Leveraging high-throughput analytics and automation to rapidly develop high-concentration mAb formulations: integrated excipient compatibility and viscosity screening.

Background: Formulation screening is essential to experimentally balance stability and viscosity in high-concentration mAb formulations. We developed a high-throughput approach with automated sample preparation and analytical workflows to enable the integrated assessment of excipient compatibility and viscosity of mAb formulations.

Methods: Ninety-six formulations of a trastuzumab biosimilar were screened by combining 8 types of excipient modifiers with 4 types of buffers across a pH range of 4.

Cohort profile: AI-driven national Platform for CCTA for clinicaL and industriaL applicatiOns (APOLLO).

Purpose: Coronary CT angiography (CCTA) is well established for the diagnostic evaluation and prognostication of coronary artery disease (CAD). The growing burden of CAD in Asia and the emergence of novel CT-based risk markers highlight the need for an automated platform that integrates patient data with CCTA findings to provide tailored, accurate cardiovascular risk assessments. This study aims to develop an artificial intelligence (AI)-driven platform for CAD assessment using CCTA in Singapore's multiethnic population.

UHRF1 ubiquitin ligase activity supports the maintenance of low-density CpG methylation.

The RING E3 ubiquitin ligase UHRF1 is an established cofactor for DNA methylation inheritance. The model posits that nucleosomal engagement through histone and DNA interactions directs UHRF1 ubiquitin ligase activity toward lysines on histone H3 tails, creating binding sites for DNMT1 through ubiquitin interacting motifs (UIM1 and UIM2). However, the extent to which DNMT1 relies on ubiquitin signaling through UHRF1 in support of DNA methylation maintenance remains unclear.

FAIM: Fairness-aware interpretable modeling for trustworthy machine learning in healthcare.

The escalating integration of machine learning in high-stakes fields such as healthcare raises substantial concerns about model fairness. We propose an interpretable framework, fairness-aware interpretable modeling (FAIM), to improve model fairness without compromising performance, featuring an interactive interface to identify a "fairer" model from a set of high-performing models and promoting the integration of data-driven evidence and clinical expertise to enhance contextualized fairness. We demonstrate FAIM's value in reducing intersectional biases arising from race and sex by predicting hospital admission with two real-world databases, the Medical Information Mart for Intensive Care IV Emergency Department (MIMIC-IV-ED) and the database collected from Singapore General Hospital Emergency Department (SGH-ED).

Molecular dynamics simulations provide insights into ULK-101 potency and selectivity toward autophagic kinases ULK1/2.

Kinase domains are highly conserved within proteins in both sequence and structure. Many factors, including phosphorylation, amino acid substitutions or mutations, and small molecule inhibitor binding, influence conformations of the kinase domain and enzymatic activity. ULK1 and ULK2 are serine/threonine kinases that serve important roles in autophagy, an intracellular recycling process capable of degrading proteins and organelles fusion with lysosomes.

Procedure-related readmissions following endoscopic retrograde cholangiopancreatography in a liver transplant cohort.

Background And Aim: Data on post-endoscopic retrograde cholangiopancreatography (ERCP) adverse events and readmission rates in liver transplantation (LT) patients remain scarce. This study determined the 30-day procedure-related readmission rate following ERCP in an LT cohort at an Australian tertiary academic center.

Methods: All unplanned readmissions within 30 days following ERCP in orthotopic LT patients between December 2012 and August 2021 were retrospectively identified.

SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins.

As of 2024, SARS-CoV-2 continues to propagate and drift as an endemic virus, impacting healthcare for years. The largest sequencing initiative for any species was initiated to combat the virus, tracking changes over time at a full virus base-pair resolution. The SARS-CoV-2 sequencing represents a unique opportunity to understand selective pressures and viral evolution but requires cross-disciplinary approaches from epidemiology to functional protein biology.

Embryonic heat conditioning increases lipolytic gene expression in broiler chicks at day 4 post-hatch.

Introduction: Exposure to elevated temperatures during incubation is known to induce epigenetic changes that are associated with immunological and stress-response differences at a later age. Reports on its effects on the adipose tissue are still scarce. In this experiment, we investigated the effect of embryonic heat conditioning (EHC) on growth, adipose tissue mRNA and global DNA methylation in broiler chicks at day 4 post-hatch.

Valsartan Rescues Suppressed Mitochondrial Metabolism during Insulin Resistance in C2C12 Myotubes.

Elevated circulating branched-chain amino acids (BCAA) have been linked with the severity of insulin resistance across numerous populations, implicating heightened BCAA metabolism as a potential therapy for insulin resistance. Recently, the angiotensin II type 1 receptor (AT1R) inhibitor Valsartan (VAL) was identified as a potent inhibitor of branched-chain alpha-keto acid dehydrogenase kinase (BCKDK), a negative regulator of BCAA metabolism. This work investigated the effect of VAL on myotube metabolism and insulin sensitivity under both insulin sensitive and insulin resistant conditions.

Excess Branched-Chain Amino Acids Suppress Mitochondrial Function and Biogenic Signaling but Not Mitochondrial Dynamics in a Myotube Model of Skeletal Muscle Insulin Resistance.

Branched-chain amino acids (BCAA) are correlated with severity of insulin resistance, which may partially result from mitochondrial dysfunction. Mitochondrial dysfunction is also common during insulin resistance and is regulated in part by altered mitochondrial fusion and fission (mitochondrial dynamics). To assess the effect of BCAA on mitochondrial dynamics during insulin resistance, the present study examined the effect of BCAA on mitochondrial function and indicators of mitochondrial dynamics in a myotube model of insulin resistance.

Effect of mTORC Agonism via MHY1485 with and without Rapamycin on C2C12 Myotube Metabolism.

Unlabelled: The mechanistic target of rapamycin complex (mTORC) regulates protein synthesis and can be activated by branched-chain amino acids (BCAAs). mTORC has also been implicated in the regulation of mitochondrial metabolism and BCAA catabolism. Some speculate that mTORC overactivation by BCAAs may contribute to insulin resistance.

Safety and efficacy of Kaffes intraductal self-expanding metal stents in the management of post-liver transplant anastomotic strictures.

Background: Endoscopic management is the first-line therapy for post-liver-transplant anastomotic strictures. Although the optimal duration of treatment with plastic stents has been reported to be 8-12 months, data on safety and duration for metal stents in this setting is scarce. Due to limited access to endoscopic retrograde cholangiopancreatography (ERCP) during the coronavirus disease 2019 pandemic in our centre, there was a change in practice towards increased usage and length-of-stay of the Kaffes biliary intraductal self-expanding stent in patients with suitable anatomy.

Oleuropein has hypophagic effects in broiler chicks.

Oleuropein, a phenolic compound derived from olives, has known glucoregulatory effects in mammalian models but effects in birds are unknown. We investigated effects of dietary supplementation and exogenous administration of oleuropein on broiler chick feed intake and glucose homeostasis during the first 7 days post-hatch. One hundred and forty-eight day-of-hatch broiler chicks were randomly allocated to one of four dietary treatments with varying oleuropein concentrations (0, 250, 500, or 1,000 mg/kg).

Fructose Reduces Mitochondrial Metabolism and Increases Extracellular BCAA during Insulin Resistance in C2C12 Myotubes.

Unlabelled: Fructose is a commonly consumed monosaccharide implicated in developing several metabolic diseases. Previously, elevated branched-chain amino acids (BCAA) have been correlated with the severity of insulin resistance. Most recently, the effect of fructose consumption on the downregulation of BCAA catabolic enzymes was observed.

The biphasic activity of autophagy and heat shock protein response in peripheral blood mononuclear cells following acute resistance exercise in resistance-trained males.

Purpose: Autophagy and heat shock protein (HSP) response are proteostatic systems involved in the acute and adaptive responses to exercise. These systems may upregulate sequentially following cellular stress including acute exercise, however, currently few data exist in humans. This study investigated the autophagic and HSP responses to acute intense lower body resistance exercise in peripheral blood mononuclear cells (PBMCs) with and without branched-chain amino acids (BCAA) supplementation.

Factorial validity and measurement invariance of the Athlete Burnout Questionnaire (ABQ).

The Athlete Burnout Questionnaire (ABQ) is the gold standard measure for burnout in athletes. However, previous assessments of factorial validity have: (a) tested overly restrictive measurement models; (b) provided mixed support for factorial validity; and (c) not been applied to assess measurement invariance across gender, sport type, or age. To address these issues, we used ABQ data provided by 914 athletes (M = 21.

Empowering the Participant Voice (EPV): Design and implementation of collaborative infrastructure to collect research participant experience feedback at scale.

Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases.

Post-translational mechanisms in psychostimulant-induced neurotransmitter efflux.

The availability of monoamine neurotransmitters in the brain is under the control of dopamine, norepinephrine, and serotonin transporters expressed on the plasma membrane of monoaminergic neurons. By regulating transmitter levels these proteins mediate crucial functions including cognition, attention, and reward, and dysregulation of their activity is linked to mood and psychiatric disorders of these systems. Amphetamine-based transporter substrates stimulate non-exocytotic transmitter efflux that induces psychomotor stimulation, addiction, altered mood, hallucinations, and psychosis, thus constituting a major component of drug neurochemical and behavioral outcomes.

UHRF1 ubiquitin ligase activity supports the maintenance of low-density CpG methylation.

The RING E3 ubiquitin ligase UHRF1 is an established cofactor for DNA methylation inheritance. Nucleosomal engagement through histone and DNA interactions directs UHRF1 ubiquitin ligase activity toward lysines on histone H3 tails, creating binding sites for DNMT1 through ubiquitin interacting motifs (UIM1 and UIM2). Here, we profile contributions of UHRF1 and DNMT1 to genome-wide DNA methylation inheritance and dissect specific roles for ubiquitin signaling in this process.

Agreement between Hammersmith Neonatal Neurological Examination (HNNE) and Test of Infant Motor Performance (TIMP) in neurodevelopmental assessment of preterm infants <32 weeks' gestation at term corrected age.

Objectives: To determine the agreement between HNNE and TIMP at TCA for preterm infants born <32 weeks' gestation, and to evaluate their correlation to PDMS-2 at 12-month corrected age (CA).

Methods: Infants born between November 2013 to June 2022 who had both HNNE and TIMP performed at TCA of 37-41 weeks gestation, and motor outcome assessed using the PDMS-2 at 12-month old were enrolled. The HNNE and 12-month PDMS-2 findings were categorized as optimal vs sub-optimal.

The BCKDH kinase inhibitor BT2 promotes BCAA disposal and mitochondrial proton leak in both insulin-sensitive and insulin-resistant C2C12 myotubes.

Elevated circulating branched-chain amino acids (BCAAs) have been correlated with the severity of insulin resistance, leading to recent investigations that stimulate BCAA metabolism for the potential benefit of metabolic diseases. BT2 (3,6-dichlorobenzo[b]thiophene-2-carboxylic acid), an inhibitor of branched-chain ketoacid dehydrogenase kinase, promotes BCAA metabolism by enhancing BCKDH complex activity. The purpose of this report was to investigate the effects of BT2 on mitochondrial and glycolytic metabolism, insulin sensitivity, and de novo lipogenesis both with and without insulin resistance.