An aptamer-mediated base editing platform for simultaneous knockin and multiple gene knockout for allogeneic CAR-T cells generation.

Gene editing technologies hold promise for enabling the next generation of adoptive cellular therapies. In conventional gene editing platforms that rely on nuclease activity, such as clustered regularly interspaced short palindromic repeats CRISPR-associated protein 9 (CRISPR-Cas9), allow efficient introduction of genetic modifications; however, these modifications occur via the generation of DNA double-strand breaks (DSBs) and can lead to unwanted genomic alterations and genotoxicity. Here, we apply a novel modular RNA aptamer-mediated Pin-point base editing platform to simultaneously introduce multiple gene knockouts and site-specific integration of a transgene in human primary T cells.

The Development and Evaluation of a Combined Infection-Rheumatology Assessment Service in Response to the Chikungunya Fever Epidemic.

The chikungunya virus is an arthritogenic alphavirus. Acute infection may be followed by persistent arthralgia, often causing significant functional impairment. The 2014-2015 chikungunya fever (CHIKF) epidemic resulted in a marked increase in cases presenting to rheumatology and tropical diseases services.

Invasive infection: shedding light on a rare pathogen in a retrospective cohort analysis.

are Gram-negative, facultatively anaerobic rods or coccobacilli that are infrequently encountered as pathogens causing infection. The range of invasive infection that cause is poorly described. The pathogenicity of species such as is debated.

breast abscesses in context, a retrospective cohort study.

breast abscesses and granulomatous mastitis have gained increased recognition in the 20 years since their association was first described. No studies to date have described this organism in the context of all breast abscess pathogens. We retrospectively reviewed 160 community-acquired breast abscess samples from 135 patients in a 3 year period, describing the organisms isolated along with risk factors, site of infection and outcomes.

Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes.

Background: This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature.

Methods/results: We combined classic plasma biochemistry and plasma biomarkers with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (morbidly obese and lipodystrophy) and lean individuals to identify the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells. Our analyses showed that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers.

Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study.

Background: We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.

Methods: We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew's Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work.

Clinical utility of 16S rRNA PCR in pleural infection.

Pleural infections cause major morbidity and mortality, particularly amongst paediatric and elderly populations. The aetiology is broad, but pleural culture fails to yield a causative pathogen in approximately 40 % of cases. Alternative pathogen identification methods are therefore required.

Lesson of the month: Late, disseminated herpes zoster reactivation in a stem cell transplant recipient: implications for post-transplant prophylaxis and immune monitoring.

Varicella zoster reactivation is a known risk following stem-cell transplantation, but has become more infrequent since universal antiviral prophylaxis. We report an unusual case of late, disseminated reactivation in a 27-year-old man with positive pre-transplant serology, and discuss implications for post-transplant prophylaxis and immune monitoring.

Reintroduction of elective cardiac interventions in the era of COVID-19: the Barts experience.

Background: The response to COVID-19 has required cancellation of all but the most urgent procedures; there is therefore a need for the reintroduction of a safe elective pathway.

Methods: This was a study of a pilot pathway performed at Barts Heart Centre for the admission of patients requiring elective coronary and structural procedures during the COVID-19 pandemic (April-June 2020). All patients on coronary and structural waiting lists were screened for procedural indications, urgency and adverse features for COVID-19 prognosis and discussed at dedicated multidisciplinary teams.

Time series analysis and mechanistic modelling of heterogeneity and sero-reversion in antibody responses to mild SARS‑CoV-2 infection.

Background: SARS-CoV-2 serology is used to identify prior infection at individual and at population level. Extended longitudinal studies with multi-timepoint sampling to evaluate dynamic changes in antibody levels are required to identify the time horizon in which these applications of serology are valid, and to explore the longevity of protective humoral immunity.

Methods: Healthcare workers were recruited to a prospective cohort study from the first SARS-CoV-2 epidemic peak in London, undergoing weekly symptom screen, viral PCR and blood sampling over 16-21 weeks.

Screening for in patients admitted to eight intensive care units in England, 2017 to 2018.

Background is an emerging multidrug-resistant fungal pathogen associated with bloodstream, wound and other infections, especially in critically ill patients. carriage is persistent and is difficult to eradicate from the hospital environment.AimWe aimed to pilot admission screening for in intensive care units (ICUs) in England to estimate prevalence in the ICU population and to inform public health guidance.

Development and Characterization of a Modular CRISPR and RNA Aptamer Mediated Base Editing System.

Conventional CRISPR approaches for precision genome editing rely on the introduction of DNA double-strand breaks (DSB) and activation of homology-directed repair (HDR), which is inherently genotoxic and inefficient in somatic cells. The development of base editing (BE) systems that edit a target base without requiring generation of DSB or HDR offers an alternative. Here, we describe a novel BE system called Pin-point that recruits a DNA base-modifying enzyme through an RNA aptamer within the gRNA molecule.

Development and internal validation of clinical prediction models for outcomes of complicated intra-abdominal infection.

Background: Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse.

Methods: A multicentre observational study was conducted from August 2016 to February 2017 in the UK.

Implementation of early management of iron deficiency in pregnancy during the SARS-CoV-2 pandemic.

Iron deficiency is the commonest cause for anaemia worldwide making it a formidable issue particularly during pregnancy because of increased iron demands. This study looked at establishing a lower limit of normal for haemoglobin concentration (Hb) in our population and to proactively address potentially symptomatic iron deficiency during the current SARS-CoV-2 pandemic. The lower limit of normal for Hb in our 1715 first trimester pregnancy cohort was 116 g/L.

Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection.

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW.

Utility of immunology, microbiology, and helminth investigations in clinical assessment of severe asthma.

Objective: Systematic assessment of patients with potential severe asthma is key to identification of treatable traits and optimal management. Assessment of antimicrobial immune function is part of that assessment at many centers although there is little evidence-base on its added value in clinical assessment of this patient group. As part of reviewing our local pathway, we have retrospectively reviewed these tests in 327 consecutive referrals to our severe asthma service, in an evaluation to describe the utility of these tests and allow refinement of the local guideline for patient assessment.

Cell type-specific novel long non-coding RNA and circular RNA in the BLUEPRINT hematopoietic transcriptomes atlas.

Transcriptional profiling of hematopoietic cell subpopulations has helped to characterize the developmental stages of the hematopoietic system and the molecular bases of malignant and non-malignant blood diseases. Previously, only the genes targeted by expression microarrays could be profiled genome-wide. High-throughput RNA sequencing, however, encompasses a broader repertoire of RNA molecules, without restriction to previously annotated genes.

Protecting people with multiple sclerosis through vaccination.

Vaccination is one of the most effective and cost-efficient methods for protecting people with multiple sclerosis (MS) from infections. However, use of vaccines has often been problematic because of misguided concerns that they may exacerbate the disease and/or that some disease-modifying therapies may influence the immune response to immunisations and/or their safety. People with MS risk higher morbidity and mortality from vaccine-preventable infections.

The Pan London Emergency Cardiac Surgery service: Coordinating a response to the COVID-19 pandemic.

Over the last 4 months, the novel coronavirus, SARS-CoV-2, has caused a significant economic, political, and public health impact on a global scale. The natural history of the disease and surge in the need for invasive ventilation has required the provision of intensive care beds in London to be reallocated. NHS England have proposed the formation of a Pan-London Emergency Cardiac surgery (PLECS) service to provide urgent and emergency cardiac surgery for the whole of London.