Impact of frailty and comorbidity on initial response to lung cancer screening invitation and low-dose CT screening uptake: Findings from the Yorkshire Lung Screening Trial.

Background: Low-dose computed tomography screening reduces lung cancer-specific mortality in high-risk individuals. Lung cancer risk factors overlap with comorbid diseases, highlighting the significance of frailty and comorbidities for lung cancer screening (LCS). Here, we describe the prevalence of frailty and comorbidity in those invited for LCS and evaluate their associations with response to telephone risk assessment invitation and subsequent uptake of LCS.

Dispersion-based cognitive intra-individual variability in former American football players: Association with traumatic encephalopathy syndrome, repetitive head impacts, and biomarkers.

Exposure to repetitive head impacts (RHI), such as those experienced in American football, is linked to cognitive dysfunction later in life. Traumatic encephalopathy syndrome (TES) is a proposed clinical syndrome thought to be linked to neuropath-ology of chronic traumatic encephalopathy (CTE), a condition associated with RHI from football. Cognitive intra-individual variability (d-CIIV) measures test-score dispersion, indicating cognitive dysfunction.

Multiomic analyses direct hypotheses for Creutzfeldt-Jakob disease risk genes.

Prions are assemblies of misfolded prion protein that cause several fatal and transmissible neurodegenerative diseases, with the most common phenotype in humans being sporadic Creutzfeldt-Jakob disease (sCJD). Aside from variation of the prion protein itself, molecular risk factors are not well understood. Prion and prion-like mechanisms are thought to underpin common neurodegenerative disorders meaning that the elucidation of mechanisms could have broad relevance.

Ethical considerations on surrogacy†.

Surrogacy is the assisted reproductive technology (ART) practice in which a person becomes pregnant, carries, and delivers a child on behalf of another couple/person, who are the intended parent(s). Surrogacy is an especially complex practice as the interests of the intended parents, the gestational carrier, and the future child may differ. This paper considers ethical questions related to different forms of surrogacy.

The Interaction Between Vasculogenic Mimicry and the Immune System: Mechanistic Insights and Dual Exploration in Cancer Therapy.

Vasculogenic mimicry (VM) represents a novel form of angiogenesis discovered in numerous malignant tumours in recent years. Unlike traditional angiogenesis, VM facilitates tumour blood supply independently of endothelial cells by enabling tumour cells to form functional vascular networks. This phenomenon, where tumour cells replace endothelial cells to form tubular structures, plays a pivotal role in tumour growth and metastasis.

RADAR-AD: assessment of multiple remote monitoring technologies for early detection of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting millions worldwide, leading to cognitive and functional decline. Early detection and intervention are crucial for enhancing the quality of life of patients and their families. Remote Monitoring Technologies (RMTs) offer a promising solution for early detection by tracking changes in behavioral and cognitive functions, such as memory, language, and problem-solving skills.

Imbalance of oral microbiome homeostasis: the relationship between microbiota and the occurrence of dental caries.

Background: Streptococcus mutans is recognized as a key pathogen responsible for the development of dental caries. With the advancement of research on dental caries, the understanding of its pathogenic mechanism has gradually shifted from the theory of a single pathogenic bacterium to the theory of oral microecological imbalance. Acidogenic and aciduric microbial species are also recognized to participate in the initiation and progression of dental caries.

Exploring the perspectives of early-stage postoperative glioblastoma patients and their caregivers on end-of-life care planning: An exploratory qualitative interview study.

Aim: Compare the convergent and divergent viewpoints of early-stage postoperative patients with glioblastoma and their caregivers on end-of-life care planning in Taiwan.

Background: Decision-making capacity in patients with glioblastoma may be compromised as disease progresses, making early future care planning essential to ensure that the provided care aligns with patients' goals. However, within many Asian cultures, the tendency to avoid discussions about death can lead patients to feel hesitant about addressing end-of-life care options.

Consensus recommendations for measuring the impact of contraception on the menstrual cycle in contraceptive clinical trials.

Objective: We sought to develop consensus recommendations for measurement and analysis of data on contraceptive-induced menstrual changes (CIMCs) in contraceptive clinical trials. We built upon previous standardization efforts over the last 50 years and prioritized input from a variety of global experts and current regulatory authority guidance on patient-reported outcomes.

Study Design: We completed a formal consensus-building process with an interdisciplinary group of 57 experts from 30 organizations and 14 countries in five global regions who work across academia, nonprofit research organizations, the pharmaceutical industry, and funding agencies.

The International Association for the Study of Lung Cancer Staging Project: The Database and Proposal for the Revision of the Staging of Pulmonary Neuroendocrine Carcinoma in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

Introduction: Pulmonary high-grade neuroendocrine carcinoma (NEC) includes small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). The seventh and eighth editions of the TNM classification for lung cancer confirmed the applicability of this staging system for SCLC. With the proposal of N2 and M1c subcategories for the ninth edition classification, we assessed the applicability to NECs.

Efficient Discovery of Robust Prognostic Biomarkers and Signatures in Solid Tumors.

Recent advancements in multi-omics and big-data technologies have facilitated the discovery of numerous cancer prognostic biomarkers and gene signatures. However, their clinical application remains limited due to poor reproducibility and insufficient independent validation. Despite the availability of high-quality datasets, achieving reliable biomarker identification across multiple cohorts continues to be a significant challenge.

Update in Clinical Science: Autoimmune Hepatitis.

Autoimmune hepatitis (AIH) is an enigmatic, relatively rare disease with a variable spectrum of presentation whose pathogenesis, diagnosis and management remain a major challenge. Methods. We have performed a review incorporating recent developments in basic science, epidemiology, clinical science, therapeutics, regulatory science and evaluated the challenges associated with the application of translational research and clinical trial design to a condition that is a chameleon in nature, where outcomes range from relatively benign disease through cirrhosis and acute liver failure.

Using Laboratory Test Results for Surveillance During a New Outbreak of Acute Hepatitis in 3-Week- to 5-Year-Old Children in the United Kingdom, the Netherlands, Ireland, and Curaçao: Observational Cohort Study.

Background: In March 2022, a concerning rise in cases of unexplained pediatric hepatitis was reported in multiple countries. Cases were defined as acute hepatitis with serum transaminases >500 U/L (aspartate transaminase [AST] or alanine transaminase [ALT]) in children aged 16 years or younger. We explored a simple federated data analytics method to search for evidence of unreported cases using routinely held data.

MRI-based modelling of left atrial flow and coagulation to predict risk of thrombogenesis in atrial fibrillation.

Atrial fibrillation (AF), impacting nearly 50 million individuals globally, is a major contributor to ischaemic strokes, predominantly originating from the left atrial appendage (LAA). Current clinical scores like CHA₂DS₂-VASc, while useful, provide limited insight into the pro-thrombotic mechanisms of Virchow's triad-blood stasis, endothelial damage, and hypercoagulability. This study leverages biophysical computational modelling to deepen our understanding of thrombogenesis in AF patients.

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.

Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.

Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC.

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.

Protocol for a systematic review and individual participant data meta-analysis for risk factors for lung cancer in individuals with lung nodules identified by low-dose CT screening.

Background: Worldwide, lung cancer (LC) is the second most frequent cancer and the leading cause of cancer related mortality. Low-dose CT (LDCT) screening reduced LC mortality by 20-24% in randomised trials of high-risk populations. A significant proportion of those screened have nodules detected that are found to be benign.

Impact of SARS-CoV-2 spike antibody positivity on infection and hospitalisation rates in immunosuppressed populations during the omicron period: the MELODY study.

Background: In the UK, booster COVID-19 vaccinations have been recommended biannually to people considered immune vulnerable. We investigated, at a population level, whether the absence of detectable anti-SARS-CoV-2 spike protein IgG antibody (anti-S Ab) following three or more vaccinations in immunosuppressed individuals was associated with greater risks of infection and severity of infection.

Methods: In this prospective cohort study using UK national disease registers, we recruited participants with solid organ transplants (SOTs), rare autoimmune rheumatic diseases (RAIRDs), and lymphoid malignancies.

Prognostic performance of the two-step clinical care pathway in metabolic dysfunction-associated steatotic liver disease.

Background & Aims: Current guidelines recommend a 2-step approach for risk stratification in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) with Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) or similar second-line tests. This study aimed to examine to prognostic performance of this approach.

Methods: The VCTE-Prognosis Study was a longitudinal study of patients with MASLD who had undergone VCTE examinations at 16 centres from the US, Europe and Asia with subsequent follow-up for clinical events.

Leveraging Epigenetic Alterations in Pancreatic Ductal Adenocarcinoma for Clinical Applications.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by late detection and poor prognosis. Recent research highlights the pivotal role of epigenetic alter- ations in driving PDAC development and progression. These changes, in conjunction with genetic mutations, contribute to the intricate molecular landscape of the disease.

A mixed method evaluation of a novel targeted health messaging intervention to promote COVID-19 protective behaviours and vaccination among Black and South Asian communities living in the UK (The COBHAM study).

Aim: To evaluate an intervention (a film and electronic leaflet) disseminated via text message by general practices to promote COVID-19 preventative behaviours in Black and South Asian communities.

Methods: We carried out a before-and-after questionnaire study of attitudes to and implementation of COVID-19 preventative behaviours and qualitative interviews about the intervention with people registered with 26 general practices in England who identified as Black or South Asian.

Results: In the 108 people who completed both questionnaires, we found no significant change in attitudes to and implementation of COVID-19 preventative behaviours, although power was too low to detect significant effects.