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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

Phages are viruses that infect bacteria and dominate every ecosystem on our planet. As well as impacting microbial ecology, physiology and evolution, phages are exploited as tools in molecular biology and biotechnology. This is particularly true for the Ff (f1, fd or M13) phages, which represent a widely distributed group of filamentous viruses. Over nearly five decades, Ffs have seen an extraordinary range of applications, yet the complete structure of the phage capsid and consequently the mechanisms of infection and assembly remain largely mysterious. In this work, we use cryo-electron microscopy and a highly efficient system for production of short Ff-derived nanorods to determine a structure of a filamentous virus including the tips. We show that structure combined with mutagenesis can identify phage domains that are important in bacterial attack and for release of new progeny, allowing new models to be proposed for the phage lifecycle.

Background Detection of circulating tumour DNA (ctDNA) in biological fluids is a minimally invasive alternative to tissue biopsy for therapy monitoring. Cytokines are released in the tumour microenvironment to influence inflammation and tumorigenic mechanisms. Here, we investigated the potential biomarker utility of circulating cytokines vis-à-vis ctDNA in ALK-rearranged+ lung adenocarcinoma (ALK + NSCLC) and explored the optimal combination of molecular parameters that could indicate disease progression. Methods Longitudinal serum samples (n = 296) were collected from ALK + NSCLC patients (n = 38) under tyrosine kinase inhibitor (TKI) therapy and assayed to quantify eight cytokines: IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, MCP1 and TNF-α. Generalised linear mixed-effect modelling was performed to test the performance of different combinations of cytokines and previously determined ctDNA parameters in identifying progressive disease. Results Serum IL-6, IL-8 and IL-10 were elevated at progressive disease, with IL-8 having the most significant impact as a biomarker. Integrating changes in IL-8 with ctDNA parameters maximised the performance of the classifiers in identifying disease progression, but this did not significantly outperform the model based on ctDNA alone. Conclusions Serum cytokine levels are potential disease progression markers in ALK + NSCLC. Further validation in a larger and prospective cohort is necessary to determine whether the addition of cytokine evaluation could improve current tumour monitoring modalities in the clinical setting.

Normothermic machine perfusion (NMP) has emerged as an innovative organ preservation technique. Developing an understanding for the donor organ immune cell composition and its dynamic changes during NMP is essential. We aimed for a comprehensive characterization of immune cell (sub)populations, cell trafficking and cytokine release during liver NMP. Single-cell transcriptome profiling of human donor livers prior to, during NMP and after transplantation shows an abundance of CXC chemokine receptor 1+/2+ (CXCR1+/CXCR2+) neutrophils, which significantly decreased during NMP. This is paralleled by a large efflux of passenger leukocytes with neutrophil predominance in the perfusate. During NMP, neutrophils shift from a pro-inflammatory state towards an aged/chronically activated/exhausted phenotype, while anti-inflammatory/tolerogenic monocytes/macrophages are increased. We herein describe the dynamics of the immune cell repertoire, phenotypic immune cell shifts and a dominance of neutrophils during liver NMP, which potentially contribute to the inflammatory response. Our findings may serve as resource to initiate future immune-interventional studies.

Goals constitute an important construct in developmental psychology. They represent a central way in which individuals shape their development. Here, we present two studies on age-related differences in one important goal dimension, goal focus, that is, the relative salience of the means and ends of goal pursuit. Extant studies on age-related differences in adults suggest a shift from focusing on the ends to focusing on the means across adulthood. The current studies aimed to expand this research to encompass the entire lifespan including childhood. The first cross-sectional study included participants spanning from early childhood into old age (N = 312, age range: 3–83 years) and used a multimethodological approach comprising eye tracking, behavioral, and verbal measures of goal focus. The second study investigated the verbal measures of the first study in more detail in an adult sample (N = 1550, age range: 17–88 years). Overall, the results do not show a clear pattern, making them difficult to interpret. There was little convergence of the measures, pointing to the difficulties in assessing a construct such as goal focus across a large range of age groups differing in social-cognitive and verbal skills.

There is an urgent need for agri-food system transformation to achieve global sustainability goals. Innovations can play a key role in this transformation but often come with both sustainability synergies and trade-offs. One such innovation is agricultural mechanization, which is spreading rapidly in parts of the Global South and is high on the policy agenda in others. The rapid spread of mechanization is fundamentally changing the character of agri-food systems in the Global South, with both positive and negative effects. However, while some of these effects have been well explored, no study so far has systematically reviewed the sustainability synergies and trade-offs associated with mechanization, undermining necessary accompanying research and policy efforts. This review provides an overview of the progress toward mechanization across the Global South, identifies drivers and barriers, assesses sustainability synergies and trade-offs, and discusses options to maximize sustainability outcomes. The review is the first to holistically assess the potentials and risks of agricultural mechanization for the sustainable transformation of agri-food systems in the Global South, taking into account all pillars of sustainability. The review suggests that agricultural mechanization is needed to make agri-food systems more sustainable concerning various economic and social aspects, such as labor productivity, poverty reduction, food security, and health and well-being. However, there are also sustainability risks concerning environmental aspects such as biodiversity loss and land degradation, and economic and social concerns related to lacking inclusiveness and growing inequalities, among others. A wide range of technological and institutional solutions is identified to harness the potential of agricultural mechanization for sustainable agri-food system transformation, while at the same time minimizing the risks. However, more efforts are needed to implement such solutions at scale and ensure that mechanization contributes to agri-food systems that respect all pillars of sustainability.

Background While early mobilization is commonly implemented in intensive care unit treatment guidelines to improve functional outcome, the characterization of the optimal individual dosage (frequency, level or duration) remains unclear. The aim of this study was to demonstrate that artificial intelligence-based clustering of a large ICU cohort can provide individualized mobilization recommendations that have a positive impact on the likelihood of being discharged home. Methods This study is an analysis of a prospective observational database of two interdisciplinary intensive care units in Munich, Germany. Dosage of mobilization is determined by sessions per day, mean duration, early mobilization as well as average and maximum level achieved. A k-means cluster analysis was conducted including collected parameters at ICU admission to generate clinically definable clusters. Results Between April 2017 and May 2019, 948 patients were included. Four different clusters were identified, comprising “Young Trauma,” “Severely ill & Frail,” “Old non-frail” and “Middle-aged” patients. Early mobilization (adj 10.0 [2.8 to 44.0], p adj 24.0 [7.4 to 86.1], p adj 4.7 [1.2 to 23.2], p = 0.035 and ORadj 8.1 [1.8 to 45.8], p = 0.010). Conclusions An artificial intelligence-based learning approach was able to divide a heterogeneous critical care cohort into four clusters, which differed significantly in their clinical characteristics and in their mobilization parameters. Depending on the cluster, different mobilization strategies supported the likelihood of being discharged home enabling an individualized and resource-optimized mobilization approach. Trial Registration: Clinical Trials NCT03666286, retrospectively registered 04 September 2018.

Studying the legume nodule microbiome is important for understanding the development and nutrition of the plants inhabited by the various microbes within and upon them. We analyzed the microbiomes of these underground organs from both an important crop plant (Medicago sativa) and a related legume (M. polymorpha) using metagenomic and culture-based techniques to identify the main cultivatable contributors to plant growth enhancement. Using high-throughput sequencing, culturing, and in planta techniques, we identified and analyzed a broad population of the bacterial taxa within Medicago nodules and the surrounding soil. Fifty-one distinct bacterial strains were isolated and characterized from nodules of both Medicago species and their growth-promoting activities were studied. Sequencing of 16S rRNA gene amplicons showed that in addition to Ensifer, the dominant genus, a large number of Gram-positive bacteria belonging to the Firmicutes and Actinobacteria were also present. After performing ecological and plant growth-promoting trait analyses, selecting the most promising strains, and then performing in planta assays, we found that strains of Bacillus and Micromonospora among others could play important roles in supporting the growth, health, and productivity of the host plant. To our knowledge, the comparison of the biodiversity of the microbiota of undomesticated vs. cultivated Medicago roots and nodules is novel and shows the range of potential Plant Growth-Promoting Bacteria that could be used for plants of agricultural interest. These and other nodule-isolated microbes could also serve as inoculants with rhizobia with the goal of replacing synthetic fertilizers and pesticides for sustainable agriculture.

Pili are filamentous surface extensions that play roles in bacterial and archaeal cellular processes such as adhesion, biofilm formation, motility, cell-cell communication, DNA uptake and horizontal gene transfer. The model archaeaon Sulfolobus acidocaldarius assembles three filaments of the type-IV pilus superfamily (archaella, archaeal adhesion pili and UV-inducible pili), as well as a so-far uncharacterised fourth filament, named “thread”. Here, we report on the cryo-EM structure of the archaeal thread. The filament is highly glycosylated and consists of subunits of the protein Saci_0406, arranged in a head-to-tail manner. Saci_0406 displays structural similarity, but low sequence homology, to bacterial type-I pilins. Thread subunits are interconnected via donor strand complementation, a feature reminiscent of bacterial chaperone-usher pili. However, despite these similarities in overall architecture, archaeal threads appear to have evolved independently and are likely assembled by a distinct mechanism.

Organisms orchestrate cellular functions through transcription factor (TF) interactions with their target genes, although these regulatory relationships are largely unknown in most species. Here we report a high-throughput approach for characterizing TF-target gene interactions across species and its application to 354 TFs across 48 bacteria, generating 17,000 genome-wide binding maps. This dataset revealed themes of ancient conservation and rapid evolution of regulatory modules. We observed rewiring, where the TF sensing and regulatory role is maintained while the arrangement and identity of target genes diverges, in some cases encoding entirely new functions. We further integrated phenotypic information to define new functional regulatory modules and pathways. Finally, we identified 242 new TF DNA binding motifs, including a 70% increase of known Escherichia coli motifs and the first annotation in Pseudomonas simiae, revealing deep conservation in bacterial promoter architecture. Our method provides a versatile tool for functional characterization of genetic pathways in prokaryotes and eukaryotes.

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 how food 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.

Purpose Adenocarcinomas of the esophagus (AEG) and stomach (AS) are among the most common cancers worldwide. Novel markers for risk stratification and guiding treatment are strongly needed. Activin is a multi-functional cytokine with context specific pro- and anti-tumorigenic effects. We aimed to investigate the prognostic role of activin tumor protein expression in AEG/ASs. Methods Tissue from a retrospective cohort of 277 patients with AEG/AS treated primarily by surgery at the Charité - Universitätsmedizin Berlin was collected and analyzed by immunohistochemistry using a specific antibody to the activin homodimer inhibin beta A. Additionally, we evaluated T-cell infiltration and PD1 expression as well as expression of PD-L1 by immunohistochemistry as possible confounding factors. Clinico-pathologic data were collected and correlated with activin protein expression. Results Out of 277 tumor samples, 72 (26.0%) exhibited high activin subunit inhibin beta A protein expression. Higher expression was correlated with lower Union for International Cancer Control (UICC) stage and longer overall survival. Interestingly, activin subunit expression correlated with CD4+ T-cell infiltration, and the correlation with higher overall survival was exclusively seen in tumors with high CD4+ T-cell infiltration, pointing towards a role of activin in the tumor immune response in AEG/ASs. Conclusion In our cohort of AEG/AS, higher activin subunit levels were correlated with longer overall survival, an effect exclusively seen in tumors with high CD4+ cell infiltration. Further mechanistic research is warranted discerning the exact effect of this context specific cytokine.

High-density lipoprotein (HDL), best known for cholesterol transport, also has anti-inflammatory effects. Previous studies suggest involvement of myeloperoxidase (MPO) in modification of HDL. HDL bound Sphingosine-1-phosphate (S1P) has been implied to be an essential protein regarding beneficial HDL effects. In this study, we analyzed anti-inflammatory HDL properties in patients with atrial fibrillation (AF), a disease involving atrial inflammation, compared to non-AF controls and whether anti-inflammatory properties improve upon catheter ablation. Additionally, association with serum concentrations of MPO and S1P were assessed. We isolated HDL from 25 AF patients, 13 non-AF individuals and 14 AF patients at follow-up (FU) after catheter ablation. S1P was measured in a cohort of 141 AF and 21 FU patients. Following preincubation with HDL from either group, bovine aortic endothelial cells were stimulated using tumor necrosis factor α and expression of pro-inflammatory genes intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), E-selectin (SELE) and P-selectin (SELP) was assessed using qPCR. Concentrations of circulating protein of these genes as well as MPO and S1P were measured in serum samples. Compared to non-AF individuals HDL from AF patients suppressed gene expression of the pro-inflammatory adhesion molecules ICAM1, VCAM1, SELE and SELP 27%, 18%, 21% and 57% less, respectively (p p = 0.06). In FU patients, the anti-inflammatory HDL activity was improved (suppression of ICAM1 + 22%, VCAM1 + 10%, SELE + 38% and SELP + 75%, p p = 0.08). AF patients using angiotensin converting enzyme inhibitors or angiotensin receptor blockers had better anti-inflammatory HDL properties than non-users (gene expression suppression at least 28% more, p p = 0.051). Circulating protein concentrations were not correlated with in vitro gene-expression, but circulating P-selectin was generally elevated in AF and FU patients compared to non-AF patients. MPO plasma concentration was positively associated with gene-expression of ICAM1, VCAM1 and SELP (r2 > 0.4, p p

Made available in DSpace on 2022-05-01T07:58:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 In this paper, the dynamical behavior of a four-dimensional magnetohydrodynamic model, consisting of a generalized Lorenz model, is investigated. A nonlinear dynamical analysis is performed using Lyapunov exponents and bifurcation diagrams, focusing on the chaotic and hyperchaotic behaviors associated with the bifurcation parameter (k1) that couples the equations of fluid displacement to the induced magnetic field. The State-dependent Riccati Equation (SDRE) and the Optimal Linear Feedback Control (OLFC) techniques are considered to design the state feedback control system that stabilizes the system to a previously defined orbit. The performance of the control systems are compared showing that the OLFC presents better results. Federal Technological University of Paraná School of Engineering São Paulo State University Faculty of Mechanical Engineering Lublin University of Technology Institute of Science and Technology São Paulo State University School of Engineering São Paulo State University Institute of Science and Technology São Paulo State University

Sialic acid Neu5Gc, a non-human glycan, is recognized as a new harmful substance that can cause vascular disease and cancer. Humans are unable to synthesize Neu5Gc due to a genetic defect that converts Neu5Ac to Neu5Gc, but Neu5Gc is often observed in human biological samples. Therefore, the demand for accurately measuring the amount of Neu5Gc present in human blood or tissues is rapidly increasing, but there is still no method to reliably quantify trace amounts of a non-human sugar. In particular, selective isolation and detection of Neu5Gc from human serum is analytically challenging due to the presence of excess sialic acid Neu5Ac, which has physicochemical properties very similar to Neu5Gc. Herein, we developed the label-free approach based on ZIC-HILIC/MRM-MS that can enrich sialic acids released from human serum and simultaneously monitor Neu5Ac and Neu5Gc. The combination of complete separation of Neu5Gc from abundant Neu5Ac by hydrophilic and electrostatic interactions with selective monitoring of structure-specific cross-ring cleavage ions generated by negative CID-MS/MS was remarkably effective for quantification of Neu5Ac and Neu5Gc at the femtomole level. Indeed, we were able to successfully determine the absolute quantitation of Neu5Gc from 30 healthy donors in the range of 3.336 ± 1.252 pg/μL (mean ± SD), 10,000 times lower than Neu5Ac. In particular, analysis of sialic acids in protein-free serum revealed that both Neu5Ac and Neu5G are mostly bound to proteins and/or lipids, but not in free form. In addition, the correlation between expression level of Neu5Gc and biological factors such as BMI, age, and sex was investigated. This method can be widely used in studies requiring sialic acid-related measurements such as disease diagnosis or prediction of immunogenicity in biopharmaceuticals as it is both fast and highly sensitive.

Carcinoma showing thymus-like elements (CASTLE) is an extremely rare malignant tumor of the thyroid gland and soft tissues of the neck with favorable prognosis. Histological features of the CASTLE are similar to thymic carcinoma, and it is assumed that it arises from the ectopic thymic tissue or the remnants of branchial pouches. The optimal treatment strategy is still uncertain because of the rarity of the tumor. The mainstay of treatment is surgery. The role of other modalities is unclear. We present a case report of a patient with locally advanced CASTLE of the thyroid gland who was not suitable for surgery and underwent radical radiotherapy with subsequent achievement of complete remission. We also present a literature review.

Sphingosin-1-phosphat (S1P) ist ein bioaktives Lipid, das wichtige Funktionen wie Barriere und Tonus der Gefase steuert. Im Gefassystem bindet S1P an 3 Rezeptoren (S1PR1-3). In der vorliegenden Arbeit wurde die Expression des S1PR3 in verschiedenen Gefasabschnitten und die Assoziation mit Atherosklerose im Menschen untersucht. Gewebeproben aus 6 Arterien (Koronararterie, A. carotis, Aorta ascendens, descendens und abdominalis sowie A. iliaca) wurden im Rahmen von Autopsien von 163 zufallig ausgewahlten Verstorbenen gewonnen. Anhand der Obduktionsprotokolle wurde die Plaquebelastung in jeder Arterie eingeschatzt (0 = keine Plaque, 1 = weiche Plaque, 2 = harte Plaque). Aus diesen 6 Scores wurde ein Gesamtwert gebildet („cumulative plaque score“, CPS). Die Expression des S1PR3 wurde mithilfe der qPCR gemessen. Die Spearman-Rangkorrelationskoeffizienten wurden berechnet, um Korrelationen zwischen klinischen Parametern und der S1PR3-Expression darzustellen. Die Expression des S1PR3 zeigte sich in den verschiedenen Regionen unterschiedlich hoch (am hochsten fur die Koronararterie, am niedrigsten fur die Aorta descendens). Mit zunehmendem Alter konnten wir einen Abfall der Expression beobachten, unabhangig vom Geschlecht, am starksten fur die Koronararterie (r = −0,225, p