Development and validation of an LC-MS/MS multiplex assay for the quantification of bedaquiline, n-desmethyl bedaquiline, linezolid, levofloxacin, and clofazimine in dried blood spots.

Dried blood spot (DBS) assays to quantify novel and repurposed drugs for the treatment of rifampicin-resistant tuberculosis (RR-TB) would facilitate pharmacokinetic studies and therapeutic drug monitoring in low-middle income settings, considering their ease of application and simple sample storage requirements. We describe a DBS method for the simultaneous quantification of bedaquiline and metabolite N-desmethyl bedaquiline, linezolid, levofloxacin, and clofazimine. The analytes were extracted from the matrix and isolated by solid-phase extraction.

The community optometry workforce in Scotland: supporting sustainable eye care delivery.

Background: In early 2024, NHS Scotland published community optometrist workforce and activity data at a national level for the first time in the UK. These data are now over two years old, and anecdotal reports suggest changes amongst optometrists' work-patterns post-pandemic. To identify if that data continues to be reflective of the community optometrist workforce, the aim of this paper is to provide equivalent data for 2022 and 2023.

Management of post-operative anaemia in patients undergoing surgery for colorectal cancer: a qualitative focus group-based study.

Background: Optimal management of anaemia following surgery for colorectal cancer remains unclear. Peri-operative anaemia is common in patients undergoing resectional surgery for colorectal cancer. A significant amount of research has been conducted into the management of pre-operative anaemia; however, little work has investigated post-operative anaemia.

PET/CT guided tuberculosis treatment shortening: a randomized trial.

Six months of chemotherapy using current agents is standard of care for pulmonary, drug-sensitive tuberculosis (TB), even though some are believed to be cured more rapidly and others require longer therapy. Understanding what factors determine the length of treatment required for durable cure in individual patients would allow individualization of treatment durations, provide better clinical tools to determine the of appropriate duration of new regimens, as well as reduce the cost of large Phase III studies to determine the optimal combinations to use in TB control programs. We conducted a randomized clinical trial in South Africa and China that recruited 704 participants with newly diagnosed, drug-sensitive pulmonary tuberculosis and stratified them based on radiographic disease characteristics as assessed by FDG PET/CT scan readers.

Complete mitochondrial genomes of and biting midge vectors of Bluetongue Virus.

Biting midges ( spp.) are important vectors of several insect borne arboviruses but are underrepresented in terms of availability of high-resolution genomic resources. We assembled and annotated complete mitochondrial genomes for two species, namely and which are proven vectors for Bluetongue Virus (BTV).

Safety and efficacy of mesenchymal stromal cells mitochondria transplantation as a cell-free therapy for osteoarthritis.

Objective: The inflammatory responses from synovial fibroblasts and macrophages and the mitochondrial dysfunction in chondrocytes lead to oxidative stress, disrupt extracellular matrix (ECM) homeostasis, and accelerate the deterioration process of articular cartilage in osteoarthritis (OA). In recent years, it has been proposed that mesenchymal stromal cells (MSC) transfer their functional mitochondria to damaged cells in response to cellular stress, becoming one of the mechanisms underpinning their therapeutic effects. Therefore, we hypothesize that a novel cell-free treatment for OA could involve direct mitochondria transplantation, restoring both cellular and mitochondrial homeostasis.

Comparison of Vendor-Pretrained and Custom-Trained Deep Learning Segmentation Models for Head-and-Neck, Breast, and Prostate Cancers.

Background/objectives: We assessed the influence of local patients and clinical characteristics on the performance of commercial deep learning (DL) segmentation models for head-and-neck (HN), breast, and prostate cancers.

Methods: Clinical computed tomography (CT) scans and clinically approved contours of 210 patients (53 HN, 49 left breast, 55 right breast, and 53 prostate cancer) were used to train and validate segmentation models integrated within a vendor-supplied DL training toolkit and to assess the performance of both vendor-pretrained and custom-trained models. Four custom models (HN, left breast, right breast, and prostate) were trained and validated with 30 (training)/5 (validation) HN, 34/5 left breast, 39/5 right breast, and 30/5 prostate patients to auto-segment a total of 24 organs at risk (OARs).

A systematic review of neurocognition and social cognition in body dysmorphic disorder.

Objective: Neurocognitive underpinnings are implicated in the aetiology and maintenance of body dysmorphic disorder (BDD); however, inconsistent findings across a range of neurocognitive domains suggest that a comprehensive synthesis of the literature using a hierarchical framework of neurocognition is needed.

Methods: A final search across OVID Medline, PsycNET, Scopus and Web of Science databases was conducted on 20 June 2024 to identify research that examined performance on behavioural tasks of objective neurocognition in BDD. Risk of bias was assessed using the Newcastle-Ottawa Scale.

Barriers and missed opportunities in PrEP uptake, use and care among men who have sex with men with recent HIV infection in the Netherlands.

Introduction: Oral pre-exposure prophylaxis (PrEP) prevents Human Immunodeficiency Virus (HIV) acquisition. In the Netherlands, PrEP is accessible through the national PrEP program (NPP) or general practitioners (GP). Still, some men who have sex with men (MSM) entering HIV care indicated having PrEP experience prior to diagnosis.

Performance Comparison of 10 State-of-the-Art Machine Learning Algorithms for Outcome Prediction Modeling of Radiation-Induced Toxicity.

Purpose: To evaluate the efficacy of prominent machine learning algorithms in predicting normal tissue complication probability using clinical data obtained from 2 distinct disease sites and to create a software tool that facilitates the automatic determination of the optimal algorithm to model any given labeled data set.

Methods And Materials: We obtained 3 sets of radiation toxicity data (478 patients) from our clinic: gastrointestinal toxicity, radiation pneumonitis, and radiation esophagitis. These data comprised clinicopathological and dosimetric information for patients diagnosed with non-small cell lung cancer and anal squamous cell carcinoma.

An automated treatment planning portfolio for whole breast radiotherapy.

Background: Automation in radiotherapy presents a promising solution to the increasing cancer burden and workforce shortages. However, existing automated methods for breast radiotherapy lack a comprehensive, end-to-end solution that meets varying standards of care.

Purpose: This study aims to develop a complete portfolio of automated radiotherapy treatment planning for intact breasts, tailored to individual patient factors, clinical approaches, and available resources.

Diagnostic Accuracy of Chest X-ray Computer-Aided Detection Software for Detection of Prevalent and Incident Tuberculosis in Household Contacts.

Background: World Health Organization (WHO) tuberculosis (TB) screening guidelines recommend computer-aided detection (CAD) software for chest radiograph (CXR) interpretation. However, studies evaluating their diagnostic and prognostic accuracy are limited.

Methods: We conducted a prospective cohort study of household contacts of rifampicin-resistant TB in South Africa.

Hybrid closed-loop systems for managing blood glucose levels in type 1 diabetes: a systematic review and economic modelling.

Background: Hybrid closed-loop systems are a new class of technology to manage type 1 diabetes mellitus. The system includes a combination of real-time continuous glucose monitoring from a continuous glucose monitoring device and a control algorithm to direct insulin delivery through an insulin pump. Evidence suggests that such technologies have the potential to improve the lives of people with type 1 diabetes mellitus and their families.

In the face of confounders: Atrial fibrillation detection - Practitioners vs. ChatGPT.

Introduction: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, yet interpretation concerns among healthcare providers persist. Confounding factors contribute to false-positive and false-negative AF diagnoses, leading to potential omissions. Artificial intelligence advancements show promise in electrocardiogram (ECG) interpretation.

Distinct roles of ascorbic acid in extracellular vesicles and free form: Implications for metabolism and oxidative stress in presymptomatic Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the first exon of the huntingtin gene. The huntingtin protein (Htt) is ubiquitously expressed and localized in several organelles, including endosomes, where it plays an essential role in intracellular trafficking. Presymptomatic HD is associated with a failure in energy metabolism and oxidative stress.

The Effect of Health Insurance on Racial Disparities in Patients With Isolated Colorectal Liver Metastases.

Background And Objectives: Although resection of colorectal liver metastases (CRLM) improves survival, factors including race and health insurance are associated with disparities in care. The aim of this study was to evaluate the effect of health insurance on racial disparities in CRLM resection.

Methods: A retrospective study of patients with CRC with synchronous CRLM was performed using the National Cancer Database (2004-2020).

Health System Factors Influencing the Integration of Pre-Exposure Prophylaxis into Antenatal and Postnatal Clinic Services in Cape Town, South Africa.

Introduction: Oral pre-exposure prophylaxis (PrEP) is an effective and safe option to prevent HIV acquisition and vertical HIV transmission in pregnant and breastfeeding women. Understanding health system factors influencing the integration of PrEP into care for pregnant and breastfeeding women is key to increasing access. We explored managers' and health care workers' (HCWs) experiences with integrating PrEP into antenatal care and postnatal care services in primary health care clinics in Cape Town, South Africa.

Novel ryanodine receptor 1 (RYR1) missense gene variants in two pet dogs with fatal malignant hyperthermia identified by next-generation sequencing.

Objective: Evaluate a precision medicine approach to confirm a tentative diagnosis of fatal malignant hyperthermia (MH) in isoflurane-anesthetized pet dogs by identifying novel risk variants in known MH susceptibility genes.

Study Design: Retrospective case series.

Animals: A male Pit Bull mix aged 7 years (case #1), a male Golden Retriever aged 12 months (case #2) and the dam and sire of case #2.

Effect of the social environment on olfaction and social skills in wild-type and a mouse model of autism.

Autism spectrum disorders (ASD) are complex, polygenic and heterogenous neurodevelopmental conditions. The severity of autism-associated variants is influenced by environmental factors, particularly social experiences during the critical neurodevelopmental period. While early behavioral interventions have shown efficacy in some children with autism, pharmacological support for core features - impairments in social interaction and communication, and stereotyped or restricted behaviors - is currently lacking.

Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC.

The EphB4-ephrinB2 signaling axis has been heavily implicated in metastasis across numerous cancer types. Our emerging understanding of the dichotomous roles that EphB4 and ephrinB2 play in head and neck squamous cell carcinoma (HNSCC) poses a significant challenge to rational drug design. We find that EphB4 knockdown in cancer cells enhances metastasis in preclinical HNSCC models by augmenting immunosuppressive cells like T regulatory cells (Tregs) within the tumor microenvironment.

Mitochondrial transfer balances cell redox, energy and metabolic homeostasis in the osteoarthritic chondrocyte preserving cartilage integrity.

Osteoarthrosis (OA) is a leading cause of disability and early mortality, with no disease modifying treatment. Mitochondrial (MT) dysfunction and changes in energy metabolism, leading to oxidative stress and apoptosis, are main drivers of disease. In reaction to stress, mesenchymal stromal/stem cells (MSCs) donate their MT to damaged tissues.

The effect of concurrent clopidogrel and omeprazole administration on clopidogrel metabolism and platelet function in healthy cats.

Background: Some studies in humans show that the concurrent use of clopidogrel and omeprazole decreases plasma clopidogrel active metabolite (CAM) concentrations and clopidogrel antiplatelet effects. Whether this drug interaction occurs in cats is unknown.

Hypothesis: We hypothesized that administration of clopidogrel with omeprazole would decrease plasma CAM concentrations and decrease clopidogrel antiplatelet effects in healthy cats.