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Extrachromosomal DNA is a common cause of oncogene amplification in cancer. The non-chromosomal inheritance of ecDNA enables tumors to rapidly evolve, contributing to treatment resistance and poor outcome for patients. The transcriptional context in which ecDNAs arise and progress, including chromosomally-driven transcription, is incompletely understood. We examined gene expression patterns of 870 tumors of varied histological types, to identify transcriptional correlates of ecDNA. Here, we show that ecDNA-containing tumors impact four major biological processes. Specifically, ecDNA-containing tumors up-regulate DNA damage and repair, cell cycle control, and mitotic processes, but down-regulate global immune regulation pathways. Taken together, these results suggest profound alterations in gene regulation in ecDNA-containing tumors, shedding light on molecular processes that give rise to their development and progression.

A non-contact slip ring is proposed in this paper. The bidirectional simultaneous wireless power and data transfer (BD-SWPDT) technology is utilized to transfer power and data bidirectionally. A bidirectional constant-voltage LC hybrid compensation topology is proposed, which utilizes the LC series parallel structure to have different equivalent models at different frequencies. By using different operating frequencies for forward and reverse power transfer, the system's forward and reverse transfer can be equivalent to different constant-voltage output compensation topologies. The resonant parameters of the system are designed to achieve consistent voltage gain for forward and reverse power transfer. And based on this topology, a data carrier injection method is designed to achieve high Signal Noise Ratio (SNR) simultaneous data transfer. To improve the flexibility of non-contact slip ring installation, a caliper-type coupling structure is proposed. Finally, the feasibility of the proposed method is verified through experiments, achieving a forward and reverse output power of 200 W and half duplex communication with a data rate of 19.2 kbps. [ABSTRACT FROM AUTHOR]

To explore whether rs2073244 at PAX9 increased susceptibility for full-term low birth weight infants and whether indoors passive smoking exposure has a combined effect with rs2073244 on newborn low birth weight (LBW), a 1:2 paired case–control study of LBW newborns was conducted at Xiamen University Affiliated Women and Children’s Hospital from March 2010 to October 2013. The rate of indoor passive smoking exposure in the LBW group was higher than it in the NBW group (p = 0.019). GG of PAX9 rs2073244 decreased the risk of LBW [OR = 0.38, 95% CI: (0.15-0.98)] and smaller HC [OR = 0.44, 95% CI:(0.20-0.98)]. The relative excess risk for LBW contributed by the additive interaction between the rs2073244 risk genotypes AG/AA and mother pregnancy passive smoking exposure was 10.679 (95%CI 1.728–65.975). Our study suggested that the AG/AA genotype of PAX9 rs2073244 might be a risk factor for LBW of full-term newborns, especially in maternal passive smoking. [ABSTRACT FROM AUTHOR]

Despite the long-term negative outcomes associated with restraining and secluding students, these practices are frequently used in schools, with disproportionate use on students with disabilities. Based on recent guidance from the U.S. Justice Department's Civil Rights Division, misusing these practices violates student rights under the Americans with Disabilities Act. This policy document aligns with research findings that seclusion and physical restraint should only be used in emergencies and only as a last resort. This article intends to provide three systems-level changes to reduce or eliminate the use of restraint and seclusion in schools: implement schoolwide positive behavior intervention and supports, support students in crisis, and include families in an ongoing collaboration process. [ABSTRACT FROM AUTHOR]

Background and Aims: Biliary atresia (BA) is a devastating fibroinflammatory biliary disease that is the leading indication for pediatric liver transplants worldwide. Although cholangiocytes are the primary target cells, the pathogenic mechanisms involving cholangiocytes remain elusive. Here, we aimed to characterize the pathogenic role of cholangiocytes in BA., Approach and Results: Integration of single-cell RNA sequencing of 12 liver tissues (from 9 BA and 3 controls) and the spatial transcriptome of another four liver sections (from 2 BA and 2 controls) provided a comprehensive spatial liver cell atlas of BA. In particular, we identified a cholangiocyte-enriched spatial niche with infiltration of activated HSCs, activated portal fibroblasts, macrovascular endothelial cells, and TREM2 + macrophages that were elevated in the portal triad of BA. This niche was positively correlated with bile duct profiles, liver fibrosis, and poor survival in 2 independent cohorts of patients with BA. Using integrative bioinformatics analyses to mine the cell-cell communication and regulatory network in BA cholangiocytes, we uncovered the fibroinflammatory phenotype of cholangiocytes with TNFSF12-TNFRSF12A as a significant signal. Genetic ablation or blockade of TNFRSF12A suppresses liver injury, inflammation, and bile duct profiles in a mouse model of disease. Using human biliary organoids, we revealed that BA organoids expressed higher levels of CCL2 in response to TNFSF12 stimulation and promoted monocyte chemotaxis via the CCL2-CCR2 axis., Conclusions: Pathogenic cholangiocytes-enriched niche identifies TNFRSF12A as a potential therapeutic target for BA., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Focal gene amplification, such as extrachromosomal DNA (ecDNA), plays an important role in cancer development and therapy resistance. While sequencing-based methodologies enable an unbiased identification of ecDNA, cytogenetic-based techniques, such as fluorescence in situ hybridization (FISH), remain time and cost-effective for identifying ecDNA in clinical specimens. The application of FISH in formalin-fixed paraffin-embedded (FFPE) tissue samples offers a unique avenue for detecting amplified genes, particularly when viable specimens are not available for karyotype examination. However, there is a lack of consensus procedures for this technique. This protocol provides comprehensive, fully optimized, step-by-step instructions for conducting FISH to detect gene amplification, including ecDNA, in FFPE tissue samples which present unique challenges that this protocol aims to overcome and standardize. By following this protocol, researchers can reproducibly acquire high-quality imaging data to assess gene amplification.

Extrachromosomal DNA is a common cause of oncogene amplification in cancer. The non-chromosomal inheritance of ecDNA enables tumors to rapidly evolve, contributing to treatment resistance and poor outcome for patients. The transcriptional context in which ecDNAs arise and progress, including chromosomally-driven transcription, is incompletely understood. We examined gene expression patterns of 870 tumors of varied histological types, to identify transcriptional correlates of ecDNA. Here, we show that ecDNA-containing tumors impact four major biological processes. Specifically, ecDNA-containing tumors up-regulate DNA damage and repair, cell cycle control, and mitotic processes, but down-regulate global immune regulation pathways. Taken together, these results suggest profound alterations in gene regulation in ecDNA-containing tumors, shedding light on molecular processes that give rise to their development and progression., Competing Interests: ML, SJ No competing interests declared, JL J.L. receives compensation as a consultant for Boundless Bio, HC Reviewing editor, eLife, SW S. Wu is a member of the scientific advisory board of Dimension Genomics Inc, PM P.S.M. is a co-founder and advisor of Boundless Bio. J.L. receives compensation as a consultant for Boundless Bio, VB V.B. is a co-founder, paid consultant, SAB member and has equity interest in Boundless Bio, Inc and Abterra Biosciences, Inc, (© 2023, Lin et al.)