B-cell infiltration distinguishes mucosal from skin patterns of rejection in facial vascularized composite allografts.

Rejection monitoring in facial vascularized composite allotransplantation (fVCA) traditionally focuses on skin biopsies. However, mucosal rejection frequently presents with more pronounced signs of immune activity. To explore mechanistic differences between skin and mucosal rejection, rejection and non-rejection biopsies from allograft skin and oral mucosa of nine fVCA recipients were retrospectively analyzed using histology, multiplex immunostaining, and gene expression profiling, with peripheral blood mononuclear cells (PBMCs) quantified via mass cytometry (CyTOF).

Exploring the Landscape of Standards and Guidelines in AgeTech Design and Development: Scoping Review and Thematic Analysis.

Background: AgeTech (technology for older people) offers digital solutions for older adults supporting aging in place, including digital health, assistive technology, Internet of Things, medical devices, robotics, wearables, and sensors. This study underscores the critical role of standards and guidelines in ensuring the safety and effectiveness of these technologies for the health of older adults. As the aging demographic expands, the focus on robust standards becomes vital, reflecting a collective commitment to improving the overall quality of life for older individuals through thoughtful and secure technology integration.

The Complexity of Tobacco Smoke-Induced Mutagenesis in Head and Neck Cancer.

Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). Here, we further explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported.

Geographic variation of mutagenic exposures in kidney cancer genomes.

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations.

COSMIC: a curated database of somatic variants and clinical data for cancer.

The Catalogue Of Somatic Mutations In Cancer (COSMIC), https://cancer.sanger.ac.

Studies of antibacterial activity (in vitro and in vivo) and mode of action for des-acyl tridecaptins (DATs).

Tridecaptins comprise a class of linear cationic lipopeptides with an N-terminal fatty acyl moiety. These 13-mer antimicrobial peptides consist of a combination of d- and l-amino acids, conferring increased proteolytic stability. Intriguingly, they are biosynthesized by non-ribosomal peptide synthetases in the same bacterial species that also produce the cyclic polymyxins displaying similar fatty acid tails.

Pharmacokinetic and pharmacodynamic evaluation of the atypical tetracyclines chelocardin and amidochelocardin in murine infection models.

There is a strong need to find novel treatment options against urinary tract infections associated with antimicrobial resistance. This study evaluates two atypical tetracyclines, namely chelocardin (CHD) and amidochelocardin (CDCHD), with respect to their pharmacokinetics and pharmacodynamics. We show CHD and CDCHD are cleared at high concentrations in mouse urine.

Human Skin T Cells Express Conserved T-Cell Receptors that Cross-React with Staphylococcal Superantigens and CD1a.

Human Langerhans cells highly express CD1a antigen-presenting molecules. To understand the functions of CD1a in human skin, we used CD1a tetramers to capture T cells and determine their effector functions and TCR patterns. Skin T cells from all donors showed CD1a tetramer staining, which in three cases exceeded 10% of skin T cells.

Phototherapy Restores Deficient Type I IFN Production and Enhances Antitumor Responses in Mycosis Fungoides.

Transcriptional profiling demonstrated markedly reduced type I IFN gene expression in untreated mycosis fungoides (MF) skin lesions compared with that in healthy skin. Type I IFN expression in MF correlated with antigen-presenting cell-associated IRF5 before psoralen plus UVA therapy and epithelial ULBP2 after therapy, suggesting an enhancement of epithelial type I IFN. Immunostains confirmed reduced baseline type I IFN production in MF and increased levels after psoralen plus UVA treatment in responding patients.

Artificial Intelligence Optical Biopsy for Evaluating the Functional State of Wounds.

Introduction: The clinical characterization of the functional status of active wounds in terms of their driving cellular and molecular biology remains a considerable challenge that currently requires excision via a tissue biopsy. In this pilot study, we use convolutional Siamese neural network (SNN) architecture to predict the functional state of a wound using digital photographs of wounds in a canine model of volumetric muscle loss (VML).

Methods: Digital images of VML injuries and tissue biopsies were obtained in a standardized fashion from an established canine model of VML.

Prevalence and clinical characteristics of non-malignant CT detected incidental findings in the SUMMIT lung cancer screening cohort.

Background: Pulmonary and extrapulmonary incidental findings are frequently identified on CT scans performed for lung cancer screening. Uncertainty regarding their clinical significance and how and when such findings should be reported back to clinicians and participants persists. We examined the prevalence of non-malignant incidental findings within a lung cancer screening cohort and investigated the morbidity and relevant risk factors associated with incidental findings.

Exploring the Role of Active Assisted Living in the Continuum of Care for Older Adults: Thematic Analysis.

Background: Active assisted living (AAL) refers to systems designed to improve the quality of life, aid in independence, and create healthier lifestyles for those who need assistance at any stage of their lives. As the population of older adults in Canada grows, there is a pressing need for nonintrusive, continuous, adaptable, and reliable health monitoring tools to support aging in place and reduce health care costs. AAL has great potential to support these efforts with the wide variety of solutions currently available; however, additional work is required to address the concerns of care recipients and their care providers with regard to the integration of AAL into care.

Low-dose interleukin-2 promotes immune regulation in face transplantation: A pilot study.

Face transplantation is a life-changing procedure for patients with severe composite facial defects. However, it is hampered by high acute rejection rates due to the immunogenicity of skin allograft and toxicity linked to high doses of immunosuppression. To reduce immunosuppression-associated complications, we, for the first time in face transplant recipients, used low-dose interleukin 2 (IL-2) therapy to expand regulatory T cells (Tregs) in vivo and to enhance immune modulation, under close immunological monitoring of peripheral blood and skin allograft.

Uptake of invitations to a lung health check offering low-dose CT lung cancer screening among an ethnically and socioeconomically diverse population at risk of lung cancer in the UK (SUMMIT): a prospective, longitudinal cohort study.

Background: Lung cancer screening with low-dose CT reduces lung cancer mortality, but screening requires equitable uptake from candidates at high risk of lung cancer across ethnic and socioeconomic groups that are under-represented in clinical studies. We aimed to assess the uptake of invitations to a lung health check offering low-dose CT lung cancer screening in an ethnically and socioeconomically diverse cohort at high risk of lung cancer.

Methods: In this multicentre, prospective, longitudinal cohort study (SUMMIT), individuals aged 55-77 years with a history of smoking in the past 20 years were identified via National Health Service England primary care records at practices in northeast and north-central London, UK, using electronic searches.

Exploring the Use of Pictograms in Privacy Agreements to Facilitate Communication Between Users and Data Collecting Entities: Randomized Controlled Trial.

Background: Privacy agreements can foster trust between users and data collecting entities by reducing the fear of data sharing. Users typically identify concerns with their data privacy settings, but due to the complexity and length of privacy agreements, users opt to quickly consent and agree to the terms without fully understanding them.

Objective: This study explores the use of pictograms as potential elements to assist in improving the transparency and explanation of privacy agreements.

The SUMMIT Study: Utilising a written 'Next Steps' information booklet to prepare participants for potential lung cancer screening results and follow-up.

Objectives: Low-Dose Computed Tomography (LDCT) screening for lung cancer can result in several potential outcomes of varying significance. Communication methods used in Lung Cancer Screening (LCS) programmes must, therefore, ensure that participants are prepared for the range of possible results and follow-up. Here, we assess perceptions of a written preparatory information booklet provided to participants in a large LCS cohort designed to convey this information.

Growing small solid nodules in lung cancer screening: safety and efficacy of a 200 mm minimum size threshold for multidisciplinary team referral.

The optimal management of small but growing nodules remains unclear. The SUMMIT study nodule management algorithm uses a specific threshold volume of 200 mm before referral of growing solid nodules to the multidisciplinary team for further investigation is advised, with growing nodules below this threshold kept under observation within the screening programme. Malignancy risk of growing solid nodules of size >200 mm at initial 3-month interval scan was 58.

Chromatin localization of nucleophosmin organizes ribosome biogenesis.

Ribosome biogenesis takes place in the nucleolus, a nuclear membrane-less organelle. Although well studied, it remains unknown how nascent ribosomal subunits separate from the central chromatin compartment and move to the outer granular component, where maturation occurs. We find that the Schizosaccharomyces pombe nucleophosmin-like protein Fkbp39 localizes to rDNA sites encoding the 60S subunit rRNA, and this localization contributes to its specific association with nascent 60S subunits.

Uncovering novel mutational signatures by extraction with SigProfilerExtractor.

Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for extraction of mutational signatures, and benchmark it against another 13 bioinformatics tools by using 34 scenarios encompassing 2,500 simulated signatures found in 60,000 synthetic genomes and 20,000 synthetic exomes. For simulations with 5% noise, reflecting high-quality datasets, SigProfilerExtractor outperforms other approaches by elucidating between 20% and 50% more true-positive signatures while yielding 5-fold less false-positive signatures.

Utilisation of primary care electronic patient records for identification and targeted invitation of individuals to a lung cancer screening programme.

Lung cancer screening (LCS) eligibility is largely determined by tobacco consumption. Primary care smoking data could guide LCS invitation and eligibility assessment. We present observational data from the SUMMIT Study, where individual self-reported smoking status was concordant with primary care records in 75.

Detection of COPD in the SUMMIT Study lung cancer screening cohort using symptoms and spirometry.

Background: COPD is a major comorbidity in lung cancer screening (LCS) cohorts, with a high prevalence of undiagnosed COPD. Combining symptom assessment with spirometry in this setting may enable earlier diagnosis of clinically significant COPD and facilitate increased understanding of lung cancer risk in COPD. In this study, we wished to understand the prevalence, severity, clinical phenotype and lung cancer risk of individuals with symptomatic undiagnosed COPD in a LCS cohort.

Telephone risk-based eligibility assessment for low-dose CT lung cancer screening.

Eligibility for lung cancer screening (LCS) requires assessment of lung cancer risk, based on smoking history alongside demographic and medical factors. Reliance on individual face-to-face eligibility assessment risks inefficiency and costliness. The SUMMIT Study introduced a telephone-based lung cancer risk assessment to guide invitation to face-to-face LCS eligibility assessment, which significantly increased the proportion of face-to-face attendees eligible for LCS.