Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.

Methods: We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles.

Global Perspectives on Returning Genetic Research Results in Parkinson Disease.

Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.

COLOFIT: Development and Internal-External Validation of Models Using Age, Sex, Faecal Immunochemical and Blood Tests to Optimise Diagnosis of Colorectal Cancer in Symptomatic Patients.

Background: Colorectal cancer (CRC) is the third most common cancer in the United Kingdom and the second largest cause of cancer death.

Aim: To develop and validate a model using available information at the time of faecal immunochemical testing (FIT) in primary care to improve selection of symptomatic patients for CRC investigations.

Methods: We included all adults (≥ 18 years) referred to Nottingham University Hospitals NHS Trust between 2018 and 2022 with symptoms of suspected CRC who had a FIT.

A Single Bioorthogonal Reaction for Multiplex Cell Surface Protein Labeling.

Small-molecule fluorophores are invaluable tools for fluorescence imaging. However, means for their covalent conjugation to the target proteins limit applications in multicolor imaging. Here, we identify 2-[(alkylhio)(ryl)ethylene]alononitrile (TAMM) molecules reacting with 1,2-aminothiol at a labeling rate over 10 M s through detailed mechanistic investigation.

Molecular and spatial analysis of tertiary lymphoid structures in Sjogren's syndrome.

Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren's disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures.

Incidence, mortality, and global burden of retinoblastoma in 204 countries worldwide from 1990 to 2021: Data and systematic analysis from the Global Burden of Disease Study 2021.

Background: Retinoblastoma (Rb), the primary intraocular malignancy in children, poses significant risks, yet its overall burden remains inadequately assessed. This study aims to analyze global Rb trends using Global Burden of Disease, Injuries, and Risk Factors study (GBD) 2021 data.

Methods: GBD 2021 data was analyzed to assess Rb incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021.

Foliar applied calcium chloride alleviated drought stress in pearl millet (Pennisetum glaucum L.) by improving growth and yield contributing traits and antioxidant activity.

Drought-induced stress presents a substantial threat as it disrupts the normal growth of cereal crops and leads to decreased yields. The persistent occurrence of drought conditions significantly impacts the growth and development of pearl millet. This study aimed to explore how calcium chloride (CaCl2) regulates the growth of pearl millet when it faces a lack of water.

Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches.

Intraocular pressure (IOP) elevation is the primary risk factor and currently the main treatable factor for progression of glaucomatous optic neuropathy. In addition to direct clinical and living animal in vivo studies, ex vivo perfusion of anterior segments and whole eyes is a key technique for studying conventional outflow function as it is responsible for IOP regulation. We present well-tested experimental details, protocols, considerations, advantages, and limitations of several ex vivo model systems for studying IOP regulation.

Recreational and Occupational Physical Activity and Risk of Adverse Events in Truncating Founder Variant Carriers.

Background: founder variants cause hypertrophic cardiomyopathy leading to heart failure and malignant ventricular arrhythmias. Exercise is typically regarded as a risk factor for disease expression although evidence is conflicting. Stratifying by type of exercise may discriminate low- from high-risk activities in these patients.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Newcastle disease virus infection induces parthanatos in tumor cells via calcium waves.

Parthanatos is distinct from caspase-dependent apoptosis in that it does not necessitate the activation of caspase cascades; Instead, it relies on the translocation of Apoptosis-inducing Factor (AIF) from the mitochondria to the nucleus, resulting in nuclear DNA fragmentation. Newcastle Disease Virus (NDV) is an oncolytic virus that selectively targets and kills tumor cells by inducing cell apoptosis. It has been reported that NDV triggers classic apoptosis through the mitochondrial pathway.

Impact of intensity standardisation and ComBat batch size on clinical-radiomic prognostic models performance in a multi-centre study of patients with glioblastoma.

Purpose: To assess the effect of different intensity standardisation techniques (ISTs) and ComBat batch sizes on radiomics survival model performance and stability in a heterogenous, multi-centre cohort of patients with glioblastoma (GBM).

Methods: Multi-centre pre-operative MRI acquired between 2014 and 2020 in patients with IDH-wildtype unifocal WHO grade 4 GBM were retrospectively evaluated. WhiteStripe (WS), Nyul histogram matching (HM), and Z-score (ZS) ISTs were applied before radiomic feature (RF) extraction.

Functional Outcome Measures to Optimize Drug Development in Spinal and Bulbar Muscular Atrophy: Results From a Meta-Analysis of the Global SBMA Dataset.

Background And Objectives: Spinal and bulbar muscular atrophy (SBMA) is a rare, slowly progressive, and debilitating disease without effective treatments available. Lack of reliable biomarkers and sensitive outcome measures makes clinical research conduct challenging. The primary objective of this study was to identify clinically meaningful and statistically sensitive outcome measures enabling the evaluation of therapeutic interventions in late-stage clinical trials.

Prebiotics in food and dietary supplements: a roadmap to EU health claims.

Numerous studies have established that prebiotic ingredients in foods and dietary supplements may play a role in supporting human health. Over the three decades that have passed since prebiotics were first defined as a concept, research has revealed a complex universe of prebiotic-induced changes to the human microbiota. There are strong indications of a direct link between these prebiotic-induced changes and specific health benefits.

Epidemiological and genomic analysis revealed the significant role of flies in dissemination of carbapenem-resistant Enterobacteriaceae (CRE) in China.

While the role of flies as potential vectors for bacterial transmission is well recognized, the epidemiological features and genomic characteristics of associated antimicrobial-resistant strains remain underexplored. This study conducted a nationwide surveillance including 3689 flies and 838 isolates from sixteen human communities (HCs) and eight animal farms (AFs) across 21 provinces in China. Our findings revealed high carriage rates of carbapenem-resistant Enterobacteriaceae (CRE) in flies, with 27.

Ignoring the food route underestimated human health risk from potentially toxic elements in agricultural environments of Ziyang, Shaanxi, China.

Staple food is a crucial exposure route for the human intake of potentially toxic elements (PTEs), but it has been neglected in previous human health risk (HHR) studies. Lack of attention to this issue will lead to an underestimation of HHR caused by PTEs. This study establishes a comprehensive regional identification method for health risk assessment (HRA), namely, soil-maize health risk assessment (SMHRA) and applies it to Ziyang, Shaanxi, which is a typical agricultural county.