Establishing a Pan-European, multi-disciplinary taphonomic research Infrastructure: The 'UK-Netherlands decomposition experimental research (UNDER) Group'.

This study unveils the establishment of the United Kingdom-Netherlands Decomposition Experimental Research (UNDER) working group, marking a pioneering initiative in practical Forensic Taphonomy within the UK. Our primary objective was to craft a cohesive multidisciplinary framework, designed to ethically orchestrate, execute, and assess human decomposition. Concurrently, we aimed to amass data through human burials, fostering collaboration among diverse forensic experts across Europe.

Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies.

Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer.

Leucine zipper-based immunomagnetic purification of CAR T cells displaying multiple receptors.

Resistance to chimaeric antigen receptor (CAR) T cell therapy develops through multiple mechanisms, most notably antigen loss and tumour-induced immune suppression. It has been suggested that T cells expressing multiple CARs may overcome the resistance of tumours and that T cells expressing receptors that switch inhibitory immune-checkpoint signals into costimulatory signals may enhance the activity of the T cells in the tumour microenvironment. However, engineering multiple features into a single T cell product is difficult because of the transgene-packaging constraints of current gene-delivery vectors.

People expect artificial moral advisors to be more utilitarian and distrust utilitarian moral advisors.

As machines powered by artificial intelligence increase in their technological capacities, there is a growing interest in the theoretical and practical idea of artificial moral advisors (AMAs): systems powered by artificial intelligence that are explicitly designed to assist humans in making ethical decisions. Across four pre-registered studies (total N = 2604) we investigated how people perceive and trust artificial moral advisors compared to human advisors. Extending previous work on algorithmic aversion, we show that people have a significant aversion to AMAs (vs humans) giving moral advice, while also showing that this is particularly the case when advisors - human and AI alike - gave advice based on utilitarian principles.

Transcriptional analysis of C. elegans fmos at different life stages and their roles in ageing.

Flavin-containing monooxygenases (FMOs) are present in most organisms including plants, fungi, bacteria, invertebrates and vertebrates, where they catalyse the oxidative metabolism of a range of xenobiotics and endogenous metabolites. FMOs have been associated with ageing and longevity in the mouse and in C. elegans.

Modulation of AAV transduction and integration targeting by topoisomerase poisons.

Adeno-associated virus (AAV) is a widely used vehicle for gene delivery, lending interest to developing methods for enhancing AAV transduction and transgene expression. Here, we profile the function of several topoisomerase poisons, which are small molecules that stabilize topoisomerase enzymatic intermediates, where topoisomerase enzymes are covalently bound at chromosomal DNA breaks. As previously observed, we found that the topoisomerase poisons camptothecin (CPT), doxorubicin (DOX), and etoposide (ETO) increased AAV transduction in cultured cell models.

TET2 regulates early and late transitions in exhausted CD8 T cell differentiation and limits CAR T cell function.

CD8 T cell exhaustion hampers control of cancer and chronic infections and limits chimeric antigen receptor (CAR) T cell efficacy. Targeting in CAR T cells provides therapeutic benefit; however, TET2's role in exhausted T cell (T) development is unclear. In chronic lymphocytic choriomeningitis virus (LCMV) infection, TET2 drove conversion from stem cell-like T progenitors toward terminally differentiated and effector (T)-like T.

Regulated GATA1 expression as a universal gene therapy for Diamond-Blackfan anemia.

Gene therapy using hematopoietic stem and progenitor cells is altering the therapeutic landscape for patients with hematologic, immunologic, and metabolic disorders but has not yet been successfully developed for individuals with the bone marrow failure syndrome Diamond-Blackfan anemia (DBA). More than 30 mutations cause DBA through impaired ribosome function and lead to inefficient translation of the erythroid master regulator GATA1, providing a potential avenue for therapeutic intervention applicable to all patients with DBA, irrespective of the underlying genotype. Here, we report the development of a clinical-grade lentiviral gene therapy that achieves erythroid lineage-restricted expression of GATA1.

Supplementation of spermidine at 40 mg/day has minimal effects on circulating polyamines: An exploratory double-blind randomized controlled trial in older men.

This study represents the first investigation into the safety of a novel, high-purity spermidine trihydrochloride supplement (hpSPD) in humans. Spermidine, a natural compound found in various foods, has demonstrated potential health benefits in animal and epidemiological studies. However, evidence from clinical trials and safety evaluations of spermidine supplements is limited because pure spermidine for human administration has not been available.

Uptake of Cancer Genetic Services for Chatbot vs Standard-of-Care Delivery Models: The BRIDGE Randomized Clinical Trial.

Importance: Increasing numbers of unaffected individuals could benefit from genetic evaluation for inherited cancer susceptibility. Automated conversational agents (ie, chatbots) are being developed for cancer genetics contexts; however, randomized comparisons with standard of care (SOC) are needed.

Objective: To examine whether chatbot and SOC approaches are equivalent in completion of pretest cancer genetic services and genetic testing.

Effects of climate warming on energetics and habitat of the world's largest marine ectotherm.

Responses of organisms to climate warming are variable and complex. Effects on species distributions are already evident and mean global surface ocean temperatures are likely to warm by up to 4.1 °C by 2100, substantially impacting the physiology and distributions of ectotherms.

Nanoscale synchrotron x-ray analysis of intranuclear iron in melanised neurons of Parkinson's substantia nigra.

Neuromelanin-pigmented neurons of the substantia nigra are selectively lost during the progression of Parkinson's disease. These neurons accumulate iron in the disease state, and iron-mediated neuron damage is implicated in cell death. Animal models of Parkinson's have evidenced iron loading inside the nucleoli of nigral neurons, however the nature of intranuclear iron deposition in the melanised neurons of the human substantia nigra is not understood.

Use of HSC-targeted LNP to generate a mouse model of lethal α-thalassemia and treatment via lentiviral gene therapy.

α-Thalassemia (AT) is one of the most commonly occurring inherited hematological diseases. However, few treatments are available, and allogeneic bone marrow transplantation is the only available therapeutic option for patients with severe AT. Research into AT has remained limited because of a lack of adult mouse models, with severe AT typically resulting in in utero lethality.

The impact of generative artificial intelligence on socioeconomic inequalities and policy making.

Generative artificial intelligence (AI) has the potential to both exacerbate and ameliorate existing socioeconomic inequalities. In this article, we provide a state-of-the-art interdisciplinary overview of the potential impacts of generative AI on (mis)information and three information-intensive domains: work, education, and healthcare. Our goal is to highlight how generative AI could worsen existing inequalities while illuminating how AI may help mitigate pervasive social problems.

Within-host influenza viral diversity in the pediatric population as a function of age, vaccine, and health status.

Seasonal influenza virus predominantly evolves through antigenic drift, marked by the accumulation of mutations at antigenic sites. Because of antigenic drift, influenza vaccines are frequently updated, though their efficacy may still be limited due to strain mismatches. Despite the high levels of viral diversity observed across populations, most human studies reveal limited intrahost diversity, leaving the origin of population-level viral diversity unclear.

The Pancreatic Cancer Early Detection (PRECEDE) Study is a Global Effort to Drive Early Detection: Baseline Imaging Findings in High-Risk Individuals.

Background: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium.

The assessment and management of foot and toe oedema as part of holistic lower limb care.

Toe and foot swelling can manifest as lymphoedema or chronic oedema but can also be a complication of the treatment of these conditions. In this article, the authors discuss the assessment and treatment options for toe and foot swelling, highlighting the importance of prevention in the first instance.

Does it matter who harmed whom? A cross-cultural study of moral judgments about harm by and to insiders and outsiders.

Unlabelled: This cross-cultural study compared judgments of moral wrongness for physical and emotional harm with varying combinations of in-group vs. out-group agents and victims across six countries: the United States of America (N = 937), the United Kingdom (N = 995), Romania (N = 782), Brazil (N = 856), South Korea (N = 1776), and China (N = 1008). Consistent with our hypothesis we found evidence of an insider agent effect, where moral violations committed by outsider agents are generally considered more morally wrong than the same violations done by insider agents.

Label-Free In Situ Chemical Characterization of Amyloid Plaques in Human Brain Tissues.

The accumulation of amyloid plaques and increased brain redox burdens are neuropathological hallmarks of Alzheimer's disease. Altered metabolism of essential biometals is another feature of Alzheimer's, with amyloid plaques representing sites of disturbed metal homeostasis. Despite these observations, metal-targeting disease treatments have not been therapeutically effective to date.

SARS-CoV-2 evolution during prolonged infection in immunocompromised patients.

Unlabelled: Prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised patients provides an opportunity for viral evolution, potentially leading to the generation of new pathogenic variants. To investigate the pathways of viral evolution, we carried out a study on five patients experiencing prolonged SARS-CoV-2 infection (quantitative polymerase chain reaction-positive for 79-203 days) who were immunocompromised due to treatment for lymphoma or solid organ transplantation. For each timepoint analyzed, we generated at least two independent viral genome sequences to assess the heterogeneity and control for sequencing error.

Moral conformity in a digital world: Human and nonhuman agents as a source of social pressure for judgments of moral character.

Could judgments about others' moral character be changed under group pressure produced by human and virtual agents? In Study 1 (N = 103), participants first judged targets' moral character privately and two weeks later in the presence of real humans. Analysis of how many times participants changed their private moral judgments under group pressure showed that moral conformity occurred, on average, 43% of the time. In Study 2 (N = 138), we extended this using Virtual Reality, where group pressure was produced either by avatars allegedly controlled by humans or AI.

Optical Microscopy Using the Faraday Effect Reveals Magnetization Dynamics of Magnetic Nanoparticles in Biological Samples.

The study of exogenous and endogenous nanoscale magnetic material in biology is important for developing biomedical nanotechnology as well as for understanding fundamental biological processes such as iron metabolism and biomineralization. Here, we exploit the magneto-optical Faraday effect to probe intracellular magnetic properties and perform magnetic imaging, revealing the location-specific magnetization dynamics of exogenous magnetic nanoparticles within cells. The opportunities enabled by this method are shown in the context of magnetic hyperthermia; an effect where local heating is generated in magnetic nanoparticles exposed to high-frequency AC magnetic fields.