Designing lipid nanoparticles using a transformer-based neural network.

The RNA medicine revolution has been spurred by lipid nanoparticles (LNPs). The effectiveness of an LNP is determined by its lipid components and their ratios; however, experimental optimization is laborious and does not explore the full design space. Computational approaches such as deep learning can be greatly beneficial, but the composite nature of LNPs limits the effectiveness of existing single molecule-based algorithms to LNPs.

Revolutionizing Allogeneic Graft Tolerance Through Chimeric Antigen Receptor-T Regulatory Cells.

: Organ transplantation is a life-saving intervention for patients with terminal organ failure, but long-term success is hindered by graft rejection and dependence on lifelong immunosuppressants. These drugs pose risks such as opportunistic infections and malignancies. Chimeric antigen receptor (CAR) technology, originally developed for cancer immunotherapy, has been adapted to regulatory T cells (Tregs) to enhance their antigen-specific immunosuppressive function.

Advanced Therapeutic Approaches Based on Small Extracellular Vehicles (sEVs) For the Regeneration of Spinal Cord Injuries.

Spinal cord injury (SCI) is severe damage to part of the central nervous system (CNS) that can result in impaired sensory and motor function, significantly impacting the quality of life for patients and creating a substantial economic burden on society. The process of SCI involves both primary and secondary injury, with the latter being a series of heightened responses triggered by the initial damage. The complex nature of SCI's pathological mechanisms has made it challenging to develop effective treatment strategies in clinical settings.

Evidence-based review of the nutritional treatment of obesity and metabolic dysfunction-associated steatotic liver disease in children and adolescents.

The growing pediatric obesity epidemic has paralleled the surge in metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis. It develops due to nutritional imbalances, microbiome dysbiosis, gene regulation, hormonal changes, and environmental factors like food deserts, low activity level, and an unhealthy lifestyle. The prevalence of MASLD and obesity is rising every year.

Percutaneous Endoscopic Debridement and Drainage as a First-Line Diagnosis and Management Intervention for Spondylodiscitis: A Novel Treatment Algorithm.

Background And Objectives: Spondylodiscitis (SD) is an infection of the intervertebral disk. In the nonseptic, MRI-positive patient without focal deficits, current guidelines recommend computed tomography-guided biopsy (CTGB) for pathogen identification. Yet, pathogen positivity from CTGB is low (37%).

Radioprotection of healthy tissue via nanoparticle-delivered mRNA encoding for a damage-suppressor protein found in tardigrades.

Patients undergoing radiation therapy experience debilitating side effects because of toxicity arising from radiation-induced DNA strand breaks in normal peritumoural cells. Here, inspired by the ability of tardigrades to resist extreme radiation through the expression of a damage-suppressor protein that binds to DNA and reduces strand breaks, we show that the local and transient expression of the protein can reduce radiation-induced DNA damage in oral and rectal epithelial tissues (which are commonly affected during radiotherapy for head-and-neck and prostate cancers, respectively). We used ionizable lipid nanoparticles supplemented with biodegradable cationic polymers to enhance the transfection efficiency and delivery of messenger RNA encoding the damage-suppressor protein into buccal and rectal tissues.

Comparison of CT-Guided needle biopsy versus percutaneous endoscopic debridement and drainage in pathogen identification and pain outcomes for spondylodiscitis patients: A systematic review and literature review.

Introduction: Spondylodiscitis (SD) is an infection of the intervertebral disc with involvement of the adjacent vertebral bodies. Diagnostic tests with CT-guided biopsy only provide a positive yield in 14%-48% of cases. Percutaneous endoscopic debridement and drainage (PEDD) has recently shown promise in the treatment of spondylodiscitis.

Exploring Synergistic Effects of Bioprinted Extracellular Vesicles for Skin Regeneration.

Regenerative medicine represents a paradigm shift in healthcare, aiming to restore tissue and organ function through innovative therapeutic strategies. Among these, bioprinting and extracellular vesicles (EVs) have emerged as promising techniques for tissue rejuvenation. EVs are small lipid membrane particles secreted by cells, known for their role as potent mediators of intercellular communication through the exchange of proteins, genetic material, and other biological components.

From the kitchen to the medicine cabinet: Examples of food products and supplements used for therapeutic intent.

"Food as medicine" has existed for centuries as the foundation of health for many cultures around the globe. It is a practice built on the knowledge that food and diet play important roles in disease prevention and management. Foods that claim to have therapeutic properties are often referred to as functional foods.

14-3-3 Family of Proteins: Biological Implications, Molecular Interactions, and Potential Intervention in Cancer, Virus and Neurodegeneration Disorders.

The 14-3-3 family of proteins are highly conserved acidic eukaryotic proteins (25-32 kDa) abundantly present in the body. Through numerous binding partners, the 14-3-3 is responsible for many essential cellular pathways, such as cell cycle regulation and gene transcription control. Hence, its dysregulation has been linked to the onset of critical illnesses such as cancers, neurodegenerative diseases and viral infections.

Single high-dose intravenous injection of Wharton's jelly-derived mesenchymal stem cell exerts protective effects in a rat model of metabolic syndrome.

Background: Metabolic syndrome (MetS) is a significant epidemiological problem worldwide. It is a pre-morbid, chronic and low-grade inflammatory disorder that precedes many chronic diseases. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) could be used to treat MetS because they express high regenerative capacity, strong immunomodulatory properties and allogeneic biocompatibility.

De-risking fault leakage risk and containment integrity for subsurface storage applications.

The subsurface is pivotal in the energy transition, for the sequestration of CO and energy storage. It is crucial to understand to what extent geological faults may form leakage pathways that threaten the containment integrity of these projects. Fault flow behavior has been studied in the context of hydrocarbon development, supported by observations from wells drilled through faults, but such observations are rare in geoenergy projects.

Proteomic Analysis of Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Systematic Review.

Numerous challenges remain within conventional cell-based therapy despite the growing trend of stem cells used to treat various life-debilitating diseases. These limitations include batch-to-batch heterogeneity, induced alloreactivity, cell survival and integration, poor scalability, and high cost of treatment, thus hindering successful translation from lab to bedside. However, recent pioneering technology has enabled the isolation and enrichment of small extracellular vesicles (EVs), canonically known as exosomes.

Successful treatment of unilateral facial nerve palsy in a pediatric patient with syringobulbia and Chiari malformation type I: illustrative case.

Background: Unlike syringomyelia, syringobulbia is not commonly observed in pediatric patients with Chiari malformation type I (CMI). Previous series have reported the incidence of syringobulbia as between 3% and 4% in these patients. Presentation is typically chronic, with the slow onset of neurological symptoms and cranial nerve (CN) palsies resulting from lower brainstem involvement.

Leveraging artificial intelligence in neurosurgery-unveiling ChatGPT for neurosurgical discharge summaries and operative reports.

Purpose: Chat generative pre-trained transformer (GPT) is a novel large pre-trained natural language processing software that can enable scientific writing amongst a litany of other features. Given this, there is a growing interest in exploring the use of ChatGPT models as a modality to facilitate/assist in the provision of clinical care.

Methods: We investigated the time taken for the composition of neurosurgical discharge summaries and operative reports at a major University hospital.

Parenteral Nutrition in the Neonatal Intensive Care Unit: Intravenous Lipid Emulsions.

Intravenous lipid emulsions (ILEs) are a source of nonprotein calories and fatty acids and help promote growth in preterm infants and infants with intestinal failure. An ILE dose and oil source determines its fatty acid, phytosterol, and vitamin E delivery. These factors play a role in the infant's risk for essential fatty acid deficiency and cholestasis, and help modulate inflammation, immunity, and organ development.

Minimally Invasive Surgery Strategies to Prevent Proximal Junctional Kyphosis.

Proximal junctional kyphosis (PJK) is a common complication following long-segment thoracolumbar fusions for patients with adult spinal deformities. PJK is described as a progressive kyphosis at the upper instrumented vertebra or 1 or 2 segments adjacent to the instrumented vertebra. This condition can lead to proximal junction failure, which results in vertebral body fractures, screw pullouts, and neurological deficits.

Angiotensin II type 1 receptor antibodies and native kidney function in pediatric liver and intestinal transplant recipients.

Background: Angiotensin II type-1 receptor antibody (AT1R-Ab) has been associated with vascular injury and kidney dysfunction in pediatric kidney transplant recipients. The role of AT1R-Ab in the development of chronic kidney disease in pediatric liver and intestinal transplant recipients has not been explored.

Methods: Twenty-five pediatric intestinal transplant recipients and 79 pediatric liver transplant recipients had AT1R-Ab levels measured at varying time points in the post-transplant period.

Van der Waals Heterostructure Mid-Infrared Emitters with Electrically Controllable Polarization States and Spectral Characteristics.

Modern infrared (IR) microscopy, communication, and sensing systems demand control of the spectral characteristics and polarization states of light. Typically, these systems require the cascading of multiple filters, polarization optics, and rotating components to manipulate light, inevitably increasing their sizes and complexities. Here, we report two-terminal mid-infrared (mid-IR) emitters, in which tuning the polarity of the applied bias can switch their emission peak wavelengths and linear polarization states along two orthogonal orientations.

Childhood Cholestatic Liver Diseases that Persist Into Adulthood: Lessons for the Adult Gastroenterologist.

Children with cholestatic liver diseases are increasingly living into adulthood, thanks to innovations in medical and surgical therapies. The excellent outcomes observed in pediatric liver transplantation for diseases, such as biliary atresia, have transformed the life trajectory of children born with once-fatal liver diseases. The evolution of molecular genetic testing, has helped expedite the diagnosis of other cholestatic disorders, improving the clinical management, disease prognosis, and family planning for inherited disorders, such as progressive familial intrahepatic cholestasis and bile acid synthesis disorders.

Natural Killer Cell-Derived Extracellular Vesicles as a Promising Immunotherapeutic Strategy for Cancer: A Systematic Review.

Cancer is the second leading contributor to global deaths caused by non-communicable diseases. The cancer cells are known to interact with the surrounding non-cancerous cells, including the immune cells and stromal cells, within the tumor microenvironment (TME) to modulate the tumor progression, metastasis and resistance. Currently, chemotherapy and radiotherapy are the standard treatments for cancers.

Polyvinylpyrrolidone-Coated Catheters Decrease Astrocyte Adhesion and Improve Flow/Pressure Performance in an Invitro Model of Hydrocephalus.

The leading cause of ventricular shunt failure in pediatric patients is proximal catheter occlusion. Here, we evaluate various types of shunt catheters to assess in vitro cellular adhesion and obstruction. The following four types of catheters were tested: (1) antibiotic- and barium-impregnated, (2) polyvinylpyrrolidone, (3) barium stripe, and (4) barium impregnated.

Machine Learning in the Classification of Pediatric Posterior Fossa Tumors: A Systematic Review.

: Posterior fossa tumors (PFTs) are a morbid group of central nervous system tumors that most often present in childhood. While early diagnosis is critical to drive appropriate treatment, definitive diagnosis is currently only achievable through invasive tissue collection and histopathological analyses. Machine learning has been investigated as an alternative means of diagnosis.