Site-selective photo-crosslinking for the characterisation of transient ubiquitin-like protein-protein interactions.

Non-covalent protein-protein interactions are one of the most fundamental building blocks in cellular signalling pathways. Despite this, they have been historically hard to identify using conventional methods due to their often weak and transient nature. Using genetic code expansion and incorporation of commercially available unnatural amino acids, we have developed a highly accessible method whereby interactions between biotinylated ubiquitin-like protein (UBL) probes and their binding partners can be stabilised using ultraviolet (UV) light-induced crosslinks.

Comparison of behind-the-ear vs. off-the-ear speech processors in cochlear implants: A systematic review and narrative synthesis.

Background: Cochlear implants (CI) with off-the-ear (OTE) and behind-the-ear (BTE) speech processors differ in user experience and audiological performance, impacting speech perception, comfort, and satisfaction.

Objectives: This systematic review explores audiological outcomes (speech perception in quiet and noise) and non-audiological factors (device handling, comfort, cosmetics, overall satisfaction) of OTE and BTE speech processors in CI recipients.

Methods: We conducted a systematic review following PRISMA-S guidelines, examining Medline, Embase, Cochrane Library, Scopus, and ProQuest Dissertations and Theses.

Using machine learning to forecast peak health care service demand in real-time during the 2022-23 winter season: A pilot in England, UK.

During winter months, there is increased pressure on health care systems in temperature climates due to seasonal increases in respiratory illnesses. Providing real-time short-term forecasts of the demand for health care services helps managers plan their services. During the Winter of 2022-23 we piloted a new forecasting pipeline, using existing surveillance indicators which are sensitive to increases in respiratory syncytial virus (RSV).

"Energetics of the outer retina II: Calculation of a spatio-temporal energy budget in retinal pigment epithelium and photoreceptor cells based on quantification of cellular processes".

The outer retina (OR) is highly energy demanding. Impaired energy metabolism combined with high demands are expected to cause energy insufficiencies that make the OR susceptible to complex blinding diseases such as age-related macular degeneration (AMD). Here, anatomical, physiological and quantitative molecular data were used to calculate the ATP expenditure of the main energy-consuming processes in three cell types of the OR for the night and two different periods during the day.

The metabolite transporters of C4 photosynthesis.

C4 photosynthesis is a highly efficient form of photosynthesis that utilises a biochemical pump to concentrate CO2 around rubisco. Although variation in the implementation of this biochemical pump exists between species, each variant of the C4 pathway is critically dependent on metabolite transport between organelles and between cells. Here we review our understanding of metabolite transport in C4 photosynthesis.

Carbonyl Reductase 1: a novel regulator of blood pressure in Down Syndrome.

Approximately one in every 800 children is born with the severe aneuploid condition of Down Syndrome, a trisomy of chromosome 21. Low blood pressure (hypotension) is a common condition associated with DS and can have a significant impact on exercise tolerance and quality of life. Little is known about the factors driving this hypotensive phenotype and therefore therapeutic interventions are limited.

Characterisation of RNA guanine-7 methyltransferase (RNMT) using a small molecule approach.

The maturation of the RNA cap involving guanosine N-7 methylation, catalyzed by the HsRNMT (RNA guanine-7 methyltransferase)-RAM (RNA guanine-N7 methyltransferase activating subunit) complex, is currently under investigation as a novel strategy to combat PIK3CA mutant breast cancer. However, the development of effective drugs is hindered by a limited understanding of the enzyme's mechanism and a lack of small molecule inhibitors. Following the elucidation of the HsRNMT-RAM molecular mechanism, we report the biophysical characterization of two small molecule hits.

The design of a striking dummy and the theoretical foundations of martial arts strikes.

The aim of the research was to develop the design of a striking dummy and the theoretical foundations of martial arts strikes and to test its effectiveness in a pedagogical experiment. This paper presents the design of a striking dummy and the foundational theories behind martial arts strikes. We used modern microelectronics, including a diverse range of sensors, for executing a multitude of electromechanical measurements.

An MRI assessment of mechanisms underlying lesion growth and shrinkage in multiple sclerosis.

Objective: To assess the pathological mechanisms contributing to white matter (WM) lesion expansion or contraction and remyelination in multiple sclerosis (MS).

Methods: We assessed 1,613 lesions in 49 people with relapsing-remitting MS in the CCMR-One bexarotene trial (EudraCT 2014-003145-99). We measured lesion orientation relative to WM tracts, surface-in gradients and veins.

Termination of Resuscitation Rules for In-Hospital Cardiac Arrest.

Importance: There are no validated decision rules for terminating resuscitation during in-hospital cardiac arrest. Decision rules may guide termination and prevent inappropriate early termination of resuscitation.

Objective: To develop and validate termination of resuscitation rules for in-hospital cardiac arrest.

Negative Pressure Dressings to Prevent Surgical Site Infection After Emergency Laparotomy: The SUNRRISE Randomized Clinical Trial.

Importance: Patients undergoing unplanned abdominal surgical procedures are at increased risk of surgical site infection (SSI). It is not known if incisional negative pressure wound therapy (iNPWT) can reduce SSI rates in this setting.

Objective: To evaluate the effectiveness of iNPWT in reducing the rate of SSI in adults undergoing emergency laparotomy with primary skin closure.

Comparative Efficacy of Nonsteroid Immunosuppressive Medications in Childhood Nephrotic Syndrome.

Importance: Cyclophosphamide and calcineurin inhibitors are the most used nonsteroid immunosuppressive medications globally for children with various chronic inflammatory conditions. Their comparative effectiveness remains uncertain, leading to worldwide practice variation. Nephrotic syndrome is the most common kidney disease managed by pediatricians globally and suboptimal treatment is associated with high morbidity.

Shifting Lithium Amide Reactivity to the Radical Domain: Regioselective Radical C-H Functionalization of 3-Iodooxetane for the Synthesis of 1,5-Dioxaspiro[2.3]hexanes.

Strained spiro-heterocycles (SSH) have gained significant attention within the medicinal chemistry community as promising (sp3)-rich bioisosteres for their aromatic and non-spirocyclic counterparts. We herein report access to an unprecedented spiro-heterocycle - 1,5-dioxaspiro[2.3]hexane.

Engineered Immunomodulatory Extracellular Vesicles from Epithelial Cells with the Capacity for Stimulation of Innate and Adaptive Immunity in Cancer and Autoimmunity.

Extracellular vesicles (EVs) are generated in all cells. Systemic administration of allogenic EVs derived from epithelial and mesenchymal cells has been shown to be safe, despite carrying an array of functional molecules, including thousands of proteins. To address whether epithelial cell-derived EVs can be modified to acquire the capacity to induce an immune response, we engineered 293T EVs to harbor the immunomodulatory molecules CD80, OX40L, and PD-L1.

Patient and Health Professional's Perspectives of Periprosthetic Joint Infection: A Systematic Review and Meta-Ethnography.

Periprosthetic joint infection (PJI) is a major challenge for surgical teams and patients following an orthopedic surgical procedure. There is limited understanding on patient and health professional's perception of PJI. The aim of this study was to examine the literature to better understand the perspectives of patients, and those who manage PJI.

Molecular dynamics investigation of structural, thermal, and dynamic properties of maghemite through thermal cycling.

We analyzed the thermal, structural, and dynamic properties of maghemite using classical molecular dynamics, focusing on bulk and nanoparticle systems. We explored their behavior when heated to high temperatures (above the melting point) and during cooling, as well as under thermal cycles ending at intermediate temperatures. Our findings show that in the bulk system, both the tetrahedral and octahedral iron sub-lattices undergo a phase transition prior to melting.

A Short Cognitive and Neuropsychiatric Assessment Scale for Progressive Supranuclear Palsy.

Background: Patients with Progressive Supranuclear Palsy (PSP) suffer from several neuropsychological impairments. These mainly affect the frontal lobe and subcortical brain structures. However, a scale for the assessment of cognitive and neuropsychiatric disability in PSP is still missing.

Investigating the threat to Sitka spruce from Ips typographus: discrimination and colonization of Britain's principal commercial conifer by a damaging forest pest.

Background: Ips typographus (L.), the eight-toothed spruce bark beetle (Coleoptera: Scolytinae), has devastated European Norway spruce (Picea abies) forests in recent years. For the first time, I.

A locally administered single-cycle influenza vaccine expressing a non-fusogenic stabilized hemagglutinin stimulates strong T-cell and neutralizing antibody immunity.

Unlabelled: Current influenza vaccination approaches protect against specific viral strains, but do not consistently induce broad and long-lasting protection to the diversity of circulating influenza viruses. Single-cycle viruses delivered to the respiratory tract may offer a promising solution as they safely express a diverse array of viral antigens by undergoing just one round of cell infection in their host and stimulate broadly protective resident memory T-cell responses in the lung. We have previously developed a vaccine candidate called S-FLU, which is limited to a single cycle of infection by inactivation of the hemagglutinin signal sequence and induces a broadly cross-reactive T-cell response and antibodies to neuraminidase, but fails to induce neutralizing antibodies to hemagglutinin after intranasal administration.

The diffusible signaling factor family in microbial signaling: a current perspective.

This review discusses the chemical properties, synthesis and detection, and biological functions of a molecular group of cis-2-unsaturated fatty acids, containing fatty acid carbon chains of various lengths and cis double-bond configurations, known as the diffusible signaling factor family (DSFF). Early postulation of the conserved nature of the DSFF among Gram-negative bacteria have now been challenged by the latest evidences that unraveled their presence in a various other distinct microorganisms. Over the last decade, a significant depth and breadth of understanding has been made on the multifaceted functions of DSFFs among bacteria, and their interactions with evolutionarily divergent fungi, plants insects and small animals.

Early-life adversity as a predictor of fibromyalgia syndrome: the central role of perceived stress over endocrine stress indicators.

This study investigates the associations between early childhood adversities, stress perception, and fibromyalgia syndrome (FMS). Although the interconnection between dysregulated stress systems and FMS is well documented, the interconnection between early adversities and FMS remains less understood. This study explores the relationship of early-life stress and FMS by examining its mediation through perceived stress, and acute and chronic endocrine stress indicators.

Avoiding causal fraud in the evaluation of clinical benefits of treatments for Alzheimer's disease.

Recent regulatory approvals of three amyloid-lowering monoclonal antibody therapies for the treatment of Alzheimer's disease (AD) have triggered a polarizing debate in the field on the clinical meaningfulness of their reported effects. The question of how to define clinical meaningfulness for any treatment that has a modest effect size is important and will likely be subject to influence from interested stakeholders. We warn of claims of evaluating meaningful within-individual change from randomized parallel-group trials of AD treatments, sometimes purportedly assessed by a commonly recognized "responder" analysis approach, and explain why it is likely to mislead and should simply be avoided.