnetic resonance imaging (fMRI) data to investigate the velocity characteristics of respiratory brain impulse propagation in patients with focal epilepsy treated with antiseizure medication (ASM) (medicated patients with focal epilepsy; ME, n = 23), drug-naïve patients with at least one seizure (DN, n = 19) and matched healthy control subjects (HC, n = 75). We detected in the two patient groups (ME and DN) several significant alterations in the respiratory brain pulsation propagation velocity, which showed a bidirectional change dominated by a reduction in speed. Furthermore, the respiratory impulses moved more in reversed or incoherent directions in both patient groups vs. the HC group. The speed reductions and directionality changes occurred in specific phases of the respiratory cycle. In conclusion, irrespective of medication status, both patient groups showed incoherent and slower respiratory brain impulses, which may contribute to epileptic brain pathology by hindering brain hydrodynamics.

Abstract We present the first version of the Ocean Circulation and Carbon Cycling (OC3) working group database, of oxygen and carbon stable isotope ratios from benthic foraminifera in deep ocean sediment cores from the Last Glacial Maximum (LGM, 23-19 ky) to the Holocene (

Abstract Respiratory rate (RR) is an often underestimated and underreported vital sign with tremendous clinical value. As a predictor of cardiopulmonary arrest, chronic obstructive pulmonary disease (COPD) exacerbation or indicator of health state for example in COVID-19 patients, respiratory rate could be especially valuable in remote long-term patient monitoring, which is challenging to implement. Contactless devices for home use aim to overcome these challenges. In this study, the contactless Sleepiz One+ respiration monitor for home use during sleep was validated against the thoracic effort belt. The agreement of instantaneous breathing rate and breathing rate statistics between the Sleepiz One+ device and the thoracic effort belt was initially evaluated during a 20-min sleep window under controlled conditions (no body movement) on a cohort of 19 participants and secondly in a more natural setting (uncontrolled for body movement) during a whole night on a cohort of 139 participants. Excellent agreement was shown for instantaneous breathing rate to be within 3 breaths per minute (Brpm) compared to thoracic effort band with an accuracy of 100% and mean absolute error (MAE) of 0.39 Brpm for the setting controlled for movement, and an accuracy of 99.5% with a MAE of 0.48 Brpm for the whole night measurement, respectively. Excellent agreement was also achieved for the respiratory rate statistics over the whole night with absolute errors of 0.43, 0.39 and 0.67 Brpm for the 10th, 50th and 90th percentiles, respectively. Based on these results we conclude that the Sleepiz One+ can estimate instantaneous respiratory rate and its summary statistics at high accuracy in a clinical setting. Further studies are required to evaluate the performance in the home environment, however, it is expected that the performance is at similar level, as the measurement conditions for the Sleepiz One+ device are better at home than in a clinical setting.

Abstract Highly specialized enamel matrix proteins (EMPs) are predominantly expressed in odontogenic tissues and diverged from common ancestral gene. They are crucial for the maturation of enamel and its extreme complexity in multiple independent lineages. However, divergence of EMPs occured already before the true enamel evolved and their conservancy in toothless species suggests that non-canonical functions are still under natural selection. To elucidate this hypothesis, we carried out an unbiased, comprehensive phenotyping and employed data from the International Mouse Phenotyping Consortium to show functional pleiotropy of amelogenin, ameloblastin, amelotin, and enamelin, genes, i.e. in sensory function, skeletal morphology, cardiovascular function, metabolism, immune system screen, behavior, reproduction, and respiratory function. Mice in all KO mutant lines, i.e. amelogenin KO, ameloblastin KO, amelotin KO, and enamelin KO, as well as mice from the lineage with monomeric form of ameloblastin were affected in multiple physiological systems. Evolutionary conserved motifs and functional pleiotropy support the hypothesis of role of EMPs as general physiological regulators. These findings illustrate how their non-canonical function can still effect the fitness of modern species by an example of influence of amelogenin and ameloblastin on the bone physiology.

Abstract Anonymization has the potential to foster the sharing of medical data. State-of-the-art methods use mathematical models to modify data to reduce privacy risks. However, the degree of protection must be balanced against the impact on statistical properties. We studied an extreme case of this trade-off: the statistical validity of an open medical dataset based on the German National Pandemic Cohort Network (NAPKON), which was prepared for publication using a strong anonymization procedure. Descriptive statistics and results of regression analyses were compared before and after anonymization of multiple variants of the original dataset. Despite significant differences in value distributions, the statistical bias was found to be small in all cases. In the regression analyses, the median absolute deviations of the estimated adjusted odds ratios for different sample sizes ranged from 0.01 [minimum = 0, maximum = 0.58] to 0.52 [minimum = 0.25, maximum = 0.91]. Disproportionate impact on the statistical properties of data is a common argument against the use of anonymization. Our analysis demonstrates that anonymization can actually preserve validity of statistical results in relatively low-dimensional data.