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Abstract Most embedding media for live and fixed samples were not designed for microscopy and have issues including long polymerization times, peak of toxicity toward the sample during the sol-gel transition, and irreversibility of this transition. Gels derived from biological sources are widely used in microscopy, but their precise composition is ill-defined and can vary between batches. Non-physiological temperatures and/or specific enzymatic solutions are often needed to revert the gel back to the sol state to allow sample recovery. Recovering the sample undamaged is important for multiple purposes, from the ability to release a living organism back into its environment and re-observe it at a later stage, to interrogating the sample once freed from the gel after imaging. We describe a supramolecular hydrogel that enables the observation of small living organisms using light microscopy, with simple sample recovery through vigorous pipetting with water. The organisms can be recovered alive and capable of further development into adulthood, which represents a significant advancement, as most other matrices require release conditions such as heating, the addition of chemicals, or mechanical disruption, which can damage or kill the embedded organisms. Furthermore, the gel is compatible with super-resolution multi-colour STED nanoscopy.

Abstract Background As ultrasound is one of the most utilized imaging procedures in clinical practice in Germany, its integration into undergraduate medical education is imperative. Thereby, the limited availability of qualified instructors is a major challenge. Peer tutors, who are trained to instruct their peers collaboratively, could resolve staff constraints. This systematic review explores the literature on peer teaching in undergraduate ultrasound education, aiming to provide an overview of methodologies, outcomes, and peer teacher training concepts. Methods Following the PRISMA guidelines, a systematic literature review was conducted on the subject of peer teaching in undergraduate ultrasound education. Using PubMed and Google Scholar as databases, studies in English or German involving training concepts for peer teachers in undergraduate ultrasound education, published up to November 21, 2023, were included. Data extraction of original studies followed the PICOS schema with special respect to didactic concepts of peer tutor training programs and the effectiveness of peer teachers compared to faculty instructors. A modified version of the Newcastle–Ottawa Scale (NOS) was used to assess the quality of included studies. Results Finally, the search resulted in 20 relevant original studies, including 16 studies exploring peer teacher training concepts. Predominantly, peer teachers studied in their 4th year of medical school and on average one year further compared to their students. Peer teacher training was integrated into curricula by course-based concepts (93.8%) and internships (50.0%). Didactic modalities varied, encompassing laboratory rotations including the scanning of patients, the scanning of fellow students, lectures, and didactic training. The median training duration was about ten days. Of six comparative studies, five found peer-assisted learning to be comparably effective and one even better than faculty-led courses. Conclusion Despite the growing amount of literature underlining the effectiveness and wide application of peer teaching in ultrasound education, training concepts stay heterogenous without a standardized system for training and qualifying peer teachers. Developing comprehensive guidelines for peer tutor education could increase acceptance and recognition of peer-assisted learning and ensure minimum training standards.

Abstract Elevated high-sensitivity cardiac troponin-T (hs-cTnT) is associated with mortality in older adults. However, little is known about the implications of changes over time. We investigated hs-cTnT 3-year change and its association with subsequent mortality in the Activity and Function in the Elderly Study. Participants with baseline and follow-up hs-cTnT 14 ng/L (n = 74). Cox-proportional hazards models evaluated the association with mortality adjusting for age, sex, education, cardiovascular disease, chronic kidney disease, number of medications, hs-CRP, and NT-proBNP. Among 745 participants (median age 75.9 years, 58.9% male) we observed 98 deaths (median follow-up 4.8 years). G1 had the lowest mortality rate (MR) (5.2 per 1000 person-years). The highest MR were observed by follow-up ≥ 14 ng/L: G3: 95.4 and G6: 100.4 per 1000 person-years, with an adjusted hazard ratio of 5.22 [95% CI 1.46, 18.65] and 3.40 [95% CI 1.02, 11.34], respectively. Hs-cTnT trajectories could help to identify older adults with a high mortality risk even after further adjustment including hs-CRP and NT-proBNP.

Abstract Introduction Medical education, especially in ultrasound training, is undergoing significant changes. This study examines practical issues in ultrasound medical education, emphasizing state-of-the-art teaching methods, their effectiveness, and implementation challenges. Methods The study analyzed advancements in ultrasound education, including randomized controlled trials comparing peer-to-peer teaching with traditional faculty-led instruction. It evaluated the effectiveness of collaborative small-group training and group size impact in simulation-based training. The study also assessed practical training components outlined in the WFUMB Position Paper Part II. Results Findings indicate that peer-to-peer and collaborative small-group training are effective and cost-efficient. Group size did not significantly affect training outcomes. Key practical training elements, including early hands-on sessions and exposure to various equipment, substantially improved learning outcomes. Simulation tools like virtual reality (VR), augmented reality (AR), and phantoms were crucial for teaching standardized procedures and rare pathologies. Challenges identified include developing robust image acquisition skills, scarcity of qualified student tutors, and the need for reliable ultrasound skill assessment methods. Conclusion Integrating peer-to-peer teaching and advanced simulation technologies significantly advances ultrasound medical education. These methods enhance cognitive and psychomotor skills but also present challenges such as ensuring quality education and developing effective assessment methods. Future research should compare different simulation tools and establish objective ultrasound proficiency assessment criteria. Continual method evaluation and improvement are essential for effective and standardized ultrasound training, ultimately enhancing patient care and clinical outcomes.

This review paper offers a concise guide on how to execute Delphi-based interdisciplinary consensus statements on imaging. Fundamental to the Delphi methodology are several core principles. First, an initial key element is the selection of experts, known as panelists. Second is the principle of anonymity among participants, ensuring that no single individual or group applies excessive influence over others. Third, the methodology involves iterative rounds where statements are presented repeatedly, allowing for controlled feedback. Lastly, after each round, participants are given insight into the collective panel’s previous responses. This knowledge enables them to potentially reconsider and adjust their positions in subsequent rounds, driving towards the group consensus. These principles emphasize the critical role of statistical group responses and the structured interaction inherent in the Delphi approach. Looking at the broader process, the development of Delphi-based interdisciplinary consensus statements on imaging unfolds through several stages. It begins with identifying the research field or the consensus statements in question. This is followed by undertaking comprehensive literature research. Subsequently, pertinent questions and their corresponding statements are crafted. The process then moves on to administering anonymous, iterative questionnaire rounds. Feedback, both on an individual and collective level, is provided between the rounds. The process culminates in the summarization and reporting of the finalized Delphi-based interdisciplinary consensus statements on imaging.

Abstract Antimicrobial resistance is one of the major health threats of the modern world. Thus, new structural classes of antimicrobial compounds are needed in order to overcome existing resistance. Cystobactamids represent one such new compound class that inhibit the well-established target bacterial type II topoisomerases while exhibiting superior antibacterial and resistance-breaking properties. Understanding potential mechanisms of emerging resistances is crucial in the development of novel antibiotics as they directly impact the future therapeutic application and market success. Therefore, the frequency and molecular basis of cystobactamid resistance in Escherichia coli was analyzed. High-level resistant E. coli mutants were selected and found to harbor single nucleotide polymorphisms in the promotor region of the ygiV gene, causing an upregulation of the respective protein. These stable mutations are contrary to what was observed as a resistance genotype in the structurally related albicidins, where ygiV gene amplifications were identified as causing resistance. Overexpression of YgiV in the mutants was additionally amplified upon cystobactamid exposition, showing further adaptation to this compound class under treatment. YgiV binds cystobactamids with high binding affinity, thereby preventing their interaction with the antimicrobial targets topoisomerase IV and DNA gyrase. In addition, we observed a substantial impact of YgiV on in vitro gyrase activity by leading to increased DNA cleavage and concurrent reduction in the efficacy of cystobactamids in inhibiting gyrase supercoiling activity. Furthermore, we identified co-upregulation of membrane-modifying proteins, such as EptC, and the transcriptional regulator QseB. This presumably contributes to the observed reduced motility and fimbrial protein expression in resistant mutants, resulting in a reduced expression of virulence factors and potentially pathogenicity, associated with ygiV promotor mutations.

O estudo investiga a compatibilidade do dano existencial com o Direito brasileiro. Delimita a abordagem em três frentes: (i) investiga o dano existencial no Direito italiano, (ii) descreve como o dano existencial foi incorporado no Direito brasileiro e, com isso, (iii) faz uma avaliação crítica da recepção deste instituto jurídico. Procura, assim, apresentar as características do dano existencial no Direito italiano e faz um escrutínio sobre a (in)adequada recepção no Direito brasileiro. A hipótese do estudo é de que a recepção dos danos existenciais, no Brasil, pode ser feita, de maneira juridicamente adequada, observando alguns parâmetros e retificações específicas. Fez-se o uso de revisão bibliográfica e análise empírica de julgamentos.

Abstract Angiogenesis, vital for tumor growth and metastasis, is a promising target in cancer therapy. Natural compounds offer potential as antiangiogenic agents with reduced toxicity. This review provides a comprehensive overview of natural product‐based antiangiogenic therapies, focusing on molecular mechanisms and therapeutic potential. A systematic search identified relevant articles from 2019 to 2023. Various natural compounds, including polyphenols, terpenes, alkaloids, cannabinoids, omega‐3 fatty acids, polysaccharides, proteins, and carotenoids, were investigated for their antiangiogenic properties. Challenges such as dose standardization, routes of administration, and potential side effects remain. Further studies, including in‐depth animal models and human epidemiological studies, must elucidate clinical efficacy and safety. Synergistic effects with current antiangiogenic therapies, such as bevacizumab and tyrosine kinase inhibitors, should be explored. Additionally, the potential hormone‐dependent effects of compounds like genistein highlight the need for safety evaluation. In conclusion, natural products hold promise as adjunctive therapies to conventional antineoplastic drugs in modulating angiogenesis in cancer. However, robust clinical trials are needed to validate preclinical findings and ensure safety and efficacy.

Abstract Excessive dietary fat intake increases plasma lipid levels and has been associated with reduced bone mineral density (BMD) and increased risk of osteoporotic fracture, especially in older postmenopausal women. The objective of this study was to investigate whether there are sex-related differences in lipid metabolism that could have an impact on large-scale bone regeneration. Because ribs provide a unique exception as the only bones capable of completely regenerating large-scale defects, we used a rib resection mouse model in which human features are recapitulated. After 10 days of exposure to a low-fat diet or high-fat diet (HFD), we performed large-scale rib resection surgeries on male and female mice (6–7 weeks old) with deletion of the low-density lipoprotein (LDL) receptor (Ldlr−/−) and age- and sex-matched wild-type (WT) mice were used as controls. Plasma analysis showed that short-term exposure to HFD significantly increases total cholesterol, LDL cholesterol, and triglycerides levels in Ldlr−/− mice but not in WT, with no differences between males and females. However, under HFD, callus bone volume was significantly reduced exclusively in male Ldlr−/− mice when compared to WT, although these differences were no longer apparent by 21 days after resection. Regardless of diet or genotype, BMD of regenerated ribs did not differ significantly between groups, although male mice typically had lower average BMD values. Together, these results suggest that short-term hyperlipidemia has transient effects on large-scale bone regeneration exclusively in male mice.

Abstract The Fourier harmonics, $$v_2$$ v 2 and $$v_3$$ v 3 of negative pions are measured at center-of-mass energy per nucleon pair of $$\sqrt{s_{\textrm{NN}}}$$ s NN = 17.3 GeV around midrapidity by the CERES/NA45 experiment at the CERN SPS in 0–30% central PbAu collisions with a mean centrality of 5.5%. The analysis is performed in two centrality bins as a function of the transverse momentum $$\mathrm {p_{\textrm{T}}}$$ p T from 0.05 GeV/c to more than 2 GeV/c. This is the first measurement of the $$v^{1/3}_{3}/v^{1/2}_{2}$$ v 3 1 / 3 / v 2 1 / 2 ratio as a function of transverse momentum at SPS energies, that reveals, independently of the hydrodynamic models, hydrodynamic behavior of the formed system. For $$\mathrm {p_{\textrm{T}}}$$ p T above 0.5 GeV/c, the ratio is nearly flat in accordance with the hydrodynamic prediction and as previously observed by the ATLAS and ALICE experiments at the much higher LHC energies. The results are also compared with the SMASH-vHLLE hybrid model predictions, as well as with the SMASH model applied alone.

Abstract Human biomonitoring (HBM) data indicate that exposure to pyrethroids is widespread in Europe, with significantly higher exposure observed in children compared to adults. Epidemiological, toxicological, and mechanistic studies raise concerns for potential human health effects, particularly, behavioral effects such as attention deficit hyperactivity disorder (ADHD) in children at low levels of exposure. Based on an exposure-response function from a single European study and on available quality-assured and harmonized HBM data collected in France, Germany, Iceland, Switzerland, and Israel, a preliminary estimate of the environmental burden of disease for ADHD associated with pyrethroid exposure was made for individuals aged 0–19 years. The estimated annual number of prevalence-based disability-adjusted life years (DALYs) per million inhabitants were 27 DALYs for Israel, 21 DALYs for France, 12 DALYs for both Switzerland and Iceland, and 3 DALYs for Germany; while the annual ADHD cases per million inhabitants attributable to pyrethroids were 2189 for Israel, 1710 for France, 969 for Iceland, 944 for Switzerland, and 209 for Germany. Direct health costs related to ADHD ranged between 0.3 and 2.5 million EUR yearly per million inhabitants for the five countries. Additionally, a substantial number of ADHD cases, on average 18%, were associated with pyrethroid exposure. Yet, these figures should be interpreted with caution given the uncertainty of the estimation. A sensitivity analysis showed that by applying a different exposure-response function from outside the EU, the population attributable fraction decreased from an average of 18 to 7%. To ensure more robust disease burden estimates and adequate follow-up of policy measures, more HBM studies are needed, along with increased efforts to harmonize the design of epidemiological studies upfront to guarantee meta-analysis of exposure-response functions. This is particularly important for pyrethroids as evidence of potential adverse health effects is continuously emerging.

This integrated pedo-geoarchaeological study focuses on three abandoned pre-Hispanic terrace agricultural systems near Laramate in the southern Andes of Peru (14.5° S), aiming to unravel the pedological and land-use history of the region, which served as a significant agricultural hub during pre-Hispanic times. The key objectives of the investigation involved contextualizing the former agricultural management system within its geomorphological and palaeoecological framework and assessing the impact of agricultural practices on soil development and quality by comparing non-irrigated agricultural terrace soils with their undisturbed palaeo-pedological counterparts. The Laramate terrace complex, with its diverse terrace systems and varied geomorphological and geological settings, provided an ideal setting for the investigation. This comprehensive examination integrated a range of methodologies, including field surveys, digital mapping, and geomorphological analysis based on GIS and remote sensing applications, soil analysis (e.g. grain size, bulk chemistry, nutrient budget), plant microfossils (phytoliths and starch), and radiocarbon dating. In the Laramate region, the geomorphological setting of terrace agricultural systems promotes their optimal functioning. The terraces are often located in sun-sheltered areas with western exposure on middle and lower slopes or valley bottoms, which mitigate intense solar radiation, reduce evapotranspiration, increase soil moisture, and minimize erosion. The study identifies three soil groups in the Laramate region: Phaeozems, Andosols, and Anthrosols. Unique characteristics of Phaeozems challenge typical descriptions, influenced by factors such as climatic seasonality, vegetation, fauna, lithology, and aeolian inputs. The terrace soils in the Laramate region are classified as Terric Anthrosols, showing no significant degradation even after long-term use. Their balanced acidity and nutrient levels support Andean crop cultivation. Traditional non-mechanized tools, such as the chaquitaclla and rucana, likely minimized soil disruption. The terrace tillage horizons have high organic matter, indicating intentional organic manuring. Phytolith concentrations suggest intensive agricultural activity, particularly maize cultivation, with varying patterns suggesting changes in cultivation, fertilization, or mulching practices over time. Starch grain identification aligns with phytolith analyses, reinforcing maize's significance in the region. Although the use of animal-origin fertilizers requires further investigation, there is no evidence of nutrient maintenance through seasonal burning. Irrigation was minimal, and the abandonment of the pre-Hispanic cultivation system was unlikely due to soil exhaustion or terrace instability. Overall, the pre-Hispanic history of terrace agriculture in the Laramate region extends over four development phases, reflecting dynamic interactions between environmental, cultural, and agricultural factors. The initial phase, from the Formative Paracas period to the Early Nasca period (800 BCE–200 CE), witnessed the establishment of agricultural terraces with simple terrace architecture, while the Middle Horizon (600–1000 CE) saw systematic areal expansion influenced by the Wari culture. Adaptations to drier conditions included terrace agriculture on volcanic soils. The Late Intermediate period (1000–1450 CE) witnessed hydrological variability and further terrace expansion to lower altitudes and less agriculturally suitable locations. The final phase, marked by the onset of the Hispanic colonial period in 1535 CE, saw the gradual abandonment of terrace agricultural systems due to demographic shifts and reorganization of production systems. Despite this, the historical trajectory underscores the adaptability and resilience of pre-Hispanic communities in the Laramate region, showcasing innovative terrace agriculture as a means of coping with changing environmental conditions across diverse landscape units.

Abstract Background The burden of disease (BOD) approach, originating with the Global Burden of Disease (GBD) study in the 1990s, has become a cornerstone for population health monitoring. Despite the widespread use of the Disability-Adjusted Life Year (DALY) metric, variations in methodological approaches and reporting inconsistencies hinder comparability across studies. To tackle this issue, we set out to develop guidelines for reporting DALY calculation studies to improve the transparency and comparability of BOD estimates. Methods and Findings The development of the STROBOD statement began within the European Burden of Disease Network, evolving from initial concepts discussed in workshops and training sessions focused on critical analysis of BOD studies. In 2021, a working group was formed to refine the preliminary version into the final Standardised Reporting of Burden of Disease studies (STROBOD) statement, consisting of 28 items structured across six main sections. These sections cover the title, abstract, introduction, methods, results, discussion, and open science, aiming to ensure transparency and standardization in reporting BOD studies. Notably, the methods section of the STROBOD checklist encompasses aspects such as study setting, data inputs and adjustments, DALY calculation methods, uncertainty analyses, and recommendations for reproducibility and transparency. A pilot phase was conducted to test the efficacy of the STROBOD statement, highlighting the importance of providing clear explanations and examples for each reporting item. Conclusions The inaugural STROBOD statement offers a crucial framework for standardizing reporting in BOD research, with plans for ongoing evaluation and potential revisions based on user feedback. While the current version focuses on general BOD methodology, future iterations may include specialized checklists for distinct applications such as injury or risk factor estimation, reflecting the dynamic nature of this field.

Abstract Vbfnlo is a flexible parton level Monte Carlo program for the simulation of vector boson fusion (VBF), QCD-induced single and double vector boson production plus two jets, and double and triple vector boson production (plus jet) in hadronic collisions at next-to-leading order (NLO) in the strong coupling constant, as well as Higgs boson plus two and three jet production via gluon fusion at the one-loop level. For the new version – Version 3.0 – several major enhancements have been included. An interface according to the Binoth Les Houches Accord (BLHA) has been added for all VBF and di/tri-boson processes including fully leptonic decays. For all dimension-8 operators affecting vector boson scattering (VBS) processes, a modified T-matrix unitarization procedure has been implemented. Several new production processes have been added, namely the VBS $$Z\gamma jj$$ Z γ j j and $$\gamma \gamma jj$$ γ γ j j processes at NLO, $$\gamma \gamma jj $$ γ γ j j , WWj and ZZj production at NLO including the loop-induced gluon-fusion contributions and the gluon-fusion one-loop induced $$\varPhi jjj$$ Φ j j j ( $$\varPhi $$ Φ is a CP-even or CP-odd scalar boson) process at LO, retaining the full top-mass dependence. Finally, the code has been parallelized using Openmpi.