Long-Lasting Cross-Linked PLGA-Inspired Nanoparticles from One-Pot Nanopolymerization of Precisely Sequenced Short Oligolactoglycolic Acid Dimethacrylates.

A novel PLGA-inspired NP polymerization technique is presented, which allows the formation of NPs via the cross-linking of precisely sequenced short oligolactoglycolic acid dimethacrylates (OLGADMAs). Following the synthesis of a range of OLGADMAs, a library of NPs via this rapid and surfactant-free nanopolymerization method is successfully generated, which permits the simultaneous NP formation and encapsulation of drugs such as dexamethasone. The results indicate that NPs produced through this nanopolymerization technique with precisely controlled sequences exhibit heightened stability compared to conventionally sequenced and non-sequence controlled PLGA, as evidenced by minimal pH changes over five weeks.

Qualitative evaluation of the implementation and national roll-out of the NHS App in England.

Background: The NHS App launched in 2019 as the 'digital front door' to the National Health Service in England with core features including General Practitioner (GP) appointment booking, repeat prescriptions, patient access to records and, later on, COVID-19 vaccination certification. Similar patient portals have been adopted in different formats and with variable levels of success. In this longitudinal study (2021-2023) we examined how the NHS App became implemented in the pandemic context and beyond.

Distribution of the four type VI secretion systems in Pseudomonas aeruginosa and classification of their core and accessory effectors.

Bacterial type VI secretion systems (T6SSs) are puncturing molecular machines that transport effector proteins to kill microbes, manipulate eukaryotic cells, or facilitate nutrient uptake. How and why T6SS machines and effectors differ within a species is not fully understood. Here, we applied molecular population genetics to the T6SSs in a global population of the opportunistic pathogen Pseudomonas aeruginosa.

Time to HIV viral rebound and frequency of post-treatment control after analytical interruption of antiretroviral therapy: an individual data-based meta-analysis of 24 prospective studies.

The only current strategy to test efficacy of novel interventions for sustained HIV control without antiretroviral therapy (ART) among people with HIV (PWH) is through an analytical treatment interruption (ATI). Inclusion of 'placebo' controls in ATIs poses ethical, logistical, and economic challenges. To understand viral dynamics and rates of post-treatment control (PTC) after ATI among PWH receiving either placebo or no intervention, we undertook an individual-participant data meta-analysis.

Study protocol for the development and pilot-testing of a Self-assessment tool for the implementation of the European Standards of Care for Newborn Health (ESCNH).

Introduction: In Europe, disparities exist in having access to optimal neonatal care. With the European Standards of Care for Newborn Health (ESCNH), evidence-based reference standards are available which provide guidance to improve the care for preterm and ill newborns. To support healthcare professionals (HCPs) and hospital/clinic management in identifying the extent of ESCNH implementation, a feasible assessment tool is required.

Autonomous learning of generative models with chemical reaction network ensembles.

Can a micron-sized sack of interacting molecules autonomously learn an internal model of a complex and fluctuating environment? We draw insights from control theory, machine learning theory, chemical reaction network theory and statistical physics to develop a general architecture whereby a broad class of chemical systems can autonomously learn complex distributions. Our construction takes the form of a chemical implementation of machine learning's optimization workhorse: gradient descent on the relative entropy cost function, which we demonstrate can be viewed as a form of integral feedback control. We show how this method can be applied to optimize any detailed balanced chemical reaction network and that the construction is capable of using hidden units to learn complex distributions.

Systems-level immunomonitoring in children with solid tumors to enable precision medicine.

Cancer is the leading cause of death from disease in children. Survival depends not only on surgery, cytostatic drugs, and radiation but also on systemic immune responses. Factors influencing these immune responses in children of different ages and tumor types are unknown.

Conjoint specification of action by neocortex and striatum.

The interplay between two major forebrain structures-cortex and subcortical striatum-is critical for flexible, goal-directed action. Traditionally, it has been proposed that striatum is critical for selecting what type of action is initiated, while the primary motor cortex is involved in specifying the continuous parameters of an upcoming/ongoing movement. Recent data indicate that striatum may also be involved in specification.

Emergence of SARS-CoV-2 subgenomic RNAs that enhance viral fitness and immune evasion.

Coronaviruses express their structural and accessory genes via a set of subgenomic RNAs, whose synthesis is directed by transcription regulatory sequences (TRSs) in the 5' genomic leader and upstream of each body open reading frame. In SARS-CoV-2, the TRS has the consensus AAACGAAC; upon searching for emergence of this motif in the global SARS-CoV-2 sequences, we find that it evolves frequently, especially in the 3' end of the genome. We show well-supported examples upstream of the Spike gene-within the nsp16 coding region of ORF1b-which is expressed during human infection, and upstream of the canonical Envelope gene TRS, both of which have evolved convergently in multiple lineages.

Diagnostic Certainty in Characterizing Liver Lesions in Rectal Cancer: Abbreviated Liver MRI versus CT.

Background: Early diagnosis of metastases is crucial but routine staging with contrast-enhanced multidetector computed tomography (ceMDCT) is suboptimal. A total of 20% will have indeterminate or too small to characterize (TSTC) liver lesions on CT, requiring formal characterization by magnetic resonance imaging (MRI). This UK cross-sectional study reports our experience undertaking routine abbreviated liver MRI (MRI).

Improved Annotation of Asthma Gene Variants with Cell Type Deconvolution of Nasal and Lung Expression-Quantitative Trait Loci.

Asthma is a genetically complex inflammatory airway disease associated with over 200 Single nucleotide polymorphisms (SNPs). However, the functional effects of many asthma-associated SNPs in lung and airway epithelial samples are unknown. Here, we aimed to conduct expression quantitative trait loci (eQTL) analysis using a meta-analysis of nasal and lung samples.

COPD Airway Epithelial Cell-derived Extracellular Vesicles Spread Cellular Senescence via MicroRNA-34a.

Chronic obstructive pulmonary disease (COPD) is associated with the acceleration of lung aging, and the accumulation of senescent cells in lung tissue. MicroRNA (miR)-34a induces senescence by suppressing the anti-aging molecule, sirtuin-1 (SIRT1). Senescent cells spread senescence to neighbouring and distant cells, favouring COPD progression and its comorbidities.

Comparing to three other enteric pathogens in OligoMM mice reveals pathogen-specific host and microbiota responses.

, non-typhoidal spp., and enteropathogenic/enterohemorrhagic (EPEC/EHEC) are leading causes of food-borne illness worldwide. has been used to model EPEC and EHEC infection in mice.

Emirates consensus recommendations on cardiovascular risk management in type 2 diabetes.

Background: The combination of cardiovascular disease and diabetes is a highly prevalent condition in the United Arab Emirates. Development and dissemination of evidence-based regional recommendations for optimal screening, treatment and referrals of people with diabetes and high cardiovascular risk is an important priority.

Consensus Panel: An expert panel of diabetologists, endocrinologists and cardiologists from the Emirates Cardiac Society and Emirates Diabetes and Endocrine Society as well as different entities in the UAE, discussed and reviewed evidence and also a consensus report from the American Diabetes Association to formulate contextualized recommendations that could be applied for optimal management of cardiovascular risk in people with diabetes in the UAE.

Long term health outcomes in people with diabetes 12 months after hospitalisation with COVID-19 in the UK: a prospective cohort study.

Background: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes.

Receiver design for the REACH global 21-cm signal experiment.

We detail the REACH radiometric system designed to enable measurements of the 21-cm neutral hydrogen line. Included is the radiometer architecture and end-to-end system simulations as well as a discussion of the challenges intrinsic to highly-calibratable system development. Following this, we share laboratory results based on the calculation of noise wave parameters utilising an over-constrained least squares approach.

Association of the Triglyceride-Glucose Index and Obesity Indicators with Multiple Chronic Diseases: A Longitudinal Cohort Study Based on CHARLS.

Objective: To explore the relationship between triglyceride glucose (TyG) and the obesity combined indexes and the occurrence of multiple chronic diseases (MCD), which will help to provide a basis for the prevention and treatment of this condition.

Methods: 3037 participants in the China Health and Retirement Longitudinal Study, which was conducted from 2011 to 2015 were selected for this study. They were divided into four groups (Q1, Q2, Q3, Q4) based on the quartiles of TyG, TyG-BMI, TyGWC and TyGWHtR in the baseline data.

Reinvestigation into the role of lipopolysaccharide Glycosyltransferases in protein glycosylation.

Protein glycosylation has been considered as a fundamental phenomenon shared by all domains of life. In , glycosylation of flagellins A and B with pseudaminic acid have been rigorously confirmed and shown to be essential for flagella assembly and bacterial colonization. In addition to flagellins, several other proteins including RecA, AlpA/B, and BabA/B in have also been reported to be glycosylated and to be dependent on the lipopolysaccharide (LPS) biosynthetic pathway.

Kisspeptin as a test of hypothalamic dysfunction in pubertal and reproductive disorders.

The hypothalamic-pituitary-gonadal axis is regulated by the gonadotropin-releasing hormone pulse generator in the hypothalamus. This is comprised of neurons that secrete kisspeptin in a pulsatile manner to stimulate the release of GnRH, and, in turn, downstream gonadotropins from the pituitary gland, and subsequently sex steroids and gametogenesis from the gonads. Many reproductive disorders in both males and females are characterized by hypothalamic dysfunction, including functional disorders (such as age-related hypogonadism, obesity-related secondary hypogonadism, hyperprolactinemia, functional hypothalamic amenorrhea and polycystic ovary syndrome), structural pathologies (such as craniopharyngiomas or radiation or surgery-related hypothalamic dysfunction), and pubertal disorders (constitutional delay of growth and puberty and congenital hypogonadotropic hypogonadism).

Combination therapy versus monotherapy: retrospective analysis of antibiotic treatment of enterococcal endocarditis.

Background: Guidelines suggest treating fully penicillin-susceptible Enterococcus faecalis strains causing infective endocarditis with amoxicillin combined with gentamicin or ceftriaxone, but clinical evidence to support this practice is limited and monotherapy cohorts were excluded from studies. We describe antibiotic treatment, complications, and outcomes in patients with Enterococcus faecalis infective endocarditis, specifically comparing monotherapy versus combination therapy.

Methods: Retrospective analysis of prospectively collected cohort of patients with definite or possible infective endocarditis from 2 English centres between 2006 and 2021.

Features of intermediate and late dry age-related macular degeneration on adaptive optics ophthalmoscopy: Pinnacle Study Report 8.

Background/objectives: Adaptive optics ophthalmoscopy (AOO) has the potential to provide insights into AMD pathology and to assess the risk of progression. We aim to utilise AOO to describe detailed features of intermediate AMD and to characterise microscopic changes during atrophy development.

Subjects/methods: Patients with intermediate AMD were recruited into PINNACLE, a prospective observational cohort study.

Imperatives and co-benefits of research into climate change and neurological disease.

Evidence suggests that anthropogenic climate change is accelerating and is affecting human health globally. Despite urgent calls to address health effects in the context of the additional challenges of environmental degradation, biodiversity loss and ageing populations, the effects of climate change on specific health conditions are still poorly understood. Neurological diseases contribute substantially to the global burden of disease, and the possible direct and indirect consequences of climate change for people with these conditions are a cause for concern.

What are the perceptions and experiences of adults using mobile applications for self-management in diabetes? A systematic review.

Objectives: Diabetes mellitus is a chronic disease that entails significant burdens to patients, caregivers and society at large. While self-management behaviours like healthy eating and monitoring of blood glucose help to reduce the care burden, they are still perceived to be burdensome. Mobile applications have emerged as promising digital tools in helping patients to self-manage their conditions.