Pluripotent stem-cell-derived therapies in clinical trial: A 2025 update.

Since the first derivation of human pluripotent stem cells (hPSCs) 27 years ago, technologies to control their differentiation and manufacturing have advanced immensely, enabling increasing numbers of clinical trials with hPSC-derived products. Here, we revew the landscape of interventional hPSC trials worldwide, highlighting available data on clinical safety and efficacy. As of December 2024, we identify 116 clinical trials with regulatory approval, testing 83 hPSC products.

Inorganic bioelectric system for nitrate removal with low NO production at cold temperatures of 4 and 10 °C.

Groundwater, essential for ecological stability and freshwater supply, faces escalating nitrate contamination. Traditional biological methods struggle with organic carbon scarcity and low temperatures, leading to an urgent need to explore efficient approaches for groundwater remediation. In this work, we proposed an inorganic bioelectric system designed to confront these challenges.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

Self-Interacting Dark Sectors in Supernovae Can Behave as a Relativistic Fluid.

We revisit supernova (SN) bounds on a hidden sector consisting of millicharged particles χ and a massless dark photon. Unless the self-coupling is fine-tuned to be small, rather than exiting the SN core as a gas, the particles form a relativistic fluid and subsequent dark QED fireball, streaming out against the drag due to the interaction with matter. Novel bounds due to excessive energy deposition in the mantle of low-energy supernovae can be obtained.

Outcomes and complications of external ventricular drainage in primary and secondary intraventricular hemorrhage: a descriptive observational study.

Objective: Intraventricular hemorrhage (IVH) is a serious condition with high mortality rates and poor functional outcome in survivors. Treatment includes external ventricular drains (EVDs), which are associated with several complications. This study reports the clinical outcome and complication rate in patients with primary IVH (pIVH) and secondary IVH treated with EVDs.

Human brain dynamics are shaped by rare long-range connections over and above cortical geometry.

A fundamental topological principle is that the container always shapes the content. In neuroscience, this translates into how the brain anatomy shapes brain dynamics. From neuroanatomy, the topology of the mammalian brain can be approximated by local connectivity, accurately described by an exponential distance rule (EDR).

A European Survey to Identify Challenges in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe subtype, metabolic dysfunction-associated steatohepatitis (MASH), are highly prevalent and strongly associated with obesity and type 2 diabetes (T2D). This study sought to identify challenges to the diagnosis, treatment and management of people living with MASLD and MASH and understand the key barriers to adopting relevant clinical guidelines.

Methods: A real-world, cross-sectional study (BARRIERS-MASLD) consisting of a quantitative survey and qualitative interviews of physicians in France, Germany, Italy, Spain and the United Kingdom was conducted from March to September 2023.

Mortality Risk Prediction Models for People With Kidney Failure: A Systematic Review.

Importance: People with kidney failure have a high risk of death and poor quality of life. Mortality risk prediction models may help them decide which form of treatment they prefer.

Objective: To systematically review the quality of existing mortality prediction models for people with kidney failure and assess whether they can be applied in clinical practice.

Mental Disorders Among Offspring Prenatally Exposed to Systemic Glucocorticoids.

Importance: Current evidence of the association between prenatal exposure to glucocorticoids and long-term mental disorders is scarce and has limitations.

Objective: To investigate the association between prenatal exposure to systemic glucocorticoids and mental disorders in offspring at the age of 15 years, comparing exposed vs unexposed offspring born to mothers with the same underlying disease (risk of preterm delivery and autoimmune or inflammatory disorders).

Design, Setting, And Participants: This nationwide population-based cohort study used data from registries in Denmark with follow-up until December 31, 2018.

Risk of Gastrointestinal Diseases in Osteogenesis Imperfecta: A Nationwide, Register-Based Cohort Study.

Osteogenesis imperfecta (OI) is a group of rare genetic disorders most commonly caused by reduced amount of biologically normal collagen type I, a structural component of the gastrointestinal tract and abdominal wall. The risk of gastrointestinal (GI) disease in individuals with OI is not well understood, despite GI complaints being frequently reported by the OI population. To investigate the risk of GI diseases in individuals with OI.

Long-Term Natural Hydroxyapatite and Synthetic Collagen Hydroxyapatite Enhance Bone Regeneration and Implant Fixation Similar to Allograft in a Sheep Model of Implant Integration.

There is an increasing demand for a suitable bone substitute to replace current clinical gold standard autografts or allografts. Majority of previous studies have focused on the early effects of substitutes on bone formation, while information on their long-term efficacies remains limited. This study investigated the efficacies of natural hydroxyapatite (nHA) derived from oyster shells and synthetic hydroxyapatite mixed with collagen (COL/HA) or chitosan (CS/HA) on bone regeneration and implant fixation in sheep.

MRI in early stages of adolescent idiopathic scoliosis indicates a neuro-osseous growth mismatch associated with curve progression.

Purpose: To investigate the relationship between spinal cord anatomy and the risk of curve progression in mild to moderate adolescent idiopathic scoliosis (AIS).

Methods: We prospectively included patients presenting with mild or moderate AIS (< 40 degrees). Irrespective of curve severity, patients underwent 3-dimensional MRI and were followed until skeletal maturity or surgery.

SNP rs6543176 is associated with extreme human longevity but increased risk for cancer.

Using whole-genome sequencing (WGS) might offer insights into rare genetic variants associated with healthy aging and extreme longevity (EL), potentially pointing to useful therapeutic targets. In this study, we conducted a genome-wide association study using WGS data from the Long Life Family Study and identified a novel longevity-associated variant rs6543176 in the SLC9A2 gene. This SNP also showed a significant association with reduced hypertension risk and an increased, though not statistically significant, cancer risk.

Prevalence and incidence of mastocytosis in adults: a Danish nationwide register study.

Mastocytosis is a group of rare heterogeneous diseases with a prevalence previously found to be 10-23 per 100,000 persons. More awareness and improvements in the diagnostic methods in later years have led to more patients being diagnosed. Here, we set out to present the prevalence and incidence rate of mastocytosis among the adult Danish population.

Long-term effect and safety of mesenchymal stromal cell therapy for radiation-induced hyposalivation in head and neck cancer survivors: A randomised, phase-2, trial.

Background: The long-term effect of adipose-derived mesenchymal stromal cells (ASCs) to restore radiation-induced salivary gland hypofunction in previous head and neck cancer patients have not been validated in larger settings.

Methods: The study was the 12-months follow-up of a randomised trial, including patients with hyposalivation. Patients were randomised to receive allogeneic ASCs or placebo in the submandibular glands.

Basic Science and Pathogenesis.

Background: Microglia are the primary immune cells of the brain and represent the main line of defense against brain environmental insults. In recent years, microglia have been implicated in Alzheimer's disease (AD) pathogenesis by having interconnected yet opposing roles: beneficial as they clear amyloid beta (Aβ) and amyloid plaques, and detrimental as being responsible for synaptic and neuronal loss. These activities are tightly regulated by microglia receptors CD33 and TREM2.

Basic Science and Pathogenesis.

Background: SORL1 encodes the retromer-associated receptor SORLA that functions in endosomal recycling. Rare variants in SORL1 have been associated with Alzheimer's disease (AD) and rare pathogenic variants are estimated to occur in up to 2.75% of early onset AD patients and in 1.

Basic Science and Pathogenesis.

Background: The sortilin-related receptor 1 protein, SORL1, interacts with retromer to regulate trafficking of cargo out of the early endosome. Genetic variants in SORL1 that lead to a premature protein truncation (PTVs) are observed almost exclusively in Alzheimer's disease (AD) patients, suggesting SORL1's haploinsufficiency may be causal for AD. However, the large majority of SORL1 variants are rare missense variants which affect diverse structural domains, some of which may be causative for disease or (strongly) risk-increasing, while others are (likely) benign.

Basic Science and Pathogenesis.

Background: Late Onset Alzheimer's Disease (LOAD) is the most common neurodegenerative disorder. Carriers of an ɛ4 allele of the apolipoprotein E gene (APOE) have significantly increased risk of developing LOAD. LOAD is also strongly sex biased.

Advancing dynamic quantum crystallography: enhanced models for accurate structures and thermodynamic properties.

X-ray diffraction (XRD) has evolved significantly since its inception, becoming a crucial tool for material structure characterization. Advancements in theory, experimental techniques, diffractometers and detection technology have led to the acquisition of highly accurate diffraction patterns, surpassing previous expectations. Extracting comprehensive information from these patterns necessitates different models due to the influence of both electron density and thermal motion on diffracted beam intensity.

Clinical Manifestations.

Background: Patients with dementia due to Alzheimer's disease may experience multiple different agitation symptoms - including excessive motor activity, verbal aggression, and physical aggression - at varying frequencies. The efficacy of brexpiprazole 2 or 3 mg/day on 29 individual agitation behaviors (Cohen-Mansfield Agitation Inventory [CMAI] items) was previously evaluated. Building upon that work, this post hoc analysis aimed to determine the efficacy of brexpiprazole on the same individual agitation behaviors, but specifically focusing on those patients who were frequently experiencing the behaviors at baseline.

Clinical Manifestations.

Background: Agitation associated with dementia due to Alzheimer's disease encompasses a wide range of behaviors, including excessive motor activity, verbal aggression, and physical aggression. In a survey of unpaid caregivers living with an individual with Alzheimer's disease, the "most bothersome" agitation behaviors (which may influence the decision to transfer the patient to long-term care) were: cursing or verbal aggression, spitting, repetitive sentences or questions, hitting, constant unwarranted requests for attention or help, trying to get to a different place, inappropriate dress or disrobing, pacing/aimless wandering, grabbing onto people, and throwing things. This post hoc analysis aimed to determine the efficacy of brexpiprazole on agitation in patients frequently exhibiting these bothersome behaviors.

Clinical Manifestations.

Background: A reduction in the frequency of agitation behaviors is a clinically meaningful outcome among patients with agitation associated with dementia due to Alzheimer's disease. This post hoc analysis aimed to determine the percentage of patients treated with brexpiprazole who achieved sustained clinically meaningful response (CMR), over 12 and 24 weeks.

Method: Data for brexpiprazole 2 or 3 mg/day were obtained from two trials of patients with agitation associated with dementia due to Alzheimer's disease: a 12-week, randomized, double-blind, placebo-controlled trial (ClinicalTrials.

Coronary revascularisation deferral based on quantitative flow ratio or fractional flow reserve: a post hoc analysis of the FAVOR III Europe trial.

Background: Safe deferral of revascularisation is a key aspect of physiology-guided percutaneous coronary intervention (PCI). While recent evidence gathered in the FAVOR III Europe trial showed that quantitative flow ratio (QFR) guidance did not meet non-inferiority to fractional flow reserve (FFR) guidance, it remains unknown if QFR might have a specific value in revascularisation deferral.

Aims: We aimed to evaluate the safety of coronary revascularisation deferral based on QFR as compared with FFR.