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THE COAST ROAD ALAN MURRIN 320pp. Bloomsbury. 16.99 [pounds sterling]. 'AND WERE YOUR PARENTS from the town?'--an innocent question that anyone from a small community knows is anything but, and [...]

THE SPOILED HEART SUNJEEV SAHOTA 336pp. Harvill Seeker. 18.99 [pounds sterling]. The narrator of Sunjeev Sahota's fourth novel is primed to be met with suspicion. Entering a pub at the [...]

Clinical evidence suggests the central nervous system is frequently impacted by SARS-CoV-2 infection, either directly or indirectly, although the mechanisms are unclear. Pericytes are perivascular cells within the brain that are proposed as SARS-CoV-2 infection points. Here we show that pericyte-like cells (PLCs), when integrated into a cortical organoid, are capable of infection with authentic SARS-CoV-2. Before infection, PLCs elicited astrocytic maturation and production of basement membrane components, features attributed to pericyte functions in vivo. While traditional cortical organoids showed little evidence of infection, PLCs within cortical organoids served as viral 'replication hubs', with virus spreading to astrocytes and mediating inflammatory type I interferon transcriptional responses. Therefore, PLC-containing cortical organoids (PCCOs) represent a new 'assembloid' model that supports astrocytic maturation as well as SARS-CoV-2 entry and replication in neural tissue; thus, PCCOs serve as an experimental model for neural infection. Findings from a pericyte-containing cortical organoid model suggests that pericytes provide an infection portal for SARS-CoV-2 and can serve as a viral amplification hub within neural tissue., Author(s): Lu Wang [sup.1] [sup.2] , David Sievert [sup.1] [sup.2] , Alex E. Clark [sup.3] , Sangmoon Lee [sup.1] [sup.2] , Hannah Federman [sup.1] [sup.2] [sup.4] , Benjamin D. Gastfriend [...]

A MEMOIR OF MY FORMER SELF A life in writing HILARY MANTEL 400pp. John Murray. 25 [pounds sterling]. 'A simple rotation of the object solves a great many problems.' This [...]

The prevalence of "long COVID" is just one of the conundrums highlighting how little we know about the lung's response to viral infection, particularly to syndromecoronavirus-2 (SARS-CoV-2), for which the lung is the point of entry. We used an in vitro human lung system to enable a prospective, unbiased, sequential single-cell level analysis of pulmonary cell responses to infection by multiple SARS-CoV-2 strains. Starting with human induced pluripotent stem cells and emulating lung organogenesis, we generated and infected three-dimensional, multi-cell-type-containing lung organoids (LOs) and gained several unexpected insights. First, SARS-CoV-2 tropism is much broader than previously believed: Many lung cell types are infectable, if not through a canonical receptor-mediated route (e.g., via Angiotensin-converting encyme 2(ACE2)) then via a noncanonical "backdoor" route (via macropinocytosis, a form of endocytosis). Food and Drug Administration (FDA)-approved endocytosis blockers can abrogate such entry, suggesting adjunctive therapies. Regardless of the route of entry, the virus triggers a lung-autonomous, pulmonary epithelial cell--intrinsic, innate immune response involving interferons and cytokine/chemokine production in the absence of hematopoietic derivatives. The virus can spread rapidly throughout human LOs resulting in mitochondrial apoptosis mediated by the prosurvival protein Bcl-xL. This host cytopathic response to the virus may help explain persistent inflammatory signatures in a dysfunctional pulmonary environment of long COVID. The host response to the virus is, in significant part, dependent on pulmonary Surfactant Protein-B, which plays an unanticipated role in signal transduction, viral resistance, dampening of systemic inflammatory cytokine production, and minimizing apoptosis. Exogenous surfactant, in fact, can be broadly therapeutic. [ABSTRACT FROM AUTHOR]

The continuing mutability of the SARS-CoV-2 virus can result in failures of diagnostic assays. To address this, we describe a generalizable bioinformatics-to-biology pipeline developed for the calibration and quality assurance of inactivated SARS-CoV-2 variant panels provided to Radical Acceleration of Diagnostics programs (RADx)-radical program awardees. A heuristic genetic analysis based on variant-defining mutations demonstrated the lowest genetic variance in the Nucleocapsid protein (Np)-C-terminal domain (CTD) across all SARS-CoV-2 variants. We then employed the Shannon entropy method on (Np) sequences collected from the major variants, verifying the CTD with lower entropy (less prone to mutations) than other Np regions. Polyclonal and monoclonal antibodies were raised against this target CTD antigen and used to develop an Enzyme-linked immunoassay (ELISA) test for SARS-CoV-2. Blinded Viral Quality Assurance (VQA) panels comprised of UV-inactivated SARS-CoV-2 variants (XBB.1.5, BF.7, BA.1, B.1.617.2, and WA1) and distractor respiratory viruses (CoV 229E, CoV OC43, RSV A2, RSV B, IAV H1N1, and IBV) were assembled by the RADx-rad Diagnostics core and tested using the ELISA described here. The assay tested positive for all variants with high sensitivity (limit of detection: 1.72–8.78 ng/mL) and negative for the distractor virus panel. Epitope mapping for the monoclonal antibodies identified a 20 amino acid antigenic peptide on the Np-CTD that an in-silico program also predicted for the highest antigenicity. This work provides a template for a bioinformatics pipeline to select genetic regions with a low propensity for mutation (low Shannon entropy) to develop robust 'pan-variant' antigen-based assays for viruses prone to high mutational rates. [ABSTRACT FROM AUTHOR]

LOVING HIGHSMITH Various cinemas; Curzon Home Cinema 'We must think of ourselves as a fertile land on which to draw', wrote Patricia Highsmith in one of the notebooks that accompanied [...]

We report a silver nanoparticle (AgNP) sensor array to detect SARS-CoV-2 viral particles utilizing five peptide receptors to produce a colorimetric response. We show that the interaction of the virus particles with the peptides interferes with the shift in plasmonic absorbance and hinders the formation of snowflake-like fractal assemblies between the AgNPs and the bridging peptides. The limit of detection in water of the sensor array was 500,000 viral copies/mL. We demonstrate the capabilities of the sensor array to distinguish between SARS-CoV-2 (Beta, Delta, and Omicron variants) from the influenza virus at the 99% confidence level through linear discriminant analysis. The sensor array was also able to discriminate three out of five negative exhaled breath condensate samples from five positive SARS-CoV-2 EBC samples. [ABSTRACT FROM AUTHOR]

SANDERSON'S ISLE JAMES CLARKE 320pp. Serpent's Tail. 16.99 [pounds sterling]. It is 1969, but only parts of London are swinging; at a grimy lockhouse on the River Lea, the war [...]

Aims: To map the existing body of heart failure (HF) telehealth interventions for vulnerable populations, and to conduct an intersectionality‐based analysis utilizing a structured checklist. Design: A scoping review and intersectionality‐based analysis. Data Sources: The search was conducted in March 2022 in the following databases: MEDLINE, CINAHL, Scopus and the Cochrane Central Register of Controlled Trials, ProQuest Dissertations and Theses Global. Review Methods: First, the titles and abstracts were screened, and then the entire articles were screened against the inclusion criteria. Two of the investigators screened the articles independently in Covidence. The studies included and excluded at various stages of screening were depicted through a PRISMA flow diagram. The quality of the included studies was assessed based on the mixed methods appraisal tool (MMAT). Each study was read thoroughly and the intersectionality‐based checklist by Ghasemi et al. (2021) was applied, whereby a yes/no response was marked for each question on the checklist and the relevant supporting data were extracted. Results: A total of 22 studies were included in this review. About 42.2% of the responses indicated that studies incorporated the principles of intersectionality at the 'problem identification' stage, followed by 42.9% and 29.44% responses indicating incorporation of these principles at the 'design and implementation' and 'evaluation' stages respectively. Conclusions: The findings suggest that the research around HF telehealth interventions for vulnerable populations is not adequately grounded in appropriate theoretical underpinning. The principles of intersectionality have been applied mostly to the problem identification and the intervention development and implementation stages, and not so much at the evaluation stage. Future research must fill the identified gaps in this area of research. No Patient or Public Contribution: Since this was a scoping, there was no patient contribution to this work; however, based on this study's findings, we are undertaking patient‐centred studies with patient contribution. [ABSTRACT FROM AUTHOR]

OLD BABES IN THE WOOD MARGARET ATWOOD 272pp. Chatto and Windus. 20 [pounds sterling]. 'Satire in extreme times is risky. Choose any excess, think you're wildly exaggerating, and it's most [...]

UK National Autism Strategy (Department of Health, 2010 and National Institute for Health and Care Excellence guidance (NICE, 2012) states that frontline staff should have a good understanding of Autism. Fifty-six clinical and administrative staff from a multidisciplinary community Learning Disability service completed an electronic questionnaire to evaluate levels of Autism knowledge. The results showed that, compared with clinical staff, administrative staff were more limited in their understanding of Autism and less able to access relevant Autism training. Autism training was provided for administrative staff. Focus group feedback about the training sessions and subsequent changes to practice concluded that the outcome of the training was positive. "Autism-friendly" changes to administrative practice included alterations to waiting environments, adapted communication for people with Autism and increased communication between clinical and administrative staff about the needs of people with Autism. Future Autism training for all frontline staff and ongoing evaluation of health professionals' Autism knowledge are discussed.