Modern humans arrived in Europe more than 45,000 years ago, overlapping at least 5,000 years with Neanderthals1,2,3,4. Limited genomic data from these early modern humans have shown that at least two genetically distinct groups inhabited Europe, represented by Zlatý kůň, Czechia3 and Bacho Kiro, Bulgaria2. Here we deepen our understanding of early modern humans by analysing one high-coverage genome and five low-coverage genomes from approximately 45,000-year-old remains from Ilsenhöhle in Ranis, Germany4, and a further high-coverage genome from Zlatý kůň. We show that distant familial relationships link the Ranis and Zlatý kůň individuals and that they were part of the same small, isolated population that represents the deepest known split from the Out-of-Africa lineage. Ranis genomes harbour Neanderthal segments that originate from a single admixture event shared with all non-Africans that we date to approximately 45,000–49,000 years ago. This implies that ancestors of all non-Africans sequenced so far resided in a common population at this time, and further suggests that modern human remains older than 50,000 years from outside Africa represent different non-African populations.

Practice-based evidence has emerged as an important complementary paradigm to studies in controlled trials. This paper presents results of a large research-practice network at German university outpatient clinics; the KODAP initiative. Pre-post effect sizes, direct assessments of change, and rates of clinically significant and reliable improvement are reported in a heterogeneous clinical sample of 6624 adult patients treated between 2023 and 2014 in 29 psychotherapeutic outpatient clinics. Clinical diagnoses, determined with structured diagnostic clinical interviews at baseline across all clinics, encompassed a wide range of psychopathology. Effectiveness was comparable to other studies in naturalistic settings (d ≈ 0.75–0.95) and somewhat lower than changes reported in disorder-specific CBT efficacy trials. In direct assessments of change, only 1.9% of the patients reported symptom worsening and 3.4% reported no change during treatment. Overall, the results show the potential of multi-site naturalistic research initiatives in general and the effectiveness of outpatient CBT at German university outpatient clinics in particular.

DNA metabarcoding of benthic diatoms has been successfully applied for biomonitoring at the national scale and can now be considered technically ready for routine application. However, protocols and methods still vary between and within countries, limiting their transferability and the comparability of results. In order to overcome this, routine use of DNA metabarcoding for diatom biomonitoring requires knowledge of the sources of variability introduced by the different steps of the procedure. Here, we examine how elements of routine procedures contribute to variability between European laboratories. A set of four experiments were performed focusing on DNA extraction and PCR amplification steps to evaluate their reproducibility between different laboratories and the variability introduced by different protocols currently applied by the scientific community. Under the guidance of a reference laboratory, 17 participants from 14 countries performed DNA extraction and PCR amplification in parallel, using the same fixed protocol and their own choice of protocol. Experiments were performed by each participant on a set of standardised DNA and biofilm samples (river, lake and mock community) to investigate potential systematic and random errors. Our results revealed the successful transferability of a protocol amongst labs and a highly similar and consistent ecological assessment outcome obtained regardless of the protocols used by each participant. We propose an “all for one but prove them all” strategy, suggesting that distinct protocols can be used within the scientific community, as long as their consistency is be proven by following minimum standard requirements.

We present a comprehensive multi-proxy analysis spanning 550,000 years from the outer Labrador Sea region at the Integrated Ocean Drilling Program (IODP) Sites U1302/1303. We combine new benthic foraminiferal stable oxygen (δ18O) and carbon (δ13C) isotope records, with sediment elemental composition and authigenic neodymium isotope measurements, to provide insights into deep-water mass sourcing and changes of the Deep Western Boundary Current (DWBC), which exports North Atlantic Deep Water (NADW) into the wider North Atlantic as part of the lower limb of the Atlantic Meridional Overturning Circulation. We find that a prominent DWBC likely remained a persistent feature within the Labrador Sea region throughout the past 550 kyr. However, glacial peaks of marine isotope stage (MIS) 14 to MIS 2 were consistently characterized by a weaker or shallower DWBC, while all interglacial periods of MIS 13a to MIS 1, with the exception of MIS 7e, were marked by enhanced DWBC. Additionally, the dominant deep-water masses feeding into the DWBC during these glacial-interglacial periods varied from regional (K-rich sediment, unradiogenic εNd) to more distal sources from the Nordic Seas (Ti-rich sediment, radiogenic εNd). Yet, these changes in deep-water provenance did not consistently correlate with DWBC strength, suggesting that additional factors may have played a significant role in shaping the DWBC strength or core depth throughout the geological past.

Museum collections harbor millions of samples, largely unutilized for long-read sequencing. Here, we use ethanol-preserved samples containing kilobase-sized DNA to show that amplification-free protocols can yield contiguous genome assemblies. Additionally, using a modified amplification-based protocol, employing an alternative polymerase to overcome PCR bias, we assemble the 3.1 Gb maned sloth genome, surpassing the previous 500 Mb protocol size limit. Our protocol also improves assemblies of other difficult-to-sequence molluscs and arthropods, including millimeter-sized organisms. By highlighting collections as valuable sample resources and facilitating genome assembly of tiny and challenging organisms, our study advances efforts to obtain reference genomes of all eukaryotes.

Pesticide application is essential for stabilizing agricultural production. However, the effects of increasing pesticide diversity on soil microbial functions remain unclear, particularly under varying nitrogen (N) fertilizer management practices. In this study, we investigated the stochasticity of soil microbes and multitrophic networks through amplicon sequencing, assessed soil community functions related to carbon (C), N, phosphorus (P), and sulfur (S) cycling, and characterized the dominant bacterial life history strategies via metagenomics along a gradient of increasing pesticide diversity under two N addition levels. Our findings show that higher pesticide diversity enriches the abundance of bacterial specialists and opportunists capable of degrading or resisting pesticides, reducing the proportion of bacterial generalists in the absence of N addition. These shifts can complicate multitrophic microbial networks. Under increased pesticide diversity, selective pressure may drive bacteria to streamline their average genome size to conserve energy while enhancing C, N, P, and S metabolic capacities, thus accelerating soil nutrient loss. In comparison, N addition was found to reduce bacterial niche differentiation at higher pesticide diversity, mitigating the impacts of network complexity and functional traits associated with pesticide diversity, ultimately alleviating soil nutrient loss. Our results reveal the contrasting impacts of pesticide diversity on microbial functions under different N input scenarios and emphasize that strategic N fertilizer management can mitigate the ecological effects of pesticide use in agricultural systems.

Lichens are complex symbiotic systems where fungi interact with an extracellular arrangement of one or more photosynthetic partners and an indeterminate number of other microbes. Recently, specific lichen–microbial community associations have been proposed. In this study, we aimed to characterize the differences in bacteria associated with closely related lichens, under a defined set of environmental conditions in Colombian paramos. Our goal was to determine if there is a correlation between microbiota and host divergence in lichen species belonging to the genus Sticta. We found that specific microbiota are defined by their mycobiont at the genus level. Further, distinct bacterial families show differences among the three studied genera, and specific amplicon sequence variants further discriminate among lichen species within each genus. A geographic component also determines the composition of these microbial communities among lichen species. Our functional analysis revealed that fungal partners play a key role in synthesizing complex polysaccharides, while bacterial-derived antioxidants and photoprotective mechanisms contribute to desiccation tolerance in lichens. These insights highlight the complex interactions within lichen symbioses that could be relevant in environments such as the paramo ecosystem.

Observations of the diurnal variations of the surface temperature of asteroid (162173) Ryugu from orbit and on the surface were performed by the Haybusa2 spacecraft and MASCOT lander. A low thermal inertia of the boulders on Ryugu was derived from these temperature variations and interpreted as the consequence of high porosity. Samples of Ryugu returned to Earth by Hayabusa2 showed higher thermal inertia when investigated by microscopic thermography. Here, we apply a simple thermal model, considering a horizontal fracture interrupting the heat flow into the surface, and investigate whether the low thermal inertia of Ryugu's boulders might be caused by fractures rather than high porosity. We find that the diurnal temperature variations on Ryugu observed by MARA can be partially explained by introducing a single horizontal crack at 9 mm depth below the surface observed by MARA.

Objective: Mastitis is the most common and costly dairy cow disease worldwide. We performed an intensive analysis of mastitis prevalence, pathogens, and treatments using retrospective data from a commercial dairy farm in Germany to estimate the severity of mastitis in the commercial production system and to give on-farm insights. Material and Methods: Milking system data and cow-individual data were collected over 9 years (2012-2021). A resilient amount of data from 1537 cows, >1,000 mastitis infections, 1901 pathogens, and 5729 treatments have been analyzed. Results: Mastitis occurrence was highest in summer (45.0%), in first lactation (51.1%), and in the late lactation stage (36.7%). The relative mastitis frequency increased sharply with a high lactation number (>7). The leading pathogens causing mastitis were coagulase-negative staphylococci (28.3%). Approximately 25% of mastitis cases were treated with non-antibiotic medicine and 75% with antibiotics. For the latter, cephalosporins and aminoglycosides were the most administered. The average mastitis treatment duration was 3.48 days. During the study time, the farm changed from a conventional milking system to an automatic milking system in 2015, which has not negatively affected the number of recorded mastitis infections. Conclusion: This case report gives detailed insights about mastitis incidences gained under practical conditions. Novel information about mastitis drug usage and duration is presented. Potential mastitis risk factors identified from the results of this study were the summer season, first or >7 lactation(s), and the late lactation stage.

Problem solving is considered an essential ability for becoming an expert in physics, and individualized feedback on the structure of problem-solving processes is a key component to support students in developing this ability. Problem-solving processes consist of multiple elements whose order forms the sequential structure of these processes. Specific sequential structures can be expected to better reflect expert problem solving and more likely lead to successful solutions. However, this sequential structure often receives limited attention in assessments, thereby neglecting possibly valuable diagnostic information that could be used for individualized feedback. Consequently, a deeper understanding of the sequential structure of students’ written physics problem-solving approaches could leverage novel potentials for physics instruction and feedback provision. This study therefore aimed to examine how the sequential structure of written problem-solving approaches differs between high- and low-performing problem solvers as well as to what extent specific sequential elements are predictive of problem-solving performance. To achieve this, we employed methods from process mining and sequence analysis research. Our findings revealed that low-performing problem solvers often lack structure in their problem-solving approaches, contrasting with notably more systematic approaches of the high-performing problem solvers. Additionally, the order in which assumptions and conceptual aspects are addressed in a problem-solving approach seems to be an indicator of problem-solving performance. The findings of this study enhance our understanding of physics problem-solving processes and highlight opportunities for improving instruction and feedback for physics problem solving by considering the sequential structure of students’ physics problem-solving approaches.

Recent interest in the crater-dating of smaller and younger features of planetary surfaces has provoked questions about how far the method's validity extends. This work addresses the problem theoretically over a range of measurement scenarios, predicting the consequent statistical measurement uncertainty, and suggesting it should be the first criterion to determine usability. We map out the relationship between crater measurement area, observable crater diameters, measured age uncertainty, and the actual age of surface structures. Constraints on the range of possible measured ages arising from particular combinations of counting area and observable crater diameter are presented in a generalised form, with the intent to provide a reference for the choice and suitability for measurements of surfaces from different epochs. Additionally, several perhaps non-obvious aspects of evaluation of the chronology model, namely, the influence of the limits of the considered crater diameter interval, of varying the counting area at fixed crater density, of varying the counting area perimeter for a buffered count of a linear feature, and the logarithmic behaviour of the time-resolving ability of the method are described and demonstrated, likewise with the intent to support well-informed choices for actual crater-dating measurements.

After the magma ocean state, secondary atmospheres build up via early volcanic degassing of planetary interiors. The terrestrial planets Venus, Earth, and Mars are believed to have originated from similar source material but reveal distinct present-day atmospheric compositions, pressures, and temperatures. To investigate how such diverse atmospheres emerge, we have built a three-step model coupling mantle and atmospheric composition. The model incorporates mantle melting, melt ascent, and volcanic degassing. Additionally, it includes atmospheric equilibrium chemistry, taking into account processes such as water condensation and hydrogen escape. Key parameters such as mantle oxygen fugacity, melt production rates, surface temperature, and volatile abundance in the mantle, were varied to understand their impact on atmospheric composition and pressure. For reduced mantles with redox states below IW +1, atmospheric pressures remain strongly limited to a maximum of 2 bar due to the outgassing of predominantly light species that are prone to atmospheric escape or condensation. Above IW +1, atmospheric pressure can reach several tens of bars depending on the outgassing efficiency. For high-pressure atmospheres, CO2 is the main atmospheric species observed in our models. For oxidized low-pressure atmospheres, depending on temperature, atmospheres can be either water-rich or also CO2-dominated. For reducing atmospheres, nitrogen species tend to dominate the atmospheres, with NH3 for colder atmospheres and N2 for warmer atmospheres. CH4 becomes dominant only in a narrow parameter space at redox states around IW +0.5 to IW +2 and is favored by lower atmospheric temperatures.

Introduction Multidisciplinary team meetings (MDMs), also known as tumor conferences, are a cornerstone of cancer treatments. However, barriers such as incomplete patient information or logistical challenges can postpone tumor board decisions and delay patient treatment, potentially affecting clinical outcomes. Therapeutic Assistance and Decision algorithms for hepatobiliary tumor Boards (ADBoard) aims to reduce this delay by providing automated data extraction and high-quality, evidence-based treatment recommendations.Methods and analysisWith the help of natural language processing, relevant patient information will be automatically extracted from electronic medical records and used to complete a classic tumor conference protocol. A machine learning model is trained on retrospective MDM data and clinical guidelines to recommend treatment options for patients in our inclusion criteria. Study participants will be randomized to either MDM with ADBoard (Arm A: MDM-AB) or conventional MDM (Arm B: MDM-C). The concordance of recommendations of both groups will be compared using interrater reliability. We hypothesize that the therapy recommendations of ADBoard would be in high agreement with those of the MDM-C, with a Cohen's kappa value of & GE; 0.75. Furthermore, our secondary hypotheses state that the completeness of patient information presented in MDM is higher when using ADBoard than without, and the explainability of tumor board protocols in MDM-AB is higher compared to MDM-C as measured by the System Causability Scale.DiscussionThe implementation of ADBoard aims to improve the quality and completeness of the data required for MDM decision-making and to propose therapeutic recommendations that consider current medical evidence and guidelines in a transparent and reproducible manner.Ethics and disseminationThe project was approved by the Ethics Committee of the Charite - Universitatsmedizin Berlin.Registration detailsThe study was registered on ClinicalTrials.gov (trial identifying number: NCT05681949; https://clinicaltrials.gov/study/NCT05681949) on 12 January 2023.

The present day concentrations of highly siderophile elements in Earth’s mantle cannot be sufficiently explained by planetary differentiation processes. Material from iron cores of large differentiated bodies, incorporated into a magma ocean due to impact during the late accretion phase, may offer an explanation for the increased abundance of highly siderophile elements, which are considered a measure of the late addition of material. For the chemical equilibration of metallic impactor core material with a silicate magma ocean it is important to know whether the core breaks up. It could shatter into fragments that mix with the magma ocean or penetrates the magma ocean as a coherent mass that does not equilibrate with the surrounding silicates. In order to quantify the fragmentation process between these two end-member cases we performed hydrocode simulations of differentiated impactors into magma oceans at different impactor sizes, impact velocities and magma ocean depths. For this, we developed and implemented a new disruption method into our simulation code, which allows for a more realistic and quantitative description than previously possible. We find that there is significant breakup of the impactor core, increasing with greater magma ocean depth, until the impactor core is completely fragmented at a depth of more than twice the impactor radius. If the magma ocean is shallower, large portions of the impactor core can reach the magma ocean bottom before fragmenting, hence avoiding chemical reequilibration with the surrounding silicates.

Background Intrinsic fitness costs are likely to have guided the selection of lineage-determining mutations during emergence of variants of SARS-CoV-2. Whereas changes in receptor affinity and antibody neutralization have been thoroughly mapped for individual mutations in spike, their influence on intrinsic replicative fitness remains understudied.MethodsWe analyzed mutations in immunodominant spike epitope E484 that became temporarily fixed over the pandemic. We engineered the resulting immune escape mutations E484K, -A, and -Q in recombinant SARS-CoV-2. We characterized viral replication, entry, and competitive fitness with and without immune serum from humans with defined exposure/vaccination history and hamsters monospecifically infected with the E484K variant. We additionally engineered a virus containing the Omicron signature mutations N501Y and Q498R that were predicted to epistatically enhance receptor binding.ResultsMultistep growth kinetics in Vero-, Calu-3, and NCI-H1299 were identical between viruses. Synchronized entry experiments based on cold absorption and temperature shift identified only an insignificant trend toward faster entry of the E484K variant. Competitive passage experiments revealed clear replicative fitness differences. In absence of immune serum, E484A and E484Q, but not E484K, were replaced by wildtype (WT) in competition assays. In presence of immune serum, all three mutants outcompeted WT. Decreased E484A fitness levels were over-compensated for by N501Y and Q498R, identifying a putative Omicron founder background that exceeds the intrinsic and effective fitness of WT and matches that of E484K. Critically, the E484A/Q498R/N501Y mutant and E484K have equal fitness also in presence of pre-Omicron vaccinee serum, whereas the fitness gain by E484K is lost in the presence of serum raised against the E484K variant in hamsters.ConclusionsThe emergence of E484A and E484Q prior to widespread population immunity may have been limited by fitness costs. In populations already exposed to the early immune escape epitope E484K, the Omicron founder background may have provided a basis for alternative immune escape evolution via E484A. Studies of major antigenic epitope changes with and without their epistatic context help reconstruct the sequential adjustments of intrinsic fitness versus neutralization escape during the evolution of major SARS-CoV-2 variants in an increasingly immune human population.

Equine daily behavior is a key welfare indicator, offering insights into how environmental and training conditions influence health and well-being. Continuous direct behavior observation, however, is labor-intensive and impractical for large-scale studies. While advances in wearable sensors and deep learning have revolutionized human and animal activity recognition, automated wearable sensor systems for recognizing a diverse repertoire of equine daily behaviors remain limited. We propose a hierarchical deep learning framework combining a Time-Distributed Residual LSTM-CNN for extracting local spatiotemporal features from short subsegments of sensor data and a bidirectional LSTM (BiLSTM) for capturing long-term temporal dependencies. Our model was validated using approximately 60 h of tri-axial accelerometer and gyroscope data collected from 10 horses wearing collar-mounted sensors. Fifteen daily behaviors were labeled based on video recordings. The model achieved an overall classification accuracy of > 93 % in 10-fold cross-validation and > 85 % in leave-one-subject-out cross-validation. The classification performance was significantly affected by housing conditions and the associated varying frequency of behaviors in the dataset. This study provides a valid framework for sensor-based automatic behavior recognition in horses, capable of capturing both local spatiotemporal and long-term temporal dependencies from raw sensor data. Our proposed framework enables scalable and reliable monitoring of equine daily behaviors and makes an important contribution to the development of automated, data-driven approaches to equine welfare assessment.

Background Lifestyle changes and physical activity can make an important contribution to reducing the risk factor for high blood pressure (BP). Whether virtual reality (VR) exergames are also appropriate and make a positive contribution to the reduction of BP has not yet been sufficiently investigated. Therefore, the aim of the study was to gain knowledge of the load intensities to be achieved during a VR exergame and to examine the short-term effects on BP.Methods For the preliminary study, 22 participants with hypertension over the age of 65 years were analyzed. The study took place in a mobile laboratory truck. All participants visited on two occasions. During visit 1, VR strength endurance training (VR-SET) and during visit 2, VR endurance training (VR-ET) was performed. Each VR session lasted approximately 25 min and was of a moderate intensity. Heart rate (HR) was measured across the entire session, as well as BP before and after the VR exergame. The Rating of Perceived Exertion (RPE) and task load using NASA Task Load Index were determined after each VR session. Included in the statistical analysis were the Shapiro-Wilk test, the paired t-test, the Wilcoxon test and ANOVA for repeated measures.Results During the "main part" (p < .001), at the "end" (p = .002) and for the "maximum HR" (p < .001), significant load differences between both VR sessions could be determined. In addition, significantly more participants in the VR-SET group achieved a moderate load intensity of at least 40% of heart rate reserve (p = .014). Regarding RPE, participants rated their subjectively perceived exertion significantly higher in the VR-SET than in the VR-ET (p = .028). Systolic BP decreased significantly in both VR sessions when compared before VR session and 5 min after VR session (p = .015; p = .003), as well as before VR session and 10 min after VR session (p = .018; p < .001).Conclusions An individual moderate load intensity of 40% can be reached during VR-SET. In addition, a positive short-term effect of the VR exergame on BP behavior (postexercise hypotension) was observed after both VR sessions. The preliminary results indicate that a VR exergaming could lead to blood pressure lowering effects for older people with hypertension.

Background Oxylipins, the oxidative metabolites of polyunsaturated fatty acids (PUFAs), serve as key mediators of oxidative stress, inflammatory responses, and vasoactive reactions in vivo. Our previous work has established that hemodialysis affects both long chain fatty acids (LCFAs) and oxylipins in plasma and erythrocytes to varying degrees, which may be responsible for excess cardiovascular complications in end-stage renal disease. In this study, we aimed to determine changes in blood oxylipins during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery to identify novel biomarkers and potential metabolites of CPB-related complications. We tested the hypothesis that CPB would differentially affect plasma oxylipins and erythrocytes oxylipins.Methods We conducted a prospective observational study of 12 patients undergoing elective cardiac surgery with expected CPB procedure. We collected venous and arterial blood samples before CPB, 15 and 45 min after the start of CPB, and 60 min after the end of CPB, respectively. Oxylipins profiling in plasma and erythrocytes was achieved using targeted HPLC-MS mass spectrometry.Results Our results revealed that most venous plasma diols and hydroxy- oxylipins decreased after CPB initiation, with a continuous decline until the termination of CPB. Nevertheless, no statistically significant alterations were detected in erythrocytes oxylipins at all time points.Conclusions CPB decreases numerous diols and hydroxy oxylipins in blood plasma, whereas no changes in erythrocytes oxylipins are observed during this procedure in patients undergoing cardiac surgery. As lipid mediators primarily responsive to CPB, plasma diols and hydroxy oxylipins may serve as potential key biomarkers for CPB-related complications.

Background: The challenges in developing new bone replacement materials and procedures reside not solely in technological innovation and advancement, but also in a broader patient therapy acceptance. Therefore, there is a need to assess patients' perspectives on the materials and approaches in use as well as the ones being developed to better steer future progress in the field. Methods: A self-initiating cross-sectional questionnaire aimed at people seeking treatment at the university hospital environment of Charite Berlin was formulated. The survey contained 15 close-ended questions directed toward the participant's epidemiological profile, willingness, acceptance, and agreement to receive different bone replacement materials, as well as, worries about the post-surgical consequences that can arise post bone replacement surgery. Descriptive and categorical analysis was performed to compare the observed number of subjects, their profile and each related response (Pearson's chi-square test or Fischer's test, p < 0.05). Results: A total of 198 people engaged with the questionnaire, most of them Millennials. Overall patients trusted scientifically developed biomaterials designed for bone replacement, as demonstrated by their willingness to participate in a clinical trial, their acceptance of alloplastic materials, and the none/few worries about the presence of permanent implants. The data revealed the preferences of patients towards autologous sources of cells and blood to be used with a biomaterial. The data have also shown that both generation and education influenced willingness to participate in a clinical trial and acceptance of alloplastic materials, as well as, worries about the presence of permanent implants and agreement to receive a material with pooled blood and cells. Conclusion: Patients were open to the implantation of biomaterials for bone replacement, with a preference toward autologous sources of blood and/or tissue. Moreover, patients are concerned about strategies based on permanent implants, which indicates a need for resorbable materials. The knowledge gained in this study supports the development of new bone biomaterials.