1,720,964 research outputs found
Geotrichum candidum as an Opportunistic Human Pathogen in Cancer Patients and Benign Conditions
No full textNot All Weight Loss Is Equal: Divergent Patterns and Prognostic Roles in Head and Neck Cancer Versus High-Grade B-Cell Lymphoma
No full textBackground: Malnutrition and unintended weight loss are frequent in cancer patients and linked to poorer outcomes. However, data on long-term weight trajectories, particularly comparing different cancer entities, remain limited. Methods: In this retrospective, multicenter study, we analyzed 145 patients diagnosed with either head and neck cancer (HNC; n = 48) or high-grade B-cell lymphoma (HGBCL; n = 97). Body weight, C-reactive protein (CrP), albumin, and modified Glasgow Prognostic Score (mGPS) were assessed at diagnosis and at 3, 6, 9, and 12 months. Clinically relevant weight loss was defined as >5% from baseline. Survival analyses were performed for HGBCL patients. Results: Weight loss was common in both cohorts, affecting 32.2% at 3 months and persisting in 42.3% at 12 months. Nearly half of HNC patients had sustained >5% weight loss at one year, whereas HGBCL patients were more likely to regain weight, with significantly higher rates of weight gain at 6 and 12 months (p = 0.04 and p = 0.02). At baseline, HGBCL patients showed elevated CrP and lower albumin compared to HNC (both p < 0.001). Weight loss at 6 months was significantly associated with reduced overall survival in HGBCL (p < 0.01). Both Δweight at 6 months and mGPS emerged as useful prognostic indicators. Conclusions: This study reveals distinct patterns of weight change and systemic inflammation between HNC and HGBCL patients during the first year after diagnosis. These findings highlight the need for entity-specific nutritional monitoring and tailored supportive care strategies extending into survivorship. Prospective studies integrating body composition analyses are warranted to better guide long-term management
Outcomes of pirtobrutinib for relapsed/refractory mantle cell lymphoma in compassionate use program in Europe.
Get PDFBACKGROUND
Mantle cell lymphoma (MCL) is a type of B-cell lymphoma that is currently incurable. Pirtobrutinib shows promising response rates in heavily pretreated MCL patients according to the approval study, but the real-world data are scarce.
METHODS
In this study, we retrospectively analyzed the efficacy and safety profile of pirtobrutinib in 10 relapsed/refractory MCL patients from compassionate use program (CUP).
RESULTS
On average, the patients underwent three lines of systemic therapy prior to pirtobrutinib and were predominantly BTKi exposed (9/10). The best overall response rate (BORR) was 67%. In a median follow-up of 8.6 months, the mean duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were not reached. No new safety signals were documented.
CONCLUSIONS
In summary, pirtobrutinib represented a safe and effective treatment option in a small real-world population
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
In ovo studies on the interaction of Hodgkin lymphoma cells with monocytes
No full textDas klassische Hodgkin-Lymphom (cHL) ist eine aggressive B-Zell-Neoplasie. Trotz außergewöhnlicher Therapie-Ansprechraten führt die aktuelle Strategie der Risikostratifizierung beim cHL dazu, dass ein Teil der Patient*innen über- oder unterbehandelt wird. Die Langzeittoxizität der Therapie steht im Kontrast zur günstigen Prognose des Hodgkin-Lymphoms. Daher liegt eine Dosisreduktion der angewandten Radio-Chemotherapie bei gleichzeitigem Erhalt der Effektivität nahe. Etwa 20 Prozent der Hodgkin-Lymphome sind therapierefraktär oder rezidivieren nach initialer kompletter Remission (r/r), was mit einer drastisch reduzierten Prognose einhergehen kann. Diese Tumorentität ist durch wenige maligne Hodgkin-Reed-Sternberg-Zellen vor dem Hintergrund eines ausgedehnten reaktiven Immuninfiltrates benigner Zellen charakterisiert, wobei Monozyten respektive Makrophagen von prognostischer Bedeutung sind. Deshalb kann die Untersuchung der Mechanismen der vielfältigen Wechselwirkungen von Lymphomzellen und den Zellen ihrer Mikroumgebung, speziell der Makrophagen, von klinischer Relevanz sein.
Um herauszufinden, welche Auswirkung eine Ko-Kultur von CD14-positiven (CD14+) peripheral blood mononuclear cells (PBMCs) mit Hodgkin-Zellen in einem präklinischen Xenograft-Modell hat, wurden Tumoren im Chorion-Allantois-Membran-(CAM)-Assay des befruchteten Hühnereis generiert und nach vier Tagen in ovo geerntet. In diesem neu etablierten CAM-Modell wurden Lymphome der Zelllinie L-428 in An- und Abwesenheit von CD14+-PBMCs untersucht. Mischtumoren aus Lymphomzellen und CD14+-PBMCs führten im Vergleich zu reinen L-428-CAM-Lymphomen zu signifikant kleineren CAM-Läsionen, in denen so gut wie keine Hämorrhagien nachgewiesen werden konnten. Die Mischtumoren hatten eine kugelige, halbrunde Form und zeichneten sich histologisch durch eine dreigliedrige Kompartimentierung aus. Sowohl Lymphomzellen als auch Makrophagen zeigten nach vier Tagen in ovo Migrationsverhalten an den Invasionsfronten zur physiologischen CAM.
Eine wichtige Beobachtung war, dass im CAM-Modell histologisch die Expression von CD206 auf CD68-positiven Zellen in Mischtumoren aus L-428-Lymphomzellen mit CD14+-PBMCs nachweisbar war. Dies spricht für einen Lymphom-induzierten Aktivierungs- oder Differenzierungsprozess von den CD14+-PBMCs hin zu alternativ aktivierten M2-ähnlichen Makrophagen und gegebenenfalls sogar hin zu Hodgkin lymphoma-educated macrophages (HEMs). Da CD206 durch zahlreiche endozytotische Prozesse, unter anderem durch Kollagen-Aufnahme, charakterisiert ist, kommt den CD206-exprimierenden tumor-associated macrophages (TAMs) im Hodgkin-Lymphom vermutlich eine Rolle als aktiver Modulator in der Umgestaltung der Lymphom-Mikroumgebung zu.
In Zukunft könnte sich CD206 als diagnostischer Biomarker im Hodgkin-Lymphom herausstellen. Vielleicht könnte es auch zur Therapiesteuerung geeignet sein und sich möglicherweise als Zielstruktur für die selektive Hemmung von HEMs erweisen, insbesondere unter dem Eindruck der neu etablierten Immun-Checkpoint-Inhibitoren, welche für Patient*innen mit r/r cHL zugelassen sind.Classical Hodgkin lymphoma (cHL) is an aggressive B-cell neoplasm. Despite exceptional treatment response rates, the current strategy of risk stratification in cHL implies a relevant proportion of patients being over- or undertreated. Long-term toxicity resulting from therapy stands in stark contrast to the favourable overall prognosis of Hodgkin lymphoma patients. This suggests a dose reduction of the administered radio-chemotherapy while maintaining its efficacy. About twenty percent of cHL are refractory to therapy or relapse (r/r) after initial complete remission, associated with poor prognosis. This lymphoid malignancy is characterised by sparse Hodgkin-Reed-Sternberg cells embedded in an abundant reactive immune infiltrate of benign cells. Monocytes and macrophages are of prognostic significance. Hence, studying the complex interplay of lymphoma cells and the cells of their microenvironment, especially macrophages, could eventually claim clinical relevance.
In order to study the effect of co-culturing CD14-positive (CD14+) peripheral blood mononuclear cells (PBMCs) with Hodgkin cells in a preclinical xenograft model by using histological methods, tumours in this study were generated in the chorio-allantoic membrane assay (CAM assay) of the fertilised chicken egg and harvested after four days in ovo. In this newly established CAM model lymphomas of the cHL cell line L-428 were studied in presence and absence of CD14+ PBMCs. Compared to pure L-428 CAM lymphomas, mixed tumours of lymphoma cells and CD14+ PBMCs resulted in significantly smaller CAM lesions in which virtually no haemorrhages could be detected. Mixed tumours had a spherical, semicircular shape and were histologically characterised by a tripartite compartmentalisation. Both lymphoma cells and macrophages showed migratory behaviour at the invasion fronts towards the physiological CAM in ovo.
An important observation was that CD206 expression was histologically detectable on the surface of CD68-positive cells in mixed tumours of L-428 lymphoma cells and CD14+ PBMCs in our CAM model. This suggests a lymphoma-induced activation or differentiation process from CD14+ PBMCs to alternatively activated macrophages that expose an M2-like phenotype and possibly even to Hodgkin lymphoma-educated macrophages (HEMs). Since CD206 is characterised by numerous endocytic processes including collagen uptake, CD206-expressing tumour-associated macrophages (TAMs) in Hodgkin lymphoma likely have a role as an active modulator in the remodelling of the lymphoma microenvironment.
In the future, CD206 could emerge as a diagnostic biomarker in Hodgkin lymphoma. It might be suitable for therapy management as well and possibly could prove to be a target for selective inhibition of HEMs, particularly in the light of the advent of immune checkpoint inhibition approved for patients affected by r/r cHL.2021-11-2
- …
