Free light chains

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management. OBJECTIVE: To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model...

BACKGROUND AND PURPOSE: Rapid detection test via lateral flow immunoassay (LFIA) is employed as an alternate method to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Gold nanoparticles (AuNPs), a vital component of LFIA, can be synthesized by laser ablation technique. This intense laser radiation may result in monodisperse gold nanoclusters, which are impurity-free and demonstrate innovative biocompatible surface chemistry. In this current research, laser-ablated AuNPs are produced and coupled with an anti-spike SARS-CoV-2 monoclonal antibody (mAb) generated in our prior study...

UNLABELLED: Insulin Wakayama is a clinical insulin variant where a conserved valine at the third residue on insulin's A chain (Val A3 ) is replaced with a leucine (Leu A3 ), impairing insulin receptor (IR) binding by 140-500 fold. This severe impact on binding from such a subtle modification has posed an intriguing problem for decades. Although experimental investigations of natural and unnatural A3 mutations have highlighted the sensitivity of insulin-IR binding to minor changes at this site, an atomistic explanation of these binding trends has remained elusive...

Elaeagnus moorcroftii Wall. ex Schlecht. (EWS) has extensive nutrients and functional active ingredients, which makes it an excellent potential substrate for fermentation. The improvement in the antioxidant activity of Elaeagnus moorcroftii Wall. ex Schlecht. juice (EWSJ) fermented by Bifidobacterium animalis subsp. lactis HN-3 (B.an3) could be attributed to the metabolism and biotransformation of plant-based products by the bacterial strain. To reveal the underlying mechanism, non-targeted metabolomics was applied in this study...

Using a rat autologous orthotopic liver transplantation (AOLT) model and liver cold ischemia-reperfusion (I/R)-induced intestinal injury, we clarified whether ferroptosis occurred in rat AOLT cold I/R-induced intestinal injury. Additionally, the role and possible mechanism of the ferroptosis activator sulfasalazine (SAS) in intestinal injury-induced ferroptosis in rats with AOLT liver cold I/R were investigated. Sixty specific pathogen free (SPF)-grade adult male Sprague‒Dawley (SD) rats were randomly divided into 5 groups using the random number table method (n = 12)...

Light chain measurements form an essential component of the testing strategy for the detection and monitoring of patients with suspected and/or proven plasma cell disorders. Urine-based electrophoretic assays remain at the centre of the international guidelines for response assessment but the supplementary role of serum-free light chain (FLC) assays in response assessment and the detection of disease progression due to their increased sensitivity has been increasingly recognised since their introduction in 2001...

INTRODUCTION: Body fluid markers could be helpful to predict the conversion into clinically definite multiple sclerosis (MS) in people with a first demyelinating event of the central nervous system (CNS). Consequently, biomarkers such as oligoclonal bands, which are integrated in the current MS diagnostic criteria, could assist early MS diagnosis. AREAS COVERED: This review examines existing knowledge on a broad spectrum of body fluid markers in people with a first CNS demyelinating event, explores their potential to predict conversion to MS, to assess MS disease activity, as well as their utility to differentiate MS from atypical demyelinating disorders such as neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein associated disease...

Analyzing human body movement is a critical aspect of biomechanical studies in road safety. While most studies have traditionally focused on assessing the head-neck system due to the restraint provided by seat belts, it is essential to examine the entire pelvis-thorax-head kinematic chain when these body regions are free to move. The absence of restraint systems is prevalent in public transport and is also being considered for future integration into autonomous vehicles operating at low speeds. This article presents an experimental study examining the movement of the pelvis, thorax and head of 18 passengers seated without seat belts during emergency braking in an autonomous bus...

Simple yet ultrasensitive and contamination-free quantification of environmental pathogenic bacteria is in high demand. In this study, we present a portable clustered regularly interspaced short palindromic repeats-associated protein 12a (CRISPR/Cas12a) powered Air-displacement enhanced Evanescent wave fluorescence Fiber-embedded microfluidic Biochip (AEFB) for the high-frequency and nucleic acid amplification-free ultrasensitive detection of Escherichia coli O157:H7. The performance of AEFB was dramatically enhanced upon employing a simple air-solution displacement process...

Metal-free organic photocatalysts for photo-mediated reversible deactivation radical polymerization (photo-RDRP) are witnessed to make increasing advancement in the precise synthesis of polymers. However, challenges still exist in the development of high-efficiency and environmentally sustainable carbon dots (CDs)-based organocatalysts. Herein, N-doped CDs derived from phenanthroline derivative (Aphen) are prepared as metal-free photocatalysts for photoinduced electron transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization...

The synthesis of synthetic intracellular polymers offers groundbreaking possibilities in cellular biology and medical research, allowing for novel experiments in drug delivery, bioimaging and targeted cancer therapies. These macromolecules, composed of biocompatible monomers, are pivotal in manipulating cellular functions and pathways due to their bioavailability, cytocompatibility and distinct chemical properties. This protocol details two innovative methods for intracellular polymerization. The first one uses 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959) as a photoinitiator for free radical polymerization under UV light (365 nm, 5 mW/cm2 )...

BACKGROUND: Cognitive impairment (CI) is a common and disabling feature of people with multiple sclerosis (pwMS), but its underlying mechanisms are heterogenous and not fully understood. A role of infiltrating immune cells in the meninges and brain parenchyma has been hypothesized. This study aimed to explore the hypothesis that intrathecal B cells might influence cognitive performance in pwMS. METHODS: A retrospective study was performed on 39 newly diagnosed pwMS who underwent cerebrospinal fluid (CSF) analysis...

Clostridioides difficile infection (CDI) is a significant concern caused by widespread antibiotic use, resulting in diarrhea and inflammation from the gram-positive anaerobic bacterium C. difficile . Although bezlotoxumab (Bez), a monoclonal antibody (mAb), was developed to address CDI recurrences, the recurrence rate remains high, partly due to reduced neutralization efficiency against toxin B2. In this study, we aimed to enhance the binding of Bez to C. difficile toxin B2 by combining computational simulations and mutational analyses...

Non-secreting multiple myeloma is a rare variant of multiple myeloma that affects a relatively young population. It is characterized by the non-secretory nature of malignant plasma cells. The following case report describes the history of a 54-year-old patient with non-secretory myeloma revealed by mechanical and inflammatory low back pain. The bone and neurological involvement, the presence of diffuse osteolytic lesions and the increase in the serum kappa free light chains (FLC) level prompted a myelogram...

BACKGROUND: Neurofilament light chain (NfL) is a frequently used biomarker in humans for both diagnostic and therapeutic monitoring purposes in various neurologic diseases. HYPOTHESIS/OBJECTIVES: It was hypothesized that dogs with diagnosed structural epilepsy (SE) would have a significantly higher serum NfL concentrations compared to dogs with idiopathic epilepsy (IE). The secondary hypothesis was that dogs would have a significantly higher serum NfL concentrations when measured within 7 days after a seizure compared to being seizure-free for at least 30 days...

Objective: This study aimed to investigate the influence of FGFR3 gene mutations on the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma (NDMM) . Methods: A total of 198 patients with NDMM admitted to the Department of Hematology in Jiangsu Province Hospital between January 2016 and February 2023 were retrospectively analyzed. Next-generation sequencing and cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization were performed for all patients...

Deeper responses are associated with improved survival in patients being treated for myeloma. However, the sensitivity of the current blood-based assays is limited. Historical studies suggested that normalisation of the serum free light chain (FLC) ratio in patients who were negative by immunofixation electrophoresis (IFE) was associated with improved outcomes. However, recently this has been called into question. Mass spectrometry (MS)-based FLC assessments may offer a superior methodology for the detection of monoclonal FLC due to greater sensitivity...

Antibody-mediated delivery of immunogenic viral CD8+ T-cell epitopes to redirect virus-specific T cells toward cancer cells is a promising new therapeutic avenue to increase the immunogenicity of tumors. Multiple strategies for viral epitope delivery have been shown to be effective. So far, most of these have relied on a free C-terminus of the immunogenic epitope for extracellular delivery. Here, we demonstrate that antibody-epitope conjugates (AECs) with genetically fused epitopes to the N-terminus of the antibody can also sensitize tumors for attack by virus-specific CD8+ T cells...

RN104 (2-[2-(cyclohexylmethylene)hydrazinyl)]-4-phenylthiazole) is a thiazolylhydrazone derivative with prominent antifungal activity. This work aimed to develop a self-emulsifying drug delivery system (SEDDS) loaded with RN104 to improve its biopharmaceutical properties and enhance its oral bioavailability. Medium chain triglycerides, sorbitan monooleate, and polysorbate 80 were selected as components for the SEDDS formulation based on solubility determination and a pseudo-ternary phase diagram. The formulation was optimized using the central composite design in response surface methodology...

We investigate the influence of varying confinement on the dynamics of polymer translocation through a cone-shaped channel. For this, a linear polymer chain is modeled using self-avoiding walks on a square lattice. The cis side of a cone-shaped channel has a finite volume, while the trans side has a semi-infinite space. The confining environment is varied either by changing the position of the back wall while keeping the apex angle fixed or altering the apex angle while keeping the position of the back wall fixed...