Deuterated water labeling in ibrutinib-treated patients with CLL: leukemia cell kinetics correlate with IGHV, ZAP-70, and MRD.

Deuterated ("heavy") water labeling in patients with chronic lymphocytic leukemia (CLL) demonstrates that IGHV unmutated and ZAP-70+ patients have higher blood and tissue CLL death rates on ibrutinib therapy, resulting in lower measurable residual disease levels with long-term ibrutinib treatment. This trial was registered at www.clinicaltrials.

The DLEU2/miR-15a/miR-16-1 cluster shapes the immune microenvironment of chronic lymphocytic leukemia.

The development and progression of chronic lymphocytic leukemia (CLL) depend on genetic abnormalities and on the immunosuppressive microenvironment. We have explored the possibility that genetic drivers might be responsible for the immune cell dysregulation that shapes the protumor microenvironment. We performed a transcriptome analysis of coding and non-coding RNAs (ncRNAs) during leukemia progression in the Rag2γ MEC1-based xenotransplantation model.

The COMPASS scale for the assessment of individuals with first episode psychotic disorders.

Background: Psychosis symptom assessment instruments are rarely used in US mental health community clinical practice despite the advantages of measurement-based care. Barriers include the length of typical scales and that data for scale evaluation often come from researcher and not clinician raters.

Study Design: The 12-item COMPASS symptom assessment was designed for the RAISE-ETP study of early phase psychosis.

A candidate loss-of-function variant in SGIP1 causes synaptic dysfunction and recessive parkinsonism.

Synaptic dysfunction is recognized as an early step in the pathophysiology of parkinsonism. Several genetic mutations affecting the integrity of synaptic proteins cause or increase the risk of developing disease. We have identified a candidate causative mutation in synaptic "SH3GL2 Interacting Protein 1" (SGIP1), linked to early-onset parkinsonism in a consanguineous Arab family.

Early brain neuroinflammatory and metabolic changes identified by dual tracer microPET imaging in mice with acute liver injury.

Background: Acute liver injury (ALI) that progresses into acute liver failure (ALF) is a life-threatening condition with an increasing incidence and associated costs. Acetaminophen (N-acetyl-p-aminophenol, APAP) overdosing is among the leading causes of ALI and ALF in the Northern Hemisphere. Brain dysfunction defined as is one of the main diagnostic criteria for ALF.

IRF5 mediates adaptive immunity via altered glutamine metabolism, mTORC1 signaling and post-transcriptional regulation following T cell receptor activation.

Although dynamic alterations in transcriptional, translational, and metabolic programs have been described in T cells, the factors and pathways guiding these molecular shifts are poorly understood, with recent studies revealing a disassociation between transcriptional responses and protein expression following T cell receptor (TCR) stimulation. Previous studies identified interferon regulatory factor 5 (IRF5) in the transcriptional regulation of cytokines, chemotactic molecules and T effector transcription factors following TCR signaling. In this study, we identified T cell intrinsic IRF5 regulation of mTORC1 activity as a key modulator of CD40L protein expression.

Brain-Controlled Augmented Hearing for Spatially Moving Conversations in Multi-Talker Environments.

Focusing on a specific conversation amidst multiple interfering talkers is challenging, especially for those with hearing loss. Brain-controlled assistive hearing devices aim to alleviate this problem by enhancing the attended speech based on the listener's neural signals using auditory attention decoding (AAD). Departing from conventional AAD studies that relied on oversimplified scenarios with stationary talkers, a realistic AAD task that involves multiple talkers taking turns as they continuously move in space in background noise is presented.

Association between Heat Vulnerability Index and Stroke Severity.

Background: Socioeconomically disadvantaged neighborhoods are particularly vulnerable to heat-related illnesses. We aim to investigate the association between the heat vulnerability index (HVI), an established neighborhood-level metric of heat-related mortality risk, and acute ischemic stroke (AIS) severity.

Methods: We conducted a retrospective analysis of consecutive AIS admissions to a comprehensive stroke center between 2012 and 2021.

Clinical and cognitive outcomes in first-episode psychosis: focus on the interplay between cannabis use and genetic variability in endocannabinoid receptors.

Introduction: Research data show the impact of the endocannabinoid system on psychosis through its neurotransmission homeostatic functions. However, the effect of the endocannabinoid system genetic variability on the relationship between cannabis use and psychosis has been unexplored, even less in first-episode patients. Here, through a case-only design, we investigated the effect of cannabis use and the genetic variability of endocannabinoid receptors on clinical and cognitive outcomes in first-episode psychosis (FEP) patients.

Perioperative Management of Patients Taking Direct Oral Anticoagulants: A Review.

Importance: Direct oral anticoagulants (DOACs), comprising apixaban, rivaroxaban, edoxaban, and dabigatran, are commonly used medications to treat patients with atrial fibrillation and venous thromboembolism. Decisions about how to manage DOACs in patients undergoing a surgical or nonsurgical procedure are important to decrease the risks of bleeding and thromboembolism.

Observations: For elective surgical or nonsurgical procedures, a standardized approach to perioperative DOAC management involves classifying the risk of procedure-related bleeding as minimal (eg, minor dental or skin procedures), low to moderate (eg, cholecystectomy, inguinal hernia repair), or high risk (eg, major cancer or joint replacement procedures).

Quercetin enhances decidualization through AKT-ERK-p53 signaling and supports a role for senescence in endometriosis.

Background: Patients with endometriosis suffer with chronic pelvic pain and infertility, and from the lack of pharmacologic therapies that consistently halt disease progression. Differences in the endometrium of patients with endometriosis vs. unaffected controls are well-documented.

Ten-year trends, disparities, and clinical impact of stroke thrombectomy and thrombolysis: A single center experience 2012-2021.

Objectives: As indications for acute ischemic stroke treatment expand, it is unclear whether disparities in treatment utilization and outcome still exist. The main objective of this study was to investigate disparities in acute ischemic stroke treatment and determine impact on outcome.

Materials And Methods: Retrospective observational cohort study of consecutive ischemic stroke admissions to a comprehensive stroke center from 2012-2021 was performed.

Machine learning model comparison for freezing of gait prediction in advanced Parkinson's disease.

Introduction: Freezing of gait (FOG) is a paroxysmal motor phenomenon that increases in prevalence as Parkinson's disease (PD) progresses. It is associated with a reduced quality of life and an increased risk of falls in this population. Precision-based detection and classification of freezers are critical to developing tailored treatments rooted in kinematic assessments.

IRF5 suppresses metastasis through the regulation of tumor-derived extracellular vesicles and pre-metastatic niche formation.

Metastasis is driven by extensive cooperation between a tumor and its microenvironment, resulting in the adaptation of molecular mechanisms that evade the immune system and enable pre-metastatic niche (PMN) formation. Little is known of the tumor-intrinsic factors that regulate these mechanisms. Here we show that expression of the transcription factor interferon regulatory factor 5 (IRF5) in osteosarcoma (OS) and breast carcinoma (BC) clinically correlates with prolonged survival and decreased secretion of tumor-derived extracellular vesicles (t-dEVs).

Electrical stimulation of the vagus nerve ameliorates inflammation and disease activity in a rat EAE model of multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating central nervous system (CNS) disorder that is associated with functional impairment and accruing disability. There are multiple U.S.