"Advancing the implementation of innovative analytical technologies in pharmaceutical manufacturing-Some regulatory considerations".

Analytical technologies and methods play a pivotal role in attribute understanding and control which are essential to the rapidly evolving field of pharmaceutical development and manufacturing. These technologies are advancing quickly, where innovations often involve both new scientific approaches and novel applications of established techniques. In many cases, the lack of harmonized global regulatory expectations presents challenges for the adoption of advanced technologies.

Interlaboratory comparison of standardised metabolomics and lipidomics analyses in human and rodent blood using the MxP Quant 500 kit.

Metabolomics and lipidomics are pivotal in understanding phenotypic variations beyond genomics. However, quantification and comparability of mass spectrometry (MS)-derived data are challenging. Standardised assays can enhance data comparability, enabling applications in multi-center epidemiological and clinical studies.

Metabolomic Fingerprints of Medical Therapy Versus Bariatric Surgery in Patients With Obesity and Type 2 Diabetes: The STAMPEDE Trial.

Objective: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are effective procedures to treat and manage type 2 diabetes (T2D). However, the underlying metabolic adaptations that mediate improvements in glucose homeostasis remain largely elusive. The purpose of this study was to identify metabolic signatures associated with biochemical resolution of T2D after medical therapy (MT) or bariatric surgery.

Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in COVID-19.

The clinical course of COVID-19 is variable and often unpredictable. To test the hypothesis that disease progression and inflammatory responses associate with alterations in the microbiome and metabolome, we analyzed metagenome, metabolome, cytokine, and transcriptome profiles of repeated samples from hospitalized COVID-19 patients and uninfected controls, and leveraged clinical information and post-hoc confounder analysis. Severe COVID-19 was associated with a depletion of beneficial intestinal microbes, whereas oropharyngeal microbiota disturbance was mainly linked to antibiotic use.

Domestic and Family Violence Affecting Children and Young People from Culturally and Racially Marginalized Migrant Backgrounds in Australia: A Scoping Review of Child Experiences and Service Responses.

In Australia, children and families from culturally and racially marginalized (CARM) migrant backgrounds experience a range of compounding structural and interpersonal factors that limit help-seeking and exacerbate the impacts of domestic and family violence (DFV). This scoping review examines the current state of knowledge on how children and young people from CARM migrant backgrounds experience DFV, and the services that respond to DFV including child protection services. A systematic search was conducted across PsycINFO, MEDLINE, and CINAHL databases and Google Scholar, alongside a complementary grey literature search.

The bioenergetic landscape of cancer.

Background: Bioenergetic remodeling of core energy metabolism is essential to the initiation, survival, and progression of cancer cells through exergonic supply of adenosine triphosphate (ATP) and metabolic intermediates, as well as control of redox homeostasis. Mitochondria are evolutionarily conserved organelles that mediate cell survival by conferring energetic plasticity and adaptive potential. Mitochondrial ATP synthesis is coupled to the oxidation of a variety of substrates generated through diverse metabolic pathways.

Quality Assessment by Bile Composition in Normothermic Machine Perfusion of Rat Livers.

The persistent challenge of organ scarcity in liver transplantation leads to an escalating dependence on organs obtained from extended criteria donors (ECD). Normothermic machine perfusion (NMP) is used for improved preservation. Due to the mimicked conditions during normothermic machine perfusion, the liver is metabolically active, which allows quality assessment during perfusion.

Ocular injuries among patients with major trauma in England and Wales from 2004 to 2021.

Background: Ocular trauma is a significant cause of blindness and is often missed in polytrauma. No contemporary studies report eye injuries in the setting of severe trauma in the UK. We investigated ocular injury epidemiology and trends among patients suffering major trauma in England and Wales from 2004 to 2021.

Mechanical heterogeneity in a soft biomaterial niche controls BMP2 signaling.

The extracellular matrix is known to impact cell function during regeneration by modulating growth factor signaling. However, how the mechanical properties and structure of biomaterials can be used to optimize the cellular response to growth factors is widely neglected. Here, we engineered a macroporous biomaterial to study cellular signaling in environments that mimic the mechanical stiffness but also the mechanical heterogeneity of native extracellular matrix.

A study protocol to characterise pathophysiological and molecular markers of rheumatic heart disease and degenerative aortic stenosis using multiparametric cardiovascular imaging and multiomics techniques.

Introduction: Rheumatic heart disease (RHD), degenerative aortic stenosis (AS), and congenital valve diseases are prevalent in sub-Saharan Africa. Many knowledge gaps remain in understanding disease mechanisms, stratifying phenotypes, and prognostication. Therefore, we aimed to characterise patients through clinical profiling, imaging, histology, and molecular biomarkers to improve our understanding of the pathophysiology, diagnosis, and prognosis of RHD and AS.

Clinically used broad-spectrum antibiotics compromise inflammatory monocyte-dependent antibacterial defense in the lung.

Hospital-acquired pneumonia (HAP) is associated with high mortality and costs, and frequently caused by multidrug-resistant (MDR) bacteria. Although prior antimicrobial therapy is a major risk factor for HAP, the underlying mechanism remains incompletely understood. Here, we demonstrate that antibiotic therapy in hospitalized patients is associated with decreased diversity of the gut microbiome and depletion of short-chain fatty acid (SCFA) producers.

Long-Term Outcomes of Medical Management vs Bariatric Surgery in Type 2 Diabetes.

Importance: Randomized clinical trials of bariatric surgery have been limited in size, type of surgical procedure, and follow-up duration.

Objective: To determine long-term glycemic control and safety of bariatric surgery compared with medical/lifestyle management of type 2 diabetes.

Design, Setting, And Participants: ARMMS-T2D (Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes) is a pooled analysis from 4 US single-center randomized trials conducted between May 2007 and August 2013, with observational follow-up through July 2022.

Promising results of a clinical feasibility study: CIRBP as a potential biomarker in pediatric cardiac surgery.

Objective: old-inducible RNA binding Protein (CIRBP) has been shown to be a potent inflammatory mediator and could serve as a novel biomarker for inflammation. Systemic inflammatory response syndrome (SIRS) and capillary leak syndrome (CLS) are frequent complications after pediatric cardiac surgery increasing morbidity, therefore early diagnosis and therapy is crucial. As CIRBP serum levels have not been analyzed in a pediatric population, we conducted a clinical feasibility establishing a customized magnetic bead panel analyzing CIRBP in pediatric patients undergoing cardiac surgery.

Effects of metformin on glucose metabolism and mitochondrial function in patients with obstructive sleep apnea: A pilot randomized trial.

Obstructive sleep apnea (OSA) is associated with increased risk for diabetes, and standard treatment with positive airway pressure (PAP) device shows inconsistent effects on glucose metabolism. Metformin is known to treat and prevent diabetes, but its effects on skeletal muscle mitochondrial function are not completely understood. Here, we evaluate the effects of metformin on glucose metabolism and skeletal muscle mitochondrial function in patients with OSA.

Restricting bioenergetic efficiency enhances longevity and mitochondrial redox capacity in Drosophila melanogaster.

Mitochondria are essential for survival and as such, impairments in organelle homeostasis significantly accelerate age-related morbidity and mortality. Here, we determined the contribution of bioenergetic efficiency to life span and health span in Drosophila melanogaster utilizing the mitochondrial uncoupler BAM15. Life span was determined in flies fed a normal diet (ND) or high fat diet (HFD) supplemented with vehicle or BAM15.

Comparing the Extraction Performance in Mouse Plasma of Different Biphasic Methods for Polar and Nonpolar Compounds.

Many metabolomic studies are interested in both polar and nonpolar analyses. However, the available sample volume often precludes multiple separate extractions. Therefore, there are major advantages in performing a biphasic extraction and retaining both phases for subsequent separate analyses.

ISG15 blocks cardiac glycolysis and ensures sufficient mitochondrial energy production during Coxsackievirus B3 infection.

Aims: Virus infection triggers inflammation and, may impose nutrient shortage to the heart. Supported by type I interferon (IFN) signalling, cardiomyocytes counteract infection by various effector processes, with the IFN-stimulated gene of 15 kDa (ISG15) system being intensively regulated and protein modification with ISG15 protecting mice Coxsackievirus B3 (CVB3) infection. The underlying molecular aspects how the ISG15 system affects the functional properties of respective protein substrates in the heart are unknown.

Working under short timescales to deliver a national trial: a case study of the ComFluCOV trial from a statistician's perspective.

Background: In early 2021, the Department of Health and Social Care in the UK called for research on the safety and immunogenicity of concomitant administration of COVID-19 and influenza vaccines. Co-administration of these vaccines would facilitate uptake and reduce the number of healthcare visits required. The ComFluCOV trial was designed to deliver the necessary evidence in time to inform the autumn (September-November) 2021 vaccination policy.

Delivering COVID-19 vaccine trials at speed: the implementation of a phase IV UK multi-centre randomised controlled trial to determine safety and immunogenicity of COVID-19 vaccines co-administered with seasonal influenza vaccines (ComFluCOV).

Background: In February 2021, the UK Department of Health and Social Care sought evidence on the safety and immunogenicity of COVID-19 and influenza vaccine co-administration to inform the 2021/2022 influenza vaccine policy. Co-administration could support vaccine uptake and reduce healthcare appointments. ComFluCOV was a randomised controlled trial designed to provide this evidence.