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We report on recent developments in positronium work in the frame of antihydrogen production through charge exchange in the AEgIS collaboration [1]. In particular, we present a new technique based on spatially imaging a cloud of positronium by collecting the positrons emitted by photoionization. This background free diagnostic proves to be highly efficient and opens up new opportunities for spectroscopy on antimatter, control and laser manipulation of positronium clouds as well as Doppler velocimetry.

Aims: Fracture-related infections (FRIs) are a devastating complication of fracture management. However, the impact of FRIs on mental health remains understudied. The aim of this study was a longitudinal evaluation of patients’ psychological state, and expectations for recovery comparing patients with recurrent FRI to those with primary FRI. Methods: A prospective longitudinal study was conducted at a level 1 trauma centre from January 2020 to December 2022. In total, 56 patients treated for FRI were enrolled. The ICD-10 symptom rating (ISR) and an expectation questionnaire were assessed at five timepoints: preoperatively, one month postoperatively, and at three, six, and 12 months. Results: Recurrent FRI cases consistently exceeded the symptom burden threshold (0.60) in ISR scores at all assessment points. The difference between preoperative-assessed total ISR scores and the 12-month follow-up was not significant in either group, with 0.04 for primary FRI (p = 0.807) and 0.01 for recurrent FRI (p = 0.768). While primary FRI patients showed decreased depression scores post surgery, recurrent FRI cases experienced an increase, reaching a peak at 12 months (1.92 vs 0.94; p < 0.001). Anxiety scores rose for both groups after surgery, notably higher in recurrent FRI cases (1.39 vs 1.02; p < 0.001). Moreover, patients with primary FRI reported lower expectations of returning to normal health at three (1.99 vs 1.11; p < 0.001) and 12 months (2.01 vs 1.33; p = 0.006). Conclusion: The findings demonstrate the significant psychological burden experienced by individuals undergoing treatment for FRI, which is more severe in recurrent FRI. Understanding the psychological dimensions of recurrent FRIs is crucial for comprehensive patient care, and underscores the importance of integrating psychological support into the treatment paradigm for such cases. Cite this article: Bone Jt Open 2024;5(7):621–627.

Introduction: Invasive pneumococcal disease is a major cause of morbidity and mortality in infectious diseases. Selective reporting of antibiotic susceptibility test results might lead to a tailored antibiotic therapy and could therefore be an important antibiotic stewardship program intervention. The aim of this study was to analyse whether a switch to selective reporting of antibiotic test results leads to a more focused antibiotic therapy in patients with a bloodstream infection with Streptococcus pneumoniae. Methods: This study was performed as a retrospective cohort study at the University Hospital Regensburg, Germany. All blood cultures positive for Streptococcus pneumoniae between 2006 and 2021 were analysed. In 2014, a switch to selective reporting of antibiotic susceptibility test results omitting sensitivity results for agents not recommended was introduced. Results: Twenty-four hours after final antibiotic susceptibility test results were available, 20.9% before (BI) versus 15.4% after implementation (AI) of selective reporting of antibiotic test results received a narrow-spectrum penicillin, while only 2.3% BI versus 5.8% AI received a narrow-spectrum penicillin from the beginning. Conclusion: Selective reporting of antibiotic susceptibility test results without further antimicrobial stewardship interventions did not lead to a higher use of a narrow-spectrum penicillin in this study.

The validity of the Weak Equivalence Principle (WEP) as predicted by General Relativity has been tested up to astounding precision using ordinary matter. The lack hitherto of a stable source of a probe being at the same time electrically neutral, cold and stable enough to be measured has prevented highaccuracy testing of the WEP on anti-matter. The AEg̅IS (Antimatter Experiment: Gravity, Interferometry, Spectroscopy) experiment located at CERN's AD (Antiproton Decelerator) facility aims at producing such a probe in the form of a pulsed beam of cold anti-hydrogen, and at measuring by means of a moiré deflectometer the gravitational force that Earth's mass exerts on it. Low temperature and abundance of the H̅ are paramount to attain a high precision measurement. A technique employing a charge-exchange reaction between antiprotons coming from the AD and excited positronium atoms is being developed at AEg̅IS and will be presented hereafter, alongside an overview of the experimental apparatus and the current status of the experiment

The AEgIS (Antimatter Experiment: Gravity, Interferometry, Spectroscopy) is a CERN based experiment with the central aim to measure directly the gravitational acceleration of antihydrogen. Antihydrogen atoms will be produced via charge exchange reactions which will consist of Rydberg-excited positronium atoms sent to cooled antiprotons within an electromagnetic trap. The resulting Rydberg antihydrogen atoms will then be horizontally accelerated by an electric field gradient (Stark effect), they will then pass through a moiré deflectometer. The vertical deflection caused by the Earth's gravitational field will test for the first time the Weak Equivalence Principle for antimatter. Detection will be undertaken via a position sensitive detector. Around 103 antihydrogen atoms are needed for the gravitational measurement to be completed. The present status, current achievements and results will be presented, with special attention toward the laser excitation of positronium (Ps) to the n=3 state and the production of Ps atoms in the transmission geometry.

Abstract Background Histopathology is the reference standard for diagnosing liver metastases of neuroendocrine tumors (NETs). Somatostatin receptor-positron emission tomography / computed tomography (SSR-PET/CT) has emerged as a promising non-invasive imaging modality for staging NETs. We aimed to assess the diagnostic accuracy of SSR-PET/CT in the identification of liver metastases in patients with proven NETs compared to histopathology. Methods Histopathologic reports of 139 resected or biopsied liver lesions of patients with known NET were correlated with matching SSR-PET/CTs and the positive/negative predictive value (PPV/NPV), sensitivity, specificity, and diagnostic accuracy of SSR-PET/CT were evaluated. PET/CT reading was performed by one expert reader blinded to histopathology and clinical data. Results 133 of 139 (95.7%) liver lesions showed malignant SSR-uptake in PET/CT while initial histopathology reported on ‘liver metastases of NET´ in 127 (91.4%) cases, giving a PPV of 91.0%. Re-biopsy of the initially histopathologically negative lesions (reference standard) nevertheless diagnosed ‘liver metastases of NET’ in 6 cases, improving the PPV of PET/CT to 95.5%. Reasons for initial false-negative histopathology were inadequate sampling in the sense of non-target biopsies. The 6 (4.3%) SSR-negative lesions were all G2 NETs with a Ki-67 between 2–15%. Conclusion SSR-PET/CT is a highly accurate imaging modality for the diagnosis of liver metastases in patients with proven NETs. However, we found that due to the well-known tumor heterogeneity of NETs, specifically in G2 NETs approximately 4–5% are SSR-negative and may require additional imaging with [18F]FDG PET/CT.

Der EuGH hat sich in einer lange erwarteten Entscheidung mit der Frage auseinandergesetzt, ob die DSGVO auf parlamentarische Untersuchungsausschüsse anwendbar ist. In der Rs C-33/22 (Österreichische Datenschutzbehörde) hat der EuGH am 16. Jänner 2024 in einem österreichischen Fall entschieden, dass die DSGVO auf parlamentarische Untersuchungsausschüsse grundsätzlich anwendbar ist. Dadurch haben Untersuchungsausschüsse in Ausübung ihrer parlamentarischen Kontrollrechte auch das Recht auf Datenschutz von Auskunftspersonen zu achten. Dies betrifft essenzielle verfassungsrechtliche Fragen zum Umgang mit diesem zentralen demokratischen Kontrollinstrument bzw Kontrollrechten allgemein und dem Verhältnis zum Datenschutz und geht weit über den Ausgangssachverhalt hinaus. Die österreichische Judikatur und Praxis, wonach die Gesetzgebung von der Anwendbarkeit der Datenschutz-Grundverordnung (DSGVO) ausgenommen ist, wird nach diesem EuGH-Urteil nicht aufrechterhalten werden können.

Background Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.Methods MVA encoding scIL-12 (MVA.scIL-12) was evaluated against peritoneal carcinomatosis models based on intraperitoneal engraftment of tumor cells. CD8-mediated immune responses, elucidated antitumor efficacy, and safety were evaluated following intravenous, intratumoral, or intraperitoneal administration of the viral vector. The immune response was measured by ELISpot (enzyme-linked immunosorbent spot), RNA sequencing, flow cytometry, intravital microscopy, and depletion of lymphocyte subsets with monoclonal antibodies. Safety was assessed by body-weight follow-up and blood testing. Tissue tropism on intravenous or intraperitoneal administration was assessed by bioluminescence analysis using a reporter MVA encoding luciferase.Results Intraperitoneal or locoregional administration, but not other routes of administration, resulted in a potent immune response characterized by increased levels of tumor-specific CD8+ T lymphocytes with the ability to produce both interferon-γ and tumor necrosis factor-α. The antitumor immune response was detectable not only in the peritoneal cavity but also systemically. As a result of intraperitoneal treatment, a single administration of MVA.scIL-12 encoding scIL-12 completely eradicated MC38 tumors implanted in the peritoneal cavity and also protected cured mice from subsequent subcutaneous rechallenges. Bioluminescence imaging using an MVA encoding luciferase revealed that intraperitoneal administration targets transgene to the omentum. The omentum is considered a key tissue in immune protection of the peritoneal cavity. The safety profile of intraperitoneal administration was also better than that following intravenous administration since no weight loss or hematological toxicity was observed when the vector was locally delivered into the peritoneal cavity.Conclusion Intraperitoneal administration of MVA vectors encoding scIL-12 targets the omentum, which is the tissue where peritoneal carcinomatosis usually begins. MVA.scIL-12 induces a potent tumor-specific immune response that often leads to the eradication of experimental tumors disseminated to the peritoneal cavity.

Abstract The induction of antiviral innate immunity by systemic immunization with live virus can be employed to positively impact the response to therapeutic vaccination. We previously demonstrated that systemic immunization with a non-replicating MVA encoding CD40 ligand (CD40L) enhances innate immune cell activation and function, and triggers potent antitumor CD8+ T cell responses in different murine tumor models. Antitumor efficacy was increased when combined with tumor targeting antibodies. Here we report the development of TAEK-VAC-HerBy (TVH), a first-in-class human tumor antibody enhanced killing (TAEK) vaccine based on the non-replicating MVA-BN viral vector. It encodes the membrane bound form of human CD40L, HER2 and the transcription factor Brachyury. TVH is designed for therapeutic use in HER2- or Brachyury-expressing cancer patients in combination with tumor targeting antibodies. To preclude possible oncogenic activities in infected cells and to prevent binding of vaccine-encoded HER2 by monoclonal antibodies trastuzumab and pertuzumab, genetic modifications of HER2 were introduced in the vaccine. Brachyury was genetically modified to prevent nuclear localization of the protein thereby inhibiting its transcriptional activity. CD40L encoded in TVH enhanced human leukocyte activation and cytokine secretion in vitro. Lastly, TVH intravenous administration to non-human primates was proven immunogenic and safe in a repeat-dose toxicity study. Nonclinical data presented here highlight TVH as a first-in-class immunotherapeutic vaccine platform currently under clinical investigation.

Abstract Osteoarthritis is a degenerative joint disease associated with pain, loss of function and reduced quality of life. Concomitant psychological disorders can significantly influence treatment outcomes. Therefore, we aimed to answer the following research questions: (1) How has the incidence of primary coxarthrosis and gonarthrosis developed over the last decade? (2) How high is the prevalence of osteoarthritis patients with concomitant psychological diagnoses? (3) Which psychological comorbidities are most prevalent in coxarthrosis and gonarthrosis patients, respectively? For this cross-sectional study, a dataset provided by the Federal Statistical Office (Destatis) consisting of annual, Germany-wide ICD-10 diagnosis codes from 2009 to 2019 was analysed. Incidences of the codes “M16.1” and “M17.1”, unilateral primary coxarthrosis and unilateral primary gonarthrosis, were quantified. Prevalence rates of secondary diagnoses of the chapter F of the ICD-10 were determined. Incidences were 230.7/100,000 inhabitants for coxarthrosis and 224.2/100,000 inhabitants for gonarthrosis. Patients with psychological comorbidities constituted 9.0% of coxarthrosis cases and 8.9% of gonarthrosis cases, respectively. Between 2009 through 2019, the proportion of patients with a concomitant “F” diagnoses of the ICD-10 increased by + 37.8% for coxarthrosis and by 17.9% for gonarthrosis. The most prevalent secondary diagnoses were affective disorders (F3), whereby numbers increased over the years. Increasing psychological comorbidities advocate for the implementation of screening tools, prevention strategies, interdisciplinary approaches and psychological support in the treatment of osteoarthritis.

This study presents a low-cost Arduino-based gas chromatography system that is suitable for teaching analytical chemistry in an undergraduate laboratory. The gas chromatography system is built with commonly available materials with a total cost less than $100. A Python code is also provided as a user interface that will record data and display the results in real-time. The functionalities of the gas chromatography system are demonstrated with the detection of in-house natural gas, product gases from a CO2 reduction, and a noble gas. Step-by-step instructions for building the gas chromatography system and detailed explanation of the Python code are provided in the Supporting Information for this paper. The goal of this project is to provide a low-cost and versatile GC platform where undergraduate students can modify each individual component of a GC and study the underlying principle of separation science in analytical chemistry.

BackgroundSensory processing sensitivity is mainly captured based on questionnaires and it’s neurophysiological basis is largely unknown. As hitherto no electroencephalography (EEG) study has been carried out, the aim of this work was to determine whether the self-reported level of SPS correlates with the EEG activity in different frequency bands.MethodsOne hundred fifteen participants were measured with 64-channel EEG during a task-free resting state. After artifact correction, a power spectrum time series was calculated using the Fast Fourier Transform (FFT) for the following frequency bands: Delta: 1–3.5 Hz, theta: 4–7.5 Hz, alpha1: 8–10 Hz, alpha2: 10.5–12 Hz, beta1: 12.5–15 Hz, beta2: 15.5–25 Hz, gamma: 25.5–45 Hz, global: 1–45 Hz. Correlations with the ‘Highly Sensitive Person Scale’ (HSPS-G) scores were determined. Then, the lowest and the highest 30% of the cohort were contrasted as polar opposites. EEG features were compared between the two groups applying a paired two-tailed t-test.ResultsThe HSPS-G scores correlated statistically significantly positive with beta 1 and 2, and global EEG power during resting with eyes open, but not during resting with eyes closed. The highly sensitive group revealed higher beta power (4.38 ± 0.32 vs. 4.21 ± 0.17, p = 0.014), higher gamma power (4.21 ± 0.37 vs. 4.00 ± 0.25, p = 0.010), and increased global EEG power (4.38 ± 0.29 vs. 4.25 ± 0.17, p = 0.041). The higher EEG activity in the HSP group was most pronounced in the central, parietal, and temporal region, whereas lower EEG activity was most present in occipital areas.ConclusionFor the first time, neurophysiological signatures associated with SPS during a task free resting state were demonstrated. Evidence is provided that neural processes differ between HSP and non-HSP. During resting with eyes open HSP exhibit higher EEG activity suggesting increased information processing. The findings could be of importance for the development of biomarkers for clinical diagnostics and intervention efficacy evaluation.

Abstract Background In Patients suffering from post-COVID syndrome, in addition to physical limitations, cognitive limitations, fatigue, dyspnea as well as depression and anxiety disorders may also be present. Up to now (as of May 2022), approx. 514 million people worldwide have been infected with SARS-CoV-2, in Germany this affects approx. 25 million. In Germany, 2.5 million people could potentially be affected by post-COVID syndrome. Post-COVID is thus a highly relevant public health issue. So far, there is no specific causal therapy for the post-COVID syndrome, but with multimodal symptom-oriented rehabilitation, the course can be favourably influenced. However, there is no study yet that focuses on patients in different rehabilitation indications and compares the focal symptomatology and coping strategies as well as the patients' benefit per indication. Methods/design As first objective, pulmonal, cardiac, neurological, cognitive or/and psychological functional impairments in rehabilitation patients after COVID-19 disease will be described. The second objective is the differentiated review of the specific rehabilitation measures, in the short term and in the longer term for the purpose of future prognoses and optimisation of therapeutic interventions. This prospective, non-randomised, controlled longitudinal study, plus multi-group comparisons will take place in seven rehabilitation clinics of different specialisations: cardiological rehab, pneumological rehab, neurological rehab, psychosomatic rehab. Within 12 months, 1000 cases across all participating centres will be included. Somatic and psychological testing will be conducted at three measurement points: Admission (t0), discharge (t1), 6-montas Catamnesis (t2). The patients receive the usual care according to the respective rehabilitation priorities, adapted to the special challenges of post-COVID symptoms. Patients of the post-COVID outpatient clinic without rehabilitation will be used as a control group. Discussion This study will precisely assess the extent to which subclinical neurological or/and psychological impairments are present in post-COVID-19 rehabilitation and the results will help, developing, providing and evaluating appropriate treatment concepts. This may also have relevant implications for the improvement of physical ability and quality of life in post-COVID-19 patients and increase the probability of return to work. Trial registration Z-2022-1749-8, registered 03. February 2022, https://studienanmeldung.zks-regensburg.de

Abstract Background Periprosthetic joint infection represents a major complication in orthopaedics and trauma surgery. For an ideal management approach, it is important to understand the distinct challenges for all persons involved in the treatment. Therefore, it was aimed at investigating (1) the impact of periprosthetic joint infection (PJI) on the well-being of nursing staff to (2) identify challenges, which could be improved facilitating the management of PJI. Methods This is a qualitative interview study. In total, 20 nurses of a German university orthopedic trauma center specialized on infectious complications were recruited using a purposive sampling strategy. Content analysis was performed on transcripts of individual in-person interviews conducted between March 2021 and June 2021. Results Three major themes could be extracted including (i) feelings associated with the management of PJI and the need for emotional support, illustrating the negative emotional impact on nurses, whereby receiving collegial support was perceived as an important coping strategy, (ii) patients’ psychological burden, highlighting the nurses’ lack of time to address mental issues adequately and, (iii) realization of the severity of PJI and compliance problems. Conclusion Identified facilitating factors for PJI management include strengthening of mental care in the treatment of PJI, providing opportunities for exchange among multidisciplinary team members and implementing compliance-enhancing strategies. The findings of this study can be beneficial for improving professionals’ satisfaction, optimising the work environment, creating organizational structures which enhance opportunities for exchange and preventing mental health issues among the nursing team.

The H3K9me3-specific histone methyltransferase SETDB1 is critical for proper regulation of developmental processes, but the underlying mechanisms are only partially understood. Here, we show that deletion of Setdb1 in mouse fetal liver hematopoietic stem and progenitor cells (HSPCs) results in compromised stem cell function, enhanced myeloerythroid differentiation, and impaired lymphoid development. Notably, Setdb1-deficient HSPCs exhibit reduced quiescence and increased proliferation, accompanied by the acquisition of a lineage-biased transcriptional program. In Setdb1-deficient HSPCs, we identify genomic regions that are characterized by loss of H3K9me3 and increased chromatin accessibility, suggesting enhanced transcription factor (TF) activity. Interestingly, hematopoietic TFs like PU.1 bind these cryptic enhancers in wild-type HSPCs, despite the H3K9me3 status. Thus, our data indicate that SETDB1 restricts activation of nonphysiological TF binding sites which helps to ensure proper maintenance and differentiation of fetal liver HSPCs. [ABSTRACT FROM AUTHOR]

ABSTRACT By examining the laboratory practices behind designing and crafting organoids—miniature, three‐dimensional cellular structures that replicate organ functions—we highlight a critical shift in biomedical research. Over the past 16 years, advances in stem cell research have transitioned from generating stem cells to utilising these cells in building sophisticated organ models and bioengineered tissues. This transition represents a significant move from the ‘what’ of cell creation to the ‘how’ of constructing and interpreting three‐dimensional human models. Through ethnographic research (including observations and interviews) in Europe and North America, we explore how organoids are constructed and the underlying logic driving their development. Our analysis underscores the growing importance of these in vitro models for human health, urging a sociological examination of their ‘near human’ status. We argue that understanding the implications of this shift—particularly how it influences perceptions of human representation and diversity in biomedical research—requires critical scrutiny from sociologists of health and illness. This paper aims to address the urgent need to investigate not just the experimental challenges but also the socio‐political dimensions of using organoids as proxies for human physiology. [ABSTRACT FROM AUTHOR]

Objectives: Somatostatin receptor positron emission tomography/computed tomography (SSTR-PET/CT) using [68Ga]-labeled tracers is a widely used imaging modality for neuroendocrine tumors (NET). Recently, [18F]SiTATE, a SiFAlin tagged [Tyr3]-octreotate (TATE) PET tracer, has shown great potential due to favorable clinical characteristics. We aimed to evaluate the reproducibility of Somatostatin Receptor-Reporting and Data System 1.0 (SSTR-RADS 1.0) for structured interpretation and treatment planning of NET using [18F]SiTATE. Methods: Four readers assessed [18F]SiTATE-PET/CT of 95 patients according to the SSTR-RADS 1.0 criteria at two different time points. Each reader evaluated up to five target lesions per scan. The overall scan score and the decision on peptide receptor radionuclide therapy (PRRT) were considered. Inter- and intra-reader agreement was determined using the intraclass correlation coefficient (ICC). Results: The ICC analysis on the inter-reader agreement using SSTR-RADS 1.0 for identical target lesions (ICC ≥ 85%), overall scan score (ICC ≥ 90%), and the decision to recommend PRRT (ICC ≥ 85%) showed excellent agreement. However, significant differences were observed in recommending PRRT among experienced readers (ER) (p = 0.020) and inexperienced readers (IR) (p = 0.004). Compartment-based analysis demonstrated good to excellent inter-reader agreement for most organs (ICC ≥ 74%), except for lymph nodes (ICC ≥ 53%). Conclusion: SSTR-RADS 1.0 represents a highly reproducible and consistent framework system for stratifying SSTR-targeted PET/CT scans, even using the novel SSTR-ligand [18F]SiTATE. Some inter-reader variability was observed regarding the evaluation of uptake intensity prior to PRRT as well as compartment scoring of lymph nodes, indicating that those categories require special attention during further clinical validation and might be refined in a future SSTR-RADS version 1.1. Clinical relevance statement: SSTR-RADS 1.0 is a consistent framework for categorizing somatostatin receptor-targeted PET/CT scans when using [18F]SiTATE. The framework serves as a valuable tool for facilitating and improving the management of patients with NET. Key Points: SSTR-RADS 1.0 is a valuable tool for managing patients with NET. SSTR-RADS 1.0 categorizes patients with showing strong agreement across diverse reader expertise. As an alternative to [68Ga]-labeled PET/CT in neuroendocrine tumor imaging, SSTR-RADS 1.0 reliably classifies [18F]SiTATE-PET/CT. [ABSTRACT FROM AUTHOR]

More and more people quantify their sleep using wearables and are becoming obsessed in their pursuit of optimal sleep (“orthosomnia”). However, it is criticized that many of these wearables are giving inaccurate feedback and can even lead to negative daytime consequences. Acknowledging these facts, we here optimize our previously suggested sleep classification procedure in a new sample of 136 self-reported poor sleepers to minimize erroneous classification during ambulatory sleep sensing. Firstly, we introduce an advanced interbeat-interval (IBI) quality control using a random forest method to account for wearable recordings in naturalistic and more noisy settings. We further aim to improve sleep classification by opting for a loss function model instead of the overall epoch-by-epoch accuracy to avoid model biases towards the majority class (i.e., “light sleep”). Using these implementations, we compare the classification performance between the optimized (loss function model) and the accuracy model. We use signals derived from PSG, one-channel ECG, and two consumer wearables: the ECG breast belt Polar® H10 (H10) and the Polar® Verity Sense (VS), an optical Photoplethysmography (PPG) heart-rate sensor. The results reveal a high overall accuracy for the loss function in ECG (86.3 %, κ = 0.79), as well as the H10 (84.4%, κ = 0.76), and VS (84.2%, κ = 0.75) sensors, with improvements in deep sleep and wake. In addition, the new optimized model displays moderate to high correlations and agreement with PSG on primary sleep parameters, while measures of reliability, expressed in intra-class correlations, suggest excellent reliability for most sleep parameters. Finally, it is demonstrated that the new model is still classifying sleep accurately in 4-classes in users taking heart-affecting and/or psychoactive medication, which can be considered a prerequisite in older individuals with or without common disorders. Further improving and validating automatic sleep stage classification algorithms based on signals from affordable wearables may resolve existing scepticism and open the door for such approaches in clinical practice.

Recombinant-modified vaccinia virus Ankara (rMVA) is known to elicit potent antitumor immune responses in preclinical models due to its inherent ability to activate the innate immune system and the activation of adaptive responses mediated by the expression of tumor antigens and costimulus-providing molecules, such as CD40L and CD137L. Here, we evaluated different rMVA vectors in preclinical peritoneal carcinomatosis models (ID8.OVA-Vegf/GFP and MC38). We compared rMVA vectors expressing a tumor antigen (OVA or gp70) either alone or co-expressed with CD40L or/and CD137L. In tumor-free mice, the vector coding for the triple combination was only slightly superior, whereas, in tumor-bearing animals, we observed a synergistic induction of T lymphocytes specific against vector-encoded and non-encoded tumor-associated antigens. The enhanced activation of the immune response was associated with improved survival in mice with peritoneal carcinomatosis treated with a rMVA vector encoding both CD40L and CD137L. Thus, the triple transgene combination in vaccinia viral vectors represents a promising strategy for the treatment of peritoneal carcinomatosis.

Aims: We aimed to evaluate the long-term impact of fracture-related infection (FRI) on patients’ physical health and psychological wellbeing. For this purpose, quality of life after successful surgical treatment of FRIs of long bones was assessed. Methods: A total of 37 patients treated between November 2009 and March 2019, with achieved eradication of infection and stable bone consolidation after long bone FRI, were included. Quality of life was evaluated with the EuroQol five-dimension questionnaire (EQ-5D) and German Short-Form 36 (SF-36) outcome instruments as well as with an International Classification of Diseases of the World Health Organization (ICD)-10 based symptom rating (ISR) and compared to normative data. Results: With a mean follow-up of 4.19 years (SD 2.7) after the last surgery, the mean SF-36 score was 40.1 (SD 14.6) regarding the physical health component and 48.7 (SD 5.1) regarding the mental health component, compared to German normative values of 48.4 (SD 9.2) (p < 0.001) and 50.9 (SD 8.8) (p = 0.143). The mean EQ-5D index reached 0.76 (SD 0.27) with a mean EQ-5D visual analogue scale (VAS) rating of 65.7 (SD 22.7) compared to reference scores of 0.88 (p < 0.001) and 72.9 (p < 0.001). Mean scores of the ISR did not reveal significant psychological symptom burden, while an individual analysis showed moderate to severe impairments in 21.6% (n = 8) of the patients. Conclusion: Even a mean 4.2 years (SD 2.7) after surgically successful treatment of FRI of long bones, patients report significantly lower quality of life in comparison to normative data. Future clinical studies on FRIs should focus on patient-related outcome measures enabling best possible shared treatment decision-making. Prevention methods and interdisciplinary approaches should be implemented to improve the overall quality of life of FRI patients.

Background: This study aimed at answering the following research questions: (1) Does the self-reported level of sensory-processing sensitivity (SPS) correlate with complexity, or criticality features of the electroencephalogram (EEG)? (2) Are there significant EEG differences comparing individuals with high and low levels of SPS? Methods: One hundred fifteen participants were measured with 64-channel EEG during a task-free resting state. The data were analyzed using criticality theory tools (detrended fluctuation analysis, neuronal avalanche analysis) and complexity measures (sample entropy, Higuchi’s fractal dimension). Correlations with the ‘Highly Sensitive Person Scale’ (HSPS-G) scores were determined. Then, the cohort’s lowest and the highest 30% were contrasted as opposites. EEG features were compared between the two groups by applying a Wilcoxon signed-rank test. Results: During resting with eyes open, HSPS-G scores correlated significantly positively with the sample entropy and Higuchi’s fractal dimension (Spearman’s ρ = 0.22, p < 0.05). The highly sensitive group revealed higher sample entropy values (1.83 ± 0.10 vs. 1.77 ± 0.13, p = 0.031). The increased sample entropy in the highly sensitive group was most pronounced in the central, temporal, and parietal regions. Conclusion: For the first time, neurophysiological complexity features associated with SPS during a task-free resting state were demonstrated. Evidence is provided that neural processes differ between low- and highly-sensitive persons, whereby the latter displayed increased neural entropy. The findings support the central theoretical assumption of enhanced information processing and could be important for developing biomarkers for clinical diagnostics.