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Hyperspectral Imaging of Human Liver Allografts for Prediction of Initial Graft Function
No full textDie Ischämie-Reperfusionsschädigung gilt als zentraler Risikofaktor für kurz- und langfristige Transplantatschäden, ihre objektive Erfassung ist jedoch schwierig. Die hyperspektrale Bildgebung, kurz HSI, stellt ein nicht-invasives Verfahren dar, das optische Gewebeeigenschaften mit der Mikroperfusion korrelieren kann. In unserer Studie wurden Bilder von 37 Lebertransplantaten während der Backtable-Präparation, der normothermen Maschinenperfusion, kurz NMP, sowie nach der Reperfusion im Empfänger aufgenommen und mithilfe der HSI-Software verschiedene optische Gewebeparameter berechnet. Bei Transplantaten mit früher Allograftdysfunktion, kurz EAD, waren die Nahinfrarot-Perfusions-Index-Werte während der NMP und nach der Reperfusion signifikant niedriger. Diese Ergebnisse deuten darauf hin, dass HSI eine valide Methode zur Beurteilung von Leberallotransplantaten ist und der NIR-Wert als potenzieller Prädiktor für eine EAD dienen könnte
Is helping always the preferred decision? Preschool- and elementary school-aged children's helping decisions in complex social situations
No full textHelping is usually perceived as a positive behavior, but it can also have negative side effects. Moreover, helping decisions are often embedded in complex social situations that can create social dilemmas for children and adults, such as the decision whether or not to help a friend steal. However, based on previous research, it remains unclear how young children decide in such complex social situations and how their decisions differ between preschool- and elementary school age. Therefore, in the present study, we investigated the moral decisions of 4- to 8-year-old children in complex social situations (N = 152 children; 69 girls; all European, urban and middle-class). In a 2 × 2 design, each child was asked whether a story protagonist should help or not help in four different conditions, namely helping a friend or a stranger to get their own object (i.e., moral conditions), or helping a friend or a stranger to take someone else's object (i.e., immoral conditions). We found that children clearly approve of helping in moral conditions and generally disapprove of helping in immoral conditions. We also found that older children were more likely to disapprove of helping in immoral conditions. Furthermore, children preferred helping friends to helping strangers only in moral but not in immoral conditions. Taken together, these findings suggest that children's decisions to help undergo significant changes from preschool to elementary school, as they are further qualified by criteria such as respecting the rights of others and avoiding harmful consequences of helping for third parties
Is long time to reimplantation a risk factor for reinfection in two-stage revision for periprosthetic infection? A systematic review of the literature
No full textThe two-stage revision arthroplasty is a common treatment option for chronic periprosthetic infection (PJI). The time to reimplantation (TTR) reported in the literature varies substantially from a few days to several hundred days. It is hypothesized that longer TTR could be associated with worse infection control after second stage. A systematic literature search was performed according to Preferred Reporting items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in Pubmed, Cochrane Library and Web of Science Core Collection in clinical studies published until January 2023. Eleven studies investigating TTR as a potential risk factor for reinfection met the inclusion criteria (ten retrospective and one prospective study, published 2012–2022). Study design and outcome measures differed notably. The cutoff points above which TTR was regarded as “long” ranged from 4 to 18 weeks. No study observed a benefit for long TTR. In all studies, similar or even better infection control was observed for short TTR. The optimal TTR, however, is not yet defined. Larger clinical studies with homogeneous patient populations and adjustment for confounding factors are needed
Lidocaine as an anti-arrhythmic drug: Are there any indications left?
No full textLidocaine is classified as a class Ib anti-arrhythmic that blocks voltage- and pH-dependent sodium channels. It exhibits well investigated anti-arrhythmic effects and has been the anti-arrhythmic of choice for the treatment of ventricular arrhythmias for several decades. Lidocaine binds primarily to inactivated sodium channels, decreases the action potential duration, and increases the refractory period. It increases the ventricular fibrillatory threshold and can interrupt life-threatening tachycardias caused by re-entrant mechanisms, especially in ischemic tissue. Its use was pushed into the background in the era of amiodarone and modern electric device therapy. Recently, lidocaine has come back into focus for the treatment of acute sustained ventricular tachyarrhythmias. In this brief overview, we review the clinical pharmacology including possible side effects, the historical course, possible indications, and current Guideline recommendations for the use of lidocaine
Neuropilin-1 als Eintrittsfaktor umhüllter Viren
No full textDer Transmembranrezeptor Neuropilin-1 (NRP1) wurde als wichtiger Eintrittsfaktor für das umhüllte Virus SARS-CoV-2 identifiziert. NRP1 interagiert mit verschiedenen Oberflächenrezeptoren wie ACE2 sowie Rezeptortyrosinkinasen wie EGFR und HGFR. Untersucht wurde, ob diese Rezeptoren gleichzeitig oder wechselnd miteinander interagieren und damit den viralen Zelleintritt beeinflussen. Reduzierte Infektionsraten von SARS-CoV-2-Pseudoviren nach Endozytose-Inhibition bestätigen die zentrale Bedeutung der Endozytose. Intrazellulär ergab sich ein dynamischer Transport von NRP1 über das endosomale System mit besonderer Rolle des Retromerkomplexes ESCPE-1. Immunfluoreszenzfärbungen belegten eine deutliche Co-Lokalisation aller vier Rezeptoren auf der Plasmamembran. Nach Stimulation mit HGF wurden NRP1 und HGFR internalisiert, während EGF-Stimulation zur alleinigen Internalisierung von EGFR führte. Die Ergebnisse stützen die Annahme von NRP1 als zentralem Faktor des endozytotischen Viruseintritts in einem komplexen Rezeptornetzwerk
Norm collisions in European Union sectoral governance during the COVID-19 pandemic: How the European Commission reconfigures norms in crises
No full textThis article argues that the COVID-19 pandemic has incited the collision of norms in sectoral European Union (EU) governance and provided an open juncture for the European Commission to engage in norm reconfiguration. Herewith, the paper expands the conceptual scope of EU-related norm research, which by focussing on the diffusion of norms within and beyond the EU has largely omitted dynamic perspectives on norms so far. We combine International Relations norm research with EU governance literature to scrutinise the normative underpinnings of the immediate crisis response within Commission sectoral strategies and working programs. Empirically, the paper focuses on the higher education and transport sectors, which have been particularly impacted by the COVID-19 crisis and targeted by the EU crisis response. The interpretative-qualitative analysis uncovers COVID-19-related collisions within the ideational constellation of EU governance and shows that the European Commission has engaged in different reconfiguration practices, potentially altering the norm constellation in the investigated sectoral governance areas
Pathogenic gene variants in CCDC39, CCDC40, RSPH1, RSPH9, HYDIN, and SPEF2 cause defects of sperm flagella composition and male infertility
No full textPrimary Ciliary Dyskinesia (PCD) is a rare genetic disorder affecting the function of motile cilia in several organ systems. In PCD, male infertility is caused by defective sperm flagella composition or deficient motile cilia function in the efferent ducts of the male reproductive system. Different PCD-associated genes encoding axonemal components involved in the regulation of ciliary and flagellar beating are also reported to cause infertility due to multiple morphological abnormalities of the sperm flagella (MMAF). Here, we performed genetic testing by next generation sequencing techniques, PCD diagnostics including immunofluorescence-, transmission electron-, and high-speed video microscopy on sperm flagella and andrological work up including semen analyses. We identified ten infertile male individuals with pathogenic variants in 'CCDC39' (one) and 'CCDC40' (two) encoding ruler proteins, 'RSPH1' (two) and 'RSPH9' (one) encoding radial spoke head proteins, and 'HYDIN' (two) and 'SPEF2' (two) encoding CP-associated proteins, respectively. We demonstrate for the first time that pathogenic variants in 'RSPH1' and 'RSPH9' cause male infertility due to sperm cell dysmotility and abnormal flagellar RSPH1 and RSPH9 composition. We also provide novel evidence for MMAF in 'HYDIN-' and 'RSPH1-mutant' individuals. We show absence or severe reduction of CCDC39 and SPEF2 in sperm flagella of 'CCDC39-' and 'CCDC40-mutant' individuals and 'HYDIN-' and 'SPEF2-mutant' individuals, respectively. Thereby, we reveal interactions between CCDC39 and CCDC40 as well as HYDIN and SPEF2 in sperm flagella. Our findings demonstrate that immunofluorescence microscopy in sperm cells is a valuable tool to identify flagellar defects related to the axonemal ruler, radial spoke head and the central pair apparatus, thus aiding the diagnosis of male infertility. This is of particular importance to classify the pathogenicity of genetic defects, especially in cases of missense variants of unknown significance, or to interpret 'HYDIN' variants that are confounded by the presence of the almost identical pseudogene 'HYDIN2'
Radiation doses to mediastinal organs at risk in early-stage unfavorable Hodgkin lymphoma– a risk stratified analysis of the GHSG HD17 trial
No full textIntroduction: The German Hodgkin Study Group (GHSG) HD17 trial established the omission of radiotherapy (RT) for patients with early-stage unfavorable Hodgkin lymphoma being PET-negative after 2 cycles of BEACOPP escalated plus 2 cycles of ABVD. This patient group reveals heterogeneity in characteristics and disease extent which prompted us to perform a decisive dosimetric analysis according to GHSG risk factors. This may help to tailor RT individually balancing risks and benefits.
Methods: For quality assurance, RT-plans were requested from the treating facilities (n= 141) and analyzed centrally. Dose-volume histograms were scanned either paper-based or digitally to obtain doses to mediastinal organs. These were registered and compared according to GHSG risk factors.
Results: Overall, RT plans of 176 patients were requested, 139 of which had dosimetric information on target volumes within the mediastinum. Most of these patients were stage II (92.8%), had no B-symptoms (79.1%) and were aged < 50 years (89.9%). Risk factors were present in 8.6% (extranodal involvement), 31.7% (bulky disease), 46.0% (elevated erythrocyte sedimentation rate) and 64.0% (three involved areas), respectively. The presence of bulky disease significantly affected the mean RT doses to the heart (p=0.005) and to the left lung (median: 11.3 Gy vs. 9.9 Gy; p=0.042) as well as V5 of the right and left lung, respectively (median right lung: 67.4% vs. 51.0%; p=0.011; median left lung: 65.9% vs. 54.2%; p=0.008). Significant differences in similar organs at risk parameters could be found between the sub-cohorts with the presence or absence of extranodal involvement, respectively. In contrast, an elevated erythrocyte sedimentation rate did not deteriorate dosimetry significantly. No association of any risk factor with radiation doses to the female breast was found. Conclusion: Pre-chemotherapy risk factors may help to predict potential RT exposure to normal organs and to critically review treatment indication. Individualized risk-benefit evaluations for patients with HL in early-stage unfavorable disease are mandatory
Reciprocal Cuntz–Krieger algebras
No full textThe reciprocality in this paper means a duality in Kirchberg algebras between strong extension groups and K-theory groups. We describe a construction of the reciprocal dual algebra  for a Kirchberg algebra A with finitely generated K-groups via K-theoretic duality for extensions. In particular, we may concretely construct and realize the reciprocal algebra ÔA for a simple Cuntz–Krieger algebra OA in several different ways. As a result, the algebra ÔA is realized as a unital simple purely infinite universal C*-algebra generated by a family of partial isometries subject to certain operator relations. We will finally study the gauge action on the reciprocal algebra ÔA and prove that there exists an isomorphism between the fundamental groups π1(Aut(OA)) and π1(Aut( ÔA)) preserving their gauge actions
Redefining the Fight Against SCLC: Standards, Innovations, and New Horizons
No full textBackground: Small cell lung cancer (SCLC) remains a highly aggressive malignancy with a poor prognosis. Despite multimodal standard therapies, most patients relapse within months, and second-line treatment options such as topotecan offer only limited benefit. Novel therapeutic strategies are therefore urgently needed. Methods: This narrative review is based on a selective literature search conducted via PubMed and ClinicalTrials.gov (last updated June 2025). Results: Emerging treatment strategies include bispecific T-cell engagers (e.g., tarlatamab), antibody-drug conjugates (ADCs) such as sacituzumab govitecan, DS-7300, and ZL-1310, as well as targeted therapies. Among these, tarlatamab has demonstrated improved survival outcomes with an acceptable safety profile and is poised to become the new second-line standard. In contrast, ADCs and targeted agents have shown only modest efficacy and have yet to deliver meaningful survival benefits, often accompanied by increased toxicity. Additionally, the identification of molecular subtypes of SCLC has revealed subtype-specific differences in treatment response. However, clinical translation is challenged by intratumoral heterogeneity, plasticity, and the lack of standardized diagnostic assays. Conclusions: While tarlatamab represents a major therapeutic advancement, other agents remain in early clinical development and require validation in large, randomized trials. The clinical implementation of molecular subtyping remains limited, though it holds promise for future personalized treatment approaches. Despite recent progress, SCLC continues to pose substantial therapeutic challenges, emphasizing the need for improved treatment strategies and validated predictive biomarkers