Estimands for Early-Phase Dose Optimization Trials in Oncology.

Phase I dose escalation trials in oncology generally aim to find the maximum tolerated dose. However, with the advent of molecular-targeted therapies and antibody drug conjugates, dose-limiting toxicities are less frequently observed, giving rise to the concept of optimal biological dose (OBD), which considers both efficacy and toxicity. The estimand framework presented in the addendum of the ICH E9(R1) guidelines strengthens the dialogue between different stakeholders by bringing in greater clarity in the clinical trial objectives and by providing alignment between the targeted estimand under consideration and the statistical analysis methods.

Use of a novel zipper device for wound closure of cutaneous abscesses in pediatric outpatients: a case series.

Background: Current management of pediatric cutaneous abscesses involves either spontaneous healing by secondary intention or suturing through tertiary intention, which are often lengthy processes that cause discomfort and distress among children. As it is noninvasive and simple, a novel zipper device is widely used for the primary wound closure of surgical incisions.

Objective: To describe the effectiveness of novel zipper device use for pediatric cutaneous abscess wound closure in an outpatient context.

A Sensitive and Comprehensive LC-MS/MS Method for the Analysis of Hallucinogens, Synthetic Cathinones, and Synthetic Cannabinoids in Urine Samples.

The laboratory analysis of new psychoactive substances and related drugs is crucial for accurate clinical and forensic diagnosis of poisonings. Given this, a new LC-MS/MS method for analyzing hallucinogens, synthetic cathinones, and synthetic cannabinoids in urine was developed. Urine samples were extracted using a liquid-liquid extraction protocol optimized via a multivariate experimental design.

Green synthesis of silver nanoparticles using Ocimum sanctum for efficient Congo red dye removal: a response surface methodology approach.

Synthetic dyes, such as Congo red (CR), pose serious threats to human health and aquatic ecosystems because of their carcinogenicity and resistance to degradation, necessitating the development of efficient and eco-friendly remediation strategies. In this study, silver nanoparticles (AgNPs) were synthesized via a green method using Ocimum sanctum (holy basil) leaf extract and applied for CR dye removal from aqueous solutions. The adsorption process was optimized using response surface methodology (RSM) based on Box-Behnken design (BBD), evaluating the influence of key parameters including pH, AgNP dosage, initial dye concentration, contact time, and temperature.

ASO Practice Guidelines Series: Soft Tissue Sarcoma of the Extremities and Superficial Trunk.

Soft tissue sarcomas (STS) are a heterogeneous group of rare malignant tumors arising from mesenchymal tissues, with extremity and superficial trunk STS (eSTS) comprising the majority of cases. The management of localized eSTS requires a multidisciplinary approach to optimize oncologic and functional outcomes. This review outlines the natural history, diagnostic workup, and treatment principles for localized eSTS, emphasizing the role of histology-specific considerations in guiding management strategies.

The impact of melatonin-enriched media on epigenetic and perinatal changes induced by embryo culture in a mouse model.

Purpose: To determine if melatonin-enriched culture media could offset loss of imprinting in mouse concepti.

Methods: Zygotes were cultured to blastocyst stage under optimized conditions in melatonin-supplemented media at either 10 M (MT 10) or 10 M (MT 10), or without supplementation (Culture + embryo transfer, or ET, positive control). Blastocysts were also developed in vivo (ET negative control).

Slowing down the clock on ovarian aging-does the ovary hold the secret to the fountain of youth?

In the past century, the human Lifespan has doubled. However, this is not equivalent to Healthspan which refers to the number of years spent healthy and free from disease. Women have an additional level of complexity on the path to optimal healthspan where health resilience dramatically decreases following menopause and this is due to their ovaries aging by midlife.

Low-grade non-muscle-invasive bladder cancer: molecular landscape, treatment strategies and emerging therapies.

Low-grade non-muscle invasive bladder cancer is a specific category of bladder cancer with a favourable prognosis; however, its management presents several challenges. The risk of stage progression is very low, but approximately half of patients will experience recurrence within the first 5 years after diagnosis. This high propensity for recurrence, coupled with the threat of progression, mandates ongoing surveillance.

You can't have your cake and eat it too: the paradox of the American public supporting road safety but reluctant to pay the price - evidence from a discrete choice experiment.

Background: An estimated 44,680 people died in motor-vehicle crashes in the United States in 2024. A disproportionate share of these deaths involved young people. In 2023 alone, these crashes cost the U.

Effect of an integrated care model on ST-segment elevation myocardial infarction management in China: a prospective, multicentre, non-randomised controlled study.

Background: Early reperfusion therapy is critical in patients with ST-segment elevation myocardial infarction (STEMI). However, limitations in resources and patient-level and system-level barriers delay the administration of reperfusion therapy. This study evaluated the impact of an integrated care strategy for STEMI management in China.

Assessing health system preparedness from trends and time delays in the management of myocardial infarctions during the COVID-19 pandemic in India: a multicentre retrospective cohort study.

Objectives: This study aimed to analyse the number of myocardial infarction (MI) admissions during the COVID-19 lockdown periods of 2020 and 2021 (March 15th to June 15th) and compare them with corresponding pre-pandemic period in 2019. The study also evaluated changes in critical treatment intervals: onset to door (O2D), door to balloon (D2B) and door to needle (D2N) and assessed 30-day clinical outcomes. This study examined MI care trends in India during the COVID-19 lockdown period, irrespective of patients' COVID-19 infection status.

Integrated Micro-CT and Computational Fluid Dynamics Analysis of Stepwise Enlargement in Mesial Root Canals of Mandibular Molars.

Introduction: To evaluate how stepwise enlargement in the mesial root canals of mandibular first molars affect shaping outcomes and irrigant dynamics.

Methods: The shaping ability and irrigant flow patterns in mesial canals of mandibular first molars enlarged with ProTaper Next instruments (25/.06v, 30/.

Development of a translational strategy for using TIMP-3 to inhibit aggrecanase activity in osteoarthritis.

Objective: Therapeutic potential of selective aggrecanase inhibition in osteoarthritis (OA) was previously demonstrated using a variant of endogenous tissue inhibitor of metalloproteinase-3 (TIMP-3); however, this relied on transgenic mice overexpressing TIMP-3. Here, we develop a translational approach for harnessing the aggrecanase-selective inhibitory activity of TIMP-3 using the latency associated peptide (LAP) technology.

Methods: We successfully produced and purified recombinant LAP-TIMP-3 fusion proteins and determined the pharmacokinetics of these proteins in vivo following systemic injection.

Biophysically Constrained Dynamical Modelling of the Brain Using Multimodal Magnetic Resonance Imaging.

We propose a Biophysically Restrained Analog Integrated Neural Network (BRAINN), an analog electrical network that models the dynamics of brain function. The network interconnects analog electrical circuits that simulate two tightly coupled brain processes: (1) propagation of an action potential, and (2) regional cerebral blood flow in response to the metabolic demands of signal propagation. These two processes are modeled by two branches of an electrical circuit comprising a resistor, a capacitor, and an inductor.

Trajectories of Synchronous Subsolid Nodules in Patients with Resected Subsolid Lung Adenocarcinoma: A Multicenter Cohort Study.

Introduction: Multifocal subsolid nodules (SSNs) are increasingly detected with widespread lung cancer screening and advanced thoracic imaging, representing a spectrum of multifocal lung adenocarcinomas (LUADs). When synchronous SSNs coexist with a surgically confirmed subsolid LUAD, their trajectories remain poorly understood, contributing to uncertainty regarding optimal management strategies. This study aimed to evaluate the clinical course and impact of synchronous SSNs in such patients and to identify features associated with their progression.

Sex Differences in Postoperative Outcomes of Hirschsprung Disease: Propensity Score Matching Analysis.

Purpose: Sex differences in Hirschsprung disease (HSCR) incidence have been well documented, yet little is known about whether the effect of sex on postoperative outcomes. This study aims to investigate the sex differences of postoperative outcomes of HSCR using propensity score matching (PSM) analysis.

Methods: Retrospective review of 304 patients with HSCR who received single-stage laparoscopic transanal pull-through modified Swenson procedure in a single-center was conducted with assessments of clinical data.

Huashi Baidu Granules Alleviates LPS-Induced Acute Lung Injury by Targeting TACE-Mediated Inflammatory Signaling and Stress Granules disassembly.

Ethnopharmacological Relevance: Acute lung injury (ALI) is a severe health issue characterized by high morbidity and mortality, driven by excessive inflammatory responses. The traditional Chinese medicine Huashi Baidu Granules (HBG) demonstrated clinical efficacy in treating severe ALI, yet its mechanisms remain unclear.

Aim Of The Study: This research aimed to examine the efficacy and underlying mechanisms of HBG in a lipopolysaccharide (LPS)-induced ALI model, identify core herbal constituents, active compounds, and therapeutic targets, providing a foundation for optimizing HBG-based treatments.

A diverse semi-synthetic humanized scFv phage display library for anti-CXCL16 antibodies.

Phage display libraries of human single-chain variable fragments (scFv) serve as a valuable resource for generating fully human antibodies for scientific and clinical applications. In this study, we designed and constructed a highly diverse semi-synthetic humanized scFv phage display library using an optimized Kunkel mutagenesis approach. Our optimizations eliminated residual template, enhancing mutagenesis efficiency and expanding library diversity with a reservoir capacity exceeding 10.

Comparison of autologous and allogeneic hematopoietic stem cell transplantation for primary plasma cell leukemia in Japan.

Primary plasma cell leukemia (pPCL) is a rare and aggressive subtype of plasma cell malignancy. Although hematopoietic stem cell transplantation (HCT), including autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT), is widely used, an optimal treatment strategy is undetermined. We retrospectively analyzed patients with pPCL who underwent HCT between 2006 and 2022 in Japan using Japanese registry data.

From prediction to precision: Artificial intelligence and emerging technologies in cardiopulmonary resuscitation.

Background: Cardiopulmonary resuscitation (CPR) is a vital intervention for managing cardiac arrest; however, enhancing survival rates remains a significant challenge. Recent advancements highlight the importance of integrating artificial intelligence (AI) to overcome existing limitations in prediction, intervention, and post-resuscitation care.

Methods: A thorough review of contemporary literature regarding AI applications in CPR was undertaken, explicitly examining its role in the early prediction of cardiac arrest, optimization of CPR quality, and enhancement of post-arrest outcomes.

Family History-Guided Physical Activity for Cardiovascular Disease Prevention.

Introduction: It remains unclear if individuals with a family history of cardiovascular disease (CVD) can achieve similar CVD incidence reductions through moderate-to-vigorous physical activity (MVPA) as those without a family history. The aim of the study was to investigate the importance of familial CVD history on the association of MVPA with CVD risk.

Methods: A prospective cohort from the UK Biobank who completed one week of accelerometer-based MVPA measurements from June 1, 2013, to December 23, 2015 was analyzed.

Hydrodynamic focusing to synthesize lipid-based nanoparticles: Computational and experimental analysis of chip design and formulation parameters.

Microfluidic hydrodynamic focusing (HF) has emerged as a powerful platform for the controlled synthesis of lipid nanoparticles (LNPs) and liposomes, offering superior precision, reproducibility, and scalability compared to traditional batch methods. However, the impact of HF inlet configuration and channel geometry on nanoparticle formation remains poorly understood. In this study, we present a comprehensive experimental and computational analysis comparing 2-inlet (2-way) and 4-inlet (4-way) HF designs across various sheath inlet angles (45°, 90°, 135°) and cross-sectional geometries (square vs.

The Role of Generative Artificial Intelligence and Large Language Models in Atrial Fibrillation: Clinical Research and Decision Support.

Atrial fibrillation (AF) is a prevalent and complex cardiac arrhythmia requiring multifaceted management strategies. This review explores the integration of large language models (LLMs) and machine learning into AF care, with a focus on clinical utility, privacy preservation, and ethical deployment. Federated and transfer learning methods have enabled high-performance predictive modeling across distributed datasets without compromising data security.

Using Machine Learning to Predict-Then-Optimize Elective Orthopedic Surgery Scheduling to Improve Operating Room Utilization: Retrospective Study.

Background: Total knee and hip arthroplasty (TKA and THA) are among the most performed elective procedures. Rising demand and the resource-intensive nature of these procedures have contributed to longer wait times despite significant health care investment. Current scheduling methods often rely on average surgical durations, overlooking patient-specific variability.

Validation of the eHealth Literacy Scale Instrument in a Restless Legs Syndrome Population: Classical Test Theory and Rasch Analysis Study.

Background: An increased use of the internet and digital health care for patients with long-term conditions implies a need for assuring digital health literacy skills. Patients with restless legs syndrome (RLS) represent a group where digital sources of information are highly valued. This is due to a difficult diagnosis and complex treatment situation that contributes to patients seeking out digital resources themselves to handle the perceived shortcomings in their care.