221 research outputs found
Intralesional TLR4 agonist treatment strengthens the organ defense against colonizing cancer cells in the brain
No full textAbstract
Brain metastasis in breast cancer remains difficult to treat and its incidence is increasing. Therefore, the development of new therapies is of utmost clinical relevance. Recently, toll-like receptor (TLR) 4 was correlated with IL6 expression and poor prognosis in 1 215 breast cancer primaries. In contrast, we demonstrated that TLR4 stimulation reduces microglia-assisted breast cancer cell invasion. However, the expression, prognostic value, or therapeutic potential of TLR signaling in breast cancer brain metastasis have not been investigated. We thus tested the prognostic value of various TLRs in two brain-metastasis gene sets. Furthermore, we investigated different TLR agonists, as well as MyD88 and TRIF-deficient microenvironments in organotypic brain-slice ex vivo co-cultures and in vivo colonization experiments. These experiments underline the ambiguous roles of TLR4, its adapter MyD88, and the target nitric oxide (NO) during brain colonization. Moreover, analysis of the gene expression datasets of breast cancer brain metastasis patients revealed associations of TLR1 and IL6 with poor overall survival. Finally, our finding that a single LPS application at the onset of colonization shapes the later microglia/macrophage reaction at the macro-metastasis brain-parenchyma interface (MMPI) and reduces metastatic infiltration into the brain parenchyma may prove useful in immunotherapeutic considerations.Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659Bundesministerium für Bildung und Forschung https://doi.org/10.13039/50110000234
Characterization of Publications on Post-Retraction Citation of Retracted Articles
No full textObjective Existing literature reviews about retraction do not analyze post-retraction citation. This research synthesizes a subgroup of empirical studies about retraction and reports what is known about post-retraction citation.
Design This is a subanalysis of a previously reported scoping review.1 A total of 386 items about retraction were found by double screening a systematic search of PubMed, Scopus, and Web of Science up to February 10, 2021; Scopus cited reference searching in January 2021; and hand searching up to July 2021.1 Items comprised published and unpublished research reports, such as journal articles, book chapters, conference abstracts and conference papers, dissertations, blog posts and magazine articles reporting research studies or data analyses, as well as work in progress such as preprints and project file repositories. Subsequent to the previous report, a custom taxonomy2 of methods, research goals, and research was iteratively created and made searchable via an online bibliography.3 For the subanalysis, the scope was narrowed to post-retraction citation after excluding items on citation-related implications for review literature and authors’ careers, publicity, and altmetrics. A codebook to guide data extraction was developed and piloted. Data extraction and analysis is ongoing.
Results This subanalysis included 92 items up to July 2021 that relate to post-retraction citation of retracted papers. Items were classified into 7 topics: database-focused analyses (n = 33) (eg, PubMed and Web of Science); field-based case studies (n = 20) (eg, genetics, radiology, and thoracic surgery); paper-focused case studies of 1 to 125 selected papers (n = 15); author-focused case studies of 1 or several authors with many retracted publications (n = 15) (eg, Bruening, Darsee, and Reuben); studies of retracted publications cited in review literature (n = 8); geographic case studies (n = 4) (focusing on Brazil, the European Union, Italy, and South Korea); and studies selecting retracted publications by method (n = 2) (eg, human subjects and randomized clinical trials). Five items were classified as belonging to 2 topics each. Empirical research about post-retraction citation has been published in a diffuse set of journals, primarily in journals of ethics; information science; meta-science and scientometrics; and domain sciences, especially medical specialties. The earliest 2 studies identified were both published in 1990; 1 study was an author-focused case study of citations to Stephen E. Breuning’s publications and the other studied 82 Index Medicus articles retracted, with retraction notices in Index Medicus as of 1990 and citations from SCISEARCH. From 1990 to 2017, 1 to 3 items were found per year except in 2016 (5 items), and from January 2018 to July 2021, 11 to 18 items per year were found on post-retraction citation. Almost all of these items focused on health sciences (eg, medicine, dentistry, nursing, psychology, and pharmacy), with 1 item focused on arts and humanities and 2 items focused on engineering.
Conclusions
Post-retraction citation has been studied consistently since 1990, with increasing attention since 2018. This analysis found an increasing number of items on post-retraction citation from January 2018 to July 2021. However, relevant work published after July 2021 was not included, and items published earlier may have been missed from the scoping review. Inclusion of work in progress may have increased publication counts for the most recent years.
References
1. Schneider J, Woods ND, Proescholdt R, Fu Y; The RISRS Team. Recommendations from the reducing the inadvertent spread of retracted science: shaping a research and implementation agenda project. MetaArXiv Preprints. Preprint posted online July 28, 2021. doi:10.31222/osf.io/ms579
2. Proescholdt R, Schneider J. Comparison set guide for empirical retraction lit.
University of Illinois IDEALS Repository. Deposited September 10, 2021. https://hdl.handle.net/2142/110389
3. Proescholdt R, Schneider J., The RISRS Team. Empirical retraction lit bibliography. Version 2.20. Zenodo. Published online September 9, 2021. doi:10.5281/zenodo.5498500
Conflicts of Interest Disclosures: Jodi Schneider has been an invited speaker for scholarly publishing organizations Committee on Publication Ethics, CrossRef, the European Association of Science Editors, the International Society of Managing and Technical Editors, the Institute of Electrical and Electronics Engineers, the National Information Standards Organization, and STM; has received data-in-kind from Retraction Watch and scite; and has received usability testing compensation from the Institute of Electrical and Electronics Engineers. No other disclosures were reported.
Funding: This project was supported by Alfred P. Sloan Foundation (G-2020-12623).
Role of the Funder/Sponsor: The study sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the abstract; and decision to submit the abstract for presentation.Alfred P. Sloan Foundation G-2020-1262
Quality of life in the GLARIUS trial randomizing bevacizumab/irinotecan versus temozolomide in newly diagnosed, MGMT-nonmethylated glioblastoma
No full textBackground: The GLARIUS trial, which investigated the efficacy of bevacizumab (BEV)/irinotecan (IRI) compared with standard temozolomide in the first-line therapy of O-6-methylguanine-DNA methyltransferase (MGMT)nonmethylated glioblastoma, showed that progression-free survival was significantly prolonged by BEV/IRI, while overall survival was similar in both arms. The present report focuses on quality of life (QoL) and Karnofsky performance score (KPS) during the whole course of the disease. Methods: Patients (n = 170) received standard radiotherapy and were randomized (2: 1) for BEV/IRI or standard temozolomide. At least every 3 months KPS was determined and QoL was measured using the European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life and 20-item Brain Neoplasm questionnaires. A generalized estimating equation (GEE) model evaluated differences in the course of QoL and KPS over time. Also, the time to first deterioration and the time to postprogression deterioration were analyzed separately. Results: In all dimensions of QoL and KPS, GEE analyses and time to first deterioration analyses did not detect significant differences between the treatment arms. At progression, 82% of patients receiving second-line therapy in the standard arm received BEV second-line therapy. For the dimensions of motor dysfunction and headaches, time to postprogression deterioration was prolonged in the standard arm receiving crossover second-line BEV in the vast majority of patients at the time of evaluation. Conclusions: GLARIUS did not find indications for a BEV-induced detrimental effect on QoL in first-line therapy of MGMT-nonmethylated GBM patients. Moreover, GLARIUS provided some indirect corroborative data supporting the notion that BEV may have beneficial effects upon QoL in relapsed GBM
Computerized Data Analysis of Neuromonitoring Parameters Identifies Patients with Reduced Cerebral Compliance as Seen on CT
No full text
Baseline T1 hyperintense and diffusion-restricted lesions are not linked to prolonged survival in bevacizumab-treated glioblastoma patients of the GLARIUS trial
No full textPurposeThe phase II GLARIUS trial assigned patients with newly diagnosed, O-6-methylguanine-DNA methyltransferase promoter non-methylated glioblastoma to experimental bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ). To identify subpopulations with a particularly favorable course, we assessed the prognostic potential of magnetic resonance imaging (MRI) markers before treatment onset.MethodsMRIs at baseline (before treatment onset) were analyzed for T1-hyperintense and diffusion-restricted lesions; as well as the presence of both hyperintense and diffusion-restricted (double positive) lesions. The MRI findings were correlated with overall and progression-free survival.ResultsMRI scans were evaluable in 71% of the GLARIUS modified intention-to-treat population (n = 121 of 170; 88 patients in the BEV/IRI arm, and 33 patients in the TMZ control arm). Diffusion-restricted and T1 hyperintense lesions were present in 60% and 65% of patients in BEV/IRI arm, while 57% and 63% were found in the TMZ arm, respectively. Double positive lesions were found in 37% of BEV/IRI patients and in 39% of TMZ patients. Neither the presence of T1-hyperintense, diffusion-restricted lesions, nor double positive lesions were associated with improved survival.ConclusionsBaseline T1-hyperintense and diffusion-restricted lesions are not suitable to predict progression-free or overall survival of patients treated with bevacizumab/irinotecan or temozolomide
Surgical resection of brain metastases-impact on neurological outcome
No full textBrain metastases (BM) develop in about 30% of all cancer patients. Surgery plays an important role in confirming neuropathological diagnosis, relieving mass effects and improving the neurological status. To select patients with the highest benefit from surgical resection, prognostic indices (RPA, GPA) have been formulated which are solely focused on survival without considering neurological improvement. In this study we analyzed the impact of surgical resection on the neurological status in addition to overall survival in 206 BM patients. Surgical mortality and morbidity was 0.0% and 10.3% respectively. New neurologic deficits occurred in 6.3% of all patients. The median overall survival was 6.3 months. Poor RPA class and short time interval between diagnosis of cancer and the occurrence of BM were independent factors predictive for poor survival. Improvement of neurological performance was achieved in 56.8% of all patients, with the highest improvement rate seen in patients presenting with increased intracranial pressure and hemiparesis. Notably, the neurological benefits were independent from RPA class. In conclusion, surgical resection leads to significant neurological improvement despite poor RPA class and short overall survival. Considering the low mortality and morbidity rates, resection should be considered as a valid option to increase neurological function and quality of life for patients with BM
- …
