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At least 793 records · Page 44Linked to original sources

PubMed2003

Radiation exposure in multi-slice versus single-slice spiral CT: results of a nationwide survey.

Multi-slice (MS) technology increases the efficacy of CT procedures and offers new promising applications. The expanding use of MSCT, however, may result in an increase in both frequency of procedures and levels of patient exposure. It was, therefore, the aim of this study to gain an overview of MSCT examinations conducted in Germany in 2001. All MSCT facilities were requested to provide information about 14 standard examinations with respect to scan parameters and frequency. Based on this data, dosimetric quantities were estimated using an experimentally validated formalism. Results are compared with those of a previous survey for single-slice (SS) spiral CT scanners. According to the data provided for 39 dual- and 73 quad-slice systems, the average annual number of patients examined at MSCT is markedly higher than that examined at SSCT scanners (5500 vs 3500). The average effective dose to patients was changed from 7.4 mSv at single-slice to 5.5 mSv and 8.1 mSv at dual- and quad-slice scanners, respectively. There is a considerable potential for dose reduction at quad-slice systems by an optimisation of scan protocols and better education of the personnel. To avoid an increase in the collective effective dose from CT procedures, a clear medical justification is required in each case.

Data Collection↗

PubMed2005

[Research strategies towards a holistic characterization of rheumatoid arthritis--a systems biology approach].

Genome-wide screening methods used in functional genomics (genome, transcriptome, proteome and metabolom analysis) have increasingly been conducted in integrative research platforms to enable a comprehensive holistic characterization of multifactorial polygenic diseases. First results of this research strategy demonstrate that extended data sets are compiled whose quality is ensured by the application of standard operating procedures (SOPs) and the integration of specific laboratory information management systems (LIMS). Experimental data derived from this technology and methodology platform are obtained by applying standardized sampling procedures followed by comprehensive experimental validation and bioinformatic comparisons with the world knowledge publicly available. This research strategy should finally lead to a holistic understanding of the pathogenesis presented in rheumatoid arthritis by identifying disease-associated regulatory networks (pathways) and assigning them to cell populations involved in the disease mechanisms. In addition, it has to be investigated to what extent genetic as well as epigenetic factors direct disease initiation and progression in potential conjunction with environmental impacts (infections, smoking, etc.).

Animals↗

PubMed2026

Cross-tissue Mendelian randomization prioritizes RAB27B as a brain-derived candidate protein for postpartum depression.

OBJECTIVE: Postpartum depression (PPD) is one of the most common and debilitating complications of childbirth, yet the candidate proteins linking genetic risk to disease remain poorly defined. Building on recent genome-wide association studies (GWAS), we sought to integrate cross-tissue proteogenomic data to identify candidate proteins for PPD and explore therapeutic opportunities. METHODS: We conducted two-sample Mendelian randomization (MR) using genome-wide significant cis-protein QTLs from brain (n = 608 proteins), cerebrospinal fluid (CSF; n = 214), and plasma (n = 612). PPD summary statistics were obtained from FinnGen R8 (13,657 cases, 236,178 controls) and replicated in an independent GWAS. Phenome-wide association (PheWAS) was used to assess pleiotropy. Potential therapeutic targets were evaluated through DSigDB drug repurposing, molecular docking, and molecular dynamics simulations. RESULTS: Among all proteins tested, RAB27B was the only brain-derived protein surpassing Bonferroni correction (OR = 1.60; 95% CI: 1.30-1.96; P = 6.6 × 10⁻⁶), whereas no significant proteins were identified in CSF or plasma. This association was replicated in an independent GWAS (OR = 1.27; 95% CI: 1.02-1.58; P = 0.037). PheWAS identified no pleiotropic associations at genome-wide significance. In silico drug repurposing identified pregnenolone as a candidate ligand with computationally predicted stable binding to RAB27B, providing a starting point for future experimental validation. CONCLUSION: This study provides the first cross-tissue proteogenomic evidence that RAB27B is a brain-derived, reproducible candidate protein genetically associated with PPD. By extending GWAS signals to functional protein-level mechanisms and therapeutic inference, our findings nominate RAB27B and pregnenolone as promising directions for postpartum psychiatric research.

Humans↗

PubMed2004

Modification of landing conditions at contact via flight.

Weight-bearing tasks performed by humans consist of a series of phases with multiple objectives. Analysis of the relationship between control and dynamics during successive phases of the tasks is essential for improving performance without sustaining injury. Experimental evidence regarding foot landings suggests that the distribution of momentum among segments at contact influences stability during interaction with the landing surface. In this study, we hypothesized that modification of control in one subsystem, in our case shoulder torque, during the flight phase of an aerial task would enable the performer to maintain behavior of other subsystems (e.g.lower extremity kinematics) and initiate contact with momentum conditions consistent with successful task performance. To test this hypothesis, an experimentally validated multilink dynamic model that incorporated modifications in shoulder torque was used to simulate the flight phase dynamics of overrotated landings. The simulation results indicate that modification in shoulder torque during the flight phase enables gymnasts to maintain lower extremity kinematics and initiate contact with trunk angular velocities consistent with those observed during successful landings. These results suggest that modifications in the control logic of one subsystem may be sufficient for achieving both global and local task objectives of landing.

Biomechanical Phenomena↗

PubMed2026

Circular RNAs orchestrate integrated post-transcriptional responses to combined heat and drought stress in rice.

Circular RNAs (circRNAs) are emerging post-transcriptional regulators, yet their landscape and functional roles in rice under combined abiotic stress remain largely unexplored. Here, we systematically reanalyzed strand-specific RNA-seq data to characterize circRNAs responsive to simultaneous heat and drought stress. Following quality control, read mapping, and dual-algorithm prediction using CIRI2 and CIRCexplorer2, we identified 208 high-confidence circRNAs distributed across all 12 chromosomes. Comparative profiling revealed 83 circRNAs uniquely expressed in control samples, 51 in stressed samples, and 74 shared between conditions, indicating stress-dependent circularization. Junction-read analysis highlighted a spectrum of circularization strength, ranging from highly abundant circRNAs with dominant junction reads to low-confidence candidates masked by linear transcript background. Genomic annotation showed that circRNAs primarily originated from exonic and intergenic regions, with a pronounced negative-strand bias; several genes generated multiple circRNA isoforms via alternative back-splicing. Functional enrichment of host genes suggested involvement in protein folding, nutrient reservoir activity, RNA degradation, and branched-chain amino acid catabolism, implicating roles in stress adaptation and metabolic regulation. Differential expression analysis identified seven circRNAs specifically induced under combined stress conditions. Network topology analysis pinpointed key miRNAs-including osa-miR414, osa-miR1439, and osa-miR2919-as candidate topological hubs within the predicted network. Their predicted target genes, such as those encoding stress-responsive transcription factors and signaling proteins, suggest potential roles in coordinating post-transcriptional responses to combined stress. Network topology analysis pinpointed key miRNAs-including osa-miR414, osa-miR1439, and osa-miR2919-as candidate topological hubs within the predicted network. Their predicted target genes, such as those encoding stress-responsive transcription factors and signaling proteins, suggest potential roles in coordinating post-transcriptional responses to combined stress. Overall, this study provides a comprehensive map of circRNAs in rice under combined heat and drought stress, suggests their potential as ceRNAs based on predictive analysis, and lays a foundation for future experimental validation of circRNA-mediated regulation.

Oryza↗

PubMed2002

Model-based optimization of viral capsid protein production in fed-batch culture of recombinant Escherichia coli.

An optimized fed-batch cultivation process for the production of the polyoma virus capsid protein VP1 in recombinant Escherichia coli BL21 bacteria is presented. The optimization procedure maximizing the amount of desired protein is based on a mathematical model. The model distinguishes an initial cell growth phase from a protein production phase initiated by inducer injection. A new approach to model the target protein formation rate was elaborated, where product formation is primarily dependent on the specific biomass growth rate. Lower growth rates led to higher specific protein concentrations. The model was identified from a series of fed-batch experiments designed for parameter identification purposes and possesses good prediction quality. Then the model was used to determine optimal open-loop control profiles by manipulating the substrate feed rates in both phases as well as the induction time. Feed-rate optimization has been solved using Pontryagin's maximum principle. The solution was validated experimentally. A significant improvement of the process performance index was achieved.

Journal Article↗

PubMed2003

Optimization of the microbial synthesis of dihydroxyacetone from glycerol with Gluconobacter oxydans.

An optimized repeated-fed-batch fermentation process for the synthesis of dihydroxyacetone (DHA) from glycerol utilizing Gluconobacter oxydans is presented. Cleaning, sterilization, and inoculation procedures could be reduced significantly compared to the conventional fed-batch process. A stringent requirement was that the product concentration was kept below a critical threshold level at all times in order to avoid irreversible product inhibition of the cells. On the basis of experimentally validated model calculations, a threshold value of about 60 kg x m(-3) DHA was obtained. The innovative bioreactor system consisted of a stirred tank reactor combined with a packed trickle-bed column. In the packed column, active cells could be retained by in situ immobilization on a hydrophilized Ralu-ring carrier material. Within 17 days, the productivity of the process could be increased by 75% to about 2.8 kg x m(-3) h(-1). However, it was observed that the maximum achievable productivity had not been reached yet.

Bioreactors↗

PubMed2006

Three-dimensional finite element analysis of the pediatric lumbar spine. Part I: pathomechanism of apophyseal bony ring fracture.

The purpose of this study was to (1) develop a three-dimensional, nonlinear pediatric lumbar spine finite element model (FEM), and (2) identify the mechanical reasons for the posterior apophyseal bony ring fracture in the pediatric patients. The pediatric spine FE model was created from an experimentally validated three-dimensional adult lumbar spine FEM. The size of the FEM was reduced to 96% taking into account of the ratio of the sitting height of an average 14-years-old children to that of an adult. The pediatric spine was created with anatomically specific features like the growth plate and the apophyseal bony ring. For the stress analyses, a 10-N m moment was applied in all the six directions of motion for the lumbar spine. A preload of 351 N was applied which corresponds to the mean body weight of the 14-years-old group. The stresses at the apophyseal bony ring, growth plate and endplate were calculated. The results indicate that the structures surrounding the growth plate including apophyseal bony ring and osseous endplate were highly stressed, as compared to other structures. Furthermore, posterior structures in extension were in compression whereas in flexion they were in tension, with magnitude of stresses higher in extension than in flexion. Over time, the higher compression stresses along with tension stresses in flexion may contribute to the apophyseal ring fracture (fatigue phenomena).

Adult↗

PubMed2003

Spectroscopic and computational characterization of the nickel-containing F430 cofactor of methyl-coenzyme M reductase.

Methyl-coenzyme M reductase (MCR) catalyzes the terminal reaction in methanogenesis, the formation of methane from methyl-coenzyme M and coenzyme B. The active site of MCR binds the prosthetic group F(430), a unique nickel hydrocorphin cofactor. Here, spectroscopy and computations are employed in developing detailed electronic descriptions of the Ni(II) and Ni(I) forms of the free cofactor. Absorption, magnetic circular dichroism (MCD), and variable-temperature variable-field MCD data are analyzed within the framework of time-dependent DFT computations to assign key electronic transitions. DFT calculations are further employed to evaluate possible reduced F(430) models-a one-electron reduced Ni(I)F(430) model and a three-electron reduced Ni(I)F(red430) model (possessing a reduced hydrocorphin ligand)-on the basis of excited-state spectra and published EPR/ENDOR parameters. While calculations on both models yield spectroscopic parameters that are consistent with most experimental data, overall better agreement is achieved using the Ni(I)F(430) model, particularly with respect to electronic absorption and (1)H ENDOR. The experimentally validated bonding descriptions generated herein show that in Ni(II)F(430) the occupied Ni 3d orbitals are too low in energy to significantly perturb the dominant electronic transition involving the pi and pi* frontier MOs of the macrocycle (i.e., the HOMO-->LUMO transition). Upon one-electron reduction of the Ni(II) ion, the occupied Ni 3d orbitals are raised in energy, shifting between the HOMO and the LUMO of the oxidized cofactor. These ground-state changes have a dramatic effect on the excited-state structure, causing a blue shift of the dominant pi-->pi* transition and the appearance of numerous Ni 3d-->hydrocorphin pi* charge-transfer features in the vis/near-IR region.

Computational Biology↗

PubMed2026

Phenotypic and phylogenomic characterization of Lactococcus garvieae isolates from rainbow trout (Oncorhynchus mykiss) in Türkiye.

Lactococcosis is an important bacterial disease of farmed fish and causes substantial economic losses in rainbow trout (Oncorhynchus mykiss) aquaculture. In this study, Lactococcus garvieae isolates recovered from rainbow trout farms in Türkiye were characterized using phenotypic, molecular, and phylogenomic methods. Among 32 presumptive Lactococcus isolates recovered from 127 dead rainbow trout, four were confirmed as L. garvieae and exhibited identical biochemical characteristics, Pulsed Field Gel Electrophoresis (PFGE) profiles, and broad growth tolerance across different pH, salinity, and temperature conditions. All isolates were presumptively classified as resistant to ciprofloxacin and florfenicol, while remaining susceptible to tetracycline and penicillin. Based on the AMR profiles, strain LG2, which exhibited the most susceptible antimicrobial profile among the isolates, was selected for whole-genome sequencing (WGS). WGS of the representative isolate LG2 generated a single 2,214,687-bp chromosomal contig with 38.5% GC content and 99.0% BUSCO completeness. In silico PCR assigned LG2 to serotype I, and the genome contained an intact capsule-associated cps/kps locus. The chromosomal lsa(D) determinant and an mdt(A)-like efflux-associated gene were detected, whereas no plasmid replicons or acquired quinolone or florfenicol resistance genes were identified, indicating discordance between the phenotypic and genomic AMR results. Taxonomic verification of 236 publicly available Lactococcus assemblies yielded 41 verified public L. garvieae genomes, which, together with LG2, formed a 42-genome within-species dataset. LG2 was most closely related to the Turkish isolate OS-37, sharing 99.96% ANI and differing by three core SNPs; both belonged to ST109, whereas the other Turkish isolates belonged to ST139. cgMLST identified a conserved genomic backbone, while pan-genome analysis identified 5,655 gene clusters and an open pan-genome characterized by a large cloud-gene fraction. These findings demonstrate the importance of species verification in Lactococcus population genomics and reveal substantial accessory-genome diversity within L. garvieae. The genomic features of LG2 provide a basis for future pathogenicity and immunogenicity studies, although experimental validation is required. Overall, these findings highlight the importance of local genomic surveillance for understanding L. garvieae population structure and provide a genomic framework for future region-specific vaccine research.

Animals↗

PubMed2026

Integrative multi-omics analyses suggest a candidate microbial metabolite-associated host gene network in ulcerative colitis.

Ulcerative colitis (UC) is associated with gut microbial dysbiosis, but the host molecular alterations potentially linked to microbially derived metabolites remain incompletely understood. We integrated Mendelian randomization (MR), microbial metabolite annotation, computational target prediction, colonic transcriptomics, network analysis, and machine learning. MiBioGen microbiome GWAS data were used as exposures and FinnGen Release 12 ULCERENTER as the outcome. Metabolites linked to MR-prioritized taxa were retrieved from GutMGene, and human targets were predicted using SwissTargetPrediction and SEA. UC-related genes were defined by integrating differential expression analysis and WGCNA and then intersected with predicted metabolite targets. MR prioritized one family and eight genera showing nominal genetically supported associations with UC, but none remained significant after Benjamini-Hochberg FDR correction. Three prioritized genera were linked to 15 microbe-metabolite records, corresponding to 13 unique metabolites; nine were retained for target prediction, yielding 277 unique predicted human targets. Transcriptomic analysis identified 1,530 DEGs and a 312-gene MEgrey60 module, with 273 overlapping genes, producing 1,569 unique UC-related genes. Their intersection with the 277 predicted targets yielded 47 candidate genes. Enrichment analyses highlighted mainly metabolic and lipid-related processes. Random Forest showed the highest mean AUC across the two independent external benchmarking cohorts, and SHAP prioritized EPHX1, HSD17B2, IGFBP5, and MMP10. IBDome analysis showed inflammation-associated expression differences in these genes. This study provides a genomics-informed, hypothesis-generating framework that prioritizes candidate microbe-metabolite-host relationships in UC for future experimental validation.

Humans↗

PubMed2026

Integrated Genome Mining and Bioactivity-Guided Isolation of Antimicrobial Peptides from Bacillus amyloliquefaciens BS4.

Bacterial resistance remains a critical global health challenge, driving the continuous search for novel antimicrobial agents. Bacillus amyloliquefaciens is a recognized repository of bioactive metabolites; however, its full biosynthetic potential requires integrated genomic and experimental validation. This study characterized the antimicrobial profile of B. amyloliquefaciens BS4 through a hybrid pipeline. Genome sequencing and de novo assembly revealed a 3.9 Mb chromosome with a G + C content of 46.14%. Functional annotation identified 3,887 coding sequences, including pathways for siderophore biosynthesis and a complete bacilysin biosynthetic cluster. BGC analysis using antiSMASH v7.1.0 and BAGEL4 identified 18 biosynthetic gene clusters, while similarity network analysis via BiG-SCAPE highlighted unique singleton BGCs, indicating untapped biosynthetic diversity. Although in silico screening via Macrel predicted two putative cationic antimicrobial peptides (AMPs), bioactivity-guided purification utilizing sequential RP-HPLC, and de novo sequencing revealed a distinct set of four active peptides. Notably, three of these sequences were identified as fragments derived from the BclA exosporium protein family, highlighting the structural proteome as a non-canonical source of antimicrobials. The purified fractions exhibited activity against M. luteus and E. coli, while displaying no significant hemolytic activity or cytotoxicity, even above the MIC values. Molecular docking further supported the interaction of these candidates with bacterial targets. Overall, this hybrid strategy effectively uncovers the antimicrobial complexity of BS4, revealing 'cryptic' peptide candidates with therapeutic potential.

Bacillus amyloliquefaciens BS4↗

PubMed2026

Expression of PIEZO1 in lung adenocarcinoma correlates with PD-L1 expression, cell migration, and poor prognosis: an exploratory study.

BACKGROUND AND AIMS: Lung adenocarcinoma (LUAD) treatment is challenging process. and the function of PIEZO1, a mechanically sensitive ion channel has not been systematically determined. In this study we aimed to explore the expression, potential associations, and clinical significance of PIEZO1 in LUAD. METHODS AND AIMS: A comprehensive bioinformatics analysis was performed using data from the Cancer Genome Atlas (TCGA) database, the Gene Expression Omnibus (GEO) database and other databases. Experimental validation was performed to confirm the expression patterns and preliminarily examine the associations of PIEZO1 in LUAD cell lines. RESULTS: PIEZO1 expression was significantly lower in LUAD tissues than in normal lung tissues (P < 0.05). Its expression was correlated with advanced pathological stage, lymph node involvement, and distant metastasis. High PIEZO1 expression was associated with a distinct immune-related tumor microenvironment, characterized by correlations with the expression levels of multiple immune checkpoint molecules, and was identified as an independent factor associated with poor overall survival (HR = 1.49; 95% CI 1.11-2; P < 0.007). In vitro experiments confirmed the downregulated PIEZO1 expression in LUAD cell lines, and functional knockdown experiments revealed its association with cell migration and PD-L1 expression. CONCLUSION: This exploratory study revealed that PIEZO1 expression in LUAD cell lines correlated with the expression of immune-related features and EMT-related genes, as well as poor prognosis. In vitro, PIEZO1 knockdown is associated with reduced cell migration and decreased PD-L1 expression. These findings provide a basis for future investigations into the potential role of PIEZO1 in LUAD.

Gene expression↗

PubMed2026

The mighty microproteins: from versatile cellular regulators to precision medicine therapeutics.

Microproteins, are tiny proteins encoded by small open reading frame (sORF), translation of these non-canonical open reading frames (ncORFs) has been implicated in diverse biological processes and diseases. This review summarizes recent developments in the discovery, biogenesis, and functional characterization of microproteins, and their involvement in various disease, with special focus on their roles in cancer, cardiovascular, metabolic, neurodegenerative and immune-related disorders. We emphasize the regulation of key cellular pathways by microproteins, including mitochondrial homeostasis, apoptosis, metabolic reprogramming, and immune signaling, all of which affect disease initiation and progression. Emerging evidence also supports their potential as disease biomarkers and therapeutic candidates for precision medicine. Finally, the review critically discusses the current challenges including discrepancies in microprotein annotation, the limitations of ribosome profiling and proteogenomic approaches, the gap between computationally predicted and experimentally validated microproteins, and the need for rigorous orthogonal validation by means of CRISPR-based genome editing, ribosome release assays, mutational analysis, high-resolution mass spectrometry, and functional studies. Finally, we review recent development of AI-assisted ORF prediction, single-cell translatomics, spatial proteomics, and integrated multi-omics as emerging technologies reshaping. Microprotein discovery and functional annotation. Finally, we discuss the translational potential of microproteins and highlight the remaining challenges to clinical application, including peptide stability, pharmacokinetics, tissue-specific delivery, immunogenicity, and the need for rigorous preclinical and clinical validation. Together, this review provides an updated and critical overview of the rapidly evolving microprotein field and highlights future research priorities for translating these molecules into clinically useful biomarkers and precision therapeutics.

Microproteins↗

PubMed2026

Optimization of protoplast based DNA isolation and genome analysis in a gamma-irradiated Aspergillus niger mutant strain.

Aspergillus niger is an important industrial fungus widely used for citric acid production and a range of biotechnological applications. In this study, a protoplast-based DNA isolation protocol was optimized for a gamma-irradiated A. niger AN-L103_M1 mutant strain, followed by whole-genome sequencing and functional genome analysis. Protoplast yield was strongly influenced by enzyme concentration and the molarity of the osmotic stabilizer. The highest yield was achieved at an enzyme concentration of 50 mg/mL (2.487 ± 0.04 × 10⁸ cells/mL) and 0.8 M KCl (2.550 ± 0.06 × 10⁸ cells/mL), with both factors showing significant effects (p < 0.0001) in GraphPad Prism 11.0.0. Whole-genome sequencing performed using an Illumina NovaSeq 6000 platform yielded a 37.06 Mb draft genome assembled into 537 contigs, with an N50 of 363,084 bp and a GC content of 48.2%. BUSCO 14 analysis showed high completeness (97.95% complete BUSCOs). Functional annotation and KEGG pathway mapping identified genes involved in glycolysis, the tricarboxylic acid cycle, and citrate biosynthesis, while biosynthetic gene cluster analysis revealed diverse potential for secondary metabolite production. These findings provide an optimized workflow for protoplast-based DNA isolation and genome-scale functional analysis in A. niger, proposing a basis for future comparative genomics, transformation studies, and experimentally validated metabolic engineering.

Aspergillus niger↗

PubMed2026

Structure-based virtual screening, multi-score docking, and molecular dynamics simulation of novel small molecules targeting the epidermal growth factor receptor for potential management of oral squamous cell carcinoma.

UNLABELLED: Oral squamous cell carcinoma (OSCC) is a major global health burden, with epidermal growth factor receptor (EGFR) serving as an important therapeutic target. However, resistance to currently available EGFR inhibitors limits the efficacy of long-term treatment. In this study, a structure-based virtual screening approach was employed using the Mcule database to identify novel small molecules with potential EGFR-inhibitory activity. The top-ranked compounds were subjected to consensus docking using multiple docking platforms and compared with established EGFR inhibitors. The most promising complexes were further evaluated using 500 ns molecular dynamics simulations to investigate their structural stability, conformational flexibility, and binding persistence. ADMET and pharmacokinetic analyses were performed to assess the drug-like and safety profiles. Five lead compounds (C1-C5) demonstrated significant binding affinities toward EGFR, ranging from - 9.9 to - 9.2 kcal/mol, while satisfying the major drug-likeness criteria. Molecular dynamics simulations suggested that C1 and C4 may form relatively stable EGFR-ligand complexes, as supported by stable RMSD convergence and persistent interactions with key active-site residues throughout the simulation period. Trajectory-based interaction analyses further indicated a sustained binding behavior. ADMET profiling predicted favorable oral bioavailability and low predicted toxicity for most compounds, particularly C3 and C5, although a potential risk of cytochrome P450-mediated drug-drug interactions was observed. Overall, the shortlisted compounds exhibited docking and dynamic stability profiles comparable to those of the reference inhibitor Lapatinib. These findings suggest the potential therapeutic relevance of structurally novel EGFR-targeting scaffolds in OSCC and provide a foundation for future experimental validation through in vitro and in vivo studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00722-4.

ADMET↗

PubMed2026

Unveiling novel transcriptomic prognostic biomarkers for specific breast cancer subtypes and treatment regimens.

BACKGROUND: Breast cancer (BRCA) is the most common cancer in women worldwide, yet current gene expression panels offer limited insight into treatment responses across different subtypes and therapies. This study aimed to identify reliable biomarkers for predicting treatment outcomes in specific BRCA subtypes and treatment regimens. METHODS: This study analyzed transcriptomic data from The Cancer Genome Atlas to identify differentially expressed genes (DEGs) in patient groups treated with different combinations of hormone therapy (H), chemotherapy (C), radiotherapy (R), and targeted therapy (T). Non-negative matrix factorization clustering was performed to stratify patients into clusters representing different BRCA subtypes. Functional enrichment analysis was performed, and survival assessments were conducted using the METABRIC dataset. RESULTS: A total of 1,148 DEGs were identified across treatment regimens, with 75 common DEGs shared across multiple regimens. Among these, 12 candidate biomarkers were associated with luminal subtypes treated with H, including LRP1B, of which high expression predicted cancer recurrence. In triple-negative breast cancer (TNBC) treated with C, 76 candidate biomarkers were identified, including TTYH1 for recurrence and ANXA8L1 and MPZ for non-recurrence. Functional analyses identified intermediate filament organization and keratinization as pathways associated with specific candidate biomarkers of TNBC following C. Survival analysis using METABRIC strengthened the prognostic ability of LRP1B and TTYH1 to predict worse survival and ANXA8L1 and MPZ to predict prolonged survival, with four additional prognostic biomarkers. CONCLUSION: This study identified gene expression prognostic biomarkers for luminal and TNBC subtypes, thereby supporting personalized therapies. Further experimental validation is required to confirm these findings for clinical application. CLINICAL TRIAL REGISTRY: No.

Breast cancer↗

PubMed1989

Quantification of left ventricular myocardial mass in humans by nuclear magnetic resonance imaging.

The ability of NMRI to assess LV mass was studied in 20 normal males. By means of a 1.5 Tesla GE superconducting magnet and a standard spin-echo pulse sequence, multiple gated short-axis and axial slices of the entire left ventricle were obtained. LV mass was determined by Simpson's rule with the use of a previous experimentally validated method. The weight of the LV apex (subject to partial volume effect in the short-axis images) was derived from axial slices and that of the remaining left ventricle from short-axis slices. The weight of each slice was calculated by multiplying the planimetered surface area of the LV myocardium by slice thickness and by myocardial specific gravity (1.05). Mean +/- standard deviation of LV mass and LV mass index were 146 +/- 23.1 gm (range 92.3 to 190.4 gm) and 78.4 +/- 7.8 gm/m2 (range 57.7 to 89.4 gm/m2), respectively. Interobserver agreement as assessed by ICC was high for determining 161 individual slice masses (ICC = 0.99) and for total LV mass (ICC = 0.97). Intraobserver agreement for total LV mass was also high (ICC = 0.96). NMRI-determined LV mass correlated with body surface area: LV mass = 55 + 108 body surface area, r = 0.83; with body weight: LV mass = 26 + 0.77 body weight, r = 0.82; and with body height: LV mass = 262 +/- 5.9 body height, r = 0.75. Normal limits were developed for these relationships. NMRI-determined LV mass as related to body weight was in agreement with normal limits derived from autopsy literature data.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗