Forty years of the Ellis–Baldwin test
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Intravenous sedation for adults with profound acquired brain injury undergoing dental treatment – a seven-year service evaluation
Dental treatment may not be possible for patients with a profound acquired brain injury without pharmacological support. Intravenous (IV) sedation with midazolam is a widely accepted, safe, and effective mode of treatment for people with a disability, but there is limited evidence in this patient cohort.
Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia
X-linked hypophosphataemia (XLH) is a rare metabolic bone disorder caused by pathogenic variants in the PHEX gene, which is predominantly expressed in osteoblasts, osteocytes and odontoblasts. XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. Patients with XLH should be provided with multidisciplinary care organized by a metabolic bone expert. Historically, these patients were treated with frequent doses of oral phosphate supplements and active vitamin D, which was of limited efficiency and associated with adverse effects. However, the management of XLH has evolved in the past few years owing to the availability of burosumab, a fully humanized monoclonal antibody that neutralizes circulating FGF23. Here, we provide updated clinical practice recommendations for the diagnosis and management of XLH to improve outcomes and quality of life in these patients.
Integrating single-cell RNA and T cell/B cell receptor sequencing with mass cytometry reveals dynamic trajectories of human peripheral immune cells from birth to old age
A comprehensive understanding of the evolution of the immune landscape in humans across the entire lifespan at single-cell transcriptional and protein levels, during development, maturation and senescence is currently lacking. We recruited a total of 220 healthy volunteers from the Shanghai Pudong Cohort (NCT05206643), spanning 13 age groups from 0 to over 90 years, and profiled their peripheral immune cells through single-cell RNA-sequencing coupled with single T cell and B cell receptor sequencing, high-throughput mass cytometry, bulk RNA-sequencing and flow cytometry validation experiments. We revealed that T cells were the most strongly affected by age and experienced the most intensive rewiring in cell–cell interactions during specific age. Different T cell subsets displayed different aging patterns in both transcriptomes and immune repertoires; examples included GNLY+CD8+ effector memory T cells, which exhibited the highest clonal expansion among all T cell subsets and displayed distinct functional signatures in children and the elderly; and CD8+ MAIT cells, which reached their peaks of relative abundance, clonal diversity and antibacterial capability in adolescents and then gradually tapered off. Interestingly, we identified and experimentally verified a previously unrecognized ‘cytotoxic’ B cell subset that was enriched in children. Finally, an immune age prediction model was developed based on lifecycle-wide single-cell data that can evaluate the immune status of healthy individuals and identify those with disturbed immune functions. Our work provides both valuable insights and resources for further understanding the aging of the immune system across the whole human lifespan.
Crop rotation increases Tibetan barley yield and soil quality on the Tibetan Plateau
Tibetan barley (Hordeum vulgare) accounts for over 70% of the total food production in the Tibetan Plateau. However, continuous cropping of Tibetan barley causes soil degradation, reduces soil quality and causes yield decline. Here we explore the benefits of crop rotation with wheat and rape to improve crop yield and soil quality. We conducted 39 field experiments on the Tibetan Plateau, comparing short-term (≤5 years), 5–10 years and long-term (≥10 years) continuous cropping with rotation of Tibetan barley with wheat or rape. Results showed that Tibetan barley–wheat and Tibetan barley–rape rotations increased yields by 17% and 12%, respectively, while improving the soil quality index by 11% and 21%, compared with long-term continuous cropping. Both Tibetan barley rotations with wheat and rape improved soil quality and consequently yield, mainly by increasing soil microbial biomass nitrogen and microbial biomass carbon and decreasing pH. By contrast, long-term continuous cropping led to decreased soil organic matter, lower microbial biomass nitrogen and increased pH, contributing to yield decline. The benefits of rotations on crop yield and soil quality increased over time. Implementing crop rotation with wheat or rape thus offers a sustainable agricultural strategy for improving food security on the Tibetan Plateau.
Integration of clinical outcomes and molecular features in extramedullary disease in multiple myeloma
Multiple myeloma (MM) remains incurable despite novel therapeutics. A major contributor to the development of relapsed/refractory and resistant MM is extraosseous extramedullary disease (EMD), whose molecular biology is still not fully understood. We analyzed 528 MM patients who presented to our institution between 2014 and 2021 and who had undergone molecular testing. We defined EMD as organ plasmacytoma distinct from bones and evaluated patients for the development of EMD with the goal of defining their molecular characteristics. Here, we show that RAS/BRAF mutations are likely essential for the development of EMD. Our results also indicate that the underlying reason for the negative outcomes in patients with poor prognostic factors such as duplication 1q and deletion 17p is largely due to the development of EMD. However, the presence of TP53 mutation remains a poor prognostic factor regardless of EMD development. Furthermore, mutation sites of TP53 were different between EMD versus non-EMD patients, with gain-of-function mutations enriched in patients with EMD. Our data highlights distinct molecular abnormalities in patients with EMD and provides potential mechanistic insights for novel therapeutic targets for the future.
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