Molecular Profiling Identifies CD49d and CD79b as Predictive Markers for Acquired Acalabrutinib Resistance in Patients With Chronic Lymphocytic Leukemia.

Contemporary studies of Bruton tyrosine kinase inhibitor (BTKi) resistance focus on mutations in the B-cell receptor (BCR) pathway, but alternative mechanisms of resistance remain undefined. Here, we sought to identify novel predictive markers of acquired resistance to acalabrutinib, a second-generation BTKi, in patients with chronic lymphocytic leukemia (CLL). Clinical samples from 41 patients with relapsed/refractory or treatment-naive CLL receiving acalabrutinib as part of a clinical trial (NCT02029443) were divided into two groups: those who continued to respond to treatment (NP, n = 23) and those who developed progressive disease on acalabrutinib therapy (PD, n = 18).

The effects of listening on speaker and listener while talking about character strengths: an open science school-wide collaboration.

Listening is understood to be a foundational element in practices that rely on effective conversations, but there is a gap in our understanding of what the effects of high-quality listening are on both the speaker and listener. This registered report addressed this gap by training one group of participants to listen well as speakers discuss their character strengths, allowing us to isolate the role relational listening plays in strengths-based conversations. Participants were paired and randomly assigned to a high-quality listening (experimental) or moderate-quality listening (comparison) condition manipulated through a validated video-based training.

Opposing regulation of endoplasmic reticulum retention under stress by ERp44 and PDIA6.

Conditions of endoplasmic reticulum (ER) stress reduce protein synthesis by provoking translation regulation, governed by the eIF2α kinase PERK. When PERK is inhibited during ER stress, retention of a selective subset of glycoproteins occurs, a phenomenon we termed selective ER retention (sERr). sERr clients are enriched with tyrosine kinase receptors (RTKs), which form large molecular weight disulfide bonded complexes in the ER.

The role of IL-1 family cytokines in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is the primary cause of heart failure in patients with diabetes and is characterised by contractile dysfunction and left ventricular hypertrophy. The complex pathological and physiological mechanisms underlying DCM have contributed to a limited number of available treatment options. A substantial body of evidence has established that DCM is a low-grade inflammatory cardiovascular disorder, with the interleukin-1 (IL-1) family of cytokines playing crucial roles in initiating inflammatory responses and shaping innate and adaptive immunity.

FBXL16: a new regulator of neuroinflammation and cognition in Alzheimer's disease through the ubiquitination-dependent degradation of amyloid precursor protein.

Background: Activating the ubiquitin-proteasome system to dismantle disease- related proteins such as tau, β-amyloid, APP, and α-synuclein is an important focus in the research of neurodegenerative proteinopathy. By analyzing the serum RNA extracted from wild-type and Alzheimer's disease (AD) transgenic mice at different ages (4, 8, and 12 months), this study revealed a new protective role of FBXL16 in AD, primarily through facilitating the degradation of disease-related proteins via the ubiquitin proteasome system.

Methods: Proteomic analysis were conducted using protein lysates from HEK293 cells overexpressing FBXL16 to identify potential interacting proteins that interact with FBXL16.

Biodiversity impacts of the 2019-2020 Australian megafires.

With large wildfires becoming more frequent, we must rapidly learn how megafires impact biodiversity to prioritize mitigation and improve policy. A key challenge is to discover how interactions among fire-regime components, drought and land tenure shape wildfire impacts. The globally unprecedented 2019-2020 Australian megafires burnt more than 10 million hectares, prompting major investment in biodiversity monitoring.

Long-term Outcomes After Total Ankle Arthroplasty: A Systematic Review.

Background: Total ankle arthroplasty has emerged as a treatment to successfully treat ankle arthritis. Recent studies have reported more than 40 000 total ankle arthroplasties (TAAs) being performed between 2009 and 2019 in the United States. Although recent studies have reported favorable patient-reported outcomes at short- and midterm follow-up, there is a paucity of aggregate literature reporting on long-term patient-reported outcomes (PROs) after TAA.

Gynostemma pentaphyllum saponins shield mice from peanut allergy by modulation of gut microbiota: A novel approach for peanut allergy management.

Background: Food allergies, particularly peanut (PN) allergies, are a growing concern, with fatal anaphylaxis incidents often reported. While palforzia is the sole FDA-approved drug for managing PN allergies, it is not universally effective.

Purpose: This study aimed to investigate the potential of Gynostemma pentaphyllum saponins (GpS) as a novel therapeutic agent for PN allergy through modulation of gut microbiota, addressing the limitations of current treatments.

Principles of resuscitation for infants with severe bronchopulmonary dysplasia.

Severe bronchopulmonary dysplasia (sBPD) requiring invasive mechanical ventilation is a heterogeneous disease process that contributes to morbidity and mortality in infants. As the most common lung disease of prematurity, sBPD has a multitude of overlapping cardiac, airway, pulmonary vascular, and infectious phenotypic presentations that progress through four different phases of care. Premature infants with sBPD are at a high risk of acute decompensation and subsequent cardiopulmonary arrest.

Circular RNA Targets the /KLF4 Axis to Modulate 4,4'-Methylene Diphenyl Diisocyanate-Glutathione Conjugate-Induced Chemokine Transcription in Macrophages.

Exposure to 4,4'-methylene diphenyl diisocyanate (MDI) in the workplace may lead to the development of occupational asthma (OA). However, the specific mechanism(s) by which MDI induces OA are poorly understood. Previous reports have demonstrated that MDI and MDI-glutathione (GSH) conjugate exposure downregulates endogenous human/murine ()-microRNA, resulting in the activation of -regulated signaling pathways in macrophages.

New mechanisms in diisocyanate-mediated allergy/toxicity: are microRNAs in play?

Purpose Of Review: To describe recent findings of diisocyanate-mediated mechanisms in allergy and toxicology by addressing the role of microRNA (miR) in immune responses that may contribute to the development of occupational asthma (OA).

Recent Findings: Studies of diisocyanate asthma have traditionally focused on the immune and inflammatory patterns associated with diisocyanate exposures; however, recognized knowledge gaps exist regarding the detailed molecular mechanism(s) of pathogenesis. Recent studies demonstrate the critical role endogenous microRNAs play as gene regulators in maintaining homeostasis of the human body, and in the pathophysiology of many diseases including asthma.

Comparison of a new type of Dark Matter with the Milky Way and M31 grand rotation curves.

In the electron Born self-energy (eBse) model, free electrons are of finite-size and possess both a rest mass, m, as well as, a Born mass, m = 74,000 m. The Born mass, which originates from the energy contained within the electric field that surrounds a finite-sized electron, serves as a Dark Matter (DM) particle in this theory (designated eBDM, electron Born Dark Matter). The equation of state for m is w = -1, which implies that two Born masses experience a repulsive gravitational interaction.

Inferring cell differentiation maps from lineage tracing data.

During development, mulitpotent cells differentiate through a hierarchy of increasingly restricted progenitor cell types until they realize specialized cell types. A cell differentiation map describes this hierarchy, and inferring these maps is an active area of research spanning traditional single marker lineage studies to data-driven trajectory inference methods on single-cell RNA-seq data. Recent high-throughput lineage tracing technologies profile lineages and cell types at scale, but current methods to infer cell differentiation maps from these data rely on simple models with restrictive assumptions about the developmental process.

GPCR-mediated natural products and compounds: Potential therapeutic targets for the treatment of neurological diseases.

G protein-coupled receptors (GPCRs), widely expressed in the human central nervous system (CNS), perform numerous physiological functions and play a significant role in the pathogenesis of diseases. Consequently, identifying key therapeutic GPCRs targets for CNS-related diseases is garnering immense interest in research labs and pharmaceutical companies. However, using GPCRs drugs for treating neurodegenerative diseases has limitations, including side effects and uncertain effective time frame.

Human keratinocyte response to 4,4'-methylene diphenyl diisocyanate-glutathione conjugate exposure.

Workplace exposure to diisocyanates like 4,4'-methylene diphenyl diisocyanate can cause occupational asthma (MDI-OA), and the underlying biological pathways are still being researched.Although uncertainty remains, evidence supports the hypothesis that dermal exposure to MDI plays an important role in the development of MDI-OA.Gene expression, proteomics, and informatics tools were utilised to characterise changes in expression of RNA and protein in cultured human HEKa keratinocyte cells following exposure to conjugates of MDI with glutathione (MDI-GSH).

Thonningianin A from Penthorum chinense Pursh as a targeted inhibitor of Alzheimer's disease-related β-amyloid and Tau proteins.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by complex pathogenesis mechanisms. Among these, β-amyloid plaques and hyperphosphorylated Tau protein tangles have been identified as significant contributors to neuronal damage. This study investigates thonningianin A (TA) from Penthorum chinense Pursh (PCP) as a potential inhibitor targeting these pivotal proteins in AD progression.

Potential of Raman-Reflectance Combination in Quantifying Liver Steatosis and Fat Droplet Size: Evidence From Monte Carlo Simulations and Phantom Studies.

This study explores a combined strategy of Raman and reflectance spectroscopy for quantifying liver fat content and fat droplet size, crucial in assessing donor livers. By using Monte Carlo simulations and experimental setups with oil-in-water phantoms, our findings indicate that Raman scattering can solely differentiate between varying fat contents. At the same time, reflectance intensity is influenced by both fat content and oil droplet size, with a more pronounced sensitivity to fat droplet size.

Structural Variations Identified in Patients with Autism Spectrum Disorder (ASD) in the Chinese Population: A Systematic Review of Case-Control Studies.

Autistic spectrum disorder (ASD) is a neurodevelopmental disability characterised by the impairment of social interaction and communication ability. The alarming increase in its prevalence in children urged researchers to obtain a better understanding of the causes of this disease. Genetic factors are considered to be crucial, as ASD has a tendency to run in families.

Far-infrared radiation and its therapeutic parameters: A superior alternative for future regenerative medicine?

In future regenerative medicine, far-infrared radiation (FIR) may be an essential component of optical therapy. Many studies have confirmed or validated the efficacy and safety of FIR in various diseases, benefiting from new insights into FIR mechanisms and the excellent performance of many applications. However, the lack of consensus on the biological effects and therapeutic parameters of FIR limits its practical applications in the clinic.

Assessing the human factors involved in chest compression with superimposed sustained inflation during neonatal and paediatric resuscitation: A randomized crossover study.

Background: A new cardiopulmonary resuscitation technique, chest compressions with sustained inflation (CC + SI) might be an alternative to both the neonatal [3:1compressions to ventilations (3:1C:V)] and paediatric [chest compression with asynchronous ventilation (CCaV)] approaches. The human factors associated with this technique are unknown. We aimed to compare the physical, cognitive, and team-based human factors for CC + SI to standard CPR (3:1C:V or CCaV).