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Ancient whole-genome duplications are believed to facilitate novelty and adaptation by providing the raw fuel for new genes. However, it is unclear how recent whole-genome duplications may contribute to evolvability within recent polyploids. Hybridization accompanying some whole-genome duplications may combine divergent gene content among diploid species. Some theory and evidence suggest that polyploids have a greater accumulation and tolerance of gene presence–absence and genomic structural variation, but it is unclear to what extent either is true. To test how recent polyploidy may influence pangenomic variation, we sequenced, assembled, and annotated 12 complete, chromosome-scale genomes of Camelina sativa, an allohexaploid biofuel crop with 3 distinct subgenomes. Using pangenomic comparative analyses, we characterized gene presence–absence and genomic structural variation both within and between the subgenomes. We found over 75% of ortholog gene clusters are core in C. sativaand <10% of sequence space was affected by genomic structural rearrangements. In contrast, 19% of gene clusters were unique to one subgenome, and the majority of these were Camelina specific (no ortholog in Arabidopsis). We identified an inversion that may contribute to vernalization requirements in winter-type Camelina and an enrichment of Camelina-specific genes with enzymatic processes related to seed oil quality and Camelina's unique glucosinolate profile. Genes related to these traits exhibited little presence–absence variation. Our results reveal minimal pangenomic variation in this species and instead show how hybridization accompanied by whole-genome duplication may benefit polyploids by merging diverged gene content of different species.

The article "Revisiting Alexander von Humboldt" provides a comprehensive overview of the life and impact of Alexander von Humboldt, a prominent naturalist and scientist from the late 18th and early 19th centuries. It explores Humboldt's wide-ranging scientific interests, his interconnected view of nature and society, and his interactions with the political and social landscapes of his time. The text emphasizes the need to understand Humboldt within the historical context of his era, shedding light on his multifaceted personality and the significant changes he witnessed during his lifetime. Additionally, the article delves into Humboldt's scientific experiments, personal relationships, and groundbreaking explorations, offering a nuanced perspective on his contributions to science and society. [Extracted from the article]

The article in Natural History delves into the life and impact of Alexander von Humboldt, a prominent naturalist and scientist of the 18th and 19th centuries. Humboldt's extensive travels and diverse interests in botany, geology, and languages have left a lasting influence on the scientific community. The text explores Humboldt's interactions with authoritarian regimes, his views on nature and society, and his role in a transformative era marked by revolutions and industrialization. It also discusses his scientific investigations, personal relationships, and decision to pursue scientific exploration in the Americas with Aimé Bonpland. Overall, the article provides a nuanced view of Humboldt's complex personality and significant contributions to various fields. [Extracted from the article]

The 2D Ruddlesden–Popper (RP) perovskites Cs2PbI2Cl2(Pb-based, n= 1) and Cs2SnI2Cl2(Sn-based, n= 1) stand out as unique and rare instances of entirely inorganic constituents within the more expansive category of organic/inorganic 2D perovskites. These materials have recently garnered significant attention for their strong UV-light responsiveness, exceptional thermal stability, and theoretically predicted ultrahigh carrier mobility. In this study, we synthesized Pb and Sn-based n= 1 2D RP perovskite films covering millimeter-scale areas for the first time, utilizing a one-step chemical vapor deposition (CVD) method under atmospheric conditions. These films feature perovskite layers oriented horizontally relative to the substrate. Multilayered Cs3Pb2I3Cl4(Pb-based, n= 2) and Cs3Sn2I3Cl4(Sn-based, n= 2) films were also obtained for the first time, and their crystallographic structures were refined by combining X-ray diffraction (XRD) and density functional theory (DFT) calculations. DFT calculations and experimental optical spectroscopy support band-gap energy shifts related to the perovskite layer thickness. We demonstrate bias-free photodetectors using the Sn-based, n= 1 perovskite with reproducible photocurrent and a fast 84 ms response time. The present work not only demonstrates the growth of high-quality all-inorganic multilayered 2D perovskites via the CVD method but also suggests their potential as promising candidates for future optoelectronic applications.

Background: Laparoscopic cholecystectomy is a very frequent surgical procedure. However, in an ageing society, less surgical staff will need to perform surgery on patients. Collaborative surgical robots (cobots) could address surgical staff shortages and workload. To achieve context-awareness for surgeon-robot collaboration, the intraoperative action workflow recognition is a key challenge. Methods: A surgical process model was developed for intraoperative surgical activities including actor, instrument, action and target in laparoscopic cholecystectomy (excluding camera guidance). These activities, as well as instrument presence and surgical phases were annotated in videos of laparoscopic cholecystectomy performed on human patients (n= 10) and on explanted porcine livers (n= 10). The machine learning algorithm Distilled-Swin was trained on our own annotated dataset and the CholecT45 dataset. The validation of the model was conducted using a fivefold cross-validation approach. Results: In total, 22,351 activities were annotated with a cumulative duration of 24.9 h of video segments. The machine learning algorithm trained and validated on our own dataset scored a mean average precision (mAP) of 25.7% and a top K= 5 accuracy of 85.3%. With training and validation on our dataset and CholecT45, the algorithm scored a mAP of 37.9%. Conclusions: An activity model was developed and applied for the fine-granular annotation of laparoscopic cholecystectomies in two surgical settings. A machine recognition algorithm trained on our own annotated dataset and CholecT45 achieved a higher performance than training only on CholecT45 and can recognize frequently occurring activities well, but not infrequent activities.

Zygnematophyceae are the algal sisters of land plants. Here we sequenced four genomes of filamentous Zygnematophyceae, including chromosome-scale assemblies for three strains of Zygnema circumcarinatum. We inferred traits in the ancestor of Zygnematophyceae and land plants that might have ushered in the conquest of land by plants: expanded genes for signaling cascades, environmental response, and multicellular growth. Zygnematophyceae and land plants share all the major enzymes for cell wall synthesis and remodifications, and gene gains shaped this toolkit. Co-expression network analyses uncover gene cohorts that unite environmental signaling with multicellular developmental programs. Our data shed light on a molecular chassis that balances environmental response and growth modulation across more than 600 million years of streptophyte evolution.

Agricultural studies mainly rely on quantitative research approaches. Despite growing interest in and uptake of qualitative, participatory, and visual methods due to their perceived advantages in gathering in-depth information and empowering participants, visual–digital research methods have yet to be largely applied. In our study on adaptation strategies to climate change among smallholder farmers in Uganda we compared different data collection methods, including: semi-structured interviews with manual note-taking, participatory impact diagrams, and adapted photovoice and cellphilm methodologies.

Genetic diversity is critical to crop breeding and improvement, and dissection of the genomic variation underlying agronomic traits can both assist breeding and give insight into basic biological mechanisms. Although recent genome analyses in plants reveal many structural variants (SVs), most current studies of crop genetic variation are dominated by single-nucleotide polymorphisms (SNPs). The extent of the impact of SVs on global trait variation, as well as their utility in genome-wide selection, is not yet understood. In this study, we built an SV data set based on whole-genome resequencing of diverse sorghum lines (n = 363), validated the correlation of photoperiod sensitivity and variety type, and identified SV hotspots underlying the divergent evolution of cellulosic and sweet sorghum. In addition, we showed the complementary contribution of SVs for heritability of traits related to sorghum adaptation. Importantly, inclusion of SV polymorphisms in association studies revealed genotype–phenotype associations not observed with SNPs alone. Three-way genome-wide association studies (GWAS) based on whole-genome SNP, SV, and integrated SNP + SV data sets showed substantial associations between SVs and sorghum traits. The addition of SVs to GWAS substantially increased heritability estimates for some traits, indicating their important contribution to functional allelic variation at the genome level. Our discovery of the widespread impacts of SVs on heritable gene expression variation could render a plausible mechanism for their disproportionate impact on phenotypic variation. This study expands our knowledge of SVs and emphasizes the extensive impacts of SVs on sorghum.

Covalent organic frameworks (COFs) are a promising class of crystalline polymer networks that are useful due to their high porosity, versatile functionality, and tunable architecture. Conventional solution-based methods of producing COFs are marred by slow reactions that produce powders that are difficult to process into adaptable form factors for functional applications, and there is a need for facile and fast synthesis techniques for making crystalline and ordered covalent organic framework (COF) thin films. In this work, we report a chemical vapor deposition (CVD) approach utilizing co-evaporation of two monomers onto a heated substrate to produce highly crystalline, defect-free COF films and coatings with hydrazone, imine, and ketoenamine COF linkages. This all-in-one synthesis technique produces highly crystalline, 40 nm–1 μm-thick COF films on Si/SiO2substrates in less than 30 min. Crystallinity and alignment were proven by using a combination of grazing-incidence wide-angle X-ray scattering (GIWAXS) and transmission electron microscopy (TEM), and successful conversion of the monomers to produce the target COF was supported by Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and UV–vis measurements. Additionally, we used atomic force microscopy (AFM) to investigate the growth mechanisms of these films, showing the coalescence of triangular crystallites into a smooth film. To show the wide applicability and scope of the CVD process, we also prepared crystalline ordered COF films with imine and ketoenamine linkages. These films show potential as high-quality size exclusion membranes, catalytic platforms, and organic transistors.

Background: With Surgomics, we aim for personalized prediction of the patient's surgical outcome using machine-learning (ML) on multimodal intraoperative data to extract surgomic features as surgical process characteristics. As high-quality annotations by medical experts are crucial, but still a bottleneck, we prospectively investigate active learning (AL) to reduce annotation effort and present automatic recognition of surgomic features. Methods: To establish a process for development of surgomic features, ten video-based features related to bleeding, as highly relevant intraoperative complication, were chosen. They comprise the amount of blood and smoke in the surgical field, six instruments, and two anatomic structures. Annotation of selected frames from robot-assisted minimally invasive esophagectomies was performed by at least three independent medical experts. To test whether AL reduces annotation effort, we performed a prospective annotation study comparing AL with equidistant sampling (EQS) for frame selection. Multiple Bayesian ResNet18 architectures were trained on a multicentric dataset, consisting of 22 videos from two centers. Results: In total, 14,004 frames were tag annotated. A mean F1-score of 0.75 ± 0.16 was achieved for all features. The highest F1-score was achieved for the instruments (mean 0.80 ± 0.17). This result is also reflected in the inter-rater-agreement (1-rater-kappa > 0.82). Compared to EQS, AL showed better recognition results for the instruments with a significant difference in the McNemar test comparing correctness of predictions. Moreover, in contrast to EQS, AL selected more frames of the four less common instruments (1512 vs. 607 frames) and achieved higher F1-scores for common instruments while requiring less training frames. Conclusion: We presented ten surgomic features relevant for bleeding events in esophageal surgery automatically extracted from surgical video using ML. AL showed the potential to reduce annotation effort while keeping ML performance high for selected features. The source code and the trained models are published open source. Graphical abstract:

Technologies of self-sovereign identity (SSI) and Web3 tools that strongly protect individual autonomy, combined with the ethics of Asian altruism, can effectively guide the governance of the emerging cyber civilization. In contrast, governance in Western industrial civilization stresses the pursuit of individual self-interest and struggles to balance the benefits of big tech with the protection of individual dignity and the preservation of the common good. We demonstrate, with reference to a local community in Japan, that SSI is successful in encouraging communal collaboration and well-being while providing individuals with greater control over their personal data. We also show that Web3 tools provide incentives for altruistic behaviors while safeguarding SSI. Integration of SSI and social protection demonstrates the potential for building an information society grounded in altruistic values, honoring individual dignity, and recognizing the government’s role in protecting social welfare. Ultimately, this research unveils how altruistic values can be fostered through SSI and Web3.

Background: Laparoscopic videos are increasingly being used for surgical artificial intelligence (AI) and big data analysis. The purpose of this study was to ensure data privacy in video recordings of laparoscopic surgery by censoring extraabdominal parts. An inside-outside-discrimination algorithm (IODA) was developed to ensure privacy protection while maximizing the remaining video data. Methods: IODAs neural network architecture was based on a pretrained AlexNet augmented with a long-short-term-memory. The data set for algorithm training and testing contained a total of 100 laparoscopic surgery videos of 23 different operations with a total video length of 207 h (124 min ± 100 min per video) resulting in 18,507,217 frames (185,965 ± 149,718 frames per video). Each video frame was tagged either as abdominal cavity, trocar, operation site, outside for cleaning, or translucent trocar. For algorithm testing, a stratified fivefold cross-validation was used. Results: The distribution of annotated classes were abdominal cavity 81.39%, trocar 1.39%, outside operation site 16.07%, outside for cleaning 1.08%, and translucent trocar 0.07%. Algorithm training on binary or all five classes showed similar excellent results for classifying outside frames with a mean F1-score of 0.96 ± 0.01 and 0.97 ± 0.01, sensitivity of 0.97 ± 0.02 and 0.0.97 ± 0.01, and a false positive rate of 0.99 ± 0.01 and 0.99 ± 0.01, respectively. Conclusion: IODA is able to discriminate between inside and outside with a high certainty. In particular, only a few outside frames are misclassified as inside and therefore at risk for privacy breach. The anonymized videos can be used for multi-centric development of surgical AI, quality management or educational purposes. In contrast to expensive commercial solutions, IODA is made open source and can be improved by the scientific community.

There are mainly two types of particle flows in the design of particle flow filters, i.e., the deterministic flows and the stochastic flows as diffusion processes. These two types of flows seem to share little commonality. In this article, we revisit the design of particle flow filters and build a connection between these two types of particle flows, i.e., a deterministic flow can be obtained by modifying a stochastic flow, and vice versa. Particle flows are represented by differential equations that are often realized in practice by difference equations through discretization. The accuracy of such numerical approximations is impacted by the transient dynamics of particle flows. We examine the role of the diffusion matrix in changing the transient dynamics of stochastic particle flows. We propose methods for the design of the diffusion matrix to improve the transient dynamics of particle flows from three perspectives, i.e., condition number reduction, feedback control, and covariance reduction. Analytical forms of optimal diffusion matrices are obtained for reducing filtering errors. Numerical examples are included to illustrate the results.

BackgroundCopy number variants (CNVs) associated with late-onset medical conditions are rare but important secondary findings in chromosomal microarray analysis (CMA) performed during pregnancy. Here, we critically review the cases at two tertiary centres to assess the criteria which guide the disclosure of such findings and develop a disclosure decision tool (DDT) aimed at facilitating disclosure decision. Parental decisions on receiving CNVs associated with risks for late-onset conditions were also recorded.MethodsPrenatal CMAs in Hadassah and Shaare Zedek Medical Centers from November 2013 to October 2021 were reviewed for CNVs associated with late-onset conditions. The DDT proposed uses a five-parameter scoring system, which considers the severity, median age of onset, penetrance, understanding of genotype-phenotype correlation and actionability of the finding.ResultsOut of 16 238 prenatal CMAs, 16 (0.1%) harboured CNVs associated with late-onset conditions, 15 of which were disclosed. Outcome information was available on 13 of the 16 pregnancies, all of which continued to delivery.ConclusionsOur suggested DDT will help clinicians to quantitatively weigh the variables associated with CNVs of this type and arrive at a well thought out clinical decision regarding disclosure. Although the prevalence of late-onset conditions as a major finding in the prenatal setup is low, it is expected to rise with the increasing use of non-invasive CMA testing and whole exome and genome sequencing.

We study the origin and formation of antiphase domains (APDs) and related defects in 7 nm thin, lattice-matched GaP buffer layers deposited by metal–organic chemical vapor deposition (MOCVD) on well-defined, nearly single-domain, double-layer stepped, low-miscut Si(100) substrates obtained by specific treatment with arsenic. Using dark-field imaging modes in low-energy electron microscopy (LEEM), the minority reconstruction domains of Si(100):As and the APDs of the deposited GaP epilayer are identified, quantified, and compared. We show that residual (2 × 1)-reconstructed terraces of the minority domain on the Si substrate cause the formation of APDs and that the fraction of the minority domain of the substrate (≅0.07) entails a comparable fraction of APDs in thin GaP epilayers. The topographies of APDs are revealed by atomic force microscopy (AFM) and by scanning tunneling microscopy (STM). We observe two very different APD-related defects in the GaP epilayer, both pinned to residual monolayer steps of the substrate. GaP growth on minority domain terraces with widths in the range of 40–100 nm gives rise to APDs of comparable lateral dimensions. Minority domain terraces of the substrate with widths <20 nm cause the formation of 7–20 nm wide trenches in the GaP layer with rampart-like mounds along their rims. Using nanoscale Auger electron spectroscopy (AES), we provide evidence that these trenches extend through the GaP layer down to the exposed, uncovered Si substrate. We conclude that nucleation of GaP on small minority domain terraces is largely inhibited as most Ga and P atoms deposited on these terraces diffuse across the domain boundary and side walls of emerging trenches to adjacent majority domain terraces where they form the observed mounds. Nucleation of GaP does take place on minority domain terraces with widths ≥40 nm and leads to the growth of APDs.

The processes leading from disturbed B-cell development to adult B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) remain poorly understood. Here, we describe Irf4−/−mice as prone to developing BCP-ALL with age. Irf4−/−preB-I cells exhibited impaired differentiation but enhanced proliferation in response to IL-7, along with reduced retention in the IL-7 providing bone marrow niche due to decreased CXCL12 responsiveness. Thus selected, preB-I cells acquired Jak3mutations, probably following irregular AID activity, resulting in malignant transformation. We demonstrate heightened IL-7 sensitivity due to Jak3mutants, devise a model to explain it, and describe structural and functional similarities to Jak2mutations often occurring in human Ph-like ALL. Finally, targeting JAK signaling with Ruxolitinib in vivo prolonged survival of mice bearing established Irf4−/−leukemia. Intriguingly, organ infiltration including leukemic meningeosis was selectively reduced without affecting blood blast counts. In this work, we present spontaneous leukemogenesis following IRF4 deficiency with potential implications for high-risk BCP-ALL in adult humans.

Background: Personalized medicine requires the integration and analysis of vast amounts of patient data to realize individualized care. With Surgomics, we aim to facilitate personalized therapy recommendations in surgery by integration of intraoperative surgical data and their analysis with machine learning methods to leverage the potential of this data in analogy to Radiomics and Genomics. Methods: We defined Surgomics as the entirety of surgomic features that are process characteristics of a surgical procedure automatically derived from multimodal intraoperative data to quantify processes in the operating room. In a multidisciplinary team we discussed potential data sources like endoscopic videos, vital sign monitoring, medical devices and instruments and respective surgomic features. Subsequently, an online questionnaire was sent to experts from surgery and (computer) science at multiple centers for rating the features’ clinical relevance and technical feasibility. Results: In total, 52 surgomic features were identified and assigned to eight feature categories. Based on the expert survey (n= 66 participants) the feature category with the highest clinical relevance as rated by surgeons was “surgical skill and quality of performance” for morbidity and mortality (9.0 ± 1.3 on a numerical rating scale from 1 to 10) as well as for long-term (oncological) outcome (8.2 ± 1.8). The feature category with the highest feasibility to be automatically extracted as rated by (computer) scientists was “Instrument” (8.5 ± 1.7). Among the surgomic features ranked as most relevant in their respective category were “intraoperative adverse events”, “action performed with instruments”, “vital sign monitoring”, and “difficulty of surgery”. Conclusion: Surgomics is a promising concept for the analysis of intraoperative data. Surgomics may be used together with preoperative features from clinical data and Radiomics to predict postoperative morbidity, mortality and long-term outcome, as well as to provide tailored feedback for surgeons. Graphical abstract:

ABSTRACTBefore the COVID-19 pandemic, online education had grown steadily over the past decade as more K-12 schools and districts expanded their educational options. This included the use of virtual school days, hybrid learning, and fully online courses. Enrollments in K-12 Online Physical Education (OLPE) had also increased steadily over the past decade, representing almost ten percent of total online course completions (Distance Learning Collaborative (DLC), (2019). The purpose of this article is to present a coherent agenda for future research related to K-12 OLPE using current research as a foundation. The Society of Health and Physical Education (SHAPE) America’s Essential Components of Physical Educationserved as the framework for this article. Overall, limited research has been conducted regarding the policies and decisions that drive the development and implementation of OLPE. Current research does, however, provide some clarity related to OLPE curriculum, instructional practices, and student assessment. K-12 OLPE is not an abstract idea that might come about in the future. It is part of the here and now, especially considering the shift toward distance learning due to the COVID-19 pandemic. Scholars must cultivate a coherent research agenda and move beyond the current exploratory studies to answer some of the most poignant questions surrounding OLPE.

In the quest to reduce global under- and malnutrition, which are particularly high among smallholder farmers, agriculture-nutrition linkages are receiving increasing attention. Researchers have analyzed the link between the quantity and diversity of food that farmers produce and nutritional outcomes but paid limited attention to a third agriculture-nutrition link: the link between howfood is produced and nutritional outcomes. This neglect persists despite the majority of smallholder farmers relying on hand tools for farming, which implies heavy physical work and, thus, high energy requirements. To address this research gap, this study compares the energy requirements of farm households in rural Zambia that are characterized by three different levels of mechanization: hand tools, animal drought power, and tractors. 1638 days of detailed time-use and nutrition data were collected from 186 male and female adults and boys and girls during different seasons (land preparation, weeding, and harvesting/processing) using an innovative picture-based smartphone app called “Timetracker”. This data served to calculate different proxies for physical activity and energy requirements using “Ainsworth’s Compendium of Physical Activities”. The results suggest that detailed time-use data offers great potentials to study physical activity and energy requirements. The findings show strong linkages between farm technologies, physical activity levels, and energy requirements, suggesting that this agriculture-nutrition link deserves more scientific and political attention to reduce under- and malnutrition among smallholder farmers.

ObjectiveA considerable proportion of patients with irritable bowel syndrome (IBS) may be wheat-sensitive and respond to a gluten-free diet (GFD) although they do not have coeliac disease. However, a diagnostic test for wheat sensitivity (WS) is missing. Our study evaluated the diagnostic accuracy (sensitivity and specificity) of confocal laser endomicroscopy (CLE) for the identification of WS as primary outcome.DesignIn this prospective, double-blind diagnostic study 147 non-coeliac patients fulfilling the Rome III criteria for IBS were tested by CLE for duodenal changes after wheat (index test), soy, yeast or milk exposure. Patients with IBS responding to 2 months of GFD were classified as having WS (reference test) using response criteria recommended by regulatory bodies for pharmaceutical trials of patients with IBS. After 2 months, CLE results were unblinded and patients were advised to exclude those food components that had led to a positive CLE reaction. The clinical response was assessed at follow-up after 6 and 12 months.ResultsOf 130 patients who completed the study per protocol, 74 (56.9%) responded to GFD and were classified as WS after 2 months, and 38 of these 74 patients were correctly identified by CLE (sensitivity 51.4%; 97.5% CI: 38.7% to 63.9%). A total of 38 of 56 patients without WS were correctly identified by CLE (specificity 67.9%; 97.5% CI: 52.9% to 79.9%). At 6 months follow-up, CLE correctly identified 49 of 59 food-sensitive patients (sensitivity 83.1%; 97.5% CI: 69.9% to 91.3%) but specificity was only 32% (97.5% CI: 15.7% to 54.3%).ConclusionIn light of the high proportion of patients with IBS responding to GFD, the diagnostic accuracy of CLE is too low to recommend widespread use of this invasive procedure.Trail registration numberThis study was registered as clinical trial in the German Registry for Clinical Studies (DRKS00010123).

The yield of chromosomal microarray analysis (CMA) is well established in structurally normal fetuses (0.4–1.4%). We aimed to determine the incremental yield of exome sequencing (ES) in this population. From February 2017 to April 2022, 1,526 fetuses were subjected to ES; 482 of them were structurally normal (31.6%). Only pathogenic and likely pathogenic (P/LP) variants, per the American College of Medical Genetics and Genomics (ACMG) classification, were reported. Additionally, ACMG secondary findings relevant to childhood were reported. Four fetuses (4/482; 0.8%) had P/LP variants indicating a moderate to severe disease in ATP7B, NR2E3, SPRED1and FGFR3, causing Wilson disease, Enhanced S-cone syndrome, Legius and Muenke syndromes, respectively. Two fetuses had secondary findings, in RETand DSP. Our data suggest that offering only CMA for structurally normal fetuses may provide false reassurance. Prenatal ES mandates restrictive analysis and careful management combined with pre and post-test genetic counseling.

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