End-to-end physics-informed deep neural network optimization of sub-Nyquist lenses.

In this paper, an approach for optimizing sub-Nyquist lenses using an end-to-end physics-informed deep neural network is presented. The simulation and optimization of these sub-Nyquist lenses is investigated for image quality, classification performance, or both. This approach integrates a diffractive optical model with a deep learning classifier, forming a unified optimization framework that facilitates simultaneous simulation and optimization.

Accuracy of digital impressions for implant-supported complete-arch prosthesis when using an auxiliary geometry device.

Background/purpose: Digital impressions using intraoral scanners have recently gained popularity. The aim of the present study was to evaluate the fit of full-arch screw-retained cobalt-chromium frameworks fabricated via two different digital impression methods.

Materials And Methods: An edentulous resin master model with four dental implants was fabricated.

Poor Translatability of Biomedical Research Using Animals - A Narrative Review.

The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades. The majority of these failures are due to unexpected toxicity - that is, safety issues revealed in human trials that were not apparent in animal tests - or lack of efficacy. However, the use of more innovative tools, such as organs-on-chips, in the preclinical pipeline for drug testing, has revealed that these tools are more able to predict unexpected safety events prior to clinical trials and so can be used for this, as well as for efficacy testing.

Phase-In to Phase-Out-Targeted, Inclusive Strategies Are Needed to Enable Full Replacement of Animal Use in the European Union.

In September 2021, the European Parliament voted overwhelmingly in favour of a resolution to phase out animal use for research, testing, and education, through the adoption of an action plan. Here we explore the opportunity that the action plan could offer in developing a more holistic outlook for fundamental and biomedical research, which accounts for around 70% of all animal use for scientific purposes in the EU. We specifically focus on biomedical research to consider how mapping scientific advances to patient needs, taking into account the ambitious health policies of the EU, would facilitate the development of non-animal strategies to deliver safe and effective medicines, for example.

Patient-Derived Xenograft vs. Organoids: A Preliminary Analysis of Cancer Research Output, Funding and Human Health Impact in 2014-2019.

Cancer remains a major threat to mortality and morbidity globally, despite intense research and generous funding. Patient-derived xenograft (PDX) models-where tumor biopsies are injected into an animal-were developed to improve the predictive capacity of preclinical animal models. However, recent observations have called into question the clinical relevance, and therefore the translational accuracy, of these.

Anaerobiosis influences virulence properties of Pseudomonas aeruginosa cystic fibrosis isolates and the interaction with Staphylococcus aureus.

The airways of individuals with cystic fibrosis (CF) are abundantly colonised by Staphylococcus aureus and Pseudomonas aeruginosa. Co-infecting hypoxic regions of static mucus within CF airways, together with decreases in pulmonary function, mucus plugging and oxygen consumption by host neutrophils gives rise to regions of anoxia. This study determined the impact of anaerobiosis upon S.

Parkinson's disease research: adopting a more human perspective to accelerate advances.

Parkinson's disease (PD) affects 1% of the population over 60 years old and, with global increases in the aging population, presents huge economic and societal burdens. The etiology of PD remains unknown; most cases are idiopathic, presumed to result from genetic and environmental risk factors. Despite 200 years since the first description of PD, the mechanisms behind initiation and progression of the characteristic neurodegenerative processes are not known.

An investigation into E-cigarette cytotoxicity in-vitro using a novel 3D differentiated co-culture model of human airways.

Currently there is a lack of consensus on the possible adverse health effects of E-cigarettes (ECs). Important factors including cell model employed and exposure method determine the physiological relevance of EC studies. The present study aimed to evaluate EC cytotoxicity using a physiologically relevant in-vitro multicellular model of human airways.

Recommendations toward a human pathway-based approach to disease research.

Failures in the current paradigm for drug development have resulted in soaring research and development costs and reduced numbers of new drug approvals. Over 90% of new drug programs fail, the majority terminated at the level of Phase 2/3 clinical trials, largely because of efficacy failures or unexplained toxicity. A recent workshop brought together members from research institutions, regulatory agencies, industry, academia, and nongovernmental organizations to discuss how existing programs could be better applied to understanding human biology and improving drug discovery.

Paediatric Rehabilitation Ingredients Measure: a new tool for identifying paediatric neurorehabilitation content.

Aim: To develop an instrument (Paediatric Rehabilitation Ingredients Measure [PRISM]) for quantitative estimation of contents of interdisciplinary neurorehabilitation for use in studies of relationships between rehabilitation treatment delivered and severity-adjusted outcomes after acquired brain injury (ABI).

Method: The measure was developed using an ingredients-mediators-outcomes model consistent with the International Classification of Functioning, Disability and Health, a literature review, and other current initiatives in the development of rehabilitation treatment taxonomies, with item codevelopment in workshops with rehabilitation professionals. Interrater reliability was assessed in inpatient and residential paediatric rehabilitation settings.

A comparative study of electronic cigarette vapor extracts on airway-related cell lines in vitro.

The use of electronic cigarettes (ECs) is rapidly increasing worldwide; however, scientific evidence regarding EC cytotoxicity is limited. The aim of this study was to evaluate the acute cytotoxicity of EC vapor extract (ECE) on airway-related cells in vitro. Cigarette smoke extract (CSE), vapor extract of fifteen brands/flavors of ECs and the extract from the E-vehicle (propylene glycol and glycerin) was collected.

Towards a 21st-century roadmap for biomedical research and drug discovery: consensus report and recommendations.

Decades of costly failures in translating drug candidates from preclinical disease models to human therapeutic use warrant reconsideration of the priority placed on animal models in biomedical research. Following an international workshop attended by experts from academia, government institutions, research funding bodies, and the corporate and non-governmental organisation (NGO) sectors, in this consensus report, we analyse, as case studies, five disease areas with major unmet needs for new treatments. In view of the scientifically driven transition towards a human pathways-based paradigm in toxicology, a similar paradigm shift appears to be justified in biomedical research.

Minimum information about tolerogenic antigen-presenting cells (MITAP): a first step towards reproducibility and standardisation of cellular therapies.

Cellular therapies with tolerogenic antigen-presenting cells (tolAPC) show great promise for the treatment of autoimmune diseases and for the prevention of destructive immune responses after transplantation. The methodologies for generating tolAPC vary greatly between different laboratories, making it difficult to compare data from different studies; thus constituting a major hurdle for the development of standardised tolAPC therapeutic products. Here we describe an initiative by members of the tolAPC field to generate a minimum information model for tolAPC (MITAP), providing a reporting framework that will make differences and similarities between tolAPC products transparent.

Investigation of the enhanced antimicrobial activity of combination dry powder inhaler formulations of lactoferrin.

The airways of most people with cystic fibrosis are colonized with biofilms of the Gram-negative, opportunistic pathogen Pseudomonas aeruginosa. Delivery of antibiotics directly to the lung in the form of dry powder aerosols offers the potential to achieve high local concentrations directly to the biofilms. Unfortunately, current aerosolised antibiotic regimes are unable to efficiently eradicate these biofilms from the airways.

A novel regulatory role for tissue transglutaminase in epithelial-mesenchymal transition in cystic fibrosis.

Cystic fibrosis (CF) is a genetic disorder caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) for which there is no overall effective treatment. Recent work indicates tissue transglutaminase (TG2) plays a pivotal intracellular role in proteostasis in CF epithelia and that the pan TG inhibitor cysteamine improves CFTR stability. Here we show TG2 has another role in CF pathology linked with TGFβ1 activation and signalling, induction of epithelial-mesenchymal transition (EMT), CFTR stability and induction of matrix deposition.

Developing accurate models of the human airways.

Objectives: Particle delivery to the airways is an attractive prospect for many potential therapeutics, including vaccines. Developing strategies for inhalation of particles provides a targeted, controlled and non-invasive delivery route but, as with all novel therapeutics, in vitro and in vivo testing are needed prior to clinical use. Whilst advanced vaccine testing demands the use of animal models to address safety issues, the production of robust in vitro cellular models would take account of the ethical framework known as the 3Rs (Replacement, Reduction and Refinement of animal use), by permitting initial screening of potential candidates prior to animal use.

The relationship between socioeconomic status and fracture in a fracture clinic setting: data from the Nottingham Fracture Liaison Service.

Background: This study aims to better understand the relationship between socioeconomic status (SES), fractures in those that attend an outpatient fracture clinic and a diagnosis of osteoporosis. This will further aid our ability to risk stratify patients' with fractures for further investigation and secondary management of their bone health.

Method: This is a cross sectional analysis using data from the Nottingham Fracture Liaison Service of patients attending the outpatient fracture clinic from 1/01/08 to 31/12/11.

Sample size bias in judgments of perceptual averages.

Previous research has shown that people exhibit a sample size bias when judging the average of a set of stimuli on a single dimension. The more stimuli there are in the set, the greater people judge the average to be. This effect has been demonstrated reliably for judgments of the average likelihood that groups of people will experience negative, positive, and neutral events (Price, 2001; Price, Smith, & Lench, 2006) and also for estimates of the mean of sets of numbers (Smith & Price, 2010).

Human aquaporins: regulators of transcellular water flow.

Background: Emerging evidence supports the view that (AQP) aquaporin water channels are regulators of transcellular water flow. Consistent with their expression in most tissues, AQPs are associated with diverse physiological and pathophysiological processes.

Scope Of Review: AQP knockout studies suggest that the regulatory role of AQPs, rather than their action as passive channels, is their critical function.

The N-terminus of CD14 acts to bind apoptotic cells and confers rapid-tethering capabilities on non-myeloid cells.

Cell death and removal of cell corpses in a timely manner is a key event in both physiological and pathological situations including tissue homeostasis and the resolution of inflammation. Phagocytic clearance of cells dying by apoptosis is a complex sequential process comprising attraction, recognition, tethering, signalling and ultimately phagocytosis and degradation of cell corpses. A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within this process.

Cell exclusion in couette flow: evaluation through flow visualization and mechanical forces.

Cell exclusion is the phenomenon whereby the hematocrit and viscosity of blood decrease in areas of high stress. While this is well known in naturally occurring Poiseuille flow in the human body, it has never previously been shown in Couette flow, which occurs in implantable devices including blood pumps. The high-shear stresses that occur in the gap between the boundaries in Couette flow are known to cause hemolysis in erythrocytes.

A copper-hydrogen peroxide redox system induces dityrosine cross-links and chemokine oligomerisation.

The activity of the chemoattractant cytokines, the chemokines, in vivo is enhanced by oligomerisation and aggregation on glycosaminoglycan (GAG), particularly heparan sulphate, side chains of proteoglycans. The chemokine RANTES (CCL5) is a T-lymphocyte and monocyte chemoattractant, which has a minimum tetrameric structure for in vivo activity and a propensity to form higher order oligomers. RANTES is unusual among the chemokines in having five tyrosine residues, an amino acid susceptible to oxidative cross-linking.