Infection or immunization can reprogram innate immune cells generating memory responses with broad protection against subsequent infection, a process referred to as "trained immunity." A new study by Stacy and colleagues demonstrates that, following acute infection, the commensal microbiota can also be "trained" to enhance colonization resistance against heterologous infection.Complex datasets provide opportunities for discoveries beyond their initial scope. Effective and rapid data sharing and management practices are crucial to realize this potential; however, they are harder to implement than post-publication access. Here, we introduce the concept of a "data sharing trust" to maximize the value of large datasets.Topologically associating domains (TADs) are fundamental units of three-dimensional (3D) nuclear organization. The regions bordering TADs-TAD boundaries-contribute to the regulation of gene expression by restricting interactions of cis-regulatory sequences to their target genes. TAD and TAD-boundary disruption have been implicated in rare-disease pathogenesis; however, we have a limited framework for integrating TADs and their variation across cell types into the interpretation of common-trait-associated variants. Here, we investigate an attribute of 3D genome architecture-the stability of TAD boundaries across cell types-and demonstrate its relevance to understanding how genetic variation in TADs contributes to complex disease. By synthesizing TAD maps across 37 diverse cell types with 41 genome-wide association studies (GWASs), we investigate the differences in disease association and evolutionary pressure on variation in TADs versus TAD boundaries. We demonstrate that genetic variation in TAD boundaries contributes more to complex-trait heritability, especially for immunologic, hematologic, and metabolic traits. We also show that TAD boundaries are more evolutionarily constrained than TADs. Next, stratifying boundaries by their stability across cell types, we find substantial variation. Compared to boundaries unique to a specific cell type, boundaries stable across cell types are further enriched for complex-trait heritability, evolutionary constraint, CTCF binding, and housekeeping genes. Thus, considering TAD boundary stability across cell types provides valuable context for understanding the genome's functional landscape and enabling variant interpretation that takes 3D structure into account.Genome-wide chromatin conformation capture technologies such as Hi-C are commonly employed to study chromatin spatial organization. In particular, to identify statistically significant long-range chromatin interactions from Hi-C data, most existing methods such as Fit-Hi-C/FitHiC2 and HiCCUPS assume that all chromatin interactions are statistically independent. Such an independence assumption is reasonable at low resolution (e.g., 40 kb bin) but is invalid at high resolution (e.g., 5 or 10 kb bins) because spatial dependency of neighboring chromatin interactions is non-negligible at high resolution. Our previous hidden Markov random field-based methods accommodate spatial dependency but are computationally intensive. It is urgent to develop approaches that can model spatial dependence in a computationally efficient and scalable manner. Here, we develop HiC-ACT, an aggregated Cauchy test (ACT)-based approach, to improve the detection of chromatin interactions by post-processing results from methods assuming independence. To benchmark the performance of HiC-ACT, we re-analyzed deeply sequenced Hi-C data from a human lymphoblastoid cell line, GM12878, and mouse embryonic stem cells (mESCs). Rituximab supplier Our results demonstrate advantages of HiC-ACT in improving sensitivity with controlled type I error. By leveraging information from neighboring chromatin interactions, HiC-ACT enhances the power to detect interactions with lower signal-to-noise ratio and similar (if not stronger) epigenetic signatures that suggest regulatory roles. We further demonstrate that HiC-ACT peaks show higher overlap with known enhancers than Fit-Hi-C/FitHiC2 peaks in both GM12878 and mESCs. HiC-ACT, effectively a summary statistics-based approach, is computationally efficient (∼6 min and ∼2 GB memory to process 25,000 pairwise interactions).Danny is the father of two boys with MEPAN syndrome and a member of Global Genes' RARE Foundation Alliance Leadership Council. We believe that IgG4 may have a role in the pathogenesis of Peyronie's disease (PD), and this role could be particularly beneficial for developing new strategies; therefore, we aimed to investigate the role of IgG4 in PD. This study included 3 groups with a total of 139 subjects (I) PD group (n=61), (II) control group (n=48), and (III) benign prostatic hyperplasia (BPH) group (n=30). IgG4 measurement was performed using the enzyme-linked immunosorbent assay. Plaque size, penile curvature, and the presence of concomitant impotence were evaluated in the PD group. Impotence was assessed based on the International Index of Erectile Function (IIEF). A significant difference was observed between the PD and control groups and between the PD and BPH groups with regard to IgG4 levels, while no significant difference was found between the BPH and control groups (p=0.0001, p=0.002, and p=0.07, respectively). The IgG4 levels were significantly higher in the PD than in the other groups. The cutoff value determined bategies. Future studies with larger patient series are needed to substantiate our findings.Rationale The transition to air-breathing at birth is a seminal respiratory event common to all humans, but the intrathoracic processes remain poorly understood. Objectives The objectives of this prospective, observational study were to describe the spatiotemporal gas flow, aeration and ventilation patterns within the lung in term neonates undergoing successful respiratory transition. Methods Electrical impedance tomography was used to image intrathoracic volume patterns for every breath until six minutes from birth in neonates born by elective cesearean section and not needing resuscitation. Breaths were classified by video data, and measures of lung aeration, tidal flow conditions and intrathoracic volume distribution calculated for each inflation. Measurements and Main results 1401 breaths from 17 neonates met all eligibility and data analysis criteria. Stable functional residual capacity was obtained by median (IQR) 43 (21, 77) breaths. Breathing patterns changed from predominantly crying (80.9% first minute) to tidal breathing (65.