Chimeric antigen receptor-induced antigen loss protects CD5.CART cells from fratricide without compromising on-target cytotoxicity.

Chimeric antigen receptor T cells (CART) targeting lymphocyte antigens can induce T cell fratricide and require additional engineering to mitigate self-damage. We demonstrate that the expression of a chimeric antigen receptor (CAR) targeting CD5, a prominent pan-T cell antigen, induces rapid internalization and complete loss of the CD5 protein on T cells, protecting them from self-targeting. Notably, exposure of healthy and malignant T cells to CD5.

Extracellular Vesicles Slow Down Aβ(1-42) Aggregation by Interfering with the Amyloid Fibril Elongation Step.

Formation of amyloid-β (Aβ) fibrils is a central pathogenic feature of Alzheimer's disease. Cell-secreted extracellular vesicles (EVs) have been suggested as disease modulators, although their exact roles and relations to Aβ pathology remain unclear. We combined kinetics assays and biophysical analyses to explore how small (<220 nm) EVs from neuronal and non-neuronal human cell lines affected the aggregation of the disease-associated Aβ variant Aβ(1-42) into amyloid fibrils.

Baculovirus entry into the central nervous system of caterpillars is independent of the viral protein tyrosine phosphatase.

Neuroparasitism concerns the hostile take-over of a host's nervous system by a foreign invader, in order to alter the behaviour of the host in favour of the parasite. One of the most remarkable cases of parasite-induced host behavioural manipulation comprises the changes baculoviruses induce in their caterpillar hosts. Baculoviruses may manipulate caterpillar behaviour in two ways: hyperactivity (increased movement in the horizontal plane) and/or tree-top disease (movement to elevated levels in the vertical plane).

An Extraordinary Voice Expressed Through Humor: A Tribute to Casey Quinlan.

The Journal of Participatory Medicine introduces Extraordinary Lives, a new journal section celebrating the voices and work of steadfast advocates of participatory medicine that we have lost. This inaugural essay spotlights Casey Quinlan, a patient activist who effectively used her humor and incisive analysis of health care to encourage others to strive for meaningful change. A first-generation "professional patient," Casey served as a role model who inspired many to share their stories and achieve genuine partnerships in care delivery.

Ginsenoside Rg3 Reduces the Toxicity of Graphene Oxide Used for pH-Responsive Delivery of Doxorubicin to Liver and Breast Cancer Cells.

Doxorubicin (DOX) is extensively used in chemotherapy, but it has serious side effects and is inefficient against some cancers, e.g., hepatocarcinoma.

Feasibility and preclinical efficacy of CD7-unedited CD7 CAR T cells for T cell malignancies.

Chimeric antigen receptor (CAR)-mediated targeting of T lineage antigens for the therapy of blood malignancies is frequently complicated by self-targeting of CAR T cells or their excessive differentiation driven by constant CAR signaling. Expression of CARs targeting CD7, a pan-T cell antigen highly expressed in T cell malignancies and some myeloid leukemias, produces robust fratricide and often requires additional mitigation strategies, such as CD7 gene editing. In this study, we show fratricide of CD7 CAR T cells can be fully prevented using ibrutinib and dasatinib, the pharmacologic inhibitors of key CAR/CD3ζ signaling kinases.

Nothing for Me or About Me, Without Me: Codesign of Clinical Decision Support.

Background: Partnerships among patients, families, caregivers, and clinicians are critical to helping patients lead their best lives given their specific genetics, conditions, circumstances, and the environments in which they live, work, and play. These partnerships extend to the development of health information technology, including clinical decision support (CDS). Design of these technologies, however, often occurs without a profound understanding of the true needs, wants, and concerns of patients and family members.

Label-free nanofluidic scattering microscopy of size and mass of single diffusing molecules and nanoparticles.

Label-free characterization of single biomolecules aims to complement fluorescence microscopy in situations where labeling compromises data interpretation, is technically challenging or even impossible. However, existing methods require the investigated species to bind to a surface to be visible, thereby leaving a large fraction of analytes undetected. Here, we present nanofluidic scattering microscopy (NSM), which overcomes these limitations by enabling label-free, real-time imaging of single biomolecules diffusing inside a nanofluidic channel.

Chemically Synthesized, Self-Assembling Small Interfering RNA-Prohead RNA Molecules Trigger Dicer-Independent Gene Silencing.

RNA interference (RNAi) mediated by small interfering RNA (siRNA) duplexes is a powerful therapeutic modality, but the translation of siRNAs from the bench into clinical application has been hampered by inefficient delivery in vivo. An innovative delivery strategy involves fusing siRNAs to a three-way junction (3WJ) motif derived from the phi29 bacteriophage prohead RNA (pRNA). Chimeric siRNA-3WJ molecules are presumed to enter the RNAi pathway through Dicer cleavage.

The COVID-19 System Shock Framework: Capturing Health System Innovation During the COVID-19 Pandemic.

Background: Coronavirus disease 2019 (COVID-19) has resulted in over 2 million deaths globally. The experience in Australia presents an opportunity to study contrasting responses to the COVID-19 health system shock. We adapted the Hanefeld et al framework for health systems shocks to create the COVID-19 System Shock Framework (CSSF).

Multiple, large intra-abdominal cystic lesions and iron deficiency anaemia as the presenting symptoms of SDHD gastrointestinal stromal tumour (GIST) in a young sub-Saharan woman.

We report the case of a 27-year-old female patient from sub-Saharan Africa who presented with non-specific abdominal complaints, iron deficiency anaemia and multiple, large intra-abdominal cystic lesions on imaging. The lesions appeared to be a most unusual presentation of gastrointestinal stromal tumour (GIST). GIST is a sarcomatous tumour that comprises only 0.

Ethical and Legal Aspects of Pandemics During COVID-19 and Beyond for the Hepatology Community.

Content available: Author Interview and Audio Recording.

High-throughput multiparametric imaging flow cytometry: toward diffraction-limited sub-cellular detection and monitoring of sub-cellular processes.

We present a sheathless, microfluidic imaging flow cytometer that incorporates stroboscopic illumination for blur-free fluorescence detection at ultra-high analytical throughput. The imaging platform is capable of multiparametric fluorescence quantification and sub-cellular localization of these structures down to 500 nm with microscopy image quality. We demonstrate the efficacy of the approach through the analysis and localization of P-bodies and stress granules in yeast and human cells using fluorescence and bright-field detection at analytical throughputs in excess of 60,000 and 400,000 cells/s, respectively.

WGO Guidance for the Care of Patients With COVID-19 and Liver Disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the least deadly but most infectious coronavirus strain transmitted from wild animals. It may affect many organ systems. Aim of the current guideline is to delineate the effects of SARS-CoV-2 on the liver.

Influence of phase of respiratory cycle on ultrasound imaging of deep abdominal muscle thickness.

Background: It is difficult to evaluate the transversus abdominis (TrA) and internal oblique (IO) due to their dual role in both trunk control and breathing.

Objectives: To investigate whether TrA and IO thickness as measured by ultrasound differs across the respiratory cycle in upright standing.

Design: Observational study.

Oscillatory Viscoelastic Microfluidics for Efficient Focusing and Separation of Nanoscale Species.

The ability to precisely control particle migration within microfluidic systems is essential for focusing, separating, counting, and detecting a wide range of biological species. To date, viscoelastic microfluidic systems have primarily been applied to the focusing, separation, and isolation of micrometer-sized species, with their use in nanoparticle manipulations being underdeveloped and underexplored, due to issues related to nanoparticle diffusivity and a need for extended channel lengths. To overcome such issues, we herein present sheathless oscillatory viscoelastic microfluidics as a method for focusing and separating both micrometer and sub-micrometer species.

A Novel Tool to Improve Shared Decision Making and Adherence in Multiple Sclerosis: Development and Preliminary Testing.

. Most people with multiple sclerosis (MS) want to be involved in medical decision making about disease-modifying therapies (DMTs), but new approaches are needed to overcome barriers to participation. .

Safety and tolerability of conditioning chemotherapy followed by CD19-targeted CAR T cells for relapsed/refractory CLL.

Background: Subgroups of patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) exhibit suboptimal outcomes after standard therapies, including oral kinase inhibitors. We and others have previously reported on safety and efficacy of autologous CD19-targeted CAR T-cells for these patients; here we report safety and long-term follow-up of CAR T-cell therapy with or without conditioning chemotherapy for patients with R/R CLL and indolent B-cell non-Hodgkin lymphoma (B-NHL).

Methods: We conducted a phase 1 clinical trial investigating CD19-targeted CAR T-cells incorporating a CD28 costimulatory domain (19-28z).

CD40 Ligand-Modified Chimeric Antigen Receptor T Cells Enhance Antitumor Function by Eliciting an Endogenous Antitumor Response.

Chimeric antigen receptor (CAR) T cells provide great efficacy in B cell malignancies. However, improved CAR T cell therapies are still needed. Here, we engineered tumor-targeted CAR T cells to constitutively express the immune-stimulatory molecule CD40 ligand (CD40L) and explored efficacy in different mouse leukemia/lymphoma models.

Environmental Fate of RNA Interference Pesticides: Adsorption and Degradation of Double-Stranded RNA Molecules in Agricultural Soils.

Double-stranded RNA (dsRNA) pesticides are a new generation of crop protectants that interfere with protein expression in targeted pest insects by a cellular mechanism called RNA interference (RNAi). The ecological risk assessment of these emerging pesticides necessitates an understanding of the fate of dsRNA molecules in receiving environments, among which agricultural soils are most important. We herein present an experimental approach using phosphorus-32 (P)-radiolabeled dsRNA that allows studying key fate processes of dsRNA in soils with unprecedented sensitivity.

Histology of portal vascular changes associated with idiopathic non-cirrhotic portal hypertension: nomenclature and definition.

Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare vascular liver disease that has attracted new interest in recent years. It is characterised by clinical signs of portal hypertension in the absence of cirrhosis or severe fibrosis and any known cause of portal hypertension. As much uncertainty exists about INCPH pathophysiology, and no definite diagnostic tests are available, liver biopsy is an essential tool for achieving a definite diagnosis.

Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo.

The efficacy of chimeric antigen receptor (CAR) T cell therapy against poorly responding tumors can be enhanced by administering the cells in combination with immune checkpoint blockade inhibitors. Alternatively, the CAR construct has been engineered to coexpress factors that boost CAR-T cell function in the tumor microenvironment. We modified CAR-T cells to secrete PD-1-blocking single-chain variable fragments (scFv).

The Imperative for Patient-Centered Clinical Decision Support.

This commentary introduces the Patient-Centered Clinical Decision Support (PCCDS) Learning Network, which is collaborating with AcademyHealth to publish "Better Decisions Together" as part of . Patient-centered clinical decision support (CDS) is an important vehicle to address broad issues in the U.S.