Disparate molecular mechanisms in cardiac ryanodine receptor channelopathies.

Aims: Mutations in the cardiac ryanodine receptor (RyR2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). This study investigates the underlying molecular mechanisms for CPVT mutations within the RyR2 N-terminus domain (NTD).

Methods And Results: We consulted the high-resolution RyR2 structure in both open and closed configuration to identify mutations G357S/R407I and A77T, which lie within the NTD intra- and inter-subunit interface with the Core Solenoid (CSol), respectively.

Crystal structure and Hirshfeld surface analysis of -(4-nitro-phen-yl)-2-(piperidin-1-yl)acetamide (lidocaine analogue).

In the title mol-ecule, CHNO, the substituents on the phenyl ring are rotated slightly out of the mean plane of the ring but the piperidine moiety is nearly perpendicular to that plane. In the crystal, C-H⋯O hydrogen bonds form chains of mol-ecules extending along the -axis direction, which are linked by C=O⋯π(ring) inter-actions. A Hirshfeld surface analysis showed the majority of inter-molecular inter-actions to be H⋯H contacts while O⋯H/H⋯O contacts are the second most numerous.

Change in frailty status in the 12 months following solid organ transplantation: a systematic review and meta-analysis.

Objectives: To investigate if frailty status alters following solid organ transplantation (lung, liver, kidney and heart) without rehabilitation intervention.

Research Design And Methods: Studies published between 1 January 2000 and 30 May 2023 were searched across five databases. Studies measuring frailty, using a validated or established frailty measure, pre- and post-transplant were included.

Five year mortality in an RCT of a lung cancer biomarker to select people for low dose CT screening.

The role of biomarkers in risk-based early detection of lung cancer may enable screening to become cost effective and widely accessible. EarlyCDT-Lung is an example of such a blood-based autoantibody biomarker which may improve accessibility to Low dose Computed Tomography (LDCT) screening for those at highest risk. We randomized 12 208 individuals aged 50-75 at high risk of developing lung cancer to either the test or to standard clinical care.

Optimization of solar water pumping systems through a combined approach based on MPPT-Bat and DTC.

This paper investigates enhancing the efficiency of solar water pumping systems (SWPS) by implementing a Maximum Power Point Tracking technique based on the Bat Metaheuristic Optimizer (MPPT-bat) for the photovoltaic generator (PVG) side, coupled with Direct Torque Control (DTC) for the induction motor powering the pump. Unlike traditional techniques, which make no compromise between tracking speed, oscillation and robustness. The integration of the MPPT-bat represents a significant advance, making it possible to improve PVG performance whatever the weather conditions.

The impact of published guidance on trends in the pharmacological management of depression in children and adolescents- a whole population e-cohort data linkage study in Wales, UK.

Background: This study evaluated the impact of 2015/2016 prescribing guidance on antidepressant prescribing choices in children.

Methods: A retrospective e-cohort study of whole population routine electronic healthcare records was conducted. Poisson regression was undertaken to explore trends over time for depression, antidepressant prescribing, indications and secondary care contacts.

PoachNet: Predicting Poaching Using an Ontology-Based Knowledge Graph.

Poaching poses a significant threat to wildlife and their habitats, necessitating advanced tools for its prediction and prevention. Existing tools for poaching prediction face challenges such as inconsistent poaching data, spatiotemporal complexity, and translating predictions into actionable insights for conservation efforts. This paper presents PoachNet, a novel predictive system that integrates deep learning with Semantic Web reasoning to infer poaching likelihood.

Thyroid Autoimmunity During Universal Salt Iodisation-Possible Short-Term Modulation with Longer-Term Stability.

Universal salt iodisation (USI) plays an essential role in the provision of iodine (I) to populations worldwide. Countries adopting USI programmes, adhering to strict criteria laid down by expert organisations such as the Iodine Global Network, are estimated to have reduced the prevalence of I deficiency by 75% (protecting 720 million individuals worldwide). Despite this success, doubts have been raised as to the desirability of continuing such programmes because of (a) the need to reduce salt intake for cardiovascular prevention and (b) the induction of thyroid autoimmunity.

α-Synuclein Deletion Impairs Platelet Function: A Role for SNARE Complex Assembly.

Granule secretion is an essential platelet function that contributes not only to haemostasis but also to wound healing, inflammation, and atherosclerosis. Granule secretion from platelets is facilitated, at least in part, by Soluble N-ethylmaleimide-Sensitive Factor (NSF) Attachment Protein Receptor (SNARE) complex-mediated granule fusion. Although α-synuclein is a protein known to modulate the assembly of the SNARE complex in other cells, its role in platelet function remains poorly understood.

Age- and Sex-Based Developmental Biomarkers in Eye Movements.

Background: Eye movement research serves as a critical tool for assessing brain function, diagnosing neurological and psychiatric disorders, and understanding cognition and behavior. Sex differences have largely been under reported or ignored in neurological research. However, eye movement features provide biomarkers that are useful for disease classification with superior accuracy and robustness compared to previous classifiers for neurological diseases.

Agreement of Image Quality Metrics with Radiological Evaluation in the Presence of Motion Artifacts.

Purpose: Reliable image quality assessment is crucial for evaluating new motion correction methods for magnetic resonance imaging. In this work, we compare the performance of commonly used reference-based and reference-free image quality metrics on a unique dataset with real motion artifacts. We further analyze the image quality metrics' robustness to typical pre-processing techniques.

Benchmarking Alzheimer's disease prediction: personalised risk assessment using polygenic risk scores across various methodologies and genome-wide studies.

Background: The success of selecting high risk or early-stage Alzheimer's disease individuals for the delivery of clinical trials depends on the design and the appropriate recruitment of participants. Polygenic risk scores (PRS) show potential for identifying individuals at risk for Alzheimer's disease (AD). Our study comprehensively examines AD PRS utility using various methods and models.

How do early weight trajectories explain social inequalities in lung function in children with cystic fibrosis? A longitudinal interventional disparity effects analysis with time-varying mediators and intermediate confounders.

Background: Children with cystic fibrosis (CF) from socioeconomically deprived areas have poorer growth, worse lung function, and shorter life expectancy than their less-deprived peers. While early growth is associated with lung function around age 6, it is unclear whether improving early growth in the most deprived children reduces inequalities in lung function.

Methods: We used data from the UK CF Registry, tracking children born 2000-2010 up to 2016.

Validation of the International Trauma Interview (ITI) among treatment-seeking people with adverse childhood experiences in South Korea.

The International Trauma Interview (ITI) is a clinician-administered assessment that has been newly developed for the International Classification of Diseases (ICD-11) diagnoses of posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD). The current study evaluated the psychometric properties of the ITI for treatment-seeking people with adverse childhood experiences (ACE) in South Korea, with the aims of verifying the validity and reliability of ITI as well as examining the differentiation of ICD-11 CPTSD and borderline personality disorder (BPD). In total, data of 103 people were analysed.

Refractory fungal infection: Three case reports highlighting good practice.

Refractory invasive fungal disease is a significant clinical problem, with high morbidity, mortality and costs. The complex causes of refractory infection include breakthrough infection due to antifungal resistance (both innate and acquired), suboptimal therapy and impaired immune responses in critically ill or immunocompromised patients. This case series details three reports on the identification and management of refractory fungal infections, two cases of azole resistance and one case of resistant candidiasis, highlighting the importance of accurate diagnosis, monitoring, implementation of biomarkers (serological markers, PCR), antifungal susceptibility testing and antifungal stewardship to optimise management and minimise risks of emergence of drug resistance.

A qualitative exploration of the prospective acceptability of the MiDerm app; a complex digital intervention for adults living with skin conditions.

Objectives: Skin conditions carry a substantial psychological burden but support for patients is limited. Digital technology could support patient self-management; we found preliminary evidence for the effectiveness and acceptability of digital psychological interventions for adults living with skin conditions. We have, therefore, developed a complex digital intervention called MiDerm with patients.

Floral morphological and chemical analyses of Dienia flowers (Orchidaceae, Malaxidinae) relative to pollination processes.

Dienia is a small, pantropical genus of epidendroid Malaxideae orchids. The floral lip is upwardly directed and does not serve as a landing platform for pollinators. This role has been assumed by sepals and/or gynostemium or whole inflorescence.

Synthesis and crystal structure of piperidinyl propanenitrile towards the preparation of piperidine based bioactive films for drug delivery applications.

Compounds containing the piperidine group are highly attractive as building blocks for designing new drugs. Functionalized piperidines are of significant interest due to their prevalence in the pharmaceutical field. Herein, 3-oxo-3-(piperidin-1-yl) propanenitrile has been synthesized, and piperidine-based sodium alginate/poly(vinyl alcohol) films have been prepared.

Design and synthesis of antiproliferative 2-oxoindolin-3-ylidenes incorporating urea function with potential VEGFR-2 inhibitory properties.

Targeted therapy is preferable over other therapeutics due to its limitation of drawbacks and better pharmaceutical outcomes. VEGF and its receptors have been observed to be hyper-activated in many cancer types and are considered promising targets for assigning anticancer agents. The current study is directed towards synthesis of novel antiproliferative 2-oxoindolin-3-ylidenes incorporating urea function with VEGFR-2 properties.

Being "resilient" and achieving "resilience": From governmental discourses to the national research agenda in the contexts of food insecurity and cost of living.

The concept of 'resilience' is pervasive, permeating academic disciplines and political discourses. This paper considers (i) the construal of 'resilience' in the contexts of food insecurity and cost-of-living in governmental discourses in the United Kingdom (UK); (ii) to what extent the political representations are reflected in research funding calls of UK national funding bodies, thus showing possibility of shaping research agendas; and (iii) to what extent official uses of 'resilience' reflect lay understandings. We are combining a corpus-based discourse analysis of UK governmental discourses and research funding calls with a study of focus group discussions.

Using DNA metabarcoding and direct behavioural observations to identify the diet of proboscis monkeys (Nasalis larvatus) in the Kinabatangan Floodplain, Sabah.

Characterizing the feeding ecology of threatened species is essential to establish appropriate conservation strategies. We focused our study on the proboscis monkey (Nasalis larvatus), an endangered primate species which is endemic to the island of Borneo. Our survey was conducted in the Lower Kinabatangan Wildlife Sanctuary (LKWS), a riverine protected area that is surrounded by oil palm plantations.

A Single Bioorthogonal Reaction for Multiplex Cell Surface Protein Labeling.

Small-molecule fluorophores are invaluable tools for fluorescence imaging. However, means for their covalent conjugation to the target proteins limit applications in multicolor imaging. Here, we identify 2-[(alkylhio)(ryl)ethylene]alononitrile (TAMM) molecules reacting with 1,2-aminothiol at a labeling rate over 10 M s through detailed mechanistic investigation.

The use of patient-generated health data in the management of low anterior resection syndrome: a qualitative study.

Background: The cornerstone of low anterior resection syndrome (LARS) treatment is self-management, which requires patient engagement. Colorectal surgeons and nurses may use patient-generated health data (PGHD) to help guide patients in their use of self-management strategies for LARS. However, the perspectives of LARS experts on the use of PGHD remain largely unexplored.

Regulation of meristem and hormone function revealed through analysis of directly-regulated SHOOT MERISTEMLESS target genes.

The Arabidopsis Knotted1-like homeobox (KNOX) gene SHOOT MERISTEMLESS (STM) encodes a homeodomain transcription factor that operates as a central component of the gene regulatory network (GRN) controlling shoot apical meristem formation and maintenance. It regulates the expression of target genes that include transcriptional regulators associated with meristem function, particularly those involved in pluripotency and cellular differentiation, as well as genes involved in hormone metabolism and signaling. Previous studies have identified KNOX-regulated genes and their associated cis-regulatory elements in several plant species.