ISCT MSC committee statement on the US FDA approval of allogenic bone-marrow mesenchymal stromal cells.

The December 2024 US Food and Drug Administration (FDA) approval of Mesoblast's Ryoncil (remestemcel-L-rknd)-allogeneic bone marrow mesenchymal stromal cell (MSC(M)) therapy-in pediatric acute steroid-refractory graft-versus-host-disease finally ended a long-lasting drought on approved MSC clinical products in the United States. While other jurisdictions-including Europe, Japan, India, and South Korea-have marketed autologous or allogeneic MSC products, the United States has lagged in its approval. The sponsor's significant efforts and investments, working closely with the FDA addressing concerns regarding clinical efficacy and consistent MSC potency through an iterative process that spanned several years, was rewarded with this landmark approval.

Influences of age and sex on the diagnostic accuracy of human epididymis secretory protein 4 for malignant pleural effusion.

Previous studies have suggested that the presence of human epididymal protein 4 (HE4) in pleural fluid can be used to diagnose malignant pleural effusion (MPE) with moderate accuracy. However, the factors that affect the diagnostic accuracy of HE4 remain unknown. This study aimed to examine how age and sex influence the diagnostic accuracy of HE4.

Spatial variations in urban woodland cooling between background climates.

Urban woodland composition and configuration have strong associations with land surface temperatures (LST), but the evidence is contradictory due to different spatial scales, regional climate zones, woodland types and urban contexts. In this study, we analyse associations between urban woodland and LST within and between five cities in different Köppen climate zones. Our consistent methodology is framed around local climate zones and conducted at a fine spatial scale.

Fuzzy reinforcement learning based control of linear systems with input saturation.

This research introduces an innovative approach to optimal control for a class of linear systems with input saturation. It leverages the synergy of Takagi-Sugeno (T-S) fuzzy models and reinforcement learning (RL) techniques. To enhance interpretability and analytical accessibility, our approach applies T-S models to approximate the value function and generate optimal control laws while incorporating prior knowledge.

Exploratory study of patients' and carers' preferences for postdischarge surgical wound monitoring using survey and interviews.

Objectives: To explore patients' and carers' preferences for postdischarge surgical wound monitoring.

Design: Explanatory mixed methods study with an online survey followed by online interviews.

Setting: The online survey was distributed via the Cardiothoracic Interdisciplinary Research Network and cardiac surgery patient and public involvement groups in London and Leicester, UK.

Adherence to tuberculosis (TB) treatment in high compared to low TB burden countries: study protocol for a systematic review and meta-analysis with a qualitative meta-synthesis of themes.

Introduction: Non-adherence to tuberculosis (TB) treatment poses a significant challenge to effective TB management globally and is a major contributor to the emergence of multidrug-resistant TB. Although adherence to TB treatment has been widely studied, a comprehensive evaluation of the comparative levels of adherence in high- versus low-TB burden settings remains lacking. The objective of this systematic review and meta-analysis is to assess the levels of adherence to TB treatment in high-TB burden countries compared to low-burden countries.

Impact of microgeography on communication dynamics in a healthcare environment.

Background: For growing healthcare organisations, anchored resources-assets that are not easily movable-may complicate expansion and distort workflow patterns. We examine work patterns at a radiation oncology department of a major Canadian hospital. As this department doubled its size, healthcare providers remained bound to treatment planning rooms and radiation machines at the original site.

Characterizing tumor-infiltrating group 1 innate lymphoid cells in PyMT breast tumors.

Breast cancer is the most common cancer in women and continues to have a significant impact in cancer-associated deaths worldwide. Investigating the complex roles of infiltrating immune subsets within the tumor microenvironment (TME) will enable a better understanding of disease progression and reveal novel therapeutic strategies for patients with breast cancer. The mammary-specific expression of polyomavirus middle T oncoprotein (MMTV-PyMT) was first established in 1992 by William Muller and is the most commonly used genetically engineered mouse model (GEMM) for breast cancer research.

Spatiotemporal metabolic mapping of ex-situ preserved hearts subjected to dialysis by integration of bio-SPME sampling with non-targeted metabolipidomic profiling.

Background: Normothermic ex situ heart perfusion (ESHP) has emerged as a valid modality for advanced cardiac allograft preservation and conditioning prior to transplantation though myocardial function declines gradually during ESHP thus limiting its potential for expanding the donor pool. Recently, the utilization of dialysis has been shown to preserve myocardial and coronary vasomotor function. Herein, we sought to determine the changes in myocardial metabolism that could support this improvement.

Assessing the performance of Microsoft Copilot, GPT-4 and Google Gemini in ophthalmology.

Objective: To evaluate the performance of large language models (LLMs), specifically Microsoft Copilot, GPT-4 (GPT-4o and GPT-4o mini), and Google Gemini (Gemini and Gemini Advanced), in answering ophthalmological questions and assessing the impact of prompting techniques on their accuracy.

Design: Prospective qualitative study.

Participants: Microsoft Copilot, GPT-4 (GPT-4o and GPT-4o mini), and Google Gemini (Gemini and Gemini Advanced).

Topographic corneal changes in children with moderate to severe blepharokeratoconjunctivitis.

Purpose To determine the corneal topographic characteristics of children with blepharokeratoconjunctivitis (BKC), a chronic inflammatory ocular surface disease involving the lid margin, conjunctiva, and cornea. Methods The corneal topography of 21 children diagnosed with BKC between March 2008 and June 2019 at a single institution were reviewed retrospectively. Pachymetry and asymmetry indices were also analyzed.

The risk of donor-acquired allergy in solid organ transplant recipients: a systematic review.

Background: Donor acquired allergy (DAA) occurs when donors transfer their allergies to recipients through solid organ transplant (SOT). However, the risk of DAA in recipients of organs from allergic donors has not been systematically characterized.

Objective: We sought to synthesize the available evidence on the risk of DAA in SOT recipients.

NUMB alternative splicing and isoform specific functions in development and disease.

The NUMB gene encodes a conserved adaptor protein with roles in asymmetric cell division and cell fate determination. First described as an inhibitor of Notch signaling, multi-functional NUMB proteins regulate multiple cellular pathways through protein complexes with ubiquitin ligases, polarity proteins and the endocytic machinery. The vertebrate NUMB protein isoforms were identified over two decades ago, yet the majority of functional studies exploring NUMB function in endocytosis, cell migration and adhesion, development and disease have largely neglected the potential for distinct isoform activity in design and interpretation.

Data Collection Variability Across Neonatal Hypoxic-Ischemic Encephalopathy Registries.

Objective: To assess variability among data elements collected among existing neonatal hypoxic-ischemic encephalopathy (HIE) data registries worldwide and to determine the need for future harmonization of standard common data elements.

Study Design: This was a cross-sectional study of data elements collected from current or recently employed HIE registry data forms. Registries were identified by literature search and email inquiries to investigators worldwide.

Neuropsychiatric manifestations in systemic lupus erythematosus and Sjogren's disease.

Introduction: Autoimmune diseases often present in a systemic manner, affecting various organs and tissues. Involvement of the central and peripheral nervous system is not uncommon in these conditions and is associated with high morbidity and mortality. Therefore, early recognition of the neuropsychiatric manifestations associated with rheumatologic diseases is essential for the introduction of appropriate therapies with the objective of providing a better quality of life for individuals.

Scoping review of registration of observational studies finds inadequate registration policies, increased registration, and a debate converging towards pro-registration.

Objective: We aimed to examine a) the policies of national and international clinical trial registries regarding observational studies; b) the time-trends of observational study registration; c) the published arguments for and against observational study registration.

Study Design And Setting: Scoping review of registry practices and published arguments. We searched the websites and databases of all 19 members of the World Health Organization's Registry Network to identify policies relating to observational studies and the number of observational studies registered annually from the beginning of the registries to 2022.

Stereotactic body radiotherapy for non-spine bone metastases: A meta-analysis and international stereotactic radiosurgery society (ISRS) clinical practice guidelines.

Background: While SBRT to NSBM has become common, particularly in the oligometastatic population, the approach to treating non-spine bone metastases (NSBM) with stereotactic body radiotherapy (SBRT) varies widely across institutions and clinical trial protocols. We present a comprehensive systematic review of the literatures to inform practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS).

Methods: A systematic literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Dosimetric comparison of CyberKnife and conventional linac prostate SBRT plans: analysis of the PACE-B Study.

Purpose: In the PACE-B study, a non-randomised comparison of toxicity outcomes between stereotactic body radiotherapy (SBRT) platforms revealed fewer urinary side-effects with CyberKnife (CK) compared to conventional linac (CL) SBRT. This analysis compares baseline characteristics and planning dosimetry between the CK-SBRT and CL-SBRT cohorts in PACE-B, aiming to provide insight into possible reasons for differing toxicity outcomes between the platforms.

Methods: Dosimetric parameters for the surrogate urethra (SU), contoured urethra, bladder, bladder trigone (BT), and rectum were extracted from available CT planning scans of PACE-B SBRT patients.

Apixaban versus aspirin for stroke prevention in people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack: subgroup analysis of the ARTESiA randomised controlled trial.

Background: People with subclinical atrial fibrillation are at increased risk of stroke, albeit to a lesser extent than those with clinical atrial fibrillation, leading to an ongoing debate regarding the benefit of anticoagulation in these individuals. In the ARTESiA trial, the direct-acting oral anticoagulant apixaban reduced stroke or systemic embolism compared with aspirin in people with subclinical atrial fibrillation, but the risk of major bleeding was increased with apixaban. In a prespecified subgroup analysis of ARTESiA, we tested the hypothesis that people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack, who are known to have an increased risk of recurrent stroke, would show a greater benefit from oral anticoagulation for secondary stroke prevention compared with those without a history of stroke or transient ischaemic attack.

Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial.

Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.

Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study.

Background: Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study.

A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

Ligand interaction landscape of transcription factors and essential enzymes in E. coli.

Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium Escherichia coli. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces.