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.

The global impact of the COVID-19 pandemic on delays and disruptions in cancer care services: a systematic review and meta-analysis.

The coronavirus disease 2019 pandemic substantially impacted the delivery of cancer services and programs. Here we reviewed and synthesized the global scale and impact of pandemic-related delays and disruptions on cancer services, including diagnosis, diagnostic procedures, screening, treatment and supportive and palliative care. Based on data from 245 articles in 46 countries, we observed declines in the number of cancer screening participation (39.

Machine learning derived retinal pigment score from ophthalmic imaging shows ethnicity is not biology.

Few metrics exist to describe phenotypic diversity within ophthalmic imaging datasets, with researchers often using ethnicity as a surrogate marker for biological variability. We derived a continuous, measured metric, the retinal pigment score (RPS), that quantifies the degree of pigmentation from a colour fundus photograph of the eye. RPS was validated using two large epidemiological studies with demographic and genetic data (UK Biobank and EPIC-Norfolk Study) and reproduced in a Tanzanian, an Australian, and a Chinese dataset.

Reporting of nutritional screening, status and intake in trials of nutritional and physical rehabilitation following critical illness: a systematic review.

Background: Surviving critical illness leads to prolonged physical and functional recovery with both nutritional and physical rehabilitation interventions for prevention and treatment being investigated. Nutritional status and adequacy may influence outcome, but no consensus on which nutritional-related variables should be measured and reported in clinical trials exists.

Objective: To undertake a systematic review investigating the reporting of nutritional screening, nutritional status and nutritional intake/delivery in randomised controlled trials (RCTs) evaluating nutritional and/or physical rehabilitation on physical and functional recovery during and following critical illness.

IPEM topical report: guidance on 3D printing in radiotherapy.

There has been an increase in the availability and utilization of commercially available 3D printers in radiotherapy, with applications in phantoms, brachytherapy applicators, bolus, compensators, and immobilization devices. Additive manufacturing in the form of 3D printing has the advantage of rapid production of personalized patient specific prints or customized phantoms within a short timeframe. One of the barriers to uptake has been the lack of guidance.

Artificial Intelligence-Enhanced Electrocardiography for Prediction of Incident Hypertension.

Importance: Hypertension underpins significant global morbidity and mortality. Early lifestyle intervention and treatment are effective in reducing adverse outcomes. Artificial intelligence-enhanced electrocardiography (AI-ECG) has been shown to identify a broad spectrum of subclinical disease and may be useful for predicting incident hypertension.

Parathyroid carcinoma: New insights.

Parathyroid carcinoma (PC) is a rare malignancy, comprising 1 % of all cases of primary hyperparathyroidism (PHPT). This narrative review explores recent advances in PC management, with a focus on molecular insights, diagnostic advancements, surgical innovations, and emerging targeted therapies. Manuscripts published between 2023 and 2024 were obtained from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL).

Janus-kinase inhibitor use in immune-mediated inflammatory diseases beyond licensed indications: A scoping review.

Introduction: The use of janus kinase inhibitors (JAKi's) in immune-mediated inflammatory conditions (IMIDs) beyond licence is expanding rapidly. The aim of this scoping review was to identify and present the available evidence on the efficacy of JAKi's in all conditions without marketing authorisation.

Methods: Through a detailed literature search we identified studies including 5 or more patients that assessed the use of any JAKi for any efficacy outcome .

Impact of Complications on Survival Outcomes in Different Temporary Mechanical Circulatory Support Techniques: A Large Retrospective Cohort Study of Cardiac Surgical and Non-surgical Patients.

Background: Temporary mechanical circulatory support (tMCS) devices have become a standard treatment option in cardiogenic shock but are associated with high complication rates. This study analyzes common complications associated with modern tMCS devices and their impact on mortality depending on the tMCS approach.

Methods: We conducted a retrospective single-center analysis of patients with all-cause cardiogenic shock treated with veno-arterial extracorporeal life support, microaxial flow pump, and a combination of both (ECMELLA).

Transcoronary cooling and dilution for cardioprotection during revascularisation for ST-segment elevation myocardial infarction: design and rationale of the STEMI-Cool study.

Background: ST-segment elevation myocardial infarction (STEMI) is treated with immediate primary percutaneous coronary intervention (pPCI) to restore coronary blood flow in the acutely ischaemic territory, but is associated with reperfusion injury limiting the benefit of the therapy. No treatment has proven effective in reducing reperfusion injury. Transcoronary hypothermia has been tested in clinical studies and is well tolerated, but is generally established after crossing the occlusion with a guidewire therefore after initial reperfusion, which might have contributed to the neutral outcomes.

Evaluation of intestinal biopsy tissue preservation methods to facilitate large-scale mucosal microbiota research.

Background: Large-scale multicentre studies are needed to understand complex relationships between the gut microbiota, health and disease. Interrogating the mucosal microbiota may identify important biology not captured by stool analysis. Gold standard tissue cryopreservation ('flash freezing') limits large-scale study feasibility.

Interpretation and classification of FBN1 variants associated with Marfan syndrome: consensus recommendations from the Clinical Genome Resource's FBN1 variant curation expert panel.

Background: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) developed standardized variant curation guidelines for Mendelian disorders. Although these guidelines have been widely adopted, they are not gene- or disease-specific. To mitigate classification discrepancies, the Clinical Genome Resource FBN1 variant curation expert panel (VCEP) was established in 2018 to develop adaptations to the ACMG/AMP criteria for FBN1 in association with Marfan syndrome.

Identification of progressive pulmonary fibrosis: consensus findings from a modified Delphi study.

Background: We sought consensus among practising respiratory physicians on the prediction, identification and monitoring of progression in patients with fibrosing interstitial lung disease (ILD) using a modified Delphi process.

Methods: Following a literature review, statements on the prediction, identification and monitoring of progression of ILD were developed by a panel of physicians with specialist expertise. Practising respiratory physicians were sent a survey asking them to indicate their level of agreement with these statements on a binary scale or 7-point Likert scale (- 3 to 3), or to select answers from a list.

Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study.

Background: Vosoritide is a C-type natriuretic peptide analog that addresses an underlying pathway causing reduced bone growth in achondroplasia. Understanding the vosoritide treatment effect requires evaluation over an extended duration and comparison with outcomes in untreated children.

Methods: After completing ≥6 months of a baseline observational growth study and 52 weeks in a double-blind, placebo-controlled study (ClinicalTrials.

Quantification of atrial cardiomyopathy disease severity by electroanatomic voltage mapping and cardiac magnetic resonance imaging.

Introduction: Atrial late gadolinium enhancement (Atrial-LGE) and electroanatomic voltage mapping (Atrial-EAVM) quantify the anatomical and functional extent of atrial cardiomyopathy. We aimed to explore the relationships between, and outcomes from, these modalities in patients with atrial fibrillation undergoing ablation.

Methods: Patients undergoing first-time ablation had disease severities quantified using both Atrial-LGE and Atrial-EAVM.

Myocardial ischaemia following COVID-19: a cardiovascular magnetic resonance study.

The pathophysiology of myocardial injury following COVID-19 remains uncertain. COVID-HEART was a prospective, multicentre study utilising cardiovascular magnetic resonance (CMR) to characterise COVID-related myocardial injury. In this pre-specified analysis, the objectives were to examine (1) the frequency of myocardial ischaemia following COVID-19, and (2) the association between ischaemia and myocardial injury.

Antibodies to the RBD of SARS-CoV-2 spike mediate productive infection of primary human macrophages.

The role of myeloid cells in the pathogenesis of SARS-CoV-2 is well established, in particular as drivers of cytokine production and systemic inflammation characteristic of severe COVID-19. However, the potential for myeloid cells to act as bona fide targets of productive SARS-CoV-2 infection, and the specifics of entry, remain unclear. Using a panel of anti-SARS-CoV-2 monoclonal antibodies (mAbs) we performed a detailed assessment of antibody-mediated infection of monocytes/macrophages.

T* relaxometry of fetal brain structures using low-field (0.55T) MRI.

Purpose: Human brain development during gestation is complex, as both structure and function are rapidly forming. Structural imaging methods using MRI are well developed to explore these changes, but functional imaging tools are lacking. Low-field MRI is a promising modality to bridge this gap.

Fatigue, pain and faecal incontinence in adult inflammatory bowel disease patients and the unmet need: a national cross-sectional survey.

Background And Aims: The co-existence of fatigue, pain and faecal incontinence in people with Inflammatory Bowel Disease (IBD) is unknown. We aimed to determine the presence of and relationship between these symptoms and patients' desire for intervention.

Methods: Adults with IBD in the UK, recruited from clinics, the national IBD-BioResource, a patient charity and social media sources, completed PROMIS validated patient-reported questionnaires to identify fatigue, pain and faecal incontinence, in addition to symptom severity and impact, disease activity, anxiety and depression questionnaires and questions about their desire for help with these symptoms.

In-silico pace mapping identifies pacing sites more accurately than inverse body surface potential mapping.

Background: Electrocardiographic imaging (ECGi) is a non-invasive technique for ventricular tachycardia (VT) ablation planning. However, it is limited to reconstructing epicardial surface activation. In-silico pace mapping combines a personalized computational model with clinical electrocardiograms (ECGs) to generate a virtual 3D pace map.

THE EFFECTIVENESS OF PLATELET RICH FIBRIN IN ALVEOLAR RIDGE RECONSTRUCTIVE OR GUIDED BONE REGENERATIVE PROCEDURES: A SYSTEMATIC REVIEW AND META-ANALYSIS.: platelet rich fibrin in alveolar ridge augmentation.

Introduction And Objectives: Clinical studies have shown favorable outcomes following use of platelet rich fibrin (PRF), either alone or in conjunction with biomaterials for alveolar ridge reconstruction (ARR) or guided bone regeneration (GBR) . While PRF application accelerates wound healing and reduces postoperative discomfort, its effects on the alveolar bone gain, as part of ARR or GBR is less clear. Therefore, this study aims to investigate the clinical effectiveness of PRF when used in ARR or GBR, as well as postoperative discomfort following these procedures.

PGE and HCN2 ion channels are critical mediators of pain initiated by angiotensin II.

Angiotensin II is well known to have an important influence on blood pressure, mediated via the angiotensin II type 1 receptor (AT1R), and more recent studies have shown that angiotensin II may play an important additional role in eliciting pain via a distinct action at the angiotensin II type 2 receptor (AT2R). Signalling pathways that link activation of AT2R to a sensation of pain are, however, incompletely understood. Here we use rodent inflammatory pain models to confirm that selective activation of AT2R triggers aversive responses, and that these are abolished by either antagonism or genetic deletion of AT2R.

Weight discrimination partially mediates the longitudinal relationship between Body Mass Index and pain.

Pain is common among individuals with high Body Mass Index (BMI). This study investigated weight discrimination as a mediator of the longitudinal relationship between BMI and the presence of moderate/severe pain among adults from the English Longitudinal Study of Ageing (ELSA) cohort. ELSA is a longitudinal study of middle-aged and older adults living in England.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.