Failures of neural tube closure are common and serious birth defects, yet we have a poor understanding of the interaction of genetics and cell biology during neural tube closure. Additionally, mutations that cause neural tube defects (NTDs) tend to affect anterior or posterior regions of the neural tube but rarely both, indicating a regional specificity to NTD genetics. To better understand the regional specificity of cell behaviors during neural tube closure, we analyzed the dynamic localization of actin and N-cadherin via high-resolution tissue-level time-lapse microscopy during Xenopus neural tube closure. To investigate the regionality of gene function, we generated mosaic mutations in shroom3, a key regulator or neural tube closure. This new analytical approach elucidates several differences between cell behaviors during cranial/anterior and spinal/posterior neural tube closure, provides mechanistic insight into the function of shroom3, and demonstrates the ability of tissue-level imaging and analysis to generate cell biological mechanistic insights into neural tube closure.

Patient-derived xenografts (PDXs) are frequently used as preclinical models, but their recapitulation of tumour metabolism in patients has not been closely examined. We developed a parallel workflow to analyse [U-¹³C]glucose tracing and metabolomics data from patient melanomas and matched PDXs. Melanomas from patients have substantial TCA cycle labelling, similar to levels in human brain tumours. Although levels of TCA cycle labelling in PDXs were similar to those in the original patient tumours, PDXs had higher labelling in glycolytic metabolites. Through metabolomics, we observed consistent alterations of 100 metabolites among PDXs and patient tumours that reflected species-specific differences in diet, host physiology and microbiota. Despite these differences, most of nearly 200 PDXs retained a ‘metabolic fingerprint’ largely durable over six passages and often traceable back to the patient tumour of origin. This study identifies both high- and low-fidelity metabolites in the PDX model system, providing a resource for cancer metabolism researchers.

Introduction: The World Health Organization (WHO) initiated a unified effort to address skin‐related neglected tropical diseases (NTDs) in 2017. This effort increased attention and resources allocated toward decreasing the burden of tropical skin diseases. It emphasized an “integrated approach” to detect and treat multiple co‐existing NTDs at once. This article will outline new diagnostic tests, treatment options, and vaccine development for neglected tropical skin diseases since the initiative began.Data Sources: A PubMed search of clinical trials, randomized controlled trials, systematic reviews, and meta‐analyses published since 2017 was performed.Results: The WHO's initiative has already seen success, increasing the surveillance of leprosy and the distribution of treatment for yaws. It has encouraged the development of new point‐of‐care tests and better‐tolerated treatment options. It has also brought new challenges, with the rise of resistant organisms. Development of point‐of‐care DNA‐RNA‐based testing may improve drug resistance monitoring. New vaccines are needed for long‐term control of skin NTDs in areas with high transmission rates.

Lymphedema is a chronic condition marked by swelling in the body’s soft tissues due to impaired or damaged lymphatic function. Lymphedema is estimated to affect about 1 in 1000 in the United States and 1.4 per 1000 based on two European studies. Lymphedema diagnosis relies on clinical visual assessment by physicians, and the quantitative evaluation of lymphatic function is not widely employed due to the lack of standardized and validated metrics. Lymphoscintigraphy is considered the practical gold standard for evaluating lymphedema. With the emergence of advanced surgical therapies, there is a growing demand for quantitative evaluation metrics to objectively evaluate treatment response. To address this unmet need, we reviewed various methods of quantitative lymphoscintigraphy (qLSG) that were used for assessing lymphedema. We found that multiple qLSG approaches have been described. Moreover, the protocols vary widely in terms of tracer type, injection route, dosage, and exercise interventions. We compared the quantitative assessment strategies and highlighted the approaches that may help provide a more objective lymphedema diagnosis and follow-up.

In the Research Letter titled “Hidradenitis Suppurativa in Older Adults,” published December 14, 2022, the Conflict of Interest Disclosures have been corrected

Baldwin AT, Kim JH, Seo H, Wallingford JB. 2022. Global analysis of cell behavior and protein dynamics reveals region-specific roles for Shroom3 and N-cadherin during neural tube closure. eLife 11:e66704. doi: 10.7554/eLife.66704.