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Background and aims: The intrahepatic processes associated with chronic hepatitis B (CHB), especially in the context of hepatitis delta virus (HDV) and HIV co-infection, require a better understanding. Spatial transcriptomics can provide new insights into the complex intrahepatic biological processes, guiding new personalised treatments. Our aim is to evaluate this method characterising the intrahepatic transcriptional landscape, cellular composition and biological pathways in liver biopsy samples from patients with hepatitis B virus (HBV) and HDV or HIV co-infection. Method: The NanoString GeoMx digital spatial profiling platform was employed to assess expression of HBV surface antigen and CD45 in formalin-fixed paraffin-embedded (FFPE) biopsies from three treatment-naïve patients with chronic HBV and HDV or HIV co-infection. The GeoMx Human Whole Transcriptome Atlas assay quantified the expression of genes enriched in specific regions of interest (ROIs). Cell type proportions within ROIs were deconvoluted using a training matrix from the human liver cell atlas. A weighted gene correlation network analysis evaluated transcriptomic signatures across sampled regions. Results: Spatially discrete transcriptomic signatures and distinct biological pathways were associated with HBV infection/disease status and immune responses. Shared features including 'cytotoxicity' and 'B cell receptor signalling' were consistent across patients, suggesting common elements alongside individual traits. HDV/HBV co-infection exhibited upregulated genes linked to apoptosis and immune cell recruitment, whereas HIV/HBV co-infection featured genes related to interferon response regulation. Varied cellular characteristics and immune cell populations, with an abundance of γδT cells in the HDV/HBV sample, were observed within analysed regions. Transcriptional differences in hepatocyte function suggest disrupted metabolic processes in HDV/HBV co-infection potentially impacting disease progression. Conclusion: This proof-of-principle study shows the value of this platform in investigating the complex immune landscape, highlighting relevant host pathways to disease pathogenesis.
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Enactive cognition emphasizes co-constructive roles of humans and their environment in shaping cognitive processes. It is specifically engaged in the mental simulation of behaviors, enhancing the connection between perception and action. Here we investigated the core network of brain regions involved in enactive cognition as applied to mental simulations of physical exercise. We used a neuroimaging paradigm in which participants (N = 103) were required to project themselves running or plogging (running while picking-up litter) along an image-guided naturalistic trail. Using both univariate and multivariate brain imaging analyses, we find that a broad spectrum of brain activation discriminates between the mental simulation of plogging versus running. Critically, we show that self-reported ratings of daily life running engagement and the quality of mental simulation (how well participants were able to imagine themselves running) modulate the brain reactivity to plogging versus running. Finally, we undertook functional connectivity analyses centered on the insular cortex, which is a key region in the dynamic interplay between neurocognitive processes. This analysis revealed increased positive and negative patterns of insular-centered functional connectivity in the plogging condition (as compared to the running condition), thereby confirming the key role of the insular cortex in action simulation involving complex sets of mental mechanisms. Taken together, the present findings provide new insights into the brain networks involved in the enactive mental simulation of physical exercise.
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Mapeo Encefálico , Encéfalo , Imagen por Resonancia Magnética , Carrera , Humanos , Masculino , Carrera/fisiología , Femenino , Adulto Joven , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Imaginación/fisiología , Vías Nerviosas/fisiología , Vías Nerviosas/diagnóstico por imagenRESUMEN
Our current planetary crisis, including multiple jointly acting factors of global change, moves the need for effective ecosystem restoration center stage and compels us to explore unusual options. We here propose exploring combinatorial approaches to restoration practices: management practices are drawn at random and combined from a locally relevant pool of possible management interventions, thus creating an experimental gradient in the number of interventions. This will move the current degree of interventions to higher dimensionality, opening new opportunities for unlocking unknown synergistic effects. Thus, the high dimensionality of global change (multiple jointly acting factors) would be more effectively countered by similar high-dimensionality in solutions. In this concept, regional restoration hubs play an important role as guardians of locally relevant information and sites of experimental exploration. Data collected from such studies could feed into a global database, which could be used to learn about general principles of combined restoration practices, helping to refine future experiments. Such combinatorial approaches to exploring restoration intervention options may be our best hope yet to achieve decisive progress in ecological restoration at the timescale needed to mitigate and reverse the most severe losses caused by global environmental change.
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Conservación de los Recursos Naturales , Ecosistema , Conservación de los Recursos Naturales/métodos , Restauración y Remediación Ambiental/métodos , Ecología/métodos , Cambio ClimáticoRESUMEN
Since its discovery in 1965, our understanding of the hepatitis B virus (HBV) replication cycle and host immune responses has increased markedly. In contrast, our knowledge of the molecular biology of hepatitis delta virus (HDV), which is associated with more severe liver disease, is less well understood. Despite the progress made, critical gaps remain in our knowledge of HBV and HDV replication and the mechanisms underlying viral persistence and evasion of host immunity. The International HBV Meeting is the leading annual scientific meeting for presenting the latest advances in HBV and HDV molecular virology, immunology, and epidemiology. In 2023, the annual scientific meeting was held in Kobe, Japan and this review summarises some of the advances presented at the Meeting and lists gaps in our knowledge that may facilitate the development of new therapies.
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Virus de la Hepatitis B , Hepatitis B , Virus de la Hepatitis Delta , Replicación Viral , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/fisiología , Virus de la Hepatitis B/inmunología , Humanos , Virus de la Hepatitis Delta/genética , Virus de la Hepatitis Delta/fisiología , Hepatitis B/virología , Hepatitis B/inmunología , Biología Molecular , Japón , Hepatitis D/virología , Interacciones Huésped-Patógeno/inmunología , Interacciones Huésped-Patógeno/genéticaRESUMEN
X-ray nanotomography is a powerful tool for the characterization of nanoscale materials and structures, but it is difficult to implement due to the competing requirements of X-ray flux and spot size. Due to this constraint, state-of-the-art nanotomography is predominantly performed at large synchrotron facilities. We present a laboratory-scale nanotomography instrument that achieves nanoscale spatial resolution while addressing the limitations of conventional tomography tools. The instrument combines the electron beam of a scanning electron microscope (SEM) with the precise, broadband X-ray detection of a superconducting transition-edge sensor (TES) microcalorimeter. The electron beam generates a highly focused X-ray spot on a metal target held micrometers away from the sample of interest, while the TES spectrometer isolates target photons with a high signal-to-noise ratio. This combination of a focused X-ray spot, energy-resolved X-ray detection, and unique system geometry enables nanoscale, element-specific X-ray imaging in a compact footprint. The proof of concept for this approach to X-ray nanotomography is demonstrated by imaging 160 nm features in three dimensions in six layers of a Cu-SiO2 integrated circuit, and a path toward finer resolution and enhanced imaging capabilities is discussed.
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BACKGROUND: Most patients with signs or symptoms (s/s) of suspected preeclampsia are not diagnosed with preeclampsia. We sought to determine and compare the prevalence of s/s, pregnancy outcomes, and costs between patients with and without diagnosed preeclampsia. METHODS: This retrospective cohort study analyzed a large insurance research database. Pregnancies with s/s of preeclampsia versus a confirmed preeclampsia diagnosis were identified using International Classification of Diseases codes. S/s include hypertension, proteinuria, headache, visual symptoms, edema, abdominal pain, and nausea/vomiting. Pregnancies were classed as 1) s/s of preeclampsia without a confirmed preeclampsia diagnosis (suspicion only), 2) s/s with a confirmed diagnosis (preeclampsia with suspicion), 3) diagnosed preeclampsia without s/s recorded (preeclampsia only), and 4) no s/s, nor preeclampsia diagnosis (control). RESULTS: Of 1,324,424 pregnancies, 29.2 % had ≥1 documented s/s of suspected preeclampsia, and 14.2 % received a preeclampsia diagnosis. Hypertension and headache were the most common s/s, leading 20.2 % and 9.2 % pregnancies developed to preeclampsia diagnosis, respectively. Preeclampsia, with or without suspicion, had the highest rates of hypertension-related severe maternal morbidity (HR [95 % CI]: 3.0 [2.7, 3.2] and 3.6 [3.3, 4.0], respectively) versus controls. A similar trend was seen in neonatal outcomes such as preterm delivery and low birth weight. Cases in which preeclampsia was suspected but not confirmed had the highest average total maternal care costs ($6096 [95 % CI: 602, 6170] over control). CONCLUSION: There is a high prevalence but poor selectivity of traditional s/s of preeclampsia, highlighting a clinical need for improved screening method and cost-effectiveness disease management.
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Bases de Datos Factuales , Preeclampsia , Resultado del Embarazo , Humanos , Femenino , Embarazo , Preeclampsia/epidemiología , Preeclampsia/economía , Preeclampsia/diagnóstico , Estudios Retrospectivos , Adulto , Prevalencia , Resultado del Embarazo/epidemiología , Adulto Joven , Estados Unidos/epidemiología , Costos de la Atención en Salud/estadística & datos numéricosRESUMEN
Management of the open abdomen has been used for decades by general surgeons. Techniques have evolved over those decades to improve control of infection, fluid loss, and improve the ability to close the abdomen to avoid hernia formation. The authors explore the history, indications, and techniques of open abdomen management in multiple settings. The most important considerations in open abdomen management include the reason for leaving the abdomen open, prevention and mitigation of ongoing organ dysfunction, and eventual plans for abdominal closure.
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Técnicas de Cierre de Herida Abdominal , Laparotomía , Humanos , Laparotomía/métodos , Abdomen/cirugía , Músculos Abdominales/cirugíaRESUMEN
Single-site copper-based catalysts have shown remarkable activity and selectivity for a variety of reactions. However, deactivation by sintering in high-temperature reducing environments remains a challenge and often limits their use due to irreversible structural changes to the catalyst. Here, we report zeolite-based copper catalysts in which copper oxide agglomerates formed after reaction can be repeatedly redispersed back to single sites using an oxidative treatment in air at 550 °C. Under different environments, single-site copper in Cu-Zn-Y/deAlBeta undergoes dynamic changes in structure and oxidation state that can be tuned to promote the formation of key active sites while minimizing deactivation through Cu sintering. For example, single-site Cu2+ reduces to Cu1+ after catalyst pretreatment (270 °C, 101 kPa H2) and further to Cu0 nanoparticles under reaction conditions (270-350 °C, 7 kPa EtOH, 94 kPa H2) or accelerated aging (400-450 °C, 101 kPa H2). After regeneration at 550 °C in air, agglomerated CuO was dispersed back to single sites in the presence and absence of Zn and Y, which was verified by imaging, in situ spectroscopy, and catalytic rate measurements. Ab initio molecular dynamics simulations show that solvation of CuO monomers by water facilitates their transport through the zeolite pore, and condensation of the CuO monomer with a fully protonated silanol nest entraps copper and reforms the single-site structure. The capability of silanol nests to trap and stabilize copper single sites under oxidizing conditions could extend the use of single-site copper catalysts to a wider variety of reactions and allows for a simple regeneration strategy for copper single-site catalysts.
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Mammalian cells have evolved strategies to regulate gene expression when oxygen is limited. Hypoxia-inducible factors (HIF) are the major transcriptional regulators of host gene expression. We previously reported that HIFs bind and activate hepatitis B virus (HBV) DNA transcription under low oxygen conditions; however, the global cellular response to low oxygen is mediated by a family of oxygenases that work in concert with HIFs. Recent studies have identified a role for chromatin modifiers in sensing cellular oxygen and orchestrating transcriptional responses, but their role in the HBV life cycle is as yet undefined. We demonstrated that histone lysine demethylase 4 (KDM4) can restrict HBV, and pharmacological or oxygen-mediated inhibition of the demethylase increases viral RNAs derived from both episomal and integrated copies of the viral genome. Sequencing studies demonstrated that KDM4 is a major regulator of the hepatic transcriptome, which defines hepatocellular permissivity to HBV infection. We propose a model where HBV exploits cellular oxygen sensors to replicate and persist in the liver. Understanding oxygen-dependent pathways that regulate HBV infection will facilitate the development of physiologically relevant cell-based models that support efficient HBV replication.
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Virus de la Hepatitis B , Histona Demetilasas con Dominio de Jumonji , Oxígeno , Replicación Viral , Humanos , ADN Viral/genética , Genoma Viral/genética , Hepatitis B/enzimología , Hepatitis B/metabolismo , Hepatitis B/virología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/crecimiento & desarrollo , Virus de la Hepatitis B/metabolismo , Histona Demetilasas con Dominio de Jumonji/metabolismo , Hígado/enzimología , Hígado/metabolismo , Hígado/virología , Oxígeno/metabolismo , Plásmidos/genética , Transcriptoma , Replicación Viral/genéticaRESUMEN
Chronic hepatitis B is a global health problem and current treatments only suppress hepatitis B virus (HBV) infection, highlighting the need for new curative treatments. Oxygen levels influence HBV replication and we previously reported that hypoxia inducible factors (HIFs) activate the basal core promoter (BCP). Here we show that the hypoxic-dependent increase in BCP-derived transcripts is dependent on N6-methyladenosine (m6A) modifications in the 5' stem loop that regulate RNA half-life. Application of a probe-enriched long-read sequencing method to accurately map the HBV transcriptome showed an increased abundance of pre-genomic RNA under hypoxic conditions. Mapping the transcription start sites of BCP-RNAs identified a role for hypoxia to regulate pre-genomic RNA splicing that is dependent on m6A modification. Bioinformatic analysis of published single cell RNA-seq of murine liver showed an increased expression of the RNA demethylase ALKBH5 in the peri-central low oxygen region. In vitro studies with a human hepatocyte derived HepG2-NTCP cell line showed increased ALKBH5 gene expression under hypoxic conditions and a concomitant reduction in m6A-modified HBV BCP-RNA and host RNAs. Silencing the demethylase reduced the level of BCP-RNAs and host gene (CA9, NDRG1, VEGFA, BNIP3, FUT11, GAP and P4HA1) transcripts and this was mediated via reduced HIFα expression. In summary, our study highlights a previously unrecognized role for ALKBH5 in orchestrating viral and cellular transcriptional responses to low oxygen.
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Virus de la Hepatitis B , Hepatitis B , Animales , Humanos , Ratones , Desmetilasa de ARN, Homólogo 5 de AlkB/genética , Desmetilasa de ARN, Homólogo 5 de AlkB/metabolismo , Fucosiltransferasas/genética , Hepatitis B/genética , Virus de la Hepatitis B/metabolismo , Hipoxia , Oxígeno , ARN , TranscriptomaRESUMEN
Hepatitis B Virus (HBV) is a small DNA virus that replicates via an episomal covalently closed circular DNA (cccDNA) that serves as the transcriptional template for viral mRNAs. The host protein, CCCTC-binding factor (CTCF), is a key regulator of cellular transcription by maintaining epigenetic boundaries, nucleosome phasing, stabilisation of long-range chromatin loops and directing alternative exon splicing. We previously reported that CTCF binds two conserved motifs within Enhancer I of the HBV genome and represses viral transcription, however, the underlying mechanisms were not identified. We show that CTCF depletion in cells harbouring cccDNA-like HBV molecules and in de novo infected cells resulted in an increase in spliced transcripts, which was most notable in the abundant SP1 spliced transcript. In contrast, depletion of CTCF in cell lines with integrated HBV DNA had no effect on the abundance of viral transcripts and in line with this observation there was limited evidence for CTCF binding to viral integrants, suggesting that CTCF-regulation of HBV transcription is specific to episomal cccDNA. Analysis of HBV chromatin topology by Assay for Transposase Accessible Chromatin Sequencing (ATAC-Seq) revealed an accessible region spanning Enhancers I and II and the basal core promoter (BCP). Mutating the CTCF binding sites within Enhancer I resulted in a dramatic rearrangement of chromatin accessibility where the open chromatin region was no longer detected, indicating loss of the phased nucleosome up- and down-stream of the HBV enhancer/BCP. These data demonstrate that CTCF functions to regulate HBV chromatin conformation and nucleosomal positioning in episomal maintained cccDNA, which has important consequences for HBV transcription regulation.
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Cromatina , Virus de la Hepatitis B , Cromatina/genética , Virus de la Hepatitis B/genética , ADN Circular/genética , Nucleosomas , Factor de Unión a CCCTC/genéticaRESUMEN
Respiratory syncytial virus (RSV) is a global healthcare problem, causing respiratory illness in young children and elderly individuals. Our knowledge of the host pathways that define susceptibility to infection and disease severity are limited. Hypoxia inducible factors (HIFs) define metabolic responses to low oxygen and regulate inflammatory responses in the lower respiratory tract. We demonstrate a role for HIFs to suppress RSV entry and RNA replication. We show that hypoxia and HIF prolyl-hydroxylase inhibitors reduce the expression of the RSV entry receptor nucleolin and inhibit viral cell-cell fusion. We identify a HIF regulated microRNA, miR-494, that regulates nucleolin expression. In RSV-infected mice, treatment with the clinically approved HIF prolyl-hydroxylase inhibitor, Daprodustat, reduced the level of infectious virus and infiltrating monocytes and neutrophils in the lung. This study highlights a role for HIF-signalling to limit multiple aspects of RSV infection and associated inflammation and informs future therapeutic approaches for this respiratory pathogen.
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OBJECTIVE: This paper highlights the occupational risk of Q fever from exposure to raw animal products in the context of multiple notified Q fever cases from 2020 to 2023 linked to four pet food manufacturing facilities in South-East Queensland, Australia. METHODS: The Queensland Government Notifiable Conditions System was used to identify Q fever cases linked to pet food manufacturing in the Metro North and Gold Coast Hospital and Health Service areas of Brisbane, Australia. Data on each case from routine public health follow-up were collected and descriptively analysed. RESULTS: Between 2020 and 2023, 12 confirmed Q fever infections (17% of total cases) were linked to four pet food manufacturing facilities. Eleven cases reported direct or environmental exposure to raw meat and animal products. None were previously vaccinated for Q fever. CONCLUSION: These cases demonstrate the increased risk of Q fever infection as part of the pet food manufacturing process, highlighting an underappreciated preventable occupational risk, which can be mitigated with the use of pre-screening and vaccination of workers. All occupations should conduct workplace-based risk assessments to identify risks such as Q fever to prevent adverse negative health outcomes.
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Exposición Profesional , Fiebre Q , Animales , Fiebre Q/epidemiología , Fiebre Q/prevención & control , Queensland/epidemiología , Australia , Exposición a Riesgos AmbientalesRESUMEN
OBJECTIVE: To explore midwives' knowledge and understanding of the law and practice of consent in the post-Montgomery world. DESIGN: Cross-sectional online survey. Descriptive statistical analysis of midwives' survey responses. SETTINGS: Social media: Instagram, Facebook and Twitter. Survey distribution was via the UCL Opinio survey platform. PARTICIPANTS: A total of 402 midwives, surveyed over a four month period between 2nd March and 2nd July 2021. MEASUREMENTS: Knowledge of legal consent, 'sureness' of meeting current legal requirements and competence to gain consent. FINDINGS: 91% of participants acknowledged correctly that consent must be voluntary. 91% reported that women must be informed of all the risks associated with their care, although 26% reported that women should be informed of some of the risks associated with their care. Most participants were 'sure' that their discussions of consent meet current legal requirements (91%). 21% rated their competence to gain consent as 'excellent', 71% rated themselves as 'very good', whilst 1% rated their competence as 'poor'. Deficiencies in fundamental knowledge of consent were noted in some participants rating themselves highest in 'sureness' of meeting legal requirements and competence to consent. KEY CONCLUSIONS: Fundamental gaps in midwives' knowledge of legal consent were identified. Participants demonstrated uncertainty regarding the extent of risk disclosure and discussion of alternative care options. Participants generally rated themselves highly in their consenting practices, despite lacking in basic knowledge of legal consent, revealing a discrepancy between midwives' self-perceptions and their actual knowledge. IMPLICATIONS FOR PRACTICE: The overconfidence displayed by some participants is concerning for clinical midwifery practice. Professional education and guidance for midwives on legal consent in keeping with Montgomery is urgently required to ensure that midwives are legally compliant in their consenting practices.
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Partería , Enfermeras Obstetrices , Embarazo , Femenino , Humanos , Enfermeras Obstetrices/educación , Estudios Transversales , Encuestas y Cuestionarios , Reino Unido , Consentimiento InformadoRESUMEN
Post-exposure prophylaxis (PEP) for potential lyssavirus exposures consists of wound management, rabies vaccination and may include rabies immunoglobulin (RIG). Rabies serology is sometimes indicated if there is risk of PEP failure. OBJECTIVES: Evaluate the benefit of serology by indication. METHODS: Chart review of potential lyssavirus exposures managed at a Public Health Unit (June 2015 - December 2022) where serology was requested was conducted. The proportion of non-therapeutic titres was compared by sex, age, Indigenous status, serology indication, and whether RIG was given. RESULTS: 46 notifications with serology were included. Males (5/19) and people over 40 (3/16) were more likely to demonstrate a non-therapeutic response. 2/3 of cases where vaccine doses were not given in the deltoid were non-therapeutic. The rate of non-therapeutic titres was similar for RIG given into the ipsilateral arm (2/11) and given excess RIG for weight (1/4). Although this small sample was inconclusive in isolation, it was also noted that all cases who did not receive RIG had therapeutic serology, whereas 6/35 of those receiving RIG had non-therapeutic serology. CONCLUSIONS: This study supports broader literature questioning the utility of systemic RIG administration as likely limited and potentially detrimental considering the increased risk of immune interference. IMPLICATIONS FOR PUBLIC HEALTH: Highlights a need to review Australian national guidelines to align with World Health Organization advice recommending local RIG administration only.
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Lyssavirus , Vacunas Antirrábicas , Rabia , Masculino , Humanos , Rabia/prevención & control , Profilaxis Posexposición , Australia , Vacunas Antirrábicas/uso terapéuticoRESUMEN
Objective: Direct oral anticoagulants (DOACs) are first-line therapy for stroke prevention for 1.4 million atrial fibrillation (AF) patients in the UK. However, the rates of DOAC dosing below evidence-based recommendations are estimated between 9% and 22%. This study explores specific patient and physician factors associated with prescribing inappropriate DOAC underdoses. Methods: DOAC-prescribing physicians within the UK completed both a clinical vignette survey, which contained 12 hypothetical patient profiles designed to replicate DOAC prescribing scenarios, and a physician survey to capture sociodemographic, clinical experience, and prescriber-related beliefs and motivations related to DOAC prescribing. Eight patient factors based on a literature search and an expert consultation process were varied within the vignettes. Associations between the prescribers' dosing choices and patient factors were explored via multilevel logistic regression. The analysis is focused on the most frequently selected DOACs, apixaban and rivaroxaban, both of which have different dosing guidelines. Results: In all, 336 prescribers (69% male; 233/336) completed the survey, mostly general physicians (GPs) (45%) or cardiology specialists (36%) with a mean of 17.9 years' experience. Most prescribers (73%; 244/336) inappropriately underdosed at least once; rates between GPs and specialists were nearly identical. Patient factors most strongly associated with apixaban inappropriate underdosing included a history of major bleeding and falls. For rivaroxaban, these were major bleeding and severe frailty. Only 32% (106/335) of prescribers reported DOAC dosing guidelines as the sole influence on their prescribing behaviour. Among prescribers who did not inappropriately underdose, greater prescribing confidence was aligned to increased perception of inappropriate underdose risk. Conclusions: Overall, patient factors such as major bleeding and severe frailty were found to be associated with inappropriate underdosing of apixaban and rivaroxaban. Furthermore, prescribers who were more confident in DOAC prescribing, and were more worried about the risk of stroke, were significantly less likely to inappropriately underdose. These findings suggest that all prescribers, regardless of speciality, may benefit from education and training to raise awareness of the risks associated with inappropriate DOAC underdosing.
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Chronic hepatitis B is a global health problem and current treatments only suppress hepatitis B virus (HBV) infection, highlighting the need for new curative treatments. Oxygen levels influence HBV replication and we previously reported that hypoxia inducible factors (HIFs) activate the basal core promoter to transcribe pre-genomic RNA. Application of a probe-enriched long-read sequencing method to map the HBV transcriptome showed an increased abundance of all viral RNAs under low oxygen or hypoxic conditions. Importantly, the hypoxic-associated increase in HBV transcripts was dependent on N6-methyladenosine (m6A) modifications and an m6A DRACH motif in the 5' stem loop of pre-genomic RNA defined transcript half-life under hypoxic conditions. Given the essential role of m6A modifications in the viral transcriptome we assessed the oxygen-dependent expression of RNA demethylases and bioinformatic analysis of published single cell RNA-seq of murine liver showed an increased expression of the RNA demethylase ALKBH5 in the peri-central low oxygen region. In vitro studies with a human hepatocyte derived HepG2 cell line showed increased ALKBH5 gene expression under hypoxic conditions. Silencing the demethylase reduced the levels of HBV pre-genomic RNA and host gene (CA9, NDRG1, VEGFA, BNIP3, FUT11, GAP and P4HA1) transcripts and this was mediated via reduced HIFα expression. In summary, our study highlights a previously unrecognized role for ALKBH5 in orchestrating viral and cellular transcriptional responses to low oxygen.