The Use of MPS in Three Rs and Regulatory Applications: Perspectives From Developers on Stakeholder Responsibilities.

Increasing the use of microphysiological systems (MPS) in Three Rs and regulatory applications is a nuanced but important goal, which would also help increase their scientific impact. There are three distinct and important stakeholder groups that each play a unique role in expediting the use of MPS for regulatory purpose - namely, commercial MPS developers, end-users and regulators. Additionally, non-profit organisations, such as the 3Rs Collaborative (3RsC), can help coordinate these efforts.

Patient's Perception of Primary Health Care Provision With Respect to Access, Continuity and Coordination-InCept: An International Qualitative Perspective.

Health care systems are confronted with an increasing burden of (multi-)morbidity and a shortfall of healthcare providers. Coordination and continuity of care in chronic and multi-morbid patient is especially important. As qualitative patient experience data within care processes is scarce, we aim to increase the understanding of chronically ill patient's perspectives by assessing patient experiences in different health systems while treated in primary care.

Accelerated Infant Brain Rhythm Maturation in Autism.

Electroencephalography (EEG) captures characteristic oscillatory shifts in infant brain rhythms over the first year of life, offering unique insights into early functional brain development and potential markers for detecting neural differences associated with autism. This study used functional principal component analysis (FPCA) to derive dynamic markers of spectral maturation from task-free EEG recordings collected at 3, 6, 9, and 12 months from 87 infants, 51 of whom were at higher likelihood of developing autism due to an older sibling diagnosed with the condition. FPCA revealed three principal components explaining over 96% of the variance in infant power spectra, with power increases between 6 and 9 Hz (FPC1) representing the most significant age-related trend, accounting for more than 71% of the variance.

Functional Mixed Membership Models.

Mixed membership models, or partial membership models, are a flexible unsupervised learning method that allows each observation to belong to multiple clusters. In this paper, we propose a Bayesian mixed membership model for functional data. By using the multivariate Karhunen-Loève theorem, we are able to derive a scalable representation of Gaussian processes that maintains data-driven learning of the covariance structure.

Comparing reported management of ureteric stones between clinical audit and administrative datasets: An opportunity to streamline clinical audit.

Objectives: To compare recorded patient management between a clinical audit and administrative dataset for patients presenting with ureteric stones in England and to assess the feasibility of using administrative data for routine audit.

Patients And Methods: The British Association of Urological Surgeons conducted a clinical audit of all patients presenting as an emergency to 107 hospitals in England during November 2020 with ureteric stones. All patients were followed up until 31st March 2021 and in-patient and out-patient management received recorded.

National audit of patient reported experience of radical cystectomy for bladder cancer pathways.

Objective: The objective of this study was to measure and describe the national patient experience of radical cystectomy (RC) pathways in the UK using the validated Cystectomy-Pathway Assessment Tool (C-PAT).

Patients And Methods: A cohort of 1081 patients who underwent RC for bladder cancer, between 1 January 2021 and 31 July 2022 at 33 UK cystectomy centres, returned completed C-PAT responses. SPSS was employed for data summary statistics, including median, interquartile range, Mann Whitney U test or Chi-square test with a 95% confidence interval to assess statistical significance between potentially associated variables.

Flexible Regularized Estimation in High-Dimensional Mixed Membership Models.

Mixed membership models are an extension of finite mixture models, where each observation can partially belong to more than one mixture component. A probabilistic framework for mixed membership models of high-dimensional continuous data is proposed with a focus on scalability and interpretability. The novel probabilistic representation of mixed membership is based on convex combinations of dependent multivariate Gaussian random vectors.

In vitro assessment of nanomedicines' propensity to cause palmar-plantar erythrodysesthesia: A Doxil vs. doxorubicin case study.

Palmar-plantar erythrodysesthesia (PPE), also known as hand and foot syndrome, is a condition characterized by inflammation-mediated damage to the skin on the palms and soles of the hands and feet. PPE limits the successful therapeutic applications of anticancer drugs. However, identifying this toxicity during preclinical studies is challenging due to the lack of accurate in vitro and in vivo animal-based models.

Multi-site EEG studies in early infancy: Methods to enhance data quality.

Brain differences linked to autism spectrum disorder (ASD) can manifest before observable symptoms. Studying these early neural precursors in larger and more diverse cohorts is crucial for advancing our understanding of developmental pathways and potentially facilitating earlier identification. EEG is an ideal tool for investigating early neural differences in ASD, given its scalability and high tolerability in infant populations.

Role of mesenchymal stem cell conditioned medium on wound healing using a developed 3D skin model.

Alternative 3-dimensional (3D) skin models that replicate in vivo human skin are required to investigate important events during wound healing, such as collective cell migration, epidermal layer formation, dermal substrate formation, re-epithelialisation and collagen production. In this study, a matched human 3D skin equivalent model (3D-SEM) was developed from human skin cells (fibroblast and keratinocytes), characterised using haematoxylin and eosin, immunofluorescence staining and microRNA profiling. The 3D-SEM was then functionally tested for its use in wound healing studies.

Notification of bacterial strains made available by the United Kingdom National Collection of Type Cultures in 2022.

Here, we report on the one hundred and twenty-five bacterial strains made available by the National Collection of Type Cultures in 2022 alongside a commentary on the strains, their provenance and significance.

Insights into the spectrum of transtibial prosthetic socket design from expert clinicians and their digital records.

Background: Transtibial prosthetic sockets are often grouped into patella tendon bearing (PTB) or total surface bearing (TSB) designs, but many variations in rectifications are used to apply these principles to an individual's personalised socket. Prosthetists currently have little objective evidence to assist them as they make design choices.

Aims: To compare rectifications made by experienced prosthetists across a range of patient demographics and limb shapes to improve understanding of socket design strategies.

Development of the ECLIPSE model of meaningful outcome domains following lower limb amputation and prosthetic rehabilitation, through systematic review and best fit framework synthesis.

Background: Little is known about which outcome domains characterise meaningful recovery following prosthetic rehabilitation and should be measured. Our previous qualitative work developed a conceptual model of outcome domains which are meaningful to patients. This qualitative synthesis aims to develop that model by exploring views and experiences of recovery captured in the limb loss literature, and use these to produce a second iteration of the model describing outcome domains of importance following prosthetic rehabilitation from the patient's perspective.

Trauma Laparoscopy: Time Efficient, Cost Effective, and Safe.

Introduction: Laparoscopy has demonstrated improved outcomes in abdominal surgery; however, its use in trauma has been less compelling. In this study, we hypothesize that laparoscopy may be observed to have lower costs and complications with similar operative times compared to open exploration in appropriately selected patients.

Methods: We retrospectively reviewed adult patients undergoing abdominal exploration after blunt and penetrating trauma at our level 1 center from 2008 to 2020.

Interleukin (IL)-1/IL-6-Inhibitor-Associated Drug Reaction With Eosinophilia and Systemic Symptoms (DReSS) in Systemic Inflammatory Illnesses.

Background: After introducing IL-1/IL-6 inhibitors, some patients with Still and Still-like disease developed unusual, often fatal, pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease.

Objective: To facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features.

Targeting Macrophage Polarization for Reinstating Homeostasis following Tissue Damage.

Tissue regeneration and remodeling involve many complex stages. Macrophages are critical in maintaining micro-environmental homeostasis by regulating inflammation and orchestrating wound healing. They display high plasticity in response to various stimuli, showing a spectrum of functional phenotypes that vary from M1 (pro-inflammatory) to M2 (anti-inflammatory) macrophages.

Retrospective analysis of the incidence and outcome of late acute and chronic graft-versus-host disease-an analysis from transplant centers across Europe.

Introduction: Chronic graft-versus-host disease (cGvHD) is a serious late complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: This multicenter analysis determined the cumulative incidence (CI) of cGvHD and late acute GvHD (laGvHD) and its impact on transplantation-related mortality (TRM), relapse (R), and overall survival (OS) in 317 patients [296 adults, 21 pediatrics (<12 years of age)] who underwent their first allo-HSCT in 2017.

Results: The CI of laGvHD was 10.

OpenHands: An Open-Source Statistical Shape Model of the Finger Bones.

This paper presents statistical shape models of the four fingers of the hand, with an emphasis on anatomic analysis of the proximal and distal interphalangeal joints. A multi-body statistical shape modelling pipeline was implemented on an exemplar training dataset of computed tomography (CT) scans of 10 right hands (5F:5M, 27-37 years, free from disease or injury) imaged at 0.3 mm resolution, segmented, meshed and aligned.

Parsing evoked and induced gamma response differences in Autism: A visual evoked potential study.

Objective: Electroencephalography (EEG) measures of visual evoked potentials (VEPs) provide a targeted approach for investigating neural circuit dynamics. This study separately analyses phase-locked (evoked) and non-phase-locked (induced) gamma responses within the VEP to comprehensively investigate circuit differences in autism.

Methods: We analyzed VEP data from 237 autistic and 114 typically developing (TD) children aged 6-11, collected through the Autism Biomarkers Consortium for Clinical Trials (ABC-CT).

An In Vitro Human Skin Test for Predicting Skin Sensitization and Adverse Immune Reactions to Biologics.

Unlabelled: Biologics, including monoclonal antibodies (mAb), have proved to be effective and successful therapeutic agents, particularly in the treatment of cancer and immune-inflammatory conditions, as well as allergies and infections. However, their use carries an inherent risk of an immune-mediated adverse drug reaction. In this study, we describe the use of a novel pre-clinical human in vitro skin explant test for predicting skin sensitization and adverse immune reactions.

Central Posterior Envelopes for Bayesian Functional Principal Component Analysis.

Bayesian methods provide direct inference in functional data analysis applications without reliance on bootstrap techniques. A major tool in functional data applications is the functional principal component analysis which decomposes the data around a common mean function and identifies leading directions of variation. Bayesian functional principal components analysis (BFPCA) provides uncertainty quantification on the estimated functional model components via the posterior samples obtained.

Modeling intra-individual inter-trial EEG response variability in autism.

Autism spectrum disorder (autism) is a prevalent neurodevelopmental condition characterized by early emerging impairments in social behavior and communication. EEG represents a powerful and non-invasive tool for examining functional brain differences in autism. Recent EEG evidence suggests that greater intra-individual trial-to-trial variability across EEG responses in stimulus-related tasks may characterize brain differences in autism.

Smoking, nicotine and pregnancy 2 (SNAP2) trial: protocol for a randomised controlled trial of an intervention to improve adherence to nicotine replacement therapy during pregnancy.

Introduction: Smoking during pregnancy is harmful to unborn babies, infants and women. Nicotine replacement therapy (NRT) is offered as the usual stop-smoking support in the UK. However, this is often used in insufficient doses, intermittently or for too short a time to be effective.

A Human Skin Explant Test as a Novel In Vitro Assay for the Detection of Skin Sensitization to Aggregated Monoclonal Antibodies.

Monoclonal antibodies (mAbs) are important therapeutics. However, the enhanced potential for aggregation has become a critical quality parameter during the production of mAbs. Furthermore, mAb aggregation may also present a potential health risk in a clinical setting during the administration of mAb therapeutics to patients.