Introduction: Thiopurine S-methyltransferase (TPTM) is a well known biomarker for thiopurine-induced leucopenia, which has limited value in Asia. Instead, NUDT15C415T is a promising predictor in Asia. Aims:To explore whether an optimised strategy based on NUDT15 C415T genotypes affects thiopurine-induced leucopenia, as well as efficacy in Chinese patients with Crohn's disease. Methods:Patients with Crohn's disease and indications for thiopurines were included from two hospitals in China. They were randomly assigned to either the intervention or the control group. In the intervention group, those with genotype CC received a standard dose (control group), those with CT genotype received 50% of the standard dose, those with TT genotype received alternative drugs. The primary endpoint was thiopurine-induced leucopenia (<3.5 × 10 9 /L). Secondary outcomes were the incidence of other adverse events and the efficacy for maintaining steroid-free remission at week 36. Results:The rate of thiopurine-induced leucopenia was lower in the intervention group (n = 52) than in the control group (n = 66) (23.7% vs 32.4%, P = 0.049, RR = 0.73, 95% CI 0.53-1.00). In CT subgroup, the incidence of leucopenia in the intervention group (n = 10) was significantly lower than in the control group (n = 28) (31.3% vs 65.1%, RR = 0.48, 95% CI 0.28-0.84). Neither other adverse events nor treatment efficacy was significantly different between the two groups during follow-up.Conclusions: Among Chinese patients with Crohn's disease, dose optimisation by NUDT15 C415T reduced the rate of thiopurine-induced leucopenia, without significant influence on efficacy. Using 50% dose reduction for heterozygotes, and alternative drugs for homozygotes, are practicable strategies.Clinical trial number: NCT02929706.

Of the 220 lines examined to date, approximately 15% have a significant variation (high or low) by μCT, most of which are not identified by the IMPC screen. Significant dimorphism between the sexes and bone compartments adds to the complexity of the skeletal findings. The μCT information that is posted at www.bonebase.org can group KOMP lines with similar morphological features. The histological data is presented in a graphic form that associates the cellular features with a specific anatomic group. The web portal presents a bone-centric view appropriate for the skeletal biologist/clinician to organize and understand the large number of genes that can influence skeletal health. Cataloging the relative severity of each variant is the first step towards compiling the dataset necessary to appreciate the full polygenic basis of degenerative bone disease.

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The Human BioMolecular Atlas Program (HuBMAP) aims to create a multi-scale spatial atlas of the healthy human body at single-cell resolution by applying advanced technologies and disseminating resources to the community. As the HuBMAP moves past its first phase, creating ontologies, protocols and pipelines, this Perspective introduces the production phase: the generation of reference spatial maps of functional tissue units across many organs from diverse populations and the creation of mapping tools and infrastructure to advance biomedical research.HuBMAP was founded with the goal of establishing state-of-the-art frameworks for building spatial multiomic maps of non-diseased human organs at single-cell resolution 1 . During the first phase (2018)(2019)(2020)(2021)(2022), the priorities of the project included the validation and development of assay platforms; workflows for data processing, management, exploration and visualization; and the establishment of protocols, quality control standards and standard operating procedures. Extensive infrastructure was established through a coordinated effort among the various HuB-MAP integration, visualization and engagement teams, tissue-mapping centres, technology and tools development and rapid technology implementation teams and working groups 1 . Single-cell maps, predominantly consisting of two-dimensional (2D) spatial data as well as data from dissociated cells, were generated for several organs. The HuBMAP Data Portal (https://portal.hubmapconsortium.org) was established for open access to experimental tissue data and reference atlas data.The infrastructure was augmented with software tools for tissue data registration, processing, annotation, visualization, cell segmentation and automated annotation of cell types and cellular neighbourhoods from spatial data. Computational methods were developed for integrating multiple data types across scales and interpretation 2 . Standard reference terminology and a common coordinate framework spanning anatomical to biomolecular scales were established to ensure interoperability across organs, research groups and consortia 3 . Guidelines to capture high-quality multiplexed spatial data 4 were established including validated panels of cell-and structure-specific antibodies 5 . The first phase produced a large number of manuscripts (https://commonfund.nih.gov/ publications?pid=43) including spatially resolved single-cell maps [6][7][8][9][10][11] .The production phase of HuBMAP was launched in the autumn of 2022. The focus is on scaling data production spanning diverse biological variables (for example, age and ethnicity) and deployment and enhancement of analytical, visualization and navigational tools to generate high-resolution 3D accessible maps of major functional tissue units from more than 20 organs. This phase involves over 60 institutions and 400 researchers with opportunities for active intra-and inter-consortia collaborations and building a foundational resource for new biological insights and precision medicine. Below, ...

In this paper, we study the optimal proportional reinsurance problem in a risk model with two dependent classes of insurance business, where the two claim number processes are correlated through a common shock component, and the criterion is to minimise the probability of drawdown, namely, the probability that the value of the surplus process reaches some fixed proportion of its maximum value to date. By the method of maximising the ratio of drift of a diffusion divided to its volatility squared, and the technique of stochastic control theory and the corresponding Hamilton–Jacobi–Bellman equation, we investigate the optimisation problem in two different cases. Furthermore, we constrain the reinsurance proportion in the interval [0,1] for each case, and derive the explicit expressions of the optimal proportional reinsurance strategy and the minimum probability of drawdown. Finally, some numerical examples are presented to show the impact of model parameters on the optimal results.