Pharmacokinetics-Based Design of Subcutaneous Controlled Release Systems for Biologics.

Protein therapeutics have emerged as an exceedingly promising treatment modality in recent times but are predominantly given as intravenous administration. Transitioning to subcutaneous (SC) administration of these therapies could significantly enhance patient convenience by enabling at-home administration, thereby potentially reducing the overall cost of treatment. Approaches that enable sustained delivery of subcutaneously administered biologics offer further advantages in terms of less frequent dosing and better patient compliance.

Salivary gland stem/progenitor cells: advancing from basic science to clinical applications.

Salivary gland stem/progenitor cells (SSPCs) hold significant potential for regenerative medicine, especially for patients suffering from salivary gland dysfunction due to various causes such as radiation therapy, Sjögren's syndrome, and aging. This review provides a comprehensive overview of SSPCs, including their characteristics, isolation, culture techniques, differentiation pathways, and their role in tissue regeneration. Additionally, we highlight recent advances in cell- and tissue-based therapies, such as SSPC transplantation and bioengineered organ replacements.

Post-discharge complications and follow-up timing after hospitalization for traumatic rib fractures.

Purpose: To evaluate frequency and timing of post-discharge complications in patients with traumatic rib fractures undergoing operative or nonoperative management.

Methods: We retrospectively reviewed adult patients with rib fractures admitted to a Level 1 trauma center from 1/2020 to 12/2021. Outcomes included rib-related complications, pneumonia within 1 month, new diagnosis of opioid- or alcohol-use disorder, and all-cause mortality.

Immune infiltrate populations within distinct tumor immune microenvironments predictive of immune checkpoint treatment outcome.

Understanding the dynamic tumor immune microenvironment (TIME) is important in guiding immunotherapy. We have previously validated signatures predictive of checkpoint inhibitor efficacy which distinguish immunomodulatory, mesenchymal stem-like, and mesenchymal phenotypes. Here we use twenty tumor types (7162 samples) to identify potentially conserved immune biology within these TIME spaces, genes co-expressed across distinct cell types involved these immune processes, and the association of these signatures with ICI response.

Life cycle comparison of industrial-scale lithium-ion battery recycling and mining supply chains.

Recycling lithium-ion batteries (LIBs) can supplement critical materials and improve the environmental sustainability of LIB supply chains. In this work, environmental impacts (greenhouse gas emissions, water consumption, energy consumption) of industrial-scale production of battery-grade cathode materials from end-of-life LIBs are compared to those of conventional mining supply chains. Converting mixed-stream LIBs into battery-grade materials reduces environmental impacts by at least 58%.

Stable laser-acceleration of high-flux proton beams with plasma collimation.

Laser-plasma acceleration of protons offers a compact, ultra-fast alternative to conventional acceleration techniques, and is being widely pursued for potential applications in medicine, industry and fundamental science. Creating a stable, collimated beam of protons at high repetition rates presents a key challenge. Here, we demonstrate the generation of multi-MeV proton beams from a fast-replenishing ambient-temperature liquid sheet.

Practice Advisory for Postoperative Pain Management of Cardiac Surgical Patients: A Report by Society of Cardiovascular Anesthesiologists.

Moderate to severe pain after cardiac surgery is relatively common, which increases the risk of postoperative cardiopulmonary complications and delays hospital discharge. Opioids have been useful agents for postoperative pain control after cardiac surgery, but are associated with serious adverse effects. As a result, multimodal analgesia has been adopted widely to decrease reliance on opioids for treating postoperative pain, reduce opioid-related adverse effects, and promote early recovery.

Diagnostic Value of Gastrin-Releasing Peptide Receptor-Targeted PET Imaging in Oncology: A Systematic Review.

Gastrin-releasing peptide receptor (GRPR), overexpressed in various cancers, is a promising target for positron emission tomography (PET). This systematic review investigated the diagnostic value of GRPR-targeted PET imaging in oncology. A systematic search was conducted on major medical databases until May 23, 2024.

Clinical outcomes of patients with unsuccessful mechanical thrombectomy versus best medical management of medium vessel occlusion stroke in the middle cerebral artery territory.

Background: Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown.

Methods: This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021.

The Relationship Between Hispanic Ethnicity and Outcomes for Infants Born Extremely Preterm.

Objective: To characterize the association between maternal ethnicity and infant survival to discharge without major morbidity.

Study Design: This is secondary analysis of a prospective cohort of infants born <27 weeks of gestation at NICHD Neonatal Research Network centers from 2006 through 2020. The primary outcome was survival to discharge without major morbidity (sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia grade 3, intracranial hemorrhage grade ≥3, periventricular leukomalacia, and advanced retinopathy of prematurity).

Large language model-augmented learning for auto-delineation of treatment targets in head-and-neck cancer radiotherapy.

Background And Purpose: Radiation therapy (RT) is highly effective, but its success depends on accurate, manual target delineation, which is time-consuming, labor-intensive, and prone to variability. Despite AI advancements in auto-contouring normal tissues, accurate RT target volume delineation remains challenging. This study presents Radformer, a novel visual language model that integrates text-rich clinical data with medical imaging for accurate automated RT target volume delineation.

The effect of a 14-day Gymnema sylvestre intervention to reduce sugar intake in people self-identifying with a sweet tooth.

Gymnema sylvestre (GS) contains gymnemic acids which can reversibly suppress sweet taste responses. This randomised crossover study aimed to investigate whether supplemental GS use can reduce sugar cravings, sweet food desire and consumption among adults that identify as high sweet food consumers (having a 'sweet tooth'). Participants were told three different mints were trialled to avoid bias.

The Circulatory Arrest Recovery Ammonia Problem (CARAP) Hypothesis: a H-MRS study of brain metabolism during neonatal cardiopulmonary bypass surgery.

Objective: Congenital heart disease affects 1% of US births, with many babies requiring major cardiothoracic surgery under cardiopulmonary bypass (CPB), exposing the more critical patients to neurodevelopmental impairment. Optimal surgical parameters to minimize neuronal injury are unknown. We used H MRS and blood ammonia assays in a neonatal pig model of CPB to compare two approaches, complete circulatory arrest (CA) versus antegrade cerebral perfusion (ACP).

Associations between weather extremes and faecal contamination along pathogen transmission pathways in rural Bangladeshi households: a prospective observational study.

Background: Weather extremes are predicted to influence pathogen exposure but their effects on specific faecal-oral transmission pathways are not well investigated. We evaluated associations between extreme rain and temperature during different antecedent periods (0-14 days) and Escherichia coli along eight faecal-oral pathways in rural Bangladeshi households.

Methods: We used data from the WASH Benefits Bangladesh cluster-randomised controlled trial (NCT01590095).

Paediatric strategy forum for medicinal product development in diffuse midline gliomas in children and adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Fewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.

Flamingo participates in multiple models of cell competition.

The growth and survival of cells with different fitness, such as those with a proliferative advantage or a deleterious mutation, is controlled through cell competition. During development, cell competition enables healthy cells to eliminate less fit cells that could jeopardize tissue integrity, and facilitates the elimination of pre-malignant cells by healthy cells as a surveillance mechanism to prevent oncogenesis. Malignant cells also benefit from cell competition to promote their expansion.

Improved daily PM estimates in India reveal inequalities in recent enhancement of air quality.

Poor ambient air quality poses a substantial global health threat. However, accurate measurement remains challenging, particularly in countries such as India where ground monitors are scarce despite high expected exposure and health burdens. This lack of precise measurements impedes understanding of changes in pollution exposure over time and across populations.

Synthesis and preclinical evaluation of tigilanol tiglate analogs as latency-reversing agents for the eradication of HIV.

Tigilanol tiglate (EBC-46) is a selective modulator of protein kinase C (PKC) isoforms that is Food and Drug Administration (FDA) approved for the treatment of mast cell tumors in canines with up to an 88% cure rate. Recently, it has been FDA approved for the treatment of soft tissue sarcomas in humans. The role of EBC-46 and, especially, its analogs in efforts to eradicate HIV, treat neurological and cardiovascular disorders, or enhance antigen density in antigen-targeted chimeric antigen receptor-T cell and chimeric antigen receptor-natural killer cell immunotherapies has not been reported.

Alteplase Purge Solution for Impella 5.5 Ventricular Assist Device Purge System Occlusion: Case Report and Review of the Literature.

The use of an alteplase (Activase) purge solution to address Impella ventricular assist device "thrombosis" or "purge system occlusion" has been mainly documented with earlier generation Impella devices (CP, 2.5, 5.0).

Macromolecular interactions and geometrical confinement determine the 3D diffusion of ribosome-sized particles in live cells.

The crowded bacterial cytoplasm is composed of biomolecules that span several orders of magnitude in size and electrical charge. This complexity has been proposed as the source of the rich spatial organization and apparent anomalous diffusion of intracellular components, although this has not been tested directly. Here, we use biplane microscopy to track the 3D motion of self-assembled bacterial genetically encoded multimeric nanoparticles (bGEMs) with tunable size (20 to 50 nm) and charge (-3,240 to +2,700 e) in live cells.

Health Care Spending Increases and Value in South Korea.

Importance: Health care spending in South Korea (hereafter Korea) nearly doubled from 2010 to 2019. However, little is known about the drivers and effectiveness of these spending increases in terms of changes in disability-adjusted life-years (DALYs).

Objectives: To evaluate the factors contributing to changes in health care spending and DALYs and estimate the value of health care spending from 2010 to 2019 in Korea.

Optimizing orthobiologic therapies with exercise, diet, and supplements.

Orthobiologic injections including platelet-rich plasma (PRP) and cell-based injections are becoming increasingly popular. Evidence suggests that these therapies can be effective in certain situations. The efficacy of these injections may be more dependent on the quality of the injectate, which given their autologous nature, may be dependent on lifestyle choices like exercise, diet, and supplements.

The Songdo consensus: Development of minimum reporting standards for studies of intervention in idiopathic anal fistula using a modified nominal group technique.

Aim: Cryptoglandular anal fistulas carry a substantial burden to quality of life. Surgery is the only effective curative treatment but requires balancing fistula healing against pain, wounds and continence impairment. Sphincter-preserving procedures do exist but demonstrate variable rates of success.

The Viral K1 Killer Yeast System: Toxicity, Immunity, and Resistance.

Killer yeasts, such as the K1 killer strain of S. Cerevisiae, express a secreted anti-competitive toxin whose production and propagation require the presence of two vertically-transmitted dsRNA viruses. In sensitive cells lacking killer virus infection, toxin binding to the cell wall results in ion pore formation, disruption of osmotic homeostasis, and cell death.