Eli Oldham

The new anticancer agent poly(L-glutamic acid)-paclitaxel (PG-TXL) is a conjugate of paclitaxel and the water-soluble polyglutamate carrier. The observation that PG-TXL appears to possess antitumor activity superior to free paclitaxel in preclinical studies suggests that PG-TXL might possess favorable pharmacokinetic properties and/or have a mechanism of action different from that of paclitaxel. The purpose of this study was to compare the pharmacological action of PG-TXL and free paclitaxel in a panel of breast cancer cell lines with emphasis on their ability to induce apoptosis, their effects on cell cycle progression, and their cellular uptake. Morphological analysis and biochemical characterizations demonstrated that both compounds have similar abilities to induce apoptosis in cells expressing wild-type p53 (MCF-7) or mutant p53 (MDA-MB435 and MDA-MB453). Although MCF-7 cells were less sensitive to each compound than MDA-MB435 and MDA-MB453 cells, transfection experiments demonstrated that p53 did not appear to play a significant role in drug-induced cell death with either agent. Flow cytometry analysis further revealed that both free paclitaxel and PG-TXL induced a characteristic G2/M arrest in the cell cycle, consistent with the disturbance of microtubule polymerization as their mechanism of action. Western blot analysis showed that paclitaxel and PG-TXL downregulated HER2/neu expression in a similar fashion. HPLC analysis revealed that paclitaxel was released from the PG-TXL conjugate in vitro. The released paclitaxel, not the glutamic acid polymer, was subsequently transported into the cells. These results suggest that PG-TXL exerts its anticancer activity by continuous release of free paclitaxel, and that the favorable pharmacokinetics and drug distribution of the PG-TXL conjugate in vivo are likely the main factors contributing to its superior anticancer activity.

BACKGROUND: Orthopaedic surgery is a critical field, impacting global health-care expenditure and patient outcomes. Despite substantial research funding, issues of transparency and reproducibility persist, undermining the credibility of published in-print findings. Data-sharing initiatives aim to address these challenges by promoting accessibility and enhancing research reliability. We aimed to assess the landscape of data-sharing practices within the field of orthopaedic surgery, focusing on the top orthopaedic journals from 2020 to 2023. METHODS: Original research articles from 10 of the top orthopaedic journals were screened and analyzed for data-sharing statements (DSSs). Furthermore, we identified variables that were influential on the inclusion of DSSs in orthopaedic clinical studies, and thematically analyzed DSS content to identify prevalent themes. Lastly, corresponding authors were contacted to assess their willingness to share their data. RESULTS: Of the 1,084 reviewed articles, only 14% included a DSS. The Journal of Bone & Joint Surgery demonstrated the highest proportion of articles with a DSS. Over time, clinical trials exhibited an increasing trend in DSS adoption, contrasting with consistently low rates among cohort studies. Thematic analysis identified the gatekeeper role and conditional data availability as predominant themes in orthopaedic DSSs. Of the 115 emails sent to corresponding authors, only 22 (19.1%) yielded responses, and of those who responded, only 12 (54.5%) expressed a willingness to share their data. CONCLUSIONS: Our findings underscore a substantial disparity in data-sharing practices across orthopaedic journals, highlighting the need for standardization and mandates for DSSs. Adopting the Transparency and Openness Promotion (TOP) Guidelines can enhance accountability and foster a culture of open science within the field. By addressing these shortcomings, orthopaedic journals can improve research reproducibility and advance scientific knowledge effectively.

OBJECTIVE: To examine the current state of data-sharing practices in gastroenterology literature, focusing on data-sharing statements (DSS) and identifying influential factors on DSS inclusion. BACKGROUND: High-quality, reproducible research is crucial in addressing the widespread prevalence of gastrointestinal diseases. Data-sharing practices enable researchers to access studies more easily, enhancing reproducibility. Our study aims to analyse the inclusion and influence of DSS in top gastroenterology journals. METHODS: We conducted a cross-sectional analysis to examine the use and contents of DSS in gastroenterology clinical trials. Using Clarivate's Journal Citation Reports, we selected five leading gastroenterology journals. Then, we searched MEDLINE (PubMed) for original research articles published between 1 January 2018 and 31 December 2023. In a double-blind, duplicate manner, data were extracted on DSS presence, funding source, study design and open-access status. We then conducted a thematic analysis of all DSS. Additionally, authors were contacted and given 14 days to respond or share data to investigate adherence to their DSS. RESULTS: has the lowest percentage of DSS (33/256; 12.9%). Impact factor is a significant indicator for DSS (estimate=0.138, p=0.01). Finally, 'conditional data availability' was the most common data theme in our study (225/303; 74.3%). Over half (153/284; 53.9%) of the authors contacted did not respond to our request for sharing data. CONCLUSION: Our findings reveal significant variability in DSS inclusion and adherence among top gastroenterology journals. Journals with mandatory data-sharing policies demonstrated higher compliance, while open-access status and journal impact factor were positively associated with data-sharing practices. However, a notable gap remains in authors' follow-through on stated data-sharing commitments.