2024 White Paper on Recent Issues in Bioanalysis: Evolution of Immunogenicity Assessment beyond ADA/NAb; Regulated Genomic/NGS Assays; Hypersensitivity Reactions; Minimum Noise Reduction; False Positive Range; Modernized Vaccine Approaches; NAb/TAb Correlation - Recommendations on Advanced Strategies for Molecular Assays and Immunogenicity of Gene Therapy, Cell Therapy, Vaccine; Biotherapeutics Immunogenicity Assessment & Clinical Relevance - Regulatory Agencies' Input on Immunogenicity/Technologies of Biotherapeutics, Gene, Cell & Vaccine Therapies).

The 18 Workshop on Recent Issues in Bioanalysis (18 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 18 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.

Heterogeneity in Fluorescence-Stained Sperm Membrane Patterns and Their Dynamic Changes Towards Fertilization in Mice.

Background: Sperm represent a heterogeneous population crucial for male reproductive success. Additionally, sperm undergo dynamic changes during maturation and capacitation. Despite these well-established processes, the complex nature of sperm heterogeneity and membrane dynamics remains elusive.

Oxidative and Excitatory Neurotoxic Stresses in CRISPR/Cas9-Induced Kynurenine Aminotransferase Knockout Mice: A Novel Model for Despair-Based Depression and Post-Traumatic Stress Disorder.

Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked to disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) metabolic pathway, which generates a variety of bioactive molecules. Dysregulation of KYN metabolism, particularly low levels of kynurenic acid (KYNA), appears to be linked to neuropsychiatric disorders.

Oral Functions and Various Cooking Methods Associated With Chewing-To-Swallowing Time in Community-Dwelling Older Adults.

Background: Oral frailty in older adults can affect their eating efficiency, prolonging meal times, which can compromise food flavour.

Objective: This study explored the association between cooking methods and chewing-to-swallowing time on the basis of different oral functions in older adults.

Methods: This cross-sectional study involved 65 community-dwelling individuals aged ≥ 65 years.

Colorimetric Detection of Naphthalene Enabled by Intra- to Intermolecular Charge Transfer Interplay Induced by π-hole···π Interactions of a TPA-Attached Pyrazinacene.

A new Donor-Acceptor type pyrazinacene derivative (1) featuring strong ICT was synthesized by linking electron-donating triphenylamine (TPA) and electron-accepting CN groups via a pyrazinacene core. The compound exhibits a dramatic color change from greenish blue to red-violet upon selective recognition of naphthalene (3) to form a 1:1 co-crystal (1•3). This color change is induced by intermolecular CT between pyrazinacene and naphthalene's aromatic moieties, driven by π-hole···π interactions.

Effects of Capsaicin on Masticatory and Swallowing Function.

Introduction: Recent studies have shown that capsaicin improves the pharyngeal swallowing reflex. However, the mechanism by which capsaicin alters mastication and oesophageal function remains unclear. This study aimed to investigate the effects of capsaicin on masticatory and oesophageal function.

CXCL-10 in Cerebrospinal Fluid Detects Neuroinflammation in HTLV-1-Associated Myelopathy with High Accuracy.

Background And Objectives: HTLV-1-associated myelopathy (HAM) is a chronic progressive inflammatory disease of the spinal cord. This study assesses the diagnostic accuracy of the neuroinflammatory biomarkers neopterin and cysteine-X-cysteine motif chemokine ligand 10 (CXCL-10) in cerebrospinal fluid (CSF) for HAM.

Methods: CSF samples from 75 patients with neurological disorders-33 with HAM (Group A), 19 HTLV-1-seronegative with other neuroinflammatory diseases (Group B), and 23 HTLV-1-seronegative with non-neuroinflammatory diseases (Group C)-were retrospectively evaluated.

Serosurvey of Bovine Viral Diarrhea Virus in Cattle in Southern Japan and Estimation of Its Transmissibility by Transient Infection in Nonvaccinated Cattle.

Bovine viral diarrhea (BVD) is caused by the BVD virus (BVDV) and has been reported worldwide in cattle. To estimate BVDV circulation among cattle where few BVD cases were reported in southern Japan, 1910 serum samples collected from 35 cattle farms without a BVD outbreak were investigated to detect antibodies against BVDV-1 and BVDV-2 using an indicator virus with a cytopathogenic effect and the luciferase gene, respectively. Neutralizing antibodies against BVDV-1 and BVDV-2 were detected more frequently in 18 vaccinated farms than in 17 nonvaccinated farms.

Decrease in HBsAg After TAF Switching from Entecavir During Long-Term Treatment of Chronic Hepatitis B Virus Infection.

Achieving HBsAg seroclearance is a key goal in treating chronic hepatitis B virus (HBV) infection but remains difficult with nucleos(t)ide analogues (NAs). Tenofovir alafenamide fumarate (TAF), a recommended NA for managing chronic HBV infection (CHB), has uncertain effects on HBsAg levels and potential adverse events when used long-term after switching from entecavir (ETV). We retrospectively evaluated 77 CHB patients, including 47 who switched from ETV to TAF with a median follow-up of 40 months post-switch and a median of 60 months of HBsAg monitoring pre-switch.

Formulation Design of Orally Disintegrating Film Using Two Cellulose Derivatives as a Blend Polymer.

: Orally disintegrating film (ODF) is prepared using water-soluble polymers as film-forming agents. To improve mechanical and disintegration properties, some polymers need to be blended with others. This study aimed to investigate the utility of hydroxypropyl cellulose (HPC) and hydroxypropyl methyl cellulose (HPMC) as blend film-forming components for ODFs.

Emerging Nanoparticle-Based Diagnostics and Therapeutics for Cancer: Innovations and Challenges.

Malignant growth is expected to surpass other significant causes of death as one of the top reasons for dismalness and mortality worldwide. According to a World Health Organization (WHO) study, this illness causes approximately between 9 and 10 million instances of deaths annually. Chemotherapy, radiation, and surgery are the three main methods of treating cancer.

Sorafenib-Loaded Silica-Containing Redox Nanoparticle Decreases Tumorigenic Potential of Lewis Lung Carcinoma.

Orally administered sorafenib has shown limited improvement in overall survival for non-small-cell lung cancer patients, likely due to poor pharmacokinetics and adverse effects, including gastrointestinal toxicity. To address these issues, we developed silica-containing antioxidant nanoparticles (siRNP) as a carrier to enhance the therapeutic efficacy of lipophilic sorafenib. Sorafenib was loaded into siRNP via dialysis (sora@siRNP).

Therapeutic Efficacy of Intranasal -Acetyl-L-Cysteine with Cell-Penetrating Peptide-Modified Polymer Micelles on Neuropathic Pain in Partial Sciatic Nerve Ligation Mice.

: We previously demonstrated that the intranasal administration of cell-penetrating Tat peptide-modified carrier, PEG-PCL-Tat, improves drug delivery to the central nervous system. This study aimed to evaluate the potential of the post-onset intranasal administration of -acetyl-L-cysteine (NAC) combined with PEG-PCL-Tat (NAC/PPT) for neuropathic pain. : Neuropathic pain was induced by partial sciatic nerve ligation (PSNL) in mice.

Enhanced Drug Skin Permeation by Azone-Mimicking Ionic Liquids: Effects of Fatty Acids Forming Ionic Liquids.

: Laurocapram (Azone) attracted attention 40 years ago as a compound with the highest skin-penetration-enhancing effect at that time; however, its development was shelved due to strong skin irritation. We had already prepared and tested an ante-enhancer (IL-Azone), an ionic liquid (IL) with a similar structure to Azone, consisting of ε-caprolactam and myristic acid, as an enhancer candidate that maintains the high skin-penetration-enhancing effect of Azone with low skin irritation. In the present study, fatty acids with different carbon numbers (caprylic acid: C8, capric acid: C10, lauric acid: C12, myristic acid: C14, and oleic acid: C18:1) were selected and used with ε-caprolactam to prepare various IL-Azones in the search for a more effective IL-Azone.

The Application of Resolvin D1-Loaded Gelatin Methacrylate in a Rat Periodontitis Model.

To evaluate the drug release, cytocompatibility with periodontal ligament cells (PDLCs), and therapeutic efficacy of GelMA hydrogel loaded with resolvin D1 (RvD1) in treating rat periodontal inflammation and alveolar bone damage. An RvD1 complexed with GelMA was prepared, and its release kinetics and compatibility with PDLCs were assessed. Rats with induced periodontitis were treated weekly with topical applications of vehicle, GelMA, RvD1, or RvD1 complexed with GelMA for four weeks.

Long-Term Therapeutic Effects of Ac-DOTA-E[c(RGDfK)] Induced by Radiosensitization via G2/M Arrest in Pancreatic Ductal Adenocarcinoma.

: Alpha radionuclide therapy has emerged as a promising novel strategy for cancer treatment; however, the therapeutic potential of Ac-labeled peptides in pancreatic cancer remains uninvestigated. : In the cytotoxicity study, tumor cells were incubated with Ac-DOTA-RGD. DNA damage responses (γH2AX and 53BP1) were detected using flowcytometry or immunohistochemistry analysis.

Inhibition of Aβ Aggregation by Cholesterol-End-Modified PEG Vesicles and Micelles.

: This study aimed to design and evaluate Chol-PEG micelles and Chol-PEG vesicles as drug delivery system (DDS) carriers and inhibitors of amyloid-β (Aβ) aggregation, a key factor in Alzheimer's disease (AD). : The physical properties of Chol-PEG assemblies were characterized using dynamic light scattering (DLS), electrophoretic light scattering (ELS), and transmission electron microscopy (TEM). Inhibitory effects on Aβ aggregation were assessed via thioflavin T (ThT) assay, circular dichroism (CD) spectroscopy, and native polyacrylamide gel electrophoresis (native-PAGE).

Defensive Mechanisms of Likely Enhance Its Invasiveness as One of the World's Worst Alien Species.

Kunth is native to tropical America and has invaded tropical and subtropical Asia and numerous Pacific Islands. It forms dense thickets and reduces native species diversity and populations in its introduced range. This invasive vine also seriously impacts many agricultural crops and is listed as one of the world's 100 worst invasive alien species.

Effects of Seed Processing with Cold Plasma on Growth and Biochemical Traits of Bertoni Under Different Cultivation Conditions: In Soil Versus Aeroponics.

This study compared the effects of seed treatment with low-pressure cold plasma (CP) and atmospheric dielectric barrier discharge (DBD) plasma on morpho-biochemical traits in Bertoni plants cultivated by two methods: in soil and aeroponics. We investigated the impact of the treatments on the germination, plant growth, and content of secondary metabolites, namely steviol glycosides (SGs), rebaudioside A (RebA), and stevioside (Stev), as well as phenolic compounds and flavonoids. Seeds were treated for 2, 5, and 7 min with CP or DBD and 5 min with vacuum six days before sowing.

Effects of Source on the Nitrogen Uptake, Allocation Patterns, and Performance of Strawberry ( Duch.): A N-Tracer Study.

Nitrogen (N) is an essential determinant of strawberry growth and productivity. However, plants exhibit varying preferences for sources of nitrogen, which ultimately affects its use efficiency. Thus, it is imperative to determine the preferred N source for the optimization of indoor strawberry production.

Differential Stress Responses to Rice Blast Fungal Infection Associated with the Vegetative Growth Phase in Rice.

During vegetative growth, plants undergo various morphological and physiological changes in the transition from the juvenile phase to the adult phase. In terms of stress resistance, it has been suggested that plants gain or reinforce disease resistance during the process of maturation, which is recognized as adult plant resistance or age-related resistance. While much knowledge has been obtained about changes in disease resistance as growth stages progress, knowledge about changes in plant responses to pathogens with progressing age in plants is limited.

Phosphorus Dynamics in Managed and Natural Soils: SEM-PLS Analysis of , Forest, and Grassland Ecosystems.

Phosphorus (P) availability in soils is often constrained by its accumulation in non-labile phosphorus (NLP) forms, limiting its accessibility to plants. This study examines how soil physical properties, chemical characteristics, and climatic conditions influence phosphorus fractionation and the transformation of NLP into plant-available labile phosphorus (LP). Utilizing global structural equation modeling (SEM), we found that silt content enhances organic phosphorus fractions, including NaHCO-Po and NaOH-Po.

Metabolite Profiling and Association Analysis of Leaf Tipburn in Heat-Tolerant Bunching Onion Varieties.

The bunching onion is an important leafy vegetable, prized for its distinctive flavor and color. It is consumed year-round in Japan, where a stable supply is essential. However, in recent years, the challenges posed by climate change and global warming have resulted in adverse effects on bunching onions, including stunted growth, discoloration, and the development of leaf tipburn, threatening both crop quality and yield.

Effect of Hydrolysate Derived from Subcritical Seawater Treatment of Buckwheat Waste on the Growth of Lettuce ( L.).

This study explores the effects of a subcritical seawater treatment (SST) on buckwheat waste (BW), and the use of the hydrolysate as a liquid fertilizer to improve the growth of lettuce ( L.). Three temperature treatments (110 °C, 170 °C, 230 °C) were used for the SST, and the ionic composition in the seawater achieved the depolymerization and degradation of BW.

Maternal Vitamin D Deficiency Is a Risk Factor for Infants' Epigenetic Gestational Age Acceleration at Birth in Japan: A Cohort Study.

Background/objectives: The DNA methylation of neonatal cord blood can be used to accurately estimate gestational age. This is known as epigenetic gestational age. The greater the difference between epigenetic and chronological gestational age, the greater the association with an inappropriate perinatal fetal environment and development.