Comparing 5 publications from China that described knockdowns of the human
TPD52L2
gene in human cancer cell lines identified unexpected similarities between these publications, flaws in experimental ...design, and mis-matches between some described experiments and the reported results. Following communications with journal editors, two of these
TPD52L2
publications have been retracted. One retraction notice stated that while the authors claimed that the data were original, the experiments had been out-sourced to a biotechnology company. Using search engine queries, automatic text-analysis, different similarity measures, and further visual inspection, we identified 48 examples of highly similar papers describing single gene knockdowns in 1–2 human cancer cell lines that were all published by investigators from China. The incorrect use of a particular
TPD52L2
shRNA sequence as a negative or non-targeting control was identified in 30/48 (63%) of these publications, using a combination of Google Scholar searches and visual inspection. Overall, these results suggest that some publications describing the effects of single gene knockdowns in human cancer cell lines may include the results of experiments that were not performed by the authors. This has serious implications for the validity of such results, and for their application in future research.
In vitro experiments in which tumour cells are seeded in a gelatinous medium, or hydrogel, show how mechanical interactions between tumour cells and the tissue in which they are embedded, together ...with local levels of an externally-supplied, diffusible nutrient (e.g., oxygen), affect the tumour’s growth dynamics. In this article, we present a mathematical model that describes these in vitro experiments. We use the model to understand how tumour growth generates mechanical deformations in the hydrogel and how these deformations in turn influence the tumour’s growth. The hydrogel is viewed as a nonlinear hyperelastic material and the tumour is modelled as a two-phase mixture, comprising a viscous tumour cell phase and an isotropic, inviscid interstitial fluid phase. Using a combination of numerical and analytical techniques, we show how the tumour’s growth dynamics change as the mechanical properties of the hydrogel vary. When the hydrogel is soft, nutrient availability dominates the dynamics: the tumour evolves to a large equilibrium configuration where the proliferation rate of nutrient-rich cells on the tumour boundary balances the death rate of nutrient-starved cells in the central, necrotic core. As the hydrogel stiffness increases, mechanical resistance to growth increases and the tumour’s equilibrium size decreases. Indeed, for small tumours embedded in stiff hydrogels, the inhibitory force experienced by the tumour cells may be so large that the tumour is eliminated. Analysis of the model identifies parameter regimes in which the presence of the hydrogel drives tumour elimination.
Is the future of peer review automated? Schulz, Robert; Barnett, Adrian; Bernard, René ...
BMC research notes,
06/2022, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The rising rate of preprints and publications, combined with persistent inadequate reporting practices and problems with study design and execution, have strained the traditional peer review system. ...Automated screening tools could potentially enhance peer review by helping authors, journal editors, and reviewers to identify beneficial practices and common problems in preprints or submitted manuscripts. Tools can screen many papers quickly, and may be particularly helpful in assessing compliance with journal policies and with straightforward items in reporting guidelines. However, existing tools cannot understand or interpret the paper in the context of the scientific literature. Tools cannot yet determine whether the methods used are suitable to answer the research question, or whether the data support the authors' conclusions. Editors and peer reviewers are essential for assessing journal fit and the overall quality of a paper, including the experimental design, the soundness of the study's conclusions, potential impact and innovation. Automated screening tools cannot replace peer review, but may aid authors, reviewers, and editors in improving scientific papers. Strategies for responsible use of automated tools in peer review may include setting performance criteria for tools, transparently reporting tool performance and use, and training users to interpret reports.
Aims and Scope:
This editorial announces the new Biomarker Insights Editor-in-Chief. The journal will continue to publish high-quality original reports and review articles in all areas of biomarker ...research, and will welcome submissions that focus on improving the quality of the biomarker research literature.
A major reason for biomarker failure is the selection of candidate biomarkers based on inaccurate or incorrect published results. Incorrect research results leading to the selection of unproductive ...biomarker candidates are largely considered to stem from unintentional research errors. The additional possibility that biomarker research may be actively misdirected by research fraud has been given comparatively little consideration. This review discusses what we believe to be a new threat to biomarker research, namely, the possible systematic production of fraudulent gene knockdown studies that target under-studied human genes. We describe how fraudulent papers may be produced in series by paper mills using what we have described as a ‘theme and variations’ model, which could also be considered a form of salami slicing. We describe features of these single-gene knockdown publications that may allow them to evade detection by journal editors, peer reviewers, and readers. We then propose a number of approaches to facilitate their detection, including improved awareness of the features of publications constructed in series, broader requirements to post submitted manuscripts to preprint servers, and the use of semi-automated literature screening tools. These approaches may collectively improve the detection of fraudulent studies that might otherwise impede future biomarker research.
The
Tumor protein D52
(
TPD52
) gene was identified nearly 20 years ago through its overexpression in human cancer, and a substantial body of data now strongly supports
TPD52
representing a gene ...amplification target at chromosome 8q21.13. This review updates progress toward understanding the significance of TPD52 overexpression and targeting, both in tumors known to be characterized by TPD52 overexpression/amplification, and those where TPD52 overexpression/amplification has been recently or variably reported. We highlight recent findings supporting microRNA regulation of TPD52 expression in experimental systems and describe progress toward deciphering TPD52’s cellular functions, particularly in cancer cells. Finally, we provide an overview of TPD52’s potential as a cancer biomarker and immunotherapeutic target. These combined studies highlight the potential value of genes such as
TPD52
, which are overexpressed in many cancer types, but have been relatively understudied.
Although it is generally accepted that human tissue biobanks are important to facilitate progress in health and medical research, many academic biobanks face sustainability challenges. We propose ...that biobank sustainability is challenged by a lack of available data describing the outputs and benefits that are produced by biobanks, as reflected by a dearth of publications that enumerate biobank outputs. We further propose that boosting the available information on biobank outputs and using a broader range of output metrics will permit economic analyses such as cost-consequence analyses of biobank activity. Output metrics and cost-consequence analyses can allow biobanks to achieve efficiencies, and improve the quality and/or quantity of their outputs. In turn, biobank output measures provide all stakeholders with explicit and accountable data on biobank value, which could contribute to the evolution of biobank operations to best match research needs, and mitigate some threats to biobank sustainability.
•Biobanks play an essential role in facilitating basic and translational health research. In particular, biobanked human specimens are a critical component in personalized medicine approaches to human disease. Nevertheless, it has proved difficult to determine a value for academic biobanks that can be interpreted and used by all stakeholders. A lack of value confers a threat to biobank sustainability, a common challenge for biobanks across the world.•To determine accurate biobank values, we describe an approach for academic biobanks to enumerate a comprehensive range of currently underreported biobank outputs. Using a broader range of output metrics also permits economic analyses such as cost-consequence analyses, providing a more comprehensive and transparent decision-making tool for funders, decision makers, and policy makers.•Consideration is given to the consequences of a lack of biobank output data, and approaches to achieve an output focus are then discussed. This includes efforts from biobanks, funders, policy makers, journal editors, and conference organizers. Finally, the benefits of focusing on biobank outputs are articulated, including operational efficiencies for biobanks and achieving explicit and accountable values for other stakeholders. This is necessary for biobank sustainability, and ultimately for better support of health and medical research.
Preserved biospecimens held in biobank inventories and clinical archives are important resources for biomarker research. Recent advances in technologies have led to an increase in use of clinical ...archives in particular, in order to study retrospective cohorts and to generate data relevant to tissue biomarkers. This raises the question of whether the current sizes of biobank inventories are appropriate to meet the demands of biomarker research. This commentary discusses this question by considering data concerning overall biobank and biospecimen numbers to estimate current biospecimen supply and use. The data suggests that biospecimen supply exceeds current demand. Therefore, it may be important for individual biobanks to reassess the targets for their inventories, consider culling unused portions of these inventories, and shift resources towards providing prospective custom biobanking services.
Inadequate research biospecimen quality may adversely impact research translation to clinical practice. Despite the development and endorsement of external quality assurance (QA) programs and ...biospecimen quality reporting tools, there has been little examination of relevant biobank practices.
An online survey was designed to describe the use and communication of QA and quality control (QC) measures within an Australian cancer biobank cohort (n=21), classified according to access policy. Survey questions examined the development and maintenance of Standard Operating Procedures (SOPs), other specific QA and biospecimen QC activities, and communication of biospecimen QC results to researchers.
Over three quarters of biobanks utilised regularly-reviewed, best-practice-referenced SOPs, and most biobanks undertook at least one QC activity. Whereas all open-access biobanks (n=11) utilised SOPs and undertook at least one QC activity, these practices were significantly less frequent in restricted-access biobanks (n=10). There were overall low rates of recording the SPREC code, with increased but incomplete recording of Tier 1 BRISQ data. Open-access biobanks were significantly more likely to provide biospecimen QC results to researchers, and to report receiving requests for QC results or additional sample data.
Improved resourcing and education may be required to boost current levels of QA and QC activities and reporting by cancer biobanks.
Display omitted
•Most biobanks utilised SOPs, and undertook biospecimen QC analysis.•Biospecimen QC analyses were more frequently performed in open-access biobanks.•Open-access biobanks were more likely to provide QC results to researchers.•There were overall low rates of recording the SPREC code.•Recording of Tier 1 BRISQ data was incomplete.
The severe acute respiratory syndrome coronavirus 2 spike protein is a critical component of coronavirus disease 2019 vaccines and diagnostics and is also a therapeutic target. However, the spike ...protein is difficult to produce recombinantly because it is a large trimeric class I fusion membrane protein that is metastable and heavily glycosylated. We recently developed a prefusion-stabilized spike variant, termed HexaPro for six stabilizing proline substitutions, that can be expressed with a yield of >30 mg/L in ExpiCHO cells. This protocol describes an optimized workflow for expressing and biophysically characterizing rationally engineered spike proteins in Freestyle 293 and ExpiCHO cell lines. Although we focus on HexaPro, this protocol has been used to purify over a hundred different spike variants in our laboratories. We also provide guidance on expression quality control, long-term storage, and uses in enzyme-linked immunosorbent assays. The entire protocol, from transfection to biophysical characterization, can be completed in 7 d by researchers with basic tissue cell culture and protein purification expertise.
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