Optimisation

Three-dimensional (3D) organoid models have been instrumental in understanding molecular mechanisms responsible for many cellular processes and diseases. However, established organic biomaterial scaffolds used for 3D hydrogel cultures, such as Matrigel, are biochemically complex and display significant batch variability, limiting reproducibility in experiments. Recently, there has been significant progress in the development of synthetic hydrogels for in vitro cell culture that are reproducible, mechanically tuneable, and biocompatible...

Additive Manufacturing (AM) enables the generation of complex geometries and controlled internal cavities that are so interesting for the biomedical industry due to the benefits they provide in terms of osseointegration and bone growth. These technologies enable the manufacturing of the so-called lattice structures that are cells with different geometries and internal pores joint together for the formation of scaffold-type structures. In this context, the present paper analyses the feasibility of using diamond-type lattice structures and topology optimisation for the re-design of a dental implant...

BACKGROUND: Prolactinomas are common tumours that significantly reduce quality-of-life (QOL) due to sellar mass effect, secondary hypogonadism, and the peripheral effects of prolactin. Understanding the factors that influence QOL would provide insights into therapeutic targets to optimise patient outcomes and improve wellbeing in prolactinoma. METHODS: A systematic review was performed in accordance with the PRISMA statement. Studies that reported patient QoL using validated metrics were included...

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. FGFR4 has been implicated in HCC progression, making it a promising therapeutic target. We introduce an approach for identifying novel FGFR4 inhibitors by sequentially adding fragments to a common warhead unit. This strategy resulted in the discovery of a potent inhibitor, 4c , with an IC50 of 33 nM and high selectivity among members of the FGFR family. Although further optimisation is required, our approach demonstrated the potential for discovering potent FGFR4 inhibitors for HCC treatment, and provides a useful method for obtaining hit compounds from small fragments...

India contributed approximately 66% of the malaria cases in the WHO South-East Asia region in 2022. In India, approximately 44% of cases have been reported to be disproportionately contributed by approximately 27 districts. A comparative analysis of reported malaria cases between January 2017 and December 2022 was performed in Mandla district, which is the site of a model malaria elimination demonstration project (MEDP) in Madhya Pradesh (MP), India. Compared to 2017, the decrease in malaria cases in Mandla from 2018 to 2022 was higher than MP and the rest of the country...

Ex vivo genetically-modified cellular immunotherapies, such as chimeric antigen receptor T cell (CAR-T) therapies, have generated significant clinical and commercial outcomes due to their unparalleled response rates against relapsed and refractory blood cancers. However, the development and scalable manufacture of these novel therapies remains challenging and further process understanding and optimisation is required to improve product quality and yield. In this study, we employ a quality-by-design (QbD) approach to systematically investigate the impact of critical process parameters (CPPs) during the expansion step on the critical quality attributes (CQAs) of CAR-T cells...

Endovascular management of intracranial aneurysms has become the mainstay of treatment in recent years; however, retreatment rates remain as high as 1 in 5. High-frequency optical coherence tomography (HF-OCT) is an emerging imaging modality for the assessment, treatment and follow-up of cerebral aneurysms. EMBASE and SCOPUS databases were searched for studies relating to the management of intracranial aneurysm with OCT. A combination of keywords were used including 'cerebral aneurysm', 'intracranial aneurysm', 'high-frequency optical coherence tomography', 'optical coherence tomography', and 'optical frequency domain imaging'...

In our preceding paper (Y. Fukui et al. , Phys. Chem. Chem. Phys. , 2023, 25 , 25594-25602), we reported a systematic study of the Ag+ -ion conducting behaviour of silver iodide (AgI)-loaded mesoporous aluminas (MPAs) with different pore diameters and AgI-loading ratios. By optimising the control parameters, the Ag+ -ion conductivity has reached 7.2 × 10-4 S cm-1 at room temperature, which is more than three orders of magnitude higher than that of bulk AgI. In the present study, the effect of silver bromide (AgBr)-doping in the AgI/MPA composites on Ag+ -ion conductivity is systematically investigated for the first time, using variable-temperature powder X-ray diffraction, differential scanning calorimetry, and electrochemical impedance spectroscopy measurements...

Thiazolidinediones (TZDs) (e.g. pioglitazone and rosiglitazone), known insulin sensitiser agents for type II diabetes mellitus, exhibit controversial effects on cardiac tissue. Despite consensus on their association with increased heart failure risk, limiting TZD use in diabetes management, the underlying mechanisms remain uncharacterised. Herein, we report a comprehensive in vitro investigation utilising a novel toxicoproteomics pipeline coupled with cytotoxicity assays in human adult cardiomyocytes to elucidate mechanistic insights into TZD cardiotoxicity...

BACKGROUND: A new interprofessional model incorporating non-dispensing pharmacists in general practice teams can improve the quality of pharmaceutical care. However, results of the model are dependent on the context. Understanding when, why and how the model works may increase chances of successful broader implementation in other general practices. Earlier theories suggested that the results of the model are achieved by bringing pharmacotherapeutic knowledge into general practices. This mechanism may not be enough for successful implementation of the model...

BACKGROUND: Loneliness is a frequently reported problem for young people aged 16 to 24 years old. A variety of interventions have been developed (but in most cases not extensively evaluated) to try and tackle loneliness in this age group. These include interpersonal, intrapersonal, and social approaches that vary in their content and mechanisms of action. The current study aimed to qualitatively examine young peoples' views on the acceptability and feasibility of different loneliness interventions...

Crop disease detection and crop baking stage judgement require large image data to improve accuracy. However, the existing crop disease image datasets have high asymmetry, and the poor baking environment leads to image acquisition difficulties and colour distortion. Therefore, we explore the potential of the self-attention mechanism on crop image datasets and propose an innovative crop image data-enhancement method for recurrent generative adversarial networks (GANs) fused with the self-attention mechanism to significantly enhance the perception and information capture capabilities of recurrent GANs...

PURPOSE: Obtaining large volumes of medical images, required for deep learning development, can be challenging in rare pathologies. Image augmentation and preprocessing offer viable solutions. This work explores the case of necrotising enterocolitis (NEC), a rare but life-threatening condition affecting premature neonates, with challenging radiological diagnosis. We investigate data augmentation and preprocessing techniques and propose two optimised pipelines for developing reliable computer-aided diagnosis models on a limited NEC dataset...

No abstract text is available yet for this article.

PURPOSE: Extensor mechanism injuries, which comprise patella fractures, patella tendon tears and quadriceps tendon tears, are severely debilitating injuries and a common cause of traumatic knee pathology that requires surgical intervention. Risk factors for short-term surgical complications and venous thromboembolism (VTE) in this population have not been well characterised. The aim of this study was to identify perioperative risk factors associated with these short-term complications...

Patients with Solid Organ Transplantations (SOTx) face long-term lifestyle adaptations, psychological and social adjustments, and complex self-care regimes to maintain health post-transplant. Self-management (SM) skills represent important aspects of nursing communication with SOTx patients; however, there is potential for SM to be defined narrowly in terms of medication adherence. The study presented here collated the existing definitions in a mixed method review in order to identify SM attributes for this group (including those unique to this population)...

Across cervical squamous and glandular lesions, a spectrum of human papillomavirus (HPV) genotypes has been identified. This review aims to provide a comprehensive summary detailing the distribution and profile of HPV genotypes detected in cervical lesions, leveraging insights from histological and cytological findings. High-risk HPV (HR-HPV) genotypes exhibit varying degrees of oncogenic potential, with HPV16 and HPV18 identified as the most prevalent and oncogenic types. The distribution of HR-HPV genotypes varies among different degrees of the cervical lesions and varies between squamous and glandular neoplasia...

Vertebrate genomes contain lower than expected frequencies of the CpG dinucleotide. Consequently, many vertebrate viruses have evolved to mimic this composition, possibly in order to evade host antiviral defences (Greenbaum et al., 2008). For example, the antiviral protein ZAP binds CpGs in viral single stranded RNA with specific spacing requirements (Gonçalves-Carneiro et al., 2022), though CpGs are also likely depleted in viral genomes due to other selective pressures (Forni et al., 2023). Increasing CpG abundance by synonymous recoding could facilitate attenuation of viruses without compromising their epitope antigenicity by changing non-CpG codons to alternatives containing CpG without changing the overall amino acid sequence (Gonçalves-Carneiro et al...

BACKGROUND: Primary healthcare in South Africa aims to transform the national health system by emphasising community-based care and preventive strategies. However, rehabilitation services, particularly for individuals with disabilities and chronic non-communicable diseases, are often overlooked in primary healthcare. This study aimed to investigate the provision of primary healthcare rehabilitation services in the Johannesburg Metropolitan District by exploring client sociodemographics and variations in services provided by rehabilitation professionals...

To formulate and optimize Ozenoxacin nano-emulsion using Quality by Design (QbD) concept by means of Box-Behnken Design (BBD) and converting it to a gel to form Ozenoxacin nano-emulgel followed by physico-chemical, in-vitro, ex-vivo and in-vivo evaluation. This study demonstrates the application of QbD methodology for the development and optimization of an effective topical nanoemulgel formulation for the treatment of Impetigo focusing on the selection of appropriate excipients, optimization of formulation and process variables, and characterization of critical quality attributes...