Pediatric T-cell lymphoblastic lymphomas but not leukemias harbor TRB::NOTCH1 fusions with unfavorable outcome.

T-cell lymphoblastic lymphoma (T-LBL) and T-cell acute lymphoblastic leukemia (T-ALL) have common and distinguishing clinical and molecular features. Molecular prognostic factors are needed for T-LBL. We assessed the prevalence and prognostic impact of the T-cell receptor β (TRB)::NOTCH1 fusion in 192 pediatric patients with T-LBL and 167 pediatric patients with T-ALL, using novel multiplex polymerase chain reaction and genomic capture high-throughput sequencing techniques.

Combining SiRPα decoy-coengineered T cells and antibodies augments macrophage-mediated phagocytosis of tumor cells.

The adoptive transfer of T cell receptor-engineered (TCR-engineered) T cells (ACT) targeting the HLA-A2-restricted cancer-testis epitope NY-ESO-1157-165 (A2/NY) has yielded favorable clinical responses against several cancers. Two approaches to improve ACT are TCR affinity optimization and T cell coengineering to express immunomodulatory molecules that can exploit endogenous immunity. By computational design we previously developed a panel of binding-enhanced A2/NY-TCRs including A97L, which augmented the in vitro function of gene-modified T cells as compared with WT.

Endoscopic ultrasound-guided portal pressure gradient measurement: a systematic review and meta-analysis.

Background: Endoscopic ultrasound-guided portal pressure gradient measurement (EUS-PPG) is a new modality where the portal pressure is measured by directly introducing a needle into the hepatic vein and portal vein. This is the first systematic review and meta-analysis to evaluate the efficacy and safety of EUS-PPG.

Methods: A comprehensive literature search was performed to identify pertinent studies.

You can't handle the truth! Comparing serum phosphatidylethanol to self-reported alcohol intake in chronic liver disease patients.

Background: Serum phosphatidylethanol (PEth) testing has emerged as a promising biomarker for assessing recent alcohol consumption, surpassing the limitations of self-reported data. Limited clinical data exists comparing PEth levels and patients' reported alcohol intake.

Aims: Compare PEth testing results with self-reported alcohol intake and assesses variables associated with underreporting.

A Library of Polymer-based Microelectrode Array Designs for Recording from the Brain of Different Animal Models.

Large-scale network recording technology is critical in linking neural activity to behavior. Stable, long-term recordings collected from behaving animals are the foundation for understanding neural dynamics and the plasticity of neural circuits. Penetrating microelectrode arrays (MEAs) can obtain high-resolution neural activity from different brain regions.

Polymer Implantable Electrode Foundry: A shared resource for manufacturing polymer-based microelectrodes for neural interfaces.

Large scale monitoring of neural activity at the single unit level can be achieved via electrophysiological recording using implanted microelectrodes. While neuroscience researchers have widely employed chronically implanted electrode-based interfaces for this purpose, a commonly encountered limitation is loss of highly resolved signals arising from immunological response over time. Next generation electrode-based interfaces improve longitudinal signal quality using the strategy of stabilizing the device-tissue interface with microelectrode arrays constructed from soft and flexible polymer materials.

Mortality Increased Among Hospitalized Patients with Cirrhosis Before and Following Different Waves of the COVID-19 Pandemic.

Background: The Coronavirus disease 2019 (COVID-19) pandemic disrupted patient care and worsened the morbidity and mortality of some chronic diseases. The impact of the COVID-19 pandemic on hospitalizations and outcomes in patients with cirrhosis both before and during different time periods of the pandemic has not been evaluated.

Aims: Describe characteristics of hospitalized patients with cirrhosis and evaluate inpatient mortality and 30-day readmission before and after the start of the COVID-19 pandemic.

Synthesis and VCD Spectroscopic Characterization of a Series of Azacryptands from a Chiral Valine-Based Derivative of Tris(2-aminoethyl)amine (TREN).

Utilizing experimental and computational vibrational circular dichroism (VCD) spectroscopy, we explored the conformational preferences of a series of chiral C -symmetric octaazacryptands with tris(2-aminoethyl)-amine head groups derived from valine. While the spectra of the smallest azacryptand with p-phenyl linkers and its elongated derivative with p-biphenyls linker were found to match well with the computed spectra, the computed conformational preferences of the m-biphenyl-based azacryptand did not seem to reflect the conformations dominating in chloroform solution. A detailed analysis revealed that structural changes resulting in a collapsed cage structure gave a notably better match with the experiment.

Acute in vivo Recording with a Generic Parylene Microelectrode Array Implanted with Dip-coating Method into the Rat Brain.

Flexible polymer-based microelectrode arrays (MEAs) can reduce tissue inflammation and foreign body response and greatly prolong the lifetime of neural implants. However, standard and customized polymer devices are only accessible to limited groups. To better promote the development and application of polymer MEAs, we have launched the Polymer Implantable Electrode (PIE) Foundry and developed a 64-channel Parylene C-based MEA with generic electrodes layout that can be used to record from both cortical and sub-cortical regions in rodents.

Anion-binding of a chiral tris(2-aminoethyl)amine-based tripodal thiourea: a spectroscopic and computational study.

Thioureas are well-known structural motifs in supramolecular anion recognition. Their conformational preferences are typically characterized by detailed NMR spectroscopy and crystallography, which are often complemented with computational results from geometry optimizations. Herein we investigate a chiral tris(thiourea) based on tris(2-aminoethyl)amine, which acts as an anion receptor for chloride and hydrogen sulfate.

Solvation of the Boc-Val-Phe-Pr peptide characterized by VCD spectroscopy and DFT calculations.

The conformational preferences of peptides are strongly determined by hydrogen bonding interactions. Intermolecular solute-solvent interactions compete with intramolecular interactions, which typically stabilize the secondary structure of the peptide. The analysis of vibrational circular dichroism (VCD) spectra can give insights into solvation-induced changes in the conformational distribution of small peptides.

A 512-Channel Multi-Layer Polymer-Based Neural Probe Array.

We present for the first time the design, fabrication, and preliminary bench-top characterization of a high-density, polymer-based penetrating microelectrode array, developed for chronic, large-scale recording in the cortices and hippocampi of behaving rats. We present two architectures for these targeted brain regions, both featuring 512 Pt recording electrodes patterned front-and-back on micromachined eight-shank arrays of thin-film Parylene C. These devices represent an order of magnitude improvement in both number and density of recording electrodes compared with prior work on polymer-based microelectrode arrays.

Basis set dependence of S[double bond, length as m-dash]O stretching frequencies and its consequences for IR and VCD spectra predictions.

Benchmarking functionals and basis sets for the computational prediction of molecular properties is usually done on very small model systems. Larger organic molecules containing heavier second row atoms are not the typical model structures. We herein present the first survey of basis sets and functionals for the prediction of the IR and VCD spectra of chiral tosylates and sulfinates as we noted drastic deviations between computed harmonic frequencies obtained at B3LYP/6-311++G(2d,p) level of theory and those observed in experimental solution phase IR and VCD spectra.

A Parylene Neural Probe Array for Multi-Region Deep Brain Recordings.

A Parylene C polymer neural probe array with 64 electrodes purposefully positioned across 8 individual shanks to anatomically match specific regions of the hippocampus was designed, fabricated, characterized, and implemented for enabling recording in deep brain regions in freely moving rats. Thin film polymer arrays were fabricated using surface micromachining techniques and mechanically braced to prevent buckling during surgical implantation. Importantly, the mechanical bracing technique developed in this work involves a novel biodegradable polymer brace that temporarily reduces shank length and consequently, increases its stiffness during implantation, therefore enabling access to deeper brain regions while preserving a low original cross-sectional area of the shanks.

Essential amino acid-enriched meal replacement promotes superior net protein balance in older, overweight adults.

Background & Aims: Older individuals are susceptible to the loss of muscle and accumulation of fat. To address this problem, we have compared protein kinetics following consumption of an essential amino acid (EAA)-enriched meal replacement (EMR) to consumption of a high-protein meal replacement beverage (Bariatric Advantage, BA) using stable isotope methodology.

Methods: Eight older (67 ± 2), obese (35 ± 2 kg/m) female and male participants completed two studies using a randomized, crossover design in which they ingested each meal replacement.

Application of Parylene-Based Flexible Multi-Electrode Array for Recording From Subcortical Brain Regions From Behaving Rats.

Obtaining multiple single-unit recordings in particular neural networks from behaving animals is crucial for the understanding of cognitive functions of the brain. Attaining stable, chronic recordings from the brain is also the foundation to develop effective cortical prosthetic devices. However, severe immune response caused by micromotion between stiff implants and surrounding brain tissue often limits the lifetime of penetrating, neural recording devices.

Techniques and Considerations in the Microfabrication of Parylene C Microelectromechanical Systems.

Parylene C is a promising material for constructing flexible, biocompatible and corrosion-resistant microelectromechanical systems (MEMS) devices. Historically, Parylene C has been employed as an encapsulation material for medical implants, such as stents and pacemakers, due to its strong barrier properties and biocompatibility. In the past few decades, the adaptation of planar microfabrication processes to thin film Parylene C has encouraged its use as an insulator, structural and substrate material for MEMS and other microelectronic devices.

A review of implantable biosensors for closed-loop glucose control and other drug delivery applications.

Closed-loop drug delivery promises autonomous control of pharmacotherapy through the continuous monitoring of biomarker levels. For decades, researchers have strived for portable closed-loop systems capable of treating ambulatory patients with chronic conditions such as diabetes mellitus. After years of development, the first of these systems have left the laboratory and entered commercial use.

Chronic multi-region recording from the rat hippocampus in vivo with a flexible Parylene-based multi-electrode array.

Neural activities of free-moving animals provide valuable insights into behavior, memory formation and cognitive function of the hippocampus. Unitary activities simultaneously recorded from multiple sub-regions of the hippocampus enable detailed study of hippocampal neural circuits, but require high fidelity recordings with high temporal and spatial resolution. In this work, we explored the possibility of using Parylene-C as the structural material for a penetrating, multi-electrode array designed to record from multiple sub-region of the rat hippocampus.

Acute in vivo testing of a conformal polymer microelectrode array for multi-region hippocampal recordings.

Objective: The success of a cortical prosthetic device relies upon its ability to attain resolvable spikes from many neurons in particular neural networks over long periods of time. Traditionally, lifetimes of neural recordings are greatly limited by the body's immune response against the foreign implant which causes neuronal death and glial scarring. This immune reaction is posited to be exacerbated by micromotion between the implant, which is often rigid, and the surrounding, soft brain tissue, and attenuates the quality of recordings over time.

Passive, wireless transduction of electrochemical impedance across thin-film microfabricated coils using reflected impedance.

A new method of wirelessly transducing electrochemical impedance without integrated circuits or discrete electrical components was developed and characterized. The resonant frequency and impedance magnitude at resonance of a planar inductive coil is affected by the load on a secondary coil terminating in sensing electrodes exposed to solution (reflected impedance), allowing the transduction of the high-frequency electrochemical impedance between the two electrodes. Biocompatible, flexible secondary coils with sensing electrodes made from gold and Parylene C were microfabricated and the reflected impedance in response to phosphate-buffered saline solutions of varying concentrations was characterized.