Profile Analysis Research Articles

Depressive Symptoms among Chinese Adolescents during the COVID-19 Pandemic: Exploring Subgroups and Changes using Latent Profile and Transition Analyses

Depressive Symptoms among Chinese Adolescents during the COVID-19 Pandemic: Exploring Subgroups and Changes using Latent Profile and Transition Analyses

Perceived stress and cognitive function in breast cancer chemotherapy patients: A latent profile analysis.

Perceived stress and cognitive function in breast cancer chemotherapy patients: A latent profile analysis.

Analysis of genetic mutation profile and CNS pharmacokinetics in relapsed/refractory primary CNS lymphoma patients responding to novel emavusertib (IRAK4i) and BTKi combination.

2085 Background: Primary Central Nervous System Lymphoma (PCNSL) is a rare and aggressive non-Hodgkin lymphoma with no approved treatments for relapsed/refractory (R/R) patients, representing a critical unmet need. MyD88 mutations in ~70% of PCNSL patients drive Interleukin-1 receptor associated kinase 4 (IRAK4) activation, promoting NF-κB signaling, inflammation, and tumor progression. Emavusertib, a potent oral IRAK4 inhibitor, crosses the blood-brain barrier and shows preclinical synergy with Bruton tyrosine kinase inhibitors (BTKi), re-sensitizing BTKi-resistant cell lines. This study evaluates the molecular and pharmacokinetic (PK) data associated with responses to emavusertib + ibrutinib combination therapy in R/R PCNSL patients. Methods: The safety, clinical activity, and potential biomarkers of emavusertib in R/R PCNSL are being investigated in the ongoing open-label, Phase 1/2 TakeAim Lymphoma trial (NCT03328078). Pre-dose and 1.5-hour post-dose plasma samples were collected on Cycle 3 Day 1, Cycle 5 Day 1 and Cycle 7 Day 1. Cerebrospinal fluid (CSF) samples were obtained via a lumbar puncture within 1.5 hrs of collection of the post-dose plasma PK sample on Cycle 3 Day 1. Mutation analysis was based on patients’ molecular pathology reports provided by trial sites. Sequencing of archival tissues, CSF and plasma are in progress. Results: As of 06 December 2024, CSF concentration data were available for 7 PCNSL patients. The mean emavusertib concentration in CSF was 81.3 ng/ml (54.7-104.0) in patients receiving 100 mg emavusertib BID (n = 4). In patients receiving 200 mg emavusertib BID (n = 3), the mean emavusertib concentration in CSF was higher at 175.7 ng/ml (114.8-209.4), which is 2.2X the mean value in patients who received 100 mg emavusertib BID (p-value = 0.02). All 7 patients received 560 mg ibrutinib QD, and the ibrutinib concentrations in the CSF were consistent with findings from previously published clinical studies. MyD88 mutation status was available for 7 patients of which all had prior exposure to BTKi regimens. Among these, 6 patients had MyD88 mutation of which 4 patients had responded (3 complete responses and 1 partial response) to emavusertib + ibrutinib combination with duration of response (DOR) up to 18.9 months with data collection ongoing. Conclusions: Preliminary CNS pharmacokinetic data demonstrates that emavusertib concentration in CSF increases with increasing emavusertib dose. Patients with MyD88 mutations showed expected promising preliminary efficacy to emavusertib + ibrutinib combination and may overcome BTKi resistance. Enrollment in this trial is ongoing. Clinical trial information: NCT03328078 .

Decoding citrus diversity: Insights from multivariate data analysis of nutritional and antioxidant profiles in diverse species and hybrids

Decoding citrus diversity: Insights from multivariate data analysis of nutritional and antioxidant profiles in diverse species and hybrids

Time- and concentration-dependent metabolic responses reveal adaptation failure in cadmium-exposed Haliotis diversicolor.

Time- and concentration-dependent metabolic responses reveal adaptation failure in cadmium-exposed Haliotis diversicolor.

Comparative analysis of adverse event profiles for CAR-T cell therapies and bispecific antibodies in lymphoma.

e19019 Background: CAR-T cell therapies and bispecific antibodies (BsAbs) emerged as transformative treatment options for relapsed or refractory lymphomas. Despite their efficacy, these therapies come with distinct safety profiles. CAR-T therapies modify the patient's T-cells to target tumor cells, while BsAbs engage both T-cells and tumor cells. This study compares the adverse event (AE) profiles of CAR-T and BsAb therapies in lymphoma treatment. Methods: A retrospective analysis was conducted using the FAERS database to assess AE reports associated with CAR-T therapies (Breyanzi, Kymriah, Yescarta, and Tecartus) and BsAbs (Epcoritamab, Glofitamab, Odronextamab, Mosunetuzumab, and Plamotamab). AEs were categorized by System Organ Classes (SOCs) using MedDRA terminology, and the frequency of events was calculated for each drug. Results: A total of 114,398 reports were analyzed: Yescarta (44,620), Kymriah (35,135), Tecartus (15,043), Epcoritamab (9,927), Glofitamab (4,373), Breyanzi (2,929), Mosunetuzumab (2,344), Odronextamab (22), and Plamotamab (5). For CAR-T therapies, the most frequently reported AEs were nervous system AEs (15.33%), General AEs (11.23%), and immune system AEs (9.59%). In contrast, BsAbs had higher incidences of AEs related to Infections (11.96%), General AEs (11.80%), and Immune system AEs (8.28%). CAR-T therapies showed an increased incidence of nervous system and psychiatric disorders, while BsAbs were more commonly associated with infection-related AEs. Notably, Immune system disorders were prevalent across both therapeutic modalities. The results are summarized in the table below. Conclusions: This analysis highlights key differences in the safety profiles of CAR-T and BsAb therapies for lymphoma. CAR-T therapies were associated with a higher incidence of neurological and psychiatric AEs, while BsAbs demonstrated a greater risk of infections. These findings may offer valuable guidance for clinicians in therapy selection and underscore the importance of vigilant monitoring, particularly for neurological toxicities in CAR-T treatments and infection-related risks with BsAbs. Further research is recommended to better understand these trends and inform improved management strategies for both therapeutic options. AE* Breyanzi % Epcoritamab % Glofitamab % Kymriah % Mosunetuzumab % Odronextamab % Plamotamab % Tecartus % Yescarta % Nerv 15 5 4 10 9 - - 15 16 Genrl 11 12 17 11 15 64 20 13 12 Immun 10 8 10 7 7 - 40 9 10 Infec 6 12 9 6 10 14 20 6 5 Resp 6 8 8 5 11 5 20 5 4 Blood 6 8 8 10 6 - - 5 6 Inv 4 5 6 13 4 9 - 4 5 Musc 2 2 2 3 2 5 20 2 2 Neopl 3 5 5 8 6 - - 4 3 Vasc 4 4 4 4 3 9 20 4 4 Card 3 3 2 2 3 - - 3 3 Metab 3 3 2 2 2 - - 2 3 Skin 2 2 2 2 4 - - 2 2 Surg 1 1 0 0 1 - - 1 1 * Nerv: Nervous system;Card: Cardiac; Genrl: General disorders; Immun: Immune system; Infec: Infections; Inv: Investigations; Metab: Metabolism; Musc: Musculoskeletal; Neopl: Neoplasms;Resp: Respiratory; Surg: Surgical and medical procedures; Vasc: Vascular.

Study of urine-based mRNA biomarkers for early detection of nonmuscle invasive bladder cancer (NMIBC).

Study of urine-based mRNA biomarkers for early detection of nonmuscle invasive bladder cancer (NMIBC).

Comparative analysis of muscle quality, transcriptomic, and metabolomic profiles in yellow-mutant and wild-type northern snakehead (Channa argus): Implications for food quality and aquaculture breeding potential

Comparative analysis of muscle quality, transcriptomic, and metabolomic profiles in yellow-mutant and wild-type northern snakehead (Channa argus): Implications for food quality and aquaculture breeding potential

Drilling parameters as predictors of the measured full scale performance of CFA piles by using statistical analysis of CPT profiles: a case study

Drilling parameters as predictors of the measured full scale performance of CFA piles by using statistical analysis of CPT profiles: a case study

Sex shapes phenotype-linked metabolic signatures of stress exposure in the mouse hypothalamus and pituitary.

Sex shapes phenotype-linked metabolic signatures of stress exposure in the mouse hypothalamus and pituitary.

Genomic landscape and biomarker analyses utilizing circulating-tumor DNA in advanced esophageal squamous cell carcinoma: Sub-analysis of SCRUM-MONSTAR GOZILA.

4024 Background: Advanced esophageal squamous cell carcinoma (ESCC) is a cancer type with a poor prognosis, with limited survival benefits from current multimodal approaches. The incomplete understanding of molecular mechanisms in advanced ESCC has hindered the development of effective targeted therapies, emphasizing the critical need for identifying predictive biomarkers and novel therapeutic targets. Methods: SCRUM-MONSTAR GOZILA is a nationwide plasma-based genomic profiling study utilizing Guardant360 in Japan, which aimed to analyze circulating tumor DNA (ctDNA) genomic alterations in patients with advanced solid tumors, including ESCC. We evaluated the genomic landscape with advanced ESCC patients and investigated associations between genomic alterations and overall survival (OS) using the log-rank test. The correlation between progression-free survival (PFS) and blood tumor mutation burden (bTMB) in immune checkpoint inhibitor (ICI) monotherapy was also assessed using multiple cut-off values (2, 4, 6, 8, and 10 mutation/Mb). Results: The present study included 313 patients with available genomic and clinical data. The gene alteration spectrum comprised mutations (single nucleotide variants, 71.6%; and insertions/deletions, 10.7%), copy number alterations (CNAs, 17.3%), and fusions (0.48%). TP53 was the most frequently altered gene (88.5%), followed by PIK3CA (36.4%), NFE2L2 (24.3%), CCND1 (22.4%), EGFR (20.1%), ATM (16.3%), FGFR1 (10.2%), BRCA2 (10.2%), MET (9.6%) and ARID1A (9.6%). Regarding the survival outcomes, PIK3CA CNA was significantly associated with worse OS compared to those with PIK3CA wild type [hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.24–2.74; p-value, 0.0002], and PIK3CA mutation showed a trend toward shorter OS (HR, 1.43; 95%CI, 0.94–2.17; p-value, 0.06). Patients with both PIK3CA mutation and CNA exhibited significantly worse OS compared to those with PIK3CA wild type (HR, 1.94; 95%CI, 0.85–4.45; p-value, 0.03). Both FGFR1 CNA and mutation were associated with poorer OS (HR, 1.98; 95%CI, 1.03–3.79; p-value, 0.005; and HR, 2.84; 95%CI, 0.89–9.07; p-value, 0.002, respectively). CNA in CCND1 and EGFR , and mutation in NFE2L2 and RB1 also significantly correlated with worse OS (any p-value≤0.01). Among 142 patients treated with ICI monotherapy, no statistically significant differences in PFS were observed at any cut-off value of bTMB (any p-value > 0.1). Conclusions: This comprehensive analysis of ctDNA profiles revealed distinct genomic alterations with prognostic significance in advanced ESCC. Multiple alterations demonstrated significant associations with poor OS, meanwhile bTMB was not validated as an effective predictive biomarker for ICI efficacy. These findings provide insights into potential therapeutic targets and prognostic biomarkers in advanced ESCC. Clinical trial information: 2021-GB-009 .

Phytochemical profiling, antioxidant capacity, acute toxicity, and gastroprotective potential of Angelica glauca root: A promising high-altitude medicinal herb.

Phytochemical profiling, antioxidant capacity, acute toxicity, and gastroprotective potential of Angelica glauca root: A promising high-altitude medicinal herb.

CtDNA beyond blood: Harnessing pleural effusion circulating tumor DNA for precision lung cancer diagnostics.

e20029 Background: Tissue biopsy-derived DNA has long been the gold standard for tumor-specific genomic profiling. Similarly, genomic profiling using circulating tumor DNA (ctDNA) has been next evolving molecular companion for treatment decisions, monitoring, and escalation/de-escalation of therapy choices. In malignant pleural effusion (MPE), DNA extracted from pleural fluid cell blocks has traditionally served as the primary source for molecular testing to inform cancer treatment decisions but it fails to pass DNA isolation due to less cellular content. The ease of pleural fluid collection, its proximity to the tumor, and its utility for ongoing monitoring position it as a less invasive, practical alternative for lung cancer diagnostics. This approach holds promise for longitudinal monitoring and may reduce the need for repeat biopsies in precision oncology diagnostics. We investigated the potential of molecular testing using ctDNA obtained from pleural effusion cytology supernatants (PE-CCS) alternative to ctDNA from blood. Methods: We conducted a retrospective analysis of the genomic profiles of 15 lung adenocarcinoma patients with samples derived from both blood and malignant pleural effusion. Circulating tumor DNA (ctDNA) extracted from both pleural fluid and plasma was analyzed and compared for actionable alterations using next-generation sequencing (NGS) with the OncoIndx comprehensive demonic panel (CGP) assay. Results: Retrospectively,ctDNA was successfully isolated from both pleural fluid and peripheral blood of 15 lung cancer patients. Among the samples with successful isolation 67% (10/15) demonstrated concordance in actionable or targetable mutations (for genes such as EGFR:p.L858R, EGFR:p.S768I, TP53:p) between ctDNA derived from pleural fluid and peripheral blood. In contrast, 33% (5/15) exhibited actionable mutations detected (EGFR) in ctDNA from pleural fluid that were not identified in ctDNA from peripheral blood. In 50% of patients, variant allele frequency (VAF) (minimum highest VAF of 1% and maximum highest VAF 80%) was higher in pleural fluid than in peripheral blood. Interestingly, in one patient a resistance mutation (EGFR Amplification (13 copies) was detected in pleural fluid but not in peripheral blood. Conclusions: Proximal samples, like pleural fluid, are closer to the tumor site and thus better capture tumor-derived DNA, making them more reliable for diagnostics and therapeutic insights.Pleural ctDNA NGS offers diagnostic performance comparable to tumor biopsies and surpasses pleural cytology and plasma ctDNA in detecting oncogenic mutations in lung adenocarcinoma.

High Risk of Metabolic Dysfunction in Nonobese Breast Cancer Survivors.

High Risk of Metabolic Dysfunction in Nonobese Breast Cancer Survivors.

S-phase kinase-associated protein 1 inhibits orbital fibroblasts adipogenesis to improve thyroid-associated ophthalmopathy (TAO).

S-phase kinase-associated protein 1 inhibits orbital fibroblasts adipogenesis to improve thyroid-associated ophthalmopathy (TAO).

The rheumatoid arthritis drug Auranofin targets peroxiredoxin 1 and peroxiredoxin 2 to trigger ROS-endoplasmic reticulum stress axis-mediated cell death and cytoprotective autophagy.

The rheumatoid arthritis drug Auranofin targets peroxiredoxin 1 and peroxiredoxin 2 to trigger ROS-endoplasmic reticulum stress axis-mediated cell death and cytoprotective autophagy.

Diverse roles for a class II BPC gene in Camellia japonica through tissue-specific regulation of gene expression.

Diverse roles for a class II BPC gene in Camellia japonica through tissue-specific regulation of gene expression.

Network pharmacology analysis of phytochemicals in targeting cancer: A systems biology approach.

e15130 Background: The intricate nature of cancer necessitates an integrative approach to uncover novel therapeutic strategies. Phytochemicals derived from medicinal plants offer a rich source of bioactive compounds with potential anti-cancer properties. Methods: This study utilises a network pharmacology framework to investigate the molecular mechanisms and multi-target effects of key phytochemicals, including quercetin, berberine, resveratrol, epigallocatechin gallate, salvianolic acids, and ginsenosides, against cancer pathways. Using a curated database of cancer-related targets, we employed molecular docking, ADMET profiling, and pathway enrichment analysis to identify and validate critical interactions between these phytochemicals and oncogenic pathways. Results: Gene Ontology (GO) analysis revealed significant enrichment in biological processes such as apoptosis regulation, cell cycle modulation, and oxidative stress responses. KEGG pathway mapping highlighted pivotal pathways, including PI3K-Akt, MAPK, and p53 signaling, as central nodes in the network, underscoring their role in tumour suppression and proliferation control. Moreover, systems pharmacology tools demonstrated the interconnectedness of phytochemicals in modulating mitochondrial function, cellular metabolism, and immune response which are recognized hallmarks of cancer progression. Conclusions: Our findings suggest that the multi-target and pleiotropic actions of these compounds are instrumental in mitigating cancer's complex pathophysiology. By integrating in silico predictions with experimental validations, we provide a blueprint for developing phytochemical-based combinatory therapies tailored to specific cancer types. This study not only advances our understanding of plant-derived compounds in oncology but also emphasizes the potential of network pharmacology as a transformative approach in drug discovery. We propose that future research and clinical trials should explore the therapeutic efficacy of these phytochemicals as part of multi-target regimens to improve treatment outcomes.

Control of aggressive 4T1-luc metastatic breast cancer using immunogenic cell lysates generated with methotrexate.

Control of aggressive 4T1-luc metastatic breast cancer using immunogenic cell lysates generated with methotrexate.

Metabolomics profiling and antioxidant analysis of enzymatically treated Okara fermented by Lactobacillus plantarum SY11

Metabolomics profiling and antioxidant analysis of enzymatically treated Okara fermented by Lactobacillus plantarum SY11