Journal of Analytical Atomic Spectrometry最新文献

The standard-of-care (SOC) first-line treatment for patients with recurrent or metastatic cervical cancer is chemotherapy with a platinum-based agent and paclitaxel, with or without bevacizumab, and with addition of an anti-PD-1 antibody in those with a PD-L1 combined positive score (CPS) ≥1. Now, data from the phase III COMPASSION-16 trial show that addition of the PD-1 × CTLA4 bispecific antibody cadonilimab to chemotherapy plus bevacizumab improves outcomes in this setting.

In this trial, conducted in China, 445 women were randomly allocated (1:1) to receive first-line chemotherapy with or without bevacizumab plus either cadonilimab or placebo. Progression-free survival (PFS) and overall survival (OS) were the co-primary end points.

We appreciate the interest of Wainberg and O’Reilly in our recently published News & Views article that critiques the design and reporting of results from the NAPOLI 3 trial (Nevala-Plagemann, C. & Garrido-Laguna, I. NALIRIFOX for metastatic pancreatic adenocarcinoma: hope or hype? Nat. Rev. Clin. Oncol. 21, 567–568 (2024))¹. In their Correspondence (Wainberg, Z. A. & O’Reilly, E. M. NALIRIFOX in the frontline for metastatic pancreatic cancer: evidence beyond NAPOLI 3. Nat. Rev. Clin. Oncol. https://doi.org/10.1038/s41571-024-00952-5 (2024))², they raise several points that we would like to address.

We read with interest the News & Views article by Nevala-Plagemann and Garrido-Laguna (Nevala-Plagemann, C. & Garrido-Laguna, I. NALIRIFOX for metastatic pancreatic adenocarcinoma: hope or hype? Nat. Rev. Clin. Oncol. 21, 567–568 (2024))¹. In this article, the authors question whether the addition of nanoliposomal irinotecan, 5-fluorouracil, leucovorin and oxaliplatin (NALIRIFOX) to therapeutic options constitutes true progress for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).

Patients with muscle-invasive bladder cancer (MIBC) typically undergo radical cystectomy with bilateral pelvic lymphadenectomy to achieve local disease control and identify pathological nodal metastases. The optimal extent of lymphadenectomy remains a matter of debate and many centres favour an extended approach, despite a lack of evidence from randomized trials. Now, results from the phase III SWOG S1011 trial demonstrate that standard lymphadenectomy provides similar survival outcomes and is safer than an extended procedure.

Patients with T2–4a N0–1 MIBC requiring radical cystectomy were randomly allocated to undergo standard (n = 300) versus extended (n = 292) bilateral pelvic lymphadenectomy. Standard pelvic lymphadenectomy involved removal of the external and internal iliac and obturator nodes. The extended procedure, in addition, involved removal of the common iliac nodes, node-bearing tissue in the presciatic region and presacral nodes. Surgeries were carried out by 36 surgeons who had performed ≥50 radical cystectomies in the previous 3 years and worked in high-volume centres (≥30 such procedures per year). Disease-free survival (DFS) was the primary end point.

RNA modifications are essential for human health — too much or too little of them leads to serious illnesses ranging from neurodevelopmental disorders to cancer. Technical advances in RNA modification sequencing are beginning to uncover the RNA targets of diverse RNA-modifying enzymes that are dysregulated in disease. However, the emerging transcriptome-wide maps of modified nucleosides installed by these enzymes should be considered as first drafts. In particular, a range of technical artefacts lead to false negatives — modified sites that are overlooked owing to technique-dependent, and often sequence-context-specific, ‘blind spots’. In this Review, we discuss potential sources of false negatives in sequencing-based RNA modification maps, propose mitigation strategies and suggest guidelines for transparent reporting of sensitivity to detect modified sites in profiling studies. Important considerations for recognition and avoidance of false negatives include assessment and reporting of position-specific sequencing depth, identification of protocol-dependent RNA capture biases and applying controls for false negatives as well as for false positives. Despite their limitations, emerging maps of RNA modifications reveal exciting and largely uncharted potential for post-transcriptional control of all aspects of RNA function.