Biology subjects

Drude, N. I.

Publications and source records attributed to Drude, N. I..

3 recordsLinked to original sources

bioRxiv2026

Multi-Lab Testing of Early Preclinical Discoveries Identifies Promising Treatments

A fundamental challenge in drug development is the frequent failure of early laboratory research to translate into clinical benefit. One promising solution is to confirm findings from exploratory single-laboratory studies across multiple laboratories before clinical testing. We investigated this approach following the conduct of preclinical multi-laboratory studies across different fields of medicine. For this, we evaluated effect sizes, experimental rigor, and a set of criteria to identify determinants of confirmation success. When tested under increased rigor, only a fraction of multi-laboratory studies confirmed the initial results. The underlying effect size reduction was associated with outcome-relevant experimental differences between exploratory and confirmatory stages. In summary, multi-laboratory studies proved highly informative and served as an effective filter for promising treatments.

scientific communication and education↗

bioRxiv2024

Reporting quality of quantitative polymerase chain reaction (qPCR) methods in scientific publications

Reproducibility is a significant concern in scientific research and complex methods like quantitative polymerase chain reaction (qPCR) demand stringent reporting standards to ensure that the methods are reproducible, data are sound, and conclusions are trustworthy. Although the MIQE (Minimum Information for Publication of Quantitative Real-Time PCR Experiments) guidelines were introduced in 2009 to improve qPCR reporting, a 2013 study identified ongoing deficiencies that hinder reproducibility. To further investigate the transparency and completeness of qPCR reporting, we systematically assessed articles published in the top 20 journals in genetics and heredity (n=186) and plant sciences (n=246) that used qPCR. Our analysis revealed frequent omissions and inadequate specification of critical information necessary for evaluating and replicating qPCR experiments. RNA integrity, along with assessment methods and instruments used to assess it, are seldom reported. Although primer sequences are often disclosed, names and accession numbers of housekeeping genes are frequently omitted. Additionally, essential details about RNA extraction, RNA-to-cDNA conversion, and qPCR, such as kit names, catalog numbers, and reagent information, are often missing. Our findings underscore the urgent need for improved reporting practices in qPCR experiments, emphasizing quality controls, detailed descriptions of reagents and materials, and greater analytical transparency. Addressing these reporting deficiencies is crucial for enhancing the reproducibility and evaluating the trustworthiness of qPCR research. Potential solutions include encouraging authors to cite protocols published in online repositories, providing reporting templates, or developing automated tools to check reporting compliance.

genetics↗

bioRxiv2019

Assessment of chemotherapy-induced organ damage with 68Ga-labeled duramycin

Compared to standard toxicological techniques in preclinical toxicity studies, non-invasive imaging of organ toxicity enables fast and longitudinal investigation of the whole animal. Therefore, we set out to evaluate [68Ga]Ga-NODAGA-duramycin as a positron emission tomography (PET)-tracer of cell death for detecting chemotherapy-induced organ toxicity.\n\nMethodsNODAGA-duramycin was radiolabeled with 68Ga, and quality control was done by thin layer chromatography and high performance liquid chromatography. Tracer specificity was determined in vitro by performing competitive binding experiments on ethanol treated cells. To optimize the timing of the PET/CT-based tracer evaluation, kinetic studies were performed in untreated and cisplatin-treated (20 mg/kg BW, intraperitoneal (i.p.)) BALB/cAnNRj mice. Organ uptake was analyzed in doxorubicin (4 mg/kg BW, i.p.)-, busulfan (18.8 mg/kg KG, i.p.)-, and cisplatin-treated (20 mg/kg BW, i.p.) mice, and in untreated control mice 2 hours after intravenous injection of 5-10 MBq [68Ga]Ga-NODAGA-duramycin. For immunofluorescence validation, tissue sections were stained with anti-active caspase-3 antibody. Blood and serum samples were collected to determine platelet count, aspartate transaminase, alanine transaminase, urea, creatinine, and creatine kinase values.\n\nResultsIn vitro experiments confirmed specific binding of [68Ga]Ga-NODAGA-duramycin to dying cells. The biodistribution analysis revealed a blood half-life of 10-17 minutes and a predominantly urinary excretion of the radiotracer. Doxorubicin-, busulfan-, and cisplatin-induced organ toxicities were detected successfully using [68Ga]Ga-NODAGA-duramycin PET/CT and confirmed by immunohistochemistry as well as blood parameter analysis. Busulfan-related spleno-, cardio-, and pneumotoxicity as well as cisplatin-induced cardio- and pneumotoxicity were detected even earlier by [68Ga]Ga-NODAGA-duramycin PET/CT than by blood parameters and histological stainings. In livers and kidneys, differences between treated and untreated animals tended to occur in PET/CT at later time points than in histology due to the relatively high background in these organs. However, trends over time were comparable.\n\nConclusion[68Ga]Ga-NODAGA-duramycin PET/CT was successfully applied to non-invasively detect chemotherapy-induced organ toxicity with high sensitivity in preclinical studies. It even depicted some toxic effects prior to immunohistochemistry and blood parameter analysis and represents a promising alternative or complementary method to standard toxicological analyses. Furthermore, the tracer has a high translational potential and may provide a valuable link between preclinical and clinical research.

pharmacology and toxicology↗