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.

The evolution of health policy and systems research in 11 low- and middle-income countries and the role of the Alliance for Health Policy and Systems Research: a bibliometric analysis for 1999-2020.

Objectives: Given the rapid growth of the field of health policy and systems research (HPSR), it is important to monitor the research environment, especially the evolution of HPSR research outputs in low- and middle-income countries (LMICs). The objective of this study was to generate quantitative metrics to assess the production of HPSR publications and the role of the Alliance for Health Policy and Systems Research (the Alliance) grant-funded projects in 11 LMICs over the past 20 years.

Methods: We conducted a systematic literature search for HPSR literature from 1999 to 2020 pertaining to 11 target LMIC countries, including grey literature.

Genetic Variants Associated With Preeclampsia and Maternal Serum sFLT1 Levels.

Background: Elevated maternal serum sFLT1 (soluble fms-like tyrosine kinase 1) has a key role in the pathophysiology of preeclampsia. We sought to determine the relationship between the maternal and fetal genome and maternal levels of sFLT1 at 12, 20, 28, and 36 weeks of gestational age (wkGA).

Methods: We studied a prospective cohort of nulliparous women (3968 mother-child pairs).

10 practical priorities to prevent and manage serious allergic reactions: GALEN ANACare and EFA Anaphylaxis Manifesto.

This Anaphylaxis Manifesto calls on communities to prioritise 10 practical actions to improve the lives of people at risk of serious allergic reactions. The Global Allergy and Asthma European Network and the European Federation of Allergy and Airways Diseases Patients' Associations (EFA) compiled patient-centric priorities. We used qualitative consensus methods, research evidence and feedback from over 200 patient groups, stakeholder organisations and healthcare professionals.

Biodiversity impacts of the 2019-2020 Australian megafires.

With large wildfires becoming more frequent, we must rapidly learn how megafires impact biodiversity to prioritize mitigation and improve policy. A key challenge is to discover how interactions among fire-regime components, drought and land tenure shape wildfire impacts. The globally unprecedented 2019-2020 Australian megafires burnt more than 10 million hectares, prompting major investment in biodiversity monitoring.

Acid Strength Effects on Dimerization during Metal-Free Catalytic Dioxygen Reduction.

Development of earth-abundant catalysts for the reduction of dioxygen (ORR) is essential for the development of alternative industrial processes and energy sources. Here, we report a transition metal-free dicationic organocatalyst () for the ORR. The ORR performance of this compound was studied in acetonitrile solution under both electrochemical conditions and spectrochemical conditions, using halogenated acetic acid derivatives spanning a p range of 12.

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.

NKX2-5 regulates vessel remodeling in scleroderma-associated pulmonary arterial hypertension.

NKX2-5 is a member of the homeobox-containing transcription factors critical in regulating tissue differentiation in development. Here, we report a role for NKX2-5 in vascular smooth muscle cell phenotypic modulation in vitro and in vascular remodeling in vivo. NKX2-5 is upregulated in scleroderma patients with pulmonary arterial hypertension.

Controlling product selectivity during dioxygen reduction with Mn complexes using pendent proton donor relays and added base.

The catalytic reduction of dioxygen (O) is important in biological energy conversion and alternative energy applications. In comparison to Fe- and Co-based systems, examples of catalytic O reduction by homogeneous Mn-based systems is relatively sparse. Motivated by this lack of knowledge, two Mn-based catalysts for the oxygen reduction reaction (ORR) containing a bipyridine-based non-porphyrinic ligand framework have been developed to evaluate how pendent proton donor relays alter activity and selectivity for the ORR, where Mn(dhbpy)Cl (1) was used as a control complex and Mn(dhbpy)Cl (2) contains a pendent -OMe group in the secondary coordination sphere.

Metal-Free Homogeneous O Reduction by an Iminium-Based Electrocatalyst.

The oxygen reduction reaction (ORR) is important for alternative energy and industrial oxidation processes. Herein, an iminium-based organoelectrocatalyst () for the ORR with trifluoroacetic acid as a proton source in acetonitrile solution under both electrochemical and spectrochemical conditions using decamethylferrocene as a chemical reductant is reported. Under spectrochemical conditions, HO is the primary reaction product, while under electrochemical conditions HO is produced.

Core Outcome Set for IgE-mediated food allergy clinical trials and observational studies of interventions: International Delphi consensus study 'COMFA'.

Background: IgE-mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions.

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.

Analysis of vector genome integrations in multicentric lymphoma after AAV gene therapy in a severe hemophilia A dog.

Adeno-associated viral (AAV) vectors have traditionally been viewed as predominantly nonintegrating, with limited concerns for oncogenesis. However, accumulating preclinical data have shown that AAV vectors integrate more often than previously appreciated, with the potential for genotoxicity. To understand the consequences of AAV vector integration, vigilance for rare genotoxic events after vector administration is essential.

Placental Streptococcus agalactiae DNA is associated with neonatal unit admission and foetal pro-inflammatory cytokines in term infants.

Streptococcus agalactiae (Group B Streptococcus; GBS) is a common cause of sepsis in neonates. Previous work detected GBS DNA in the placenta in ~5% of women before the onset of labour, but the clinical significance of this finding is unknown. Here we re-analysed this dataset as a case control study of neonatal unit (NNU) admission.

Association between adverse pregnancy outcome and placental biomarkers in the first trimester: A prospective cohort study.

Objective: To determine the inter-relationships between five first-trimester biomarkers (pregnancy associated plasma protein A [PAPP-A], alpha-fetoprotein [AFP], beta human chorionic gonadotrophin [beta-hCG], placenta growth factor [PlGF] and soluble fms-like tyrosine kinase receptor-1 [sFlt-1]) and a range of adverse pregnancy outcomes (APOs).

Design: Prospective cohort study of nulliparous singleton pregnancy.

Setting: Cambridge, UK.

Objective measures of smoking and caffeine intake and the risk of adverse pregnancy outcomes.

Background: In pregnancy, women are encouraged to cease smoking and limit caffeine intake. We employed objective definitions of smoking and caffeine exposure to assess their association with adverse outcomes.

Methods: We conducted a case cohort study within the Pregnancy Outcome Prediction study to analyse maternal serum metabolomics in samples from 12, 20, 28 and 36 weeks of gestational age.

Occupational impacts of early inflammatory arthritis: results from the National Early Inflammatory Arthritis Audit.

Objectives: Inflammatory arthritis causes significant work disability. Studies regarding this frequently fail to report important contextual information such as employment type. Our objective was to explore work participation, by gender and occupation type, in early inflammatory arthritis.

Anthropological and sociological perspectives on food allergy.

This review explores the anthropological and sociological literature on food allergy and identifies four primary areas of research to date. The first explores the relationality and management of risk, uncertainty and stigma among parents and sufferers of food allergies. The second analyses the influence of intersectionality, specifically the effects of class, gender, race/ethnicity and disability on experiences of food allergy.

The human placenta exhibits a unique transcriptomic void.

The human placenta exhibits a unique genomic architecture with an unexpectedly high mutation burden and many uniquely expressed genes. The aim of this study is to identify transcripts that are uniquely absent or depleted in the placenta. Here, we show that 40 of 46 of the other organs have no selectively depleted transcripts and that, of the remaining six, the liver has the largest number, with 26.

Nonadherence to systemic immune-modifying therapy in people with psoriasis during the COVID-19 pandemic: findings from a global cross-sectional survey.

Background: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic.

Objectives: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence.

Having less means wanting more: Children hold an intuitive economic theory of diminishing marginal utility.

Judgments surrounding resource acquisition and valuation are ubiquitous in daily life. How do humans decide what something is worth to themselves or someone else? One important cue to value is that of resource quantity. As described by economists, the principle of diminishing marginal utility (DMU) holds that as resource abundance increases, the value placed on each unit decreases; likewise, when resources become more scarce, the value placed on each unit rises.