SLO co-opts host cell glycosphingolipids to access cholesterol-rich lipid rafts for enhanced pore formation and cytotoxicity.

Unlabelled: Streptolysin O (SLO) is a virulence determinant of group A (), the agent of streptococcal sore throat and severe invasive infections. SLO is a member of a family of bacterial pore-forming toxins known as cholesterol-dependent cytolysins, which require cell membrane cholesterol for pore formation. While cholesterol is essential for cytolytic activity, accumulating data suggest that cell surface glycans may also participate in the binding of SLO and other cholesterol-dependent cytolysins to host cells.

Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus.

The basal ganglia (BG) are an evolutionarily conserved and phylogenetically old set of sub-cortical nuclei that guide action selection, evaluation, and reinforcement. The entopeduncular nucleus (EP) is a major BG output nucleus that contains a population of GABA/glutamate cotransmitting neurons (EP) that specifically target the lateral habenula (LHb) and whose function in behavior remains mysterious. Here, we use a probabilistic switching task that requires an animal to maintain flexible relationships between action selection and evaluation to examine when and how GABA/glutamate cotransmitting neurons contribute to behavior.

Rome Foundation Working Team Report: Consensus Statement on the Design and Conduct of Behavioural Clinical Trials for Disorders of Gut-Brain Interaction.

Background: Brain-gut behaviour therapies (BGBT) have gained widespread acceptance as therapeutic modalities for the management of disorders of gut-brain interaction (DGBI). However, existing treatment evaluation methods in the medical field fail to capture the specific elements of scientific rigour unique to behavioural trial evaluation.

Aims: To offer the first consensus on the development and testing of BGBT in DGBI.

χ-sepnet: Deep Neural Network for Magnetic Susceptibility Source Separation.

Magnetic susceptibility source separation (χ-separation), an advanced quantitative susceptibility mapping (QSM) method, enables the separate estimation of paramagnetic and diamagnetic susceptibility source distributions in the brain. Similar to QSM, it requires solving the ill-conditioned problem of dipole inversion, suffering from so-called streaking artifacts. Additionally, the method utilizes reversible transverse relaxation ( ) to complement frequency shift information for estimating susceptibility source concentrations, requiring time-consuming data acquisition for (e.

Current Status and Future Trends in Myocarditis Related to the COVID-19 Vaccines: A Visual and Bibliometric Analysis.

Aims: This study aims to conduct a bibliometric and visual analysis of published studies on myocarditis and coronavirus disease 2019 (COVID-19) vaccines.

Background: The widespread epidemic of COVID-19 has caused millions of deaths and profoundly affected the global medical landscape. Studies on COVID-19 vaccination and related myocarditis have also increased significantly.

Aging and Cancer-Inextricably Linked Across the Lifespan.

Aging (as old man wind) alters the trajectory of cancer (dangerous seas) through changes in the immune system and metabolism (among many others), leading to altered cancer epidemiology, pathogenesis, and therapeutic responses, as represented by the research areas (boats)-artwork by Michael DeGregori.

Larger Perfusion Mismatch Volume Is Associated With Longer Hospital Length of Stay in Medium Vessel Occlusion Stroke.

Background And Purpose: Prolonged length of stay (LOS) following a stroke is associated with unfavorable clinical outcomes. Factors predicting LOS in medium vessel occlusion (MeVO), impacting up to 40% of acute ischemic stroke (AIS) cases, remain underexplored. This study aims to investigate the predictors of LOS in AIS-MeVO.

Emirates consensus recommendations on cardiovascular risk management in type 2 diabetes.

Background: The combination of cardiovascular disease and diabetes is a highly prevalent condition in the United Arab Emirates. Development and dissemination of evidence-based regional recommendations for optimal screening, treatment and referrals of people with diabetes and high cardiovascular risk is an important priority.

Consensus Panel: An expert panel of diabetologists, endocrinologists and cardiologists from the Emirates Cardiac Society and Emirates Diabetes and Endocrine Society as well as different entities in the UAE, discussed and reviewed evidence and also a consensus report from the American Diabetes Association to formulate contextualized recommendations that could be applied for optimal management of cardiovascular risk in people with diabetes in the UAE.

Antidiabetic agent use and clinical outcomes in patients with diabetes hospitalized for COVID-19: a systematic review and meta-analysis.

Background: The effect of antidiabetic agents on mortality outcomes is unclear for individuals with diabetes mellitus (DM) who are hospitalized for COVID-19.

Purpose: To examine the relationship between antidiabetic agent use and clinical outcomes in individuals with DM hospitalized for COVID-19.

Methods: A systematic review of the literature (2020-2024) was performed across five databases.

The impact of different exercise modalities on chronic kidney disease: an umbrella review of meta-analyses.

Introduction: Exercise is widely recognized for its benefits to chronic kidney disease (CKD) patients. However, the specific impact of different exercise modalities on CKD-related outcomes remains unclear. This study sought to summarize the effects of different exercise modalities on the main outcomes impacted by CKD.

Safety and Efficacy of Ferric Carboxymaltose for Iron Deficiency Anemia in Inflammatory Bowel Disease: A Systematic Review.

Ulcerative colitis and Crohn's disease, two types of inflammatory bowel disease (IBD), often cause anemia, primarily due to iron deficiency and chronic inflammation. Anemia negatively affects patients' daily functioning and quality of life, causing symptoms including headaches, exhaustion, and dyspnea. In IBD, iron deficiency arises from reduced intake, chronic blood loss, and impaired absorption.

Targeted detection of sequence variants in cell-free DNA from cerebrospinal fluid in pediatric central nervous system tumors.

The emergence of liquid biopsy technologies holds great promise in the cancer setting, including in pediatric central nervous system (CNS) tumors. In contrast to broad lower-depth sequencing, commonly referred to as low pass whole genome sequencing (WGS), targeted platforms with a higher depth of coverage have also been established. Here, we review targeted liquid biopsy techniques with applicability to pediatric CNS tumors.

Diagnostic and prognostic performance of urine ubiquitin carboxy-terminal hydrolase L1 across multiple acute brain injury types - A longitudinal prospective cohort study.

Introduction: Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is recognized as a diagnostic and prognostic blood biomarker for traumatic brain injury (TBI). This study aimed to evaluate whether UCH-L1 concentrations measured in patients' urine post-injury could serve as a diagnostic or prognostic biomarker for outcomes in various types of acute brain injuries (ABI).

Material And Methods: This pilot study included 46 ABI patients: aneurysmal subarachnoid hemorrhage (n = 22), ischemic stroke (n = 16), and traumatic brain injury (n = 8), along with three healthy controls.

A time for sex: circadian regulation of mammalian sexual and reproductive function.

The circadian clock regulates physiological and biochemical processes in nearly every species. Sexual and reproductive behaviors are two processes controlled by the circadian timing system. Evidence supporting the importance of proper clock function on fertility comes from several lines of work demonstrating that misalignment of biological rhythms or disrupted function of the body's master clock, such as occurs from repeated shift work or chronic jet lag, negatively impacts reproduction by interfering with both male and female fertility.

Association between gut microbiome profiles and host metabolic health across the life course: a population-based study.

Background: The human gut microbiome changes considerably over time. Previous studies have shown that gut microbiome profiles correlate with multiple metabolic traits. As disease development is likely a lifelong process, evidence gathered at different life stages would help gain a better understanding of this correlation.

Age-related disturbances in rest-activity rhythms and integrity of the hippocampal network: An exploratory study.

To better understand the relationship between the rest-activity rhythms and cognitive impairments during aging, we assessed the longitudinal changes in the rest-activity rhythms in an elderly population and their possible detrimental effect on the hippocampal network. This was done longitudinally in a rural cohort with two actigraphic assessments and brain imaging examinations, seven years apart. A segmentation of the hippocampus and its related structures was used to assess volumes and functional connectivity in this network based on anatomical and resting state functional data.

Fabrication and functional validation of a hybrid biomimetic nanovaccine (HBNV) against -mutant melanoma.

Cancer nanovaccines hold the promise for personalization, precision, and pliability by integrating all the elements essential for effective immune stimulation. An effective immune response requires communication and interplay between antigen-presenting cells (APCs), tumor cells, and immune cells to stimulate, extend, and differentiate antigen-specific and non-specific anti-tumor immune cells. The versatility of nanomedicine can be adapted to deliver both immunoadjuvant payloads and antigens from the key players in immunity (i.

Targeting Monounsaturated Fatty Acid Metabolism for Radiosensitization of KRAS Mutant 3D Lung Cancer Models.

Mutations in the KRAS oncogene can mediate resistance to radiation. KRAS mutation (mut) driven tumors have been reported to express cancer stem cell (CSC)-like features and may harbor metabolic liabilities through which CSC-associated radioresistance can be overcome. We established a radiation/drug screening approach that relies on the growth of 3D spheres under anchorage-independent and lipid-limiting culture conditions, which promote stemness and lipogenesis.

A phase II study of ramucirumab and somatostatin analog therapy in patients with advanced neuroendocrine tumors.

Objectives: Well-differentiated neuroendocrine tumors (NET) are highly vascular tumors characterized by their expression of vascular endothelial growth factor (VEGF). This trial investigated the activity of ramucirumab, a monoclonal antibody that targets VEGF receptor-2 (VEGFR-2) and inhibits activity of VEGF, in combination with somatostatin analog therapy in patients (pts) with advanced extra-pancreatic NET.

Methods: We conducted a single-arm phase II trial enrolling pts with advanced, progressive extra-pancreatic NET.

A Bayesian Interpretation of CABANA and Other Randomized Controlled Trials for Catheter Ablation in Patients With Atrial Fibrillation.

Background: Catheter ablation improves symptoms and quality of life in atrial fibrillation patients, but its effect on adverse cardiovascular outcomes and mortality remains uncertain. Bayesian analysis of randomized controlled trials offers a deeper understanding of treatment effects beyond conventional p-value thresholds.

Methods: We conducted a post hoc Bayesian reanalysis of CABANA and four similar trials to estimate catheter ablation's effect on cardiovascular and survival outcomes.

Single- versus two-test criteria for cognitive impairment: associations with CSF and imaging markers in former American football players.

 Cognitive impairment is a core feature of traumatic encephalopathy syndrome (TES), the putative clinical syndrome of chronic traumatic encephalopathy-a neuropathological disease associated with repetitive head impacts (RHI). Careful operationalization of cognitive impairment is essential to improving the diagnostic specificity and accuracy of TES criteria. We compared single- versus two-test criteria for cognitive impairment in their associations with CSF and imaging biomarkers in male former American football players.

From physical activity patterns to cognitive status: development and validation of novel digital biomarkers for cognitive assessment in older adults.

Background: This study aims to investigate the associations between signal-level physical activity (PA) features derived from wrist accelerometry data and cognitive status in older adults, and to evaluate their potential predictive value when combined with demographics.

Methods: We analyzed PA data from 3,363 older adults (NHATS: n = 747; NHANES: n = 2,616), with each participant contributing a complete 3-day continuous activity sequence. We extracted the most relevant PA features associated with cognitive function using feature engineering and recursive feature elimination.