Subunit specific altered expression and activity of casein kinase 2 in the brain tissues resected from mesial temporal lobe epilepsy with hippocampal sclerosis patients & rodent temporal lobe epilepsy model.

Introduction: Mesial temporal lobe epilepsy (MTLE), is associated with dysregulated excitatory-inhibitory balance in the brain. Numerous enzymes, protein kinases, that are modulated through phosphorylation, have been linked with key processes involved in the pathogenesis of epilepsy. Therefore, in this study, we determined the subunit specific expression and activity of multi-subunit casein Kinase 2 (CK2) which influences NMDARs through phosphorylation events, in MTS patients as well as pilocarpine model of TLE.

Clinical Characteristics of Virologically Confirmed Respiratory Syncytial Virus in English Primary Care: Protocol for an Observational Study of Acute Respiratory Infection.

Background: There are gaps in our understanding of the clinical characteristics and disease burden of the respiratory syncytial virus (RSV) among community-dwelling adults. This is in part due to a lack of routine testing at the point of care. More data would enhance our assessment of the need for an RSV vaccination program for adults in the United Kingdom.

Pathology-specific lipid alterations with triacylglycerol as a potential biomarker in Focal cortical dysplasia (FCD) and Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS).

Focal Cortical Dysplasia (FCD) & Mesial Temporal Lobe Epilepsy-Hippocampal Sclerosis (MTLE-HS) are two common pathologies of drug-resistant focal epilepsy (DRE). Inappropriate localization of the epileptogenic zones (EZs) in FCD is a significant contributing factor to the unsatisfactory surgical results observed in FCD cases. Currently, no molecular or cellular indicators are available which can aid in identifying the epileptogenic zones (EZs) in FCD.

Creating a Modified Version of the Cambridge Multimorbidity Score to Predict Mortality in People Older Than 16 Years: Model Development and Validation.

Background: No single multimorbidity measure is validated for use in NHS (National Health Service) England's General Practice Extraction Service Data for Pandemic Planning and Research (GDPPR), the nationwide primary care data set created for COVID-19 pandemic research. The Cambridge Multimorbidity Score (CMMS) is a validated tool for predicting mortality risk, with 37 conditions defined by Read Codes. The GDPPR uses the more internationally used Systematized Nomenclature of Medicine clinical terms (SNOMED CT).

Qualitative evaluation of a molecular point-of-care testing study for influenza in UK primary care.

Background: Influenza contributes to the surge in winter infections and the consequent winter pressures on the health service. Molecular point-of-care testing (POCT) for influenza may improve patient management by providing rapid and accurate clinical diagnosis to inform the timely initiation of antiviral therapy and reduce unnecessary admissions and antibiotics use.

Aim: To explore factors that influence the adoption or non-adoption of POCT in English general practices and provide insights to enable its integration into routine practice workflows.

A Profile of Influenza Vaccine Coverage for 2019-2020: Database Study of the English Primary Care Sentinel Cohort.

Background: Innovation in seasonal influenza vaccine development has resulted in a wider range of formulations becoming available. Understanding vaccine coverage across populations including the timing of administration is important when evaluating vaccine benefits and risks.

Objective: This study aims to report the representativeness, uptake of influenza vaccines, different formulations of influenza vaccines, and timing of administration within the English Primary Care Sentinel Cohort (PCSC).

Interim 2023/2024 Season Influenza Vaccine Effectiveness in Primary and Secondary Care in the United Kingdom.

Background: We report 2023/2024 season interim influenza vaccine effectiveness for three studies, namely, primary care in Great Britain, hospital settings in Scotland and hospital settings in England.

Methods: A test negative design was used to estimate vaccine effectiveness.

Results: Estimated vaccine effectiveness against all influenzas ranged from 63% (95% confidence interval 46 to 75%) to 65% (41 to 79%) among children aged 2-17, from 36% (20 to 49%) to 55% (43 to 65%) among adults 18-64 and from 40% (29 to 50%) to 55% (32 to 70%) among adults aged 65 and over.

End of 2022/23 Season Influenza Vaccine Effectiveness in Primary Care in Great Britain.

Background: The 2022/23 influenza season in the United Kingdom saw the return of influenza to prepandemic levels following two seasons with low influenza activity. The early season was dominated by A(H3N2), with cocirculation of A(H1N1), reaching a peak late December 2022, while influenza B circulated at low levels during the latter part of the season. From September to March 2022/23, influenza vaccines were offered, free of charge, to all aged 2-13 (and 14-15 in Scotland and Wales), adults up to 49 years of age with clinical risk conditions and adults aged 50 and above across the mainland United Kingdom.

Phenotype execution and modeling architecture to support disease surveillance and real-world evidence studies: English sentinel network evaluation.

Objective: To evaluate Phenotype Execution and Modelling Architecture (PhEMA), to express sharable phenotypes using Clinical Quality Language (CQL) and intensional Systematised Nomenclature of Medicine (SNOMED) Clinical Terms (CT) Fast Healthcare Interoperability Resources (FHIR) valuesets, for exemplar chronic disease, sociodemographic risk factor, and surveillance phenotypes.

Method: We curated 3 phenotypes: Type 2 diabetes mellitus (T2DM), excessive alcohol use, and incident influenza-like illness (ILI) using CQL to define clinical and administrative logic. We defined our phenotypes with valuesets, using SNOMED's hierarchy and expression constraint language, and CQL, combining valuesets and adding temporal elements where needed.

The multifaceted role of Wnt canonical signalling in neurogenesis, neuroinflammation, and hyperexcitability in mesial temporal lobe epilepsy.

Epilepsy is a neurological disorder characterised by unprovoked, repetitive seizures caused by abnormal neuronal firing. The Wnt/β-Catenin signalling pathway is involved in seizure-induced neurogenesis, aberrant neurogenesis, neuroinflammation, and hyperexcitability associated with epileptic disorder. Wnt/β-Catenin signalling is crucial for early brain development processes including neuronal patterning, synapse formation, and N-methyl-d-aspartate receptor (NMDAR) regulation.

Postpandemic Sentinel Surveillance of Respiratory Diseases in the Context of the World Health Organization Mosaic Framework: Protocol for a Development and Evaluation Study Involving the English Primary Care Network 2023-2024.

Background: Prepandemic sentinel surveillance focused on improved management of winter pressures, with influenza-like illness (ILI) being the key clinical indicator. The World Health Organization (WHO) global standards for influenza surveillance include monitoring acute respiratory infection (ARI) and ILI. The WHO's mosaic framework recommends that the surveillance strategies of countries include the virological monitoring of respiratory viruses with pandemic potential such as influenza.

Uptake of COVID-19 vaccinations amongst 3,433,483 children and young people: meta-analysis of UK prospective cohorts.

SARS-CoV-2 infection in children and young people (CYP) can lead to life-threatening COVID-19, transmission within households and schools, and the development of long COVID. Using linked health and administrative data, we investigated vaccine uptake among 3,433,483 CYP aged 5-17 years across all UK nations between 4th August 2021 and 31st May 2022. We constructed national cohorts and undertook multi-state modelling and meta-analysis to identify associations between demographic variables and vaccine uptake.

AZD1222 effectiveness against severe COVID-19 in individuals with comorbidity or frailty: The RAVEN cohort study.

Objectives: Despite being prioritized during initial COVID-19 vaccine rollout, vulnerable individuals at high risk of severe COVID-19 (hospitalization, intensive care unit admission, or death) remain underrepresented in vaccine effectiveness (VE) studies. The RAVEN cohort study (NCT05047822) assessed AZD1222 (ChAdOx1 nCov-19) two-dose primary series VE in vulnerable populations.

Methods: Using the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub, linked to secondary care, death registration, and COVID-19 datasets in England, COVID-19 outcomes in 2021 were compared in vaccinated and unvaccinated individuals matched on age, sex, region, and multimorbidity.

Surface entrenched β-sitosterol niosomes for enhanced cardioprotective activity against isoproterenol induced cardiotoxicity in rats.

Cardiotoxicity (CT) is a severe condition that negatively impacts heart function. β-sitosterol (BS) is a group of phytosterols and known for various pharmacological benefits, such as managing diabetes, cardiac protection, and neuroprotection. This study aims to develop niosomes (NS) containing BS, utilizing cholesterol as the lipid and Tween 80 as the stabilizer.

Risk of severe COVID-19 outcomes after autumn 2022 COVID-19 booster vaccinations: a pooled analysis of national prospective cohort studies involving 7.4 million adults in England, Northern Ireland, Scotland and Wales.

Background: UK COVID-19 vaccination policy has evolved to offering COVID-19 booster doses to individuals at increased risk of severe Illness from COVID-19. Building on our analyses of vaccine effectiveness of first, second and initial booster doses, we aimed to identify individuals at increased risk of severe outcomes (i.e.

Adverse events after first and second doses of COVID-19 vaccination in England: a national vaccine surveillance platform self-controlled case series study.

Objectives: To estimate the incidence of adverse events of interest (AEIs) after receiving their first and second doses of coronavirus disease 2019 (COVID-19) vaccinations, and to report the safety profile differences between the different COVID-19 vaccines.

Design: We used a self-controlled case series design to estimate the relative incidence (RI) of AEIs reported to the Oxford-Royal College of General Practitioners national sentinel network. We compared the AEIs that occurred seven days before and after receiving the COVID-19 vaccinations to background levels between 1 October 2020 and 12 September 2021.

Thrombocytopenic, thromboembolic and haemorrhagic events following second dose with BNT162b2 and ChAdOx1: self-controlled case series analysis of the English national sentinel cohort.

Background: Thrombosis associated with thrombocytopenia was a matter of concern post first and second doses of BNT162b2 and ChAdOx1 COVID-19 vaccines. Therefore, it is important to investigate the risk of thrombocytopenic, thromboembolic and haemorrhagic events following a second dose of BNT162b2 and ChAdOx1 COVID-19 vaccines.

Methods: We conducted a large-scale self-controlled case series analysis, using routine primary care data linked to hospital data, among 12.

COVID-19 vaccine effectiveness against hospitalisation and death of people in clinical risk groups during the Delta variant period: English primary care network cohort study.

Background: COVID-19 vaccines have been shown to be highly effective against hospitalisation and death following COVID-19 infection. COVID-19 vaccine effectiveness estimates against severe endpoints among individuals with clinical conditions that place them at increased risk of critical disease are limited.

Methods: We used English primary care medical record data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre sentinel network (N > 18 million).

Novel Synergistic Approach: Tazarotene-Calcipotriol-Loaded-PVA/PVP-Nanofibers Incorporated in Hydrogel Film for Management and Treatment of Psoriasis.

Psoriasis is an autoimmune skin disease that generally affects 1%-3% of the total population globally. Effective treatment of psoriasis is limited because of numerous factors, such as ineffective drug delivery and efficacy following conventional pharmaceutical treatments. Nanofibers are widely being used as nanocarriers for effective treatment because of their multifunctional and distinctive properties, including a greater surface area, higher volume ratio, increased elasticity and improved stiffness and resistance to traction, favorable biodegradability, high permeability, and sufficient oxygen supply, which help maintain the moisture content of the skin and improve the bioavailability of the drugs.

ECM Mimicking Biodegradable Nanofibrous Scaffold Enriched with Curcumin/ZnO to Accelerate Diabetic Wound Healing via Multifunctional Bioactivity.

Introduction: Foot ulceration is one of the most severe and debilitating complications of diabetes, which leads to the cause of non-traumatic lower-extremity amputation in 15-24% of affected individuals. The healing of diabetic foot (DF) is a significant therapeutic problem due to complications from the multifactorial healing process. Electrospun nanofibrous scaffold loaded with various wound dressing materials has excellent wound healing properties due to its multifunctional action.

Interdisciplinary Informatics to Support Primary Care Sentinel Surveillance of Respiratory Infectious Disease Including COVID-19: Donabedian Evaluation.

The Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) is one of Europe's oldest sentinel systems, providing sentinel surveillance since 1967. We report the interdisciplinary informatics required to run such a system. We used the Donabedian framework to describe the interdisciplinary informatics roles that support the structures, processes and outcomes of the RSC.

Assessing the Clinical and Socioeconomic Burden of Respiratory Syncytial Virus in Children Aged Under 5 Years in Primary Care: Protocol for a Prospective Cohort Study in England and Report on the Adaptations of the Study to the COVID-19 Pandemic.

Background: Respiratory syncytial virus (RSV) commonly causes lower respiratory tract infections and hospitalization in children. In 2019-2020, the Europe-wide RSV ComNet standardized study protocol was developed to measure the clinical and socioeconomic disease burden of RSV infections among children aged <5 years in primary care. RSV has a recognized seasonality in England.