The Ellipsoid Zone Is a Structural Biomarker for Visual Outcomes in Diabetic Macular Edema and Macular Hole Management.

Objectives: The goal was to study the ellipsoid zone (EZ) as a structural biomarker for final visual outcomes after pharmacological intervention in center-involving diabetic macular edema (DME) and surgical intervention for full-thickness macular holes (FTMHs).

Methods: This was a tertiary care center-based retrospective study. After sample size calculations, data from 64 consecutive cases were collected, with subjects aged between 40 and 60 years.

Effect of Hydration on Viscoelastic Tensile Properties of Sclera.

The present work characterized the effects of hydration on the viscoelastic tensile properties of the sclera. Scleral strips were dissected from the posterior region near the optic nerve head of porcine eyes in the superior-inferior direction. The samples were divided into four hydration groups and their mechanical response was characterized by conducting uniaxial tensile stress-relaxation experiments.

A Strategy for Simultaneous Engineering of Interspecies Cross-Reactivity, Thermostability, and Expression of a Bispecific 5T4 x CD3 DART Molecule for Treatment of Solid Tumors.

Bispecific antibodies represent a promising class of biologics for cancer treatment. However, their dual specificity and complex structure pose challenges in the engineering process, often resulting in molecules with good functional but poor physicochemical properties. To overcome limitations in the properties of an anti-5T4 x anti-CD3 (α5T4 x αCD3) DART molecule, a phage-display method was developed, which succeeded in simultaneously engineering cross-reactivity to the cynomolgus 5T4 ortholog, improving thermostability and the elevating expression level.

Phenomenological Modeling of Antibody Response from Vaccine Strain Composition.

The elicitation of broadly neutralizing antibodies (bnAbs) is a major goal of vaccine design for highly mutable pathogens, such as influenza, HIV, and coronavirus. Although many rational vaccine design strategies for eliciting bnAbs have been devised, their efficacies need to be evaluated in preclinical animal models and in clinical trials. To improve outcomes for such vaccines, it would be useful to develop methods that can predict vaccine efficacies against arbitrary pathogen variants.

Rat as a Predictive Model for Human Clearance and Bioavailability of Monoclonal Antibodies.

Background: The prediction of human clearance (CL) and subcutaneous (SC) bioavailability is a critical aspect of monoclonal antibody (mAb) selection for clinical development. While monkeys are a well-accepted model for predicting human CL, other preclinical species have been less-thoroughly explored. Unlike CL, predicting the bioavailability of SC administered mAbs in humans remains challenging as contributing factors are not well understood, and preclinical models have not been systematically evaluated.

Coupling high-throughput and modeling approaches to streamline early-stage process development for biologics.

Platforms have long been implemented for downstream process development of monoclonal antibodies (mAbs) to streamline development and reduce timelines. These platforms are also increasingly being used for other complex biologics modalities. While development has traditionally been conducted at the lab bench scale in a sequential manner, automated miniaturized and parallelized approaches like RoboColumns and resin plates have also been implemented for chromatographic screening.

Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS/MS Proteomic Assay for Wilson Disease and Inborn Errors of Immunity.

For many genetic disorders, there are no specific metabolic biomarkers nor analytical methods suitable for newborn population screening, even where highly effective preemptive treatments are available. The direct measurement of signature peptides as a surrogate marker for the protein in dried blood spots (DBSs) has been shown to successfully identify patients with Wilson Disease (WD) and three life-threatening inborn errors of immunity, X-linked agammaglobulinemia (XLA), Wiskott-Aldrich syndrome (WAS), and adenosine deaminase deficiency (ADAD). A novel proteomic-based multiplex assay to detect these four conditions from DBS using high-throughput LC-MS/MS was developed and validated.

Development, Validation, and Application of the Paya Hamsan Technologies Underivatized Newborn Screening Assay (PHUNSA) for Inborn Metabolic Disorders in Dried Blood Spot Samples from Iranian Infants.

Screening for inborn metabolic disorders (IMDs) in newborns is an important way to prevent serious metabolic and developmental difficulties that can result in lasting disabilities or even death. Electrospray ionization tandem mass spectrometry (MS/MS) provides an efficacious newborn blood spot screening (NBS) mechanism for analyzing dried blood spot specimens (DBSs) for biochemical markers for these conditions. Where possible, the elimination of derivatization in specimen preparation can simplify and streamline analysis.

Parent Reports of Developmental Service Utilization After Newborn Screening.

Newborn screening (NBS) presents an opportunity to identify a subset of babies at birth who are at risk for developmental delays and could benefit from a range of developmental services. Potential developmental services in the United States include Part C Early Intervention (EI), private therapies, and school-based services. Using parent-reported outcomes, this study examined the rates at which a sample of children diagnosed with NBS conditions used each developmental service.

Consolidated Newborn Bloodspot Screening Efforts in Developing Countries in the Asia Pacific-2024.

Approximately half of all births globally occur in the Asia Pacific Region. Concerted efforts to support local activities aimed at developing national newborn screening (NBS) have been ongoing for almost 30 years, first by the International Atomic Energy Agency (IAEA) and then through volunteer efforts. Sustainable newborn bloodspot screening (NBS) continues to be initiated and develop in many of the countries with developing economies in the region.

Genetic Predisposition to Hippocampal Atrophy and Risk of Amnestic Mild Cognitive Impairment and Alzheimer's Dementia.

Background: There is a paucity of evidence on the association between genetic propensity for hippocampal atrophy with cognitive outcomes. Therefore, we examined the relationship of the polygenic risk score for hippocampal atrophy (PRShp) with the incidence of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) as well as the rates of cognitive decline.

Methods: Participants were drawn from the population-based HELIAD cohort.

Two Clinically Implementable Digital PCR Assessments of DNA Methylation for Diagnosing Heavy Alcohol Consumption.

Background: Heavy alcohol consumption (HAC) has a profound adverse effect on human health. Unfortunately, there is a relative lack of tools that are easily implementable in clinical settings and that can be used to supplement self-reporting in the diagnosis and management of HAC. In part, this paucity is due to limitations of currently available biological measures and a mismatch between available biological measures and the needs of clinicians managing HAC.

Distinguishing Early from Late Mild Cognitive Impairment Using Magnetic Resonance Free-Water Diffusion Tensor Imaging.

Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease. Differentiating early MCI (EMCI) from late MCI (LMCI) is crucial for early diagnosis and intervention. This study used free-water diffusion tensor imaging (fw-DTI) to investigate white matter differences and voxel-based correlations with Mini-Mental State Examination (MMSE) scores.

Trends and Disparities in Parkinson's Disease Mortality in the United States with Predictions Using Machine Learning.

Background: Parkinson's disease (PD) is a progressive neurodegenerative condition characterized by the degradation of dopaminergic pathways in the brain. As the population in the United States continues to age, it is essential to understand the trends in mortality related to PD. This analysis of PD's mortality characterizes temporal shifts, examines demographic and regional differences, and provides machine-learning predictions.

Discovery of Innate Immune Response mRNAs That Are Impacted by Structure-Specific Oral Baker's Yeast Beta Glucan Consumption.

The study of nutritional compounds with the potential to train the innate immune response has implications for human health. The objective of the current study was to discover by what means 6 weeks of oral baker's yeast beta glucan (BYBG) supplementation altered the mRNA expression of genes that reflect innate immune training in the absence of a physical stressor. Nineteen adults were randomly assigned to either a Wellmune BYBG or Placebo for 6 weeks.

Current Approaches for Genetic Manipulation of spp.-Key Bacteria for Biotechnology and Environment.

Organisms from the genus feature actinobacteria with complex developmental cycles and a great ability to produce a variety of natural products. These soil bacteria produce more than 2/3 of antibiotics used in medicine, and a large variety of bioactive compounds for industrial, medical and agricultural use. Although spp.

Advances in magnetic nanoparticles for molecular medicine.

Magnetic nanoparticles (MNPs) are highly versatile nanomaterials in nanomedicine, owing to their diverse magnetic properties, which can be tailored through variations in size, shape, composition, and exposure to inductive magnetic fields. Over four decades of research have led to the clinical approval or ongoing trials of several MNP formulations, fueling continued innovation. Beyond traditional applications in drug delivery, imaging, and cancer hyperthermia, MNPs have increasingly advanced into molecular medicine.

Endocrine Disrupting Toxicity of Bisphenol A and Its Analogs: Implications in the Neuro-Immune Milieu.

Endocrine-disrupting chemicals (EDCs) are natural or synthetic substances that are able to interfere with hormonal systems and alter their physiological signaling. EDCs have been recognized as a public health issue due to their widespread use, environmental persistence and the potential levels of long-term exposure with implications in multiple pathological conditions. Their reported adverse effects pose critical concerns about their use, warranting their strict regulation.

Assessing Variability in Children's Exposure to Contaminants in Food: A Longitudinal Non-Targeted Analysis Study in Miami, Florida.

Food is essential for human survival; however, food can be an important route of exposure to contaminants. This study investigated the presence and distribution of anthropogenic contaminants in food consumed by families with small children in South Florida, United States, evaluating seasonal and socio-economic variabilities in chemical composition. QuEChERS protocols, followed by non-targeted analysis (NTA) using an LC-Orbitrap HRMS system, were used for the comprehensive screening of organic contaminants.

Joint Effects of Lifestyle Habits and Heavy Metals Exposure on Chronic Stress Among U.S. Adults: Insights from NHANES 2017-2018.

Background: Chronic stress, characterized by sustained activation of physiological stress response systems, is a key risk factor for numerous health conditions. Allostatic load (AL), a biomarker of cumulative physiological stress, offers a quantitative measure of this burden. Lifestyle habits such as alcohol consumption and smoking, alongside environmental exposures to toxic metals like lead, cadmium, and mercury, were individually implicated in increasing AL.

Impact of Varying Sleep Pressure on Daytime Sleep Propensity in Healthy Young and Older Adults.

Fixed sleep schedules with an 8 h time in bed (TIB) are used to ensure participants are well-rested before laboratory studies. However, such schedules may lead to cumulative excess wakefulness in young individuals. Effects on older individuals are unknown.

Impact of a Structured Social Skills Training Program on Adolescents and Young Adults with Level 1 Autism.

Background/objectives: Level 1 autism spectrum disorder (ASD) is a neurodevelopmental condition characterised by challenges in social and communication skills. Despite these difficulties, individuals with level 1 ASD often exhibit average intelligence and typical language development. Improving socialisation skills in this population requires tailored approaches that address their specific needs and include targeted strategies.

Exploring Dysphagia in Congenital Diaphragmatic Hernia: A Retrospective Analysis.

Congenital diaphragmatic hernia (CDH) is a complex congenital disorder often accompanied by long-term feeding difficulties. There is a paucity of published data regarding the impact of swallowing difficulties on long-term patient outcomes. Our study attempts to evaluate this phenomenon.

In-line prediction of viability and viable cell density through machine learning-based soft sensor modeling and an integrated systems approach: An industrially relevant PAT case study.

The biopharmaceutical industry is shifting toward employing digital analytical tools for improved understanding of systems biology data and production of quality products. The implementation of these technologies can streamline the manufacturing process by enabling faster responses, reducing manual measurements, and building continuous and automated capabilities. This study discusses the use of soft sensor models for prediction of viability and viable cell density (VCD) in CHO cell culture processes by using in-line optical density and permittivity sensors.

Ear pinna growth and differentiation is conserved in murids and requires BMP signaling for chondrocyte proliferation.

Despite being a major target of reconstructive surgery, development of the ear pinna remains poorly studied. Here we provide a cellular characterization of late gestational and postnatal ear pinna development in two rodents and investigate the role of BMP5 in expansion and differentiation of auricular elastic cartilage. We find that ear pinna development is largely conserved between Mus musculus and the highly regenerative Acomys dimidiatus.