Stable Iodine Intake During Pregnancy and Children's Thyroid Screening Outcomes After the 2011 Fukushima Nuclear Disaster in Japan: A Municipality-based Descriptive Study.

Objectives: Stable iodine intake is an essential preventive strategy against thyroid cancer following a nuclear disaster. However, the rate of stable iodine intake during pregnancy and thyroid outcomes among their children have remaifned unclear.

Methods: This observational study used data from a thyroid screening program at Research Institute of Radiation Safety for Disaster Recovery Support in Fukushima, Japan.

Immunogenicity risk assessment for tailored mitigation and monitoring of biotherapeutics during development: recommendations from the European Immunogenicity Platform.

Bringing safe and effective drugs to patients is of utmost importance for the pharmaceutical industry, with immunogenicity (IG) being a critical factor that influences both aspects. Biotherapeutics can elicit unwanted immune responses, potentially leading to (severe) safety implications, reduced patient benefits, and may result in termination of development. Therefore, understanding IG risks throughout drug development is essential for both drug developers and health agencies (HAs).

Stable iodine intake and thyroid screening outcomes after the Fukushima Nuclear Disaster: an observational study.

Context: Stable iodine intake is crucial in preventing thyroid cancer after radiological emergencies; however, the association between stable iodine intake and thyroid outcomes in children after the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident remains unclear.

Objective: To describe thyroid screening outcomes and investigate the association between stable iodine intake and those outcomes in children after the FDNPP accident.

Design: Observational study.

CSF proteomics of semorinemab Alzheimer's disease trials identifies cell-type specific signatures.

Targeting of tau pathology has long been proposed as a potential therapeutic strategy for Alzheimer's disease (AD). Semorinemab is a humanized IgG4 monoclonal antibody that binds to all known isoforms of full-length tau with high affinity and specificity. Semorinemab's safety and efficacy have been studied in two Phase 2 randomized, double-blind, placebo-controlled, parallel-group clinical trials: Tauriel (prodromal-to-mild AD; NCT03289143; in which semorinemab failed to demonstrate clinical efficacy) and Lauriet (mild-to-moderate AD; NCT03828747.

Impact of germline variants on breast and ovarian cancer risk in Japanese women: an original cohort study and meta-analysis.

Background: Pathogenic variants (PVs) of BRCA1 and BRCA2 predispose individuals to a higher risk of breast and ovarian cancer; however, the precise risks posed by other cancer susceptibility genes remain unclear, particularly in Asian populations.

Methods: We executed a case-control study of 11 and 26 genes associated with breast and ovarian cancer susceptibility, respectively, in 7220 women with breast cancer, 2464 women with ovarian cancer, and 4032 controls from a multicentre, hospital-based registry in Japan. Furthermore, we conducted a meta-analysis of 23,193 patients with breast and/or ovarian cancer and 31,190 controls from six other hospital-based studies.

Dose Optimization in Oncology Drug Development: Risk Factors for Postmarketing Requirements and Commitments.

Optimal dosing of oncological drugs is historically determined based on the "higher is better" paradigm. However, a paradigm shift in optimal dose selection has occurred in the development of new modalities, including molecularly targeted drugs, antibody drugs, and immunotherapies. In 2021, Project Optimus was launched by the Food and Drug Administration Oncology Center of Excellence to reform the dose optimization and dose selection paradigm in oncology drug development.

Generalizable AI predicts immunotherapy outcomes across cancers and treatments.

Immune checkpoint inhibitors have become standard care across many cancers, but most patients do not respond. Predicting response remains challenging due to complex tumor-immune interactions and the poor generalizability of current biomarkers and models. Predictors such as tumor mutational burden, PD-L1 expression, and transcriptomic signatures often fail across cancer types, therapies, and clinical settings.

Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic-Resistant Organisms (FERARO): A feasibility randomised controlled trial.

Objectives: The gastrointestinal tract (GIT) is a reservoir of multidrug-resistant organisms (MDRO). Colonisation with MDRO precedes invasive infections, which can be challenging to treat with excess morbidity and mortality compared to antimicrobial-susceptible infections. Currently, there are no effective GIT decolonisation strategies.

A comprehensive review of 20 years of progress in nonclinical QT evaluation and proarrhythmic assessment.

The assessment of drug-induced QT interval prolongation and associated proarrhythmic risks, such as Torsades de Pointes (TdP), has evolved significantly over the past decades. This review traces the development of nonclinical QT evaluation, highlighting key milestones and innovations that have shaped current practices in cardiac safety assessment. The emergence of regulatory guidelines, including International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) S7B, established a nonclinical framework for evaluating drug effects on cardiac repolarization, addressing concerns raised by drug withdrawals in the 1990s.

A Novel B7-H4xCD3 Bispecific T-cell Engager (PF-07260437) Synergizes with Breast Cancer Standard of Care and Immune Checkpoint Therapies.

Immune checkpoint inhibitors have shown limited success in breast cancer, the most common and deadly cancer in women worldwide. Novel immune therapies, such as CD3-engaging bispecific antibodies, have shown clinical promise in hematologic malignancies. However, developing CD3 bispecifics for solid tumors has been challenging due to the difficulty in identifying tumor-specific antigens.

Bacterial diversity, viability and stability in lyophilised faecal microbiota capsules support ongoing clinical use.

Lyophilised encapsulated faecal microbiota provides a practical and cost-effective treatment option to patients with recurrent Clostridioides difficile infection. This study focused on quality assurance of an enteric-coated capsule formulation of FMT as a medicinal product by evaluating bacterial composition, diversity and viability through manufacturing steps and upon product storage at a range of temperatures. Faecal donations from pre-screened healthy individuals (n = 5) were processed according to a published protocol into one or more treatments; 5 capsules = 1 treatment dose/patient.

Pharmacokinetic-pharmacodynamic (PK/PD) modelling of cotadutide effect in patients with chronic kidney disease and type 2 diabetes mellitus.

Aims: Cotadutide is a dual glucagon-like peptide-1/glucagon receptor agonist. The objective of the analysis was to develop a pharmacokinetic-pharmacodynamic (PK/PD) model to describe the relationship between cotadutide exposure and response on urine albumin-to-creatinine ratio (UACR), urinary albumin (UALB), and body weight in participants with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) using data from a Phase2b study (NCT04515849).

Methods: A total of 247 participants with CKD and T2DM were randomized and titrated to either 100, 300 or 600 μg cotadutide, 1 mg semaglutide or placebo.

Improved Transplant Outcomes With Alternative Donors in Myelofibrosis: A 20-Year Japanese Registry Analysis of Donor Sources and the Impact of Ruxolitinib.

This study of 308 myelofibrosis patients shows that in recent years (2013-2019), alternative donors (mismatched unrelated donors and cord blood) achieved survival rates comparable to HLA-matched donors-a significant improvement compared to earlier years (2000-2012) when outcomes differed substantially. Ruxolitinib showed significant benefits in older patients (≥ 57), particularly with mismatched unrelated donors. Cord blood transplantation outcomes improved with MMF-based GVHD prophylaxis.

A subgroup analysis of the MiroCIP study to evaluate chemotherapy-induced peripheral neuropathy: symptom profile, severity, and analgesia efficacy depending on type of chemotherapy.

Background: The multicenter, prospective MiroCIP observational study investigated the incidence, risk factors, and outcomes of chemotherapy-induced peripheral neuropathy (CIPN) by oxaliplatin- and taxane-based chemotherapies but did not examine their differences in detail. This post hoc subanalysis explored the differences between oxaliplatin- and taxane-based chemotherapy, in terms of CIPN symptom profile, severity, and response to analgesics.

Research Design And Methods: Patients with colorectal, gastric, non-small cell lung, or breast cancer, scheduled to receive oxaliplatin- or taxane-based chemotherapy, were followed for 12 months to assess the severity of sensory CIPN, by the Common Terminology Criteria for Adverse Events, and associated subjective and objective symptoms.

Enhancer of zeste homolog 1/2 dual inhibitor valemetostat outperforms enhancer of zeste homolog 2-selective inhibitors in reactivating latent HIV-1 reservoirs .

For the eradication of human immunodeficiency virus type 1 (HIV-1) provirus from people living with HIV-1, reactivation of latently HIV-1-infected cells is essential. Although several latency reversing agents have been identified, eradication of HIV-infected cells has been a challenge. Here, we investigated whether the novel enhancer of zeste homolog 1/2 (EZH1/2) dual inhibitor valemetostat/DS-3201/()-OR-S2 could efficiently reactivate latently HIV-1-infected cells and .

Design and Implementation of a Multi-Center Trial of Xe Gas Exchange MRI and MRS to Evaluate Longitudinal Progression of COPD.

MR imaging holds the potential to enhance drug development efficiency by de-risking early phase studies and increasing confidence in results. It can improve patient selection, increase repeatability, and provide greater sensitivity to change, thereby enabling smaller, faster clinical trials. For trials in the pulmonary space, hyperpolarized Xe MRI is appealing because it provides 3-dimensional imaging of pulmonary ventilation and gas exchange in a brief, non-invasive exam.

A multi-omics microbiome signature is associated with the benefits of gastric bypass surgery and is differentiated from diet induced weight loss through 2 years of follow-up.

Roux-en-Y gastric bypass (GBP) surgery is an effective treatment for reducing body weight and correcting metabolic dysfunction in individuals with severe obesity. Herein, we characterize the differences between very low energy diet (VLED) and GBP induced weight loss by multi-omic analyses of microbiome and host features in a non-randomized, controlled, single-center study. Eighty-eight participants with severe obesity were recruited into two arms - GBP versus VLED with matching weight loss for 6 weeks and 2-years of follow-up.

An Oral PCSK9 Inhibitor for Treatment of Hypercholesterolemia: The PURSUIT Randomized Trial.

Background: Most patients at high-risk for cardiovascular events do not achieve lipid goals advocated by American College of Cardiology/American Heart Association (ACC/AHA) guidelines despite the wide availability of lipid-lowering therapy. AZD0780 is a novel, oral, small molecule inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) in development as a once-daily treatment for hypercholesterolemia.

Objectives: The phase 2 randomized, double-blind, placebo-controlled, multicenter PURSUIT trial evaluated the efficacy and safety of AZD0780 in patients with hypercholesterolemia already on background moderate-to-high-intensity statin treatment.

Chromosomal Instability Is Associated with cGAS-STING Activation in EGFR-TKI Refractory Non-Small-Cell Lung Cancer.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard therapies for -mutated non-small-cell lung cancer (NSCLC); however, their efficacy is inconsistent. Secondary mutations in the or other genes that lead to resistance have been identified, but resistance mechanisms have not been fully identified. Chromosomal instability (CIN) is a hallmark of cancer and results in genetic diversity.

18F-FLT PET, a Noninvasive Pharmacodynamic Biomarker of Tumor Cell Proliferation, Detected Differential Response to Various Cyclin-Dependent Kinase (CDK) Inhibitors.

A dysregulated cell cycle is a hallmark of cancer and inhibition of cyclin-dependent kinases (CDK) is a proven therapeutic strategy in treating hormone receptor-positive/HER2- breast cancer and a variety of other cancers. 18F-3'-deoxy-3'-fluorothymidine (18F-FLT) is a validated PET biomarker to measure cell proliferation. In this study, we show the utility of 18F-FLT PET imaging as a pharmcodynamic biomarker in differentiating the efficacy of PF-07104091 (CDK2-selective inhibitor) in palbociclib (CDK4/6 inhibitor)-sensitive and -resistant tumor models.

Effect of prevaccination blood and T-cell phenotypes on antibody responses to a COVID-19 mRNA vaccine.

Despite the high effectiveness of the coronavirus disease 2019 (COVID-19) mRNA vaccines, both immunogenicity and reactogenicity show substantial interindividual variability. One key challenge is predicting high and low responders using easily measurable parameters. In this study, we performed multivariate linear regression analysis, which allows adjustment for confounding, to explore independent predictive factors for antibody responses.

Hyperkalemia Is an Underestimated Risk Factor in COPD.

Background: Hyperkalemia increases mortality in various patient populations. The risk of hyperkalemia in COPD patients is poorly recognized. Hyperkalemia may increase cardiovascular mortality during and soon after COPD exacerbations.