A protocol for a systematic review of standardised tools used in perinatal death review programmes [version 2; peer review: 2 approved]

Introduction: Perinatal mortality encompasses stillbirths and early neonatal deaths. A perinatal death surveillance and response cycle has been recommended by the World Health Organization for use in the review of perinatal deaths. The main components of the cycle include identifying and reporting perinatal deaths, and reviewing the deaths, including potentially modifiable factors, in order to measure and improve quality of care provided to women and infants. There is no consensus on the best way to design, implement and conduct perinatal death reviews. This systematic review aims to identify standardised tools that are used to review perinatal deaths.  Objectives: The primary aim of this protocol is to describe methodology for a systematic search of the literature to identify standardised tools that are used to review perinatal deaths in upper-middle to high-income countries. Review tools may include standardised checklists, forms, frameworks or other structured documents used to review perinatal deaths. Review tools will be appraised to see if they incorporate the identification of modifiable factors in perinatal deaths and establish recommendations for improvements to quality of care provided. Methods: A systematic review of the literature will be performed to identify peer-reviewed publications and grey literature describing the use of perinatal mortality review tools without date restrictions. The eligibility of review tools for inclusion will be based on inclusion and exclusion criteria applied to the SPIDER framework. Data will be extracted based on the structure and content of included review tools, and the tools will be appraised using the Appraisal of Guidelines Research and Evaluation Health Systems (AGREE-HS) instrument. Conclusion: This systematic review protocol for identifying and appraising standardised perinatal mortality review tools may help to establish the optimal way to structure a standardised review process for perinatal mortality in middle- to high-income countries. PROSPERO registration: CRD4202232687

Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth

The Hippo pathway is an important regulator of organ size and tumorigenesis. It is unclear, however, how Hippo signaling provides the cellular building blocks required for rapid growth. Here, we demonstrate that transgenic zebrafish expressing an activated form of the Hippo pathway effector Yap1 (also known as YAP) develop enlarged livers and are prone to liver tumor formation. Transcriptomic and metabolomic profiling identify that Yap1 reprograms glutamine metabolism. Yap1 directly enhances glutamine synthetase (glul) expression and activity, elevating steady-state levels of glutamine and enhancing the relative isotopic enrichment of nitrogen during de novo purine and pyrimidine biosynthesis. Genetic or pharmacological inhibition of GLUL diminishes the isotopic enrichment of nitrogen into nucleotides, suppresses hepatomegaly and the growth of liver cancer cells. Consequently, Yap-driven liver growth is susceptible to nucleotide inhibition. Together, our findings demonstrate that Yap1 integrates the anabolic demands of tissue growth during development and tumorigenesis by reprogramming nitrogen metabolism to stimulate nucleotide biosynthesis

What is known about pregnancy and motherhood among women doctors working in the EU? A scoping review protocol

Background: Negative experiences around family planning, pregnancy and motherhood can have several impacts on women doctors and the health system. Women doctors experience pregnancy complications or loss, infertility, and workplace discrimination. They are also more likely to experience burnout which is associated with poor productivity, increased turnover, increased costs, and poorer healthcare access for patients. Previous reviews relating to pregnancy and motherhood among doctors have been dominated by research from North America. The proposed review aims to synthesise existing research on experiences of family planning, pregnancy, and motherhood among women doctors working in the EU. Methods: The scoping review will be conducted in accordance with best practice and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Electronic databases will be searched including MEDLINE (Ovid), CINAHL (EBSCO), Academic Search Complete (EBSCO), PsycInfo (EBSCO), and Web of Science (ISI). Backwards and forwards citation chasing of all included articles will also be performed. The reference lists of a number of existing, relevant reviews will also be screened. A sample of articles will be screened by two researchers and the data extraction will be conducted in duplicate. Narrative synthesis will be used to summarise the resulting data. Conclusions: This proposed review is crucial for developing an understanding of the experiences of women doctors in the EU. It is anticipated that the resulting data will inform evidence-based recommendations for improving the experiences of women doctors