Category: Nevin Manimala

Clin Ther. 2025 Nov 1:S0149-2918(25)00345-5. doi: 10.1016/j.clinthera.2025.09.019. Online ahead of print.

ABSTRACT

PURPOSE: Human epidermal growth factor receptor 2 (HER2 [ERBB2]) gene mutations occur in ∼3-5% of non-small cell lung cancer (NSCLC) cases and are associated with poor prognosis. However, real-world data on patients with HER2-mutant (HER2m) NSCLC are needed.

METHODS: This retrospective, observational study evaluated characteristics, treatment patterns, and clinical outcomes of patients with advanced nonsquamous HER2m NSCLC from the Institut Curie (France) and Thoraxklinik Heidelberg (Germany) between 2011 and 2022.

FINDINGS: Of the 55 patients (Curie: n = 17; Heidelberg: n = 38) included in the study, median age at diagnosis was 66 years (range, 22-90), 63.6% were female, and 50.9% had no history of smoking. Forty-eight (87.3%) patients received ≥1 line of therapy, 29 (52.7%) received ≥2 lines of therapy, and 19 (34.5%) received ≥3 lines of therapy. The most common first-line treatment was platinum-based and non-platinum-based chemotherapy (54.2%, n/n = 26/48); treatment patterns in the second- and third-line settings were more diverse than in the first-line setting. Median overall survival was 14.2 months (95% confidence interval [CI] 11.2, 23.2; n = 55) from the diagnosis of advanced disease and 16.5 months (12.3, 29.8; n = 48) from the start of first-line treatment. Median progression-free survival was 5.1 months (95% CI 3.5, 8.5; n = 48) and 4.0 months (2.4, 6.3; n = 29) from the start of first- and second-line treatment, respectively.

IMPLICATIONS: Patients with advanced HER2m NSCLC had a poor prognosis despite treatment with standard-of-care regimens available during the study period. These findings highlight the need for novel therapeutic options to improve clinical outcomes for patients with HER2m NSCLC.

PMID:41177727 | DOI:10.1016/j.clinthera.2025.09.019

Comput Biol Med. 2025 Nov 1;198(Pt B):111240. doi: 10.1016/j.compbiomed.2025.111240. Online ahead of print.

ABSTRACT

Glioblastoma is the most common and deadly brain cancer, known for its rapid progression and heterogeneity at microscopic and macroscopic levels. This heterogeneity is influenced by factors such as tumor cell density, involvement of normal tissue, and gene expression profiles. Mutations in EGFR gene are associated with shorter recurrence intervals and poorer survival outcomes in GBM patients. Non-invasive imaging techniques like MRI can provide valuable insights into EGFR mutations. To reduce the risks of brain biopsies and sampling errors, this study introduces an AI-based decision support system (DSS) for classifying EGFR mutations in GBM patients through automated segmentation of tumorous regions using MRI. The DSS employs deep neural networks (Inception ResNet-v2, DenseNet-121, and ResNet-50) trained on a GBM dataset from Memorial Hospital in Istanbul, which includes three MRI input types: expert segmented, without segmentation, and without tumor. Information criteria (IC) were used to guide model selection by balancing predictive performance and structural complexity. DenseNet-121 showed superior performance, with accuracy scores of 0.952, 0.942, and 0.938 for expert segmented, without segmentation, and absence of tumor inputs, respectively. Precision and recall metrics were also highest for DenseNet-121, especially with expert-segmented inputs. A multivariate statistical analysis confirmed significant differences across model performances. The results underscore the value of integrating information criteria into deep learning pipelines to enhance model robustness and interpretability in medical imaging applications.

PMID:41176824 | DOI:10.1016/j.compbiomed.2025.111240

Eur J Radiol. 2025 Oct 2;194:112463. doi: 10.1016/j.ejrad.2025.112463. Online ahead of print.

ABSTRACT

OBJECTIVE: To develop a deep learning model utilizing conventional MRI sequences integrated with Transformer-based feature fusion to differentiate spinal osteolytic bone metastases (OBM) from multiple myeloma (MM).

MATERIALS AND METHODS: This retrospective study included 663 patients (mean age: 62.13 ± 9.57 years; 378 males) from two medical centers, comprising 342 cases of OBM and 321 cases of MM. All patients underwent MRI examinations with T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and fat-suppressed T2-weighted imaging (T2WI-fs) sequences. Deep learning features were extracted with DenseNet169 to construct classification models, including Multilayer Perceptron (MLP), Support Vector Machine (SVM), Gradient Boosting, AdaBoost, and Naive Bayes. Both feature-level fusion and Transformer-based fusion methods were applied to enhance diagnostic performance. Models were trained (n = 421) and externally tested (n = 242). Their performance was evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA), with the AUC serving as the primary evaluation metric. The Delong test was used to compare model performance.

RESULTS: Among the single-sequence models, T2WI-fs achieved the highest performance, with an AUC of 0.765 and an accuracy of 0.726. Among the fusion methods, the T2WI+T2WI-fs_Transformer fusion model performed best, with an AUC of 0.783, an accuracy of 0.723, followed by the T2WI+T2WI-fs_early fusion model (AUC = 0.762). Although the differences among models were not statistically significant in the external test set (all P > 0.05), the Transformer fusion model demonstrated superior clinical net benefit and robust generalizability.

CONCLUSION: Transformer-based feature fusion of conventional MRI sequences enables accurate, non-invasive differentiation between spinal OBM and MM, providing significant clinical utility.

PMID:41176822 | DOI:10.1016/j.ejrad.2025.112463

Eur J Radiol. 2025 Oct 30;194:112484. doi: 10.1016/j.ejrad.2025.112484. Online ahead of print.

ABSTRACT

OBJECTIVES: Elevated liver iron concentration (LIC) promotes liver inflammation and fibrosis. LIC can be invasively measured in liver biopsies (Biopsy-LIC) but also non-invasively quantified by MRI. This study compared Biopsy-LIC to whole-liver MRI-LIC in chronic liver disease (CLD) patients using two relaxometry techniques: 3D multi-echo gradient echo processed with Liver-Lab (LL-LIC) and 2D multi-echo gradient echo processed with MRQuantif (MRQ-LIC).

MATERIALS AND METHODS: Retrospectively, 64 CLD patients (35 females; mean age 50.9 ± 13.5 years) underwent both liver biopsy and 3 T MRI within a median interval of 19 (6-76) days. Two independent readers compared Biopsy-LIC with LL-LIC and MRQ-LIC. Group differences were assessed via regression models adjusted for age, gender, BMI, fat fraction, liver stiffness, and iron panel values. Statistical agreement between measurements was analyzed using Pearson correlation, ICC, and Bland-Altman methodology.

RESULTS: Mean Biopsy-LIC, LL-LIC, and MRQ-LIC were 0.73 ± 0.80, 0.93 ± 0.59, and 1.06 ± 0.54 mg /g, respectively. Biopsy-LIC strongly correlated with both LL-LIC (r = 0.83) and MRQ-LIC (r = 0.84). Correlation between LL-LIC and MRQ-LIC was even stronger (r = 0.95, p < 0.001). Agreement was excellent between LL-LIC and MRQ-LIC (ICC = 0.946, CI 0.912-0.967) and good between Biopsy-LIC and MR-LICs (ICC = 0.821-0.824). Median biases were -0.29 mg /g (Biopsy-LIC vs. LL-LIC), -0.43 mg /g (Biopsy-LIC vs. MRQ-LIC), and -0.14 mg /g (LL-LIC vs. MRQ-LIC).

CONCLUSION: In CLD patients, MRI-based LIC estimates showed strong correlation and excellent agreement with biopsy-derived LIC, regardless of MRI technique.

PMID:41176821 | DOI:10.1016/j.ejrad.2025.112484

Eur J Surg Oncol. 2025 Oct 30;52(1):111160. doi: 10.1016/j.ejso.2025.111160. Online ahead of print.

ABSTRACT

OBJECTIVE: By comparing with the actual Gleason score findings of whole-prostate organ sections, this study aimed to evaluate the consistency between the overall biopsy score, the highest biopsy score, and the score grouping of cases with an actual Gleason score 3 + 4 or 4 + 3.

PATIENTS AND METHODS: The present study adopted one hundred and twenty-four prostate cancer cases that were admitted to our center between January 2023 and January 2025. All cases underwent prostate biopsy at our center, and were subsequently diagnosed with prostate cancer. Radical prostatectomy was then carried out. Whole-prostate organ sections were prepared from the postoperative specimens, and the pathological reports indicated a Gleason score 3 + 4 or 4 + 3. The Gleason scores of all positive biopsy cores and the pre-biopsy prostate magnetic resonance imaging (MRI) findings of the included cases were collected. The biopsy outcomes of these cases were scored using both the overall biopsy score and the highest biopsy score. These scores were then compared with the actual Gleason score to assess the consistency of the two different score approaches with the actual Gleason score. Subsequently, a further analysis was conducted to determine the impact of MRI results on the consistency between the two score methods and the actual Gleason score. Statistical analysis was performed using the SPSS 26 software package.

RESULT: Among the 124 enrolled cases, the concordance rate between the overall biopsy score and the actual Gleason score was 64.5 % (n = 80). Specifically, in the Gleason score 3 + 4 group, the concordance rate was 66.2 % (n = 51), and in the Gleason score 4 + 3 group, it was 61.7 % (n = 29). The concordance rate between the highest biopsy score and the actual Gleason score was 47.6 % (n = 59). Among them, in the Gleason score 3 + 4 group, the concordance rate was 49.4 % (n = 38), and in the Gleason score 4 + 3 group, it was 42.6 % (n = 21). A statistically significant difference was observed in the concordance rates between the two scoring methods and the actual Gleason score (64.5 % vs. 47.6 %, P < 0.05). Through the analysis of pre-biopsy MRI data, the results indicated that when the Prostate Imaging Reporting and Data System (PI-RADS) score ≥3, the concordance of both scoring methods with the actual Gleason score was significantly enhanced (P < 0.05). Furthermore, when the PI – RADS score≥ 3, the accuracy of the overall biopsy score remained superior to that of the highest biopsy score (71.6 % vs. 54.3 %, P < 0.05).

CONCLUSION: In cases with the actual Gleason score of 3 + 4 or 4 + 3, when both Gleason score 3 and Gleason score 4 components are concurrently detected in the needle biopsy results, the consistency between the overall biopsy score and the actual Gleason score is higher than that of the highest biopsy score. When magnetic resonance imaging (MRI) reveals well – defined target lesions, the consistency of both the overall biopsy score and the highest biopsy score with the actual Gleason score is significantly enhanced. Moreover, the overall biopsy score remains superior to the highest biopsy score.

PMID:41176817 | DOI:10.1016/j.ejso.2025.111160

Clin Nutr. 2025 Oct 24;55:3-10. doi: 10.1016/j.clnu.2025.10.005. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Critically ill patients are believed to experience a dynamic progression of energy metabolism according to the severity and phase of the illness. Although optimizing nutrition and physical therapy to the metabolic profile is recommended for better outcomes, the mechanisms for disease-related metabolic changes remain unclear. This study aimed to elucidate key metabolites and pathways associated with time-course metabolic changes and clinical parameters in acute-phase critically ill patients using untargeted metabolomics.

METHODS: We conducted a single-center prospective case series study on critically ill adults expected to require mechanical ventilation for at least 7 days in our intensive care unit. Data collection was started within 48 h of ICU admission, and daily serum samples from day 1 to day 7 were collected. Untargeted metabolomics was performed using liquid chromatography/mass spectrometry. Statistical analyses included principal component analysis, (orthogonal) partial least squares discriminant analysis, and pathway analysis.

RESULTS: Ten patients were analyzed during the study period from July 2021 to September 2022. A total of 123 metabolites were annotated by untargeted metabolomics, with significant time-course changes in galactonic acid, ornithine, and l-arginine. Pathway analysis indicated alterations in the arginine biosynthesis pathway. A subgroup analysis showed distinct metabolic profiles for sepsis and non-sepsis patients, with creatine phosphate, uric acid, and creatinine being significant markers. In sepsis patients, metabolic changes strongly correlated with the sequential organ failure assessment (SOFA) score.

CONCLUSION: Using untargeted metabolomics, we annotated several metabolites and metabolic pathways strongly associated with time-course changes in the metabolic profile. In addition, it is suggested that nutritional therapy can be optimized according to specific pathophysiology.

PMID:41176813 | DOI:10.1016/j.clnu.2025.10.005

Clin Nutr. 2025 Oct 28;55:11-23. doi: 10.1016/j.clnu.2025.10.009. Online ahead of print.

ABSTRACT

Recent advances in artificial intelligence, wearable biosensors, and multi-omics technologies, combined with interdisciplinary translational collaborations, are transforming the landscape of nutrition, particularly by enabling precision nutrition. We propose computational nutrition as an emerging interdisciplinary field that aims to address complex challenges in nutrition and health and drive paradigm shifts in nutrition research through computational methods in statistics and computer science (e.g., statistical modeling, simulation, causal inference, machine learning, and deep learning) and multi-modal data. Computational nutrition employs epidemiology and data science as its methodologies and integrates expertise from nutrition, food science, computer science, statistics, systems biology, and public health. The main research directions of computational nutrition are: 1) prediction of personalized metabolic responses to foods and establishment of individualized dietary reference intakes; 2) causal inference in nutrition and diseases and evaluation of individualized treatment effects of nutritional interventions; 3) precise and dynamic assessment and monitoring of diet-related disease risks; 4) simulation and evaluation of public health nutrition policies and sustainability assessment of dietary patterns. Critical challenges such as the reliability of wearable biosensors, trade-offs in feature selection, ethics of algorithms and health equity, and interpretability of algorithms are raised, which must be addressed to ensure human well-being and rights.

PMID:41176812 | DOI:10.1016/j.clnu.2025.10.009

Reprod Biol. 2025 Nov 1;26(1):101097. doi: 10.1016/j.repbio.2025.101097. Online ahead of print.

ABSTRACT

Animal cloning remains inefficient, with live birth rates below 5 % in most mammalian species, slightly higher in bovines (20-25 %). Among various factors, nuclear donor cells play crucial roles, and their passage numbers may influence cloning efficiency. However, a definitive association between passage numbers and outcomes in cloning remains inconclusive due to insufficient data and inconsistent results. In the present meta-analytical study, we compared research using high (>6) and low (≤6) cell passage numbers across various types, breeds, and sexes of donor cells to assess their impact on embryo development and associated gene expressions in bovine clones. Our findings revealed that cell passaging influences developmental competence at the cleavage and blastocyst rates, with lower passage numbers yielding better results. Higher acetylation of H3K9 in low-passage cells is consistently associated with improved developmental competence through the blastocyst stage, although the difference was not statistically significant. Donor cells with higher histone acetylation may undergo reprogramming more easily and completely, thus improving cloning efficiency. Further analysis elucidated that the types and breeds of donor cells also affected the blastocyst outcome. Nevertheless, high heterogeneity and meta-bias were identified in the meta-analytical outcomes, particularly in cleavage, 2-cell, 8-cell, blastocyst, the total cell number (TCN), the ratio of inner cell mass and total cell number (ICM/TCN), NANOG, and birth rate, which may contribute to inconsistencies in embryo quality results and hinder comparisons between development-related gene expressions and the embryo transfer outcome.

PMID:41176811 | DOI:10.1016/j.repbio.2025.101097

Sleep Med. 2025 Oct 31;137:106889. doi: 10.1016/j.sleep.2025.106889. Online ahead of print.

ABSTRACT

This study conducted a narrative review of Iranian Traditional Medicine (ITM) texts to identify recommendations related to sleep hygiene. The review analyzed the available literature and compared ITM practices to contemporary scientific understanding. Findings indicate a partial alignment between traditional and modern medical perspectives, with recommendations for a comfortable sleep environment, consistent sleep schedules, and adequate sleep duration. However, several ITM concepts, including the four humors, the effects of clothing on health, specific sleep positions, and the use of opium for insomnia, lack scientific evidence. Statistically, the present study revealed that only 31.4 % of the ITM sleep hygiene recommendations aligned with contemporary scientific findings. Conversely, 27.5 % of these recommendations directly contradicted current scientific research. The remaining 41.1 % required further investigation, as no conclusive scientific evidence was found to support or refute them. These findings suggest a need for additional clinical trials to definitively assess the scientific validity of these traditional practices.

PMID:41176809 | DOI:10.1016/j.sleep.2025.106889

Biochemistry (Mosc). 2025 Oct;90(10):1366-1375. doi: 10.1134/S0006297925601881.

ABSTRACT

This study investigated permeability of the apical and basolateral membranes of rat corneal endothelial cells to water and urea. We demonstrated that the apparent water permeability of the basolateral membrane of endothelial cells (4.43E-05 ± 7.57E-07 cm/s) is more than three times higher than that of the apical membrane (1.21E-05 ± 1.03E-07 cm/s). Permeability of the basolateral membrane to urea (1.23E-04 ± 1.56E-06 cm/s) was statistically significantly higher than that of the apical membrane (9.52E-05 ± 1.02E-06 cm/s) by approximately 30%. We examined contribution of the phloretin-inhibited urea transport across the apical and basolateral membranes in these cells. Phloretin at concentration of 0.1 mM significantly reduced urea permeability by more than 20% through both the apical and basolateral membranes. The results suggest that the compositions of transporters involved in water transport in the apical and basolateral membranes differ significantly. It is hypothesized that high apparent water permeability of the basolateral membrane of endothelial cells is due to contribution of the concomitant water transport with ions involved in active transport processes. Presence of the phloretin-sensitive urea transporters in the plasma membrane of endothelial cells, likely involved in its transcellular transport, has been demonstrated. The results indicate potential significance of urea for corneal function.

PMID:41176795 | DOI:10.1134/S0006297925601881