Beyond the marrow:insights from comprehensive next-generation sequencing of extramedullary multiple myeloma tumors

Extramedullary multiple myeloma (EMM) is an aggressive form of multiple myeloma (MM). This study represents the most comprehensive next-generation sequencing analysis of EMM tumors (N = 14) to date, uncovering key molecular features and describing the tumor microenvironment. We observed the co-occurrence of 1q21 gain/amplification and MAPK pathway mutations in 79% of EMM samples, suggesting that these are crucial mutational events in EMM development. We also demonstrated that patients with mutated KRAS and 1q21 gain/amplification at the time of diagnosis have a significantly higher risk of EMM development (HR = 2.4, p = 0.011) using data from a large CoMMpass dataset. We identified downregulation of CXCR4 and enhanced cell proliferation, along with reduced expression of therapeutic targets (CD38, SLAMF7, GPRC5D, FCRH5), potentially explaining diminished efficacy of immunotherapy. Conversely, we identified significantly upregulated EZH2 and CD70 as potential future therapeutic options. For the first time, we report on the tumor microenvironment of EMM, revealing CD8+ T cells and NK cells as predominant immune effector cells using single-cell sequencing. Finally, this is the first longitudinal study in EMM revealing the molecular changes from the time of diagnosis to EMM relapse.</p

(Certified) Humane Violence? Animal Production, the Ambivalence of Humanizing the Inhumane, and What International Humanitarian Law Has to Do with It

The chapter draws a comparison with the self-certifying of production methods as ‘humane’ or animal-friendly in the labelling of animal products—that is, according to companies’ own self-imposed codes of conduct. It likens the idea of humanizing animal slaughter, factory farms, and other forms of production to the notion of humanizing warfare. Like international humanitarian law (IHL), animal welfare law is marked by the tension inherent in its attempt to humanize innately inhumane practices. Given these parallels, the analysis of animal welfare law might benefit from existing insights into the potential and limits of IHL. Both areas of law endorse a principle of ‘humanity’ while arguably facilitating and legitimizing the use of violence, and might thereby ultimately perpetuate the suffering of living beings. The implicit justification of violence percolating from the IHL-like animal ‘protection’ laws could only be outweighed by complementing this body of law with a ius contra bellum for animals

Non-infectious factors associated with macroscopic and microscopic lung lesions in slaughter pigs from farrow-to-finish herds.

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