2024 White paper on recent issues in bioanalysis: Impact of LDT in US and IVDR in EU; AI/ML for High Parameter Flow Cytometry; The rise of Olink Technology; CDx for AAV Gene Therapies; Integrative Bioanalysis by Multiple Platforms; Super Sensitive ADA/NAb LBA ( - Recommendations on Advanced Strategies for Biomarkers, IVD/CDx Assays (BAV), Cell Based Assays (CBA), and Ligand-Binding Assays (LBA) - Regulatory Agencies' Input on Biomarkers, IVD/CDx, and Biomarker Assay Validation).

The 18th Workshop on Recent Issues in Bioanalysis (18th WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Avirulence depletion assay: Combining R gene-mediated selection with bulk sequencing for rapid avirulence gene identification in wheat powdery mildew.

Wheat production is threatened by multiple fungal pathogens, such as the wheat powdery mildew fungus (Blumeria graminis f. sp. tritici, Bgt).

Yes, We Can! Ensuring That our Graduating Resident's Procedural Skills Meet the Needs of Their Patients.

Objectives: There is a burgeoning discrepancy between the procedural competency of graduating diagnostic radiology residents and the needs of our patient population. The causes of this mismatch and opportunities for improvement are explored by the APDR Procedural Competency of Graduating DR Residents Task Force.

Materials And Methods: The APDR convened a task force consisting of diverse broad stakeholder viewpoints, drawing from organized radiology, academic and private practices.

Covalently Cross-Linked Polyelectrolyte Complex Nanoparticles with Enhanced Stability against Dissociation at High Ionic Strength.

Polyelectrolyte complex nanoparticles (PECNPs) often fully dissociate into individual polycations (PC) and polyanions (PA) at high salinities. Herein, we introduce a novel type of colloidally stable PECNP in which the PC is cross-linked, in this case branched polyethylenimine (PEI) to limit this dissociation, even in solutions up to 5.2 M NaCl or 5.

Genetic variants in DDX53 contribute to autism spectrum disorder associated with the Xp22.11 locus.

Autism spectrum disorder (ASD) exhibits an ∼4:1 male-to-female sex bias and is characterized by early-onset impairment of social/communication skills, restricted interests, and stereotyped behaviors. Disruption of the Xp22.11 locus has been associated with ASD in males.

Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches.

Intraocular pressure (IOP) elevation is the primary risk factor and currently the main treatable factor for progression of glaucomatous optic neuropathy. In addition to direct clinical and living animal in vivo studies, ex vivo perfusion of anterior segments and whole eyes is a key technique for studying conventional outflow function as it is responsible for IOP regulation. We present well-tested experimental details, protocols, considerations, advantages, and limitations of several ex vivo model systems for studying IOP regulation.

Exploration of (R)-[C]YH168 as a PET tracer for imaging monoacylglycerol lipase in the brain: from mice to non-human primates.

Purpose: The monoacylglycerol lipase (MAGL) plays a pivotal role in modulating the endocannabinoid system and is considered an attractive therapeutic target for diseases in both the central nervous system and periphery. The current study aimed to develop and evaluate a suitable carbon-11 labeled tracer for imaging MAGL in preclinical studies.

Methods: (R)-YH168 was synthesized via a multi-step pathway and its half-maximal inhibitory concentration (IC) values were measured using an enzymatic assay.

Derivation of toxicity parameters from field data: Analysis of lake zooplankton species responses to metals and acidity.

The WHAM-Fβ model describes the toxic effects of mixtures of protons and metal cations towards biological species, using a set of intrinsic parameters for the cations (α, α*) and a sensitivity parameter (β) for each species. We applied the model to extensive water chemistry and zooplankton species occurrence data for four lakes contaminated with acidity and metals (Al, Ni, Cu, Zn) at Sudbury, Ontario, over the period 1973-2018, during which cation contamination declined, and zooplankton species numbers increased. Assuming that the appearance of a species resulted solely from decreases in water toxicity, and that α and α* values previously derived from laboratory toxicity test data could be applied in the field, we used the field data to estimate values of β for individual lake zooplankton species.

Gut microbiota strain richness is species specific and affects engraftment.

Despite the fundamental role of bacterial strain variation in gut microbiota function, the number of unique strains of a species that can stably colonize the human intestine is still unknown for almost all species. Here we determine the strain richness (SR) of common gut species using thousands of sequenced bacterial isolates with paired metagenomes. We show that SR varies across species, is transferable by faecal microbiota transplantation, and is uniquely low in the gut compared with soil and lake environments.

Ravulizumab and Efgartigimod in Myasthenia Gravis: A Real-World Study.

Background And Objectives: Biologics that target pathogenic antibodies (Abs) and their effector functions such as the complement inhibitor ravulizumab and the neonatal Fc receptor agonist efgartigimod have recently been approved for the treatment of acetylcholine receptor (AChR)-Ab-positive myasthenia gravis (MG), but comparative studies are lacking.

Methods: In a prospective, exploratory real-world study, we assessed clinical efficacy, safety, and biological effects of ravulizumab and efgartigimod treatment initiation. Myasthenia Gravis-Activities of Daily Living and Quantitative Myasthenia Gravis scores were used as clinical endpoints.

Pathogenic proteotoxicity of cryptic splicing is alleviated by ubiquitination and ER-phagy.

RNA splicing enables the functional adaptation of cells to changing contexts. Impaired splicing has been associated with diseases, including retinitis pigmentosa, but the underlying molecular mechanisms and cellular responses remain poorly understood. In this work, we report that deficiency of ubiquitin-specific protease 39 (USP39) in human cell lines, zebrafish larvae, and mice led to impaired spliceosome assembly and a cytotoxic splicing profile characterized by the use of cryptic 5' splice sites.

Enhancing vascular access planning in CKD: validating the 40% KFRE threshold for predicting ESKD in a French retrospective cohort study.

Background: Establishing the optimal timing for creating vascular access in patients with chronic kidney disease (CKD) is a critical and challenging aspect of patient management. The Kidney Disease: Improving Global Outcomes guidelines propose using a 40% 2-year threshold based on the Kidney Failure Risk Equation (KFRE) for this purpose. However, the effectiveness of this threshold compared with traditional methods, such as estimated glomerular filtration rate (eGFR), is not well-established.

Contrastive Functional Connectivity Defines Neurophysiology-informed Symptom Dimensions in Major Depression.

Background: Major depressive disorder (MDD) is a prevalent psychiatric disorder characterized by substantial clinical and neurobiological heterogeneity. Conventional studies that solely focus on clinical symptoms or neuroimaging metrics often fail to capture the intricate relationship between these modalities, limiting their ability to disentangle the complexity in MDD. Moreover, patient neuroimaging data typically contains normal sources of variance shared with healthy controls, which can obscure disorder-specific variance and complicate the delineation of disease heterogeneity.

Method for Quantitative Analysis of Vitreoretinal Adhesion in Ex Vivo Model.

Purpose: Posterior vitreous detachment (PVD) is implicated in numerous retinal pathologies. A necessary step in developing new therapies, an area of significant interest, is a quantifiable assessment of posterior vitreous adhesion (PVA) that is also clinically relevant.

Methods: A 23-gauge vitrector was used at varying levels of vacuum to attempt PVD induction in a porcine eye model injected with either balanced salt solution (BSS) (control) or plasmin (2, 3, or 5 U), which can pharmacologically induce PVD.

Impact of Cystic Fibrosis Transmembrane Conductance Regulator Modulators on Maternal Outcomes During and After Pregnancy.

Background: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators are available to the majority of people with CF in the United States; little is known about pregnancy outcomes with modulator use. The aim of this retrospective study was to determine the impact of CFTR modulators on maternal outcomes.

Research Question: Does pregnancy differentially affect outcomes in female individuals with CF with and without CFTR modulator exposure?

Study Design And Methods: Data on pregnancies from 2010 to 2021 were collected from 11 US adult CF centers.

Discriminative functional connectivity signature of cocaine use disorder links to rTMS treatment response.

Cocaine use disorder (CUD) is prevalent, and repetitive transcranial magnetic stimulation (rTMS) shows promise in reducing cravings. However, the association between a consistent CUD-specific functional connectivity signature and treatment response remains unclear. Here we identify a validated functional connectivity signature from functional magnetic resonance imaging to discriminate CUD, with successful independent replication.