Development and validation of the post-CAR prognostic index for large B-cell lymphoma patients after CAR-T progression in third or later line treatment.

Chimeric antigen receptor (CAR) T-cell therapy fails to achieve durable responses in over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients in the third or later line setting. After CAR-T failure, survival outcomes are heterogeneous and a prognostic model in this patient population is lacking. A training cohort of 216 patients with progressive disease (PD) after CAR-T from 12 Spanish centers was used to develop the Post-CAR Prognostic Index (PC-PI); primary endpoint was overall survival (OS) from CAR-T progression.

Home-based transcranial direct current stimulation treatment for major depressive disorder: a fully remote phase 2 randomized sham-controlled trial.

Transcranial direct current stimulation (tDCS) has been proposed as a new treatment in major depressive disorder (MDD). This is a fully remote, multisite, double-blind, placebo-controlled, randomized superiority trial of 10-week home-based tDCS in MDD. Participants were 18 years or older, with MDD in current depressive episode of at least moderate severity as measured using the Hamilton Depression Rating Scale (mean = 19.

SPMs exert anti-inflammatory and pro-resolving effects through positive allosteric modulation of the prostaglandin EP4 receptor.

Inflammation is a protective response to pathogens and injury. To be effective it needs to be resolved by endogenous mechanisms in order to avoid prolonged and excessive inflammation, which can become chronic. Specialized pro-resolving mediators (SPMs) are a group of lipids derived from omega-3 fatty acids, which can induce the resolution of inflammation.

Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias.

The interaction between menin and histone-lysine N-methyltransferase 2A (KMT2A) is a critical dependency for KMT2A- or nucleophosmin 1 (NPM1)-altered leukemias and an emerging opportunity for therapeutic development. JNJ-75276617 (bleximenib) is a novel, orally bioavailable, potent, and selective protein-protein interaction inhibitor of the binding between menin and KMT2A. In KMT2A-rearranged (KMT2A-r) and NPM1-mutant (NPM1c) acute myeloid leukemia (AML) cells, JNJ-75276617 inhibited the association of the menin-KMT2A complex with chromatin at target gene promoters, resulting in reduced expression of several menin-KMT2A target genes, including MEIS1 and FLT3.

Design Strategies of Spinel Oxide Frameworks Enabling Reversible Mg-Ion Intercalation.

ConspectusReversible Mg intercalation in metal oxide frameworks is a key enabler for an operational Mg-ion battery with high energy density needed for the next generation of energy storage technologies. While functional Mg-ion batteries have been achieved in structures with soft anions (e.g.

Experimental co-infection of calves with SARS-CoV-2 Delta and Omicron variants of concern.

Since emerging in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has repeatedly crossed the species barrier with natural infections reported in various domestic and wild animal species. The emergence and global spread of SARS-CoV-2 variants of concern (VOCs) has expanded the range of susceptible host species. Previous experimental infection studies in cattle using Wuhan-like SARS-CoV-2 isolates suggested that cattle were not likely amplifying hosts for SARS-CoV-2.

Effects of music therapy as an alternative treatment on depression in children and adolescents with ADHD by activating serotonin and improving stress coping ability.

Objective: The objective of this study was to determine the effect of music therapy as an alternative treatment on depression in children and adolescents with attention-deficit hyperactivity disorder (ADHD) by activating serotonin (5-HT) and improving stress coping ability.

Methods: This study is designed based on randomization method. A total of 36 subjects participated in the experiment, consisting of an ADHD control group (n = 18) and ADHD music therapy group (n = 18).

Dopamine-induced astrocytic Ca signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice.

Dopamine (DA) plays a vital role in brain physiology and pathology such as learning and memory, motor control, neurological diseases, and psychiatric diseases. In neurons, it has been well established that DA increases or decreases intracellular cyclic AMP (cAMP) through D-like or D-like dopamine receptors, respectively. In contrast, it has been elusive how astrocytes respond to DA via Ca signaling and regulate synaptic transmission and reward systems.

An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases.

While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance.

Infection and transmission of ancestral SARS-CoV-2 and its alpha variant in pregnant white-tailed deer.

SARS-CoV-2 was first reported circulating in human populations in December 2019 and has since become a global pandemic. Recent history involving SARS-like coronavirus outbreaks have demonstrated the significant role of intermediate hosts in viral maintenance and transmission. Evidence of SARS-CoV-2 natural infection and experimental infections of a wide variety of animal species has been demonstrated, and and studies have indicated that deer are susceptible to SARS-CoV-2 infection.

Physical Properties of Thermally Crosslinked Fluorinated Polyimide and Its Application to a Liquid Crystal Alignment Layer.

This study demonstrated the use of a thermally crosslinked polyimide (PI) for the liquid crystal (LC) alignment layer of an LC display (LCD) cell. Polyamic acid was prepared using 4,4'-oxydianiline (ODA) and 4,4'-(hexafluoroisopropylidene) diphthalic anhydride (6FDA). The 6FDA-ODA-based polyimide (PI) prepared by the thermal cyclic dehydration of the polyamic acid (PAA) was soluble in various polar solvents.

Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma.

Tisagenlecleucel (tisa-cel) is a second-generation autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa-cel in the standard-of-care (SOC) setting for R/R LBCL.

A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein.

Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect.

Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate.

Gallbladder cancer (GBC) is an aggressive gastrointestinal malignancy with no approved targeted therapy. Here, we analyze exomes (n = 160), transcriptomes (n = 115), and low pass whole genomes (n = 146) from 167 gallbladder cancers (GBCs) from patients in Korea, India and Chile. In addition, we also sequence samples from 39 GBC high-risk patients and detect evidence of early cancer-related genomic lesions.

Multifunctional Epoxy-Based Solid Polymer Electrolytes for Solid-State Supercapacitors.

Solid polymer electrolytes (SPEs) have drawn attention for promising multifunctional electrolytes requiring very good mechanical properties and ionic conductivity. To develop a safe SPE for energy storage applications, mechanically robust cross-linked epoxy matrix is combined with fast ion-diffusing ionic liquid/lithium salt electrolyte (ILE) via a simple one-pot curing process. The epoxy-rich SPEs show higher Young's modulus ( E), with higher glass transition temperature ( T) but lower ionic conductivity (σ) with a higher activation energy, compared to the ILE-rich SPEs.

Trial of everolimus-eluting stents or bypass surgery for coronary disease.

Background: Most trials comparing percutaneous coronary intervention (PCI) with coronary-artery bypass grafting (CABG) have not made use of second-generation drug-eluting stents.

Methods: We conducted a randomized noninferiority trial at 27 centers in East Asia. We planned to randomly assign 1776 patients with multivessel coronary artery disease to PCI with everolimus-eluting stents or to CABG.

Insights into tRNA-dependent amidotransferase evolution and catalysis from the structure of the Aquifex aeolicus enzyme.

Many bacteria form Gln-tRNA(Gln) and Asn-tRNA(Asn) by conversion of the misacylated Glu-tRNA(Gln) and Asp-tRNA(Asn) species catalyzed by the GatCAB amidotransferase in the presence of ATP and an amide donor (glutamine or asparagine). Here, we report the crystal structures of GatCAB from the hyperthermophilic bacterium Aquifex aeolicus, complexed with glutamine, asparagine, aspartate, ADP, or ATP. In contrast to the Staphylococcus aureus GatCAB, the A.

Identification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92.

A series of small compounds acting at the orphan G protein-coupled receptor GPR92 were screened using a signaling pathway-specific reporter assay system. Lipid-derived molecules including farnesyl pyrophosphate (FPP), N-arachidonylglycine (NAG), and lysophosphatidic acid were found to activate GPR92. FPP and lysophosphatidic acid were able to activate both G(q/11)- and G(s)-mediated signaling pathways, whereas NAG activated only the G(q/11)-mediated signaling pathway.

Suppression of drinking by exposure to a high-strength static magnetic field.

High-strength static magnetic fields of 7 T and above have been shown to have both immediate and delayed effects on rodents, such as the induction of locomotor circling and the acquisition of conditioned taste aversions. In this study, the acute effects of magnet field exposure on drinking were examined. Exposure to a 14.