Highlights d Endogenous and recombinant Tinagl1 suppress growth and metastasis of breast cancer d Tinagl1 inhibits EGFR and integrin/FAK activation through distinct mechanisms d Tinagl1 level negatively correlates with EGFR and FAK activation in TNBC d Tinagl1 is a good prognosis marker and candidate therapeutic agent for TNBC

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To identify pan-ancestry and ancestry-specific loci associated with attempting suicide among veterans, we conducted a genome-wide association study (GWAS) of suicide attempts within a large, multi-ancestry cohort of U.S. veterans enrolled in the Million Veterans Program (MVP). Cases were defined as veterans with a documented history of suicide attempts in the electronic health record (EHR; N =14,089) and controls were defined as veterans with no documented history of suicidal thoughts or behaviors in the EHR ( N =395,064). GWAS was performed separately in each ancestry group, controlling for sex, age and genetic substructure. Pan-ancestry risk loci were identified through meta-analysis and included two genome-wide significant loci on chromosomes 20 ( p =3.64×10 −9 ) and 1 ( p =3.69×10 −8 ). A strong pan-ancestry signal at the Dopamine Receptor D2 locus ( p =1.77×10 −7 ) was also identified and subsequently replicated in a large, independent international civilian cohort ( p =7.97×10 −4 ). Additionally, ancestry-specific genome-wide significant loci were also detected in African-Americans, European-Americans, Asian-Americans, and Hispanic-Americans. Pathway analyses suggested overrepresentation of many biological pathways with high clinical significance, including oxytocin signaling, glutamatergic synapse, cortisol synthesis and secretion, dopaminergic synapse, and circadian rhythm. These findings confirm that the genetic architecture underlying suicide attempt risk is complex and includes both pan-ancestry and ancestry-specific risk loci. Moreover, pathway analyses suggested many commonly impacted biological pathways that could inform development of improved therapeutics for suicide prevention.

The EVAHEART LVAS caused significantly less vWF degradation than the HeartMate II in a mock circulatory loop with whole human blood. LVAD design features may minimize vWF degradation. These data may inform the design and operation of next-generation LVADs to minimize blood trauma.

Abnormal intestinal vascular architecture and LVAD-associated vWF degradation were consistent findings in multiple species supported with a continuous-flow LVAD. These are the first direct evidence that LVAD support causes gastrointestinal angiodysplasia. Pathologic vWF metabolism may be a mechanistic link between LVAD support, abnormal angiogenesis, gastrointestinal angiodysplasia, and bleeding.