Alström syndrome: the journey to diagnosis.

Background: Alström syndrome (AS) is a recessively inherited genetic condition which is ultra-rare and extremely complex. Symptoms include retinal dystrophy, nystagmus, photophobia, hearing loss, obesity, insulin resistance, diabetes and cardiomyopathy. The condition is progressive, but it is important to note that not all the complications associated with AS occur in everyone affected.

Benchmarking Alzheimer's disease prediction: personalised risk assessment using polygenic risk scores across various methodologies and genome-wide studies.

Background: The success of selecting high risk or early-stage Alzheimer's disease individuals for the delivery of clinical trials depends on the design and the appropriate recruitment of participants. Polygenic risk scores (PRS) show potential for identifying individuals at risk for Alzheimer's disease (AD). Our study comprehensively examines AD PRS utility using various methods and models.

Treatment outcomes with oral anti-hyperglycaemic therapies in people with diabetes secondary to a pancreatic condition (type 3c diabetes): A population-based cohort study.

Aims: To assess outcomes of oral anti-hyperglycaemic therapies in people with diabetes secondary to a pancreatic condition (type 3c), where specific treatment guidance is limited.

Materials And Methods: Using hospital-linked UK primary care records (Clinical Practice Research Datalink; 2004-2020), we identified 7084 people with a pancreatic condition (acute pancreatitis, chronic pancreatitis, pancreatic cancer and haemochromatosis) preceding diabetes diagnosis (type 3c cohort), initiating oral glucose-lowering therapy (metformin, sulphonylureas, SGLT2-inhibitors, DPP4-inhibitors or thiazolidinediones), and without concurrent insulin treatment. We stratified by pancreatic exocrine insufficiency [PEI] (n = 5917 without PEI, 1167 with PEI) and matched to 97 227 type 2 diabetes (T2D) controls.

Patient and public involvement in neonatal research - experiences and insights from parents and researchers.

Background: Involving parents in decisions about the care of their infant is common practice in most neonatal intensive care units. However, involvement is less common in neonatal research and a gap appears to exist in understanding the process of patient and public involvement. The aim of this study was to explore parents and researchers' experiences of patient and public involvement in a neonatal research project.

Depressive symptoms in older adults are associated with changes in stress-related markers, functional connectivity and brain volume.

Background: Subclinical depressive symptoms increase the risk of developing Alzheimer's disease (AD). The neurobiological mechanisms underlying this link may involve stress system dysfunction, notably related to the hippocampus which is particularly sensitive to AD. We aimed to investigate the links between blood stress markers and changes in brain regions involved in the stress response in older adults with or without subclinical depressive symptoms.

The effect of post-exercise heat exposure (passive heat acclimation) on endurance exercise performance: a systematic review and meta-analysis.

Background: "Active" heat acclimation (exercise-in-the-heat) can improve exercise performance but the efficacy of "passive" heat acclimation using post-exercise heat exposure is unclear. Therefore, we synthesised a systematic review and meta-analysis to answer whether post-exercise heat exposure improves exercise performance.

Methods: Five databases were searched to identify studies including: (i) healthy adults; (ii) an exercise training intervention with post-exercise heat exposure via sauna or hot water immersion (treatment group); (iii) a non-heat exposure control group completing the same training; and (iv) outcomes measuring exercise performance in the heat (primary outcome), or performance in thermoneutral conditions, V̇Omax, lactate threshold, economy, heart rate, RPE, core temperature, sweat rate, and thermal sensations.

Progression of the faecal microbiome in preweaning dairy calves that develop cryptosporidiosis.

Background: Cryptosporidiosis is a diarrheal disease that commonly affects calves under 6 weeks old. The causative agent, Cryptosporidium parvum, has been associated with the abundance of specific taxa in the faecal microbiome during active infection. However, the long-term impact of these microbiome shifts, and potential effects on calf growth and health have not yet been explored in depth.

Extrication following a motor vehicle collision: a consensus statement on behalf of The Faculty of Pre-hospital Care, Royal College of Surgeons of Edinburgh.

Background: Road traffic injury is the leading cause of death among young people globally, with motor vehicle collisions often resulting in severe injuries and entrapment. Traditional extrication techniques focus on limiting movement to prevent spinal cord injuries, but recent findings from the EXIT project challenge this approach. This paper presents updated recommendations from the Faculty of Pre-Hospital Care (FPHC) that reflect the latest evidence on extrication practices.

Quality, topics, and demographic trends of animal systematic reviews - an umbrella review.

Background: Animal systematic reviews are critical to inform translational research. Despite their growing popularity, there is a notable lack of information on their quality, scope, and geographical distribution over time. Addressing this gap is important to maintain their effectiveness in fostering medical advancements.

Can integrated care interventions strengthen primary care and improve outcomes for patients with chronic diseases? A systematic review and meta-analysis.

Background: An increasing number of people live with chronic disease or multi-morbidity. Current consensus is that their care requires an integrated model bringing different professionals together to provide person-centred care. Although primary care has a central role in managing chronic disease, and integration may be important in strengthening this role, previous research has shown insufficient attention to the relationships between primary care and integration.

The impact of Covid-19 on harm reduction policies in Iran: an interrupted time series analysis.

Background: The global emergence of the Covid-19 pandemic in 2019 posed unprecedented challenges to healthcare systems, disrupting routine services and necessitating swift adaptations. Harm reduction programs, vital for addressing substance use-related health risks, faced unique challenges during the pandemic, impacting vulnerable populations. This study focuses on the repercussions of Covid-19 on harm reduction policies in Iran, specifically examining the distribution of condoms, syringes, and methadone to high-risk individuals attending Triangle Centers.

External validation of AI-based scoring systems in the ICU: a systematic review and meta-analysis.

Background: Machine learning (ML) is increasingly used to predict clinical deterioration in intensive care unit (ICU) patients through scoring systems. Although promising, such algorithms often overfit their training cohort and perform worse at new hospitals. Thus, external validation is a critical - but frequently overlooked - step to establish the reliability of predicted risk scores to translate them into clinical practice.

Deep analysis of the major histocompatibility complex genetic associations using covariate analysis and haploblocks unravels new mechanisms for the molecular etiology of Elite Control in AIDS.

Introduction: We have reanalyzed the genomic data from the International Collaboration for the Genomics of HIV (ICGH), focusing on HIV-1 Elite Controllers (EC).

Methods: A genome-wide association study (GWAS) was performed, comparing 543 HIV-1 EC individuals with 3,272 uninfected controls (CTR) of European ancestry. 8 million single nucleotide polymorphisms (SNPs) and HLA class I and class II gene alleles were imputed to compare EC and CTR.

Effectiveness of AZD7442 (Tixagevimab/Cilgavimab) for Pre-Exposure Prophylaxis Against COVID-19 Hospitalization in Israel During the Omicron Sub-Variant Time Period.

Introduction: The effectiveness of AZD7442 (tixagevimab/cilgavimab) against COVID-19 hospitalizations was determined at 3 and 6 months among immunocompromised individuals in Israel during different variant circulations.

Methods: This was a retrospective cohort study using data from Clalit Health Services in Israel. Immunocompromised individuals eligible to receive AZD7442 300 mg between 15 February and 11 December 2022 were identified.

Impact of extended-course oral nirmatrelvir/ritonavir in established Long COVID: a case series.

Background: Prior case series suggest that a 5-day course of oral Paxlovid (nirmatrelvir/ritonavir) benefits some people with Long COVID, within and/or outside of the context of an acute reinfection. To the best of our knowledge, there have been no prior case series of people with Long COVID who have attempted longer courses of nirmatrelvir/ritonavir.

Methods: We documented a case series of 13 individuals with Long COVID who initiated extended courses (>5 days; range: 7.

Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standard for PET imaging of brain metastases: version 1.0.

This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neuro-Oncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO). Brain metastases are the most common malignant central nervous system (CNS) tumors. PET imaging with radiolabeled amino acids and to lesser extent [F]FDG has gained considerable importance in the assessment of brain metastases, especially for the differential diagnosis between recurrent metastases and treatment-related changes which remains a limitation using conventional MRI.

Application of a high-throughput swarm-based deep neural network Algorithm reveals SPAG5 downregulation as a potential therapeutic target in adult AML.

Gene‒gene interactions play pivotal roles in disease pathogenesis and are fundamental in the development of targeted therapeutics, particularly through the elucidation of oncogenic gene drivers in cancer. The systematic analysis of pathways and gene interactions is critical in the drug discovery process for various cancer subtypes. SPAG5, known for its role in spindle formation during cell division, has been identified as an oncogene in several cancers, although its specific impact on AML remains underexplored.

Outcomes of Hematopoietic Stem Cell Transplantation in 5 Patients with Autosomal Recessive RIPK1-Deficiency.

Receptor Interacting Serine/Threonine Kinase 1 (RIPK1) is widely expressed and integral to inflammatory and cell death responses. Autosomal recessive RIPK1-deficiency, due to biallelic loss of function mutations in RIPK1, is a rare inborn error of immunity (IEI) resulting in uncontrolled necroptosis, apoptosis and inflammation. Although hematopoietic stem cell transplantation (HSCT) has been suggested as a potential curative therapy, the extent to which disease may be driven by extra-hematopoietic effects of RIPK1-deficiency, which are non-amenable to HSCT, is not clear.

The introduction of the SARS-CoV-2 BA.4 lineage into Pakistan.

Pakistan has experienced a total of six COVID-19 waves throughout the pandemic, each driven by distinct SARS-CoV-2 lineages. This study explores the introduction of Omicron lineage BA.4 into Pakistan, which contributed to the sixth wave between June and September 2022.

Assessing three novel composite anthropometric-metabolic indices for predicting 10-year incidence of metabolic syndrome: findings from the kerman coronary artery disease risk factors study (KERCADRS).

Purpose: Metabolic syndrome (MetS) is a condition of high prevalence worldwide associated with increased risk of cardiovascular disease. The predictive value of novel indices of combined anthropometric and serum lipid parameters as predictors of MetS is, to our knowledge, unexplored. We aimed to assess the 10-year predictive value of three indices of triglyceride-glucose index (TyG), visceral adiposity index (VAI), and lipid accumulation product (LAP) for incidence of MetS in Southeastern Iran.

Heterogeneities in landed costs of traded grains and oilseeds contribute to unequal access to food.

Despite the growing accessibility of international grain and oilseed markets, high production costs and trade frictions are still prevalent, contributing to regional heterogeneities in the landed cost of grain imports. Here we quantify the landed cost for six grain commodities across 3,500 administrative regions, capturing regional cost differences to produce grain and transport it across international borders. We find large heterogeneities in the costs of imported grain, which are highest in Oceania, Central America and landlocked Africa.

Causal genes identification of giant cell arteritis in CD4+ Memory t cells: an integration of multi-omics and expression quantitative trait locus analysis.

Background: Giant cell arteritis (GCA) is a prevalent artery and is strongly correlated with age. The role of CD4+ Memory T cells in giant cell arteritis has not been elucidated.

Method: Through single-cell analysis, we focused on the CD4+ Memory T cells in giant cell arteritis.