Literature Watch

Analyzing handwriting legibility through hand kinematics

Deep learning - Thu, 2025-04-10 06:00

Front Artif Intell. 2025 Mar 26;8:1426455. doi: 10.3389/frai.2025.1426455. eCollection 2025.

ABSTRACT

INTRODUCTION: Handwriting is a complex skill that requires coordination between human motor system, sensory perception, cognitive processing, memory retrieval, and linguistic proficiency. Various aspects of hand and stylus kinematics can affect the legibility of a handwritten text. Assessing handwriting legibility is challenging due to variations in experts' cultural and academic backgrounds, which introduce subjectivity biases in evaluations.

METHODS: In this paper, we utilize a deep-learning model to analyze kinematic features influencing the legibility of handwriting based on temporal convolutional networks (TCN). Fifty subjects are recruited to complete a 26-word paragraph handwriting task, designed to include all possible orthographic combinations of Arabic characters, during which the hand and stylus movements are recorded. A total of 117 different spatiotemporal features are recorded, and the data collected are used to train the model. Shapley values are used to determine the important hand and stylus kinematics features toward evaluating legibility. Three experts are recruited to label the produced text into different legibility scores. Statistical analysis of the top 6 features is conducted to investigate the differences between features associated with high and low legibility scores.

RESULTS: Although the model trained on stylus kinematics features demonstrates relatively high accuracy (around 76%), where the number of legibility classes can vary between 7 and 8 depending on the expert, the addition of hand kinematics features significantly increases the model accuracy by approximately 10%. Explainability analysis revealed that pressure variability, pen slant (altitude, azimuth), and hand speed components are the most prominent for evaluating legibility across the three experts.

DISCUSSION: The model learns meaningful stylus and hand kinematics features associated with the legibility of handwriting. The hand kinematics features are important for accurate assessment of handwriting legibility. The proposed approach can be used in handwriting learning tools for personalized handwriting skill acquisition as well as for pathology detection and rehabilitation.

PMID:40206709 | PMC:PMC11979204 | DOI:10.3389/frai.2025.1426455

Categories: Literature Watch

Internet of things driven hybrid neuro-fuzzy deep learning building energy management system for cost and schedule optimization

Deep learning - Thu, 2025-04-10 06:00

Front Artif Intell. 2025 Mar 26;8:1544183. doi: 10.3389/frai.2025.1544183. eCollection 2025.

ABSTRACT

Optimizing building energy consumption holds significant untapped potential, particularly in a developing economy such as India. Existing solutions have yet to concentrate on a methodology that is cost-effective, small-scale, precise, and open source data-driven. In response, we have implemented an automated, DL-enabled approach to predict energy consumption with the goal to enable cost and schedule optimization. For two years from December 2021 to December 2023 the energy consumption and twenty seven associated energy parameters was monitored by developing an IoT enabled BEMS. The data collected was preprocessed, cleaned, transformed and used for training a machine learning model. Based on the previous literature, a hybrid DL model was developed using artificial neural networks and fuzzy logic by integrating fuzzy layers in the deep neural architecture. The collected electrical data was used for training, hyper-parameter tuning and testing the hybrid DL model. The proposed model when tested for out-of-sample dataset had comparable results on error and performance metrics as compared to other states of the art models. On deployment in the premises of a university, the BEMS achieved a reduction in the electricity bill of 20% highlighting its effectiveness and efficacy.

PMID:40206707 | PMC:PMC11979119 | DOI:10.3389/frai.2025.1544183

Categories: Literature Watch

The pathogenesis of idiopathic pulmonary fibrosis: from "folies a deux" to "Culprit cell Trio"

Idiopathic Pulmonary Fibrosis - Thu, 2025-04-10 06:00

Pathologica. 2025 Feb;117(1):3-9. doi: 10.32074/1591-951X-1123.

NO ABSTRACT

PMID:40205925 | DOI:10.32074/1591-951X-1123

Categories: Literature Watch

Engineering of Conserved Sequence Motif 1 Residues in Halohydrin Dehalogenase HheC Simultaneously Enhances Activity, Stability, and Enantioselectivity

Systems Biology - Thu, 2025-04-10 06:00

ACS Catal. 2025 Mar 13;15(7):5257-5272. doi: 10.1021/acscatal.5c00819. eCollection 2025 Apr 4.

ABSTRACT

Halohydrin dehalogenases (HHDHs) are powerful enzymes for the asymmetric diversification of oxyfunctionalized synthons. They feature two characteristic sequence motifs that distinguish them from homologous short-chain dehydrogenases and reductases. Sequence motif 1, carrying a conserved threonine, glycine, and a central aromatic residue, lines the nucleophile binding pocket of HHDHs. It could therefore impact nucleophile binding and presumably also the activity of the enzymes. However, experimental evidence supporting this theory is largely missing. Herein, we systematically studied the mutability of the three conserved motif 1 residues as well as their resulting impact on enzyme activity, stability, and selectivity in two model HHDHs: HheC from Agrobacterium radiobacter AD1 and HheG from Ilumatobacter coccineus. In both HheC and HheG, the conserved threonine and glycine tolerated mutations to only structurally similar amino acids. In contrast, the central aromatic (i.e., phenylalanine or tyrosine) residue of motif 1 demonstrated much higher variability in HheC. Remarkably, some of these variants featured drastically altered activity, stability, and selectivity characteristics. For instance, variant HheC F12Y displayed up to 5-fold increased specific activity in various epoxide ring opening and dehalogenation reactions as well as enhanced enantioselectivity (e.g., an E-value of 74 in the azidolysis of epichlorohydrin compared to E = 22 for HheC wild type) while also exhibiting a 10 K higher apparent melting temperature. QM and MD simulations support the experimentally observed activity increase of HheC F12Y and reveal alterations in the hydrogen bonding network within the active site. As such, our results demonstrate that multiple enzyme properties of HHDHs can be altered through the targeted mutagenesis of conserved motif 1 residues. In addition, this work illustrates that motif 1 plays vital roles beyond nucleophile binding by impacting the solubility and stability properties. These insights advance our understanding of HHDH active sites and will facilitate their future engineering.

PMID:40207069 | PMC:PMC11976700 | DOI:10.1021/acscatal.5c00819

Categories: Literature Watch

The Protective Effect of Ellagic Acid and Its Metabolites Against Organ Injuries: A Mitochondrial Perspective

Systems Biology - Thu, 2025-04-10 06:00

Food Sci Nutr. 2025 Apr 9;13(4):e70077. doi: 10.1002/fsn3.70077. eCollection 2025 Apr.

ABSTRACT

Mitochondria are essential for maintaining health, and dysfunction of them leads to various diseases. Their role is not limited to energy production but serves multiple mechanisms varying from calcium hemostasis, reactive oxygen species production, and regulation of apoptotic cell death. In recent years, several strategies have been developed to preserve mitochondria. Ellagic acid (EA) is a polyphenol extracted from many plants. The intestinal microflora converts EA to urolithins with high bioavailability. EA and urolithins exhibit mitochondrial-protective effects by regulating mitochondrial complexes, sirtuins, mitophagy, and mitochondrial antioxidant enzymes. This review highlights the mito-protective effects of EA and urolithins on mitochondrial injuries induced by various drugs and toxic compounds.

PMID:40206693 | PMC:PMC11979624 | DOI:10.1002/fsn3.70077

Categories: Literature Watch

Identification of angiotensin II-responsive circadian clock gene expression in adrenal zona glomerulosa cells and human adrenocortical H295R cells

Systems Biology - Thu, 2025-04-10 06:00

Front Endocrinol (Lausanne). 2025 Mar 26;16:1525844. doi: 10.3389/fendo.2025.1525844. eCollection 2025.

ABSTRACT

The mammalian circadian timing system is organized in a hierarchy, with the master clock residing in the suprachiasmatic nucleus (SCN) of the hypothalamus and subsidiary peripheral clocks in peripheral tissues. Because of the diversity of peripheral tissues and cell-types in the body, the existence of autonomous clock and identification of its potential entrainment signals need to be empirically defined on a cell type-by-cell type basis. In this study, we characterized the basic circadian clock properties of the adrenal zona glomerulosa cells, or ZG cells. Using isolated adrenal explants from Per2Luc mice, dissociated ZG cells from Per2-dluc rats, and a related human adrenocortical cell line H295R, we showed that ZG cells possess genetically-encoded, self-sustained and cell-autonomous circadian clock. As to the potential entrainment signals, angiotensin II (Ang II) caused phase-dependent phase-shifts of adrenal ZG cells in cultured slices. Ang II treatment also drove initiation (or reset) of circadian clock gene expression in H295R cells with associated immediate up-regulation of PER1 and E4BP4 mRNA expression. We found that the type I Ang II receptor blocker CV11974, one of the most widely used clinical drugs for hypertensive diseases, caused attenuation of the phase resetting of H295R cells. Our in vitro data provide a basis to understand and argue for the adrenal gland ZG cells as a component of autonomous and entrainable peripheral clocks.

PMID:40206597 | PMC:PMC11978646 | DOI:10.3389/fendo.2025.1525844

Categories: Literature Watch

Histopathologic Alterations between <em>Echinococcus granulosus sensu stricto</em> and <em>E. canadensis</em> Genotypes of Human Cystic Echinococcosis Cysts in Shiraz, Iran

Systems Biology - Thu, 2025-04-10 06:00

Iran J Parasitol. 2025 Jan-Mar;20(1):21-31. doi: 10.18502/ijpa.v20i1.18102.

ABSTRACT

BACKGROUND: We aimed to determine the genotypes of Echinococcus granulosus sensu lato (s.l.) using DNA regions within the NADH dehydrogenase subunit-1 (nad1) mitochondrial genes in formalin-fixed paraffin-embedded (FFPE) isolates of human cystic echinococcosis cysts (CE cysts) and compare their histopathologic alterations.

METHODS: Out of 135 samples, 21 high-quality PCR positive samples were selected for sequencing and were deposited into GenBank database. Moreover, histopathological changes of E. granulosus sensu stricto (G1 genotype) and E. canadensis (G6 genotype) cases were also compared.

RESULTS: Based on the sequencing results, 16 cases were diagnosed as E. granulosus s.s. (G1-G3 genotype) and 5 cases as E. canadensis (G6 genotype). Five haplotypes of E. granulosus were identified from 21 nad1 sequences. The histopathological alterations in both genotypes showed laminated layer of CE without inflammatory cells. In a few cases of the G6 genotype, neutrophils in the outer cuticular layer with mild vascular and congestion were observed. Cell debris with multiple areas of necrosis, as well as scanty lymphoplasma cells in the outer cuticular layer were observed in G1-G3 genotype cases. So, the histopathological differences between the two genotypes are not noticeable enough to be differentiated by microscopical observations.

CONCLUSION: E. granulosus s.s. (G1-G3) and E. canadensis (G6 genotype) are prevalent among CE patients. In general, five haplotypes were identified by nad1 genes analysis. The histopathological differences between the two genotypes have not been so big to be differentiated by microscopic observations.

PMID:40206365 | PMC:PMC11978209 | DOI:10.18502/ijpa.v20i1.18102

Categories: Literature Watch

Editorial: State-of-the-art hypothesis-driven systems pharmacology and artificial intelligence approaches to decipher disease complexity

Systems Biology - Thu, 2025-04-10 06:00

Front Pharmacol. 2025 Mar 26;16:1593164. doi: 10.3389/fphar.2025.1593164. eCollection 2025.

NO ABSTRACT

PMID:40206057 | PMC:PMC11979609 | DOI:10.3389/fphar.2025.1593164

Categories: Literature Watch

Altered Huntingtin-Chromatin Interactions Predict Transcriptional and Epigenetic Changes in Huntington's Disease Mouse Models

Systems Biology - Thu, 2025-04-10 06:00

Dis Model Mech. 2025 Apr 10:dmm.052282. doi: 10.1242/dmm.052282. Online ahead of print.

ABSTRACT

While progressive striatal gene expression changes and epigenetic alterations are a prominent feature of Huntington's disease (HD), the mechanistic basis remains poorly understood. Using chromatin immunoprecipitation and sequencing (ChIP-seq), we show that the huntingtin protein (HTT) reproducibly occupies specific locations in the mouse genome. Striatal HTT ChIP-seq peaks were enriched in coding regions of spiny projection neuron identity genes, which are found to have reduced expression in HD patients and mouse models, and had reduced occupancy in expanded polyglutamine HTT knock-in mice (HttQ111/Q111). Conversely, HTT occupancy was depleted near genes that are up-regulated in HD. ChIP-seq of striatal histone modifications revealed genotype-specific colocalization of HTT with active chromatin marks and enhancer of zeste homolog 2 (EZH2), a key enzymatic component of the PRC2 complex. Near genes that are differentially regulated in HD, greater HTT occupancy in HttQ111/Q111 vs. wildtype mice was associated with increased EZH2 binding, increased H3K4me3, and decreased H3K27me3. Our study suggests that huntingtin-chromatin interactions may play a role in organizing chromatin and promoting cell type-specific gene expression, with HTT occupancy predicting transcriptional dysregulation in HD.

PMID:40205980 | DOI:10.1242/dmm.052282

Categories: Literature Watch

Psychoeducational Program Increases Telomerase Activity in Bipolar Disorder: A Gender-Based Randomized Controlled Trial

Systems Biology - Thu, 2025-04-10 06:00

CNS Neurosci Ther. 2025 Apr;31(4):e70292. doi: 10.1111/cns.70292.

ABSTRACT

AIMS: This randomized controlled trial evaluated the efficacy of a psychoeducational program in enhancing telomerase activity (TA) among patients with bipolar disorder (BD), with a specific focus on gender differences.

METHODS: A total of 62 participants were assigned to either the psychoeducation (PE) group or the control (CTR) group, with TA measured both before and after the intervention.

RESULTS: Results demonstrated a significant increase in TA in the PE group compared to the controls at the conclusion of the study. Notably, gender-specific analyses revealed that female participants showed significant increases in both TA and delta TA (ΔTA), with ΔTA PE = 0.586 ± 0.273 and ΔTA CTR = -0.251 ± 0.177. In contrast, male participants exhibited significant changes only in ΔTA, with ΔTA PE = 0.257 ± 0.138 and ΔTA CTR = -0.144 ± 0.1194.

CONCLUSION: These findings suggest that psychoeducational interventions have differential gender-specific effects, underscoring the importance of personalized approaches in the treatment of BD.

PMID:40205817 | DOI:10.1111/cns.70292

Categories: Literature Watch

Vaccine-associated poliomyelitis: safety of the oral poliovirus vaccine, Brazil, 2013-2023Poliomielitis asociada a poliovirus derivados de la vacuna: seguridad de la vacuna oral contra la poliomielitis en Brasil, 2013-2023

Drug-induced Adverse Events - Thu, 2025-04-10 06:00

Rev Panam Salud Publica. 2025 Apr 9;49:e27. doi: 10.26633/RPSP.2025.27. eCollection 2025.

ABSTRACT

OBJECTIVE: To quantify the occurrence of vaccine-associated paralytic poliomyelitis (VAPP) cases in Brazil from January 2013 to May 2023.

METHODS: A descriptive study was conducted on VAPP cases reported as events supposedly attributable to vaccination or immunization (ESAVI) following oral poliovirus vaccine (OPV) administration. VAPP cases were defined as acute flaccid paralysis (AFP) with isolation of vaccine-derived poliovirus in stool samples and persistence of motor deficits after 60 days.

RESULTS: A total of 200 suspected cases were identified, with two confirmed as VAPP (<1 case per 10 million doses administered) based on the isolation of the vaccine virus. Risk factors associated with VAPP included incomplete vaccination schedules, malnutrition, and/or immunodeficiency.

CONCLUSIONS: VAPP occurrence was rare and aligned with expected values. Continued surveillance of ESAVI and suspected VAPP cases is essential to support poliomyelitis eradication efforts and ensure vaccine safety.

PMID:40206565 | PMC:PMC11980524 | DOI:10.26633/RPSP.2025.27

Categories: Literature Watch

A rare case of factor X deficiency induced by valproic acid

Drug-induced Adverse Events - Thu, 2025-04-10 06:00

Res Pract Thromb Haemost. 2025 Mar 3;9(2):102721. doi: 10.1016/j.rpth.2025.102721. eCollection 2025 Feb.

ABSTRACT

BACKGROUND: Factor X (FX) deficiency (FXD) significantly disrupts coagulation, potentially leading to severe bleeding. While inherited FXD is rare, with a prevalence of 1 in 500,000, acquired FXD is also uncommon and frequently linked to conditions such as light-chain amyloidosis. In rare cases, certain medications can cause FXD.

KEY CLINICAL QUESTION: Here, we present a rare case of acquired FXD induced by valproic acid (VPA). This deficiency is associated with the presence of anti-FX antibodies.

CLINICAL APPROACH: A 65-year-old man undergoing treatment for various conditions, including chronic kidney disease and type 2 diabetes, developed severe FXD (activity <2 U/L) following VPA administration for epilepsy. During FXD, the patient experienced significant bleeding episodes, necessitating FX replacement with prothrombin complex concentrate. Upon discontinuation of VPA, FX activity improved in 9 days, possibly suggesting a role of the drug in FXD. Interestingly, antibodies directed against FX have been identified.

CONCLUSION: This case emphasizes the necessity for clinicians to be vigilant of hemostasis disorders associated with VPA, even though such occurrences are rare.

PMID:40206323 | PMC:PMC11981724 | DOI:10.1016/j.rpth.2025.102721

Categories: Literature Watch

Expert Consensus on the Clinical Application of PI3K/AKT/mTOR Inhibitors in the Treatment of Breast Cancer (2025 Edition)

Drug-induced Adverse Events - Thu, 2025-04-10 06:00

Cancer Innov. 2025 Apr 9;4(3):e70008. doi: 10.1002/cai2.70008. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: The phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB or AKT)/mammalian target of rapamycin (mTOR) signaling pathway (PAM pathway) plays a critical role in breast cancer pathogenesis and progression, and is closely linked with resistance to endocrine therapy in advanced breast cancer. Randomized clinical trials have shown that PI3K/AKT/mTOR inhibitors deliver significant clinical benefits, particularly for patients with advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

METHODS: In 2022, the Breast Cancer Expert Committee of the National Cancer Quality Control Center convened specialists in related fields to draft the "Expert Consensus on the Clinical Application of PI3K/AKT/mTOR Inhibitors in the Treatment of Advanced Breast Cancer." This consensus raised awareness of these inhibitors among oncologists in China and improved the precision of clinical decision-making. In recent years, growing evidence has emphasized the importance of targeting the PAM pathway, reflected in the approval of several innovative agents. This consensus is an updated 2025 edition that retains the foundational structure of the 2022 edition while incorporating notable updates.

RESULTS: Updates to the consensus include the introduction of newly approved PAM pathway inhibitors, updated data from recent clinical trials, and expanded therapeutic applications. The revised guidance also offers updated recommendations for genetic testing to detect alterations in relevant pathways. The section on managing drug-related adverse events has been significantly expanded, providing detailed insights into different types of adverse events and their management. These updates aim to enhance the clinical application of PAM pathway inhibitors, promote precision medicine, and ultimately, improve survival outcomes for patients with breast cancer.

PMID:40206206 | PMC:PMC11981814 | DOI:10.1002/cai2.70008

Categories: Literature Watch

Drug-induced herpes zoster: a pharmacovigilance analysis of FDA adverse event reports from 2004 to 2024

Drug-induced Adverse Events - Thu, 2025-04-10 06:00

Front Pharmacol. 2025 Mar 26;16:1565480. doi: 10.3389/fphar.2025.1565480. eCollection 2025.

ABSTRACT

BACKGROUND: Herpes zoster severely impacts patients' quality of life and therapeutic results. This research utilized data from the FDA Adverse Event Reporting System (FAERS) to examine the prevalence and attributes of drug-induced herpes zoster.

METHODS: We analyzed FAERS reports about zoster from Q1 2004 to Q3 2024 and developed a list of possible pathogenic agents. Ranked the 30 medicines with the greatest incidence of reported herpes zoster cases. Statistical disproportionality analysis was employed to identify an elevated reporting frequency of herpes zoster linked to a particular medication.

RESULTS: Herpes zoster was referenced in 50,164 FAERS reports from 2004 to 2024. The majority of the implicated drugs were immunosuppressants. Anifrolumab exhibited the greatest ROR and PRR ratings among the drugs evaluated. Furthermore, rozanolixizumab, tozinameran, elapegademase, and other medications not indicated for inducing herpes zoster were recognized, underscoring the necessity for increased clinical vigilance and awareness. Nonetheless, these correlations should be regarded with caution, as they do not establish a direct causative relationship.

CONCLUSION: This study underscores the need of pharmacovigilance in recognizing and comprehending drug-induced herpes zoster. Additional research is required to validate these findings and to design strategies for risk management and reduction to enhance treatment outcomes in patients.

PMID:40206093 | PMC:PMC11979123 | DOI:10.3389/fphar.2025.1565480

Categories: Literature Watch

DIA-based quantitative proteomics explores the mechanism of amelioration of APAP-induced liver injury by anoectochilus roxburghii (Wall.) Lindl

Drug-induced Adverse Events - Thu, 2025-04-10 06:00

Front Pharmacol. 2025 Mar 26;16:1508290. doi: 10.3389/fphar.2025.1508290. eCollection 2025.

ABSTRACT

BACKGROUND: Drug-induced liver injury (DILI) is the most common cause of acute liver injury. Anoectochilus roxburghii (Wall.) Lindl. (AR) and its polysaccharide fractions (ARPs) have been shown to have effective therapeutic effects with minimal side effects on a wide range of diseases including hepatopathy. This study aims to determine the therapeutic effects of ARPs on acetaminophen (APAP)-induced liver injury and to explore the mechanistic pathways involved.

METHODS: C57BL/6J male mice at 8 weeks were used to construct a model of APAP-induced liver injury. The acute hepatic injury was induced by oral administration of APAP (300 mg/kg) before 16 h fasting. For therapeutic experiment, mice were gavaged with the water extract of AR (AR.WE) or the purified ARPs before and after APAP administration. Biochemical analyses, ELISA analyses, H&E staining, RT-PCR, and Quantitative proteomic analysis were used to investigate the effects and mechanisms of AR on DILI.

RESULTS: Both AR.WE. and the purified ARPs treatment reduced APAP-induced liver injury, decreased hepatic glutathione and TNF-α levels, alleviated oxidative stress and inflammation. Quantitative proteomic analysis revealed that ARPs downregulated the protein levels involved in apoptosis, inflammation, oxidative stress, necroptosis, while upregulated the protein levels involved in autophagy. These protective effects of ARPs are possibly related to the downregulation of vATPase activity and thus participating in the autophagic process and ferroptosis.

CONCLUSION: ARPs can protect mice against APAP-induced liver injury, alleviate oxidative stress and inflammation. Our study reveals a potential therapeutic effect for ARPs in protecting APAP-induced liver injury.

PMID:40206085 | PMC:PMC11979217 | DOI:10.3389/fphar.2025.1508290

Categories: Literature Watch

'We are the engine': a focus group study on clinical practice guideline development with European patient advocates for rare congenital malformations and/or intellectual disability

Orphan or Rare Diseases - Wed, 2025-04-09 06:00

Orphanet J Rare Dis. 2025 Apr 10;20(1):169. doi: 10.1186/s13023-025-03673-9.

ABSTRACT

BACKGROUND: Individuals living with rare congenital malformations and/or intellectual disability often face challenges in accessing appropriate healthcare. Clinical practice guidelines (CPGs) may serve as a tool to provide evidence-based care for rare diseases, but their development is complex, and the views of affected individuals and families often remain unknown.

METHODS: Patient advocates of the European Reference Network ITHACA (Intellectual disability, TeleHealth, Autism and Congenital Anomalies) participated in focus groups in which their experiences with and perspectives on CPG use and development were discussed.

RESULTS: Patient advocates considered CPGs relevant to address information and care needs and support advocacy efforts. Important characteristics included representation of heterogeneity within conditions, a holistic approach in which and how topics are addressed, user-friendly availability for individuals and families, and reliability of information. Guideline development and implementation were described as challenging, iterative processes in which effective partnership between clinicians, patient advocates, and other stakeholders is essential.

CONCLUSIONS: Understanding the perspectives of patient advocates is essential to develop CPGs that meet the life-long and complex care needs of individuals and families living with rare conditions. Identified challenges include balancing the urgency of information needs with thorough guideline development processes, as well as the integration and interpretation of different types of knowledge.

PMID:40205602 | DOI:10.1186/s13023-025-03673-9

Categories: Literature Watch

Pharmacovigilance study of adverse reactions of anti-HER-2 drugs for the treatment of HER-2-positive breast cancer based on the FAERS database

Drug-induced Adverse Events - Wed, 2025-04-09 06:00

Breast Cancer Res. 2025 Apr 9;27(1):54. doi: 10.1186/s13058-025-02013-w.

ABSTRACT

OBJECTIVE: There are three categories of drugs that treat human epidermal growth factor receptor type 2 (HER-2) positive breast cancer: monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs). The purpose of this study is to analyze and compare the adverse reactions of three classes of anti-HER-2 drugs to various body systems in patients based on the FDA Adverse Event Reporting System (FAERS).

METHODS: All data reports were extracted from the FAERS between 2004 and 2024. Data mining of adverse events associated with anti-HER-2 drugs was carried out using disproportionality analysis. A multivariate logistic regression analysis was conducted to explore the risk factors associated with AEs leading to hospitalization.

RESULTS: A total of 47,799 patients were screened for the three classes of drugs, among which ADC drugs caused the largest proportion of deaths. MAb has the strongest ADR signals associated with "cardiac disorders". Moreover, trastuzumab was associated with a greater risk of cardiotoxicity. Logistic regression analysis revealed that the treatment with mAbs should be wary of serious adverse reactions in "infections and infestations" and "metabolism and nutrition disorders". Moreover, "endocrine disorders" were the factor associated with the highest risk of prolonged hospitalization due to trastuzumab deruxtecan (T-DXd). The safety of tucatinib among TKI drugs is greater than that of other drugs.

CONCLUSION: In general, from the perspective of the effects of the three classes of drugs on the various body systems of patients, we should focus on mAb-associated "cardiac disorders", ADC-associated "hepatobiliary disorders", "respiratory, thoracic and mediastinal disorders", and TKI-associated "gastrointestinal disorders.

PMID:40205546 | DOI:10.1186/s13058-025-02013-w

Categories: Literature Watch

Novel deep learning algorithm based MRI radiomics for predicting lymph node metastases in rectal cancer

Deep learning - Wed, 2025-04-09 06:00

Sci Rep. 2025 Apr 9;15(1):12089. doi: 10.1038/s41598-025-96618-y.

ABSTRACT

To explore the value of applying the MRI-based radiomic nomogram for predicting lymph node metastasis (LNM) in rectal cancer (RC). This retrospective analysis used data from 430 patients with RC from two medical centers. The patients were categorized into the LNM negative (LNM-) and LNM positive (LNM+) according to their surgical pathology results. We developed a physician model by selecting clinical independent predictors through physician assessments. Additionally, we developed deep learning radscore (DLRS) models by extracting deep features from multiparametric MRI (mpMRI) images. A nomogram model was constructed by combining the physician model and DLRS models. Among the patients, 192 (44.65%, 192/430) experienced LNM+. Six prediction models were developed, namely the physician model, three sequence models, the DLRS, and the nomogram. The physician model achieved AUC of the receiver operating characteristic (ROC) values of 0.78, 0.79, and 0.7, whereas the sequence models, DLRS model, and nomogram model achieved AUC values ranging from 0.83 to 0.99. The predictive performance of the DLRS and nomogram models was superior to that of the physician model. DLRS and nomogram models based on mpMRI provided higher accuracy in predicting LNM status in patients with RC than the other models.

PMID:40204902 | DOI:10.1038/s41598-025-96618-y

Categories: Literature Watch

Comprehensive evaluation of U-Net based transcranial magnetic stimulation electric field estimations

Deep learning - Wed, 2025-04-09 06:00

Sci Rep. 2025 Apr 9;15(1):12204. doi: 10.1038/s41598-025-95767-4.

ABSTRACT

Transcranial Magnetic Stimulation (TMS) is a non-invasive method to modulate neural activity by inducing an electric field in the human brain. Computational models are an important tool for informing TMS targeting and dosing. State-of-the-art modeling techniques use numerical methods, such as the finite element method (FEM), to produce highly accurate simulation results. However, these methods operate at a high computational cost, limiting real-time integration and high throughput applications. Deep learning (DL) methods, particularly U-Nets, are being investigated for TMS electric field estimations. However, their performance across large datasets and whole-head stimulation conditions has not been systematically evaluated. Here, we develop a DL framework to estimate TMS-induced electric fields directly from an anatomical magnetic resonance image (MRI) and TMS coil parameters. We perform a comprehensive evaluation of the performance of our U-Net approach compared to the FEM gold standard. We selected a dataset of 100 MRI scans from a diverse population demographic (ethnic, gender, age) made available by the Human Connectome Project. For each MRI, we generated a FEM head model and simulated the electric fields for 13 TMS coil orientations and 1206 positions (a total of 15,678 coil configurations per participant). We trained a modified U-Net architecture to predict individual TMS-induced electric fields in the brain based on an input T1-weighted MRI scan and stimulation parameters. We characterized the model's performance according to computational efficiency and simulation accuracy compared to FEM using an independent testing dataset. The U-Net results demonstrated an accelerated electric field modeling speed at 0.8 s per simulation (×97,000 times acceleration over the FEM-based approach). Sampling stimulation conditions across the whole brain yielded an average DICE coefficient of 0.71 ± 0.06 mm and an average center of gravity deviation of 7.52 ± 4.06 mm from the FEM-based approach. Our findings indicate that while deep learning has the potential to significantly accelerate electric field predictions, the precision it achieves needs to be evaluated for the specific TMS application.

PMID:40204769 | DOI:10.1038/s41598-025-95767-4

Categories: Literature Watch

Deep learning for cerebral vascular occlusion segmentation: A novel ConvNeXtV2 and GRN-integrated U-Net framework for diffusion-weighted imaging

Deep learning - Wed, 2025-04-09 06:00

Neuroscience. 2025 Apr 7:S0306-4522(25)00287-8. doi: 10.1016/j.neuroscience.2025.04.010. Online ahead of print.

ABSTRACT

Cerebral vascular occlusion is a serious condition that can lead to stroke and permanent neurological damage due to insufficient oxygen and nutrients reaching brain tissue. Early diagnosis and accurate segmentation are critical for effective treatment planning. Due to its high soft tissue contrast, Magnetic Resonance Imaging (MRI) is commonly used for detecting these occlusions such as ischemic stroke. However, challenges such as low contrast, noise, and heterogeneous lesion structures in MRI images complicate manual segmentation and often lead to misinterpretations. As a result, deep learning-based Computer-Aided Diagnosis (CAD) systems are essential for faster and more accurate diagnosis and treatment methods, although they can sometimes face challenges such as high computational costs and difficulties in segmenting small or irregular lesions. This study proposes a novel U-Net architecture enhanced with ConvNeXtV2 blocks and GRN-based Multi-Layer Perceptrons (MLP) to address these challenges in cerebral vascular occlusion segmentation. This is the first application of ConvNeXtV2 in this domain. The proposed model significantly improves segmentation accuracy, even in low-contrast regions, while maintaining high computational efficiency, which is crucial for real-world clinical applications. To reduce false positives and improve overall accuracy, small lesions (≤5 pixels) were removed in the preprocessing step with the support of expert clinicians. Experimental results on the ISLES 2022 dataset showed superior performance with an Intersection over Union (IoU) of 0.8015 and a Dice coefficient of 0.8894. Comparative analyses indicate that the proposed model achieves higher segmentation accuracy than existing U-Net variants and other methods, offering a promising solution for clinical use.

PMID:40204150 | DOI:10.1016/j.neuroscience.2025.04.010

Categories: Literature Watch

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