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Henning Plage,1 Poline Pielka,1 Lutz Liefeldt,2 Klemens Budde,2 Jan Ebbing,3 Nesrin Sugünes,1 Kurt Miller,1 Hannes Cash,1 Anna Bichmann,4 Arne Sattler,5 Katja Kotsch,5 Frank Friedersdorff1 1Department of Urology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany; 2Department of Nephrology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany; 3Department of Urology, University Hospital Basel, Urological University Clinic Basel-Liestal, Basel, Switzerland; 4Department of Anaesthesia and Operative Intensive Care Medicine, Charité –Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany; 5Department of General, Visceral- and Vascular Surgery, Charité –Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyCorrespondence: Frank FriedersdorffDepartment of Urology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charitéplatz 1, Berlin 10117, GermanyTel +49 30 450615219Fax +49 30 450515910Email frank.friedersdorff@charite.dePurpose: An expansion of selection criteria for deceased organ transplantation already exists to manage the current donor shortage. Comparable evaluation of risk factors for living donors should be investigated to improve this issue.Patients and Methods: Our retrospective single-centre study analysed 158 patients with living kidney transplants performed between February 2006 and June 2012. We investigated the influence of donor risk factors (RF) including body mass index over 30 kg/m2, age > 60 years, active nicotine abuse and arterial hypertension on postoperative kidney function with focus on the recipients. This was measured for long-term survival and glomerular filtration rate (GFR) in a 5-year follow-up.Results: Overall, out of 158 living donors, 84 donors were identified to have no risk factors, whereas 74 donors had at least one risk factor. We noted a significant higher delayed graft function (p=0.042) in the first 7 days after transplantation, as well as lower GFR of recipients of allografts with risk factors in the first-year after transplantation. In our long-term results, there was no significant difference in the functional outcome (graft function, recipient and graft survival) between recipients receiving kidneys from donors with no and at least one risk factors. In the adjusted analysis of subgroups of different risk factors, recipients of donors with “age over 60 years” at time of transplantation had a decreased transplant survival (p=0.014).Conclusion: Thus, a careful expansion for selection criteria for living donors with critical evaluation could be possible, but especially the age of the donors could be a limited risk factor.Keywords: living donor nephrectomy, risk factor, selection criteria, survival, GFR

Abstract Background In Germany, around 2.250 children and adolescents are diagnosed with cancer each year. Despite generally positive long-term survival rates, many patients must cope with late effects of the disease and its treatment. This highlights the need for a well-structured, long-term approach addressing both physical and mental health issues. Currently, the German healthcare system lacks such comprehensive structures. Our study aims to evaluate the effectiveness of a structured, multidisciplinary long-term approach compared to conventional “treatment as usual” (TAU). Methods A prospective, multicenter study with ten pediatric university clinics in Germany will be conducted. The cluster-randomization takes place at the clinic level. Children and adolescents who completed their cancer treatment at least five years ago and their parents will be eligible to participate. While the control group (CG) receives TAU, the intervention group (IG) participates in a structured program. This program includes risk-based medical treatment and psychosocial interventions tailored to each patient’s individual needs within a two-month timeframe. The primary outcome is the improvement of self-efficacy. Secondary outcomes are satisfaction with health care, improvement of health-related quality of life (HRQoL), reduction of mental health problems, and improvement of transition readiness. Discussion This approach has the potential to optimize the health care for individuals who survived cancer during childhood or adolescence. It addresses the challenges of overuse, underuse, and misuse of health care resources. By considering both medical and psychosocial factors and promoting increased self-efficacy, independent from parental involvement, it may facilitate a smoother transition to adult medicine and enhance adherence to lifelong aftercare. If proven successful, this approach will contribute to the integration of multidisciplinary strategies into standard healthcare practice. Trial registration German Clinical Trials Register DRKS00029269. Registered on December 23, 2022.

L Cortejoso,1 RA Dietz,2 G Hofmann,1 M Gosch,2 A Sattler1 1Department of Pharmacy, 2Department of Geriatrics, Hospital Nuremberg, Paracelsus Medical Private University Nuremberg, Nuremberg, Germany Background: Inappropriate pharmacotherapy among older adults remains a critical issue in our health care systems. Besides polypharmacy and multiple comorbidities, the age-related pharmacokinetic and pharmacodynamic changes may increase the risk of adverse drug reactions and medication errors.Objective: The main target of this study was to describe the characteristics of pharmaceutical interventions in two geriatric wards (orthogeriatric ward and geriatric day unit) of a general teaching hospital and to evaluate the clinical significance of the detected medication errors.Materials and methods: The study was conducted between August 2014 and October 2015 and was based on a triple approach that included validation of medical orders, medication reconciliation at patients’ admission, and a predischarge planning appointment with the patient. The validation of medical orders was based on analyzing the suitability of the drugs prescribed, the drug dose depending on the patient’s characteristics, the presence of contraindications and interactions between drugs, and the proposal of alternative drugs included in the hospital formulary.Results: A total of 2,307 interventions associated to a medication error in 15,282 medical orders for 1,859 older patients were recorded. The greater part of the interventions carried out on the orthogeriatric ward at admission and at discharge were due to omission of a drug in the medical order (20.0%) and clinically significant interactions requiring monitoring (30.4%), respectively. The main factor triggering pharmacist’s recommendations on the geriatric day unit was clinically significant interactions (21.1%). With regard to the clinical severity of the detected errors, 68.1% were considered significant, 24.8% were of minor significance, and 7.2% were clinically serious.Conclusion: Our findings show the importance of clinical pharmacist involvement in the optimization of pharmacotherapy in older adults, ensuring that they receive effective, safe, and efficient drug therapy. Keywords: older adults, medication errors, pharmacist interventions

Background: The participation of people with intellectual disabilities in Special Olympics sports and training opportunities offers numerous benefits for health and inclusion. However, little is known about the impact of such training on physical activity behaviour. Here, we evaluate the differences in physical activity volume and intensity of Special Olympics athletes between Unified and non-Unified football training. Method: Accelerometer data of 12 male athletes from eight standardised training sessions (four Unified, four non-Unified) were analysed. Results: While there was no statistically significant difference for the main part of the training, athletes showed higher levels of physical activity intensity (MVPA: M[subscript diff] = 11.74%; 95% CI = 5.50-17.97) and volume (average acceleration ENMO: M[subscript diff] = 112.82 mg; 95% CI = 24.73-200.90) in a Unified compared to non-Unified endurance-related exercise task. Conclusion: Understanding physical activity participation in different training types can help to design and implement future training programmes.

While degrowth as a plural and decolonial movement actively invites the Global South to be part of its transformative project, the current NorthSouth dichotomy threatens to miss the variety of semi-peripheral contexts. Against this backdrop, we aim to contribute to dialogues on degrowth from the often-overlooked ‘East’ – specifically post-socialist Central and Eastern Europe (CEE). Instead of being viewed as a site for transformative examples and inspiration for degrowth-oriented socio-ecological transformation, CEE is often portrayed as ‘lagging behind’. Problematising such reductionist narratives, this essay explores CEE as a lively and rich site of postcapitalist alternatives. Based on two special sessions organised at the 2023 International Degrowth Conference in Zagreb, we reflect upon insights gathered on various degrowth-aligned traditions and practices in CEE with a goal to 1) advance an equitable dialogue between the global degrowth scholarship and the East, and 2) strengthen a context-sensitive degrowth agenda in CEE.

Abstract Malaria vaccination approaches using live Plasmodium parasites are currently explored, with either attenuated mosquito-derived sporozoites or attenuated blood-stage parasites. Both approaches would profit from the availability of attenuated and avirulent parasites with a reduced blood-stage multiplication rate. Here we screened gene-deletion mutants of the rodent parasite P. berghei and the human parasite P. falciparum for slow growth. Furthermore, we tested the P. berghei mutants for avirulence and resolving blood-stage infections, while preserving sporozoite formation and liver infection. Targeting 51 genes yielded 18 P. berghei gene-deletion mutants with several mutants causing mild infections. Infections with the two most attenuated mutants either by blood stages or by sporozoites were cleared by the immune response. Immunization of mice led to protection from disease after challenge with wild-type sporozoites. Two of six generated P. falciparum gene-deletion mutants showed a slow growth rate. Slow-growing, avirulent P. falciparum mutants will constitute valuable tools to inform on the induction of immune responses and will aid in developing new as well as safeguarding existing attenuated parasite vaccines.

Abstract Deregulation of transcription factors (TFs) leading to uncontrolled proliferation of tumor cells within the microenvironment represents a hallmark of cancer. However, the biological and clinical impact of transcriptional interference, particularly in multiple myeloma (MM) cells, remains poorly understood. The present study shows for the first time that MYC and JUNB, two crucial TFs implicated in MM pathogenesis, orchestrate distinct transcriptional programs. Specifically, our data revealed that expression levels of MYC, JUNB, and their respective downstream targets do not correlate and that their global chromatin-binding patterns are not significantly overlapping. Mechanistically, MYC expression was not affected by JUNB knockdown, and conversely, JUNB expression and transcriptional activity were not affected by MYC knockdown. Moreover, suppression of MYC levels in MM cells via targeting the master regulator BRD4 by either siRNA-mediated knockdown or treatment with the novel proteolysis targeting chimera (PROTAC) MZ-1 overcame bone marrow (BM) stroma cell/IL-6-induced MYC- but not MEK-dependent JUNB-upregulation and transcriptional activity. Consequently, targeting of the two non-overlapping MYC- and JUNB-transcriptoms by MZ-1 in combination with genetic or pharmacological JUNB-targeting approaches synergistically enhanced MM cell death, both in 2D and our novel dynamic 3D models of the BM milieu as well as in murine xenografts. In summary, our data emphasize the opportunity to employ MYC and JUNB dual-targeting treatment strategies in MM as another exciting approach to further improve patient outcomes.

Abstract Physical mapping evidences the chromosome organization and structure. Despite the data about plant cytogenomics, physical mapping has been conducted from single-copy and/or low-copy genes for few species. Carica papaya cytogenomics has been accomplished from BAC-FISH and repeatome sequences. We aimed to map the serk 2, svp-like and mdar 4 sequences in C. papaya. The sequences were amplified and the amplicons sequenced, showing similarity in relation to serk 2, svp-like and mdar 4 genes. Carica papaya diploidy was confirmed and the mitotic chromosomes characterized. The chromosome 1 exhibited the secondary constriction pericentromeric to the centromere of the long arm. So, we concluded that it is the sex chromosomes. serk 2 was mapped in the long arm interstitial portion of the sex chromosomes, and the interphase nuclei showed two fluorescence signals. Considering these results and the sequencing data from the C. papaya sex chromosomes, svp-like and mdar 4 genes were mapped in the interstitial region of the sex chromosome long arm. Both sequences showed only one fluorescence signal in the interphase nuclei. The procedure adopted here can be reproduced for other single-copy and/or low-copy genes, allowing the construction of cytogenetic maps. In addition, we revisited the cytogenomics data about C. papaya sex chromosomes, presenting a revised point of view about the structure and evolution to these chromosomes.

Abstract We conducted spatial immune tumor microenvironment (iTME) profiling using formalin-fixed paraffin-embedded (FFPE) samples of 25 KRAS-mutated non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), including 12 responders and 13 non-responders. An eleven-marker panel (CD3, CD4, CD8, FOXP3, CD68, arginase-1, CD33, HLA-DR, pan-keratin (PanCK), PD-1, and PD-L1) was used to study the tumor and immune cell compositions. Spatial features at single cell level with cellular neighborhoods and fractal analysis were determined. Spatial features and different subgroups of CD68+ cells and FOXP3+ cells being associated with response or resistance to ICIs were also identified. In particular, CD68+ cells, CD33+ and FOXP3+ cells were found to be associated with resistance. Interestingly, there was also significant association between non-nuclear expression of FOXP3 being resistant to ICIs. We identified CD68dim cells in the lung cancer tissues being associated with improved responses, which should be insightful for future studies of tumor immunity.

Abstract Background Primary Health Care (PHC) plays a crucial role in managing the COVID-19 pandemic, with only 8% of cases requiring hospitalization. However, PHC COVID-19 data often goes unnoticed on European government dashboards and in media discussions. This project aims to examine official information on PHC patient care during the COVID-19 pandemic in Europe, with specific objectives: (1) Describe PHC’s clinical pathways for acute COVID-19 cases, including long-term care facilities, (2) Describe PHC COVID-19 pandemic indicators, (3) Develop COVID-19 PHC activity indicators, (4) Explain PHC’s role in vaccination strategies, and (5) Create a PHC contingency plan for future pandemics. Methods A mixed-method study will employ two online questionnaires to gather retrospective PHC data on COVID-19 management and PHC involvement in vaccination strategies. Validation will occur through focus group discussions with medical and public health (PH) experts. A two-wave Delphi survey will establish a European PHC indicators dashboard for future pandemics. Additionally, a coordinated health system action plan involving PHC, secondary care, and PH will be devised to address future pandemic scenarios. Analysis: Quantitative data will be analysed using STATA v16.0 for descriptive and multivariate analyses. Qualitative data will be collected through peer-reviewed questionnaires and content analysis of focus group discussions. A Delphi survey and multiple focus groups will be employed to achieve consensus on PHC indicators and a common European health system response plan for future pandemics. The Eurodata research group involving researchers from 28 European countries support the development. Discussion While PHC manages most COVID-19 acute cases, data remains limited in many European countries. This study collects data from numerous countries, offering a comprehensive perspective on PHC’s role during the pandemic in Europe. It pioneers the development of a PHC dashboard and health system plan for pandemics in Europe. These results may prove invaluable in future pandemics. However, data may have biases due to key informants’ involvement and may not fully represent all European GP practices. PHC has a significant role in the management of the COVID-19 pandemic, as most of the cases are mild or moderate and only 8% needed hospitalization. However, PHC COVID-19 activity data is invisible on governments’ daily dashboards in Europe, often overlooked in media and public debates.

Abstract Background Metformin and sodium-glucose-cotransporter-2 inhibitors (SGLT2i) are cornerstone therapies for managing hyperglycemia in diabetes. However, their detailed impacts on metabolic processes, particularly within the citric acid (TCA) cycle and its anaplerotic pathways, remain unclear. This study investigates the tissue-specific metabolic effects of metformin, both as a monotherapy and in combination with SGLT2i, on the TCA cycle and associated anaplerotic reactions in both mice and humans. Methods Metformin-specific metabolic changes were initially identified by comparing metformin-treated diabetic mice (MET) with vehicle-treated db/db mice (VG). These findings were then assessed in two human cohorts (KORA and QBB) and a longitudinal KORA study of metformin-naïve patients with Type 2 Diabetes (T2D). We also compared MET with db/db mice on combination therapy (SGLT2i + MET). Metabolic profiling analyzed 716 metabolites from plasma, liver, and kidney tissues post-treatment, using linear regression and Bonferroni correction for statistical analysis, complemented by pathway analyses to explore the pathophysiological implications. Results Metformin monotherapy significantly upregulated TCA cycle intermediates such as malate, fumarate, and α-ketoglutarate (α-KG) in plasma, and anaplerotic substrates including hepatic glutamate and renal 2-hydroxyglutarate (2-HG) in diabetic mice. Downregulated hepatic taurine was also observed. The addition of SGLT2i, however, reversed these effects, such as downregulating circulating malate and α-KG, and hepatic glutamate and renal 2-HG, but upregulated hepatic taurine. In human T2D patients on metformin therapy, significant systemic alterations in metabolites were observed, including increased malate but decreased citrulline. The bidirectional modulation of TCA cycle intermediates in mice influenced key anaplerotic pathways linked to glutaminolysis, tumorigenesis, immune regulation, and antioxidative responses. Conclusion This study elucidates the specific metabolic consequences of metformin and SGLT2i on the TCA cycle, reflecting potential impacts on the immune system. Metformin shows promise for its anti-inflammatory properties, while the addition of SGLT2i may provide liver protection in conditions like metabolic dysfunction-associated steatotic liver disease (MASLD). These observations underscore the importance of personalized treatment strategies.

Abstract Spaceflight and terrestrial spaceflight analogs can alter immune phenotypes. Macrophages are important immune cells that bridge the innate and adaptive immune systems and participate in immunoregulatory processes of homeostasis. Furthermore, macrophages are critically involved in initiating immunity, defending against injury and infection, and are also involved in immune resolution and wound healing. Heterogeneous populations of macrophage-type cells reside in many tissues and cause a variety of tissue-specific effects through direct or indirect interactions with other physiological systems, including the nervous and endocrine systems. It is vital to understand how macrophages respond to the unique environment of space to safeguard crew members with appropriate countermeasures for future missions in low Earth orbit and beyond. This review highlights current literature on macrophage responses to spaceflight and spaceflight analogs.

This abstract presents a soiling forecasting tool (SFT) for assessing the deposition of dust on parabolic trough collector (PTC) mirrors and its cumulative impact on their reflectivity. The SFT was developed by the University of Patras in the frame of the Smart Solar System (S3) project (Horizon 2020 Solar-Era.net). An initial version of the model was presented at the SolarPACES 2022 conference, where the adaptation of the model to dust transport phenomena was demonstrated. The subsequent step in the evolution of the algorithm concerned the calibration of the SFT under different atmospheric conditions. In addition, the model was modified to incorporate meteorological and aerosol forecast data as inputs. The atmospheric predictions of dust and aerosol optical depth are from the global atmospheric forecasts of the Copernicus Atmosphere Monitoring Service. Regarding the meteorological data, three independent sources are used. Those are the Norwegian Meteorological Institute's meteorological forecasts (YR), the METAR meteorological observations from the closest airport, and lastly, the data from the automatic weather station at the location of the PTC system at the KEAN Soft Drinks Ltd factory in Limassol, Cyprus. The aim of this paper is to assess the impact of the three distinct meteorological input sources on the modelled reflectivity and its comparison to measurements taken during the experimental campaign.

A novel approach towards thermal energy storage of surplus renewable energy (RE) is introduced via a hybrid thermochemical/sensible heat storage concept implemented with the aid of porous structures made of redox metal oxides, capable of reversible reduction/oxidation upon heating/cooling in direct contact with air, accompanied, respectively, by endothermic/ exothermic heat effects and demonstrating fully reversible dimensional changes under cyclic operation. The proposed modular storage units can be heated during the day to a level exceeding the metal oxide’s reduction onset temperature either by hot air streams from air-operated Concentrated Solar Power (CSP) tower plants or via surplus/cheap RE-electricity from photovoltaics, wind, or other renewable sources (“charging”/energy storage step). When this RE sources become non-available or upon demand, the fully charged system can transfer its energy to a controlled airflow that passes through the porous oxide block and initiates the exothermic oxidation of the reduced metal oxide. Thus, a hot air stream is produced which can be used to provide electricity or exploitable heat for industrial processes. The present work elaborates on the operating principles and the potential application of this concept and reports progress in the preparation and shaping of reticulated porous ceramics (RPCs also known as “ceramic foams”) from CaMnO3-based perovskite compositions and their preliminary testing with respect to cyclic reduction-oxidation.

In the research project Smart Solar System (S3), the Solar-Institut Jülich (SIJ) developed forecast tools to predict the direct normal irradiance (DNI) in hourly resolution for the current day. The aim of the daily DNI forecast is to use it as input to enable a smart operation of a parabolic trough collector (PTC) system with a concrete thermal energy storage (C-TES) located at the company KEAN Soft Drinks Ltd in Limassol, Cyprus. The main focus in this work is on the development of a DNI forecast tool based on long short-term memory (LSTM), which is a recurrent neural network (RNN), and its comparison with a DNI forecast tool based on analytical algorithms (non-machine learning). Only the non-machine learning DNI forecast tool with hourly update was tested in real-life PTC plant operation since end of 2022. The comparisons between the three DNI forecast tools show that the potential of using machine learning is very high. Different comparisons were made including an evaluation of the accuracy of the tool (i.e. comparison of the DNI forecast data with DNI measurement data). The DNI forecast based on the LSTM network proved to be more accurate than the non-machine learning DNI forecasts when considering errors greater than ±100 W/m2. The error of the LSTM network compared to DNI measurement data was as follows: 43.6 % of the data was within ±100 W/m2, 74.8 % was within ±200 W/m2, 89.8 % was within ±300 W/m2 and 95.8 % was within ±400 W/m2.

Mineral carbonation of secondary materials offers an innovative way of storing carbon dioxide in materials that instead would mostly go to waste. This study investigates the carbonation efficiency (CE) of 11 different secondaries from refractory production, waste incineration, and the paper industry compared to untreated and thermally activated serpentinite. To determine the chemical and mineralogical composition of the materials, various analytical methods, like X-ray fluorescence, X-ray diffraction, scanning electron microscopy, Brunauer-Emmet-Teller and thermogravimetric analysis have been employed, both before and after the direct aqueous carbonation process. Each material was examined over reaction times of 6 & 10 hours at 180 °C and a starting pressure of 20 bar in a 0.6 L stainless steel batch reactor. The received results were then compared to the theoretical CO2 uptake, defined as the maximum carbon dioxide storage potential achievable if all Ca, Fe and Mg ions were converted to carbonates. The findings indicate carbonation efficiencies of 14–65 % for secondary materials, compared to 0.7–14 % observed in the serpentinite samples. The highest uptakes were achieved by the refractory materials, primarily due to their high metal oxide content. However, a negative impact was observed from graphite-based carbon binders in the refractories, with increased leaching of these binders leading to a decrease in carbonation efficiency. Materials with higher SiO2 content showed reduced performance, suggesting a passivation layer buildup during carbonation.

BackgroundTo date, there are no official diagnostic criteria for the frequently reported phenomenon of exercise addiction. Therefore, the aim of the present study was to investigate how mental disorders, specifically depression and attention-deficit hyperactivity disorder (ADHD), are related to exercise addiction (EA).MethodsA total of 173 participants aged between 18 and 70 years, who reported exercising more than 10 h a week and continued to exercise despite injury or illness, answered questionnaires including the Exercise Dependence Scale, the Beck Depression Inventory, and the Homburger ADHD scale for adults. Multiple linear regression analyses were performed adjusting for relevant confounders (age, gender) and stepwise regression was used to identify which of the two mental disorders is the more influential predictor of EA.ResultsPearson correlation analysis showed that depressive symptoms [r (171) = 0.422, p