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.

Development of a Deep Learning Tool to Support the Assessment of Thyroid Follicular Cell Hypertrophy in the Rat.

Thyroid tissue is sensitive to the effects of endocrine disrupting substances, and this represents a significant health concern. Histopathological analysis of tissue sections of the rat thyroid gland remains the gold standard for the evaluation for agrochemical effects on the thyroid. However, there is a high degree of variability in the appearance of the rat thyroid gland, and toxicologic pathologists often struggle to decide on and consistently apply a threshold for recording low-grade thyroid follicular hypertrophy.

Proteins Involved in Endothelial Function and Inflammation Are Implicated in Cerebral Small Vessel Disease.

Background: Endothelial dysfunction and inflammation have been implicated in the pathophysiology of cerebral small vessel disease (SVD). However, whether they are causal, and if so which components of the pathways represent potential treatment targets, remains uncertain.

Methods: Two-sample Mendelian randomization (MR) was used to test the association between the circulating abundance of 996 proteins involved in endothelial dysfunction and inflammation and SVD.

Genomic epidemiology of extended-spectrum beta-lactamase-producing from humans and a river in Aotearoa New Zealand.

In Aotearoa New Zealand, urinary tract infections in humans are commonly caused by extended-spectrum beta-lactamase (ESBL)-producing . This group of antimicrobial-resistant bacteria are often multidrug resistant. However, there is limited information on ESBL-producing found in the environment and their link with human clinical isolates.

Predicting purification process fit of monoclonal antibodies using machine learning.

In early-stage development of therapeutic monoclonal antibodies, assessment of the viability and ease of their purification typically requires extensive experimentation. However, the work required for upstream protein expression and downstream purification development often conflicts with timeline pressures and material constraints, limiting the number of molecules and process conditions that can reasonably be assessed. Recently, high-throughput batch-binding screen data along with improved molecular descriptors have enabled development of robust quantitative structure-property relationship (QSPR) models that predict monoclonal antibody chromatographic binding behavior from the amino acid sequence.

Illustrating the structures of bias from immortal time using directed acyclic graphs.

Background: Immortal time is a period of follow-up during which death or the study outcome cannot occur by design. Bias from immortal time has been increasingly recognized in epidemiological studies. However, the fundamental causes and structures of bias from immortal time have not been explained systematically.

Opioid use disorder and brain health: observational and genetic associations.

Background: The long-term impact of opioid use disorder (OUD) on brain health has been little explored although of potentially high public health importance.

Objectives: To investigate the potential causal impact of OUD on later life brain health outcomes, including dementia, stroke and brain structure.

Methods: Observational and Mendelian randomization (MR) analyses were conducted.

The under-representation of women in cardiovascular clinical trials: State-of-the-art review and ethical considerations.

This review describes and evaluates the representation of women in cardiovascular randomized controlled trials (RCT), it reports significant under-representation of women in clinical trials both as participants and researchers and discusses the ethical implications of under-representation. The under-representation of women as participants in cardiovascular RCTs is evident in trials investigating cardiovascular drugs, acute coronary syndrome, heart failure and interventional procedures and devices. Under-representation of women is also evident in the authorship of cardiovascular clinical trials and in trial leadership roles, and under-representation of women as trial investigators is independently associated with under- recruitment of women as trial participants.

A study of sheep scab in Northern Ireland including detection and identifying barriers to control.

Background: Sheep scab, caused by the highly infectious mite, is considered to be endemic in Northern Ireland, although little investigation has been reported. A pilot project was undertaken to engage farmers, confirm cases with diagnostic methods and identify specific barriers to control, with the aim of informing future control programmes.

Methods: Through farmers self-reporting suspected outbreaks, on-farm risk assessments and clinical investigations were carried out by the farm's veterinary surgeon, who utilised light microscopy and serological testing to diagnose scab.

New Campylobacter Lineages in New Zealand Freshwater: Pathogenesis and Public Health Implications.

This study investigated the diversity of thermophilic Campylobacter species isolated from three New Zealand freshwater catchments affected by pastoral and urban activities. Utilising matrix-assisted laser desorption ionisation-time of flight and whole genome sequence analysis, the study identified Campylobacter jejuni (n = 46, 46.0%), C.

Novel loci and biomedical consequences of iron homoeostasis variation.

Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported.

Simple indices of infarct size post ST-Elevation Myocardial Infarction (STEMI) provides similar risk stratification to cardiac MRI.

Introduction: Myocardial Infarct Size (IS) determined soon after ST-segment elevation myocardial infarction (STEMI) has prognostic significance, and can be assessed by cardiac biomarker levels, electrocardiographic (ECG) parameters, and imaging modalities (including echocardiography and cardiac magnetic resonance imaging [CMRI]).

Objectives And Methods: We evaluated methods of IS assessment, 12-lead ECG Selvester QRS scores and high-sensitivity Troponin T (hsTnT) levels measured ≥48hr (plateau phase of hsTnT elevation), compared to paired CMRIs and echocardiograms, in a prospective cohort of patients with STEMI undergoing percutaneous coronary intervention (PCI) during the index hospitalisation. Associations were determined between IS, as assessed by these methods, and 24-month major adverse cardiac events (MACE), a hierarchical composite of: death, stroke and hospitalization for heart failure.

Proteome-Wide Genetic Investigation of Large Artery Stiffness.

The molecular mechanisms contributing to large artery stiffness (LAS) are not fully understood. The aim of this study was to investigate the association between circulating plasma proteins and LAS using complementary proteomic and genomic analyses. A total of 106 proteins associated with carotid-femoral pulse-wave velocity, a noninvasive measure of LAS, were identified in 1,178 individuals from the Asklepios study cohort.

A hierarchical hepatic de novo lipogenesis substrate supply network utilizing pyruvate, acetate, and ketones.

Hepatic de novo lipogenesis (DNL) is a fundamental physiologic process that is often pathogenically elevated in metabolic disease. Treatment is limited by incomplete understanding of the metabolic pathways supplying cytosolic acetyl-CoA, the obligate precursor to DNL, including their interactions and proportional contributions. Here, we combined extensive C tracing with liver-specific knockout of key mitochondrial and cytosolic proteins mediating cytosolic acetyl-CoA production.

Assessing antimicrobial resistance in pasture-based dairy farms: a 15-month surveillance study in New Zealand.

Antimicrobial resistance is a global public and animal health concern. Antimicrobial resistance genes (ARGs) have been detected in dairy farm environments globally; however, few longitudinal studies have utilized shotgun metagenomics for ARG surveillance in pasture-based systems. This 15-month study aimed to undertake a baseline survey using shotgun metagenomics to assess the relative abundance and diversity of ARGs in two pasture-based dairy farm environments in New Zealand with different management practices.