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Abstract Background Retroperitoneal dedifferentiated liposarcoma is a rare, aggressive malignancy, characterized by high rates of recurrences and the potential for metastasis. On imaging, these tumors typically present as a solid mass with lipomatous and non-lipomatous components. Cystic changes of dedifferentiated liposarcomas is exceedingly rare and might pose significant diagnostic challenges, with only a few cases reported in the literature. Report of 2 cases We here present two cases of retroperitoneal dedifferentiated liposarcoma with a rare cystic presentation in two female patients aged 51 and 62 years. Imaging revealed large perinephric cystic masses measuring up to 13.0 cm and 16.1 cm, respectively, with calcifications of the cyst wall observed in the second case. Differential diagnoses included cystic echinococcosis, mesenchymal neoplasms, and benign cystic lesions (e.g. endometrial cyst). Both patients underwent upfront compartmental en-bloc surgical resection of the tumor mass and the kidney after multidisciplinary tumor board (MDT) discussion. Macroscopically, the tumors were adherent to but sharply demarcated from the kidney. Histological examination of the first case revealed a small component of well-differentiated liposarcoma (WDLPS) adjacent to a large non-lipogenic sarcoma with a prominent whirling pattern, compatible with dedifferentiation. The second case demonstrated a spindle cell neoplasm with prominent osteosarcomatous heterologous differentiation. MDM2 amplification was confirmed in both cases by molecular testing. No long-term follow-up data is available for either patient. Conclusion In conclusion, these cases highlight the importance of recognizing unusual and extensive cystic changes of dedifferentiated liposarcoma, which can complicate the diagnostic work-up.

Abstract Traceability is critical for achieving seafood sustainability goals. However, trade restrictions highlight challenges for identifying basic information, including country of harvest. We use new seafood trade data to illustrate how trade can elude enforcement using the case of responses following Russian sanctions and quantify pathways through which the US imports Russian-harvested products. We then discuss the current policy landscape for enforcing trade restrictions and highlight priorities for improving seafood traceability.

Abstract Cell death programs such as apoptosis and ferroptosis are associated with aberrant redox homeostasis linked to lipid metabolism and membrane function. Evidence for cross-talk between these programs is emerging. Here, we show that cytotoxic stress channels polyunsaturated fatty acids via lysophospholipid acyltransferase 12 into phospholipids that become susceptible to peroxidation under additional redox stress. This reprogramming is associated with altered acyl-CoA synthetase isoenzyme expression and caused by a decrease in growth factor receptor tyrosine kinase (RTK)-phosphatidylinositol-3-kinase signaling, resulting in suppressed fatty acid biosynthesis, for specific stressors via impaired Akt-SREBP1 activation. The reduced availability of de novo synthesized fatty acids favors the channeling of polyunsaturated fatty acids into phospholipids. Growth factor withdrawal by serum starvation mimics this phenotype, whereas RTK ligands counteract it. We conclude that attenuated RTK signaling during cell death initiation increases cells’ susceptibility to oxidative membrane damage at the interface of apoptosis and alternative cell death programs.

Abstract Transmission systems for the aviation industry are continuously pushed to new and extreme limits. Gears in rotorcraft transmissions or geared turbofans must withstand considerable torques while operating at high rotational speeds and temperatures. Such high-power density makes continuous lubricant supply indispensable for the transmission to operate safely. However, loss of lubrication events can occur during operation, potentially leading to gear failure and, consequently, to catastrophic events. The research community is striving to propose alternative solutions for increasing the lifetime of gears in loss of lubrication conditions. Surface and lubricant technologies, such as tribological coatings or ionic liquid additives, have shown great potential to reduce friction and wear and to increase the lifetime of gears under loss of lubrication. This paper reviews the main progress in surface technologies, such as coatings, surface texturing, and thermochemical treatments, with a focus on gear surface treatments. Furthermore, ways to decrease friction in the gear contact to increase wear and scoring resistance by lubricants and additives are discussed. The main findings highlighted in this review can support the future design of new transmission systems for aircraft and helicopters to reduce the need for the yet required secondary lubrication supply, thereby reducing space, cost, weight, and most importantly, CO2 emissions.

Abstract The opioid receptor family, particularly the µ opioid receptor, are the main drug targets in the management of severe pain. However, their pain-relieving effects are often accompanied by severe adverse effects, underlining the necessity for extensive research on this receptor family. Opioids, the agonists targeting these receptors, differ in their chemical structure and also in their mode of action in different aspects of signaling. Here we introduce novel tools that facilitate the analysis of this receptor family, by the development of FRET- and BRET-based receptor conformation sensors. With these sensors we were able to characterize especially the µ opioid receptor in more detail and reveal a strongly agonist-dependent activation kinetics for this receptor. Moreover, our sensors offer an assay independent from other signaling pathways, thereby minimizing the potential for interfering influences or biases within the system.

Audio packet loss concealment hides gaps in VoIP audio streams caused by network packet loss. It operates in real-time with low computational requirements and latency, as demanded by modern communication systems. With the ICASSP 2024 Audio Deep Packet Loss Concealment Grand Challenge, we build on the success of the previous Audio PLC Challenge held at INTERSPEECH 2022. For the 2024 challenge at ICASSP, we update the challenge by introducing an overall harder blind evaluation set and extending the task from wideband to fullband audio, in keeping with current trends in internet telephony. In addition to the Word Accuracy metric, we also use a questionnaire based on an extension of ITU-T P.804 to more closely evaluate the performance of systems specifically on the PLC task. We evaluate a total of 9 systems submitted by different academic and industry teams, 8 of which satisfy the strict real-time performance requirements of the challenge, using both P.804 and Word Accuracy evaluations. Two systems share first place, with one of the systems having the advantage in terms of naturalness, while the other wins in terms of intelligibility. These systems are the current state of the art for Deep PLC.

Abstract The collective dynamics around the second-order O(4) chiral phase transition in QCD with two massless quark flavors can be understood by appealing to universality. We present a novel formulation of the real-time functional renormalization group (FRG) that describes the stochastic hydrodynamic equations of motion for systems in the same dynamic universality class, which corresponds to Model G in the Halperin-Hohenberg classification. Our approach preserves all relevant symmetries of such systems with reversible mode couplings, which establishes the real-time FRG as a valuable tool complementary to classical-statistical simulations. As a first application we show that our approach is consistent with dynamic scaling relations and reproduces the non-trivial value z = d/2 for the dynamic critical exponent in d spatial dimensions. Moreover, we extract a novel dynamic scaling function that describes the universal momentum and temperature dependence of the diffusion coefficient of iso-(axial-)vector charge densities in the symmetric phase.

Abstract There are three Anopheles mosquito species in East Africa that are responsible for the majority of malaria transmission, posing a significant public health concern. Understanding the vector competence of different mosquito species is crucial for targeted and cost-effective malaria control strategies. This study investigated the vector competence of laboratory reared strains of East African An. gambiae sensu stricto, An. funestus s.s., and An. arabiensis mosquitoes towards local isolates of Plasmodium falciparum infection. Mosquito feeding assays using gametocytaemic blood from local donors revealed significant differences in both prevalence and intensity of oocyst and sporozoite infections among the three vectors. An. funestus mosquitoes presented the highest sporozoite prevalence 23.5% (95% confidence interval (CI) 17.5–29.6) and intensity of infection 6-58138 sporozoites. Relative to An. funestus, the odds ratio for sporozoites prevalence were 0.46 (95% CI 0.25–0.85) in An. gambiae and 0.19 (95% CI 0.07–0.51) in An. arabiensis, while the incidence rate ratio for sporozoite intensity was 0.31 (95% CI 0.14–0.69) in An. gambiae and 0.66 (95% CI 0.16–2.60) in An. arabiensis. Our findings indicate that all three malaria vector species may contribute to malaria transmission in East Africa, with An. funestus demonstrating superior vector competence. In conclusion, there is a need for comprehensive malaria control strategies targeting major malaria vector species, an update of malaria transmission models to consider vector competence and evaluation of malaria transmission blocking interventions in assays that include An. funestus mosquitoes.

Abstract Background Rhabdomyolysis is frequently associated with acute kidney injury (AKI). Due to the nephrotoxic properties of myoglobin, its rapid removal is relevant. If kidney replacement therapy (KRT) is necessary for AKI, a procedure with effective myoglobin elimination should be preferred. This pilot trial was designed to compare different KRT modes that enable myoglobin elimination. Methods In this prospective randomized single-center study, 15 patients with rhabdomyolysis and severe AKI requiring KRT were randomized 1:1:1 into three groups: continuous veno-venous hemofiltration (CVVH), continuous veno-venous hemodialysis (CVVHD) using a high cut-off dialyzer (CVVHD-HCO), or CVVHD using a high-flux dialyzer in combination with the adsorber CytoSorb (CVVHD-CS). Concentrations of serum myoglobin, urea, creatinine, β2-microglobulin, interleukin-6, and albumin were measured before and after the dialyzer 1, 6, 12, and 24 h after initiating KRT. Results There was no significant difference in the median myoglobin clearance between the KRT modes during the 24-h study period. Nevertheless, the CVVHD-CS group showed a significantly higher myoglobin elimination compared to the other modes in the first hours of treatment. However, as a greater decline in clearance performance was observed over time, no better performance was detected over the whole study period. Simulation of different device combinations showed the highest myoglobin clearance for CVVHD-HCO combined with CS with a 12-hourly adsorber exchange interval. Conclusions All tested modes showed an effective myoglobin elimination capacity. The time-dependent elimination performance could be further increased by combining KRT with more frequent adsorber exchange. Trial registration German Clinical Trials Registry ( DRKS00023998 ); date of registration 03/03/2021.

Background: Solubility is a common feature of allergens. However, the causative relationship between this protein-intrinsic feature and sensitization capacity of allergens is not fully understood. This study aimed to proof the concept of solubility as a protein intrinsic feature of allergens. Methods: The soluble birch pollen allergen Bet v 1 was covalently coupled to 1 μm silica particles. IgE-binding and -cross-linking capacity was assessed by inhibition ELISA and mediator release assay, respectively. Alterations in adjuvanticity by particle-loading were investigated by activation of dendritic cells, mast cells and the Toll-like receptor 4 pathway as well as by Th2 polarization in an IL-4 reporter mouse model. In BALB/c mice, particle-loaded and soluble Bet v 1 were compared in a model of allergic sensitization. Antigen uptake and presentation was analysed by restimulating human Bet v 1-specific T cell lines. Results: Covalent coupling of Bet v 1 to silica particles resulted in an insoluble antigen with retained IgE-binding and -cross-linking capacity and no increase in adjuvanticity. In vivo, particle-loaded Bet v 1 induced significantly lower Bet v 1-specific (s)IgE, whereas sIgG1 and sIgG2a levels remained unaffected. The ratio of Th2 to Th1 cells was significantly lower in mice sensitized with particle-loaded Bet v 1. Particle-loading of Bet v 1 resulted in a 24-fold higher T cell activation capacity in Bet v 1-specific T cell lines, indicating more efficient uptake and presentation than of soluble Bet v 1. Conclusions: Our results show that solubility is a decisive factor contributing to the sensitization capacity of allergens. The reduction in sensitization capacity of insoluble, particle-loaded antigens results from enhanced antigen uptake and presentation compared to soluble allergens.

ABSTRACT Background CREB binding protein (CREBBP) is a key epigenetic regulator, altered in a fifth of relapsed cases of acute lymphoblastic leukemia (ALL). Selectively targeting epigenetic signaling may be an effective novel therapeutic approach to overcome drug resistance. Anti‐tumor effects have previously been demonstrated for GSK‐J4, a selective H3K27 histone demethylase inhibitor, in several animal models of cancers. Methods To characterize the effect of GSK‐J4, drug response profiling, CRISPR‐Dropout Screening, BH3 profiling and immunoblotting were carried out in ALL cell lines or patient derived samples. Results Here we provide evidence that GSK‐J4 downregulates cyclic AMP‐responsive element‐binding protein (CREB) and CREBBP in B‐cell precursor‐ALL cell lines and patient samples. High CREBBP expression in BCP‐ALL cell lines correlated with high GSK‐J4 sensitivity and low dexamethasone sensitivity. GSK‐J4 treatment also induced Bcl‐2 and Bcl‐XL dependency and apoptosis. Conclusions This study proposes H3K27 demethylase inhibition as a potential treatment strategy for patients with treatment‐resistant ALL, using CREBBP as a biomarker for drug response and combining GSK‐J4 with venetoclax and navitoclax as synergistic partners.

Abstract Background The COVID-19 pandemic entailed a global health crisis, significantly affecting medical service delivery in Germany as well as elsewhere. While intensive care capacities were overloaded by COVID cases, not only elective cases but also non-COVID cases requiring urgent treatment unexpectedly decreased, potentially leading to a deterioration in health outcomes. However, these developments were only uncovered retrospectively. Especially university hospitals, which were meant to take on a central coordinating role, did not have detailed information on expected healthcare utilization, available resources and capacities, and the quality of medical care. The experience of compromised healthcare and a lack of monitoring during the COVID-19 pandemic made it clear that healthcare systems should be better prepared. Therefore, the aim of this work was to develop a set of indicators suited to detect undesirable developments concerning the provision of inpatient healthcare. Material & methods The study employed a literature review, online surveys, expert interviews, and a multistep evaluation process to develop a core set of quality indicators (QIs) suitable for assessing the resilience of university hospitals during pandemics. This initial set of indicators was refined through consultations with a) quality and risk management officials from German university hospitals via an online survey and b) a diverse panel of experts. Results The comprehensive evaluation identified two primary strands: organizational/management indicators (Strand A, 60 indicators) and disease-specific clinical quality and patient safety indicators (Strand B, 20 indicators for critical conditions like stroke, myocardial infarction, and cancer.) Three additional indicators were added after a final expert panel meeting, resulting in a final set of 83 indicators. Discussion and conclusion The developed QIs mark a significant advancement in the operational preparedness of university hospitals for pandemics. The study contributes to quality management in healthcare during pandemics by creating the basis for a structured approach to pandemic preparedness and response. This unique set of QIs within the German context presents an opportunity for establishing quality improvement, underscoring the importance of a robust, adaptable quality management framework as a basis for safeguarding against future health crises.

Abstract Background Cannabis is increasingly used and debates about the legalisation of the recreational use of cannabis are ongoing. In this prospective, placebo-controlled study in healthy volunteers not regularly consuming cannabis, subjective psychotropic and somatic effects after a single dose of intravenous THC were assessed and quantified over 48 h. Methods Twenty-five healthy volunteers received a single IV bolus of THC and 6 received normal saline. Psychotropic and somatic effects of THC were assessed by two questionnaires that were completed at up to 14 timepoints from shortly before drug administration to 48 h later. Results Demographic data did not differ between groups. Differences between THC and placebo for all assessed effects, except for euphoria, irritation and headache, were clearly discernible. Subdimensions related to positive mood were less and those related to negative mood were more pronounced in the THC group. Peak plasma concentrations were observed at 1 to 5 min after THC administration while peak effects occurred between 45 and 60 min. Differences between THC and placebo were pronounced and seen for up to 90 to 120 min for most effects, except for “sleepiness” and “deactivation”, where the effect of THC was discernible for up to 5 h. At 24 and 48 h, there were no statistically significant difference between THC and placebo group. Conclusions THC triggers a large range of psychotropic and somatic effects with peak effects at 45 to 60 min after IV administration of THC, much later than plasma peak levels. Most effects are short-lasting with a duration of up to 2 h, but some effects like sleepiness and deactivation can be longer-lasting and persist for 5 h or longer in cannabis-naïve or cannabis-abstinent individuals. Since effects of THC demonstrate a time course that differs from the time course of plasma concentrations it might be important to base the judgment of a possible impairment related to THC consumption on clinical or behavioral tests in addition to THC plasma levels. Trial registration www.isrctn.com ; registration number ISRCTN53019164.

Abstract Background The national malaria control programmes in Cambodia, Nepal, and Bhutan aim to achieve malaria elimination by 2025–2030. While the vivax malaria burden remains challenging, the consistent decline in falciparum malaria in these countries over the last five years suggests that the goal is achievable. However, unexpected cases in previously falciparum malaria-free districts continue to occur. A virtual meeting was convened in May 2024, followed by smaller meetings, to discuss and share experiences among regional partners, focusing on falciparum malaria elimination. Main text The discussion among regional partners from these three countries was prompted by an isolated outbreak of falciparum malaria in April 2022 in a previously malaria-free district in Pursat province, Cambodia. The National Center for Parasitology, Entomology and Malaria Control (CNM) worked with stakeholders to contain the outbreak, which was likely to have originated in forest goers. Community-based village malaria workers (VMWs) were augmented with the additional resources required to test and treat malaria among forest goers under the supervision of health centres and district hospitals. This response rapidly reduced malaria cases in the subsequent months. Regional partners from Nepal and Bhutan, who are also engaged in the final phase of malaria elimination, reported that isolated malaria outbreaks in their countries were not unusual and were mostly imported from a neighbouring country, India. Importation of cases was facilitated by unsupervised transborder travel including the movement of migrant workers. The imported cases were only established during the case investigation such as when responding to the isolated outbreaks. In contrast, in Cambodia, spread of malaria was known to be facilitated by mobile and migrant workers, and forest goers within the country. The specific differences between Nepal and Bhutan (South Asia), and Cambodia (Greater Mekong Subregion) offered insights into strategies for malaria elimination. A relevant component for countries embarking on malaria elimination included strengthening of local malaria surveillance and response in collaboration with the community health workers, and community members targeting the ‘at risk’ population. Conclusion In countries approaching malaria elimination, resourcing community-based health workers could play a critical role in enhancing malaria surveillance, early case detection and treatment, including interventions targeting migrant populations such as forest goers and seasonal migrant workers.

Abstract Prime editing (PE) allows for precise genome editing in human pluripotent stem cells (hPSCs), such as introducing single nucleotide modifications, small insertions or deletions at a specific genomic locus. Here, we systematically compare a panel of prime editing conditions in hPSCs and generate a potent prime editor, “PE-Plus”, through co-inhibition of mismatch repair and p53-mediated cellular stress responses. We further establish an inducible prime editing platform in hPSCs by incorporating the PE-Plus into a safe-harbor locus and demonstrated temporal control of precise editing in both hPSCs and differentiated cells. By evaluating disease-associated mutations, we show that this platform allows efficient creation of both monoallelic and biallelic disease-relevant mutations in hPSCs. In addition, this platform enables the efficient introduction of single or multiple edits in one step, demonstrating potential for multiplex editing. Our method presents an efficient and controllable multiplex prime editing tool in hPSCs and their differentiated progeny.

Abstract The emergence of Plasmodium falciparum parasites resistant to artemisinins compromises the efficacy of Artemisinin Combination Therapies (ACTs), the global first-line malaria treatment. Artemisinin resistance is a complex genetic trait in which nonsynonymous SNPs in PfK13 cooperate with other genetic variations. Here, we present population genomic/transcriptomic analyses of P. falciparum collected from patients with uncomplicated malaria in Cambodia and Vietnam between 2018 and 2020. Besides the PfK13 SNPs, several polymorphisms, including nonsynonymous SNPs (N1131I and N821K) in PfRad5 and an intronic SNP in PfWD11 (WD40 repeat-containing protein on chromosome 11), appear to be associated with artemisinin resistance, possibly as new markers. There is also a defined set of genes whose steady-state levels of mRNA and/or splice variants or antisense transcripts correlate with artemisinin resistance at the base level. In vivo transcriptional responses to artemisinins indicate the resistant parasite’s capacity to decelerate its intraerythrocytic developmental cycle (IDC), which can contribute to the resistant phenotype. During this response, PfRAD5 and PfWD11 upregulate their respective alternatively/aberrantly spliced isoforms, suggesting their contribution to the protective response to artemisinins. PfRAD5 and PfWD11 appear under selective pressure in the Greater Mekong Sub-region over the last decade, suggesting their role in the genetic background of the artemisinin resistance.

Background and aims: The 2019 European Society of Cardiology guidelines for the management of dyslipidemia consider the use of high-dose marine omega-3 fatty acid (FA) eicosapentaenoic acid (EPA) supplementation (icosapent ethyl 2 × 2g/day) to lower residual cardiovascular risk in high-risk patients with hypertriglyceridemia. This study aimed to assess the eligibility for omega-3 FA-EPA supplementation in patients with acute coronary syndromes (ACS). Methods: In a prospective Swiss cohort of patients hospitalized for ACS, eligibility for marine omega-3 FA-EPA, defined as plasma triglyceride levels ranging from 1.5 to 5.6 mmol/l, was assessed at baseline and one-year follow-up and compared across subgroups. Lipid-lowering therapy intensification with statin and ezetimibe was modelled to simulate a hypothetical systematic treatment and its effect on omega-3 FA-EPA supplementation eligibility. Results: Of 2643 patients, 98 % were prescribed statin therapy at discharge, including 62 % at a high-intensity regimen; 93 % maintained it after one year, including 53 % at a high-intensity regimen. The use of ezetimibe was 3 % at discharge and 7 % at one year. Eligibility was observed in 32 % (32 % men, 29 % women) one year post-ACS. After modelling systematic treatment with statins, ezetimibe, and both, eligibility decreased to 31 %, 25 % and 24 %, respectively. Eligibility was higher in individuals aged

Abstract The mosquito-lethal effect of commercially available standard and long-lasting ivermectin formulations were evaluated in cattle and buffalo against wild-caught Anopheles on Sumba Island, Indonesia. Cattle have substantially higher blood-level concentrations of ivermectin compared to buffalo after receiving similar doses, irrespective of formulation. In total, nine Anopheles species were captured to assess the mosquito-lethal effects of ivermectin with susceptibility ranked from lowest to highest: An. flavirostris

Abstract Although balance training can improve balance across various populations, the underlying mechanisms, such as how balance training may alter sensory integration, remain unclear. This study examined the effects of balance training with visual input manipulations provided by virtual reality versus conventional balance training on measures of postural sway and sensory integration during balance control. Twenty-two healthy young adults were randomly allocated into a balance training group (BT) or a balance training with virtual reality group (BT + VR). The BT received traditional balance training, while the BT + VR additionally received visual manipulations during the 4-week balance training to elicit sensory conflicts. Static balance was measured in the form of center of pressure (COP) sway speed in trained (eyes open) and untrained (eyes closed) balance conditions. A model-based analysis quantified the sensory integration and feedback characteristics of the balance control mechanism. Herein, the visual weight quantifies the contribution of visual orientation information to balance while the proportional and derivative feedback loop-gains correct for deviations from the desired angular position and angular velocity, respectively. Significant main time effects were observed for the visual sensory contribution to balance (p = 0.002, $$\:{\eta\:}_{p}^{2}$$ = 0.41) and for the derivative feedback loop-gain (p = 0.011, $$\:{\eta\:}_{p}^{2}$$ = 0.29). Significant group-by-time interactions were observed for COP sway speed in the untrained task (p = 0.023, $$\:{\eta\:}_{p}^{2}$$ = 0.23) in favor of BT + VR and in the proportional feedback loop-gain, with reductions only in the BT + VR group (p = 0.043, $$\:{\eta\:}_{p}^{2}$$ = 0.2). BT + VR resulted in larger performance improvements compared with traditional BT in untrained tasks, most likely due to reduced reliance on visual information. This suggests that the systematic modulation of sensory inputs leads to enhanced capacity for motor adaptation in balance training.

Abstract Transition of highly pathogenic clade 2.3.4.4b H5 avian influenza virus (HPAIV) from epizootic to enzootic status in Northern European countries was associated with severe losses and even mass mortalities among various wild bird species. Both avian and mammalian raptors hunting infected debilitated birds or scavenging on virus-contaminated avian carcasses contracted HPAIV infection. This precarious pathogen-prey-predator relation further worsened when in 2021 and 2022 outbreaks in Germany overlapped with the hatching season of avian raptor species. Retro- and prospective surveillance revealed avian raptors as important indicators of HPAIV and its genetic diversity on the one hand. On the other hand, their role as victims of HPAIV is stipulated. The first case of an HPAIV H5N1-related death of a white-tailed sea eagle (Haliaeetus albicilla; WTSE) hatch in Germany, 2021, followed by several such cases in 2022, and a low overall seropositivity rate of 5.0–7.9% among WTSE nestlings, raised fears of a serious negative impact on reproduction rates of WTSEs and other birds of prey when HPAIV becomes enzootic in an ecosystem. However, comparably stable breeding success of WTSE in the study area in 2022 and a potentially evolving natural immunity raises hope for a less severe long-term impact.

Abstract Background The risk of breast cancer patients for long-term side effects of therapy such as neurotoxicity and cardiotoxicity as well as late effects regarding comorbidities varies from individual to individual. Personalised follow-up care concepts that are tailored to individual needs and the risk of recurrences, side effects and late effects are lacking in routine care in Germany. Methods We describe the methodology of BETTER-CARE, a parallel-arm cluster-randomised controlled trial conducted at 15 intervention and 15 control centres, aiming to recruit 1140 patients, and the results of the pilot phase. The needs- and risk-adapted complex intervention, based on existing development frameworks, includes a multidisciplinary network and digital platforms for symptom and need documentation and just-in-time adaptive interventions. The control group comprises usual care according to clinical guidelines. The primary outcome is health-related quality of life (EORTC QLQ-C30 global health), and secondary outcomes include treatment adherence. Results The 2-month pilot phase comprising 16 patients in one intervention and one control pilot centre demonstrated the feasibility of the BETTER-CARE approach. Discussion BETTER-CARE is a feasible intervention and study concept, investigating individualised needs- and risk-adapted breast cancer follow-up care in Germany. If successful, the approach could be implemented in German routine care. Trial registration German Clinical Trial Register DRKS00028840. Registered on April 2022.

Abstract Background Cardiac arrhythmia has been reported as a significant complication of thoracic radiotherapy. Both bradyarrhythmias and tachyarrhythmias have been reported, highlighting the arrhythmia-modulating potential of radiation in certain oncologic therapies. This study aimed to analyse the arrhythmic burden in patients with cardiac implantable electrical devices (CIEDs) undergoing thoracic irradiation, examining both immediate effects of radiotherapy and long-term sequelae post-therapy. Methods and results A retrospective cohort study was conducted involving patients with CIEDs who received thoracic radiotherapy between January 2012 and December 2022. Two distinct analyses were performed involving (1) daily CIED follow-ups during radiotherapy and (2) long-term arrhythmic outcomes post-therapy. For long-term outcomes, Patients were matched in a 1:2 ratio with non-irradiated controls based on age, sex, cardiovascular risk factors, cardiac disease, and beta-blocker use. Statistical analyses included negative binomial regression and propensity score matching. A total of 186 patients underwent daily CIED monitoring during radiotherapy, with 79 receiving thoracic irradiation. Thoracic irradiation was negatively associated with atrial arrhythmia (OR 0.11 [0.02;0.70, 95% CI], adjusted p = 0.0498) and there was a tendency towards less ventricular events (OR 0.14 [0.02;1.41, 95% CI], adjusted p = 0.3572) during radiotherapy in a univariate regression analysis. This association was not significant in the multivariate (OR 0.44 [0.10;1.80, 95%-CI], p = 0.16) model including a history of atrial fibrillation, diabetes and beta-blocker use. Coronary artery disease was associated with an increase in atrial and ventricular arrhythmia. For the long-term analysis, 122 patients were followed up after thoracic (N = 33) and non-thoracic radiation (N = 89) and compared to 244 matched controls drawn from approximately 10.000 CIED-patients. There was no significant increase in arrhythmic events compared to controls over a median follow-up of 6.6 months. A previous history of ventricular or atrial arrhythmic events was the strongest predictor for events during the follow-up. Conclusion Thoracic radiotherapy can be safely administered in patients with CIEDs. However, patients with a history of arrhythmia are more prone to arrhythmic events during and after radiation. These findings highlight the need for personalized arrhythmia management strategies and further research to understand the mechanisms underlying the antiarrhythmic effects of thoracic radiation. Graphical Abstract

Abstract Background Endometriosis is a chronic, estrogen-dependent, benign condition, affecting 10–15% of women of reproductive age. It is associated with a prevalence of sexual dysfunction that is nearly twice as high as that seen in women with other benign gynecological conditions. Our study aimed to assess the effect of surgical intervention on sexual function, as measured by the FSFI (Female Sexual Function Index) score, in women with endometriosis compared to those with other benign gynecological conditions, both before and after surgery. Methods A comparative analysis was conducted at the Medical University of Vienna from 2015 to 2020. The study included patients suspected of having endometriosis, fibroids, adnexal cysts, and/or infertility. Based on findings during surgery, patients were categorized into two groups: those with endometriosis (n = 64) and control patients (n = 38). All participants completed the FSFI questionnaire before surgery and again 8 to 18 weeks after the operation. Results No significant differences were observed in the preoperative FSFI scores between the endometriosis patients and the control group. Similarly, no significant differences were found between the two groups in postoperative scores. However, in women diagnosed with endometriosis, surgical removal of endometriotic lesions significantly increased their full-scale FSFI score, and resulted in a significant improvement in the areas “desire” and “satisfaction”. Improvements were noted in all other areas as well, though they were not statistically significant. Conclusions Our research indicates that the surgical removal of endometriotic lesions can lead to an improvement in sexual function, as measured by the FSFI, within 8 to 18 weeks post-surgery. This improvement was not observed in the control group, which underwent surgery for other benign gynecological issues.

Abstract Background The major breakthrough in cancer therapy with immune checkpoint inhibitors (ICIs) has highlighted the important role of immune checkpoints in antitumoral immunity. However, most patients do not achieve durable responses, making biomarker research in this setting essential. CD27 is a well known costimulatory molecule, however the impact of its soluble form in ICI is poorly investigated. Therefore, we aimed at testing circulating concentrations of soluble CD27 (sCD27) and CD27 bound to extracellular vesicles (EVs) as potential biomarkers to predict response and overall survival (OS) in patients undergoing ICI. Methods Serum and plasma levels of sCD27 were assessed by immunoassay in three patient cohorts (n = 187) with advanced solid malignancies including longitudinal samples (n = 126): a training (n = 84, 210 specimens, Aachen ICI) and validation cohort (n = 70, 70 specimens, Hamburg ICI), both treated with ICI therapy, and a second independent validation cohort (n = 33, 33 specimens, Hamburg non-ICI) undergoing systemic therapy without any ICI. In a subset (n = 36, 36 baseline and 108 longitudinal specimens), EV-bound CD27 from serum was measured, while EV characterization studies were conducted on a fourth cohort (n = 45). Results In the Aachen and Hamburg ICI cohorts, patients with lower circulating sCD27 levels before and during ICI therapy had a significantly longer progression-free survival (PFS) and OS compared to patients with higher levels, a finding that was confirmed by multivariate analysis (MVA) (Aachen ICI: pPFS = 0.012, pOS = 0.001; Hamburg ICI: pPFS = 0.040, pOS = 0.004) and after randomly splitting both cohorts into training and validation. This phenomenon was not observed in the Hamburg non-ICI cohort, providing a rationale for the predictive biomarker role of sCD27 in immune checkpoint blockade. Remarkably, EV-bound CD27 baseline levels and dynamics during ICI therapy also emerged as potent predictive biomarkers, acting however antagonistically to soluble sCD27, i.e. higher levels were associated with PFS and OS benefit. Combining both molecules (“multi-CD27” score) enhanced the predictive ability (HRPFS: 17.21 with p

We tested 130 rats captured in Berlin for coronaviruses. SARS-CoV-2 antibodies were detected in 1 rat, but all animals were negative by reverse transcription PCR, suggesting SARS-CoV-2 was not circulating in the rat population. However, alphacoronaviruses were found. Monitoring rodent populations helps to determine coronavirus occurrence, transmission, and zoonotic potential.

Abstract Aims Tafamidis improves clinical outcomes in transthyretin amyloid cardiomyopathy (ATTR‐CM), yet how tafamidis affects cardiac structure and function remains poorly described. This study prospectively analysed the effect of tafamidis on 12‐month longitudinal changes in cardiac structure and function by cardiac magnetic resonance (CMR) compared with the natural course of disease in an untreated historic control cohort. Methods and results ATTR‐CM patients underwent CMR at tafamidis initiation and at 12 months. Untreated patients with serial CMRs served as reference to compare biventricular function, global longitudinal strain (GLS), LV mass and extracellular volume fraction (ECV). Thirty‐six tafamidis‐treated (n = 35; 97.1% male) and 15 untreated patients (n = 14; 93.3% male) with a mean age of 78.3 ± 6.5 and 76.9 ± 6.5, respectively, and comparable baseline characteristics were included. Tafamidis was associated with preserving biventricular function (LVEF (%): 50.5 ± 12 to 50.7 ± 11.5, P = 0.87; RVEF (%): 48.2 ± 10.4 to 48.2 ± 9.4, P = 0.99) and LV‐GLS (−9.6 ± 3.2 to −9.9 ± 2.4%; P = 0.595) at 12 months, while a significantly reduced RV‐function (50.8 ± 7.3 to 44.2 ± 11.6%, P = 0.028; P (change over time between groups) = 0.032) and numerically worsening LVGLS (−10.9 ± 3.3 to −9.1 ± 2.9%, P = 0.097; P (change over time between groups) = 0.048) was observed without treatment. LV mass significantly declined with tafamidis (184.7 ± 47.7 to 176.5 ± 44.3 g; P = 0.011), yet remained unchanged in untreated patients (163.8 ± 47.5 to 171.2 ± 39.7 g P = 0.356, P (change over time between groups) = 0.027). Irrespective of tafamidis, ECV and native T1‐mapping did not change significantly from baseline to 12‐month follow‐up (P > 0.05). Conclusions Compared with untreated ATTR‐CM patients, initiation of tafamidis preserved CMR‐measured biventricular function and reduced LV mass at 12 months. ECV and native T1‐mapping did not change significantly comparable to baseline in both groups.

Abstract Personalized treatment for patients with advanced solid tumors critically depends on the deep characterization of tumor cells from patient biopsies. Here, we comprehensively characterize a pan-cancer cohort of 150 malignant serous effusion (MSE) samples at the cellular, molecular, and functional level. We find that MSE-derived cancer cells retain the genomic and transcriptomic profiles of their corresponding primary tumors, validating their use as a patient-relevant model system for solid tumor biology. Integrative analyses reveal that baseline gene expression patterns relate to global ex vivo drug sensitivity, while high-throughput drug-induced transcriptional changes in MSE samples are indicative of drug mode of action and acquired treatment resistance. A case study exemplifies the added value of multi-modal MSE profiling for patients who lack genetically stratified treatment options. In summary, our study provides a functional multi-omics view on a pan-cancer solid tumor cohort and underlines the feasibility and utility of MSE-based precision oncology.

Abstract Bacterial biofilms represent a prominent biological barrier against physical and chemical attacks. Disturbing the anaerobic microenvironment within biofilms by co-delivery of oxygen appears as a promising strategy to enhance the activity of an antibiotic. Here, we report the effect of oxygen-producing calcium peroxide nanoparticles (CaO2 NP) in combination with tobramycin sulfate (Tob). On Pseudomonas aeruginosa PAO1 biofilms in vitro, the additive effect of CaO2 NP towards Tob activity enhanced biofilm eradication by 2 log compared to Tob alone. For natural biofilms grown in the oral cavity of human volunteers in situ, treatment by CaO2 NP alone slightly increased the fraction of dead bacteria from 44% in various controls, including Tob alone, to 57%. However, the combination of CaO2 NP with Tob further increased the fraction of dead bacteria to 69%. These data confirm the intrinsic antimicrobial and antibiotic-potentiating effect of CaO2 NP also in a clinically relevant setting.

Abstract Vaccines have played a central role in combating the COVID-19 pandemic, but newly emerging SARS-CoV-2 variants are increasingly evading first-generation vaccine protection. To address this challenge, we designed “single-cycle infection SARS-CoV-2 viruses” (SCVs) that lack essential viral genes, possess distinctive immune-modulatory features, and exhibit an excellent safety profile in the Syrian hamster model. Animals intranasally vaccinated with an Envelope-gene-deleted vaccine candidate were fully protected against an autologous challenge with the SARS-CoV-2 virus through systemic and mucosal humoral immune responses. Additionally, the deletion of immune-downregulating viral genes in the vaccine construct prevented challenge virus transmission to contact animals. Moreover, vaccinated animals displayed neither tissue inflammation nor lung damage. Consequently, SCVs hold promising potential to induce potent protection against COVID-19, surpassing the immunity conferred by natural infection, as demonstrated in human immune cells.

Abstract Improved ability to assess and categorize the spatial characteristics of settlement patterns is required for a deeper understanding of how urbanization is driving land use and land cover transformation and its effects. Two approaches to the globally available settlement maps of the World Settlement Footprint 3D support a detailed assessment of spatial characteristics of settlement patterns in rural to urban landscapes and across scales: graph-based spatial network analysis and elements of fractal theory. Based on first comprehensive tests for the Punjab (India), the Nile Delta (Egypt) and the North China Plain, the results of our study suggest that the presented methods allow a quantitative and qualitative characterization and comparison of settlement patterns between different regions of the world. The approache allows to generate standardized baseline data for arbitrary regions in the world to analyze structuring principles of settlement hierarchies (e.g., self-organized fractal geometries) and their dependence on - or interaction with - cultural, political, socioeconomic, or environmental conditions.

Abstract Current guidelines recommend reflex testing for hepatitis D virus (HDV) coinfection in hepatitis B surface antigen (HBsAg)-positive patients over risk-factor based screening. We aimed to evaluate the feasibility and diagnostic yield of reflex anti-HDV testing at a Central European tertiary care center. We retrospectively included 560 consecutive patients who had a recorded (first) positive HBsAg test result at the Vienna General Hospital between 2018 and 2022. While reflex anti-HDV testing had been implemented in our hepatitis outpatient clinic (n = 153, ‘reflex testing cohort’), HDV screening needed to be manually ordered in the remaining patients (n = 407, ‘standard testing cohort’). Overall, 98.0% and 65.1% of patients in the reflex and standard testing cohort were screened for anti-HDV, respectively, and the overall seroprevalence of anti-HDV among screened patients was 6.7% (n = 28, reflex testing cohort: 9.3%, standard testing cohort: 5.3%). Risk factors for HDV were present in 49.1% of all included and in 89.3% of anti-HDV positive patients, respectively. Anti-HDV positive patients showed higher ALT (54 [33–83] vs. 29 [19–49] U/L; p = 0.005) and a higher proportion of low-to-undetectable HBV-DNA (61.5% vs. 33.2%; p

Background & Aims: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS). Methods: In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B. The primary outcome of PPS was defined as time from first radiographic progression on A/B to death. Results: A total of 406 patients alive after progression on first-line A/B were included in the final analysis, of whom 45.3% (n = 184) received best supportive treatment (BST) and 54.7% (n = 222) continued active systemic treatment. In the second line, 155 patients were treated with tyrosine kinase inhibitors (TKIs), 45 with immune checkpoint inhibitor (IO)-based regimens, and 3 had missing data. Median PPS of the whole cohort (mPPS) was 6.0 months (95% CI 5.2-7.2). On multivariate Cox regression analysis, absence of portal vein tumor thrombus, ECOG

The use of hyperpolarized media in combination with benchtop NMR spectrometers is currently extensively investigated to enable cost effective but highly sensitive applications. In this work, the instrumentation for the use of hyperpolarized 129Xe gas on a commercial benchtop-NMR spectrometer in a fully controllable yet automated mode is presented. A continuous-flow 129Xe polarizer is operated inline with the benchtop spectrometer. While the adjustment of the xenon gas partial pressure in the range of mbar to bar as well as the volume flow through the NMR sample is facilitated by the polarizer’s mass-flow controllers and two back-pressure regulators, respectively, the gas flow towards the NMR sample in situ in the benchtop magnet is time-controlled within the spectrometer’s RF pulse sequence programming. A calibration procedure for the gas flow control as well as thermally polarized xenon gas standards are introduced for quantification of the absolute 129Xe polarization. In this way, the 129Xe polarization achieved in the NMR measurement is determined in the 50% to 5% regime for very lean 1mbar to high 500mbar xenon partial pressure, respectively – in the optimum a more than 250,000-fold increase in comparison to thermal polarization. Such instrumentation may be implemented by combining any of the well-established continuous-flow 129Xe polarizer with any of the commercial benchtop spectrometers, thus facilitating high-performance hyperpolarized 129Xe benchtop NMR studies.

ABSTRACT Although many tree species frequently hybridize and backcross, management decisions in forestry and nature conservation are usually concentrated on pure species. Therefore, understanding which environmental factors drive the distribution and admixture of tree species on a local stand scale is of great interest to support decision‐making in the establishment and management of resilient forests. Here, we extensively sampled a mixed stand of hybridizing white oaks (Quercus petraea and Q. pubescens) near Lake Neuchâtel (Switzerland), where limestone and glacier moraine geologies coexist in proximity, to test whether micro‐environmental conditions can predict taxonomic distribution and genetic admixture. We collected DNA from bud tissue, individual soil samples, and extracted high‐resolution topographic data for 385 oak trees. We used 50 species‐discriminatory single nucleotide polymorphism (SNP) markers to determine the taxonomic composition and admixture levels of individual trees and tested their association with micro‐environmental conditions. We show that the trees' taxonomic distribution can be explained mainly by geographic position, soil pH, and potential rooting depth, a proxy for soil water availability. We found that admixed individuals tend to grow in habitats that are characteristic of the more drought‐tolerant species Q. pubescens rather than in intermediate habitats. Using in situ measurements, we are the first to show that fine‐scale variation in soil properties related to pH and water availability potentially drives the distribution of hybridizing tree species in a mixed stand. Microenvironmental variation therefore promotes local taxonomic diversity, facilitates admixture and adaptive introgression, and contributes to the resilience of forests under environmental change. Consequently, species such as white oaks should be managed and protected as a species complex rather than as pure species.

Risk communication has been found to be a driver of nocebo effects in medical settings by enhancing negative expectations. In fact, merely disclosing the risk of side effects and complications of treatments or medical procedures increases reports of adverse events. Along these lines, it has been proposed that the occurrence of headache after lumbar puncture (LP), a routine diagnostic procedure in neurology, is caused to a large degree by the information delivered by the physician during the informed consent procedure. As withholding information conflicts with principles of patient autonomy, strategies are needed to mitigate nocebo-associated headaches without omitting the disclosure of risks. Here, we present a detailed study protocol for a preregistered, prospective, double-blind, randomized controlled clinical trial with N = 80 inpatients at the neurology department of the University Hospital Essen who have an indication for a diagnostic LP. The trial is designed to test whether optimized communication strategies aimed at minimizing nocebo effects during the informed consent procedure reduce headache-related impairment after LP compared to standard-of-care. Secondary outcomes include expectation of side effects, state anxiety, headache intensity and duration, use of on-demand pain medication, perceived warmth and competence of the physician, and satisfaction with the procedure.

The anammox bacteria “Candidatus Kuenenia stuttgartiensis” (Ca. Kuenenia) are able to gain energy by combining ammonium and nitrite to produce nitrogen gas, which is an ecologically and technically significant activity process. In this reaction, nitric oxide serves as a recognized intermediate in the reduction of nitrite, which is subsequently combined with ammonium to produce hydrazine. However, the enzyme that converts nitrite to nitric oxide remains elusive. In this study, we investigated the nitrite-reducing activity in “Ca. Kuenenia stuttgartiensis” strain CSTR1 to identify candidates for such an enzyme. An optimized in vitro assay was established to measure nitrite-reducing activities, with which we followed the activity in protein fractions obtained from various fractionation methods. Separation of the cell extract of strain CSTR1 with size exclusion chromatography yielded active fractions corresponding to a molecular size range of 150–200 kDa. Several proteins coeluted with the nitrite-reducing activity, including the hydroxylamine dehydrogenase HOX, an NADP-dependent isopropanol dehydrogenase (Adh), an electron-transfer 4Fe-4S subunit protein (Fcp), and a nitric oxide detoxifying flavorubredoxin (NorVW). However, further separation of the cell extract with anion exchange chromatography, resulted in much lower activity yields, and activities were distributed among several fractions. In addition, fractionation of cell extracts using ultracentrifugation and ultrafiltration linked the activity to HOX, but could not exclude the involvement of other proteins in the activity. Overall, our results suggest that the molecular mechanism for nitrite reduction in “Ca. Kuenenia” strains is more complex than that currently described in the literature. Nitrite reduction appears to be strongly associated with HOX but may additionally require the participation of other proteins.

Objective When it comes to prospective studies on the incidence of rheumatoid arthritis (RA), the Norfolk study from 1994 is still frequently cited as prospective incidence data by many countries lacking comprehensive RA registries, including Austria. The aim of this study was, therefore, to gather robust data on the incidence of RA among Austrian adults for the first time.Methods All Upper Austrian rheumatologists reported newly diagnosed RA patients with symptom onset between 2016 and 2018, together with demographic data, laboratory and radiographic results. Cases still unclear at the end of 2018 were tracked in an extended observation period until 2023.Results In total, 701 RA cases were reported. 583 complete patient datasets were analysed. In all 551 individuals with a mean age of 60.2 (±14.2) years, 359 (65.2%) being females, the diagnosis of RA was ascertained clinically by a rheumatologist, optionally applying RA-classification criteria. Across all 3 years, the annual RA incidence rate was 14.9/100 000 (95% CI 12.9 to 17.3), ranging from 20.0/100 000 (95% CI 17.6 to 22.7) in 2016 to 13.5/100 000 (95% CI 11.5 to 15.7) in 2017 and 11.3/100 000 (95% CI 9.5 to 13.3) in 2018. The incidence was highest in individuals >65 years (21.6/100 000, 95% CI 16.4 to 27.9). Women had a higher RA incidence (18.1/100 000, 95% CI 14.9 to 21.7) than men (10.4/100 000, 95% CI 8.0 to 13.3).Conclusions This study provided prospective population-based data on the incidence of RA in Austrian adults for the first time. Incidence rates were comparable with other European countries. Compared with the Norfolk study, we found lower rates in both genders, more pronounced in females, however.

Objectives The purpose of this European survey was to describe current preprocedural planning, procedure techniques and post-implantation management of left atrial appendage closure (LAAC).Design Prospective survey regarding current practice for LAAC between March and August 2023.Setting 357 participating European LAAC centres in 14 countries.Results In 2022, the participating centres performed a total number of 9447 LAAC procedures, with a mean of 26 LAAC cases per centre (median 20; IQR 10–35). Preprocedure planning was performed with transoesophageal echocardiography (TOE) in 63% of centres, cardiac CT in 16%, or both in 21%. LAAC procedures were performed under general anaesthesia (59%), conscious sedation (36%) or with local anaesthesia only (5%). Device implantation was guided by conventional TOE (94%), intracardiac echocardiography (6%), miniaturised TOE probes (4%) or CT/fluoroscopy fusion (2%). The standard post-procedural antithrombotic regimen was dual antiplatelet therapy (73%), followed by single antiplatelet therapy (18%), conventional dose direct oral anticoagulant (DOAC) (7%) or half dose DOAC (1%), and no antithrombotic treatment (1%). There was a large heterogeneity between regions in terms of procedure volumes, hospital organisation, preprocedural planning, as well as procedural techniques and post-procedure management.Conclusions The present survey indicates that LAAC has become a widespread procedure in Europe. The findings highlight considerable heterogeneity among European countries in terms of preprocedural planning, procedural techniques including guidance and the post-procedural antithrombotic regimen. There is a need to evaluate the outcomes of different practices.

Background: Bursitis iliopectinea (BI) is a condition that is characterized by swelling of the iliopsoas bursa, leading to compression of inguinal neurovascular structures, causing swelling, pain, paresthesia, or thrombosis of the leg. Questions: Due to the rare occurrence of BI, the available literature consists of case reports. Our study aims to systematically review the literature for a comprehensive analysis of the etiology, treatment modalities, and clinical outcomes of patients with BI. Methods: We systematically analyzed 217 studies with 502 cases of BI and extracted information about the terminology, risk factors, diagnostic and treatment strategies, association with neurovascular compression syndromes, treatment outcomes, and recurrence rates. Results: The overall quality of the analyzed studies was moderate to good. The terminology uses for BI was heterogeneous and included ganglion, tumor, mass, and bursitis. In addition to conventional X-ray, ultrasound, CT, or MRI were used to diagnose BI. The most prevalent etiology of BI was osteoarthritis of the hip or wear-related soft-tissue reactions after total hip replacement (THA). Nearly one-third of the patients suffered from compression syndromes, most frequently of the femoral vein (16%). Only rheumatoid arthritis showed an association with the occurrence of compression syndromes. The most common operative treatments were the resection of the bursa (30%), total hip arthroplasty (29%), and aspiration (24%). Use of analgesics (17%), injection of corticoids (11%), and physiotherapy (9%) were used for conservative treatments. The recurrence rate was highest after physiotherapy (OR: 4.1) or aspiration (4.5) and lowest after THA (OR: 0.2). Conclusions: Although BI is a condition commonly associated with hip arthritis or local tissue reactions following total hip prosthesis, its impact extends beyond typical hip-related symptoms. Notably, BI related to rheumatoid arthritis shows a high correlation with neurovascular compression symptoms, with femoral vein compression being the most frequently reported. This underscores the necessity of considering BI in patients presenting with nonspecific inguinal pain or neurovascular symptoms of the lower extremity. Additionally, standardizing the nomenclature of BI nomenclature could improve future research.

We study the critical dynamics of a scalar field theory with Z2 symmetry in the dynamic universality class of Model A in two and three spatial dimensions with classical-statistical lattice simulations. In particular, we measure the non-equilibrium behavior of the system under a quench protocol in which the symmetry-breaking external field is changed at a constant rate through the critical point. Using the well-established Kibble-Zurek scaling theory we compute non-equilibrium scaling functions of cumulants of the order parameter up to fourth order. Together with the static critical exponents and the dynamic critical exponent, these fully describe the universal non-equilibrium evolution of the system near the critical point. We further extend the analysis to include finite-size effects and observe good collapse of our data onto two-dimensional universal non-equilibrium and finite-size scaling functions.

In this study, an advanced nanofiber breast cancer in vitro model was developed and systematically characterized including physico-chemical, cell-biological and biophysical parameters. Using electrospinning, the architecture of tumor-associated collagen signatures (TACS5 and TACS6) was mimicked. By employing a rotating cylinder or static plate collector set-up, aligned fibers (TACS5-like structures) and randomly orientated fibers (TACS6-like structures) fibers were produced, respectively. The biocompatibility of these fibers was enhanced by collagen coating, ensuring minimal toxicity and improved cell attachment. Various breast cancer cell lines (MCF7, HCC1954, MDA-MB-468, and MDA-MB-231) were cultured on these fibers to assess epithelial-to-mesenchymal transition (EMT) markers, cellular morphology, and migration.Aligned fibers (TACS5) significantly influenced EMT-related changes, promoting cellular alignment, spindle-shaped morphology and a highly migratory phenotype in mesenchymal and hybrid EMT cells (MDA-MB-468, MDA-MB-231). Conversely, epithelial cells (MCF7, HCC1954) showed limited response, but - under growth factor treatment - started to infiltrate the fibrous scaffold and underwent EMT-like changes, particularly on TACS5-mimicks, emphasizing the interplay of topographical cues and EMT induction.The biophysical analysis revealed a clear correlation between cellular EMT status and cell mechanics, with increased EMT correlating to decreased total cellular stiffness. Cancer cell mechanics, however, were found to be dynamic during biochemical and topographical EMT-induction, exceeding initial stiffness by up to 2-fold. These findings highlight the potential of TACS5-like nanofiber scaffolds in modeling the tumor microenvironment and studying cancer cell behavior and mechanics.

This paper is envisioned as a primarily methodological contribution towards a more sophisticated and systematic approach to conflict research in archaeology and history. Studies of conflicts in these fields have often focused on violence and war. Instead, we offer a more holistic approach to conflict research, taking into account different levels of both escalation and de-escalation that embrace all the possible aspects of a conflict from a mere undeveloped potential over complete annihilation to various countermeasures and stages of resolution. A model taking into account different levels of escalation and de-escalation is presented which embodies our multi-faceted view of conflicts and which also allows for a systematic, comparative analysis of conflict situations anywhere and any time in (pre)history. Through ten relatively detailed European case studies spanning the Bronze Age to the 20th century we demonstrate the comparative potential of our model and suggest ways in which it may help to identify typical patterns in conflict situations.

BACKGROUND: When Cox regression models are used to analyse time-to-event data, the proportional hazard assumption (PHA) must be reassured to obtain valid results. Transparent reporting of the statistics used is therefore essential to interpret research. This study aimed to assess the quality of statistical reporting and testing of the PHA in subgroup analysis of surgical randomised controlled trials (RCTs). METHODS: All published articles (see appendix 1) in the top quartile (25%) of surgical journals from 2019 to 2021 were screened in a literature review according to the ClarivateTM journal citation report impact factor. Subgroup analyses of surgical RCT data that used Cox models were identified. Statistical reporting was rated using a previously established 12-item PHA Reporting Score as our primary endpoint. For original surgical publications, the PHA was formally tested on reconstructed time-to-event data from Kaplan-Meier estimators. Methodological reporting quality was rated according to the CONSORT statement. Digitalisation was only possible in studies where a Kaplan-Meier estimator including numbers at risk per time interval was published. All results from the subgroup analyses were compared to primary surgical RCT reports and benchmark RCTs using Cox models published in the New England Journal of Medicine and The Lancet. RESULTS: Thirty-two studies reporting secondary subgroup analyses on surgical RCT data using Cox models were identified. Statistical reporting of surgical subgroup publications was significantly inferior compared to original benchmark publications: median PHA Reporting Score 50% (interquartile range [IQR]: 39 to 58) vs 58% (IQR: 42 to 67), p

BackgroundWith the increasing availability and use of digital tools such as virtual reality in medical education, there is a need to evaluate their impact on clinical performance and decision-making among healthcare professionals. The Trauma SimVR study is investigating the efficacy of virtual reality training in the context of traumatic in-hospital cardiac arrest.Methods and analysisThis study protocol (clinicaltrials.gov identifier: NCT06445764) for a single-center, prospective, randomized, controlled trial focuses on first-year residents in anesthesiology/intensive care, traumatology, and emergency medicine. The study will compare the clinical performance in a simulated scenario between participants who received virtual reality training and those who received traditional e-learning courses for preparation. The primary endpoint is the time to a predefined intervention to treat the underlying cause of the simulated traumatic cardiac arrest. Secondary endpoints include protocol deviations, cognitive load during simulated scenarios, and the influence of gender and personality characteristics on learning outcomes. The e-learning and the virtual reality training content will be developed in collaboration with experts from various medical specialties and nursing, focusing on procedural processes, guideline adherence specific to trauma patient care, and traumatic in-hospital cardiac arrest.ResultsThe results of this study will provide valuable insights into the efficacy of virtual reality training, contributing to the advancement of medical education, and serve as a foundation for future research in this rapidly evolving field.

IntroductionTo evaluate the impact of a novel design "Star Home" on the incidence of malaria, respiratory tract infections and diarrheal diseases among children, randomly selected households in Mtwara, Tanzania were offered a free, new Star Home. Drawing on longitudinal qualitative research that accompanied the Star Homes study, this article describes the experiences of residents and the wider community of living with these buildings.MethodsA total of four rounds of face-to-face interviews were undertaken with residents of Star Homes (n = 37), control (wattle/daub) homes (n = 21), neighboring households n = 6), community members (n = 17) and community leaders (n = 6). The use of Star Homes was also observed over these four time periods between 2021 and 2023. Interviews were conducted in Swahili, transcribed, and translated into English for thematic analysis.ResultsStar Homes residents appreciated several aspects of the Star Homes, including overall comfort, access to water and electricity, and clean toilets. There were concerns about some design elements, such as poorly closing doors, stoves perceived as inefficient, and the façade, which was susceptible to rainwater ingress. The houses were not always used as intended by their developers, for example, residents were sleeping downstairs instead of upstairs because of cold floors or difficulties using the stairs. Star Homes residents described how the structures triggered praise but also envy from other community members.ConclusionsThe findings highlight the need for close attention to the use of novel design houses and careful sensitization around the potential benefits of dwellings to ensure that the intended health impacts of interventions are achieved.