Clinical use of tau PET in Aβ PET positive individuals: a case series.

Background: Identifying individuals’ levels of tau PET pathology could prove to be beneficial in clinical settings, given that emerging therapies aimed reducing Aβ seem to be most effective in these individuals. Here, we present the cases of four patients who visited the memory clinic at the University of Pittsburgh Medical Center between June and December 2023 and underwent both Aβ and tau‐PET scans.

Method: These individuals had standard clinical and cognitive outcomes, typical blood tests order in patients with memory impairment, MRI, and, as part of the HEAD study, PET PIB Aβ and two tau PET tracers (MK6240 and Flortaucipir).

Gene regulation by convergent promoters.

Convergent transcription, that is, the collision of sense and antisense transcription, is ubiquitous in mammalian genomes and believed to diminish RNA expression. Recently, antisense transcription downstream of promoters was found to be surprisingly prevalent. However, functional characteristics of affected promoters are poorly investigated.

Design of Cell-Penetrating Domain Antibodies via a Genetically Encoded β-Lactam Amino Acid.

Domain antibodies such as monobodies provide an attractive immunoglobin fold for evolving high-affinity protein binders targeting the intracellular proteins implicated in cell signalling. However, it remains a challenge to endow cell permeability to these small and versatile protein binders. Here, we report a streamlined approach combining orthogonal crosslinking afforded by a genetically encoded β-lactam-lysine (BeLaK) and genetic supercharging to generate cell-penetrating monobodies.

Semisynthesis of Alkaloid Derivatives: Pyranoacridone-Hydroxamic Acid Cytotoxic Conjugates with HDAC and Topoisomerase II α Dual Inhibitory Activity.

Inspired by our previous efforts in the semisynthetic modification of naturally occurring pyranoacridones, we report the targeted design and semisynthesis of dual inhibitors of HDAC and topoisomerase II α (Topo II α) derived from des--methylacronycine () and noracronycine () pyranoacridone alkaloids. Designed from the clinically approved SAHA, the cytotoxic pyranoacridone nuclei from the alkaloids served as the capping group, while a hydroxamic acid moiety functioned as the zinc-binding group. Out of 16 compounds evaluated in an cytotoxicity assay, KT32 () with noracronycine () as the capping group and five-carbon linker hydroxamic acid side chains showed good cytotoxic activity with IC values of 1.

Ecological Momentary Assessment of Momentary Associations Between Availability of Physical Activity Space and Physical Activity Opportunities Among Children from Rural, Urban, and Suburban Locales.

Using Ecological Momentary Assessment (EMA), this study examined associations between momentary availability of physical activity (PA) space and accessibility of PA opportunities among 608 elementary and middle school students who were participating in an obesity prevention trial in one mid-Atlantic state in the U.S. Smartphones prompted EMA surveys at random times to assess children's perceived availability of PA space and accessibility of PA opportunities during out-of-school time, three to seven times each day over seven days.

Small-molecule MMRi36 induces apoptosis in p53-mutant lymphomas by targeting MDM2/MDM4/XIAP for degradation.

Rituximab combined with systemic chemotherapy significantly improves the rate of complete response in B-cell lymphomas. However, acquired rituximab resistance develops in most patients leading to relapse. The mechanisms underlying rituximab resistance are not well-understood.

Microbial and chemically induced reductive dechlorination of polychlorinated biphenyls in the environment.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants and are emitted during e-waste activities. Once they enter into the environment, PCBs could pose toxic effects to environmental compartments and public health. Reductive dechlorination offers a sustainable solution to manage the PCBs-contaminated environment.

Vascular Organoid Generation from Human-Induced Pluripotent Stem Cells.

Vascular organoids derived from human induced pluripotent stem cells (hiPSCs) recapitulate the cell type diversity and complex architecture of human vascular networks. This three-dimensional (3D) model holds substantial potential for vascular pathology modeling and in vitro drug screening. Despite recent advances, a key technical challenge remains in reproducibly generating organoids with consistent quality, which is crucial for downstream assays and applications.

PFAS biodegradation by Labrys portucalensis F11: Evidence of chain shortening and identification of metabolites of PFOS, 6:2 FTS, and 5:3 FTCA.

The biodegradation of three per- and polyfluoroalkyl substances (PFAS), namely perfluorooctane sulfonic acid (PFOS), 6:2-fluorotelomer sulfonic acid (6:2 FTS), and 5:3-fluorotelomer carboxylic acid (5:3 FTCA), were evaluated using Labrys portucalensis F11, an aerobic bacteria known to defluorinate fluorine-containing compounds. Cultures of L. portucalensis F11 were grown in minimal salts media and treated with 10,000 μg/L of individual PFAS as the sole carbon source in separate flasks.

A bipartite bacterial virulence factor targets the complement system and neutrophil activation.

The complement system and neutrophils constitute the two main pillars of the host innate immune defense against infection by bacterial pathogens. Here, we identify T-Mac, a novel virulence factor of the periodontal pathogen Treponema denticola that allows bacteria to evade both defense systems. We show that T-Mac is expressed as a pre-protein that is cleaved into two functional units.

Physiologically Based Pharmacokinetic Modeling of Cannabidiol, Delta-9-Tetrahydrocannabinol, and Their Metabolites in Healthy Adults After Administration by Multiple Routes.

The two most extensively studied cannabinoids, cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), are used for myriad conditions. THC is predominantly eliminated via the cytochromes P450 (CYPs), whereas CBD is eliminated through both CYPs and UDP-glucuronosyltransferases (UGTs). The fractional contributions of these enzymes to cannabinoid metabolism have shown conflicting results among studies.

A comprehensive benchmark study of methods for identifying significantly perturbed subnetworks in cancer.

Network-based methods utilize protein-protein interaction information to identify significantly perturbed subnetworks in cancer and to propose key molecular pathways. Numerous methods have been developed, but to date, a rigorous benchmark analysis to compare the performance of existing approaches is lacking. In this paper, we proposed a novel benchmarking framework using synthetic data and conducted a comprehensive analysis to investigate the ability of existing methods to detect target genes and subnetworks and to control false positives, and how they perform in the presence of topological biases at both gene and subnetwork levels.

CD38 Coordinates with NF-κB to Promote Cochlear Inflammation in Noise-Induced Hearing Loss: the Protective Effect of Apigenin.

Noise exposure is one of the most common causes of sensorineural hearing loss. Although many studies considered inflammation to be a major contributor to noise-induced hearing loss, the process of cochlear inflammation is still unclear. Studies have found that activation of the NF-κB signaling pathway results in the accumulation of macrophages in the inner ear plays an important role in hair cell damage.

Immune regulatory adjuvant approach to mitigate subcutaneous immunogenicity of monoclonal antibodies.

Introduction: Immunogenicity continues to be a challenge for development and clinical utility of monoclonal antibodies, and there are gaps in our current ability to prevent anti-drug antibody development in a safe and antigen-specific manner.

Methods: To mitigate immunogenicity of monoclonal antibodies administered subcutaneously, O-phospho-L-serine (OPLS)-the head group of the tolerance-inducing phospholipid, phosphatidylserine-was investigated as an immunoregulatory adjuvant.

Results: Formulations of adalimumab, trastuzumab or rituximab with OPLS showed reduction in relative immunogenicity in mice compared to vehicle formulations, indicated by reduced anti-drug antibody development and significant reductions in CD138+ plasma cell differentiation in bone marrow.

The power of friends in reducing sexual assault risk in college women: A preliminary test of dyad-based motivational intervention approach.

Objective: Sexual assault (SA) is unfortunately common in U.S. college campuses.

Recognition of Noncanonical RNA Base Pairs Using Triplex-Forming Peptide Nucleic Acids.

Noncanonical base pairs play an important role in enabling the structural and functional complexity of RNA. Molecular recognition of such motifs is challenging because of their diversity, significant deviation from the Watson-Crick structures, and dynamic behavior, resulting in alternative conformations of similar stability. Triplex-forming peptide nucleic acids (PNAs) have emerged as excellent ligands for the recognition of Watson-Crick base-paired double helical RNA.

Machine Learning Mapping Approach for Computing Spin Relaxation Dynamics.

In this work, a machine learning mapping approach for predicting the properties of atomistic systems is reported. Within this approach, the atomic orbital overlap, density, or Kohn-Sham (KS) Fock matrix elements obtained at a low level of theory such as extended tight-binding have been used as input features to predict the electric field gradient (EFG) tensors at a higher level of theory such as those obtained with hybrid functionals. It is shown that the machine-learning-predicted EFG tensors can be used to compute spin relaxation rates of several ions in aqueous solutions.

Enzyme fragment complementation driven by nucleic acid hybridization sans self-labeling protein.

A modified enzyme fragment complementation assay has been designed and validated as a turn-on biosensor for nucleic acid detection in dilute aqueous solution. The assay is target sequence-agonistic and uses fragments of NanoBiT, the split luciferase reporter enzyme, that are esterified enzymatically at their C-termini to steramers, sterol-linked oligonucleotides. The Drosophila hedgehog autoprocessing domain, DHhC, serves as the self-cleaving enzyme for the NanoBiT-steramer bioconjugations.

PK/PD Evaluation of Antibody-Drug Conjugates with Enhanced Immune Effector Functions.

Optimizing the interaction between antibody (mAb)-based therapeutics and immune effector functions (EFs) offers opportunities to improve the therapeutic window of these molecules. However, the role of EFs in antibody-drug conjugate (ADC) efficacy and toxicity remains unknown, with limited studies that have investigated how modulation of EF affects the pharmacology of ADCs. This study aimed to evaluate the effect of EF modulation on ADC efficacy using trastuzumab-vc-MMAE as a model ADC.

Updates on Breast Reconstruction: Surgical Techniques, Challenges, and Future Directions.

The increasing global incidence of breast cancer underscores the significance of breast reconstruction in enhancing patients' quality of life. Breast reconstruction primarily falls into two categories: implant-based techniques and autologous tissue transfers. In this study, we present a comprehensive review of various aspects of implant-based reconstruction, including different types of implants, surgical techniques, and their respective advantages and disadvantages.

Correction to: Infection's Association With Decreased Risk of Breast Cancer.

[This corrects the article DOI: 10.14740/wjon1617.].

Is it time to Reassess The Role of Preoperative HypoalbuminemiaAmong Geriatric Distal Femur Fracture Patients?

Background: Hypoalbuminemia, blanketly defined as Albumin < 3.5 g/dL, is often utilized as a threshold associated with postoperative complications and mortality among orthopedic and non-orthopedic surgical procedures. Albumin level is influenced by a myriad of factors including liver function, malnutrition, and inflammation.

Computer modeling of bevacizumab drug distribution after intravitreal injection in rabbit and human eyes.

Age-related macular degeneration (AMD) is a progressive eye disease that causes loss of central vision and has no cure. Wet AMD is the late neovascular form treated with vascular endothelial growth factor (VEGF) inhibitors. VEGF is the critical driver of wet AMD.