Proof-of-concept Study of Blood Markers of Tumor Dissemination in Patients With Versus Without Intestinal Polyps
Ontology highlight
ABSTRACT:
DISEASE(S): Intestinal Polyps,Neoplasm Metastasis,Disseminated Cancer,Colorectal Cancer
PROVIDER: 2201 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Today, novel candidate therapeutics are identified in an environment which is intrinsically different from the clinical context in which they are ultimately evaluated. We present a strategy that allows biological relevance to be assessed in the early stages of drug discovery. Using molecular phenotyping and an in vitro model of diabetic cardiomyopathy, we show that by quantifying pathway reporter gene expression, molecular phenotyping can cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes simultaneously. Molecular phenotyping identified a class of calcium-signaling modulators that can reverse disease-regulated pathways and phenotypes, which was validated by structurally distinct compounds of relevant classes. The technique was applicable to compounds with a range of binding specificities and detected false-positive hits missed by classical phenotypic assays. Our results advocate application of molecular phenotyping in drug discovery, promoting biological relevance as a key selection criterion early in the drug development cascade.
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Project description:Infant sociability is generally conceived in terms of dyadic capacities and behaviors. Recently, quantitative evidence has been published to support arguments that infants achieve a criterion for groupness: the capacity to interact simultaneously with two others. Such studies equate this capacity with alternating dyadic acts to the two other members of an interacting trio. Here we propose a stricter threefold criterion for infant groupness, of which the crux is whether the social behavior of an infant at time B is shown to be influenced by what two or more group-members were previously doing at time A. We test the viability of this conceptualization: (a) through its justification of the novel laboratory procedure of studying infant sociability in infant-peer quartets (rather than trios); and, (b) in an analysis of a pilot study of gaze-behavior recorded in 5-min interactions among two quartets of infants aged 6-9 months. We call this a 'proof of concept' because our aim is to show that infants are capable of groupness, when groupness is conceptualized in a supra-dyadic way-not that all infants will manifest it, nor that all conditions will produce it, nor that it is commonplace in infants' everyday lives. We found that both quartets did achieve the minimum criterion of groupness that we propose: mutual gaze predicting coordinated gaze (where two babies, A and B, are looking at each other, and B is then looked at by C, and sometimes D) more strongly than the reverse. There was a significant absence of 'parallel mutual gaze,' where the four babies pair off. We conclude that, under specific conditions, preverbal infants can manifest supra-dyadic groupness. Infants' capacities to exhibit groupness by 9 months of age, and the paucity of parallel mutual gaze in our data, run counter to the assumption that infant sociability, when in groups, is always generated by a dyadic program. Our conceptualization and demonstration of groupness in 8-month-olds thus opens a host of empirical, theoretical, and practical questions about the sociability and care of young babies.
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Project description:In this proof-of-concept study, spatial transcriptomics combined with public single-cell RNA sequencing data were used to explore the potential of this technology to study kidney allograft rejection. We aimed to map gene expression patterns within diverse pathological states by examining biopsies classified across non-rejection, T cell-mediated acute rejection, and interstitial fibrosis and tubular atrophy (IFTA). Our results revealed distinct immune cell signatures, including those of T and B lymphocytes, monocytes, mast cells, and plasma cells, and their spatial organization within the renal interstitium. We also mapped chemokine receptors and ligands to study immune-cell migration and recruitment. Finally, our analysis demonstrated differential spatial enrichment of transcription signatures associated with kidney allograft rejection across various biopsy regions. Interstitium regions displayed higher enrichment scores for rejection-associated gene expression patterns than did tubular areas, which had negative scores. This implies that these signatures are primarily driven by processes unfolding in the renal interstitium. Overall, this study highlights the value of spatial transcriptomics for revealing cellular heterogeneity and immune signatures in renal transplant biopsies, and demonstrates its potential for studying the molecular and cellular mechanisms associated with rejection. However, certain limitations must be borne in mind regarding the development and future applications of this technology.
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Project description:BackgroundMultiple symptoms of suicide risk have been assessed based on visual and auditory information, including flattened affect, reduced movement, and slowed speech. Objective quantification of such symptomatology from novel data sources can increase the sensitivity, scalability, and timeliness of suicide risk assessment.ObjectiveWe aimed to examine measurements extracted from video interviews using open-source deep learning algorithms to quantify facial, vocal, and movement behaviors in relation to suicide risk severity in recently admitted patients following a suicide attempt.MethodsWe utilized video to quantify facial, vocal, and movement markers associated with mood, emotion, and motor functioning from a structured clinical conversation in 20 patients admitted to a psychiatric hospital following a suicide risk attempt. Measures were calculated using open-source deep learning algorithms for processing facial expressivity, head movement, and vocal characteristics. Derived digital measures of flattened affect, reduced movement, and slowed speech were compared to suicide risk with the Beck Scale for Suicide Ideation controlling for age and sex, using multiple linear regression.ResultsSuicide severity was associated with multiple visual and auditory markers, including speech prevalence (β=-0.68, P=.02, r2=0.40), overall expressivity (β=-0.46, P=.10, r2=0.27), and head movement measured as head pitch variability (β=-1.24, P=.006, r2=0.48) and head yaw variability (β=-0.54, P=.06, r2=0.32).ConclusionsDigital measurements of facial affect, movement, and speech prevalence demonstrated strong effect sizes and linear associations with the severity of suicidal ideation.
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2022-07-31 | GSE173359 | GEO
Project description:Nanoparticles have been making their way in biomedical applications and personalized medicine, allowing for the coupling of diagnostics and therapeutics into a single nanomaterial-nanotheranostics. Gold nanoparticles, in particular, have unique features that make them excellent nanomaterials for theranostics, enabling the integration of targeting, imaging and therapeutics in a single platform, with proven applicability in the management of heterogeneous diseases, such as cancer. In this review, we focus on gold nanoparticle-based theranostics at the lab bench, through pre-clinical and clinical stages. With few products facing clinical trials, much remains to be done to effectively assess the real benefits of nanotheranostics at the clinical level. Hence, we also discuss the efforts currently being made to translate nanotheranostics into the market, as well as their commercial impact.
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2018-12-21 | GSE109514 | GEO
Project description:BACKGROUND:Friedreich's ataxia is an autosomal recessive, severely incapacitating disorder. There is little objective evidence regarding FRDA management. Abnormalities in the insulin/insulin-like growth factor 1 (IGF-1) system (IIS) signalling pathway were thought to play a role in the physiopathological processes of various neurodegenerative disorders, including spinocerebellar ataxias. The objective of the study was to test the safety, tolerability, and efficacy of therapy with IGF-1 in Friedreich's ataxia (FRDA) patients in a clinical pilot study. RESULTS:A total of 4 females and 1 male were included in the study; 23 to 36 years of age (average 26.6?±?5.4), diagnosed with FRDA with normal ventricular function. Patients were treated with IGF-1 therapy with 50 ?g/kg twice a day subcutaneously for 12 months. The efficacy of this therapy was assessed by changes from baseline on the scale for the assessment and rating of ataxia, (SARA) and by changes from baseline in echocardiogram parameters. The annual worsening rate (AWR) was estimated in this series as a SARA score of -0.4?±?0.83 (CI 95%: -1.28 to 0.48) SARA score, whereas the AWR for our FRDA cohort was estimated as a SARA score of 2.05?±?1.23 (CI 95%: 1.58 to 2.52). Echocardiographic parameters remained normal and stable. CONCLUSION:Our results seem to indicate a benefit of this IGF-1 therapy to neurological functions in FRDA.
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