Differences in standing behavior between Jersey and Holstein dairy cows during the periparturient period.

Jerseys are the second most popular breed in the US dairy industry, yet there are few studies that directly compare their behavior with Holsteins. The objective of this observational study was to describe differences in the standing behavior of healthy Jersey and Holstein dairy cows during the periparturient period. A total of 51 Jerseys (11 primiparous [PP] and 40 multiparous [MP]) and 36 Holsteins (8 PP, 28 MP) were used for this analysis.

Mixture Experimentation in Pharmaceutical Formulations: A Tutorial.

Mixture experimentation is commonly seen in pharmaceutical formulation studies, where the relative proportions of the individual components are modeled for effects on product attributes. The requirement that the sum of the component proportions equals 1 has given rise to the class of designs, known as mixture designs. The first mixture designs were published by Quenouille in 1953 but it took nearly 40 years for the earliest mixture design applications to be published in the pharmaceutical sciences literature by Kettaneh-Wold in 1991 and Waaler in 1992.

Targeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma.

Targeting Anaplastic lymphoma kinase (ALK) is a promising therapeutic strategy for aberrant ALK-expressing malignancies including neuroblastoma, but resistance to ALK tyrosine kinase inhibitors (ALK TKI) is a distinct possibility necessitating drug combination therapeutic approaches. Using high-throughput, genome-wide CRISPR-Cas9 knockout screens, we identify miR-1304-5p loss as a desensitizer to ALK TKIs in aberrant ALK-expressing neuroblastoma; inhibition of miR-1304-5p decreases, while mimics of this miRNA increase the sensitivity of neuroblastoma cells to ALK TKIs. We show that miR-1304-5p targets NRAS, decreasing cell viability via induction of apoptosis.

STAT3 couples activated tyrosine kinase signaling to the oncogenic core transcriptional regulatory circuitry of anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is an aggressive, CD30 T cell lymphoma of children and adults. ALK fusion transcripts or mutations in the JAK-STAT pathway are observed in most ALCL tumors, but the mechanisms underlying tumorigenesis are not fully understood. Here, we show that dysregulated STAT3 in ALCL cooccupies enhancers with master transcription factors BATF3, IRF4, and IKZF1 to form a core regulatory circuit that establishes and maintains the malignant cell state in ALCL.

Challenging our understanding of B-cell lymphomagenesis and risk: Paediatric high-grade B-cell lymphoma, not otherwise specified with a DDX3X::MLLT10 fusion and an IGH deletion.

We report a unique case of high-grade B-cell lymphoma, not otherwise specified in a 5-year-old child. Whole-genome sequencing revealed a DDX3X::MLLT10 fusion, usually seen in T-cell acute lymphoblastic leukaemia (ALL). This suggests the novel idea that MLLT10 fusions are capable of driving B-cell malignancies.