Literature Watch

Peritoneal Metastasis Mimicking Chemotherapy-Induced Complications in Lung Adenocarcinoma: A Diagnostic Challenge of a Case Report

Drug-induced Adverse Events - Mon, 2025-05-19 06:00

Cureus. 2025 Apr 18;17(4):e82530. doi: 10.7759/cureus.82530. eCollection 2025 Apr.

ABSTRACT

We report a case of a 64-year-old man with advanced non-small cell lung cancer (NSCLC) who developed peritoneal metastasis during systemic treatment. Initially diagnosed with lung adenocarcinoma with pleural dissemination and bone metastases, he received carboplatin, pemetrexed, and pembrolizumab, followed by docetaxel due to clinical progression. While primary lung lesions responded to docetaxel, the patient developed new-onset abdominal pain and ascites. Radiologic findings suggested peritoneal thickening, raising suspicion for either docetaxel-induced toxicity or disease progression. Given the rarity of peritoneal metastasis in NSCLC and concurrent treatment response elsewhere, drug-induced complications were initially considered. However, worsening symptoms and further imaging prompted cytological evaluation of ascitic fluid, which confirmed metastatic adenocarcinoma consistent with lung origin. This case highlights the diagnostic challenge of distinguishing treatment-related adverse events from disease progression, especially in patients presenting with nonspecific abdominal symptoms during therapy. Clinicians should maintain a high index of suspicion for uncommon metastatic sites when new symptoms arise, even in the setting of apparent response at the primary site.

PMID:40385873 | PMC:PMC12085952 | DOI:10.7759/cureus.82530

Categories: Literature Watch

Can large language models detect drug-drug interactions leading to adverse drug reactions?

Drug-induced Adverse Events - Mon, 2025-05-19 06:00

Ther Adv Drug Saf. 2025 May 16;16:20420986251339358. doi: 10.1177/20420986251339358. eCollection 2025.

ABSTRACT

BACKGROUND: Drug-drug interactions (DDI) are an important cause of adverse drug reactions (ADRs). Could large language models (LLMs) serve as valuable tools for pharmacovigilance specialists in detecting DDIs that lead to ADR notifications?

OBJECTIVE: To compare the performance of three LLMs (ChatGPT, Gemini, and Claude) in detecting and explaining clinically significant DDIs that have led to an ADR.

DESIGN: Observational cross-sectional study.

METHODS: We used the French National Pharmacovigilance Database to randomly extract Individual Case Safety Reports (ICSRs) of ADRs with DDI (positive controls) and ICSRs of ADRs without DDI (negative controls) registered in 2022. Interaction cases were classified by difficulty level (level-1 DDI being the easiest and level-2 DDI being the most difficult). We give each LLM (ChatGPT, Gemini, and Claude) the same prompt and case summary. Sensitivity, specificity, and F-measure were calculated for each LLM in detecting DDIs in the case summaries.

RESULTS: We assessed 82 ICSRs with DDIs and 22 ICSRs without DDIs. Among ICSRs with DDIs, 37 involved level-1 DDIs, and 45 involved level-2 DDIs. Correct responses were more frequent for level-1 DDIs than for level-2 DDIs. Regardless of difficulty level, ChatGPT detected 99% of DDI cases, and Claude and Gemini detected 95%. The percentage of correct answers to all DDI-related questions was 66% for ChatGPT, 68% for Claude, and 33% for Gemini. ChatGPT and Claude produced comparable results and outperformed Gemini (F-measure between 0.83 and 0.85 for ChatGPT and Claude and 0.63-0.68 for Gemini) to detect drugs involved in DDI. All exhibited low specificity (ChatGPT 0.68, Claude 0.64, and Gemini 0.36) and reported nonexistent DDIs for negative controls.

CONCLUSION: LLMs can detect DDIs leading to pharmacovigilance cases, but cannot reliably exclude DDIs in cases without interactions. Pharmacologists are crucial for assessing whether a DDI is implicated in an ADR.

PMID:40385316 | PMC:PMC12084699 | DOI:10.1177/20420986251339358

Categories: Literature Watch

Repurposing Nitroimidazoles: A New Frontier in Combatting Bacterial Virulence and Quorum Sensing via In Silico, In Vitro, and In Vivo Insights

Drug Repositioning - Mon, 2025-05-19 06:00

Drug Dev Res. 2025 May;86(3):e70101. doi: 10.1002/ddr.70101.

ABSTRACT

The global antibiotic resistance crisis demands innovative strategies targeting bacterial virulence rather than survival. Quorum sensing (QS), a key regulator of virulence and biofilm formation, offers a promising avenue to mitigate resistance by disarming pathogens without bactericidal pressure. This study investigates the repurposing of nitroimidazoles as anti-QS and anti-virulence agents at subminimum inhibitory concentrations (sub-MICs). In Silico analyses, including molecular docking and molecular dynamics (MD) simulations, were performed to investigate ligand-receptor interactions with structurally distinct Lux-type QS receptors and assess binding stability and conformational dynamics over time. In Vitro assays evaluated the effects of representative nitroimidazoles, metronidazole (MET) and secnidazole (SEC), on QS-controlled phenotypes, including violacein production in Chromobacterium violaceum and biofilm formation and protease activity in Pseudomonas aeruginosa, Acinetobacter baumannii, Salmonella enterica, and Proteus mirabilis. In Vivo efficacy was assessed using a murine infection model and HeLa cell invasion assays. Molecular docking revealed high-affinity binding to QS receptors, corroborating their mechanistic interference. Sub-MIC MET/SEC significantly suppressed violacein synthesis, biofilm biomass, and protease secretion in Gram-negative pathogens. Both compounds reduced bacterial invasiveness in HeLa cells and In Vivo protected mice from lethal P. aeruginosa infections. Crucially, nitroimidazoles attenuated virulence without affecting bacterial viability, preserving microbial ecology. These findings position nitroimidazoles as dual-function agents; antimicrobial at bactericidal doses and anti-virulence at sub-MICs. Their validated efficacy across In Silico, In Vitro, and In Vivo models underscores their potential as adjunctive therapies, bridging the gap between drug repurposing and next-generation anti-infective development.

PMID:40384051 | DOI:10.1002/ddr.70101

Categories: Literature Watch

<em>Trichosanthes kirilowii</em> Maxim. and Bioactive Compound Cucurbitacin D Alleviate Cisplatin-Induced Peripheral Neuropathy In Vitro and In Vivo

Drug Repositioning - Mon, 2025-05-19 06:00

Integr Cancer Ther. 2025 Jan-Dec;24:15347354251339121. doi: 10.1177/15347354251339121. Epub 2025 May 18.

ABSTRACT

Chemotherapy-induced peripheral neuropathy (CIPN) has a markedly deleterious impact on a patient's quality of life. It manifests as pain, paresthesia, numbness, and weakness, particularly in the context of cisplatin (CDDP), a widely utilised chemotherapeutic agent renowned for its pronounced peripheral nerve toxicity. Trichosanthes kirilowii Maxim. (Cucurbitaceae, TK) and cucurbitacin D(CucD), its bioactive compound, have been demonstrated to possess anti-tumour, anti-inflammatory, and antioxidant properties. However, their potential to alleviate CIPN has not been fully exploredyet. The present study evaluated effectiveness of TK and CucD in mitigating CDDP-induced neuropathic pain using both cellular and animal models. CDDP, TK extracts (TKD and TKE), and CucD dose-dependently reduced viability and apoptosis of PC12 cells. Conversely, pre-treatment with TKD, TKE, and CucD exhibited significant protective effects against CDDP-induced cytotoxicity, preserving cell viability and morphology while enhancing neurite outgrowth. In vivo, administration of CDDP resulted in the development of mechanical allodynia and thermalhyperalgesia in rats. However, treatment with TKD and TKE led to a notable improvement in pain threshold and a reduction in hyperalgesia, while CucD demonstrated less pronounced effects. Although body weight was reduced in the CDDP-treated group, it was not significantly mitigated bytreatments. In conclusion, results of this study indicate that TKD, TKE, and CucD have the potential to alleviate CDDP-induced neuropathic pain by protecting against cell damage, promoting neuriteregeneration, and improving pain responses in animal models. Further investigation into TK and CucD as therapeutic options for managing CIPN is warranted.

PMID:40383960 | DOI:10.1177/15347354251339121

Categories: Literature Watch

A GLP1R gene variant and sex influence the response to semaglutide treatment in patients with severe obesity

Pharmacogenomics - Mon, 2025-05-19 06:00

Obesity (Silver Spring). 2025 May 19. doi: 10.1002/oby.24300. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study is to identify whether the glucagon-like peptide-1 receptor (GLP1R) gene variant rs6923761G→A has an influence on semaglutide response in individuals with severe obesity.

METHODS: From March 2023 to July 2024, we prospectively genotyped 112 patients treated with semaglutide 2.4 mg weekly. All patients had been treated over 4 months for grade 3 obesity (BMI ≥ 40 kg/m2).

RESULTS: The frequency of the rs6923761 AA variant was 9 out of 112 patients (8%), GA was 42 out of 112 (37.5%), and GG was 61 out of 112 (54.5%). The mean weight loss kinetics was 1.64% (SD 0.78%) per month in homozygotes of variant A in comparison with a mean weight loss of 1.04% (SD 0.79%) per month in carriers of at least one G variant (p = 0.03). Multivariate analysis demonstrated that rs6923761G→A and sex were independent predictors of weight loss. The rate of weight loss in women homozygous for the A allele was more than double that observed in men carrying the G allele: mean (SD) 1.89% (0.75%) per month versus 0.7% (0.7%) per month (p = 0.0009). No woman homozygous for the A allele was a nonresponder, compared with 56% (21 out of 37) of the men carrying the G allele.

CONCLUSIONS: The rs6923761G→A gene variant and sex profoundly affect weight loss in response to semaglutide in patients with severe obesity.

PMID:40384505 | DOI:10.1002/oby.24300

Categories: Literature Watch

Portable Ultrasound Bladder Volume Measurement Over Entire Volume Range Using a Deep Learning Artificial Intelligence Model in a Selected Cohort: A Proof of Principle Study

Deep learning - Mon, 2025-05-19 06:00

Neurourol Urodyn. 2025 May 19. doi: 10.1002/nau.70057. Online ahead of print.

ABSTRACT

OBJECTIVE: We aimed to prospectively investigate whether bladder volume measured using deep learning artificial intelligence (AI) algorithms (AI-BV) is more accurate than that measured using conventional methods (C-BV) if using a portable ultrasound bladder scanner (PUBS).

PATIENTS AND METHODS: Patients who underwent filling cystometry because of lower urinary tract symptoms between January 2021 and July 2022 were enrolled. Every time the bladder was filled serially with normal saline from 0 mL to maximum cystometric capacity in 50 mL increments, C-BV was measured using PUBS. Ultrasound images obtained during this process were manually annotated to define the bladder contour, which was used to build a deep learning AI model. The true bladder volume (T-BV) for each bladder volume range was compared with C-BV and AI-BV for analysis.

RESULTS: We enrolled 250 patients (213 men and 37 women), and a deep learning AI model was established using 1912 bladder images. There was a significant difference between C-BV (205.5 ± 170.8 mL) and T-BV (190.5 ± 165.7 mL) (p = 0.001), but no significant difference between AI-BV (197.0 ± 161.1 mL) and T-BV (190.5 ± 165.7 mL) (p = 0.081). In bladder volume ranges of 101-150, 151-200, and 201-300 mL, there were significant differences in the percentage of volume differences between [C-BV and T-BV] and [AI-BV and T-BV] (p < 0.05), but no significant difference if converted to absolute values (p > 0.05). C-BV (R2 = 0.91, p < 0.001) and AI-BV (R2 = 0.90, p < 0.001) were highly correlated with T-BV. The mean difference between AI-BV and T-BV (6.5 ± 50.4) was significantly smaller than that between C-BV and T-BV (15.0 ± 50.9) (p = 0.001).

CONCLUSION: Following image pre-processing, deep learning AI-BV more accurately estimated true BV than conventional methods in this selected cohort on internal validation. Determination of the clinical relevance of these findings and performance in external cohorts requires further study.

TRIAL REGISTRATION: The clinical trial was conducted using an approved product for its approved indication, so approval from the Ministry of Food and Drug Safety (MFDS) was not required. Therefore, there is no clinical trial registration number.

PMID:40384598 | DOI:10.1002/nau.70057

Categories: Literature Watch

Baseline correction of Raman spectral data using triangular deep convolutional networks

Deep learning - Mon, 2025-05-19 06:00

Analyst. 2025 May 19. doi: 10.1039/d5an00253b. Online ahead of print.

ABSTRACT

Raman spectroscopy requires baseline correction to address fluorescence- and instrumentation-related distortions. The existing baseline correction methods can be broadly classified into traditional mathematical approaches and deep learning-based techniques. While traditional methods often require manual parameter tuning for different spectral datasets, deep learning methods offer greater adaptability and enhance automation. Recent research on deep learning-based baseline correction has primarily focused on optimizing existing methods or designing new network architectures to improve correction performance. This study proposes a novel deep learning network architecture to further enhance baseline correction effectiveness, building upon prior research. Experimental results demonstrate that the proposed method outperforms existing approaches by achieving superior correction accuracy, reducing computation time, and more effectively preserving peak intensity and shape.

PMID:40384579 | DOI:10.1039/d5an00253b

Categories: Literature Watch

Federated Learning for Renal Tumor Segmentation and Classification on Multi-Center MRI Dataset

Deep learning - Mon, 2025-05-19 06:00

J Magn Reson Imaging. 2025 May 19. doi: 10.1002/jmri.29819. Online ahead of print.

ABSTRACT

BACKGROUND: Deep learning (DL) models for accurate renal tumor characterization may benefit from multi-center datasets for improved generalizability; however, data-sharing constraints necessitate privacy-preserving solutions like federated learning (FL).

PURPOSE: To assess the performance and reliability of FL for renal tumor segmentation and classification in multi-institutional MRI datasets.

STUDY TYPE: Retrospective multi-center study.

POPULATION: A total of 987 patients (403 female) from six hospitals were included for analysis. 73% (723/987) had malignant renal tumors, primarily clear cell carcinoma (n = 509). Patients were split into training (n = 785), validation (n = 104), and test (n = 99) sets, stratified across three simulated institutions.

FIELD STRENGTH/SEQUENCE: MRI was performed at 1.5 T and 3 T using T2-weighted imaging (T2WI) and contrast-enhanced T1-weighted imaging (CE-T1WI) sequences.

ASSESSMENT: FL and non-FL approaches used nnU-Net for tumor segmentation and ResNet for its classification. FL-trained models across three simulated institutional clients with central weight aggregation, while the non-FL approach used centralized training on the full dataset.

STATISTICAL TESTS: Segmentation was evaluated using Dice coefficients, and classification between malignant and benign lesions was assessed using accuracy, sensitivity, specificity, and area under the curves (AUCs). FL and non-FL performance was compared using the Wilcoxon test for segmentation Dice and Delong's test for AUC (p < 0.05).

RESULTS: No significant difference was observed between FL and non-FL models in segmentation (Dice: 0.43 vs. 0.45, p = 0.202) or classification (AUC: 0.69 vs. 0.64, p = 0.959) on the test set. For classification, no significant difference was observed between the models in accuracy (p = 0.912), sensitivity (p = 0.862), or specificity (p = 0.847) on the test set.

DATA CONCLUSION: FL demonstrated comparable performance to non-FL approaches in renal tumor segmentation and classification, supporting its potential as a privacy-preserving alternative for multi-institutional DL models.

EVIDENCE LEVEL: 4.

TECHNICAL EFFICACY: Stage 2.

PMID:40384349 | DOI:10.1002/jmri.29819

Categories: Literature Watch

Transformer model based on Sonazoid contrast-enhanced ultrasound for microvascular invasion prediction in hepatocellular carcinoma

Deep learning - Mon, 2025-05-19 06:00

Med Phys. 2025 May 19. doi: 10.1002/mp.17895. Online ahead of print.

ABSTRACT

BACKGROUND: Microvascular invasion (MVI) is strongly associated with the prognosis of patients with hepatocellular carcinoma (HCC).

PURPOSE: To evaluate the value of Transformer models with Sonazoid contrast-enhanced ultrasound (CEUS) in the preoperative prediction of MVI.

METHODS: This retrospective study included 164 HCC patients. Deep learning features and radiomic features were extracted from arterial and Kupffer phase images, alongside the collection of clinicopathological parameters. Normality was assessed using the Shapiro-Wilk test. The Mann‒Whitney U-test and least absolute shrinkage and selection operator algorithm were applied to screen features. Transformer, radiomic, and clinical prediction models for MVI were constructed with logistic regression. Repeated random splits followed a 7:3 ratio, with model performance evaluated over 50 iterations. The area under the receiver operating characteristic curve (AUC, 95% confidence interval [CI]), sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), decision curve, and calibration curve were used to evaluate the performance of the models. The DeLong test was applied to compare performance between models. The Bonferroni method was used to control type I error rates arising from multiple comparisons. A two-sided p-value of < 0.05 was considered statistically significant.

RESULTS: In the training set, the diagnostic performance of the arterial-phase Transformer (AT) and Kupffer-phase Transformer (KT) models were better than that of the radiomic and clinical (Clin) models (p < 0.0001). In the validation set, both the AT and KT models outperformed the radiomic and Clin models in terms of diagnostic performance (p < 0.05). The AUC (95% CI) for the AT model was 0.821 (0.72-0.925) with an accuracy of 80.0%, and the KT model was 0.859 (0.766-0.977) with an accuracy of 70.0%. Logistic regression analysis indicated that tumor size (p = 0.016) and alpha-fetoprotein (AFP) (p = 0.046) were independent predictors of MVI.

CONCLUSIONS: Transformer models using Sonazoid CEUS have potential for effectively identifying MVI-positive patients preoperatively.

PMID:40384312 | DOI:10.1002/mp.17895

Categories: Literature Watch

Bayesian Optimization with Gaussian Processes Assisted by Deep Learning for Material Designs

Deep learning - Mon, 2025-05-19 06:00

J Phys Chem Lett. 2025 May 18:5244-5251. doi: 10.1021/acs.jpclett.5c00592. Online ahead of print.

ABSTRACT

Machine learning (ML) approaches have become ubiquitous in the search for new materials in recent years. Bayesian optimization (BO) based on Gaussian processes (GPs) has become a widely recognized approach in material exploration. However, feature engineering has critical impacts on the efficiency of GP-based BO, because GPs cannot automatically generate descriptors. To address this limitation, this study applies deep kernel learning (DKL), which combines a neural network with a GP, to BO. The efficiency of the DKL model was comparable to or significantly better than that of a standard GP in a data set of 922 oxide data sets, covering band gaps, ionic dielectric constants, and effective masses of electrons, as well as in experimental data sets, the band gaps of 610 hybrid organic-inorganic perovskite alloys. When searching for the alloy with the highest Curie temperature among 4560 alloys, the standard GP outperformed the DKL model because a strongly correlated descriptor of the Curie temperature could be directly utilized. Additionally, DKL supports transfer learning, which further enhances its efficiency. Thus, we believe that BO based on DKL paves the way for exploring diverse material spaces more effectively than GPs.

PMID:40383929 | DOI:10.1021/acs.jpclett.5c00592

Categories: Literature Watch

A quantitative comparison of the deleteriousness of missense and nonsense mutations using the structurally resolved human protein interactome

Systems Biology - Mon, 2025-05-19 06:00

Protein Sci. 2025 Jun;34(6):e70155. doi: 10.1002/pro.70155.

ABSTRACT

The complex genotype-to-phenotype relationships in Mendelian diseases can be elucidated by mutation-induced disturbances to the networks of molecular interactions (interactomes) in human cells. Missense and nonsense mutations cause distinct perturbations within the human protein interactome, leading to functional and phenotypic effects with varying degrees of severity. Here, we structurally resolve the human protein interactome at atomic-level resolutions and perform structural and thermodynamic calculations to assess the biophysical implications of these mutations. We focus on a specific type of missense mutation, known as "quasi-null" mutations, which destabilize proteins and cause similar functional consequences (node removal) to nonsense mutations. We propose a "fold difference" quantification of deleteriousness, which measures the ratio between the fractions of node-removal mutations in datasets of Mendelian disease-causing and non-pathogenic mutations. We estimate the fold differences of node-removal mutations to range from 3 (for quasi-null mutations with folding ΔΔG ≥2 kcal/mol) to 20 (for nonsense mutations). We observe a strong positive correlation between biophysical destabilization and phenotypic deleteriousness, demonstrating that the deleteriousness of quasi-null mutations spans a continuous spectrum, with nonsense mutations at the extreme (highly deleterious) end. Our findings substantiate the disparity in phenotypic severity between missense and nonsense mutations and suggest that mutation-induced protein destabilization is indicative of the phenotypic outcomes of missense mutations. Our analyses of node-removal mutations allow for the potential identification of proteins whose removal or destabilization lead to harmful phenotypes, enabling the development of targeted therapeutic approaches, and enhancing comprehension of the intricate mechanisms governing genotype-to-phenotype relationships in clinically relevant diseases.

PMID:40384578 | DOI:10.1002/pro.70155

Categories: Literature Watch

BEscreen: a versatile toolkit to design base editing libraries

Systems Biology - Mon, 2025-05-19 06:00

Nucleic Acids Res. 2025 May 19:gkaf406. doi: 10.1093/nar/gkaf406. Online ahead of print.

ABSTRACT

Base editing enables the high-throughput screening of genetic variants for phenotypic effects. Base editing screens require the design of single guide RNA (sgRNA) libraries to enable either gene- or variant-centric approaches. While computational tools supporting the design of sgRNAs exist, no solution offers versatile and scalable library design enabling all major use cases. Here, we introduce BEscreen, a comprehensive base editing guide design tool provided as a web server (bescreen.ostendorflab.org) and as a command line tool. BEscreen provides variant-, gene-, and region-centric modes to accommodate various screening approaches. The variant mode accepts genomic coordinates, amino acid changes, or rsIDs as input. The gene mode designs near-saturation libraries covering the entire coding sequence of given genes or transcripts, and the region mode designs all possible guides for given genomic regions. BEscreen enables selection of guides by biological consequence, it features comprehensive customization of base editor characteristics, and it offers optional annotation using Ensembl's Variant Effect Predictor. In sum, BEscreen is a highly versatile tool to design base editing screens for a wide range of use cases with seamless scalability from individual variants to large, near-saturation libraries.

PMID:40384567 | DOI:10.1093/nar/gkaf406

Categories: Literature Watch

Digitizing the Blue Light-Activated T7 RNA Polymerase System with a <em>tet</em>-Controlled Riboregulator

Systems Biology - Mon, 2025-05-19 06:00

ACS Synth Biol. 2025 May 19. doi: 10.1021/acssynbio.5c00142. Online ahead of print.

ABSTRACT

Optogenetic systems offer precise control over gene expression, but leaky activity in the dark limits their dynamic range and, consequently, their applicability. Here, we enhanced an optogenetic system based on a split T7 RNA polymerase fused to blue-light-inducible Magnets by incorporating a tet-controlled riboregulatory module. This module exploits the photosensitivity of anhydrotetracycline and the designability of synthetic small RNAs to digitize light-controlled gene expression, implementing a repressive action over the translation of a polymerase fragment gene that is relieved with blue light. Our engineered system exhibited 13-fold improvement in dynamic range upon blue light exposure, which even raised to 23-fold improvement when using cells preadapted to chemical induction. As a functional demonstration, we implemented light-controlled antibiotic resistance in bacteria. Such integration of regulatory layers represents a suitable strategy for engineering better circuits for light-based biotechnological applications.

PMID:40384364 | DOI:10.1021/acssynbio.5c00142

Categories: Literature Watch

Cutaneous reactions during treatment with Nifurtimox or Benznidazole among Trypanosoma cruzi seropositive adults without symptomatic cardiomyopathy: A safety sub analysis of a placebo-controlled randomised trial

Drug-induced Adverse Events - Mon, 2025-05-19 06:00

Trop Med Int Health. 2025 May 19. doi: 10.1111/tmi.14123. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine, in a randomised placebo-controlled trial, if cutaneous adverse reactions during treatment (CARDT) with Benznidazole occur as often as with Nifurtimox, and whether the dose and duration of treatment change that frequency.

METHODS: We conducted the EQUITY trial (NCT02369978), allocating Trypanosoma cruzi seropositive adults with no apparent clinical disease to a 120-day, blinded treatment with Benznidazole, Nifurtimox, or Placebo (ratio 2:2:1). Active treatment groups included either 60-day conventional-dose (60CD) regimens (Benznidazole 300 mg/day or Nifurtimox 480 mg/day, followed or preceded by, 60 days of placebo) or 120-day half-dose (120HD) regimens (Benznidazole 150 mg/day or Nifurtimox 240 mg/day). CARDT had blinded adjudication as moderate to severe during the follow-up visits.

RESULTS: Among 307 participants, 42 CARDT (17.1%, 95% confidence interval [CI] 12.6-22.4) occurred in 246 receiving active treatment, compared to two CARDT (3.3%, 95% CI 0.0-11.3) in 61 participants receiving placebo. In 122 patients treated with Benznidazole, there were 31 CARDT (25.4%, including eight severe), compared to 11 CARDT (8.9%, including four severe) in 124 individuals treated with Nifurtimox (p < 0.001). Among the 125 participants assigned to the 120HD regimen, there were 26 CARDT (20.8%, including six severe), compared to 16 CARDT (13.2%, including six severe) among 121 in the 60CD group (p = 0.005). The agent-regime interaction was not significant (p = 0.443). Eleven participants (25%) with CARDT did not complete their treatment.

CONCLUSION: CARDT occurred more frequently with Benznidazole treatment, particularly with longer exposure despite the half-dose regimen. Clinicians should consider these differences when discussing treatment options with patients receiving nitro derivative agents.

PMID:40384408 | DOI:10.1111/tmi.14123

Categories: Literature Watch

Repurposing chlorpromazine for anti-leukaemic therapy with the drug-in-cyclodextrin-in-liposome nanocarrier platform

Drug Repositioning - Sun, 2025-05-18 06:00

Carbohydr Polym. 2025 Jun 15;358:123478. doi: 10.1016/j.carbpol.2025.123478. Epub 2025 Mar 6.

ABSTRACT

Acute myeloid leukaemia (AML) accounts for 30 % of adult leukaemia cases, predominantly affecting individuals over 60. The standard "7 + 3" intensive chemotherapy regimen is unsuitable for many elderly patients, contributing to AML's poor prognosis. While progress in drug therapies has been made, breakthroughs remain limited, indication-specific, and slow to expand. Drug repurposing offers a faster route to therapy development, while nanocarrier encapsulation broadens the scope of viable drug candidates. Chlorpromazine (CPZ) is an antipsychotic which has been identified as a potential anti-leukaemic agent. Due to its ability to cross the blood-brain barrier, it is likely to cause central nervous system (CNS) effects. The drug-in-cyclodextrin-in-liposome (DCL) nanocarrier platform enables the formulation of CPZ encapsulated with cyclodextrins (CDs) such as HP-γ-CD, SBE-β-CD, and Sugammadex. The CD/CPZ formulations were equally, or more efficient than free CPZ in inducing AML cell death. Uptake of the DCL in AML cells quickly reached saturation, with minimal differences among formulations, except for SBE-β-CD. When injected intravenously in zebrafish larvae, the different DCLs did not differ in biodistribution, and no brain accumulation was observed at two days post-injection. These DCL-based CPZ formulations maintain anti-leukaemic activity, avoid CNS accumulation, and allow drug availability adjustments based on the included CD.

PMID:40383608 | DOI:10.1016/j.carbpol.2025.123478

Categories: Literature Watch

3D+t Multifocal Imaging Dataset of Human Sperm

Deep learning - Sun, 2025-05-18 06:00

Sci Data. 2025 May 18;12(1):814. doi: 10.1038/s41597-025-05177-4.

ABSTRACT

Understanding human fertility requires dynamic and three-dimensional (3D) analysis of sperm movement, which extends beyond the capabilities of traditional datasets focused primarily on two-dimensional sperm motility or static morphological characteristics. To address this limitation, we introduce the 3D+t Multifocal Imaging Dataset of Human Sperm (3D-SpermVid), a repository comprising 121 multifocal video-microscopy hyperstacks of freely swimming sperm cells, incubated under non-capacitating conditions (NCC) and capacitating conditions (CC). This collection enables detailed observation and analysis of 3D sperm flagellar motility patterns over time, offering novel insights into the capacitation process and its implications for fertility. Data were captured using a multifocal imaging (MFI) system based on an optical microscope equipped with a piezoelectric device that adjusts focus at various heights, recording sperm movement in a volumetric space. By making this data publicly available, we aim to enable applications in deep learning and pattern recognition to uncover hidden flagellar motility patterns, fostering significant advancements in understanding 3D sperm morphology and dynamics, and developing new diagnostic tools for assessing male fertility, as well as assisting in the self-organizaton mechanisms driving spontaneous motility and navigation in 3D.

PMID:40383860 | DOI:10.1038/s41597-025-05177-4

Categories: Literature Watch

An ensemble deep learning framework for emotion recognition through wearable devices multi-modal physiological signals

Deep learning - Sun, 2025-05-18 06:00

Sci Rep. 2025 May 18;15(1):17263. doi: 10.1038/s41598-025-99858-0.

ABSTRACT

The widespread availability of miniaturized wearable fitness trackers has enabled the monitoring of various essential health parameters. Utilizing wearable technology for precise emotion recognition during human and computer interactions can facilitate authentic, emotionally aware contextual communication. In this paper, an emotion recognition system is proposed for the first time to conduct an experimental analysis of both discrete and dimensional models. An ensemble deep learning architecture is considered that consists of Long Short-Term Memory and Gated Recurrent Unit models to capture dynamic temporal dependencies within emotional data sequences effectively. The publicly available wearable devices EMOGNITION database is utilized to facilitate result reproducibility and comparison. The database includes physiological signals recorded using the Samsung Galaxy Watch, Empatica E4 wristband, and MUSE 2 Electroencephalogram (EEG) headband devices for a comprehensive understanding of emotions. A detailed comparison of all three dedicated wearable devices has been carried out to identify nine discrete emotions, exploring three different bio-signal combinations. The Samsung Galaxy and MUSE 2 devices achieve an average classification accuracy of 99.14% and 99.41%, respectively. The performance of the Samsung Galaxy device is examined for the 2D Valence-Arousal effective dimensional model. Results reveal average classification accuracy of 97.81% and 72.94% for Valence and Arousal dimensions, respectively. The acquired results demonstrate promising outcomes in emotion recognition when compared with the state-of-the-art methods.

PMID:40383809 | DOI:10.1038/s41598-025-99858-0

Categories: Literature Watch

Enhancing sparse data recommendations with self-inspected adaptive SMOTE and hybrid neural networks

Deep learning - Sun, 2025-05-18 06:00

Sci Rep. 2025 May 18;15(1):17229. doi: 10.1038/s41598-025-02593-9.

ABSTRACT

Personalized recommendation systems are vital for enhancing user satisfaction and reducing information overload, especially in data-sparse environments like e-commerce platforms. This paper introduces a novel hybrid framework that combines Long Short-Term Memory (LSTM) with a modified Split-Convolution (SC) neural network (LSTM-SC) and an advanced sampling technique-Self-Inspected Adaptive SMOTE (SASMOTE). Unlike traditional SMOTE, SASMOTE adaptively selects "visible" nearest neighbors and incorporates a self-inspection strategy to filter out uncertain synthetic samples, ensuring high-quality data generation. Additionally, Quokka Swarm Optimization (QSO) and Hybrid Mutation-based White Shark Optimizer (HMWSO) are employed for optimizing sampling rates and hyperparameters, respectively. Experiments conducted on the goodbooks-10k and Amazon review datasets demonstrate significant improvements in RMSE, MAE, and R² metrics, proving the superiority of the proposed model over existing deep learning and collaborative filtering techniques. The framework is scalable, interpretable, and applicable across diverse domains, particularly in e-commerce and electronic publishing.

PMID:40383722 | DOI:10.1038/s41598-025-02593-9

Categories: Literature Watch

Technology Advances in the placement of naso-enteral tubes and in the management of enteral feeding in critically ill patients: a narrative study

Deep learning - Sun, 2025-05-18 06:00

Clin Nutr ESPEN. 2025 May 16:S2405-4577(25)00319-5. doi: 10.1016/j.clnesp.2025.05.022. Online ahead of print.

ABSTRACT

Enteral feeding needs secure access to the upper gastrointestinal tract, an evaluation of the gastric function to detect gastrointestinal intolerance, and a nutritional target to reach the patient's needs. Only in the last decades has progress been accomplished in techniques allowing an appropriate placement of the nasogastric tube, mainly reducing pulmonary complications. These techniques include point-of-care ultrasound (POCUS), electromagnetic sensors, real-time video-assisted placement, impedance sensors, and virtual reality. Again, POCUS is the most accessible tool available to evaluate gastric emptying, with antrum echo density measurement. Automatic measurements of gastric antrum content supported by deep learning algorithms and electric impedance provide gastric volume. Intragastric balloons can evaluate motility. Finally, advanced technologies have been tested to improve nutritional intake: Stimulation of the esophagus mucosa inducing contraction mimicking a contraction wave that may improve enteral nutrition efficacy, impedance sensors to detect gastric reflux and modulate the rate of feeding accordingly have been clinically evaluated. Use of electronic health records integrating nutritional needs, target, and administration is recommended.

PMID:40383254 | DOI:10.1016/j.clnesp.2025.05.022

Categories: Literature Watch

FlowMRI-Net: A Generalizable Self-Supervised 4D Flow MRI Reconstruction Network

Deep learning - Sun, 2025-05-18 06:00

J Cardiovasc Magn Reson. 2025 May 16:101913. doi: 10.1016/j.jocmr.2025.101913. Online ahead of print.

ABSTRACT

BACKGROUND: Image reconstruction from highly undersampled 4D flow MRI data can be very time consuming and may result in significant underestimation of velocities depending on regularization, thereby limiting the applicability of the method. The objective of the present work was to develop a generalizable self-supervised deep learning-based framework for fast and accurate reconstruction of highly undersampled 4D flow MRI and to demonstrate the utility of the framework for aortic and cerebrovascular applications.

METHODS: The proposed deep-learning-based framework, called FlowMRI-Net, employs physics-driven unrolled optimization using a complex-valued convolutional recurrent neural network and is trained in a self-supervised manner. The generalizability of the framework is evaluated using aortic and cerebrovascular 4D flow MRI acquisitions acquired on systems from two different vendors for various undersampling factors (R=8,16,24) and compared to compressed sensing (CS-LLR) reconstructions. Evaluation includes an ablation study and a qualitative and quantitative analysis of image and velocity magnitudes.

RESULTS: FlowMRI-Net outperforms CS-LLR for aortic 4D flow MRI reconstruction, resulting in significantly lower vectorial normalized root mean square error and mean directional errors for velocities in the thoracic aorta. Furthermore, the feasibility of FlowMRI-Net's generalizability is demonstrated for cerebrovascular 4D flow MRI reconstruction. Reconstruction times ranged from 3 to 7minutes on commodity CPU/GPU hardware.

CONCLUSION: FlowMRI-Net enables fast and accurate reconstruction of highly undersampled aortic and cerebrovascular 4D flow MRI, with possible applications to other vascular territories.

PMID:40383184 | DOI:10.1016/j.jocmr.2025.101913

Categories: Literature Watch

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