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Current practice of pathologic response assessment following chemoimmunotherapy for non‐small cell lung cancer ( NSCLC ) in Germany: first real‐world data from the multicentre Re‐ GraDE study
No full textBackground Given that pathologists now frequently assess pathologic response following neoadjuvant or perioperative chemoimmunotherapy for NSCLC, we set up a multicentre study to evaluate the current practice of re gression gra ding in Germany (Re‐GraDE NSCLC). Methods 133 cases of NSCLC resection specimens following chemoimmunotherapy (IO) were collected from 9 high‐volume lung cancer centres in Germany. Case characteristics were obtained from pathology reports/electronic medical records. In 107 cases, pretreatment biopsies were available on‐site. Results Residual viable tumour (% RVT) was commonly used to measure therapy response (106/133 resection specimens, 79.7%). The entire tumour bed was submitted for histology in 55.6% of cases; however, in 18%, a tumour bed of ≤3 cm was not completely submitted. Either Junker or IASLC regression grading was applied in 97.7% of primary tumours and 60.2% of lymph nodes with comparable results. Almost half of the tumours (45.9%) showed pathological complete response (pCR and/or regression grade (RG) III) with a very weak correlation between % RVT and pretreatment PD‐L1 TPS ( r 2 = 0.078, P = 0.007). Pretreatment PD‐L1 levels ranged from 0% to 100% (median, 60%) in cases with complete regression, and pCR was observed in 40% of cases with pretreatment PD‐L1 TPS <1%. Conclusions Our multicentre study describes the current practice of histopathological regression grading of NSCLC after IO in Germany, highlighting the widespread use of the Junker system, which is basically comparable to IASLC regression grading. For standardization, we recommend following the IASLC guidelines (submitting of the complete tumour bed if ≤3 cm), while the reporting of % RVT might represent a continuous parameter for therapy response. Our digital nationwide registry, which aims to integrate biopsy results, molecular profiling and % RVT in resection specimens, might develop into a valuable tool to investigate novel predictive biomarkers of IO efficacy
Maize Diterpenoid Sensing via the Ste3 A‐Pheromone Receptor Guide Oval Conidia of Colletotrichum graminicola to Host Roots
No full textABSTRACT Colletotrichum graminicola , the maize anthracnose fungus, is known for its ability to invade above‐ground tissues. This fungus forms two distinct asexual spore types in its life cycle, falcate conidia in acervuli on infected leaves and oval conidia in parenchyma cells in leaf and stem lesions. Our study reveals a previously unknown role for oval conidia in the infection of roots. We investigated whether root exudate from maize could redirect the growth of germlings generated by C. graminicola . Our results showed that only germlings derived from oval conidia were able to respond to root exudates, whereas those from falcate conidia did not. High‐performance liquid chromatography/mass spectrometry (HPLC–MS) analyses combined with biological assays and genetic studies identified diterpenoids from maize as attractants perceived by the a‐pheromone receptor CgSte3. We further explored the root–fungus interaction by analysing the germination of oval and falcate spores in soils of different composition. Oval conidia germinated rapidly under all conditions, whereas falcate conidia remained dormant and became highly vacuolated even in the presence of the host plant. Microscopic evaluation of root infection experiments showed that both conidia types attached to root material and formed penetration structures. However, only oval conidia enabled the pathogenic fungus to reach upper plant parts from infected roots. Our findings suggest a novel role for oval conidia in the infection of roots, highlighting the complexity of the anthracnose disease cycle.Deutsche Forschungsgemeinschaft https://doi.org/10.13039/50110000165
Isolation, Culture, and Analyses of Keratinocytes, Fibroblasts, and Hair Follicles from Normal Human Skin and Cancer-Associated Fibroblasts from Skin Tumors
No full textComprehensive utilization of NMR spectra–evaluation of NMR-based quantification of amino acids for research and patient care
No full textAbstract Objectives In 1 H nuclear magnetic resonance spectroscopy (NMR), a single measurement can yield insights into hundreds of metabolites. The use of NMR is expanding in research, with comprehensive datasets readily available. To fully leverage the spectral data, e.g. for amino acid (AA) detection, evaluating the quality of NMR quantification is crucial. For this, we compared the results for 15 AAs obtained from 1 H NMR and a clinical HPLC platform. Methods 1 H NMR and HPLC measurements of 15 AAs from 90 samples are compared by Spearman correlation coefficients and Passing-Bablok analysis. Imprecision is evaluated by coefficients of variation based on duplicates. Results 1 H NMR measurements of two AAs show high correlation and good agreement to HPLC measured levels (phenylalanine, alanine). Three more AA measurements reveal high correlation but systematic bias (tyrosine, valine, glycine). NMR results of six investigated AAs are less comparable (ornithine, threonine, histidine, isoleucine, leucine, lysine). Four measurands could not be evaluated (glutamine, glutamic acid, asparagine, methionine). Conclusions Analytical quality varies considerably among the investigated AAs. A limited number of AAs show good concordance with results from HPLC supporting selective use of NMR spectra for AA analysis. While NMR holds promise in both research and clinical settings, it is currently not suitable for comprehensive AA monitoring for diagnostic purpose
Preferences of Dermato-oncologists for Adjuvant Therapy in Stage II Melanoma: A Nationwide Discrete Choice Experiment
No full textAdjuvant treatment decisions in stage IIB/C melanoma require careful weighing of benefits and risks. Our aim was to investigate how dermato-oncologists in Germany prioritize efficacy, toxicity, and application mode of modern adjuvants in these stages. In a nationwide discrete choice experiment physicians evaluated hypothetical treatment scenarios that varied in recurrence risk, risk of severe adverse events, type of adverse events, and mode of administration. Two patient profiles were presented, including a 55-year-old healthy patient in stage IIB (P1) and an 83-year-old patient in stage IIC with comorbidity (P2). Physicians (n = 112) preferred adjuvant therapy to the opt-out option in 86.4% of scenarios for P1 and in 60.5% for P2. The risk of severe adverse events was considered most important for both patients and significantly more relevant for P2 (relative importance score (RIS) 53.6 vs 40.2, p < 0.001), while recurrence risk was more relevant for P1 (RIS 36.3 vs 21.8, p < 0.001). Immune-related adverse events were less acceptable than gastrointestinal symptoms or pyrexia. Infusions at longer intervals were favoured compared with oral therapies. In conclusion, dermato-oncologists prioritized safety over efficacy, particularly in the older, comorbid patient. These preferences should be reconciled with patients’ preferences and treatment goals during shared decision-making
Impact of Acute Myeloid Leukemia Cells on the Metabolic Function of Bone Marrow Mesenchymal Stem Cells
No full textAcute myeloid leukemia (AML) proliferation is significantly influenced by the interactions between leukemia blasts and the bone marrow (BM) microenvironment. Specifically, bone marrow mesenchymal stem cells (BMSCs) derived from AML patients (AML-MSCs) are known to support leukemia growth and facilitate disease progression. Studies have demonstrated that the transfer of mitochondria from MSCs to AML blasts not only aids in disease progression but also contributes to chemotherapy resistance. Furthermore, BM stromal cells can trigger a metabolic shift in malignant cells from mitochondrial respiration to glycolysis, which enhances both growth and chemo-resistance. This study focuses on identifying transcriptional and metabolic alterations in AML-MSCs to uncover potential targeted therapies for AML. We employed RNA sequencing and microarray analysis on MSCs cocultured with leukemic cells (MLL-AF9) and on MSCs isolated from both non-leukemic and MLL-AF9 leukemic mice. The Gene Set Enrichment Analysis (GSEA) indicated a significant downregulation of gene sets associated with oxidative phosphorylation and glycolysis in AML-MSCs. Furthermore, coculture of MSCs from wild-type mice (WT-MSCs) and a healthy donor individual (HD-MSCs) with AML cells demonstrated reduced oxidative phosphorylation and glycolysis. These metabolic changes were consistent in AML-MSCs derived from both leukemic mice and patients. Our results indicate that AML cells diminish the metabolic capacity of MSCs, specifically targeting oxidative phosphorylation and glycolysis. These findings suggest potential metabolic vulnerabilities that could be exploited to develop more effective therapeutic strategies for AML
Tenecteplase—What Have We Learned till Now? A Narrative Review
No full textTenecteplase (TNK), a genetically modified tissue plasminogen activator, has emerged as a promising alternative to alteplase (ALT) for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Our aim was to synthesize the current clinical evidence on TNK use in AIS patients, comparing efficacy, safety, and workflow benefits to ALT. A narrative review was conducted by searching PubMed and Scopus (January 2024–March 2025) for studies comparing TNK and ALT in AIS. A total of 35 eligible papers were included. Data were grouped by treatment scenario: IVT-only, bridging before endovascular therapy (EVT), and intra-arterial thrombolysis (IAT). The results showed that TNK is non-inferior—and in some analyses, superior—to ALT regarding functional outcomes, especially in large vessel occlusion. TNK facilitates shorter treatment delays due to its single-bolus administration. While some trials report higher rates of intracranial hemorrhage, overall safety and mortality are comparable. In conclusion, TNK appears to exert equivalent or superior efficacy and safety compared to ALT in multiple AIS scenarios. Its pharmacological and logistical advantages support its broader clinical adoption. Further trials are needed, especially for IAT, central retinal artery occlusion, and patients on dabigatran
Replication of blood DNA methylomic signatures associated with cerebrospinal fluid levels of YKL‐40 and NfL biomarkers
No full textMedical Research Council https://doi.org/10.13039/501100000265University of Texas System https://doi.org/10.13039/100007130National Institutes of Health https://doi.org/10.13039/100000002Instituto de Salud Carlos III https://doi.org/10.13039/501100004587Innovative Medicines Initiative https://doi.org/10.13039/501100010767Deutsche Forschungsgemeinschaft https://doi.org/10.13039/50110000165
Simulation Models for Exploring Magnetic Reconnection
No full textAbstract Simulations have played a critical role in the advancement of our knowledge of magnetic reconnection. However, due to the inherently multiscale nature of reconnection, it is impossible to simulate all physics at all scales. For this reason, a wide range of simulation methods have been crafted to study particular aspects and consequences of magnetic reconnection. This article reviews many of these methods, laying out critical assumptions, numerical techniques, and giving examples of scientific results. Plasma models described include magnetohydrodynamics (MHD), Hall MHD, Hybrid, kinetic particle-in-cell (PIC), kinetic Vlasov, Fluid models with embedded PIC, Fluid models with direct feedback from energetic populations, and the Rice Convection Model (RCM).National Aeronautics and Space Administration http://dx.doi.org/10.13039/100000104National Science Foundation http://dx.doi.org/10.13039/100000001National Coordination Office http://dx.doi.org/10.13039/10001407
“Class is not a thing”. Towards analyzing processes of class formation
No full textZusammenfassung Im Artikel „Klasse gegen Klima?“ von Klaus Dörre, Steffen Liebig, Kim Lucht und Johanna Sittel wird hochinteressantes Material zu Transformationskonflikten in der Automobilindustrie präsentiert. Die Argumentation wird jedoch in dreierlei Hinsicht nicht konsequent genug zu Ende gedacht: Erstens sind die Ausführungen zur „Klassenachse der Transformation“ allenfalls lose mit der Interpretation der empirischen Fallstudien verbunden. Zweitens stellt das Jenaer Klassenschema, das dem ersten Teil des Artikels zugrunde liegt, zwar ein nützliches sozialstrukturelles Kategoriensystem dar, verstellt aber den analytischen Blick auf Prozesse von Klassenformierung, weil damit weder die komplexen und in permanenter Veränderung begriffenen Beziehungen zwischen Kapital und Arbeit noch die wechselhaften Beziehungen innerhalb der arbeitenden Klasse zu fassen sind. Klasse ist jedoch kein „Ding“, wie E. P. Thompson bemerkt, sondern ein (immer widersprüchliches und dynamisches) soziales Verhältnis. In Hinblick auf alltägliche Prozesse von Klassenformierung, die sich nicht zuletzt im betrieblichen Kontext vollziehen, enthält das von den Autor*innen präsentierte Material eine Fülle von Hinweisen darauf, inwiefern im Zuge der „Transformation“ der Automobilindustrie die Beziehungen zwischen Management und Belegschaft und zwischen verschiedenen Beschäftigtengruppen in Bewegung geraten. Hier könnte und sollte, drittens, eine klassenanalytische Spurensuche nach Potenzialen für die Erweiterung eines solidarischen „Wir“ unter Lohnabhängigen und für eine emanzipatorische Politik der Arbeit (im Betrieb und darüber hinaus) ansetzen, die eine „Transformation von unten“ als utopisches Projekt überhaupt erst denkbar machen könnte.Abstract In their paper “Class versus climate?”, Klaus Dörre, Steffen Liebig, Kim Lucht and Johanna Sittel present fascinating empirical material on conflicts over the “transformation” of the German automotive industry. However, the argument is not pursued thoroughly enough: First of all, the authors’ reflections on the “class axis of transformation” are only loosely connected to the interpretation of the empirical case studies. Secondly, the “Jena class scheme,” on which the first part of the paper is based, constitutes a useful system of sociostructural categorization, but by obscuring the complex and permanently changing relations between capital and labor as well as within the working class, it gets in the way of critically analyzing processes of class formation. However, “class is not a thing,” as E. P. Thompson rightly argues, but an (ambivalent and dynamic) social relation. With regard to everyday processes of class formation, which can be studied not least on the shopfloor, the authors’ empirical material is actually very rich, indicating how much the social relations between management and workforce, but also between different groups of employees have been set in motion in the course of the “transformation” of car manufacturing. This could and should be used as a starting point for exploring, from the vantage point of class analysis, the potentials for a more inclusive “we” among wage earners and emancipatory politics of labor (at the workplace and beyond) that would be required in order to render the utopian project of a “transformation from below” thinkable.Zusammenfassung Im Artikel „Klasse gegen Klima?“ von Klaus Dörre, Steffen Liebig, Kim Lucht und Johanna Sittel wird hochinteressantes Material zu Transformationskonflikten in der Automobilindustrie präsentiert. Die Argumentation wird jedoch in dreierlei Hinsicht nicht konsequent genug zu Ende gedacht: Erstens sind die Ausführungen zur „Klassenachse der Transformation“ allenfalls lose mit der Interpretation der empirischen Fallstudien verbunden. Zweitens stellt das Jenaer Klassenschema, das dem ersten Teil des Artikels zugrunde liegt, zwar ein nützliches sozialstrukturelles Kategoriensystem dar, verstellt aber den analytischen Blick auf Prozesse von Klassenformierung, weil damit weder die komplexen und in permanenter Veränderung begriffenen Beziehungen zwischen Kapital und Arbeit noch die wechselhaften Beziehungen innerhalb der arbeitenden Klasse zu fassen sind. Klasse ist jedoch kein „Ding“, wie E. P. Thompson bemerkt, sondern ein (immer widersprüchliches und dynamisches) soziales Verhältnis. In Hinblick auf alltägliche Prozesse von Klassenformierung, die sich nicht zuletzt im betrieblichen Kontext vollziehen, enthält das von den Autor*innen präsentierte Material eine Fülle von Hinweisen darauf, inwiefern im Zuge der „Transformation“ der Automobilindustrie die Beziehungen zwischen Management und Belegschaft und zwischen verschiedenen Beschäftigtengruppen in Bewegung geraten. Hier könnte und sollte, drittens, eine klassenanalytische Spurensuche nach Potenzialen für die Erweiterung eines solidarischen „Wir“ unter Lohnabhängigen und für eine emanzipatorische Politik der Arbeit (im Betrieb und darüber hinaus) ansetzen, die eine „Transformation von unten“ als utopisches Projekt überhaupt erst denkbar machen könnte.Abstract In their paper “Class versus climate?”, Klaus Dörre, Steffen Liebig, Kim Lucht and Johanna Sittel present fascinating empirical material on conflicts over the “transformation” of the German automotive industry. However, the argument is not pursued thoroughly enough: First of all, the authors’ reflections on the “class axis of transformation” are only loosely connected to the interpretation of the empirical case studies. Secondly, the “Jena class scheme,” on which the first part of the paper is based, constitutes a useful system of sociostructural categorization, but by obscuring the complex and permanently changing relations between capital and labor as well as within the working class, it gets in the way of critically analyzing processes of class formation. However, “class is not a thing,” as E. P. Thompson rightly argues, but an (ambivalent and dynamic) social relation. With regard to everyday processes of class formation, which can be studied not least on the shopfloor, the authors’ empirical material is actually very rich, indicating how much the social relations between management and workforce, but also between different groups of employees have been set in motion in the course of the “transformation” of car manufacturing. This could and should be used as a starting point for exploring, from the vantage point of class analysis, the potentials for a more inclusive “we” among wage earners and emancipatory politics of labor (at the workplace and beyond) that would be required in order to render the utopian project of a “transformation from below” thinkable