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Profiler: an open web platform for multi-omics analysis.

MOTIVATION: High-throughput multi-omics technologies produce increasingly large and heterogeneous datasets that are difficult to analyze without advanced computational expertise. Existing bioinformatics tools are often fragmented or limited to specific omics types, hindering reproducibility and accessibility. There is a critical need for an integrated, user-friendly, and scalable platform capable of supporting multi-omics analyses across different data modalities. RESULTS: We present Profiler, an open-source, modular platform that unifies data import, quality control, preprocessing, statistical testing, machine and deep learning, biomarker discovery, pathway and drug-target enrichment, and survival modeling within a single reproducible environment. Built in Python with Streamlit, Profiler is available as both a web-based platform deployed on high-performance computing and a desktop version for local execution, enabling flexible usage across computational infrastructures. Profiler supports diverse omics modalities, including proteomics, transcriptomics, lipidomics, and electroencephalogram data. Through applications to glioblastoma proteomic, pancancer, and multi-omics datasets, Profiler reproduced known molecular subtypes, revealed potential therapeutic targets, and generated fully traceable analysis reports within minutes. By integrating advanced analytics behind an intuitive interface, Profiler democratizes multi-omics analysis and provides a robust, scalable foundation for systems biology and precision medicine research. AVAILABILITY AND IMPLEMENTATION: Profiler is open-source and freely available via its web platform (https://prism-profiler.univ-lille.fr) and GitHub (web version: https://github.com/yanisZirem/Profiler_v1_requests_datatests, desktop version: https://github.com/yanisZirem/prism-profiler), and archived on Zenodo (DOI: https://doi.org/10.5281/zenodo.17478158).

Software

Long-term outcomes of top-down therapy versus a conventional step-up strategy in adults newly diagnosed with Crohn's disease: 5-year follow-up of the PROFILE trial.

BACKGROUND: The PROFILE trial previously reported better 48-week outcomes for patients with Crohn's disease who received top-down anti-TNF treatment from diagnosis, compared with a conventional step-up strategy. Through subsequent follow-up of PROFILE participants, we aimed to assess whether the benefit of top-down treatment from diagnosis results in modification of the long-term disease course. METHODS: PROFILE was a multicentre, open-label, randomised controlled trial completed in 40 hospitals in the UK, which included patients aged 16-80 years with newly diagnosed Crohn's disease. Eligible patients were randomly assigned via a secure online platform to a top-down (infliximab plus immunomodulator) or a step-up protocolised treatment strategy for 48 weeks, after which participants reverted to local standards of care. Objective outcome data were extracted for up to 5 years after the week 48 visit, including need for Crohn's-related abdominal surgery as the primary outcome. Data were analysed based on the original PROFILE randomisation and intention-to-treat population. Participants without long-term follow-up data were censored at the week 48 visit. Time-to-event analyses were performed using the Kaplan-Meier method and Cox proportional hazards model. The trial was registered with the ISRCTN registry, number 11808228 and is complete. FINDINGS: Between Dec 29, 2017, and Jan 5, 2022, 483 patients were assessed for inclusion. 389 patients were enrolled and randomly assigned (three patients were excluded due to ineligibility), 193 to top-down treatment and 193 to step-up treatment. Of the 386 participants in the PROFILE primary trial, 358 (93%) had post-week 48 records available for review (182 [51%] top-down and 176 [49%] step-up). Median follow-up was approximately 5 years from randomisation (1809 days [IQR 1300-2101]), by which point 172 (89%) of 193 patients in the step-up group and 191 (99%) of 193 patients in the top-down group had received biological or immunomodulator therapy. Relating to the primary outcome, during follow-up there were 28 Crohn's disease-related abdominal surgeries in 26 patients treated with a step-up approach versus six surgeries in six patients treated with a top-down approach. Time to surgery was shorter in the step-up group than the top-down group (adjusted hazard ratio [aHR] 5·23 [95% CI 1·99-13·76]; p=0·0008). For the secondary outcomes, incidence of Crohn's disease-related hospital admissions was higher in patients originally managed with step-up treatment versus top-down treatment (41 [21%] of 193 patients vs 22 [11%] of 193 patients); and time to first hospital admission was shorter with step-up treatment than with top-down treatment (aHR 2·01 [95% CI 1·18-3·41], p=0·017). Progression to B2 or B3 complications was also more frequent in those originally managed with step-up treatment compared with top-down treatment (32 [17%] of 192 patients vs 13 [7%] of 193 patients); with time to disease progression being shorter in the step-up group than in the top-down group (aHR 2·46 [95% CI 1·25-4·86]; p=0·010). There was no difference in safety outcomes between groups for either serious infections (12 [6%] of 193 step-up patients and 14 [7%] of 193 top-down patients) or malignancies (five patients [3%] and three patients [2%] respectively). INTERPRETATION: Early top-down anti-TNF treatment from diagnosis was associated with improved long-term outcomes at 5 years compared with step-up treatment and is suggestive of a disease-modifying effect in Crohn's disease. FUNDING: Wellcome and Celltrion.

Journal Article

Integrative Multiomics and Drug Sensitivity Profiling Reveal Potential Biomarkers and Therapeutic Strategies in Pediatric Solid Tumors.

UNLABELLED: Cure rates for childhood malignancies using established therapy protocols have increased to an average of 80% but have reached a plateau. Moreover, survival rates are particularly low for some pediatric tumors-such as high-risk group 3 medulloblastomas, osteosarcomas, Ewing sarcomas, high-risk neuroblastomas, and high-grade gliomas-and dismal for patients with relapsed malignancies. A functional drug response profiling platform for pediatric solid and brain tumors has been established within the INFORM program to identify patient-specific vulnerabilities and biomarkers and to unravel molecular mechanisms associated with drug response profiles for clinical translation. In this study, we performed a multiomics analysis using drug sensitivity profiles, as well as genomic and transcriptomic data, of 81 pediatric solid tumor samples. The integrative analysis suggested two multiomics signatures associated with drug sensitivity. One signature distinguished neuroblastoma samples with sensitivity to navitoclax, a BCL2 family inhibitor. A second signature was specific to a subset of Wilms tumors harboring the SIX1 (Q177R) hotspot mutation that displayed high expression of MGAM, PTPN14, STAT4, and KDM2B and high sensitivity to MEK inhibitors. A patient-specific causal interaction network analysis suggested possible molecular interactions between MEK inhibitors and the SIX1 mutation in Wilms tumor samples. In conclusion, the integration of drug sensitivity profiling and multiomics data revealed potential biomarkers that may be associated with drug sensitivity in pediatric solid tumors. Patient-specific causal interaction network analysis further elucidated the interaction between inhibitors and signature biomarkers, providing insights that may inform clinical translation. SIGNIFICANCE: The combination of multiomics analysis and drug sensitivity profiling identified two signatures related to drug sensitivity in pediatric solid tumors, contributing to the advancement of functional precision medicine and personalized treatment strategies. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI .

Humans

Genomic profiling and expanded use of targeted anticancer drugs in solid cancers with exhausted evidence-based treatment options (PRECODE): study protocol of a prospective, non-randomized, cohort study.

BACKGROUND: Genomic profiling of advanced solid cancer in patients with no further evidence based standard treatment options is a novel approach to identify potential experimental treatment options based on specific genomic alterations. Due to the expected short survival of these patients timely assessment of potential druggable targets is critical to minimize the risk of deterioration during the analysis. The primary objective of this prospective study is to evaluate the turnaround time for genomic profiling and the clinical investigational procedures. The secondary objectives are to investigate how often genomic alterations in tumor tissue gives rise to a matched treatment offer and evaluate the clinical outcome. METHODS: The PRECODE study is a prospective, non-randomized, single-center cohort study conducted at Departments of Oncology and Pathology, Odense University Hospital, Denmark. Enrollment between March 1, 2019 and December 31, 2024. Eligibility criteria are age ≥ 18 years, written informed consent, advanced solid tumors, exhausted treatment options, ECOG performance status 0-2, adequate organ function and life expectancy ≥ 3 months. A core needle biopsy is analyzed by next generation sequencing using a pan-cancer comprehensive panel. Results are discussed weekly at institutional/local and national multidisciplinary tumor boards. DISCUSSION: Strategies and methods for genomic profiling of advanced solid cancers differ. Rapid analysis and interpretation of sequencing data are key to avoiding delays in initiation potential experimental treatments, as these late-stage patients may quickly deteriorate. Although a highly optimized setup with fast-track clinical evaluation and genomic profiling has been established a subset will not be offered a targeted treatment due to deterioration. Local and national multidisciplinary teams have been established to optimize individualized treatment decisions. After genomic profiling a subset of patients will take part in clinical trials, which will constrain the reporting of overall survival or progression free survival. TRIAL REGISTRATION: Danish Ethics Committee, Projekt-ID: S-2018014, date of approval: 27- FEB- 2019) Danish Data Protection Agency (Journal no: 18/58329, date of approval: 23-NOV-2018). CLINICALTRIALS: gov Identifier: NCT05385081 (retrospectively registered).

Humans

Spinal low-grade ependymal tumors harboring telomerase reverse transcriptase promoter mutation and chromosome 7 gain with methylation profile of spinal subependymoma.

Spinal intramedullary tumors comprise a heterogeneous group of entities with diverse histopathological features, making their diagnosis particularly challenging. With the introduction of DNA methylation profiling, the underlying biological diversity of these tumors has been increasingly clarified and systematized; however, owing to the rarity of these tumors, case accumulation remains limited, and significant challenges persist. In this study, we identified two cases of spinal ependymal tumors exhibiting a methylation profile of spinal (SP-) subependymoma (SEPN). Both cases occurred in elderly patients and demonstrated circumscribed growth consistent with low-grade ependymal tumors; however, these tumors did not exhibit the typical histopathological features required for a diagnosis of SEPN in the 2021 WHO classification of central nervous system (CNS) tumors, showing indistinct cluster formation, an astrocytic immunohistochemical profile suggested by Olig2 expression, and relatively elevated Ki-67 labeling indices of 4.5% and 3.1%. At the molecular level, both cases harbored telomerase reverse transcriptase promoter mutations and whole chromosome 7 gain. On two-dimensional t-distributed stochastic neighbor embedding analysis, both clustered within the SP-SEPN methylation class at its periphery, with low classifier calibration scores (0.70 and 0.69). According to the current WHO classification, these cases are designated as low-grade ependymal tumors (CNS WHO grade 2) with methylation profile of SP-SEPN because they do not meet the essential WHO histopathological criteria. Ependymal tumors exhibiting a methylation profile consistent with SEPN, but discordant histopathological features have been increasingly recognized, and the appropriate classification of such tumors remains a subject of ongoing debate. These cases provide important insights into the histopathological diversity of ependymal tumors and contribute to establishing a more comprehensive and systematic classification of ependymal tumors.

Aged

Meningioma methylation profiling as a complement to WHO grading: a single-center experience.

OBJECTIVE: The methylation profile of meningiomas is a promising predictive tool that may improve risk stratification beyond WHO grading. This study aimed to evaluate the clinical relevance and real-world applicability of routine epigenetic testing in meningioma management. METHODS: The authors retrospectively analyzed patients who underwent meningioma resection between January 2021 and December 2023. Histopathological grading (WHO 2021) and methylation profiling (methylation class [MC]) with the MethylationEPIC v1.0 (850k) chip were performed by an independent neuropathologist. RESULTS: A total of 106 patients were included; 81 tumors (76%) were classified as WHO grade 1, 20 (19%) as grade 2, and 5 (5%) as grade 3. Epigenetically, 55 tumors (52%) were classified as benign, 18 (17%) as intermediate, and 2 (2%) as malignant; 31 (29%) could not be classified. Discordances between WHO grading and methylation profiling were observed in 18 of 74 cases. Tumor board decisions were made after a median of 8 days postoperatively, guided by WHO grading; however, the epigenetic report was only available after a median of 23 days. During follow-up, 20 patients experienced tumor progression. Progression was significantly associated with the MC (r = -0.4, p < 0.001) and tumor volume (r = 0.4, p = 0.0005), but not with WHO grading (r = 0.17, p = 0.084). However, the relatively high rate of unclassified tumors and delayed result availability limited the direct impact of MC profiling on immediate clinical decision-making. Interestingly, progression-free survival in MC-unclassified tumors mirrored that of the intermediate group. CONCLUSIONS: Methylation profiling demonstrates superior predictive accuracy for meningioma progression and complements WHO grading, especially in identifying malignant meningiomas. However, its current clinical utility is constrained by technical and logistical limitations. In real-world practice, epigenetic classification should therefore be considered a complementary tool rather than a replacement for established histopathological assessment.

Humans

Proteomic Profile in Retinopathy of Prematurity: A Secondary Analysis of the Mega Donna Mega Randomized Clinical Trial.

IMPORTANCE: Identifying early proteomic profiles in infants who develop severe retinopathy of prematurity (ROP) may reveal targets for preventive interventions to reduce retinal vessel loss and the subsequent risk of severe ROP. OBJECTIVE: To assess early longitudinal profiles of blood protein levels in preterm infants with or without severe ROP and the effect of arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation. DESIGN, SETTING, AND PARTICIPANTS: This was an exploratory, post hoc analysis of serum proteome profiles in preterm infants in the double-masked Mega Donna Mega (MDM) randomized clinical trial using targeted Olink Proximity Extension Assay proteomics covering 538 analytes. The setting was 3 university hospitals in Sweden and included extremely preterm infants born before 28 weeks of gestational age (GA), from 2016 to 2019. Data were analyzed from January to March 2025. EXPOSURES: All infants received standard nutrition; additionally, half received enteral lipid supplementation with AA/DHA (100/50 mg/kg per day) from birth to term equivalent age. MAIN OUTCOMES AND MEASURES: Longitudinal protein profiles during the first month of life were examined using mixed models for repeated measures, adjusted for GA, study center, and AA/DHA supplementation, and tested for the interaction between severe ROP (stage &#x2265;3 and/or treated) and postnatal age. RESULTS: A total of 177 extremely preterm infants (mean [SD] GA, 25.6 [1.4] weeks; 100 male [56.5%]) were included, of whom 50 (28.2%) developed severe ROP. Of 538 longitudinal analyzed proteins, 109 protein profiles in the first month of life associated with severe ROP, proteins related to immune response, apoptotic processes, blood coagulation, and lipid metabolism. The most pronounced association with severe ROP was a fast rise in fibroblast growth factor 21 (FGF-21; &#x3b2;&#x2009;=&#x2009;0.68; 95% CI,&#x2009;0.39-0.97; Q =.002) and tissue plasminogen activator (tPA; &#x3b2;&#x2009;=&#x2009;0.21; 95% CI,&#x2009;0.13-0.29; Q <.001) during the first postnatal days. The increase in serum FGF-21 level in the first week of life was associated with lower GA, lower birth weight, low enteral energy intake, and more days receiving mechanical ventilation. No association was observed between AA/DHA supplementation and the proteome. CONCLUSIONS AND RELEVANCE: In this post hoc exploratory analysis of data from the MDM randomized clinical trial, a fast rise in FGF-21 levels, a metabolic stress-induced hormone, during the first postnatal days was strongly associated with the development of severe ROP in extremely preterm infants. These findings suggest that early interventions improving bioenergetic status may help prevent severe ROP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03201588.

Humans

Saliva and salivary pellicle composition and proteomic profile in smokers vs. non-smokers and its effect on dental erosion.

OBJECTIVE: To analyse the salivary composition and proteomic profile of saliva and the salivary pellicle in smokers compared to non-smokers, and to examine potential differences in the erosion-protective capacity of the salivary pellicle. METHODS: Twenty-five smokers and 25 non-smokers were included. Unstimulated and stimulated saliva samples were analysed regarding flow rate, pH, buffer capacity, calcium, phosphate, fluoride, and protein content. Saliva and salivary pellicle samples were analysed by data-independent acquisition mass spectrometry (DIA-MS) for proteome profiling. In an in situ experiment, intraoral splints were loaded with bovine enamel and dentine specimens for 120 min. Pellicle-covered specimens were extraorally eroded (HCl, pH 2.3, 60 s). Calcium release was determined photometrically and compared to pellicle-free controls. RESULTS: Except for phosphate in stimulated saliva (padj.=0.003), salivary parameters were not significantly different between smokers and non-smokers. Proteome profiling detected 1759&#xb1;154 proteins (cumulative 1963) in saliva, and 4262&#xb1;362 proteins (cumulative 4625) in the salivary pellicle. The relative abundances of 282 (unstimulated saliva), 338 (stimulated saliva), and 4 (salivary pellicle) protein groups differed significantly between smokers and non-smokers. Functional enrichment analysis of differentially abundant human proteins revealed biological processes such as coagulation, immune response, and carcinogenic reactive oxygen species processes to be impacted by smoking. The salivary pellicle had a significant erosion-protective effect in enamel compared to the control (41.4 &#xb1; 6.3 nmol/mm2), but no differences between smokers (33.2 &#xb1; 10.6 nmol/mm2, padj.=0.001) and non-smokers (32.7 &#xb1; 8.6 nmol/mm2, padj.=0.001) were found. CONCLUSION: The proteomic profiles of both unstimulated and stimulated saliva and the salivary pellicle differ between smokers and non-smokers. CLINICAL SIGNIFICANCE: Despite the different proteomic profiles indicating a significant impact of smoking on the oral cavity, the erosion-protective capacity of the salivary pellicle of smokers and non-smokers does not differ.

Dental Pellicle

The Epstein-Barr virus (EBV) in human pathology. II. Serologic profiles of EBV infections.

Antibodies to EBV induced intracellular antigens, (VCA, EA, NA) and VCA-IgM antibodies have been investigated to define EBV serologic profile of 245 individuals. This profile was a first studied in EBV primary infections. In infectious mononucleosis, the efficiency of EBV serodiagnosis is lower than Paul Bunnel Davidsohn reaction (PBD) : primary infection profile is only characterised in 80% of the positive PBD infectious mononucleosis (IM). On the other hand, EBV antibodies are preponderant for diagnosis in other clinical manifestations of EBV primary-infection were PBD is not alwasy positive (47%). EBV antibodies of patients with various diseases and antibodies of normal subjects show different profiles. By interpretation of these profiles one discuss the possibility to characterize reinfection, and either latent or active persistant infection.

Antibodies, Viral

EEG profile and behavioral changes after a single dose of clozapine in normals and schizophrenics.

Clozapine, a powerful neuroleptic with unique clinical efficacy (and without parkinsonic side effects), has been shown to have an unusual EEG profile. The EEG changes after clozapine, especially when instrumentally quantified, demonstrated the predictive value of EEG. The similarities of the EEG profile of clozapine with the profile of thymoleptic compounds indicated its possible thymoleptic effect. This later proved to be the case with therapeutic studies in depression. The EEG profile of clozapine in volunteers is similar to the EEG profile in schizophrenics (with appropriately higher doses). Instrumental quantification was performed with spectral and iterative interval analysis to show the advantages of each method and also the complementary value of both of them.

Adult

Numerical evaluation of cytologic data: II. Comparison of profiles.

Results of cytologic studies are often presented as profiles of some type. The numerical characterization of these profiles may be statistically compared using methods of multivariate analysis. This article describes the determination of the statistically significant differences between portions of profiles, the computation of the Mahalanobis distance measure between profiles and the use of the chi-square statistic as a measure of the typicality of a profile. Fully worked numerical examples suitable for execution on a pocket calculator are given.

Cytological Techniques

Metax enables accurate cross-domain taxonomic profiling of metagenomes.

Taxonomic profiling is fundamental to microbiome research, yet achieving high species-level accuracy remains challenging for complex communities that span bacteria, viruses, eukaryotes, and archaea, and these limitations are exacerbated in low-biomass, host-dominated samples. We introduce Metax, a cross-domain taxonomic profiler that integrates coverage-based probabilistic modeling with an expectation-maximization framework to distinguish true microbial signals from artifacts. Across >600 samples from host-associated, environmental, wastewater, and low-biomass clinical settings, including benchmarks with limited reference representation, Metax improved profiling accuracy, achieving on average 55% higher F1 scores and 45% lower Bray-Curtis dissimilarity than other methods. Moreover, this broad evaluation demonstrated that Metax resolved bacterial and viral signatures of peri-implantitis in oral microbiomes and revealed signals suggestive of reagent-borne contaminants and reference misassemblies in plasma-cell-free DNA. By leveraging genome-wide coverage evidence, Metax enables robust cross-domain profiling across diverse sample types and sequencing depths, including settings where reference databases are highly incomplete.

abundance estimation

Single-cell glycome and transcriptome profiling enabled by a library of anti-glycan antibodies.

Glycans play critical roles in cellular processes and clinical applications, but they remain difficult to study due to a shortage of well-characterized anti-glycan reagents and high-throughput technologies for glycome profiling, especially ones capable of single-cell resolution. To meet these needs, we generated a database of 650 anti-glycan antibody sequences, recombinantly expressed a library of 154 antibodies, and extensively characterized their binding properties using glycan microarrays. In addition to providing valuable information and resources for the field, the sequence database and microarray data also enabled development of "Glycomic-seq" (Glycome profiling via multiplexed immunoglobulins combined with sequencing), a DNA-barcoded anti-glycan antibody platform that enables high-throughput, single-cell profiling of both RNA and cell-surface glycan expression. Using Glycomic-seq, we profiled two isogenic colorectal cancer cell lines. The results revealed various glycans associated with cancer stem cells and metastasis, demonstrating the power of integrating glycomic information with multi-omic efforts to discover biomarkers and therapeutic targets.

Polysaccharides

Genomic profiling as an option for ovarian cancer diagnostics.

INTRODUCTION: Ovarian cancer (OC) is a highly heterogeneous and lethal gynecological malignancy. Precision oncology has shifted the management paradigm to comprehensive molecular profiling. Genomic-based diagnostics are now a clinical necessity for accurate prognostic stratification and the rational selection of targeted therapeutics, such as PARP and immune checkpoint inhibitors. AREAS COVERED: This review evaluates current literature regarding the distinct genomic landscapes defining OC histotypes to underlined the role of molecular profiling in the diagnostic field of OC. We discuss the practical implementation, technical aspect, and clinical validity of the main molecular diagnostic platforms, focusing on tissue-based Comprehensive Genomic Profiling (CGP) and Homologous Recombination Deficiency (HRD). Furthermore, we explore emerging translational data on liquid biopsy (LBx) applications. EXPERT OPINION: While current tissue-based methodologies provide critical baseline data, the OC diagnostic paradigm must pivot from static testing to proactive and longitudinal tracking. Integrating advanced LBx approaches enables a real-time monitoring of dynamic parameters as minimal residual disease (MRD) and acquired resistance. Integrating these dynamic blood-based assays with multi-omic profiling and artificial intelligence (AI)-driven tools allows a full understanding of the complex tumor behavior.

Humans

Comprehensive quality profiling and comparative metabolic characterization of seven dominant fresh-eating Chinese olive (Canarium album Lour.) cultivars in Southern China.

Fresh-eating Chinese olive (Canarium album Lour.) is a subtropical fruit endemic to southern China with considerable commercial value, yet systematic quality characterization of dominant cultivars remains scarce. This study established a multi-dimensional quality dataset for seven dominant cultivars from Fujian and Guangdong provinces, integrating nutritional components, soluble sugars, organic acids, mineral elements, volatile profiles, and non-targeted metabolomics. Significant cultivar-specific differences were observed across all evaluated dimensions: "Lingfeng" exhibited a sugar-dominant low-acid profile, whereas "Sanleng" showed elevated phenolic constituents accumulation. Volatile profiling identified terpenoid-based candidate discriminatory biomarkers, and metabolomic analysis revealed phenylpropanoid biosynthesis, tryptophan metabolism, and starch and sucrose metabolism as the most variable pathways. Correlations between untargeted profiling and targeted absolute quantification validated untargeted result reliability and revealed their complementarity in nutritional evaluation. These findings provide baseline data for FECO germplasm evaluation and targeted industrial utilization.

China

Flavoromics-based profiling reveals taste and aroma differences between infant formula and breast milk.

Flavor differences between infant formula (IF) and breast milk (BM) are considered a potential factor affecting infants' acceptance of IF. This experiment employs flavoromics combined with multivariate statistical analysis to systematically compare the flavor profiles of IF and BM. Electronic tongue analysis and amino acid correlation revealed that IF was characterised by pronounced saltiness and umami richness, whereas BM exhibited greater bitterness and astringency. Volatile compound profiling identified five key flavor constituents in IF, predominantly aldehydes such as hexanal and pentanal. In contrast, BM contained a broader array of compounds-including acids, aldehydes, and esters-resulting in a more complex flavor profile. Kyoto Encyclopedia of Genes and Genomes (KEGG)-based metabolic pathway annotation, together with fatty acid profiling, suggested that some volatiles may be associated with lipid oxidation, Maillard reaction and sulfur-containing amino acid degradation pathways, offering a theoretical basis for the targeted optimisation of IF flavor.

Humans

Relationships between childhood adversity, resilience, and inflammatory profiles in Taiwanese young adults.

Psychological resilience is the capacity to withstand and bounce back from stressors, trauma, and negative life events, such as childhood adverse experiences (ACEs). Yet, little is known about the biological mechanisms by which resilience mitigates the psychological effects of ACEs. We aimed to identify differentially expressed proteins (DEPs) that reflect the combined effects of early life stress and psychological resilience by using an inflammatory proteomics panel. Three different resilience and ACE questionnaires were employed to classify participants into four groups according to high vs. low levels of resilience and ACEs. Forty-five age-matched and sex-matched participants were selected for proteomics profiling with Olink's 92-protein inflammatory panel. Of these, only 32 passed quality control filtering for analysis. Results showed that CD274 emerged as a protein hub in resilient profiles, while CXCL5 was central to ACE-related profiles. Network co-expression analysis revealed group-specific protein rewiring, suggesting dysregulated inflammation in individuals with high ACE. In contrast, high-resilience profiles showed stronger immune checkpoint co-expression, indicating more effective inflammatory resolution as a key trait of resilience. These findings suggest that resilience maintains an adaptive immune network architecture that may be leveraged to promote resilience after early adversity.

Humans

Identification of miRNA expression profile in middle ear cholesteatoma using small RNA-sequencing.

BACKGROUND: The present study aims to identify the differential miRNA expression profile in middle ear cholesteatoma and explore their potential roles in its pathogenesis. METHODS: Cholesteatoma and matched normal retroauricular skin tissue samples were collected from patients diagnosed with acquired middle ear cholesteatoma. The miRNA expression profiling was performed using small RNA sequencing, which further validated by quantitative real-time PCR (qRT-PCR). Target genes of differentially expressed miRNAs in cholesteatoma were predicted. The interaction network of 5 most significantly differentially expressed miRNAs was visualized using Cytoscape. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses were processed to investigate the biological functions of miRNAs in cholesteatoma. RESULTS: The miRNA expression profile revealed 121 significantly differentially expressed miRNAs in cholesteatoma compared to normal skin tissues, with 56 upregulated and 65 downregulated. GO and KEGG pathway enrichment analyses suggested their significant roles in the pathogenesis of cholesteatoma. The interaction network of the the 2 most upregulated (hsa-miR-21-5p and hsa-miR-142-5p) and 3 most downregulated (hsa-miR-508-3p, hsa-miR-509-3p and hsa-miR-211-5p) miRNAs identified TGFBR2, MBNL1, and NFAT5 as potential key target genes in middle ear cholesteatoma. CONCLUSIONS: This study provides a comprehensive miRNA expression profile in middle ear cholesteatoma, which may aid in identifying therapeutic targets for its management.

Humans