Inducible localized delivery of an anti-PD-1 scFv enhances anti-tumor activity of ROR1 CAR-T cells in TNBC.

Background: Chimeric antigen receptor (CAR)-T cells can induce powerful immune responses in patients with hematological malignancies but have had limited success against solid tumors. This is in part due to the immunosuppressive tumor microenvironment (TME) which limits the activity of tumor-infiltrating lymphocytes (TILs) including CAR-T cells. We have developed a next-generation armored CAR (F i-CAR) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), which is expressed at high levels in a range of aggressive tumors including poorly prognostic triple-negative breast cancer (TNBC).

Respiratory virus coinfections with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) continue to be rare one year into the coronavirus disease 2019 (COVID-19) pandemic in Alberta, Canada (June 2020-May 2021).

To assess the burden of respiratory virus coinfections with severe acute respiratory coronavirus virus 2 (SARS-CoV-2), this study reviewed 4,818 specimens positive for SARS-CoV-2 and tested using respiratory virus multiplex testing. Coinfections with SARS-CoV-2 were uncommon (2.8%), with enterovirus or rhinovirus as the most prevalent target (88.

Targeted Clinical Interventions for Reducing Pediatric Readmissions.

Background: In this interventional study, we addressed the selection and application of clinical interventions on pediatric patients identified as at risk by a predictive model for readmissions.

Methods: A predictive model for readmissions was implemented, and a team of providers expanded corresponding clinical interventions for at-risk patients at a freestanding children's hospital. Interventions encompassed social determinants of health, outpatient care, medication reconciliation, inpatient and discharge planning, and postdischarge calls and/or follow-up.

Machine learning and artificial intelligence research for patient benefit: 20 critical questions on transparency, replicability, ethics, and effectiveness.

Machine learning, artificial intelligence, and other modern statistical methods are providing new opportunities to operationalise previously untapped and rapidly growing sources of data for patient benefit. Despite much promising research currently being undertaken, particularly in imaging, the literature as a whole lacks transparency, clear reporting to facilitate replicability, exploration for potential ethical concerns, and clear demonstrations of effectiveness. Among the many reasons why these problems exist, one of the most important (for which we provide a preliminary solution here) is the current lack of best practice guidance specific to machine learning and artificial intelligence.

Novel Bispecific Domain Antibody to LRP6 Inhibits Wnt and R-spondin Ligand-Induced Wnt Signaling and Tumor Growth.

Unlabelled: Aberrant WNT signaling is associated with the formation and growth of numerous human cancer types. The low-density lipoprotein receptor-related protein 6 (LRP6) is the least redundant component of the WNT receptor complex with two independent WNT ligand-binding sites. Using domain antibody (dAb) technology, a bispecific antibody (GSK3178022) to LRP6 was identified that is capable of blocking stimulation in the presence of a range of WNT and R-spondin (RSPO) ligands in vitro GSK3178022 was also efficacious in reducing WNT target gene expression in vivo, in both cancer cell line and patient-derived xenograft models, and delays tumor growth in a patient-derived RSPO fusion model of colorectal cancer.

Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis.

We aimed to develop a quantitative antibody-based near infrared fluorescence (NIRF) approach for the imaging of oxidized LDL in atherosclerosis. LO1, a well- characterized monoclonal autoantibody that reacts with malondialdehyde-conjugated LDL, was labeled with a NIRF dye to yield LO1-750. LO1-750 specifically identified necrotic core in ex vivo human coronary lesions.

Explicet: graphical user interface software for metadata-driven management, analysis and visualization of microbiome data.

Studies of the human microbiome, and microbial community ecology in general, have blossomed of late and are now a burgeoning source of exciting research findings. Along with the advent of next-generation sequencing platforms, which have dramatically increased the scope of microbiome-related projects, several high-performance sequence analysis pipelines (e.g.

No substantial changes in estrogen receptor and estrogen-related receptor orthologue gene transcription in Marisa cornuarietis exposed to estrogenic chemicals.

Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs are reported to be highly susceptible to effects caused by very low concentrations of environmental estrogens which, if substantiated, would have a major impact on the risk assessment of many chemicals. The present paper describes the most thorough evaluation to-date of the susceptibility of Marisa cornuarietis ER and ERR gene transcription to modulation by vertebrate estrogens in vivo and in vitro.

Complete genome sequence of the oral pathogenic Bacterium porphyromonas gingivalis strain W83.

The complete 2,343,479-bp genome sequence of the gram-negative, pathogenic oral bacterium Porphyromonas gingivalis strain W83, a major contributor to periodontal disease, was determined. Whole-genome comparative analysis with other available complete genome sequences confirms the close relationship between the Cytophaga-Flavobacteria-Bacteroides (CFB) phylum and the green-sulfur bacteria. Within the CFB phyla, the genomes most similar to that of P.

Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14.

The mosquito-borne malaria parasite Plasmodium falciparum kills an estimated 0.7-2.7 million people every year, primarily children in sub-Saharan Africa.