Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in Osteoarthritis.

Interleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, the precise mechanism through which IL-6 and other immune-regulatory factors influence the therapeutic efficacy of autologous adipose-derived stem cells (ASCs) transplantation in OA treatment remains to be fully elucidated. This study aims to investigate the relationship between IL-6 expression in autologous ASCs isolated from OA patients and their impact on immune modulation, particularly focusing on the regulation of Receptor Activator of Nuclear factor Kappa-Β Ligand (RANKL), a key mediator of immune-driven cartilage degradation in OA.

Exploring the Epigenetic Landscape of Spermatozoa: Impact of Oxidative Stress and Antioxidant Supplementation on DNA Methylation and Hydroxymethylation.

Reproductive success is dependent on gamete integrity, and oxidative stress alters male nuclei, meaning that no DNA repair is possible due to chromatin compaction. The composition of sperm makes it highly sensitive to reactive oxygen species (ROS) but, at the same time, ROS are needed for sperm physiology. Over the past 30 years, much attention has been paid to the consequences of oxidative stress on sperm properties and the protective effects of antioxidant formulations to help fertility.

Same-Slide Spatial Multi-Omics Integration Reveals Tumor Virus-Linked Spatial Reorganization of the Tumor Microenvironment.

The advent of spatial transcriptomics and spatial proteomics have enabled profound insights into tissue organization to provide systems-level understanding of diseases. Both technologies currently remain largely independent, and emerging same slide spatial multi-omics approaches are generally limited in plex, spatial resolution, and analytical approaches. We introduce IN-situ DEtailed Phenotyping To High-resolution transcriptomics (IN-DEPTH), a streamlined and resource-effective approach compatible with various spatial platforms.

Genetics of intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage(ICH) represents a life-threatening form of stroke, marked by its impact on survival and quality of life. ICH can be categorized from monogenic disorders linked to causal germline variants in ICH-related genes to complex sporadic cases, highlighting the interaction among lifestyle factors, environmental influences, and genetic components in determining risk. Among sporadic ICH, the influence of these factors varies across ICH subtypes, evidenced by heritability rates of up to 73% for lobar ICH versus 34% for non-lobar ICH.

Burdens of type 2 diabetes and cardiovascular disease attributable to sugar-sweetened beverages in 184 countries.

The consumption of sugar-sweetened beverages (SSBs) is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). However, an updated and comprehensive assessment of the global burden attributable to SSBs remains scarce. Here we estimated SSB-attributable T2D and CVD burdens across 184 countries in 1990 and 2020 globally, regionally and nationally, incorporating data from the Global Dietary Database, jointly stratified by age, sex, educational attainment and urbanicity.

Perspectives on Implementing a Communication Facilitator Intervention From a Critical Care Setting.

Context: Critically-ill patients and their families often experience communication challenges during their ICU stay and across care transitions. An intervention using communication facilitators may help address these challenges.

Objectives: Using clinicians' perspectives, we identified facilitators and barriers to implementing a communication intervention.

Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution.

Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cell types and their heterogeneity within the human liver, but the spatial organization at single-cell resolution has not yet been described. Here we apply multiplexed error robust fluorescent in situ hybridization (MERFISH) to map the zonal distribution of hepatocytes, spatially resolve subsets of macrophage and mesenchymal populations, and investigate the relationship between hepatocyte ploidy and gene expression within the healthy human liver. Integrating spatial information from MERFISH with the more complete transcriptome produced by single-nucleus RNA sequencing (snRNA-seq), also reveals zonally enriched receptor-ligand interactions.

Targeting chromosomally unstable tumors with a selective KIF18A inhibitor.

Chromosome instability is a prevalent vulnerability of cancer cells that has yet to be fully exploited therapeutically. To identify genes uniquely essential to chromosomally unstable cells, we mined the Cancer Dependency Map for genes essential in tumor cells with high levels of copy number aberrations. We identify and validate KIF18A, a mitotic kinesin, as a vulnerability of chromosomally unstable cancer cells.

Multi-tiered proteome analysis displays the hyper-permeability of the rheumatoid synovial compartment for plasma proteins.

Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and cartilage/bone destruction. RA affects the synovial joints, the synovial lining and the permeability of the synovium. As the latter is of central relevance for the distribution of systemically delivered therapeutics into synovial fluid (SF), we here assessed the protein composition of paired plasma and SF of patients diagnosed with RA at three distinct levels of depth using mass spectrometric approaches: the "total" proteome, the "total" IgG1 antibody repertoire and the RA-specific ACPA IgG1 autoantibody repertoire.

Therapeutic plasma exchange for fibrinogen-associated hyperviscosity: results of the COVID-19 PLasma EXchange (COPLEX) randomized controlled trial.

Background: Therapeutic plasma exchange (TPE) is the primary intervention for treating symptomatic hyperviscosity from hypergammaglobulinemia, yet its efficacy for treating hyperviscosity related to hyperfibrinogenemia is unclear.

Objectives: Define the safety and efficacy of TPE for critically ill COVID-19 patients with elevated blood viscosity from hyperfibrinogenemia.

Methods: We performed a prospective randomized controlled trial in critically ill COVID-19 patients in a single US healthcare system.

Getting school-provided meals to the table: an international multiple-case study of school food service.

A school food service, which is the way children access food during the school day, is one of the many aspects in creating a health-promoting school environment. School-provided meal services differ greatly, depending on the country, region and school contexts, however, there is limited understanding of the diverse meal delivery within these settings. Therefore, the aim of this study was to understand different school-provided meal systems across different countries and contexts.

Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study.

Background: Vosoritide is a C-type natriuretic peptide analog that addresses an underlying pathway causing reduced bone growth in achondroplasia. Understanding the vosoritide treatment effect requires evaluation over an extended duration and comparison with outcomes in untreated children.

Methods: After completing ≥6 months of a baseline observational growth study and 52 weeks in a double-blind, placebo-controlled study (ClinicalTrials.

Highly Pathogenic Avian Influenza A(H5N1) Virus Infections in Humans.

Background: Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States.

Methods: We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit.

Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma.

Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4 T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL.

Evaluation of an assistive exosuit for alleviating neck and shoulder muscle fatigue during prolonged flexed neck posture.

Introduction: Neck pain affects 203 million people globally and is prevalent in various settings due to factors like poor posture, lack of exercise, and occupational hazards. Therefore, addressing ergonomic issues with solutions like a wearable robotic device is crucial. This research presents a novel assistive exosuit, characterized by its slim and lightweight structure and intuitive control without the use of hands, designed to mitigate muscle fatigue in the neck and shoulders during prolonged flexed neck posture.

Phase 1b/2 study of orally administered pexidartinib in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma.

Background: Glioblastoma (GBM) has a median survival of <2 years. Pexidartinib (PLX3397) is a small-molecule inhibitor of CSF1R, KIT, and oncogenic FTL3, which are implicated in GBM treatment resistance. Results from glioma models indicate that combining radiation therapy (RT) and pexidartinib reduces radiation resistance.

Evaluating Self-Directed Rehabilitation for Knee and Hip Arthroplasty During the COVID-19 Pandemic: A Multicenter Study.

The COVID-19 pandemic has triggered the adoption of new technologies to reduce the need for in-person physical therapy (PT). This study evaluated the impact of the COVID-19 pandemic on PT utilization and outcomes of patients prescribed a smartphone-based care management platform (sbCMP) for self-directed rehabilitation (SDR). A secondary analysis of data collected in a multicenter, prospective cohort trial investigating a mobile platform to deliver SDR after arthroplasty was performed.

The historical evolution of smallpox treatment in Japan visualised through Japanese artwork and woodblock prints.

Art reveals core human emotions during catastrophes like epidemics, allowing people to narrate their coping stories. This review examines smallpox's historical evolution and treatment in Japan, integrating visual art with medical history. It provides chronological insights from smallpox's arrival and traditional remedies to the era of vaccination and public health measures leading to eventual eradication.

Determining the Optimal Age for Extracranial-Intracranial Bypass Surgery: A Post Hoc Analysis of the CMOSS Randomized Trial.

Background: Previous trials have failed to demonstrate the benefits of extracranial-intracranial (EC-IC) bypass surgery for patients with carotid or middle cerebral artery occlusion. However, little evidence has focused on the effect of age on prognosis. This study aimed to explore whether EC-IC bypass surgery can provide greater benefits than medical therapy alone in specific age groups.