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Abstract Objectives Achieving a consensus on a definition for different aspects of radiomics workflows to support their translation into clinical usage. Furthermore, to assess the perspective of experts on important challenges for a successful clinical workflow implementation. Materials and methods The consensus was achieved by a multi-stage process. Stage 1 comprised a definition screening, a retrospective analysis with semantic mapping of terms found in 22 workflow definitions, and the compilation of an initial baseline definition. Stages 2 and 3 consisted of a Delphi process with over 45 experts hailing from sites participating in the German Research Foundation (DFG) Priority Program 2177. Stage 2 aimed to achieve a broad consensus for a definition proposal, while stage 3 identified the importance of translational challenges. Results Workflow definitions from 22 publications (published 2012–2020) were analyzed. Sixty-nine definition terms were extracted, mapped, and semantic ambiguities (e.g., homonymous and synonymous terms) were identified and resolved. The consensus definition was developed via a Delphi process. The final definition comprising seven phases and 37 aspects reached a high overall consensus (> 89% of experts “agree” or “strongly agree”). Two aspects reached no strong consensus. In addition, the Delphi process identified and characterized from the participating experts’ perspective the ten most important challenges in radiomics workflows. Conclusion To overcome semantic inconsistencies between existing definitions and offer a well-defined, broad, referenceable terminology, a consensus workflow definition for radiomics-based setups and a terms mapping to existing literature was compiled. Moreover, the most relevant challenges towards clinical application were characterized. Critical relevance statement Lack of standardization represents one major obstacle to successful clinical translation of radiomics. Here, we report a consensus workflow definition on different aspects of radiomics studies and highlight important challenges to advance the clinical adoption of radiomics. Key Points Published radiomics workflow terminologies are inconsistent, hindering standardization and translation. A consensus radiomics workflow definition proposal with high agreement was developed. Publicly available result resources for further exploitation by the scientific community. Graphical Abstract

Semantic segmentation neural networks require pixel-level annotations in large quantities to achieve a good performance. In the medical domain, such annotations are expensive because they are time-consuming and require expert knowledge. Active learning optimizes the annotation effort by devising strategies to select cases for labeling that are the most informative to the model. In this work, we propose an uncertainty slice sampling (USS) strategy for the semantic segmentation of 3D medical volumes that selects 2D image slices for annotation and we compare it with various other strategies. We demonstrate the efficiency of USS on a CT liver segmentation task using multisite data. After five iterations, the training data resulting from USS consisted of 2410 slices (4% of all slices in the data pool) compared to 8121(13%), 8641(14%), and 3730(6%) slices for uncertainty volume (UVS), random volume (RVS), and random slice (RSS) sampling, respectively. Despite being trained on the smallest amount of data, the model based on the USS strategy evaluated on 234 test volumes significantly outperformed models trained according to the UVS, RVS, and RSS strategies and achieved a mean Dice index of 0.964, a relative volume error of 4.2%, a mean surface distance of 1.35mm, and a Hausdorff distance of 23.4mm. This was only slightly inferior to 0.967, 3.8%, 1.18mm, and 22.9mm achieved by a model trained on all available data. Our robustness analysis using the 5th percentile of Dice and the 95th percentile of the remaining metrics demonstrated that USS not only resulted in the most robust model compared to other strategies, but also outperformed the model trained on all data according to the 5th percentile of Dice (0.946 vs. 0.945) and the 95th percentile of mean surface distance (1.92mm vs. 2.03mm).

Objectives: Achieving a consensus on a definition for different aspects of radiomics workflows to support their translation into clinical usage. Furthermore, to assess the perspective of experts on important challenges for a successful clinical workflow implementation. Materials and methods: The consensus was achieved by a multi-stage process. Stage 1 comprised a definition screening, a retrospective analysis with semantic mapping of terms found in 22 workflow definitions, and the compilation of an initial baseline definition. Stages 2 and 3 consisted of a Delphi process with over 45 experts hailing from sites participating in the German Research Foundation (DFG) Priority Program 2177. Stage 2 aimed to achieve a broad consensus for a definition proposal, while stage 3 identified the importance of translational challenges. Results: Workflow definitions from 22 publications (published 2012–2020) were analyzed. Sixty-nine definition terms were extracted, mapped, and semantic ambiguities (e.g., homonymous and synonymous terms) were identified and resolved. The consensus definition was developed via a Delphi process. The final definition comprising seven phases and 37 aspects reached a high overall consensus (> 89% of experts "agree" or "strongly agree"). Two aspects reached no strong consensus. In addition, the Delphi process identified and characterized from the participating experts' perspective the ten most important challenges in radiomics workflows. Conclusion: To overcome semantic inconsistencies between existing definitions and offer a well-defined, broad, referenceable terminology, a consensus workflow definition for radiomics-based setups and a terms mapping to existing literature was compiled. Moreover, the most relevant challenges towards clinical application were characterized. Critical relevance statement: Lack of standardization represents one major obstacle to successful clinical translation of radiomics. Here, we report a consensus workflow definition on different aspects of radiomics studies and highlight important challenges to advance the clinical adoption of radiomics. Key Points: Published radiomics workflow terminologies are inconsistent, hindering standardization and translation. A consensus radiomics workflow definition proposal with high agreement was developed. Publicly available result resources for further exploitation by the scientific community. [ABSTRACT FROM AUTHOR]

Abstract Despite progress in the prevention and diagnosis of cancer, current technologies for tumor detection present several limitations including invasiveness, toxicity, inaccuracy, lengthy testing duration and high cost. Therefore, innovative diagnostic techniques that integrate knowledge from biology, oncology, medicinal and analytical chemistry are now quickly emerging in the attempt to address these issues. Following this approach, here we developed a paper-based electrochemical device for detecting cancer-derived Small Extracellular Vesicles (S-EVs) in fluids. S-EVs were obtained from cancer cell lines known to express, at a different level, the αvβ6 integrin receptor, a well-established hallmark of numerous epithelial cancer types. The resulting biosensor turned out to recognize αvβ6-containing S-EVs down to a limit of 0.7*103 S-EVs/mL with a linear range up to 105 S-EVs /mL, and a relative standard deviation of 11%, thus it may represent a novel opportunity for αvβ6 expressing cancers detection.

We studied the regeneration of orthotopic and heterotopic tails in larval axolotls. First, we analyzed tail regeneration following reciprocal exchange of cuffs of tail integument between dark-colored (wild-type) and yellow-colored (hybrid) larval animals. Second, we studied tail regeneration in larval axolotls following transplantation of cuffs of tail integument from metamorphosed dark-colored conspecifics and from an adult fire salamander. In all cases, the amputation planes involved the transplanted integumental cuffs. In the first experiment, the regenerated tails showed the color of the host animals, not that of the transplanted cuffs. This suggests that the melanocytes of the regenerated tails were derived from the host hypodermis. Following transplantation of metamorphosed skin from axolotls and a fire salamander onto larval axolotls, the metamorphosed epidermis reverted to a larval condition. This indicates that the state of differentiation of the metamorphosed epidermis was not permanent. Rather, in order to maintain the metamorphosed epidermal structure, a continuous exposure of the animals to sufficient levels of thyroid hormones was required. Transplantation of tail buds from yellow-colored onto dark-colored axolotl embryos caused the formation of yellow-colored tails both in the head and the anterior limb region of the hosts. Incomplete resection of these heterotopic tails was followed by tail regeneration, while no tail regeneration occurred following complete resection of the heterotopic tails. Successful tail regeneration depended on the presence of neural tissue along the resection plane.

Heart failure remains one of the largest clinical burdens globally, with little to no improvement in the development of disease-eradicating therapeutics. Integrin targeting has been used in the treatment of ocular disease and cancer, but little is known about its utility in the treatment of heart failure. Here we sought to determine whether the second generation orally available, αvβ3-specific RGD-mimetic, 29P, was cardioprotective. Male mice were subjected to transverse aortic constriction (TAC) and treated with 50 μg/kg 29P or volume-matched saline as Vehicle control. At 3 weeks post-TAC, echocardiography showed that 29P treatment significantly restored cardiac function and structure indicating the protective effect of 29P treatment in this model of heart failure. Importantly, 29P treatment improved cardiac function giving improved fractional shortening, ejection fraction, heart weight and lung weight to tibia length fractions, together with partial restoration of Ace and Mme levels, as markers of the TAC insult. At a tissue level, 29P reduced cardiomyocyte hypertrophy and interstitial fibrosis, both of which are major clinical features of heart failure. RNA sequencing identified that, mechanistically, this occurred with concomitant alterations to genes involved molecular pathways associated with these processes such as metabolism, hypertrophy and basement membrane formation. Overall, targeting αvβ3 with 29P provides a novel strategy to attenuate pressure-overload induced cardiac hypertrophy and fibrosis, providing a possible new approach to heart failure treatment.

Abstract Using stable isotope analysis, we assessed the relative contributions of the main protein contributors fishmeal, soya and sunflower meal to mature abalone muscle and gonad tissue over 1 year. Prerequisites for the use of stable isotope mixing models were established in this species. The δ13C and δ15N discrimination factors and turnover rates were influenced by diet composition, and there were tissue‐specific and sex‐specific differences. Abalone were fed the two combination diets (fishmeal–soya and fishmeal–sunflower meal) grew at similar rates. However, feed was most efficiently utilised in abalone fed a combination of fishmeal and soya. The relative contribution of fishmeal, soya and sunflower meal to female and male abalone tissue growth fluctuated throughout the 1‐year study. Overall, fishmeal contributed over 50% of the gonad (54%–82%) and muscle (54%–84%) tissue growth in females. Similarly, fishmeal contributed over 50% of gonad tissue growth of male abalone, ranging from 59% to 87%, while the contribution to meat tissue growth in males ranged from 44% to 94%. These findings support the importance of laboratory studies when using stable isotope analysis and mixing models for nutrient allocation in aquaculture.

The COVID-19 pandemic has left behind mental health issues like anxiety, depression, and sleep disorders among survivors. This study assessed the efficacy of spa therapy in enhancing psychological well-being and sleep quality in individuals with chronic arthro-rheumatic, respiratory, and otorhinolaryngological diseases, including COVID-19 recoverees. Our prospective observational study included 144 Caucasian subjects from three Italian spas who underwent a 2-week spa therapy cycle, involving balneotherapy and/or inhalation treatments. Symptoms were assessed with the Visual Analogue Scale (VAS), psychological well-being with Depression Anxiety Stress Scales-21 items (DASS-21), and sleep quality with the Insomnia Severity Index (ISI). Significant reductions in VAS scores for arthro-rheumatic, respiratory, and otorhinolaryngological symptoms were observed after spa therapy, as well as for DASS-21 and ISI scores for sleep quality, transitioning to less severe insomnia categories. Females had more pronounced improvements in DASS-21 scores and sleep quality. Subjects with and without prior SARS-CoV-2 infection experienced significant reductions in anxiety, depression, and stress, with more pronounced improvements in those without prior infection. COVID-19 survivors also showed significant ISI score improvements. Spa therapy is a promising complementary treatment for improving mental health and sleep quality in chronic disease patients, including COVID-19 survivors.

Geyser geothermal fields are scenic volcanic landforms that often contain tens to hundreds of thermal spot vents that erupt boiling water or contain bubbling mud pools. The fields are potentially hazardous sites due to boiling water temperatures and changes in vent locations and eruption dynamics, which are poorly understood. Here we report on the rapid and profound changes that can affect such a geyser field and ultimately lead to a dangerous, unanticipated eruption. We studied the Geyser Valley, Kamchatka Peninsula, which is a field of geysers and other thermal features and boiling pools. Using high-resolution tri-stereo satellite data and unmanned aerial systems (UAS) with optical and thermal infrared cameras in 2018 and 2019, we were able to identify a newly emerging explosion site. Structure-from-motion analysis of data acquired before and after the explosion reveals morphological and thermal details of the new vent. The explosion site produced an aureole zone of more than 150 m3 of explosively redeposited gravel and clay, a slightly elliptical crater with a diameter of 7.5 m and a crater rim 0.30 m high. However, comparison with archives of photogrammetric data suggests that this site was thermally active years earlier and contained a crater that was obscured and covered by landslides and river sediments. The results allow us to develop a conceptual model and highlight the hazard potential of thermal features buried by landslides and clastic deposits. Sudden explosions may occur at similar sites elsewhere, highlighting the need for careful assessment and monitoring of geomorphological and hydrological changes at geyser sites in other regions.

In this paper, we offer some ideas for the treatment of somatoform patients and related pathologies based on the concept of embodiment. Embodiment refers to the interplay between body and mind in behavior. The word refers to giving a body to something, “incarnate”. Spinoza wrote extensively about the topic in the 17th century. In the 20th century, picking up on Spinoza’s work, Damasio presented extensive and important neuro-scientific evidence that feelings can be direct perceptions of internal body states, substantiating the growing understanding of emotions and feelings as a core component of the embodied experience. Here, we summarize the evidence for the intersection of emotion and cognition in the body, which impinges on the effectiveness of using the body and movement in psychotherapy and the management of somatic symptoms and related disorders. We present evidence indicating that movement would be a way to reach unconscious processes dealing with body-mind interaction and body awareness.

Abstract Human brain cells generated by in vitro cell programming provide exciting prospects for disease modeling, drug discovery and cell therapy. These applications frequently require efficient and clinically compliant tools for genetic modification of the cells. Recombinant adeno-associated viruses (AAVs) fulfill these prerequisites for a number of reasons, including the availability of a myriad of AAV capsid variants with distinct cell type specificity (also called tropism). Here, we harnessed a customizable parallel screening approach to assess a panel of natural or synthetic AAV capsid variants for their efficacy in lineage-related human neural cell types. We identified common lead candidates suited for the transduction of directly converted, early-stage induced neural stem cells (iNSCs), induced pluripotent stem cell (iPSC)-derived later-stage, radial glia-like neural progenitors, as well as differentiated astrocytic and mixed neuroglial cultures. We then selected a subset of these candidates for functional validation in iNSCs and iPSC-derived astrocytes, using shRNA-induced downregulation of the citrate transporter SLC25A1 and overexpression of the transcription factor NGN2 for proofs-of-concept. Our study provides a comparative overview of the susceptibility of different human cell programming-derived brain cell types to AAV transduction and a critical discussion of the assets and limitations of this specific AAV capsid screening approach.

We describe a bilateral craniodorsal dislocation of the hip joint in a free-ranging young roe buck and the associated pathological changes in the ossa coxae and femora of the animal. The highly symmetrical dislocation, which is considered to have developed secondary to hip dysplasia, caused the formation of two false acetabula that each consist of several, partially fused bone portions. The femora exhibit symmetrical outgrowths that extend from the greater trochanter along the intertrochanteric crest to the lesser trochanter. Formation of these outgrowths is attributed to abnormal traction at muscle attachment sites due to the displacement of the femora. On radiographic examination, both femora show signs of avascular necrosis in their head regions and of fatty marrow necrosis in their shafts, which is attributed to the damage of the arterial blood supply of the femora that was associated with the dislocation. The fact that, according to the hunter who shot the buck, the animal’s locomotion was inconspicuous suggests that the false hip joints functioned quite well, thereby demonstrating a remarkable capacity of the musculoskeletal system for functional recovery.

Heavy metals transported by rivers are deposited in sediments and floodplains, and floodplain soils act as both sinks and sources of these metals. The Innerste River is contaminated by historical metal ore mining, processing, and smelting in the Harz Mountains (Germany). Our study compared the uptake of lead (Pb) and zinc (Zn) in wild blackberries (Rubus fruticosus L. agg.) growing within and outside the Innerste floodplain in a downstream area. The potential of blackberries as bioindicators and for phytoremediation of soils polluted by Pb and Zn was assessed based on bioconcentration factors (BCF) and the intra-plant mobility of the two metals based on translocation (TF) factors.Concentrations of Pb and Zn were significantly higher in soils and blackberry plants from the Innerste floodplain compared to adjacent non-flooded area, while soil pH and organic matter content did not differ significantly between the two zones. Mean concentrations (mg/kg d.w.) of Pb (1457.2) and Zn (1365.2) in the regularly flooded soils far exceeded the precautionary limits of the German Federal Soil Protection and Contaminated Sites Ordinance. Concentrations of both heavy metals in blackberry roots and leaves increased with their levels in soil. Except for BCFRoot Pb, BCFs and TFs decreased exponentially with increasing heavy metal concentration in soil and roots, respectively. This indicates that the uptake of Pb and Zn by R. fruticosus and their translocation within the plant are reduced at higher soil levels of both heavy metals. BCF < 1 were determined for both heavy metals and a TF < 1 for Pb. Only blackberries growing outside the floodplain showed a TF > 1 for Zn.Our results indicate that blackberries can be used as bioindicators of soil contamination by Pb and Zn. Regarding their uptake characteristics, blackberries constitute excluders rather than accumulators, and are thus unsuited for phytoremediation.

Antlers are paired deciduous bony cranial appendages of deer that undergo a regular cycle of growth, death and casting, and constitute the most rapidly growing bones in mammals. Antler growth occurs in an appositional mode and involves a modified form of endochondral ossification. In endochondral bones, calcified cartilage is typically a transient tissue that is eventually completely replaced by bone tissue. We studied the distribution and characteristics of calcified cartilage in hard antlers from three deer species (Capreolus capreolus, Cervus elaphus, Dama dama), i.e., in antlers from which the skin (velvet) had been shed. Remnants of calcified cartilage were regularly present as part of the trabecular framework in the late formed, distal antler portions in all three species, whereas this tissue was largely or completely missing in the more proximal antler portions. The presence of calcified cartilage remnants in the distal antler portions is attributed to the limited antler lifespan of only a few months, which is also the reason for the virtual lack of bone remodeling in antlers. The calcified cartilage matrix was more highly mineralized than the antler bone matrix. Mineralized deposits were observed in some chondrocyte lacunae and occasionally also in osteocyte lacunae, a phenomenon that has not previously been reported in antlers. Using synchrotron radiation-induced X-ray fluorescence (SR-XRF) mapping, we further demonstrated increased zinc concentrations in cement lines, along the inner borders of incompletely formed primary osteons, along the walls of partly or completely mineral-occluded chondrocyte and osteocyte lacunae, and in intralacunar mineralized deposits. The present study demonstrates that antlers are a promising model for studying the mineralization of cartilage and bone matrices and the formation of mineralized deposits in chondrocyte and osteocyte lacunae.

Abstract Astrocytes have crucial functions in the central nervous system (CNS) and are major players in many CNS diseases. Research on astrocyte‐centered diseases requires efficient and well‐characterized gene transfer vectors. Vectors derived from the Adeno‐associated virus serotype 9 (AAV9) target astrocytes in the brains of rodents and nonhuman primates. A recombinant (r) synthetic peptide‐displaying AAV9 variant, rAAV9P1, that efficiently and selectively transduces cultured human astrocytes, has been described previously. Here, it is shown that rAAV9P1 retains astrocyte‐targeting properties upon intravenous injection in mice. Detailed analysis of putative receptors on human astrocytes shows that rAAV9P1 utilizes integrin subunits αv, β8, and either β3 or β5 as well as the AAV receptor AAVR. This receptor pattern is distinct from that of vectors derived from wildtype AAV2 or AAV9. Furthermore, a CRISPR/Cas9 genome‐wide knockout screening revealed the involvement of several astrocyte‐associated intracellular signaling pathways in the transduction of human astrocytes by rAAV9P1. This study delineates the unique receptor and intracellular pathway signatures utilized by rAAV9P1 for targeting human astrocytes. These results enhance the understanding of the transduction biology of synthetic rAAV vectors for astrocytes and can promote the development of advanced astrocyte‐selective gene delivery vehicles for research and clinical applications.

We studied the structure and attachment modes of the teeth of adult Anoplogaster cornuta using light- and scanning-electron microscopic techniques. All teeth were monocuspid, composed solely of orthodentin, and lacked a covering enameloid cap. Fourteen teeth were present in the oral jaws, with three teeth each on the left and right premaxilla and four teeth each on the left and right dentary. The anteriormost premaxillary and dentary teeth were considerably larger than the more posteriorly located ones. The oral jaw teeth were transparent, non-depressible and firmly ankylosed to their respective dentigerous bone by a largely anosteocytic bone of attachment. No evidence for replacement of the large oral jaw teeth was found in the analyzed adult specimens. The bone of attachment exhibited lower calcium and phosphorus concentrations and a higher Ca/P ratio than the orthodentin. The connection between dentinal tooth shaft and bone of attachment was stabilized by a collar of mineralized collagen fibers. In contrast to the oral jaw teeth, the pharyngeal teeth exhibited a ring-like fibrous attachment to their supporting bones. This mode of attachment provides the teeth with some lateral mobility and allows their depression relative to their supporting bones, which may facilitate intra-pharyngeal prey transport. In contrast, a firm ankylosis was observed in numerous small teeth located on the branchial arches. The function of these teeth is presumably to increase the tightness of the pharyngeal basket and thereby the retention of small prey items in a species living in a habitat with only sparse food supply. Our findings corroborate earlier statements on the tooth attachment modes of the oral jaw teeth of Anoplogaster cornuta, but provide new findings for the attachment modes of pharyngeal teeth in this species.

The critically endangered estuarine pipefish, Syngnathus watermeyeri, is one of Africa’s rarest fish species and currently faces a significant risk of extinction. A combination of anthropogenic and natural factors threaten submerged macrophyte beds in the two South African estuaries (Bushmans and Kariega) in which the species’ only two known remaining populations reside. Here, we genotyped 34 pipefish from both populations using genome-wide data to determine whether the two estuaries harbour distinct genetic diversity, such that translocating individuals between them might improve the genetic health of both. Our results show that both populations are highly inbred, and no statistically significant genetic structure was found between them. Moreover, individuals both within and between estuaries were very closely related to each other. These results indicate that the remaining populations of the estuarine pipefish suffer from the adverse genetic effects of small population sizes. Even though recent surveys have estimated population sizes in the order of thousands of individuals, these may fluctuate considerably. Although the translocation of genetically similar individuals between habitats will not increase local genetic diversity, the creation of additional populations across the species’ historical range may be a suitable conservation strategy to prevent further loss of genetic diversity, and to minimise the overall extinction risk posed by environmental stochasticity.

As a consequence of the issues resulting from global climate change many nations are starting to transition to being low or net zero carbon economies. To achieve this objective practical alternative fuels are urgently required and hydrogen gas is deemed one of the most desirable substitute fuels to traditional hydrocarbons. A significant challenge, however, is obtaining hydrogen from sources with low or zero carbon footprint i.e. so called ‘green’ hydrogen. Consequently, there are a number of strands of research into processes that are practical techniques for the production of this ‘green’ hydrogen. Over the past five decades there has been a significant body of research into photocatalytic (PC)/photoelectrocatalytic processes for hydrogen production through water splitting or water reduction. There have, however been significant issues faced in terms of the practical capability of this promising technology to produce hydrogen at scale. This road map article explores a range of issues related to both PC and photoelectrocatalytic hydrogen generation ranging from basic processes, materials science through to reactor engineering and applications for biomass reforming.

Fresh vegetables harbour diverse bacterial populations on their surfaces which are important for plant health and growth. Information on epiphytic bacteria is limited to only a few types of vegetables and it is unknown how the lettuce epiphytic bacterial community structure may respond when a probiotic product is added to an aquaponic system. In this study, we evaluated lettuce growth and analysed epiphytic bacterial communities of lettuce based on metabarcoding analysis of the V3-V4 region of the 16S rRNA gene obtained from paired-end Illumina MiSeq reads. The addition of Bacillus probiotics resulted in a significant increase of nitrate and phosphate in the deep-water culture solution, as well as increased vegetative growth of lettuce. Metabarcoding analysis revealed that the most abundant phyla on lettuce leaf surfaces were Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria. The in-depth bacterial composition analysis indicated that genera Chryseobacterium, Bacillus, Pantoea, Pseudoduganella, Flavobacterium, Paludibacter, and Cloacibacterium were dominant in leaf samples obtained from Bacillus-treated systems. Analysis of lettuce epiphytic bacterial communities of the fresh lettuce leaf surfaces also indicated the presence of food-borne pathogens belonging to the Shigella and Aeromonas genera, which were less abundant in the probiotic treated systems. This study provides the first characterization of the epiphytic bacterial community structure and how it can be modulated by the addition of a probiotic mixture to the nutrient solution of aquaponic systems.

Purpose: In polytrauma patients, injuries involving the extremities are frequently seen. Treatment concepts vary from early definitive care to temporary fixation and delayed definite stabilization. This analysis therefor aims to illuminate the impact of timing for operative stabilization of extremity fractures on outcome factors in adult polytrauma patients., Methods: We searched PubMed and Cochrane CENTRAL to identify studies from inception of each database to 14 September 2022. We included systematic reviews and RCTs comparing immediate versus delayed operative fracture stabilization and early definite care versus primary external fixation in adult polytrauma patients., Results: Five randomized controlled trials were included, with a total of 335 patients. The analysis found no statistically significant difference in overall mortality or improvement in ICU admission between early (< 24 h) and late fracture stabilization. Comparing femoral nailing and external fixation, findings showed that femoral nailing reduce ICU length of stay and duration of invasive mechanical ventilation., Conclusion: The results indicate that immediate surgical treatment by nailing is superior to delayed treatment or a staged surgical approach in stable polytrauma patients with long-bone fractures. As there is a lack of clear evidence regarding the optimal timing for definitive operative stabilization of extremity fractures in polytrauma patients, further high-quality studies are essential to enhance the certainty of evidence and provide more conclusive treatment algorithms., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s).)

Background: C-reactive protein (CRP) represents a routine diagnostic marker of inflammation. Dissociation of native pentameric CRP (pCRP) into the monomeric structure (mCRP) liberates proinflammatory features, presumably contributing to excessive immune cell activation via unknown molecular mechanisms., Results: In a multi-translational study of systemic inflammation, we found a time- and inflammation-dependent pCRP dissociation into mCRP. We were able to confirm that mCRP co-localizes with leukocytes at the site of injury after polytrauma and therefore assessed whether the CRP conformation potentiates neutrophil activation. We found mCRP-induced neutrophil-extracellular trap formation in vitro and ex vivo involving nicotinamide adenine dinucleotide phosphate oxidase activation, p38/mitogen-activated protein kinase signaling, and histone H3 citrullination. Mimicking the trauma milieu in a human ex vivo whole blood model, we found significant mCRP generation as well as NET formation, prevented by blocking pCRP conformational changes., Conclusions: Our data provide novel molecular insights how CRP dissociation contributes to neutrophil activation as driver of various inflammatory disorders., Competing Interests: Declarations. Ethics approval and consent to participate: A prospective clinical study was conducted in patients after severe PT (Injury Severity Score ≥ 32) that were admitted to the University Hospital Ulm between December 2013 and May 2015. The study protocol was approved by the Independent Local Ethics Committee of the University of Ulm (approval numbers 244/11 and 94/14). The study was registered on ClinicalTrials.gov, identifiers NCT00710411 and NCT02682550, and was performed in accordance with the Declaration of Helsinki and its recent modifications. Consent for publication: Not applicable. Competing interests: The authors have declared that no conflict of interest exists., (© 2025. The Author(s).)

Aim: We evaluated the quality of noncontrast chest computed tomography (CT) for pediatric patients at two dose levels with and without denoising using a deep convolutional neural network (CNN)., Materials and Methods: Forty children underwent noncontrast chest CTs for "chronic cough" using a routine dose (RD) protocol. Images were reconstructed using iterative reconstruction (IR). A validated noise insertion method was used to simulate 20% dose (TD) data for each case. A deep CNN model was trained and validated on 10 cases and then applied to the remaining 30 cases. Three certificate of qualification (CAQ)-certified pediatric radiologists evaluated 30 cases under 4 conditions: (1) RD + IR; (2) RD + CNN; (3) TD + IR; and (4) TD + CNN. Likert scales were used to score subjective image quality (1-5, 5 = excellent) and subjective noise artifact (1-4, 4 = no noise). Images were reviewed for specific findings., Results: For the 30 patients evaluated (14 female, mean age: 10.8 years, range: 0.17-17), the mean effective dose was 0.46 ± 0.21 mSv for the original RD exam, with an effective dose of 0.09 mSv for the TD exam. Both RD + CNN (3.6 ± 1.1, p < 0.001) and TD + CNN (3.4 ± 0.9, p = 0.023) had higher image quality than RD + IR (3.1 ± 0.9). Both RD + CNN (3.2 ± 0.9, p-value = <0.001) and TD + CNN (2.9 ± 0.6, p-value = 0.001) showed significantly lower subjective noise artifact scores than RD + IR (2.7 ± 0.7). There was excellent intrareader (RD + IR-RD + CNN: mean κ = 0.96, RD + IR-TD + CNN = 0.96, RD + IR-TD + IR = 0.98) and moderate inter-reader reliability (RD + IR: mean κ = 0.55, RD + CNN = 0.50, TD + CNN = 0.54, TD + IR = 0.57) on all 4 image reconstructions., Conclusion: CNN denoising outperforms IR as a means of radiation dose reduction in pediatric CT., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objective: To examine the factors that make such programs successful, this systematic review compared the outcomes of children's participation in cooking interventions based on intervention characteristics., Design: Systematic review of randomized controlled trials of children's participation in cooking interventions published between 1998 and 2022 guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement., Setting: All settings PARTICIPANTS: Children and parents., Main Outcome Measures: Cooking skills, food acceptance and dietary behavior., Analysis: Systematic search of 1,104 articles and review of 23 studies (42 articles) meeting inclusion criteria., Results: Interventions varied in participant age, settings, cooking sessions, and program length. Knowledge of cooking skills, self-efficacy, and child cooking involvement were the most frequent positive outcomes; improvements in dietary intake were rarely achieved. Seven studies had a high rating for research quality., Conclusion and Implications: Lack of standardized assessment, large variability in program characteristics, and insufficient intervention description made it difficult to discern best practices for children's cooking programs. Improvements in intervention development and measurement instruments are needed. Interventions that include hands-on cooking lessons seem promising in improving knowledge and self-efficacy; however, further exploration is required on the factors that make cooking programs successful in the long term., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Polytrauma and hemorrhagic shock can lead to direct and indirect liver damage involving intricate pathophysiologic mechanisms. While hepatic function has been frequently highlighted, there is minimal research on how the receptor activator of the NF-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system is regulated in the liver following trauma. Furthermore, cross-talking complement and toll-like-receptor (TLR) systems can contribute to the posttraumatic response. Therefore, we investigated the hepatic consequences of polytrauma focusing on the RANK-RANKL-OPG axis, and evaluated the effects of a dual blockade of complement factor C5 and TLR-cofactor CD14 on hepatic features., Methods: The established pig model of polytrauma (PT) and hemorrhagic shock included pulmonary contusion, hepatic dissection, and bilateral femur fractures, surgically addressed either by external fixation (Fix ex) or intramedullary nailing (Nail). Four groups were investigated: 1) sham animals; 2) PT treated by Fix ex (Fix ex); 3) PT by Nail (Nail); or 4) PT by Nail plus combined C5/CD14 inhibition (Nail+Therapy). Serum samples were obtained between 0 - 72 h, and liver samples at 72 h after PT. Liver tissues were histologically scored and subjected to RT-qPCR-analyses, immunohistochemistry and ELISAs to evaluate the posttraumatic hepatic response with a focus on the RANK-RANKL-OPG system., Results: Following PT, the liver injury score of the Nail+Therapy group was significantly lower than in the Fix ex or Nail group without immunomodulation (p<0.05). Similarly, the degree of necrosis, lobular stasis, and inflammation were significantly reduced when treated with C5/CD14-inhibitors. Compared to the Nail group, AST serum concentrations were significantly decreased in the Nail+Therapy group after 72 h (p<0.05). PCR analyses indicated that RANK, RANKL, and OPG levels in the liver were increased after PT in the Nail group compared to lower levels in the Nail+Therapy group. Furthermore, liver tissue analyses revealed increased RANK protein levels and cellular immunostaining for RANK in the Nail group, both of which were significantly reduced in the case of C5/CD14-inhibition (p<0.05)., Conclusion: Following experimental PT, dual inhibition of C5/CD14 resulted in altered, mainly reduced hepatic synthesis of proteins relevant to bone repair. However, a comprehensive investigation of the subsequent effects on the liver-bone axis are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Li, Horst, Greven, Mert, Lupu, Palmer, Doerfer, Zhao, Zhang, Halbgebauer, Ignatius, Marzi, van Griensven, Balmayor, Hildebrand, Mollnes and Huber-Lang.)

Background: Atrial fibrillation (AF) has been associated with thoracic radiotherapy, but the specific risk with irradiating different cardiac substructures remains unknown., Objectives: This study sought to examine the relationship between irradiation of cardiac substructures and the risk of clinically significant (grade ≥3) AF., Methods: We analyzed data from patients who underwent definitive radiotherapy for localized cancers (non-small cell lung, breast, Hodgkin lymphoma, or esophageal) at our institution between 2004 and 2022. The 2-Gy fraction equivalent dose was calculated for cardiac substructures, including the pulmonary veins (PVs), left atrium, sinoatrial node, and left coronary arteries (the left main, left anterior descending, and left circumflex arteries). Competing risk models (subdistribution HRs [sHRs]) for AF incidence were adjusted for the Mayo AF risk score (MAFRS)., Results: Among 539 patients, the median follow-up was 58.8 months. The 5-year cumulative incidence of AF was 11.1% for non-small cell lung cancer, 8.3% for esophageal cancer, 1.3% for breast cancer, and 0.8% for Hodgkin lymphoma. Increased AF risk was associated with a higher PV maximum dose (d max ) (sHR: 1.22; P < 0.001), larger left atrial volume (sHR: 1.01; P = 0.002), greater smoking history in pack-years (sHR: 1.01; P = 0.010), and higher MAFRS (sHR: 1.16; P <  0.001). PV d max remained a significant predictor of AF across different MAFRS subgroups ( P interaction  = 0.11), and a PV d max  >39.7 Gy was linked to a higher AF risk, even when stratified by MAFRS., Conclusions: PV d max is a significant predictor of grade ≥3 AF regardless of underlying risk factors. These findings highlight the importance of cardiac substructures in radiation toxicity and suggest that various PV dose metrics should be further validated in clinical settings., Competing Interests: Dr No has received materials/services from Limbus AI and Coreline Soft; has received payment/honoraria from AAMD; and has received grants from RSNA and ACRO. Dr Loo is a lecturer for Mevion; is a consultant for Beigene; holds equity in TibaRay; and is an advisor for NCCN. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Respiratory failure can be a severe complication after polytrauma. Extensive systemic inflammation due to surgical interventions, as well as exacerbated post-traumatic immune responses influence the occurrence and progression of respiratory failure. This study investigated the effect of different surgical treatment modalities as well as combined inhibition of the complement component C5 and the toll-like receptor molecule CD14 (C5/CD14 inhibition) on the pulmonary microRNA (miRNA) signature after polytrauma, using a translational porcine polytrauma model., Methods: After induction of general anesthesia, animals were subjected to polytrauma, consisting of blunt chest trauma, bilateral femur fractures, hemorrhagic shock, and liver laceration. One sham group (n=6) and three treatment groups were defined; Early Total Care (ETC, n=8), Damage Control Orthopedics (DCO, n=8), and ETC + C5/CD14 inhibition (n=4). Animals were medically and operatively stabilized, and treated in an ICU setting for 72 h. Lung tissue was sampled, miRNAs were isolated, transcribed, and pooled for qPCR array analyses, followed by validation in the individual animal population. Lastly, mRNA target prediction was performed followed by functional enrichment analyses., Results: The miRNA arrays identified six significantly deregulated miRNAs in lung tissue. In the DCO group, miR-129, miR-192, miR-194, miR-382, and miR-503 were significantly upregulated compared to the ETC group. The miRNA expression profiles in the ETC + C5/CD14 inhibition group approximated those of the DCO group. Bioinformatic analysis revealed mRNA targets and signaling pathways related to alveolar edema, pulmonary fibrosis, inflammation response, and leukocytes recruitment. Collectively, the DCO group, as well as the ETC + C5/CD14 inhibition group, revealed more anti-inflammatory and regenerative miRNA expression profiles., Conclusion: This study showed that reduced surgical invasiveness and combining ETC with C5/CD14 inhibition can contribute to the reduction of pulmonary complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zhou, Groven, Horst, Mert, Greven, Mollnes, Huber-Lang, van Griensven, Hildebrand and Balmayor.)

Background: Femoral neck fractures pose significant surgical challenges with high morbidity and mortality. Traditional freehand screw placement often yields variable outcomes. Recent robotic advancements offer a promising alternative with enhanced precision. Methods: This systematic review compares the efficacy and safety of robot-assisted versus freehand techniques. A comprehensive literature search across multiple databases up to July 2024 included studies comparing both techniques. Primary outcomes were the union rate and time, functional outcomes, operative time, intraoperative parameters, and complication rates. Meta-regression analyses identified treatment response determinants. Results: Twenty-four studies (1437 patients) were included. Robot-assisted screw placement significantly improved the union rate, reduced the union time, and showed superior functional outcomes. Additionally, it resulted in shorter operative times, less intraoperative blood loss, and fewer instances of fluoroscopy and guide pin insertion. The risk of femoral neck necrosis was notably lower with robotic assistance. Meta-regression highlighted the robot type, patient age, and sample size as significant factors. Conclusions: Despite the promise of robot-assisted screw placement, limitations exist. The evidence being mainly from China raises concerns about generalizability. The lack of long-term follow-up data hinders assessment of technique durability. Unreported surgeon expertise levels and learning curves affect result validity. High initial costs and steep learning curves of robotic systems also present barriers to widespread adoption.

Background: Chest injury is an important factor regarding the prognosis of patients with polytrauma (PT), and the rapid diagnosis of chest injury is of utmost importance. Therefore, the current study focused on patients' physiology and laboratory findings to quickly identify PT patients with chest injury., Method: Data on 64 PT patients treated at a trauma center level I between June 2020 and August 2021 were retrospectively collected. The patients were divided into a PT group without chest injury (Group A) and a PT group including chest injury (Group B). The relationship between chest injury and the patients' baseline characteristics and biochemical markers was analyzed., Results: Heart rate, respiration rate, Sequential Organ Failure Assessment (SOFA) score, glutamate oxaloacetate aminotransferase (GOT), glutamate pyruvate transaminase (GPT), creatine kinase MB (CK-MB), leucocytes, hemoglobin (Hb), platelets, urine output, lactate, and lactate dehydrogenase (LDH) in groups A and B exhibited statistically significant differences at certain time points. Multifactorial analysis showed that blood LDH levels at admission were associated with chest injury (P = 0.039, CI 95% 1.001, 1.022)., Conclusion: LDH may be a promising indicator for screening for the presence of chest injury in patients with severe polytrauma., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Scores are widely used for the assessment of injury severity and therapy guidance in severely injured patients. They differ vastly regarding complexity, applicability, and prognostic accuracy. The objective of this study was to compare well-established with more recently developed trauma scores as well as intensive care unit (ICU) scores., Methods: Retrospective analysis of severely injured patients treated at a level I trauma centre from 2010 to 2015., Inclusion Criteria: Age ≥ 18 years, Injury Severity Score ≥ 16 and ICU treatment. Primary endpoint was in-hospital mortality. Several scores (ISS, APACHE II, RTS, Marshall Score, SOFA, NISS, RISC II, EAC and PTGS) were assessed to determine their predictive quality for mortality. Statistical analysis included correlation analysis and receiver operating characteristic (ROC)., Results: 444 patients were included. 71.8% were males, mean age was 51 ± 20.26 years. 97.4% sustained a blunt trauma. The area under the ROC curve (AUROC) revealed RISC II (0.92) as strongest predictor regarding mortality, followed by APACHE II (0.81), Marshall score (0.69), SOFA (0.70), RTS (0.66), NISS (0.62), PTGS (0.61) and EAC (0.60). ISS did not reach statistical significance., Conclusions: RISC II provided the strongest predictive capability for mortality. In comparison, more simple scores focusing on injury pattern (ISS, NISS), physiological abnormalities (RTS, EAC), or a combination of both (PTGS) only provided inferior mortality prediction. Established ICU scores like APACHE II, SOFA and Marshall score were proven to be helpful tools in severely injured trauma patients., (© 2022. The Author(s).)

Proximal femoral fractures occur at an annual incidence of approximately 200/100,000 inhabitants and mortality rates range up to 30% especially in geriatric patients where complications are not necessarily associated to surgery. In nearly all cases surgical treatment is required. Procedures to preserve the femoral head have to be performed as early as possible (as specified by the Federal Joint Committee, GBA, within 24 h). For joint-preserving approaches in medial femoral neck fractures a time to surgery within 6 h is considered to be advantageous. Perioperative patient care is of high importance regarding the prevention of pneumonia, renal failure, delirium and further complications. Postoperatively full weight bearing enables for early mobilization and prevention of surgery-related complications. Nonunions, avascular necrosis of the femoral head, cut-out and prosthetic dislocation must be avoided by the selection of the appropriate procedure. Minimally displaced femoral neck fractures are primarily treated by osteosynthesis and conservative management is only considered in isolated cases. For displaced femoral neck fractures, factors such as a young biological age with high activity levels, the absence of arthritis and good bone quality with a successful reduction favor for a femoral head-preserving osteosynthesis. Otherwise, (hybrid) total hip replacement (THR) is the preferred method for unstable and displaced fractures, whereby hemiarthroplasty should only be considered for very old and patients with pre-existing diseases. Fractures in the trochanteric region are treated with a proximal femoral nail and subtrochanteric fractures are managed using a long proximal femoral nail. To avoid secondary complications, the choice of optimal treatment should be based on a good understanding of the injury pattern, biomechanical and technical aspects of each procedure., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Obesity is associated with low-grade inflammation and insulin resistance (IR). The contribution of adipose tissue (AT) and hepatic inflammation to IR remains unclear. We conducted a study across three cohorts to investigate this relationship. The first cohort consists of six women with normal weight and twenty with obesity. In women with obesity, we found an upregulation of inflammatory markers in subcutaneous and visceral adipose tissue, isolated AT macrophages, and the liver, but no linear correlation with tissue-specific insulin sensitivity. In the second cohort, we studied 24 women with obesity in the upper vs lower insulin sensitivity quartile. We demonstrated that several omental and mesenteric AT inflammatory genes and T cell-related pathways are upregulated in IR, independent of BMI. The third cohort consists of 23 women and 18 men with obesity, studied before and one year after bariatric surgery. Weight loss following surgery was associated with downregulation of multiple immune pathways in subcutaneous AT and skeletal muscle, alongside notable metabolic improvements. Our results show that obesity is characterised by systemic and tissue-specific inflammation. Subjects with obesity and IR show a more pronounced inflammation phenotype, independent of BMI. Bariatric surgery-induced weight loss is associated with reduced inflammation and improved metabolic health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)