Overcoming target interference in bridging anti-drug antibody (ADA) assay by optimizing sample treatment.

Background: Drug bridging immunoassays are widely employed as the standard approach for detecting anti-drug antibodies (ADAs) in the development of new biological entities. A major challenge in these assays is mitigating target interference, particularly when the soluble target exists in dimeric forms, which can result in false positive signals and compromise assay specificity.

Research Design And Methods: We developed sensitive and robust ADA assays capable of overcoming target interference to detect antibodies against BI X in both cynomolgus monkey (cyno) plasma and human serum matrices.

Lifetime water arsenic, genetic susceptibility, and bladder cancer in the New England Bladder Cancer Study.

Background: Exposure to arsenic in drinking water may interact with common genetic variants in urinary bladder cancer risk.

Methods: We conducted a gene-environment interaction analysis among 1091 bladder cancer cases and 928 controls from the New England Bladder Cancer Study. Genetic variants tested as effect modifiers included those associated with bladder cancer and arsenic metabolism.

Proceedings of the 15 European immunogenicity platform open symposium on immunogenicity of biopharmaceuticals.

The European Immunogenicity Platform (EIP) celebrated the 15th edition of its Open Symposium on Immunogenicity of Biopharmaceuticals and its associated one-day workshop on 22-24 February 2024 in Lisbon. The meeting attracted experts and newcomers across industry, regulatory agencies, and academia, who actively participated in 3 days of discussion on risk assessment, monitoring, and mitigation of unwanted immunogenicity of biologics. Besides oral presentations, poster sessions were held to maximize scientific exchange and networking opportunities.

Solvent Exposure, Genetic Susceptibility, and Risk of Bladder Cancer.

The New England Bladder Cancer Study has recently reported an increased bladder cancer risk with occupational exposure to mononuclear aromatic organic solvents, including exposure to benzene, toluene, and xylene and their combination BTX. However, the mechanisms by which BTX influence bladder cancer are unclear. In this study, we evaluated the interaction between BTX and genetic markers in known bladder cancer susceptibility loci and in variants shown to impact the metabolism of these solvents.

Modeling Historic Arsenic Exposures and Spatial Risk for Bladder Cancer.

Arsenic is a bladder carcinogen though less is known regarding the specific temporal relationship between exposure and bladder cancer diagnosis. In this study, we modeled time-varying mixtures of arsenic exposures at many historic temporal windows to evaluate their association with bladder cancer risk in the New England Bladder Cancer Study. We used arsenic exposure estimates up to 60 years prior to study entry and compared the goodness of fit of models using these mixtures to those using summary measures of arsenic exposures.

The impact of introducing deep learning based [F]FDG PET denoising on EORTC and PERCIST therapeutic response assessments in digital PET/CT.

Background: [F]FDG PET denoising by SubtlePET™ using deep learning artificial intelligence (AI) was previously found to induce slight modifications in lesion and reference organs' quantification and in lesion detection. As a next step, we aimed to evaluate its clinical impact on [F]FDG PET solid tumour treatment response assessments, while comparing "standard PET" to "AI denoised half-duration PET" ("AI PET") during follow-up.

Results: 110 patients referred for baseline and follow-up standard digital [F]FDG PET/CT were prospectively included.

Tools and frameworks for evaluating the implementation of learning health systems: a scoping review.

Introduction: Despite increased interest in learning health systems (LHS), a paucity of guidance and tools for evaluating LHS implementation exists. To address this, we aim to undertake a scoping review on existing tools and evaluation of exemplars of LHS implementation.

Methods: We conducted a scoping review of peer-reviewed studies within Scopus, EMBASE, MEDLINE, and MEDLINE in-process that described (1) the evaluation of the implementation of an operating LHS or (2) the development of a framework or tool to facilitate this evaluation.

Accelerating COVID-19 Vaccination Among People Living With HIV and Health Care Workers in Tanzania: A Case Study.

Background: There is limited evidence on COVID-19 vaccination uptake among people living with HIV (PLHIV) and health care workers (HCWs), with the current evidence concentrated in high-income countries. There is also limited documentation in the published literature regarding the feasibility and lessons from implementing targeted vaccination strategies to reach PLHIV and HCWs in low- and middle-income countries.

Program Development, Piloting, And Implementation: We designed and implemented multifaceted strategies to scale up targeted COVID-19 vaccination among PLHIV and HCWs in 11 administrative regions on the mainland of Tanzania plus Zanzibar.

Comparative evaluation of three real-time polymerase chain reaction assays to detect Myxobolus cerebralis.

Objective: We sought to evaluate accurate and reproducible detection of Myxobolus cerebralis (Mc), the causative agent of whirling disease, by using nested polymerase chain reaction (nPCR) and three previously established real-time quantitative PCR (qPCR) assays: K18S (Kelley 18S), C18S (Cavender 18S), and Hsp70 (heat shock protein 70). We used a "fit for purpose" approach combined with intra- and interlaboratory testing to identify a molecular testing method that would be equivalent to the currently accepted nPCR procedure for Mc.

Methods: Assay performance was compared using a combination of intra- and interlaboratory testing that used synthetic gBlocks along with naturally and experimentally infected fish tissue.

Impact of Radiation Therapy Modalities on Loco-regional Control in Inflammatory Breast Cancer.

Purpose: In inflammatory breast cancer, radiation therapy intensification is considered a standard of care by some teams, although the level of evidence remains low. We sought to analyze the impact of radiation therapy modalities on the risk of loco-regional and distant relapse.

Methods And Materials: This retrospective multicenter study included patients with localized inflammatory breast cancer treated between 2010 and 2017.

Urinary mutagenicity and bladder cancer risk in northern New England.

The etiology of bladder cancer among never smokers without occupational or environmental exposure to established urothelial carcinogens remains unclear. Urinary mutagenicity is an integrative measure that reflects recent exposure to genotoxic agents. Here, we investigated its potential association with bladder cancer in rural northern New England.

Occupational exposure to organic solvents and risk of bladder cancer.

Background: Bladder cancer has been linked to several occupations that involve the use of solvents, including those used in the dry-cleaning industry.

Objectives: We evaluated exposure to solvents and risk of bladder cancer in 1182 incident cases and 1408 controls from a population-based study.

Methods: Exposure to solvents was quantitatively assessed using a job-exposure matrix (CANJEM).

Stable isotope ratios and current-use pesticide levels in edible insects: Implications on chemical food safety.

In the past years, the European Union (EU) has added edible insects to the list of novel foods, allowing an increasing number of insect-based products into the European market. With insects gaining more popularity in the Western world, it is crucial to investigate their chemical food safety. This study aimed at investigating possible isotopic patterns in different edible insect species (n = 52) from Asia, Africa and Europe using stable isotope ratio analysis (SIRA) to provide a framework for future investigations on food authenticity and traceability.

Implementation of Artificial Intelligence Applications in Australian Healthcare Organisations: Environmental Scan Findings.

Artificial Intelligence (AI) has great potential to improve healthcare, but implementation into routine practice remains a challenge. This study scoped the extent to which AI and Natural Language Processing (NLP) is being implemented into routine practice in Australian healthcare organisations. An environmental scan of publicly available data was undertaken to identify AI applications.

Development of an Enzyme-Linked Immunosorbent Spot Assay for the Assessment of Adeno-Associated Virus Peptides to Examine Immune Safety.

Adeno-associated virus (AAV)-based gene therapies have shown promise as novel treatments for rare genetic disorders such as hemophilia A and spinal muscular atrophy. However, cellular immune responses mediated by cytotoxic (CD8) and helper (CD4) T cells may target vector-transduced cells as well as healthy immune cells, impacting safety and efficacy. In this study, we describe the optimization and reproducibility of interferon-γ (IFNγ)-based and interleukin-2 (IL-2)-based enzyme-linked immunosorbent spot (ELISpot) assays for measuring T cell responses against AAV peptide antigens.

Impact of web application support versus standard management on adherence with adjuvant hormone therapy in patients treated for breast cancer: the WEBAPPAC study.

Background: Non-metastatic breast cancer treatment is mainly based on surgery, with or without chemotherapy, radiotherapy and/or hormone therapy. To reduce the risk of hormone receptor positive (HR+) disease recurrence, hormone therapy is prescribed for at least 5 years. It may induce adverse drug reactions (ADRs) as joint pain, sexual dysfunction, weight increase, fatigue, mood disorders and vasomotor symptoms.

Analysis of Several Common APOBEC-type Mutations in Bladder Tumors Suggests Links to Viral Infection.

Unlabelled: FGFR3 and PIK3CA are among the most frequently mutated genes in bladder tumors. We hypothesized that recurrent mutations in these genes might be caused by common carcinogenic exposures such as smoking and other factors. We analyzed 2,816 bladder tumors with available data on FGFR3 and/or PIK3CA mutations, focusing on the most recurrent mutations detected in ≥10% of tumors.

Pairwise comparative analysis of six haplotype assembly methods based on users' experience.

Background: A haplotype is a set of DNA variants inherited together from one parent or chromosome. Haplotype information is useful for studying genetic variation and disease association. Haplotype assembly (HA) is a process of obtaining haplotypes using DNA sequencing data.

Urine pH and Risk of Bladder Cancer in Northern New England.

Background: Acidic urine pH is associated with rapid hydrolysis of N-glucuronide conjugates of aromatic amines into metabolites that may undergo metabolism in the bladder lumen to form mutagenic DNA adducts. We previously reported that consistently acidic urine was associated with increased bladder cancer risk in a hospital-based case-control study in Spain. Here, we conducted a separate study in northern New England to replicate these findings.

Identifying Duplicate Cancer Cases Across State Boundaries: Pseudonymization as a Method to Encrypt Identifiers.

Identifying potential duplicate cancer cases across state boundaries has been a topic of interest for many years. Duplicate cases could distort our understanding of the burden of cancer in a state, region, or even nationally, and waste cancer surveillance resources. This paper reports a pilot quality improvement project to use a publicly available tool to encrypt a standard set of patient identifiers and then link cases across state boundaries as a way to identify and reconcile possible duplicate cases among a group of neighboring states.

Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors.

Background: Diesel exhaust is a complex mixture, including polycyclic aromatic hydrocarbons (PAH) and nitrated PAHs (nitro-PAH), many of which are potent mutagens and possible bladder carcinogens. To explore the association between diesel exposure and bladder carcinogenesis, we examined the relationship between exposure and somatic mutations and mutational signatures in bladder tumors.

Methods: Targeted sequencing was conducted in bladder tumors from the New England Bladder Cancer Study.

Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors.

Background: Cyclin dependent kinase inhibitors (CdK4/6i) changed the course of hormone receptor positive (HR+) HER2 negative (HER2-) metastatic breast cancer (mBC). To date, no factors have been shown to predict response to CdK4/6i. Neutrophil-to-lymphocyte ratio (NLR), an indicator of the host systemic inflammatory response, is an independent prognostic factor for survival in cancers.

HELENA: HER2-Low as a prEdictive factor of response to Neoadjuvant chemotherapy in eArly breast cancer.

Background: HER2 expression has a prognostic and predictive impact in early-stage breast cancer (BC). HER2 positive BC (immunohistochemistry (IHC) score 3 + or 2 + with in situ hybridization (ISH) amplification) are treated with HER2 targeted therapies. The concept of HER2-low BC (IHC score 1 + or 2 + without ISH amplification) is drawing attention as anti-HER2 treatment has recently shown efficacy in this subgroup.