Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease.

This review demonstrates the value of central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and peripheral PD for determining the target dose range for clinical efficacy testing of emestedastat, an 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor. Combined data from 6 clinical trials in cognitively normal volunteers and patients with Alzheimer disease included a population PK model, endocrine PD, a human PET trial (11β-HSD1 brain imaging), and computerized cognitive testing. PK and PET findings were similar in volunteers and patients with Alzheimer disease.

Baricitinib Treatment in RNU7-1-Associated Aicardi-Goutières Syndrome in a South African Child: A Case Report.

Aicardi-Goutières syndrome (AGS) is a rare monogenic type I interferonopathy. Janus kinase (JAK) inhibition has emerged as a potential treatment for AGS. RNU7-1 is one of the most recently discovered genes for AGS, and the clinical effects of JAK inhibition in these patients have not been reported.

Thermal Annealing-Induced Phase Conversion in N-type Triple-Cation Lead-Based Perovskite Field Effect Transistors.

The field of perovskite optoelectronics and electronics has rapidly advanced, driven by excellent material properties and a diverse range of fabrication methods available. Among them, triple-cation perovskites such as CsFAMAPbI offer enhanced stability and superior performance, making them ideal candidates for advanced applications. However, the multicomponent nature of these perovskites introduces complexity, particularly in how their structural, optical, and electrical properties are influenced by thermal annealing─a critical step for achieving high-quality thin films.

Corpus Linguistics as a Research Method in Nursing: A Practical Approach to Analysing Language Data.

Aim: To highlight the use of corpus linguistics for analysing language data and to provide a worked example of this approach in nursing research.

Design: Methodology discussion paper.

Methods: This paper introduces corpus linguistics as a distinct approach to undertaking qualitative research in nursing.

Outcomes of neoadjuvant chemoradiotherapy in T4 rectal cancer patients: a real-world single institution experience.

Purpose: Treatment outcomes of locally advanced rectal cancer have improved significantly in recent decades. This retrospective study aimed to assess the efficacy of neoadjuvant chemoradiotherapy (nCRT) followed by surgery in patients with T4 rectal cancer and the different outcomes between T4a and T4b patients.

Materials And Methods: A total of 60 clinically T4 rectal cancer patients who underwent nCRT were included in the analysis.

Lymphopenia is an adverse prognostic factor in rectal adenocarcinoma patients receiving long-course chemoradiotherapy.

Purpose: Neoadjuvant radiotherapy (RT) or chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal adenocarcinoma. The recent emerging data on preoperative immunotherapy as an effective therapeutic modality for mismatch repair deficient rectal carcinomas suggests that the immune system plays a significant role in tumor eradication. Although RT has been shown to stimulate anti-tumor immunity, it also leads to substantial lymphopenia, hindering the effect of immune response.

Paranoia, Functioning, and the Moderating Effect of Well-Being in a Community Sample of Adolescents.

Introduction: Paranoid ideation is a relatively common experience in adolescence, yet it has not been well-explored in relation to psychological well-being and functioning in general population samples of youth. The current study aimed to investigate the relations between paranoia (operationalized as "persecutory ideation"), well-being, and two domains of functioning, social (e.g.

Hyperactive delta isoform of PI3Kinase enables long distance regeneration of adult rat corticospinal tract.

Neurons in the central nervous system (CNS) lose regenerative potential with maturity, leading to minimal corticospinal tract (CST) axon regrowth after spinal cord injury (SCI). In young rodents, knockdown of PTEN, which antagonises PI3K signalling by hydrolysing PIP3, promotes axon regeneration following SCI. However, this effect diminishes in adults, potentially due to lower PI3K activation leading to reduced PIP3.

Soft palate angle and basihyoid depth increase with tongue size and with body condition score in horses.

Background: Obesity has been associated with human obstructive sleep apnoea and canine brachycephalic obstructive airway syndrome. The effect of body condition score (BCS) on structures of the oropharynx, nasopharynx and upper airway of the horse has not been investigated.

Objectives: To investigate the effect of BCS on tongue measurements, soft palate angle and basihyoid depth in horses.

Physiologically Based Pharmacokinetic Modeling of Cannabidiol, Delta-9-Tetrahydrocannabinol, and Their Metabolites in Healthy Adults After Administration by Multiple Routes.

The two most extensively studied cannabinoids, cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), are used for myriad conditions. THC is predominantly eliminated via the cytochromes P450 (CYPs), whereas CBD is eliminated through both CYPs and UDP-glucuronosyltransferases (UGTs). The fractional contributions of these enzymes to cannabinoid metabolism have shown conflicting results among studies.

Human misconnection A response to Beuthin and Bruce on medical assistance in dying providers' lived experience.

Beuthin and Bruce's study 'MAiD as human connection: Stories and metaphors of physician providers existential lived experience' in this journal describes the affective experiences of Canadian Medical Assistance in Dying (MAiD) providers. A critical response to this work shows it is based on flawed premises and interpretations of its data, which centers on praising its participants in lethal injection for their very positive emotions. Their study also seems to unproblematically construct people dying by MAiD as "the other," a term that usually describes members of groups subject to individual and systemic oppression.

Food Allergy Prevalence in Two Population-Based UK Cohorts Born 12 Years Apart.

Background: Adverse food reactions include food allergy (FA; immune-mediated) and food intolerances (non-immune-mediated). FA are classified into IgE- and non-IgE-mediated FA. There is limited information available about changes in FA prevalence over time.

A mixed method exploration of job morale of physicians working in public healthcare settings in Kazakhstan during the COVID-19 pandemic.

Background: Physicians faced increased workloads during the COVID-19 pandemic, which exposed them to considerable physical and psychological stress. Gaining insight into shapers of job morale of physicians can help healthcare administrators assess the effectiveness of current work conditions and support systems, enabling them to develop policies that improve work environments and prepare healthcare systems for future resurgences of COVID-19 and other future unknown challenges. Therefore, the present study aimed to improve the understanding of physicians' experiences of job morale in Kazakhstan during the COVID-19 pandemic.

Pan-cancer drivers of metastasis.

Metastasis remains a leading cause of cancer-related mortality, irrespective of the primary tumour origin. However, the core gene regulatory program governing distinct stages of metastasis across cancers remains poorly understood. We investigate this through single-cell transcriptome analysis encompassing over two hundred patients with metastatic and non-metastatic tumours across six cancer types.

Optimising (re-)irradiation for locally recurrent head and neck cancer: impact of dose-escalation, salvage surgery, PEG tube and biomarkers on oncological outcomes-a single centre analysis.

Introduction: Locoregional recurrence (LR) is common in locally advanced head and neck cancer (HNSCC), posing challenges for treatment. We analysed outcome parameters and toxicities for patients being treated with radiotherapy (RT) for LR-HNSCC and investigated patient and disease related prognostic factors in this prognostically unfavourable group.

Methods: This analysis includes 101 LR-HNSCC patients treated with RT, radio-chemotherapy (RCT) or radio-immunotherapy (RIT) between 2010 and 2018 at a high-volume tertiary centre.

Interprofessional collaborative practice in health and social care for people living with multimorbidity: a scoping review protocol.

Background: Multimorbidity, the co-existence of two or more conditions within an individual at any one time, is globally increasing and forecasted to rise. This poses a significant challenge for current models of healthcare delivery, which are now ill-equipped to meet the future population health needs. Interprofessional collaborative practice is a specific way professionals work closely together and with patients and their families to improve patient outcomes.

Impact of diagnosis-related group payment on medical expenditure and treatment efficiency on people with drug-resistant tuberculosis: a quasi-experimental study design.

Background: The severe health challenge and financial burden of drug-resistant tuberculosis (DR-TB) continues to be an impediment in China and worldwide. This study aimed to explore the impact of Diagnosis-related group (DRG) payment on medical expenditure and treatment efficiency among DR-TB patients.

Methods: This retrospective cohort study included all DR-TB patients from the digitized Hospital Information System (HIS) of Wuhan Pulmonary Hospital and the TB Information Management System (TBIMS) with completed full course of National Tuberculosis Program (NTP) standard treatment in Wuhan from January 2016 to December 2022, excluding patients whose treatment spanned both before and after the DRG timepoint.

Practices supporting cue-based breastfeeding of preterm infants in neonatal intensive care units across Europe.

Background: Emerging knowledge about supportive neurodevelopmental neonatal care shows the need for an individual approach to establish breastfeeding. However, evidence on how cue-based breastfeeding is supported in neonatal intensive care units (NICUs) is scarce. Therefore, the aim was to describe supporting practices for cue-based breastfeeding.

Addressing the emerging threat of Oropouche virus: implications and public health responses for healthcare systems.

Oropouche fever is an increasingly significant health concern in tropical and subtropical areas of South and Central America, and is primarily spread by midge vectors. The Oropouche virus (OROV) was first identified in 1955 and has been responsible for numerous outbreaks, particularly in urban environments. Despite its prevalence, the disease is often under-reported, making it difficult to fully understand its impact.

Deep-learning prediction of cardiovascular outcomes from routine retinal images in individuals with type 2 diabetes.

Background: Prior studies have demonstrated an association between retinal vascular features and cardiovascular disease (CVD), however most studies have only evaluated a few simple parameters at a time. Our aim was to determine whether a deep-learning artificial intelligence (AI) model could be used to predict CVD outcomes from routinely obtained diabetic retinal screening photographs and to compare its performance to a traditional clinical CVD risk score.

Methods: We included 6127 individuals with type 2 diabetes without myocardial infarction or stroke prior to study entry.

Host genetics maps to behaviour and brain structure in developmental mice.

Gene-environment interactions in the postnatal period have a long-term impact on neurodevelopment. To effectively assess neurodevelopment in the mouse, we developed a behavioural pipeline that incorporates several validated behavioural tests to measure translationally relevant milestones of behaviour in mice. The behavioral phenotype of 1060 wild type and genetically-modified mice was examined followed by structural brain imaging at 4 weeks of age.

Orbital reactive lymphoid hyperplasia: Case series and literature review.

This study aimed to describe a case series of patients diagnosed with orbital reactive lymphoid hyperplasia (RLH) at a single tertiary care centre. A retrospective review was conducted by searching electronic medical records at Liverpool University NHS Foundation Trust (LUHFT) from 1 December 2021 - 1 December 2023, to identify all patients with a histological diagnosis. Ten patients with an orbital histological diagnosis of RLH were identified.

Influence of next-generation artificial intelligence on headache research, diagnosis and treatment: the junior editorial board members' vision - part 2.

Part 2 explores the transformative potential of artificial intelligence (AI) in addressing the complexities of headache disorders through innovative approaches, including digital twin models, wearable healthcare technologies and biosensors, and AI-driven drug discovery. Digital twins, as dynamic digital representations of patients, offer opportunities for personalized headache management by integrating diverse datasets such as neuroimaging, multiomics, and wearable sensor data to advance headache research, optimize treatment, and enable virtual trials. In addition, AI-driven wearable devices equipped with next-generation biosensors combined with multi-agent chatbots could enable real-time physiological and biochemical monitoring, diagnosing, facilitating early headache attack forecasting and prevention, disease tracking, and personalized interventions.