HER2 and HLA-A*02 dual CAR-T cells utilize LOH in a NOT logic gate to address on-target off-tumor toxicity.

Background: One of the major challenges in chimeric antigen receptor (CAR)-T cell therapy for solid tumors is the potential for on-target off-tumor toxicity due to the expression of CAR tumor antigens in essential tissues and organs. Here, we describe a dual CAR NOT gate incorporating an inhibitory CAR (iCAR) recognizing HLA-A*02 ("A2") that enables effective treatment with a potent HER2 activating CAR (aCAR) in the context of A2 loss of heterozygosity (LOH).

Methods: A CAR-T cell screen was conducted to identify inhibitory domains derived from natural immune receptors (iDomains) to be used in a NOT gate, to kill A2 HER2 lung cancer cell lines but spare A2 HER2 lung cancer cell-lines with high specificity.

Implementation of an Electronic Health Records-Based Safe Contrast Limit for Preventing Contrast-Associated Acute Kidney Injury After Percutaneous Coronary Intervention.

Background: Contrast-associated acute kidney injury (CA-AKI) after percutaneous coronary intervention is associated with increased mortality. We assessed the effectiveness of an electronic health records safe contrast limit tool in predicting CA-AKI risk and reducing contrast use and CA-AKI.

Methods: We created an alert displaying the safe contrast limit to cardiac catheterization laboratory staff prior to percutaneous coronary intervention.

Climate Change Impacts Can Be Differentially Perceived Across Time Scales: A Study Among the Tuareg of the Algerian Sahara.

As an Indigenous community of Algeria and the broader Sahel, the Tuareg hold unique ecological knowledge, which might contribute to broader models of place-based climate change impacts. Between January and April 2019, we carried out semi-structured interviews ( = 23) and focus group discussions ( = 3) in five villages of the province of Illizi, Algeria, to document the local Tuareg community's timeline and ecological calendar, both of which are instruments used to understand place-based reports of climate change impacts. The livelihoods of the Tuareg of Illizi are finely tuned to climate variability as reflected in changes reported in the cadence of events in their ecological calendar (marked by cyclical climatic and religious events).

Psychotropic drug treatment for agitated behaviour in dementia: what if the guideline prescribing recommendations are not sufficient? A qualitative study.

Background: Agitation is a common challenging behaviour in dementia with a negative influence on patient's quality of life and a high caregiver burden. Treatment is often difficult. Current guidelines recommend restrictive use of psychotropic drug treatment, but guideline recommendations do not always suffice.

Preeclampsia is Associated With Reduced Levels Impairing Extravillous Trophoblast Invasion.

Among several interleukin (IL)-6 family members, only IL-6 and IL-11 require a gp130 protein homodimer for intracellular signaling due to lack of intracellular signaling domain in the IL-6 receptor (IL-6R) and IL-11R. We previously reported enhanced decidual IL-6 and IL-11 levels at the maternal-fetal interface with significantly higher peri-membranous IL-6 immunostaining in adjacent interstitial trophoblasts in preeclampsia (PE) vs. gestational age (GA)-matched controls.