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AbstractBoth individuals and organizations extensively use the internet and social media for communications and other purposes in the present era. The study examines the impact of social media effectiveness on informativeness and communication. It also explores the effect of informativeness and communication on the recruitment process. The study also examined the mediating roles of informativeness and communication and the moderating role of social presence. The study has focused on the banking sector of Karachi, Pakistan. The study’s enumerators distributed 450 questionnaires to the HR departments of the targeted banks and received 427 valid questionnaires. For data analysis, the study used Smart PLS version 3.2. It includes reliability, validity analyses, and generating a structural model for testing the hypotheses. The study’s results support seven hypotheses and reject one hypothesis. The study found that social media positively affect informativeness, communication, and recruitment. The study also validated the (i) mediating role of informativeness on social media effectiveness and (ii) the mediating role of communication on social media effectiveness and recruitment process. The study also supported the positive moderating roles of social presence on informativeness and the recruitment process, but it failed to support that social presence positively moderates communication and the recruitment process.

Damage mechanics play an important role in the analysis of rock deformation and failure. Numerous damage variables have been proposed and the corresponding continuum damage models were suggested. Knowing how to apply these theoretical models appropriately in numerical simulations is the key to whether they can be adopted to solve practical problems. The continuum damage models were grouped into empirical damage models, statistical damage models, and elastoplastic damage models in this article. Their applicability and limitations were studied according to some numerical simulations of the most basic uniaxial compression test of a cylinder rock sample. Three representative damage models were chosen from the literature and applied to FEM numerical simulations by introducing a self-developed program. The stress-strain curves due to damage were obtained from the numerical simulation results and compared to those from the experimental results. The damage distribution and evolution of different damage models were investigated to evaluate their influences on rock deformation. It can be concluded that strain-softening stages presented by both the empirical damage models and the statistical damage models are caused by subtracting the elastic modulus gradually while those presented by the elastoplastic damage models are caused by reducing plastic yield stress gradually. Damage-elastic coupling cannot well reflect the irreversibility of damage. The elastoplastic damage models combine damage with plastic history, and thus the irreversibility of damage can be represented. Furthermore, the compulsory reduction of the elastic modulus can probably lead to extreme element distortion and even an unreasonable negative modulus when damage is very serious, which inevitably causes the numerical simulation to fail prematurely under complex stress states. Although the elastoplastic damage models are recommended at present rather than the other models, a more appropriate definition of the damage variable can be expected that should track the whole deformation and failure process. Knowing how to treat the adverse effect of local deterioration due to damage is the challenge numerical simulations have to face when they are applied in the actual project with complex stress states.

Even when the maximum stress is less than the peak stress under conventional loading, fatigue failure of rock is likely to occur, thereby showing its unique characteristics. The present study summarized the factors affecting rock fatigue life from the perspective of phenomenology and studied the fatigue damage process of rock from the microscopic perspective. However, the meso-mechanical mechanism of fatigue–tension failure of rocks is still not very clear, and there are few studies on rock fatigue life that use meso-crack propagation models. In this paper, a mesoscopic model considering wing crack propagation is introduced to examine the fatigue failure of sandstone. A fatigue life prediction formula of sandstone was deduced via a combination with the Paris formula. This formula can quantitatively characterize the impact of upper limit stress and lower limit stress on the fatigue life of sandstone and explain the reason why upper limit stress has a greater influence on the fatigue process of sandstone. Such a prediction formula is applicable only under the condition of low confining pressures, which mainly cause tensile failure due to mesoscopic wing crack propagation. Acoustic emission signals during fatigue failure were monitored and then analyzed using a clustering method and a moment tensor inversion method. Therefore, the tensile or shear properties of mesoscopic failure could be distinguished according to acoustic emission characteristics in different stages of fatigue crack propagation. The results showed that crack sources causing sandstone fatigue failure are mainly tension-type when confining pressure is less than 10 MPa, which further verifies the proposed prediction model of sandstone fatigue life under low confining pressures.

Trying to reveal the mechanism of gas seepage in coal is of significance to both safe mining and methane exploitation. A series of FEM numerical models were built up and studied so as to explore the mesoscale mechanism of seepage in coal fractures. The proposed mesoscale FEM model is a cube with micron fractures along three orthogonal directions. The distribution of velocity and pressure under fluid-solid coupling was obtained, and furthermore, the seepage flow flux and an equivalent permeability of the whole model were calculated. The influences of fracture width, outlet velocity, and in situ stress level on seepage were investigated. The numerical results show that nonlinear Darcy seepage occurs during low velocity zone. The permeability is increased linearly with the increasing of facture width and outlet velocity. A certain change of lateral coefficient of in situ stress also affects seepage. The permeability is increased sharply once deviating the isotropic spherical stress state, but it is no longer changed obviously after the lateral coefficient has been increased or decreased more than 20%. The mesoscale seepage mechanism in coal fractures has been preliminarily revealed by considering fluid-solid coupling effect, and the key factors influencing fluid seepage in coal fractures were demonstrated. The proposed methods and results will be helpful to the further study of seepage behaviour in coal with more complex structures.

Producing a sufficient volume of multiscale crack networks is key to enhancing recovery of shale gas. The formation of crack network largely depends on initiation and propagation of microcracks. To reveal the influence of different loading methods on the propagation of mineral-scale microcracks, this study used the Voronoi tessellation technique to establish a cohesive zone model of shale mineral distribution and applied six different boundary conditions to represent different loading methods. Crack path characteristics, rupture characteristics, continuous crack propagation and turning, and en echelon intermittent crack propagation under different loading methods were compared and analyzed. The essence of different loading methods affecting the length and complexity of cracks was the spreading range of tensile microcracks. The mechanical properties of minerals led to dissimilarities in continuous crack propagation and turning. The formation and propagation of en echelon intermittent fractures of different scales were mainly impacted by the heterogeneity of minerals and mineral aggregates. The spreading direction and connection form of en echelon intermittent fractures were mainly affected by the loading method. Conclusions arising from mineral-scale simulations contribute to understanding the mechanism of microcrack propagation resulting from different loading methods, and these conclusions have a guiding significance to enhanced shale gas recovery.

This study explored the preliminary structural characteristics and in vivo anti-tumor activity of an acidic water-soluble polysaccharide (BCP) separated purified from Bupleurum chinense DC root. The preliminary structural characterization of BCP was established using UV, HPGPC, FT-IR, IC, NMR, SEM, and Congo red. The results showed BCP as an acidic polysaccharide with an average molecular weight of 2.01 × 103 kDa. Furthermore, we showed that BCP consists of rhamnose, arabinose, galactose, glucose, and galacturonic acid (with a molar ratio of 0.063:0.788:0.841:1:0.196) in both α- and β-type configurations. Using the H22 tumor-bearing mouse model, we assessed the anti-tumor activity of BCP in vivo. The results revealed the inhibitory effects of BCP on H22 tumor growth and the protective actions against tissue damage of thymus and spleen in mice. In addition, the JC-1 FITC-AnnexinV/PI staining and cell cycle analysis have collectively shown that BCP is sufficient to induce apoptosis and of H22 hepatocarcinoma cells in a dose-dependent manner. The inhibitory effect of BCP on tumor growth was likely attributable to the S phase arrest. Overall, our study presented significant anti-liver cancer profiles of BCP and its promising therapeutic potential as a safe and effective anti-tumor natural agent.

A common problem in cold regions is the influence of freeze–thaw damage on the stability of rock engineering. Therefore, a series of uniaxial compression tests of sandstone after freeze–thaw treatment was carried out in this study. The purpose was to express the initial damage of rock after freezing and thawing treatment more quantitatively and to study the influence of freeze–thaw damage on the rock crack growth process to provide some reference for the stability evaluation of rock engineering in cold regions. The results showed that the number of freeze–thaw cycles and the lowest freeze–thaw temperature had a significant effect on the rock damage and characteristic stress value, and the number of cycles had a more obvious effect: with an increase in the number of freeze–thaw cycles and a decrease in the freeze–thaw temperature, the initial damage DNT had an increasing trend. In addition, the intrinsic mechanism of the freeze–thaw effect on the rock characteristic stress was explained from the perspective of a meso-mechanical mechanism. From the inversion results of the acoustic emission (AE) moment tensor, it was found that the proportion of tensile cracks gradually increased with the increase in the initial damage of the rock in the stable and unsteady stages of the rock crack propagation.

Abstract Background Many approaches have been developed to overcome technical noise in single cell RNA-sequencing (scRNAseq). As researchers dig deeper into data—looking for rare cell types, subtleties of cell states, and details of gene regulatory networks—there is a growing need for algorithms with controllable accuracy and fewer ad hoc parameters and thresholds. Impeding this goal is the fact that an appropriate null distribution for scRNAseq cannot simply be extracted from data in which ground truth about biological variation is unknown (i.e., usually). Results We approach this problem analytically, assuming that scRNAseq data reflect only cell heterogeneity (what we seek to characterize), transcriptional noise (temporal fluctuations randomly distributed across cells), and sampling error (i.e., Poisson noise). We analyze scRNAseq data without normalization—a step that skews distributions, particularly for sparse data—and calculate p values associated with key statistics. We develop an improved method for selecting features for cell clustering and identifying gene–gene correlations, both positive and negative. Using simulated data, we show that this method, which we call BigSur (Basic Informatics and Gene Statistics from Unnormalized Reads), captures even weak yet significant correlation structures in scRNAseq data. Applying BigSur to data from a clonal human melanoma cell line, we identify thousands of correlations that, when clustered without supervision into gene communities, align with known cellular components and biological processes, and highlight potentially novel cell biological relationships. Conclusions New insights into functionally relevant gene regulatory networks can be obtained using a statistically grounded approach to the identification of gene–gene correlations.

Aims: Rotator cuff disease (RCD) can considerably decrease quality of life. Here, we investigated whether health-related quality of life (HRQoL) influences the need for surgery in patients with RCD. Methods: We performed an analysis of 417 patients with symptomatic RCD who were recruited from two hospitals between June 2008 and December 2014 to be randomized to receive non-surgical or surgical treatment. After a three-month rehabilitation period, 36-Item Short-Form Health Survey questionnaire (SF-36), shoulder pain (visual analogue scale (VAS)), and shoulder function (Constant-Murley score) data were available from 191 still-symptomatic patients who were eligible for surgery. A control group was formed from 87 excluded patients who were no longer eligible for surgery due to relief of symptoms. Results: Mean pain on the VAS was 51.3 (SD 20.1) in the patients eligible for surgery and 41.7 (SD 21.2) in the control group. The following domains of the SF-36 were associated with being eligible for surgery in univariate analyses: bodily pain, general health, vitality, social functioning, and emotional wellbeing. In multivariate analysis, only bodily pain was associated with pursuing surgical treatment. The RCD population’s values for physical role, bodily pain, and physical functioning were poorer compared to the values of the general population. Conclusion: Lower HRQoL, as indicated by the lower bodily pain score on the SF-36, was associated with the decision to undergo surgical treatment in patients with RCD. Therefore, HRQoL should be considered when determining treatment options for RCD. Cite this article: Bone Jt Open 2024;5(9):793–799.

Abstract Complex neutrosophic soft groups represent a significant advancement in handling uncertainty by integrating the concepts of fuzzy logic, soft sets, and neutrosophic logic. These groups generalize complex fuzzy soft groups and introduce an additional dimension through neutrosophic membership functions, namely truth, indeterminacy, and falsity. This creates a richer framework for dealing with uncertainty and ambiguity, making it well-suited for managing complex data structures in real-world applications. We explore some important definitions and theoretical frameworks surrounding complex neutrosophic soft groups, highlighting the unique aspect of neutrosophic membership functions. Additionally, we present an overview of neutrosophic soft groups, exploring some of their key operations and fundamental properties. We then examine the basics of homogeneous complex neutrosophic soft sets and their roles in establishing complex neutrosophic soft groups.

Introduction: The global rise in ageing populations poses challenges for healthcare systems. By 2030, Singapore anticipates a quarter of its population to be aged 65 or older. This study addresses the dearth of research on frailty’s impact on emergency laparotomy (EL) outcomes in this demographic, emphasising the growing significance of this surgical intervention. Method: Conducted at 2 tertiary centres in Singapore from January to December 2019, a retrospective cohort study examined EL outcomes in patients aged 65 or older. Frailty assessment, using the Clinical Frailty Scale (CFS), was integrated into demographic, diagnostic and procedural analyses. Patient data from Tan Tock Seng Hospital and Khoo Teck Puat Hospital provided a comprehensive view of frailty’s role in EL. Results: Among 233 participants, 26% were frail, revealing a higher vulnerability in the geriatric population. Frail individuals exhibited elevated preoperative risk, prolonged ICU stays, and significantly higher 90-day mortality (21.3% versus 6.4%). The study illuminated a nuanced connection between frailty and adverse outcomes, underlining the critical need for robust predictive tools in this context. Conclusion: Frailty emerged as a pivotal factor influencing the postoperative trajectory of older adults undergoing EL in Singapore. The integration of frailty assessment, particularly when combined with established metrics like P-POSSUM, showcased enhanced predictive accuracy. This finding offers valuable insights for shared decision-making and acute surgical unit practices, emphasising the imperative of considering frailty in the management of older patients undergoing emergency laparotomy.

The article focuses on optimization strategies for trans cranial magnetic stimulation (TMS) in treating Major Depressive Disorder (MDD). It explores various TMS techniques, including high-frequency TMS, bilateral TMS, accelerated TMS, deep TMS, priming TMS and synchronized TMS, highlighting their efficacy in enhancing treatment outcomes for MDD.

Abstract Background Preoperative carbohydrate loading in Enhanced Recovery After Surgery is an independent predictor of postoperative outcomes. By reducing the impact of surgical stress response, fasting-induced insulin resistance is modulated. As a clear fluid, consuming carbohydrate drink is safe up to 2 h preoperatively. Widely practiced in abdominal surgeries, its implementation in hip fracture surgeries is yet to be recognized. This study aimed to identify the feasibility of preoperative carbohydrate loading in hip fracture surgery and assess its clinical effects. Methods This was a randomized controlled, open labelled trial. Patients ≥ 65 years old without diabetes mellitus, has hip fracture were recruited in a tertiary hospital between November 2020 and May 2021. The intervention was carbohydrate loading versus standard preoperative fasting. Results Thirty-four ASA I-III patients (carbohydrate loading and control, n = 17 each), mean age 78 years (SEM ± 1.5), mean body mass index 23.7 (SEM ± 0.6 kg/m2) were recruited. Analysis for feasibility of carbohydrate loading (n = 17) demonstrated attrition rate of 29% (n = 5). Otherwise, all recruited patients were compliant (100% compliance) with no adverse events reported. There was no significant difference among groups in the postoperative nausea and vomiting, pain score, fatigue level, muscle strength, postoperative infection and length of hospital stay assessed at 24–48 h postoperatively. Conclusion The implementation of preoperative carbohydrate loading was found to be feasible preoperatively in hip fracture surgeries but requires careful coordination among multidisciplinary teams. An adequately powered randomized controlled study is needed to examine the full benefits of preoperative carbohydrate loading in this group of patients. Trial registration This study was registered in ClinicalTrial.gov (ClinicalTrials.gov identifier: NCT04614181, date of registration: 03/11/2020).

Abstract Sound is sensed by the ear but can also be felt on the skin, by means of vibrotactile stimulation. Only little research has addressed perceptual implications of vibrotactile stimulation in the realm of music. Here, we studied which perceptual dimensions of music listening are affected by vibrotactile stimulation and whether the spatial segregation of vibrations improves vibrotactile stimulation. Forty-one listeners were presented with vibrotactile stimuli via a chair’s surfaces (left and right arm rests, back rest, seat) in addition to music presented over headphones. Vibrations for each surface were derived from individual tracks of the music (multi condition) or conjointly by a mono-rendering, in addition to incongruent and headphones-only conditions. Listeners evaluated unknown music from popular genres according to valence, arousal, groove, the feeling of being part of a live performance, the feeling of being part of the music, and liking. Results indicated that the multi- and mono vibration conditions robustly enhanced the nature of the musical experience compared to listening via headphones alone. Vibrotactile enhancement was strong in the latent dimension of ‘musical engagement’, encompassing the sense of being a part of the music, arousal, and groove. These findings highlight the potential of vibrotactile cues for creating intensive musical experiences.

Shockmounts in naval applications are used to mount technical equipment onto the structure of naval vessels. The insulating effect against mechanical shock is important here, as it can excite the structure in the event of underwater explosions and otherwise cause damage to the equipment. Although knowledge of the dynamic properties of shockmounts is important to naval architects, the dynamic force-displacement characteristics of shockmounts are often tested and measured statically and/or in the harmonic field. Recently, an inertia-based method and a dynamic model for measuring the dynamic force-displacement characteristics of shockmounts was described. This paper presents a full description of a testbench for implementing this method. The testbench incorporates a drop table for excitation. The proposed setup can be configured for measuring the dynamic characteristics of elastomer and wire rope shockmounts, with shock loads in compression, tension, shear and roll directions. The advanced Kelvin–Voigt model for shockmounts is applied, showing that the dynamic force-displacement characteristics measured with this setup are qualified to generate model parameters for further use.

IntroductionType 2 diabetes (T2D) onset, progression and outcomes differ substantially between individuals. Multi-omics analyses may allow a deeper understanding of these differences and ultimately facilitate personalised treatments. Here, in an unsupervised “bottom-up” approach, we attempt to group T2D patients based solely on -omics data generated from plasma.MethodsCirculating plasma lipidomic and proteomic data from two independent clinical cohorts, Hoorn Diabetes Care System (DCS) and Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS), were analysed using Similarity Network Fusion. The resulting patient network was analysed with Logistic and Cox regression modelling to explore relationships between plasma -omic profiles and clinical characteristics.ResultsFrom a total of 1,134 subjects in the two cohorts, levels of 180 circulating plasma lipids and 1195 proteins were used to separate patients into two subgroups. These differed in terms of glycaemic deterioration (Hazard Ratio=0.56;0.73), insulin sensitivity and secretion (C-peptide, p=3.7e-11;2.5e-06, DCS and GoDARTS, respectively; Homeostatic model assessment 2 (HOMA2)-B; -IR; -S, p=0.0008;4.2e-11;1.1e-09, only in DCS). The main molecular signatures separating the two groups included triacylglycerols, sphingomyelin, testican-1 and interleukin 18 receptor.ConclusionsUsing an unsupervised network-based fusion method on plasma lipidomics and proteomics data from two independent cohorts, we were able to identify two subgroups of T2D patients differing in terms of disease severity. The molecular signatures identified within these subgroups provide insights into disease mechanisms and possibly new prognostic markers for T2D.

Abstract Objectives The aim of the study was to investigate computed tomography-based thermography (CTT) for ablation zone prediction in microwave ablation (MWA). Methods CTT was investigated during MWA in an in vivo porcine liver. For CTT, serial volume scans were acquired every 30 s during ablations and every 60 s immediately after MWA. After the procedure, contrast-enhanced computed tomography (CECT) was performed. After euthanasia, the liver was removed for sampling and further examination. Color-coded CTT maps were created for visualization of ablation zones, which were compared with both CECT and macroscopy. Average CT attenuation values in Hounsfield units (HU) were statistically correlated with temperatures using Spearman’s correlation coefficient. CTT was retrospectively evaluated in one patient who underwent radiofrequency ablation (RFA) treatment of renal cell carcinoma. Results A significant correlation between HU and temperature was found with r = − 0.77 (95% confidence interval (CI), − 0.89 to − 0.57) and p

Abstract The human plasma lipidome captures risk for cardiometabolic diseases. To discover new lipid-associated variants and understand the link between lipid species and cardiometabolic disorders, we perform univariate and multivariate genome-wide analyses of 179 lipid species in 7174 Finnish individuals. We fine-map the associated loci, prioritize genes, and examine their disease links in 377,277 FinnGen participants. We identify 495 genome-trait associations in 56 genetic loci including 8 novel loci, with a considerable boost provided by the multivariate analysis. For 26 loci, fine-mapping identifies variants with a high causal probability, including 14 coding variants indicating likely causal genes. A phenome-wide analysis across 953 disease endpoints reveals disease associations for 40 lipid loci. For 11 coronary artery disease risk variants, we detect strong associations with lipid species. Our study demonstrates the power of multivariate genetic analysis in correlated lipidomics data and reveals genetic links between diseases and lipid species beyond the standard lipids.

Pseudomonas aeruginosa is the most commonly isolated Gram-negative pathogen causing sight-threatening microbial keratitis (MK). Contact lens wear is the most significant risk factor associated with pseudomonal MK. Understanding the pathogenesis of MK due to P. aeruginosa and its interactions with contact lenses is crucial in preventing these often rapidly progressive and highly antibiotic-resistant infections. Bacterial virulence factor Type III secretion system (T3SS) has significant interplays between contact lens material, antibiotic sensitivity, disinfectant selectivity, and bacterial cell invasion. Depending on the T3SS exotoxins produced, P. aeruginosa strains are divided into cytotoxic or invasive strains. Cytotoxic strains are relatively resistant to commercial disinfectants, while invasive strains are more antibiotic resistant. Therefore, contact lens wearers are more predisposed to cytotoxic P. aeruginosa infections, and patients with trauma or previous surgery are more prone to infection by invasive strains. Previous studies with mutant P. aeruginosa strains unable to produce T3SS exotoxins were more susceptible to disinfectants and less able to adhere to soft contact lenses, indicating an essential role of T3SS in bacterial virulence. Invasion of P. aeruginosa intracellularly was found to be associated with control of scaffold protein IQ-domain GTPase-activating protein 1 (IQGAP1) and human corneal epithelial cell tight junctions. Knockdown of IQGAP1 strengthened tight junctions that prevented intracellular survival of invasive P. aeruginosa strains and enhanced corneal epithelial cell survival. These novel findings of the vital role of T3SS in the pathogenesis of pseudomonal MKs will provide new guidelines in both prevention and treatment of this common eye-blinding infection. [ABSTRACT FROM AUTHOR]

A perforated peptic ulcer (PPU) is a surgical emergency with a high mortality rate. PPUs cause secondary peritonitis due to bacterial and fungal peritoneal contamination. Surgery is the main treatment modality and patient’s comorbidites impacts perioperative morbidity and surgical outcomes. Even after surgery, resuscitation efforts should continue. While empiric antibiotics are recommended, the role of empiric anti-fungal treatment is unclear due to a lack of scientific evidence. This literature review demonstrated a paucity of studies evaluating the role of empiric anti-fungals in PPUs, and with conflicting results. Studies were heterogeneous in terms of patient demographics and underlying surgical pathology (PPUs vs. any gastrointestinal perforation), type of anti-fungal agent, timing of administration and duration of use. Other considerations include the need to differentiate between fungal colonization vs. invasive fungal infection. Despite positive fungal isolates from fluid culture, it is important for clinical judgement to identify the right group of patients for anti-fungal administration. Biochemistry investigations including new fungal biomarkers may help to guide management. Multidisciplinary discussions may help in decision making for this conundrum. Moving forward, further research may be conducted to select the right group of patients who may benefit from empiric anti-fungal use.

Abstract Background Assessment of quality of life (QoL) has become an important indicator for chronic neurological diseases. While these conditions often limit personal independence and autonomy, they are also associated with treatment-related problems and reduced life expectancy. Epilepsy has a tremendous impact on the QoL of patients and their families, which is often underestimated by practitioners. The aim of this work was to identify relevant factors affecting QoL in adults with epilepsy. Methods This cross-sectional, multicenter study was conducted at four specialized epilepsy centers in Germany. Patients diagnosed with epilepsy completed a standardized questionnaire focusing on QoL and aspects of healthcare in epilepsy. Univariate regression analyses and pairwise comparisons were performed to identify variables of decreased QoL represented by the overall Quality of Life in Epilepsy Inventory (QOLIE-31) score. The variables were then considered in a multivariate regression analysis after multicollinearity analysis. Results Complete datasets for the QOLIE-31 were available for 476 patients (279 [58.6%] female, 197 [41.4%] male, mean age 40.3 years [range 18–83 years]). Multivariate regression analysis revealed significant associations between low QoL and a high score on the Liverpool Adverse Events Profile (LAEP; beta=-0.28, p

Abstract We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine and 2-aminoadipic acid, eight triacylglycerol species, and lowered sphingomyelin 42:2;2 levels are predictive of faster progression towards insulin requirement. Of ~1,300 proteins examined in two cohorts, levels of GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 are associated with faster progression, whilst SMAC/DIABLO, SPOCK1 and HEMK2 predict lower progression rates. In an external replication, proteins and lipids are associated with diabetes incidence and prevalence. NogoR/RTN4R injection improved glucose tolerance in high fat-fed male mice but impaired it in male db/db mice. High NogoR levels led to islet cell apoptosis, and IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. This comprehensive, multi-disciplinary approach thus identifies biomarkers with potential prognostic utility, provides evidence for possible disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression.