Mediate Interactions Research Articles

Exploratory mediation analysis of the effect of semaglutide on cardiovascular outcomes in people with overweight or obesity in the SELECT randomised trial

Abstract Background Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to reduce major adverse cardiovascular (CV) events (MACE) in people with diabetes. The SELECT trial investigated weekly subcutaneous semaglutide 2.4 mg versus placebo in people with pre-existing CV disease and body mass index ≥27kg/m², but without diabetes at randomisation. Over a mean duration of follow-up of 39.8 months, risk of MACE was lower in patients treated with semaglutide vs placebo (6.5% vs 8.0%, hazard ratio, 0.80; 95% CI, 0.72, 0.90; P<0.001). There were improvements in several CV risk factors; however, mechanisms underlying the MACE reduction are unclear. Purpose This prespecified analysis explored whether the effects on measured CV risk factors may mediate the 20% reduction in MACE in SELECT. Methods CV risk factors measured during the trial and included as potential mediators in the analysis were: body weight, waist circumference, high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA1c), lipids, blood pressure, estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). Mediation analyses were performed using the Vansteelandt repeated regression approach. First, the observed difference in MACE-free survival between semaglutide and placebo at 36 months was estimated as the total effect. The direct effect of semaglutide was then estimated as the difference in MACE-free survival, had the semaglutide arm experienced the values of the mediator observed in the placebo arm during follow-up. The % mediation was then calculated as 100 × (1 – [direct effect] / [total effect]). A reversed counterfactual approach estimating the direct effect as the difference between arms in MACE-free survival, had the placebo arm experienced the mediator values observed in the semaglutide arm, was also conducted. A large disparity between the % mediation from the two approaches can indicate potential treatment–mediator interaction or hidden confounding. Results Statistically significant (P<0.05) improvements in all potential mediators were observed with semaglutide. Table 1 shows the estimated mediation of each potential mediator when evaluated separately. Point estimates for the % mediation were largest for waist circumference (64.0%), hsCRP (42.1%), HbA1c (29.0%) and body weight (19.5%), but with wide 95% CIs. For waist circumference, the estimated mediation was markedly lower using the reversed counterfactual approach, suggesting potential hidden confounding or treatment–mediator interaction (Figure 1). In a multivariable analysis, the estimated joint mediation was 31.4% (−30.1%, 143.6%). Conclusions The results suggest that neither change in body weight nor other measured CV risk factors fully explain the effect of semaglutide on MACE in SELECT. Substantial unmeasured pleiotropic effects of semaglutide on MACE not mediated through these risk factors remain possible.

Novel risk loci in LGI1-antibody encephalitis: genome-wide association study discovery and validation cohorts.

Encephalitis with antibodies to leucine-rich glioma-inactivated 1 (LGI1-Ab-E) is a common form of autoimmune encephalitis, presenting with seizures and neuropsychiatric changes, predominantly in older males. More than 90% of patients carry the human leucocyte antigen (HLA) class II allele, HLA-DRB1*07:01. However, this is also present in 25% of healthy controls. Therefore, we hypothesised the presence of additional genetic predispositions. In this genome-wide association study and meta-analysis, we studied a discovery cohort of 131 French LGI1-Ab-E and a validation cohort of 126 American, British and Irish LGI1-Ab-E patients, ancestry-matched to 2613 and 2538 European controls, respectively. Outside the known major HLA signal, we found two single nucleotide polymorphisms (SNPs) at genome-wide significance (p < 5 x 10-8), implicating PTPRD, a protein tyrosine phosphatase, and LINC00670, a non-protein coding RNA gene. Meta-analysis defined four additional non-HLA loci, including the protein coding COBL gene. Polygenic risk scores with and without HLA variants proposed a contribution of non-HLA loci. In silico network analyses suggested LGI1 and PTPRD mediated interactions via the established receptors of LGI1, ADAM22 and ADAM23. Our results identify new genetic loci in LGI1-Ab-E. These findings present opportunities for mechanistic studies and offer potential markers of susceptibility, prognostics and therapeutic responses.

Engineering impurity Bell states through coupling with a quantum bath

We theoretically demonstrate the feasibility of creating Bell states in multicomponent ultracold atomic gases by solely using the ability to control the interparticle interactions via Feshbach resonances. For this we consider two distinguishable impurities immersed in an atomic background cloud of a few bosons, with the entire system being confined in a one-dimensional harmonic trap. By analyzing the numerically obtained ground states we demonstrate that the two impurities can form spatially entangled bipolaron states due to mediated interactions from the bosonic bath. Our analysis is based on calculating the correlations between the two impurities in a two-mode basis, which is experimentally accessible by measuring the particle positions in the left or right sides of the trap. While interspecies interactions are crucial in order to create the strongly entangled impurity states, they can also inhibit correlations depending on the ordering of the impurities and three-body impurity-bath correlations. We show how these drawbacks can be mitigated by manipulating the properties of the bath, namely its size, mass, and intraspecies interactions, allowing one to create impurity Bell states over a wide range of impurity-impurity interactions. Published by the American Physical Society 2024

Taming XeO3 with Aza-Crowns: Computational Studies into σ-Hole Mediated Host-Guest Interactions.

Various aza-crowns with different sizes and substituents have been explored computationally as potential hosts for stabilizing the explosive guest xenon trioxide (XeO3) through σ-hole-mediated aerogen bonding interactions. Interestingly, aza-crowns demonstrate superior binding towards XeO3 compared to their oxygen and thio counterparts. However, unlike the latter cases, where the binding was found to be increasingly favorable with the increase in the size of the crowns, aza-crowns exhibit a variable size preference for XeO3, peaking with aza-15-crown-5, and reducing thereafter with increase in crown size.

Phases and dynamics of few fermionic impurities immersed in two-dimensional boson droplets

We unravel the ground state properties and emergent nonequilibrium dynamics of a mixture consisting of a few spin-polarized fermions embedded in a two-dimensional bosonic quantum droplet. For an increasingly attractive droplet-fermion interaction we find a transition from a spatially delocalized fermion configuration to a state where the fermions are highly localized and isolated. This process is accompanied by the rise of induced fermion-fermion interactions mediated by the droplet. Additionally, for increasing attractive droplet-fermion coupling, undulations in the droplet density occur in the vicinity of the fermions manifesting the back-action of the latter. Following interaction quenches from strong to weaker attractive droplet-fermion couplings reveals the spontaneous nucleation of complex excitation patterns in the fermion density such as ring- and cross-shaped structures. These stem from the enhanced interference of the fermions that remain trapped within the droplet, which emulates, to a good degree, an effective potential for the fermions. The non-negligible back-action of the droplet manifests itself in the fact that the effective potential predictions are less accurate at the level of the many-body wave function. Our results provide a paradigm for physics beyond the reduced single-component droplet model, unveiling the role of back-action in droplets and the effect of induced mediated interactions. Published by the American Physical Society 2024

ScreenDMT reveals DiHOMEs are replicably inversely associated with BMI and stimulate adipocyte calcium influx

Activating brown adipose tissue (BAT) improves systemic metabolism, making it a promising target for metabolic syndrome. BAT is activated by 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), which we previously identified to be inversely associated with BMI and which directly improves metabolism in multiple tissues. Here we profile plasma lipidomics from 83 people and test which lipids’ association with BMI replicates in a concordant direction using our novel tool ScreenDMT, whose power and validity we demonstrate via mathematical proofs and simulations. We find that the linoleic acid diols 12,13-diHOME and 9,10-diHOME are both replicably inversely associated with BMI and mechanistically activate calcium influx in mouse brown and white adipocytes in vitro, which implicates this signaling pathway and 9,10-diHOME as candidate therapeutic targets. ScreenDMT can be applied to test directional mediation, directional replication, and qualitative interactions, such as identifying biomarkers whose association is shared (replication) or opposite (qualitative interaction) across diverse populations.

Urban residential greenness and cancer mortality: Evaluating the causal mediation role of air pollution in a large cohort

Evidence linking greenness to all-site and site-specific cancers remains limited, and the complex role of air pollution in this pathway is unclear. We aimed to fill these gaps by using a large cohort in southern China. A total of 654,115 individuals were recruited from 2009 to 2015 and followed-up until December 2020. We calculated the normalized difference vegetation index (NDVI) in a 500-m buffer around the participants’ residences to represent the greenness exposure. Cox proportional-hazards models were used to evaluate the impact of greenness on the risk of all-site and site-specific cancer mortality. Additionally, we assessed both the mediation and interaction roles of air pollution (i.e., PM2.5, PM10, and NO2) in the greenness–cancer association through a causal mediation analysis using a four-way decomposition method. Among the 577,643 participants, 10,088 cancer deaths were recorded. We found a 10% (95% CI: 5–16%) reduction in all-site cancer mortality when the NDVI increased from the lowest to the highest quartile. When stratified by cancer type, our estimates suggested 18% (95% CI: 8–27%) and 51% (95% CI: 16–71%) reductions in mortality due to respiratory system cancer and brain and nervous system cancer, respectively. For the above protective effect, a large proportion could be explained by the mediation (all-site cancer: 1.0–27.7%; respiratory system cancer: 1.2–32.3%; brain and nervous system cancer: 3.6–109.1%) and negative interaction (all-site cancer: 2.1–25.7%; respiratory system cancer: 2.0–25.7%; brain and nervous system cancer: not significant) effects of air pollution. We found that particulate matter (i.e., PM2.5 and PM10) had a stronger causal mediation effect (25.0–109.1%) than NO2 (1.0–3.6%), while NO2 had a stronger interaction effect (25.7%) than particulate matter (2.0–2.8%). In summary, greenness was significantly beneficial in reducing the mortality of all-site, respiratory system, and brain and nervous system cancer in southern China, with the impact being modulated and mediated by air pollution.

Re-conceptualising communicative expertise in professional practice through the lens of sign language intercultural mediation

The Candlin Lecture When we consider language, communication and the professions, we know that talk (speech or signs) is critical to professional practice and to relationships between professionals and service users. In a multilingual and multicultural world where people do not share the same languages or language repertoires, they must either adapt the way they talk to others (intercultural communication) or, if they cannot communicate directly, allow others to mediate communication on their behalf – a process labelled intercultural mediation. The latter occurs through professional or non-professional interpreting or language brokering. Current theories in interpreting studies consider (professional) interpreters as co-constructors of meaning and co-participants in any interaction. Communicative expertise is usually conceptualized in direct, monolingual communication. Using an explorative illustrative case study, this paper extends this theoretical framework to examine how communicative expertise manifests in interpreter-mediated communication, and particularly in relational aspects of intercultural mediation between a signed language and a spoken language and how professional interpreters and non-professional interpreters (brokers) draw on and apply their expert or lay knowledge about communication in a mediated interaction.

Association Between education and walking speed: counterfactual mediation analysis in favor of a motor reserve hypothesis.

We quantified the extent to which the association between education and fast walking speed (FWS) is explained by 17 mediators (cardiovascular risk factors/diseases, comorbidities, health behaviours, socio-professional characteristics, cognition), and examined whether mediators interact with education, in favor of a reserve hypothesis. Cross-sectional analyses are based on Constances (population-based study of French adults 45-69y). 3m-FWS was measured using photoelectric cells. Education was categorized as lower/higher. After multiple imputation of missing values, we used counterfactual mediation models for multiple mediators allowing for education×mediator interactions, to estimate the total effect (TE), total indirect effect (TIE), and mediated interaction (IMD) of lower education on FWS. Analyses are based on 71,222 participants (52.6% women; mean age=57.2y; 27.2% higher education; mean FWS=180.2cm/s). In joint mediation analyses, the TE of lower education was -8.19cm/s (95% confidence interval [CI]=-8.87;-7.51), with a TIE of -5.76cm/s (95%CI=-6.10;-5.41; proportion mediated=70.3%, 95%CI=65.6;75.0). The IMD was negative (-2.52, 95%CI=-3.31;-1.72); 30.8% of the TE and 43.8% of the TIE were attributable to the IMD. Several mediators explain a large part of the association between lower education and slower FWS. The detrimental effect of mediators was more pronounced in participants with lower than in those with higher education, in agreement with a reserve hypothesis.

Guide to Decomposition of Causal Effects Into Mediation, Interaction, and Direct Effects: Case Study on Aerobic Exercise and Parkinson Disease.

Mediation analysis can be applied in medical research with the aim of understanding the pathways that operate between an exposure and its effects on an outcome. This method can help to improve our understanding of pathophysiologic mechanisms and may guide the choice of potential treatment strategies. Traditional mediation analysis decomposes the total effect of an intervention on the outcome into 2 effects: (1) an indirect effect, from exposure using a mediator to the outcome, and (2) a direct effect, directly from exposure to outcome. A limitation of this method is that it assumes no interaction between the exposure and the mediator, which can either lead to an over- or underestimation of clinically relevant effects. The "4-way decomposition" method has the advantage of overcoming this limitation. Specifically, the total effect of an exposure on the outcome is decomposed into 4 elements: (1) reference interaction (interaction only), (2) mediated interaction (mediation and interaction), (3) the pure indirect effect (mediation but not interaction), and (4) the direct effect (no mediation and no interaction). We provide a guide to select the most appropriate method to investigate and decompose any causal effect given the research question at hand. We explain the application of the 4-way decomposition and illustrate this with a real-world example of how aerobic exercise may influence motor function in persons with Parkinson disease.

A distinct subset of urothelial cells with enhanced EMT features promotes chemotherapy resistance and cancer recurrence by increasing COL4A1-ITGB1 mediated angiogenesis

Drug resistance and tumor recurrence remain clinical challenges in the treatment of urothelial carcinoma (UC). However, the underlying mechanism is not fully understood. Here, we performed single-cell RNA sequencing and identified a subset of urothelial cells with epithelial-mesenchymal transition (EMT) features (EMT-UC), which is significantly correlated with chemotherapy resistance and cancer recurrence. To validate the clinical significance of EMT-UC, we constructed EMT-UC like cells by introducing overexpression of two markers, Zinc Finger E-Box Binding Homeobox 1 (ZEB1) and Desmin (DES), and examined their histological distribution characteristics and malignant phenotypes. EMT-UC like cells were mainly enriched in UC tissues from patients with adverse prognosis and exhibited significantly elevated EMT, migration and gemcitabine tolerance in vitro. However, EMT-UC was not specifically identified from tumorous tissues, certain proportion of them were also identified in adjacent normal tissues. Tumorous EMT-UC highly expressed genes involved in malignant behaviors and exhibited adverse prognosis. Additionally, tumorous EMT-UC was associated with remodeled tumor microenvironment (TME), which exhibited high angiogenic and immunosuppressive potentials compared with the normal counterparts. Furthermore, a specific interaction of COL4A1 and ITGB1 was identified to be highly enriched in tumorous EMT-UC, and in the endothelial component. Targeting the interaction of COL4A1 and ITGB1 with specific antibodies significantly suppressed tumorous angiogenesis and alleviated gemcitabine resistance of UC. Overall, our findings demonstrated that the driven force of chemotherapy resistance and recurrence of UC was EMT-UC mediated COL4A1-ITGB1 interaction, providing a potential target for future UC treatment.

An IDR-dependent mechanism for nuclear receptor control of Mediator interaction with RNA polymerase II

The essential Mediator (MED) coactivator complex plays a well-understood role in regulation of basal transcription in all eukaryotes, but the mechanism underlying its role in activator-dependent transcription remains unknown. We investigated modulation of metazoan MED interaction with RNA polymerase II (RNA Pol II) by antagonistic effects of the MED26 subunit and the CDK8 kinase module (CKM). Biochemical analysis of CKM-MED showed that the CKM blocks binding of the RNA Pol II carboxy-terminal domain (CTD), preventing RNA Pol II interaction. This restriction is eliminated by nuclear receptor (NR) binding to CKM-MED, which enables CTD binding in a MED26-dependent manner. Cryoelectron microscopy (cryo-EM) and crosslinking-mass spectrometry (XL-MS) revealed that the structural basis for modulation of CTD interaction with MED relates to a large intrinsically disordered region (IDR) in CKM subunit MED13 that blocks MED26 and CTD interaction with MED but is repositioned upon NR binding. Hence, NRs can control transcription initiation by priming CKM-MED for MED26-dependent RNA Pol II interaction.

Toward Programmable Quantum Processors Based on Spin Qubits with Mechanically Mediated Interactions and Transport.

Solid-state spin qubits are promising candidates for quantum information processing, but controlled interactions and entanglement in large, multiqubit systems are currently difficult to achieve. We describe a method for programmable control of multiqubit spin systems, in which individual nitrogen-vacancy (NV) centers in diamond nanopillars are coupled to magnetically functionalized silicon nitride mechanical resonators in a scanning probe configuration. Qubits can be entangled via interactions with nanomechanical resonators while programmable connectivity is realized via mechanical transport of qubits in nanopillars. To demonstrate the feasibility of this approach, we characterize both the mechanical properties and the magnetic field gradients around the micromagnet placed on the nanobeam resonator. We demonstrate coherent manipulation of a spin qubit in the proximity of a transported micromagnet by utilizing nuclear spin memory and use the NV center to detect the time-varying magnetic field from the oscillating micromagnet, extracting a spin-mechanical coupling of 7.7(9)Hz. With realistic improvements, the high-cooperativity regime can be reached, offering a new avenue toward scalable quantum information processing with spin qubits.

Internal Communication Quality in a Telecommuting Context: A Phenomenological Exploration of Telecommuters’ Communication Experiences

Information and Communication Technologies (ICT) mediated interactions, such as audio and video calls, are part of all companies’ routines. Despite technological advances, no current ICT can perfectly mimic the unique characteristics of face-to-face interactions. As good-quality internal communication is critical to companies’ operations, the increased demand for work-from-home jobs raises relevant questions regarding employees’ capability to communicate properly. To better understand if the physical and temporal distance associated with the work-from-home represents a threat to employees’ capacity to establish clear communications, this study explores the internal communication experiences of full-time home-based telecommuters. Adopting a transcendental phenomenological strategy and based on a mix of purposeful and snowball sampling, 23 employees were interviewed online. Two additional interviews with top managers from a company where all employees work from home were also performed. Following a thematic analysis, results did not reveal a direct relationship between physical and temporal distance and the quality of internal communication. Indeed, the increased media options adopted by employees after starting to work from home contributed to improving internal communication quality. The main identified communication issues, such as information segregation, are related to how internal communications are managed, and may happen whether employees work side-by-side or physically apart.

What Eyeblinks Reveal: Interpersonal Synchronization in Dyadic Interaction

This study examines eyeblink synchronization in interactions characterized by mutual gaze without task-related or conversational elements that can trigger similarities in visual, auditory, or cognitive processing. We developed a study design capable of isolating the role of gaze in human-human interaction and observed the blinking behavior of dyads with mobile eye tracking glasses under three conditions: face-to-face mutual gaze, mediated mutual gaze through a mirror, and self-directed gaze in a mirror. The results revealed that when the interaction was through direct mutual gaze, eyeblink synchronization increased concurrently with a more structured temporal pattern. Also, the sense of connection between partners mimicked the synchronization. These findings suggest that even minor deviations caused by mediated interaction lead to reduced synchronization and a weakened sense of connection among partners. The paper also discusses the need for methodologies to enhance the efficacy and authenticity of online environments and human-robot interaction.

Greening the Path: The Three-Way Interactive Effects of Psychological Ownership, Green Knowledge Sharing, and Social Media

ABSTRACT This study develops an integrated framework grounded in service-dominant logic theory to examine green destination psychological ownership, customer engagement, knowledge sharing, and social media usage as drivers of green electronic word of mouth. A multi-wave survey analysis conducted among 507 Vietnamese travelers supported the hypothesized direct effect, mediation, and three-way interaction between the factors. The results revealed that green customer engagement mediates the relationship between green destination psychological ownership and word of mouth. Additionally, companies’ green knowledge sharing and travelers’ social network proneness strengthen the positive influence of ownership feelings on engagement, subsequently enhancing word of mouth. The findings contribute novel insights into integrated green marketing effects, with implications for leveraging customer psychology and behaviors to promote green word of mouth. By fostering ownership feelings, actively sharing sustainability knowledge, and understanding social media habits, tourism organizations can enhance participation in green initiatives and recommendations. This study advances the theoretical and practical understanding of strategies for nurturing green behaviors and outcomes in the digital age through an integrated framework grounded in service-dominant logic theory. Further research should investigate additional variables and contexts to deepen knowledge on enabling collaborative value creation for sustainability.

The effect of parental age on child development at 36 months: Insights from the Japan environment and children's study

BackgroundThe impact of parent-childbearing age on child development at 36 months of age is controversial. AimsWe used data from a large cohort study with multiple imputation and mediation analyses of variables. Methods and ProceduresA total of 72,606 parent–child pairs from the Japan Environment and Children's Study were included in the study. Parents' ages were categorized into five groups. We used five domains of the Japanese translation of the Ages and Stages Questionnaire, Third Edition (J-ASQ-3). Scores below the cutoff value at 36 months were defined as developmental delays in each domain. We used three logistic analysis models. In Model 3, we analyzed maternal and paternal age using other variables and covariates. Outcomes and ResultsThe outcome was a developmental delay in the five domains of J-ASQ-3. In Model 3, ORs for the developmental delay scores regarding parental age were significantly associated with all five domains of J-ASQ-3. The mediation analysis showed a significant mediation interaction effect for mothers but localized for fathers. ConclusionAdvanced paternal and maternal ages were associated with developmental delay in children. Awareness of the risks of childbearing at an advanced age is crucial. What’s the paper addsThis manuscript used data from a large cohort study with multiple imputation and mediation analyses. With these analyses, we identified the pure effect of advanced parental age on their children’s development at 36 months.

The biology of classical Hodgkin lymphoma

Classical Hodgkin lymphoma (cHL) is distinguished by several important biological characteristics. The presence of Hodgkin Reed Sternberg (HRS) cells is a defining feature of this disease. The tumor microenvironment with relatively few HRS cells in an expansive infiltrate of immune cells is another key feature. Numerous cell-cell mediated interactions and a plethora of cytokines in the tumor microenvironment collectively work to promote HRS cell growth and survival. Aberrancy and constitutive activation of core signal transduction pathways are a hallmark trait of cHL. Genetic lesions contribute to these dysregulated pathways and evasion of the immune system through a variety of mechanisms is another notable feature of cHL. While substantial elucidation of the biology of cHL has enabled advancements in therapy, increased understanding in the future of additional mechanisms driving cHL may lead to new treatment opportunities.

Plasma proteomic biomarkers and the association between poor cardiovascular health and incident dementia: The UK Biobank study

BackgroundThe study examined how plasma proteome indicators may explain the link between poor cardiovascular health (CVH) and dementia risk. MethodsThe present study involved 28,974 UK Biobank participants aged 50-74y at baseline (2006–2010) who were followed-up for ≤ 15 y for incidence of dementia. CVH was calculated using Life’s Essential 8 (LE8) total scores. The scores were standardized and reverse coded to reflect poor CVH (LE8z_rev). OLINK proteomics was available on this sample (k = 1,463 plasma proteins). The study primarily tested the mediating effects of the plasma proteome in LE8z_rev-dementia effect. The total effect was decomposed into “mediation only” or pure indirect effect (PIE), “interaction only” or interaction referent (INTREF), “neither mediation nor interaction” or controlled direct effect (CDE), and “both mediation and interaction” or mediated interaction (INTMED). ResultsThe study found poorer CVH assessed by LE8z_rev increased the risk of all-cause dementia by 11 % [per 1 SD, hazard ratio, (HR) = 1.11, 95 % CI: 1.03–1.20, p = 0.005). The study identified 11 plasma proteins with strong mediating effects, with GDF15 having the strongest association with dementia risk (per 1 SD, HR = 1.24, 95 % CI: 1.16, 1.33, P < 0.001 when LE8z_rev is set at its mean value) and the largest proportion mediated combining PIE and INTMED (62.6 %; 48 % of TE is PIE), followed by adrenomedullin or ADM. A first principal component with 10 top mediators (TNFRSF1A, GDF15, FSTL3, COL6A3, PLAUR, ADM, GFRAL, ACVRL1, TNFRSF6B, TGFA) mediated 53.6 % of the LE8z_rev-dementia effect. Using all the significant PIE (k = 526) proteins, we used OLINK Insight pathway analysis to identify key pathways, which revealed the involvement of the immune system, signal transduction, metabolism, disease, protein metabolism, hemostasis, membrane trafficking, extracellular matrix organization, developmental biology, and gene expression among others. STRING analysis revealed that five top consistent proteomic mediators were represented in two larger clusters reflecting numerous interconnected biological gene ontology pathways, most notably cytokine-mediated signaling pathway for GDF15 cluster (GO:0019221) and regulation of peptidyl-tyrosine phosphorylation for the ADM cluster (GO:0050730). ConclusionDementia is linked to poor CVH mediated by GDF15 and ADM among several key proteomic markers which collectively explained ∼ 54 % of the total effect.

Chitosan lecithin nanocomposite based electrochemical biosensor for glycine detection in biological matrices

Increased glycine concentrations are associated with altered metabolism of cancer cells and is reflected in the bodily fluids of the brain cancer patients. Various studies have been conducted in past to detect glycine as an imaging biomarker via NMR Spectroscopy tools. However, the use is limited because of the low concentration and different in vivo detection due to overlapping of peaks with myo-inositol in same spectral position. Alongside, little is known about the electrochemical potential of Glycine as a biomarker for brain cancer. The prime impetus of this study was to check the feasibility of glycine as non-invasive biomarker for brain cancer. A divergent approach to detect glycine “non-enzymatically” via unique chitosan lecithin nanocomposite has been utilised during this study. The electrochemical inactivity at provided potential that prevented glycine to get oxidized or reduced without mediator was compensated utilising the chitosan-lecithin nanocomposite. Thus, a redox mediator (Prussian blue) was used for high sensitivity and indirect detection of glycine. The chitosan nanoparticles-lecithin nanocomposite is used as a matrix. The electrochemical analysis of the onco-metabolomic biomarker (glycine) utilizing cyclic voltammetry in glycine spiked multi-Purpose artificial urine was performed to check distribution of glycine over physiological range of glycine. A wide linear range of response varying over the physiological range from 7 to 240 μM with a LOD 8.5 μM was obtained, showing potential of detection in biological samples. We have further evaluated our results via simulating the interaction of mediator and matrix with Glycine by HOMO-LUMO band fluctuations.