Gingipains protect Porphyromonas gingivalis from macrophage-mediated phagocytic clearance.

Porphyromonas gingivalis (Pg) is a keystone pathogen in periodontitis, a highly prevalent disease manifested by chronic inflammation of the periodontium, alveolar bone resorption and tooth loss. During periodontitis pathobionts such as Pg can enter the bloodstream and growing evidence correlates periodontitis with increased risk of cardiovascular and neurodegenerative diseases. However, the mechanism by which immune cells respond to Pg challenge in vivo remains elusive.

Natural History and Long Term Follow-Up of Incidental Thyroid Nodules on Computed Tomography Imaging.

Objectives: incidental thyroid nodules (ITNs) are found in up to 25% of CT scans. Increased use of cross-sectional imaging has contributed to the increased incidence of thyroid cancer worldwide. ITNs pose a management dilemma since nodule malignancy rate is 5-15% but most cancers are indolent and prognosis in differentiated thyroid cancer is excellent.

Viral and immune dynamics of genital human papillomavirus infections in young women with high temporal resolution.

Human papillomavirus (HPV) infections drive one in 20 new cancer cases, exerting a particularly high burden on women. Most anogenital HPV infections are cleared in less than two years, but the underlying mechanisms that favour persistence in around 10% of women remain largely unknown. Notwithstanding, it is precisely this information that is crucial for improving treatment, screening, and vaccination strategies.

A Systematic Literature Review on the Burden of Disease for Patients With Moderate to Severe Acute Ischemic Stroke.

Background: A vast amount of literature is available on the burden of acute ischemic stroke (AIS). Yet, most information on AIS burden does not stratify by stroke severity, and the inclusion of mild strokes (National Institute of Health Stroke Scale < 5) might obscure the true impact of moderate-to-severe AIS. Therefore, it is important to understand the literature as it pertains to the epidemiological, clinical, humanistic, and economic burden of moderate-to-severe AIS from a global perspective.

Neuromuscular Electrostimulation Increases Microcirculatory Flux in Mixed Etiology Leg Ulcers.

Objective: To determine if intermittent neuromuscular electrostimulation (NMES) of the common peroneal nerve increases microvascular flow and pulsatility in and around the wound bed of patients with combined venous and arterial etiology.

Methods: Seven consenting participants presenting with mixed etiology leg ulcers participated in this study. Microvascular flow and pulsatility was measured in the wound bed and in the skin surrounding the wound using laser speckle contrast imaging.

Replicating Dynamic Immune Responses at Single-Cell Resolution within a Microfluidic Human Skin Equivalent.

To enable in vitro investigation of human skin immunology, this study develops a microfluidic human skin equivalent (HSE) that supports the delivery of circulating immune cells via a vascular microchannel embedded within the dermis of a full-thickness construct. Within this platform, activation of keratinocyte inflammation promotes monocyte migration out of the vascular channel and into the dermal and epidermal compartments. Single-cell transcriptomic analysis reveals dynamic and cell-specific patterns of gene expression that are characteristic of acute activation and resolution of an inflammatory immune response, and the gene signatures of the monocyte-derived cells closely matches the differentiation trajectory of the monocytes into mature dermal macrophages.

Identification of a vimentin-expressing α-cell phenotype in CF and normal pancreas.

Endocrine dysfunction and diabetes can develop secondary to fibrotic diseases within the pancreas including cystic fibrosis (CF). Phenotypic shift within epithelial cells has been recognised in association with pro-fibrotic signalling. We sought evidence of endocrine cell epithelial-to-mesenchymal transition in CF and non-CF pancreas.

Guided Multispectral Optoacoustic Tomography for 3D Imaging of the Murine Colon.

Multispectral optoacoustic tomography is a promising medical imaging modality that combines light and sound to provide molecular imaging information at depths of several centimeters, based on the optical absorption of endogenous chromophores, such as hemoglobin. Assessment of inflammatory bowel disease has emerged as a promising clinical application of optoacoustic tomography. In this context, preclinical studies in animal models are essential to identify novel disease-specific imaging biomarkers and understand findings from emerging clinical pilot studies, however to-date, these studies have been limited by the precise identification of the bowel wall.

Modifiable Psychological Mechanisms of Resilience Among UK Trainee and Newly Qualified Teachers.

Teaching is identified as a stressful occupation, with elevated levels of burnout among the profession. Research suggests that resilience may buffer against stress and psychological distress and potentially be a useful resource for this occupational group. This research aimed to identify mechanisms associated with trainee teachers' resilience across time.

"I Look in the Mirror and Say 'You Know What, There Is Hope for You'"-An Interpretative Qualitative Study of Current and Future Well-Being in Black African Women Older Than 50 Years With HIV in the United Kingdom.

Effective antiretroviral treatment means that people with HIV are living for longer. This includes Black African women, who represent a large proportion of people aging with HIV in the United Kingdom. Despite this, the impact of living and aging with HIV on the well-being of Black African women aging with HIV has not been investigated.

Safety of Human USH1C Transgene Expression Following Subretinal Injection in Wild-Type Pigs.

Purpose: This study aimed to evaluate early-phase safety of subretinal application of AAVanc80.CAG.USH1Ca1 (OT_USH_101) in wild-type (WT) pigs, examining the effects of a vehicle control, low dose, and high dose.

Macroporosity-Heightened Mass Transfer Enabling Complete Benzene Oxidation over Pt/SiO Catalyst.

Mass transfer governs the overall catalytic performance of heterogeneous catalysts considerably; however, this fundamental research has often been ignored. Here, macroporous SiO-supported Pt nanoparticle (Pt/SiO-M) and mesoporous SiO-supported Pt nanoparticle (Pt/SiO-m) catalysts were specifically fabricated by a facile thermal reduction step to engineer the resultant Pt nanoparticles showing similar physiochemical properties while possessing completely different porous microstructures exclusively originating from SiO supports. On this basis, a platform to explore the crucial mass transfer difference affecting catalytic activity is then established by systematically practicing industry-important benzene oxidation measurements.

Non-canonical Wnt signaling pathway activated NFATC3 promotes GDF15 expression in MASH: prospective analyses of UK biobank proteomic data.

Background: Our previous research demonstrated that growth differentiation factor 15 (GDF15) exhibited superior predictive capability for metabolic dysfunction-associated steatohepatitis (MASH) development with an AUC of 0.86 at 10 years before disease diagnosis. However, the specific pathways and molecular mechanisms associated with GDF15 expression during MASH development remain to be fully investigated in humans.

Cytoophidium complexes resonate with cell fates.

Metabolism is a fundamental characteristic of life. In 2010, we discovered that the metabolic enzyme CTP synthase (CTPS) can assemble a snake like structure inside cells, which we call the cytoophidium. Including CTPS, an increasing number of metabolic enzymes have been found to form cytoophidia in cells.

A life course approach to examine cumulative impacts of parental migration on children's psychological well-being and education in Southeast Asia.

Researchers have raised concerns about parental migration's effects on various aspects of the left-behind children's development. However, there is limited understanding of how parental migration influences children over the life course. This study aimed to fill this gap by investigating how exposure to parental migration during childhood shapes later development in Indonesia and the Philippines, two major labor-sending countries in Southeast Asia.

The COVID-19 pandemic's impact on UK social workers working with people with learning disabilities: A mixed methods study.

The impact of the COVID-19 pandemic on the health and wellbeing of social workers working with people with learning disabilities has not been fully explored. This paper reports findings from a large United Kingdom study that surveyed health and care workers in six phases of the pandemic and shortly thereafter (2020-23) relating to 310 social workers who worked with people with learning disabilities. Mann-Whitney U tests revealed that these social workers experienced a decline in wellbeing over the pandemic period, but this lessened as time passed.

Effects of noise and metabolic cost on cortical task representations.

Cognitive flexibility requires both the encoding of task-relevant and the ignoring of task-irrelevant stimuli. While the neural coding of task-relevant stimuli is increasingly well understood, the mechanisms for ignoring task-irrelevant stimuli remain poorly understood. Here, we study how task performance and biological constraints jointly determine the coding of relevant and irrelevant stimuli in neural circuits.

Highly accurate real-space electron densities with neural networks.

Variational ab initio methods in quantum chemistry stand out among other methods in providing direct access to the wave function. This allows, in principle, straightforward extraction of any other observable of interest, besides the energy, but, in practice, this extraction is often technically difficult and computationally impractical. Here, we consider the electron density as a central observable in quantum chemistry and introduce a novel method to obtain accurate densities from real-space many-electron wave functions by representing the density with a neural network that captures known asymptotic properties and is trained from the wave function by score matching and noise-contrastive estimation.

Advances in the Release of Amide-Containing Molecules.

The ability to release a molecule from a larger construct in a controlled manner is of great importance to produce effective prodrugs, antibody-drug conjugates, and chemical probes. Amides are ubiquitous functional groups and yet methods to utilise them as molecular release handles are seldom reported. This concept article highlights the advances made in amide release strategies and how these approaches have been utilised.

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.

Dynamic photosynthetic labeling and carbon-positional mass spectrometry monitor in vivo Rubisco carbon assimilation rates.

RIBULOSE-1,5-BISPHOSPHATE CARBOXYLASE/OXYGENASE (RUBISCO) is the most abundant enzyme and CO2 bio-sequestration system on Earth. Its in vivo activity is usually determined by 14CO2 incorporation into 3-phosphoglycerate (3PGA). However, the radiometric analysis of 3PGA does not distinguish carbon positions.

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.

Germ cell quantification in human fetal and prepubertal testis tissues - a comparison of current methodologies.

Methods to quantify germ cell number in human immature testicular tissues are essential to evaluate the impact of chemotherapy exposures and for optimising cryopreservation protocols used in fertility preservation for prepubertal boys. Established quantification methods rely on the presence of round tubules within the tissue. However, round tubular cross sections are limited in human prepubertal testicular tissues, especially when using in vitro culture.