Phase I study of CD19 CAR T-cell therapy harboring a fully human scFv in CAR-naïve adult B-ALL patients.

CD19-directed chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy elicits high response rates but fails to induce durable responses in most adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In a previous clinical trial (NCT01865617), we observed anti-CAR immune responses associated with impaired in vivo CAR T-cell expansion after second infusions. Because these CD8+ T-cell responses were predominantly directed at peptides derived from the murine single chain variable fragment (scFv) in the CAR, we conducted a clinical trial investigating the safety and efficacy of CD19 CAR T-cells engineered with a CAR incorporating a fully human scFv (JCAR021) in adults with R/R B-ALL (NCT03103971).

The Specialized Donor Care Facility Model Improves Operating Room Efficiency.

Background: Organ procurement organizations coordinate organ donation through 2 distinct models of care: the conventional model, in which donors are managed at hospitals where brain death occurs, and the specialized donor care facility (SDCF) model, where brain dead donors are transferred to a freestanding facility. The aim of this study is to compare operating room efficiency for procurements between the SDCF and conventional models of care.

Methods: We performed a prospective analysis of operating room efficiency between thoracic donor procurement operations performed at a SDCF and other organ procurement organizations using the conventional model of care.

Long-duration type 1 diabetes is associated with deficient cortical bone mechanical behavior and altered matrix composition in human femoral bone.

Type 1 diabetes (T1D) is associated with an increased risk of hip fracture beyond what can be explained by reduced bone mineral density, possibly due to changes in bone material from accumulation of advanced glycation end-products (AGEs) and altered matrix composition, though data from human cortical bone in T1D are limited. The objective of this study was to evaluate cortical bone material behavior in T1D by examining specimens from cadaveric femora from older adults with long-duration T1D (≥50 yr; n = 20) and age- and sex-matched nondiabetic controls (n = 14). Cortical bone was assessed by mechanical testing (4-point bending, cyclic reference point indentation, impact microindentation), AGE quantification [total fluorescent AGEs, pentosidine, carboxymethyl lysine (CML)], and matrix composition via Raman spectroscopy.

Chromosome-Scale Genomes of the Flightless Caterpillar Hunter Beetles Calosoma tepidum and Calosoma wilkesii From British Columbia (Coleoptera: Carabidae).

The giant ground beetle genus Calosoma (Coleoptera, Carabidae) comprises ca. 120 species distributed worldwide. About half of the species in this genus are flightless due to a process of wing reduction likely resulting from the colonization of remote habitats such as oceanic islands, highlands, and deserts.