Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.

Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3).

Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.

Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases.

Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review.

Schizophrenia spectrum disorders (SSD) involve disturbances in the integration of perception, emotion and cognition. The corticolimbic system is an interacting set of cortical and subcortical brain regions critically involved in this process. Understanding how neural circuitry and molecular mechanisms within this corticolimbic system may contribute to the development of not only positive symptoms but also negative and cognitive deficits in SSD has been a recent focus of intense research, as the latter are not adequately treated by current antipsychotic medications and are more strongly associated with poorer functioning and long-term outcomes.

Protocol for a first-in-human feasibility study of T regulatory cells (TR004) for inflammatory bowel disease using (ex vivo) Treg expansion (TRIBUTE).

Introduction: Crohn's disease (CD) is a chronic, immune-mediated inflammatory bowel disease (IBD), presenting with symptoms of abdominal pain and bleeding from the gastrointestinal tract. There is no known cure. In vitro-expanded 'thymus-derived' regulatory T cells (tTreg) have shown promise in preclinical models of IBD, leading to interest in their use as a potential therapy in CD.

At mid gestation, markers of placental function rather than maternal cardiac function are stronger determinants of birthweight.

Background: The role of maternal cardiac and hemodynamic assessment during normal and complicated pregnancies has gained attention during the last few years. Some researchers suggested that the manifestation of complications in pregnancy suffering from impaired placentation is mainly driven by pre-existing cardiac changes, identifiable at an early stage by echocardiographic and hemodynamic assessment. It is therefore of great importance to determine the link between placental perfusion and maternal cardiac function and hemodynamics.

Molecular allergy diagnosis enabling personalized medicine.

Allergic patients are characterized by complex and patient-specific IgE sensitization profiles to various allergens, which are accompanied by different phenotypes of allergic disease. Molecular allergy (MA) diagnosis establishes the patient's IgE reactivity profile at a molecular allergen level and has moved allergology into the "Precision Medicine" era. Molecular allergology started in the late 1980s with the isolation of the first allergen-encoding DNA sequences.

Raman spectroscopic probe provides optical biomarkers of cartilage composition predictive of tissue function.

Objective: The diagnosis of early osteoarthritis when therapeutic interventions may be most effective at reversing cartilage degeneration presents a clinical challenge. We describe a Raman arthroscopic probe and spectral analysis that measures biomarkers reflective of the content of predominant cartilage extracellular matrix (ECM) constituents-glycosaminoglycans (GAG), collagen, water-essential to cartilage function. We compare the capability of Raman-probe-derived biomarkers to predict functional properties of cartilage to quantitative MRI and histopathology assessments.

Predicting a strongly positive fluid balance in critically ill patients with acute kidney injury: A multicentre, international study.

Background: In critically ill patients with acute kidney injury (AKI), a fluid balance (FB) > 2 L at 72 h after AKI diagnosis is associated with adverse outcomes. Identification of patients at high-risk for such fluid accumulation may help prevent it.

Methods: We used Australian electronic medical record (EMR)-based clinical data to develop the "AKI-FB risk score", validated it in a British cohort and used it to predict a positive FB >2 L at 72 h after AKI diagnosis.

Exploring specific alterations at the explicit and perceptual levels in sense of ownership, agency, and body schema in Functional Motor Disorder: A pilot comparative study with Irritable Bowel Syndrome.

Functional Motor Disorders (FMD) consists in symptoms of altered motor function not attributable to typical neurological and medical conditions. This study aimed to explore explicit and perceptual measures of Sense of Ownership, Agency, and Body Schema in FMD patients, and assess whether these alterations are specific to FMD or shared with other functional disturbances. Twelve FMD patients, ten with Irritable Bowel Syndrome (IBS, a functional gastrointestinal disorder) and fifteen healthy controls (HC) underwent: (i) the Mirror Box Illusion (MBI), requiring participants to perform tapping movements with their dominant hand concealed from sight, while visual feedback was provided by an alien hand under visuo-motor congruency or incongruency conditions; (ii) a Forearm Bisection Task before and after exposure to the MBI, and the Embodiment Questionnaire after the MBI, as perceptual and explicit indices of the embodiment illusion, respectively.

Personalized topology-informed localization of standard 12-lead ECG electrode placement from incomplete cardiac MRIs for efficient cardiac digital twins.

Cardiac digital twins (CDTs) offer personalized in-silico cardiac representations for the inference of multi-scale properties tied to cardiac mechanisms. The creation of CDTs requires precise information about the electrode position on the torso, especially for the personalized electrocardiogram (ECG) calibration. However, current studies commonly rely on additional acquisition of torso imaging and manual/semi-automatic methods for ECG electrode localization.

Surgical Site Infection after Craniotomy in Neuro-Oncology (SINO): A protocol for an international prospective multicentre service evaluation across the United Kingdom and Ireland.

Introduction: Given its proximity to the central nervous system, surgical site infections (SSIs) after craniotomy (SSI-CRAN) represent a serious adverse event. SSI-CRAN are associated with substantial patient morbidity and mortality. Despite the recognition of SSI in other surgical fields, there is a paucity of evidence in the neurosurgical literature devoted to skin closure, specifically in patients with brain tumors.

A Parallel Human and Rat Investigation of the Interaction Between Descending and Spinal Modulatory Mechanisms.

Background: Healthy individuals demonstrate considerable heterogeneity upon dynamic quantitative sensory testing assessment of endogenous pain modulatory mechanisms. For those who stratify into a 'pro-nociceptive profile' cohort, consisting of inefficient conditioned pain modulation (CPM) and elevated temporal summation of pain (TSP), the optimal approach for balancing the net output of pain modulatory processes towards anti-nociception remains unresolved. In this translational healthy human and rat study, we examined whether descending modulation countered spinal amplification during concurrent application of a CPM and TSP paradigm alongside pupillometry since pontine activity was previously linked to functionality of endogenous pain modulatory mechanisms and pupil dilation.

Congenital Titinopathy: Comprehensive Characterization of the Most Severe End of the Disease Spectrum.

Unlabelled: Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders.

Objective: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.

Methods: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.

Scanner-based real-time three-dimensional brain + body slice-to-volume reconstruction for T2-weighted 0.55-T low-field fetal magnetic resonance imaging.

Background: Motion correction methods based on slice-to-volume registration (SVR) for fetal magnetic resonance imaging (MRI) allow reconstruction of three-dimensional (3-D) isotropic images of the fetal brain and body. However, all existing SVR methods are confined to research settings, which limits clinical integration. Furthermore, there have been no reported SVR solutions for low-field 0.

Immunobridging Trials: An Important Tool to Protect Vulnerable and Immunocompromised Patients Against Evolving Pathogens.

Safeguarding patients from emerging infectious diseases demands strategies that prioritise patient well-being and protection. Immunobridging is an established trial methodology which has been increasingly employed to ensure patient protection and provide clinicians with swift access to vaccines. It uses immunological markers to infer the effectiveness of a new drug through a surrogate measure of efficacy.

Protocol of an Efficacy Study on Nursing Consultation in Weight Management and Metabolic Syndrome Based on the Carbohydrate-Insulin Theory in Individuals with First-Episode Psychosis.

: Individuals with severe mental illness live, on average, up to 30 years less than the general population, with cardiovascular disease being the leading cause of death. Metabolic syndrome (MetS) plays a significant role in this, making it crucial to manage this issue in individuals with psychosis at the onset of the illness. The approach to managing this issue has evolved from a focus on calorie counting to a deeper understanding of hormone function, particularly the role of insulin resistance in MetS.

Development of Prevascularized Synthetic Block Graft for Maxillofacial Reconstruction.

Cranio-maxillofacial bone reconstruction, especially for large defects, remains challenging. Synthetic biomimetic materials are emerging as alternatives to autogenous grafts. Tissue engineering aims to create natural tissue-mimicking materials, with calcium phosphate-based scaffolds showing promise for bone regeneration applications.

The Use of SGLT-2 Inhibitors and GLP-1RA in Frail Older People with Diabetes: A Personalised Approach Is Required.

Frailty is an increasingly recognised complication of diabetes in older people and should be taken into consideration in management plans, including the use of the new therapies of sodium glucose cotransporter-2 (SGLT-2) inhibitors and glucagon like peptide-1 receptor agonists (GLP-1RA). The frailty syndrome appears to span across a spectrum, from a sarcopenic obese phenotype at one end, characterised by obesity, insulin resistance, and prevalent cardiovascular risk factors, to an anorexic malnourished phenotype at the other end, characterised by significant weight loss, reduced insulin resistance, and less prevalent cardiovascular risk factors. Therefore, the use of the new therapies may not be suitable for every frail older individual with diabetes.

Physician Perceptions of the Safety and Efficacy of GLP-1 Receptor Agonists: Underestimation of Cardiovascular Risk Reduction and Discrepancies with Clinical Evidence.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists (GIP/GLP-1 RAs) are emerging as effective treatments for obesity and cardiometabolic disease. This study evaluated physician perceptions of the safety and efficacy of semaglutide and tirzepatide through a questionnaire administered to 165 attending physicians specializing in internal or family medicine, with 122 responses received. Physicians reported an average patient weight loss of 9.

Exploring the Intersection of ADHD and Music: A Systematic Review.

Attention Deficit Hyperactivity Disorder (ADHD) is a highly prevalent neurodevelopmental disorder, affecting both children and adults, which often leads to significant difficulties with attention, impulsivity, and working memory. These challenges can impact various cognitive and perceptual domains, including music perception and performance. Despite these difficulties, individuals with ADHD frequently engage with music, and previous research has shown that music listening can serve as a means of increasing stimulation and self-regulation.