Literature Watch

Erratum: Volumetric Breast Density Estimation From Three-Dimensional Reconstructed Digital Breast Tomosynthesis Images Using Deep Learning

Deep learning - Tue, 2025-01-14 06:00

JCO Clin Cancer Inform. 2025 Jan;9:e2400325. doi: 10.1200/CCI-24-00325. Epub 2025 Jan 14.

NO ABSTRACT

PMID:39807853 | DOI:10.1200/CCI-24-00325

Categories: Literature Watch

CircZMYM2 Alleviates TGF-β1-Induced Proliferation, Migration and Activation of Fibroblasts via Targeting miR-199b-5p/KLF13 Axis

Idiopathic Pulmonary Fibrosis - Tue, 2025-01-14 06:00

Appl Biochem Biotechnol. 2025 Jan 14. doi: 10.1007/s12010-024-05168-y. Online ahead of print.

ABSTRACT

Dysregulated circular RNAs (circRNAs) has been revealed to be involved in pulmonary fibrosis progression. Herein, this study focused on exploring the function and mechanism of circRNA Zinc Finger MYM-Type Containing 2 (circZMYM2) on idiopathic pulmonary fibrosis (IPF) using transforming growth factor (TGF)-β1-stimulated fibroblasts. Human fibroblast cell lines IMR-90 and HFL1 were stimulated with TGF-β1 to mimic fibrosis condition in vitro. Levels of genes and proteins were detected by qRT-PCR and western blotting. Cell proliferation and migration were analyzed using cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine (EdU) and wound healing assays. The fibrosis progression was determined by the change of E-cadherin, α-smooth muscle actin (α-SMA), collagen type I α 1 (COL1A1) and collagen type III α 1 (COL3A1). The interaction between miR-199b-5p and circZMYM2 or KLF13 (Kruppel Like Factor 13) was analyzed using dual-luciferase reporter, RIP and RNA-pull-down assays. CircZMYM2 was decreased in TGF-β1-induced IMR-90 and HFL1 fibroblasts. Functionally, re-expression of circZMYM2 in IMR-90 and HFL1 cells could attenuate TGF-β1-evoked proliferation, migration and fibrosis in cells. Mechanistically, the circZMYM2/miR-199b-5p/KLF13 constituted a competing endogenous RNA (ceRNA). TGF-β1 reduced KLF13 expression and increased miR-199b-5p expression in IMR-90 and HFL1 cells. Further rescue experiments suggested that miR-199b-5p up-regulation or KLF13 knockdown reversed the anti-fibrotic effects of circZMYM2; moreover, silencing of miR-199b-5p exhibited anti-fibrotic effects, which was counteracted by KLF13 knockdown. CircZMYM2 had an anti-fibrotic effect that could suppress fibroblast activation via miR-199b-5p/KLF13 axis, pointing a novel perspective into the potential action pattern of circ_0022383 in IPF.

PMID:39808406 | DOI:10.1007/s12010-024-05168-y

Categories: Literature Watch

Survival and early outcomes following lung transplantation for interstitial lung disease associated with non-scleroderma connective tissue disease: a national cohort study

Idiopathic Pulmonary Fibrosis - Tue, 2025-01-14 06:00

Clin Exp Rheumatol. 2025 Jan 14. doi: 10.55563/clinexprheumatol/tjnyz5. Online ahead of print.

ABSTRACT

OBJECTIVES: The progressive decline in interstitial lung disease associated with non-scleroderma connective tissue disease (ILD-NSCTD) is linked to poor prognosis and frequently results in respiratory failure. Lung transplantation (LTx) offers a viable treatment option, yet its outcomes in ILD-NSCTD remain contentious, particularly across different subtypes.

METHODS: This retrospective cohort study included patients with idiopathic pulmonary fibrosis (IPF) (n=11,610) and ILD-NSCTD (n=610) listed in the United Network for Organ Sharing (UNOS) database who underwent lung transplantation between May 5, 2005, and December 31, 2022. We used the Kaplan-Meier method to evaluate cumulative survival rates and logistic regression to assess the risk of post-operative complications.

RESULTS: Compared to IPF patients, those with ILD-NSCTD are generally younger, with a lower proportion of male and white patients. After propensity matching, overall survival rates remained similar between the groups (log-rank, p=0.953). However, ILD-NSCTD was associated with a significantly higher risk of post-operative stroke (adjusted OR 1.75, 95% CI 1.12-2.74, p=0.015) and longer post-operative hospital stays (p<0.001). Subgroup analyses yielded consistent results. Finally, infection was identified as the leading cause of death.

CONCLUSIONS: Compared to IPF, patients with ILD-NSCTD have a significantly higher risk of post-operative stroke and extended hospital stays, potentially due to complications inherent to ILD-NSCTD. However, the underlying causes of these outcomes remain unclear. Despite these differences, short-term and long-term survival rates are comparable between the two groups, with consistent findings across various ILD-NSCTD subgroups. Therefore, ILD-NSCTD should not be regarded as a relative contraindication for lung transplantation. Nonetheless, the influence of extra-pulmonary complications in ILD-NSCTD patients requires further investigation.

PMID:39808303 | DOI:10.55563/clinexprheumatol/tjnyz5

Categories: Literature Watch

Regulatory T Cell Phenotype Related to Cytokine Expression Patterns in Post-COVID-19 Pulmonary Fibrosis and Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis - Tue, 2025-01-14 06:00

Immun Inflamm Dis. 2025 Jan;13(1):e70123. doi: 10.1002/iid3.70123.

ABSTRACT

BACKGROUND: Post-coronavirus disease 19 lung fibrosis (PCLF) shares common immunological abnormalities with idiopathic pulmonary fibrosis (IPF), characterized by an unbalanced cytokine profile being associated with the development of lung fibrosis. The aim of the present study was to analyze and compare the different subsets of CD4- and CD8-T cells, along with specific cytokine expression patterns, in peripheral blood (PB) from patients affected by PCLF and IPF and healthy controls (HCs).

METHODS: One-hundred patients followed at the Rare Lung Disease Center of Siena University Hospital were enrolled. Eight HCs were recruited. PB samples were collected, and CD4- and CD8-T subsets were analyzed through flow cytometry. Multiplex bead-based LEGENDplex™ were used for cytokine quantification.

RESULTS: Higher CD8 percentages were observed in IPF than in HCs and PCLF (p = 0.020 and p = 0.007, respectively). PCLF subgroup showed higher Th-naïve, Th-effector, Tc-naïve, and Tc-reg percentages than IPF (p < 0.001; p = 0.018; p = 0.005; p = 0.017, respectively). Th-naïve and Tc-naïve inversely correlated with Tc-reg (p < 0.0001, r = -0.61 and p = 0.005, r = -0.39, respectively). Tc-naïve-PD1 and Tc-effector-PD1 percentages were higher in PCLF than IPF (p < 0.001), while Tfh-reg and Tfc-reg were significantly higher in IPF than PCLF (p < 0.001). IL-4, IL-2, TNF-α, and IL-17A were more expressed in PCLF than IPF (p < 0.001). IL-8 directly correlated with Tc-naïve percentages in PCLF (p = 0.018, r = 0.35).

CONCLUSION: A variety of immune cells is involved in the development and progression of pulmonary fibrosis confirming an immunological similarity between IPF and PCLF. T-reg cells play a key role in the worsening of the disease. High cytokine values showed a pro-fibrotic environment in PCLF patients, suggesting dysregulation of the immune system of these patients. Moreover, the immunological similarity between IPF and PCLF patients suggests that SARS-CoV2 infection may trigger the activation of biological pathways common with IPF.

PMID:39807767 | DOI:10.1002/iid3.70123

Categories: Literature Watch

LIN28B-mediated PI3K/AKT pathway activation promotes metastasis in colorectal cancer models

Systems Biology - Tue, 2025-01-14 06:00

J Clin Invest. 2025 Jan 14:e186035. doi: 10.1172/JCI186035. Online ahead of print.

ABSTRACT

Colorectal cancer (CRC) remains a leading cause of cancer death due to metastatic spread. LIN28B is overexpressed in 30% of CRCs and promotes metastasis, yet its mechanisms remain unclear. In this study, we genetically modified CRC cell lines to overexpress LIN28B, resulting in enhanced PI3K/AKT pathway activation and liver metastasis in mice. We developed genetically modified mouse models with constitutively active Pik3ca that form intestinal tumors progressing to liver metastases with an intact immune system, addressing the limitations of previous Pik3ca-mutant models, including long tumor latency, mixed histology, and lack of distant metastases. The PI3Kα-specific inhibitor alpelisib reduced migration and invasion in vitro and metastasis in vivo. We present the first comprehensive analysis of vertical inhibition of the PI3K/AKT pathway in CRC using FDA-approved drugs alpelisib and capivasertib (an AKT inhibitor) in combination with LY2584702 (an S6K inhibitor) in CRC cell lines and mouse- and patient-derived organoids (PDOs). Tissue microarrays from CRC patients confirmed that LIN28B and PI3K/AKT pathway activation correlate with CRC progression. These findings highlight the critical role of the LIN28B-mediated PI3K/AKT pathway in CRC metastasis, the therapeutic potential of targeted inhibition, and the promise of PDOs in precision medicine in metastatic CRC.

PMID:39808497 | DOI:10.1172/JCI186035

Categories: Literature Watch

Characterization and design of dipeptide media formulation for scalable therapeutic production

Systems Biology - Tue, 2025-01-14 06:00

Appl Microbiol Biotechnol. 2025 Jan 14;109(1):7. doi: 10.1007/s00253-024-13402-0.

ABSTRACT

Process intensification and simplification in biopharmaceutical manufacturing have driven the exploration of advanced feeding strategies to improve culture performance and process consistency. Conventional media design strategies, however, are often constrained by the stability and solubility challenges of amino acids, particularly in large-scale applications. As a result, dipeptides have emerged as promising alternatives. Despite extensive research on amino acids, dipeptide supplementation in Chinese hamster ovary (CHO) cell-based manufacturing has received comparatively less attention. In this review, we critically analyze challenges associated with amino acids prone to instability and poor solubility (e.g., glutamine, cysteine, and tyrosine), and explore the potential of dipeptides to address these limitations. We explore the intricate mechanisms of dipeptide transport and enzymatic cleavage, highlighting how chemical properties, stereoisomerism, and competitive metabolites influence their utilization. Notably, while most dipeptides exhibit enhanced solubility, their stabilization effects and culture performance remain variable, underlining the need for rational design. To guide future innovations, we propose tailored dipeptide strategies derived for specific biomanufacturing needs by integrating multi-omics analysis, metabolic flux modeling, and artificial intelligence (AI) modeling. KEY POINTS : •Explored dipeptides as a solution to amino acid instability and poor solubility, enhancing cell culture performance. •Discussed transporter kinetics and cleavage enzymes influencing dipeptide utilization in biomanufacturing. •Suggested various design strategies for identifying appropriate dipeptide pairs to improve bioprocess efficiency.

PMID:39808320 | DOI:10.1007/s00253-024-13402-0

Categories: Literature Watch

Utilising bioinformatics and systems biology methods to uncover the impact of dermatomyositis on interstitial lung disease

Systems Biology - Tue, 2025-01-14 06:00

Clin Exp Rheumatol. 2025 Jan 3. doi: 10.55563/clinexprheumatol/fok820. Online ahead of print.

ABSTRACT

OBJECTIVES: Dermatomyositis (DM) is frequently associated with interstitial lung disease (ILD); however, the molecular mechanisms underlying this association remain unclear. This study aimed to employ bioinformatics approaches to identify potential molecular mechanisms linking DM and ILD.

METHODS: GSE46239 and GSE47162 were analysed to identify common differentially expressed genes (DEGs). These DEGs underwent Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis. A protein-protein interaction (PPI) network was constructed to identify hub genes and transcriptional regulators. Potential therapeutic drugs were predicted using the Drug-Gene Interaction Database (DGIDB).

RESULTS: A total of 122 common DEGs were identified between the DM and ILD datasets. These DEGs were significantly enriched in signal transduction, transcriptional regulation, inflammation, and cell proliferation. Key pathways included the NOD-like receptor signalling pathway, cytokine-cytokine receptor interaction, and TNF signalling pathway. PPI network analysis revealed the top 10 hub genes: CD163, GZMB, IRF4, CCR7, MMP9, AIF1, CXCL10, CCL5, IRF8, and NLRP3. Additionally, interactions between hub genes and transcription factors/miRNAs were constructed. Eleven drugs targeting four hub genes (CXCL10, MMP9, GZMB, and NLRP3) were predicted using the DGIDB.

CONCLUSIONS: In summary, the study identified 10 key genes involved in the molecular pathogenesis of DM and ILD. Moreover, 11 potential drugs were identified that may offer viable therapeutic options for treating DM and ILD in the future.

PMID:39808289 | DOI:10.55563/clinexprheumatol/fok820

Categories: Literature Watch

Detection and quantification of ergothioneine in human serum using surface enhanced Raman scattering (SERS)

Systems Biology - Tue, 2025-01-14 06:00

Analyst. 2025 Jan 14. doi: 10.1039/d4an01323a. Online ahead of print.

ABSTRACT

Ergothioneine (ERG) is a natural sulfur-containing amino acid found in many organisms, including humans. It accumulates at high concentrations in red blood cells and is distributed to various organs, including the brain. ERG has numerous health benefits and antioxidant capabilities, and it has been linked to various human physiological processes, such as anti-inflammatory, neuroprotective, and anti-aging effects. Accurate, rapid, and cost-effective quantification of ERG levels in human biofluids is crucial for understanding its role in oxidative stress-related diseases. Surface-enhanced Raman scattering (SERS) is an effective approach for measuring compounds at concentrations similar to those at which ERG is present in serum. However, while SERS has been used to characterize or detect ERG, quantification has not yet been achieved due to the variability in the signal enhancement that can arise during sample preparation and analysis. This study introduces a highly efficient and reliable technique for quickly (20 min is typical per sample) measuring ERG levels in human serum using SERS. This employs an internal standard highly specific for ERG which resulted in limit of quantification values of 0.71 μM. To validate this approach, we analysed real human serum with unknown ERG levels as a blind test set and primary reference levels of ERG were produced using a targeted UHPLC-MS/MS reference method.

PMID:39807959 | DOI:10.1039/d4an01323a

Categories: Literature Watch

Romosozumab adverse event profile: a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) from 2019 to 2023

Drug-induced Adverse Events - Tue, 2025-01-14 06:00

Aging Clin Exp Res. 2025 Jan 14;37(1):23. doi: 10.1007/s40520-024-02921-5.

ABSTRACT

OBJECTIVE: This study aims to analyze adverse drug events (ADE) related to romosozumab from the second quarter of 2019 to the third quarter of 2023 from FAERS database.

METHODS: The ADE data related to romosozumab from 2019 Q2 to 2023 Q3 were collected. After data normalization, four signal strength quantification algorithms were used: ROR (Reporting Odds Ratios), PRR (Proportional Reporting Ratios), BCPNN (Bayesian Confidence Propagation Neural Network), and EBGM (Empirical Bayesian Geometric Mean).

RESULTS: Screening for romosozumab-related AEs (adverse events) included 23 system organ categories (SOCs). PT (preferred terms) levels were screened for adverse drug reaction (ADR) signals. A total of 7055 reports with romosozumab as the primary suspect (PS) and 14,041 PTs induced by romosozumab as PS were identified. Common significant signals of general disorders and administration site conditions, musculoskeletal and connective tissue disorders have emerged. Specifically, unexpected AEs such as gastrointestinal disorder, respiratory, thoracic and mediastinal disorders also occur. Notably, fracture (n = 503, ROR = 107.8, PRR = 103.83, IC = 6.6, EBGM = 97.02) and bone density abnormal (n = 429, ROR = 343.65, PRR = 332.77, IC = 8.08, EBGM = 271.34) exhibited relatively high occurrence rates and signal strengths.

CONCLUSION: Our study identifies potential new AE signals and provides broader data support for the safety of romosozumab. In clinical application, doctors are provided with a warning to closely monitor adverse reactions to support their rational use in diseases such as osteoporosis.

PMID:39808360 | DOI:10.1007/s40520-024-02921-5

Categories: Literature Watch

Phase I Dose Volume Escalation of Rectally Administered PC-1005 to Assess Safety, Pharmacokinetics, and Antiviral Pharmacodynamics as a Multipurpose Prevention Technology (MTN-037)

Drug-induced Adverse Events - Tue, 2025-01-14 06:00

J Acquir Immune Defic Syndr. 2024 Dec 1;97(4):379-386. doi: 10.1097/QAI.0000000000003506.

ABSTRACT

BACKGROUND: On demand, topical PrEP is desired by those preferring episodic, nonsystemic PrEP. PC-1005 gel (MIV-150, zinc, and carrageenan) exhibits in vitro antiviral HIV-1, human papillomavirus (HPV), and herpes simplex virus type 2 (HSV-2) activity, attractive for a multipurpose prevention technology candidate. We evaluated the safety, pharmacokinetics, and antiviral effect of rectally applied PC-1005.

METHODS: HIV-uninfected adults received a series of 3 rectal PC-1005 doses-4, 16, and 32 mL separated by 2-week washout periods. Following each dose, plasma, rectal fluid and tissue, and vaginal fluid were collected over 48 hours.

RESULTS: Thirteen adults enrolled; 12 completed all 3 doses. All 13 adverse events reported were grade 1 or 2; 5 were judged study drug related. Plasma MIV-150 peaked 1-2 h after dosing with a median peak concentrations range of 0.07-0.23 ng/mL and median half-life range of 4.9-7.4 hours across dose volumes; median concentrations were below assay quantitation limits (BLQ) 24 hours after dosing. Rectal tissue MIV-150 peaked 0.5-1 hours after dosing at 1.4 ng/g (ng/mL) (0.8, 1.9), 46.0 (30.7, 831.0), and 79.7 (11.9, 116.0), respectively, after each dose volume; median tissue concentrations were BLQ beyond 5 hours for all doses. All vaginal fluid samples were BLQ. Ex vivo antiviral assays showed 5 hours of antiviral HPV and HSV effects but no anti-HIV activity.

CONCLUSIONS: MIV-150 rectal tissue concentrations were below the 100 ng/g target concentration and transient. Ex vivo assays demonstrated antiviral HSV and HPV effects but not against HIV. PC-1005 requires a more potent antiviral and longer-lasting formulation for further consideration as a multipurpose prevention technology candidate.

CLINICAL TRIALS: NCT03408899.

PMID:39808074 | DOI:10.1097/QAI.0000000000003506

Categories: Literature Watch

Efficacy and safety of rivaroxaban in preventing venous thromboembolism in postoperative patients with gynecological malignancies: protocol for a randomised controlled open-label trial (G-alfalfa trial)

Pharmacogenomics - Tue, 2025-01-14 06:00

BMJ Open. 2024 Dec 20;14(12):e092164. doi: 10.1136/bmjopen-2024-092164.

ABSTRACT

INTRODUCTION: Compared with the guideline-recommended use of low-molecular weight heparin (LMWH) for 28 days to prevent venous thromboembolism (VTE) after cytoreductive surgery, oral rivaroxaban avoids the pain and inconvenience of daily injections and reduces medical expenses. The proposed randomised controlled trial (RCT) aims to compare the efficacy and safety of rivaroxaban and enoxaparin in preventing VTE in patients after surgery for gynaecological malignancies and to provide a reference for clinical medication prevention.

METHODS AND ANALYSIS: This is a single-centre, randomised, controlled, open-label and assessor-blind clinical trial. Patients undergoing surgery for gynaecological malignancies will be randomly assigned in a 1:1 ratio to an oral rivaroxaban study group and a subcutaneous injection enoxaparin control group for anticoagulant prophylaxis. The medication administration begins 12-24 hours after surgery and continues for 28 days, with a 30-day follow-up after surgery. Clinical events during the treatment and the follow-up period will be observed. The primary endpoint will be any VTE. Secondary endpoints will be any bleeding event, medication compliance rate, rivaroxaban pharmacokinetics and pharmacogenomics. The sample size required for the G-alfalfa trial is derived based on power calculations of the VTE incidence in the two intervention regimens in previous literature.

ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Fujian Maternal and Child Health Hospital on 2 April 2024 (Approval No.:2023KY174-03). The results of the trial will be submitted for publication in a peer-reviewed journal and presented at relevant conferences.

TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR) 2300078535.

PMID:39806649 | DOI:10.1136/bmjopen-2024-092164

Categories: Literature Watch

Epidemiology, microbiology and clinical impacts of non-tuberculous mycobacteria in adult patients with cystic fibrosis

Cystic Fibrosis - Tue, 2025-01-14 06:00

Heliyon. 2024 Dec 17;11(1):e41324. doi: 10.1016/j.heliyon.2024.e41324. eCollection 2025 Jan 15.

ABSTRACT

BACKGROUND: Due to its increasing prevalence and suboptimal treatment, non-tuberculous mycobacterial (NTM) infection is an emerging problem in patients with cystic fibrosis (CF). Detailed description of regional NTM prevalence and distribution, and identification of predictors of NTM acquisition in CF are essential to optimise treatment and surveillance guidelines.

METHODS: A retrospective, multi-center analysis was conducted between the years 2020 and 2022 on data from 232 adult patients registered in the Hungarian CF Registry in 2022. In a case-control analysis of NTM-positive (n = 39) and NTM-negative (n = 73) CF patients, demographic, clinical, and microbiological data were analysed to identify potential predictors for NTM acquisition. The distribution of NTM species, their antibiotic susceptibility patterns were also evaluated.

RESULTS: The prevalence of NTM-positive sputum increased from 4.7 % to 12.9 % over study period. The most prevalent NTMs were M. avium complex (41.0 %), M. abscessus complex (MABSC) (38.5 %) and M. xenopi (15.4 %). MABSC strains were highly resistant to doxycycline, fluoroquinolones, and sulfonamides, while amikacin, macrolides, tigecycline and linezolid were often effective. Forced expiratory volume in 1 s (FEV1) was lower in the NTM-positive group at the index date and 1 and 2 years before NTM detection (p < 0.01), predicting NTM infection. Previous NTM-positive sputum culture enhanced the risk of NTM reacquisition in the airway (odds ratio: 7).

CONCLUSION: The results demonstrate a high prevalence of NTM in the Hungarian adult CF population and a high rate of multidrug-resistant MABSC isolates in their sputum. The risk of acquiring airway NTM is higher in CF patients with significantly impaired lung function and previous respiratory mycobacteriosis.

PMID:39807497 | PMC:PMC11728951 | DOI:10.1016/j.heliyon.2024.e41324

Categories: Literature Watch

Development of ICF-based patient-reported outcome and experience measures to study social participation among people with chronic diseases: a mixed-methods protocol

Cystic Fibrosis - Tue, 2025-01-14 06:00

BMJ Open. 2024 Dec 22;14(12):e087798. doi: 10.1136/bmjopen-2024-087798.

ABSTRACT

INTRODUCTION: Living with a chronic disease impacts many aspects of life, including the ability to participate in activities that enable interactions with others in society, that is, social participation (SP). Despite efforts to monitor the quality of care and life of chronically ill people in Belgium, no disease-specific patient-reported measures (PRMs) have been used. These tools are essential to understand SP and to develop evidence-based recommendations to support its improvement. This protocol presents the phases for the disease-specific development of patient-reported outcome and experience measures to assess SP and its potential determinants among people living in Belgium with cancer, cystic fibrosis, diabetes, HIV or a neuromuscular disease.

METHODS AND ANALYSIS: This protocol applies the PROMIS Instrument Development and Validation Scientific Standards and COnsensus-based Standards for the selection of health Measurement INstruments to develop PRMs in a disease-specific manner to quantify the components of the International Classification of Functioning, Disability and Health (ICF). A mixed-method approach is used to create broad initial item pools based on patient (focus groups) and literature perspectives which are compared within ICF-standardised language by applying the refined ICF linking rules. An item set is first created based on this cross-matching exercise and then validated by multidisciplinary expert panels. Cognitive assessment and pilot testing are followed by the dissemination of the survey to a representative sample in Belgium. Advanced psychometric testing (classical test theory and item response theory) is applied to inform an item reduction strategy for the final measures and to develop scales for the ICF components.

ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Committee of the Ghent University Hospital on 20 February 2023 to organise the patient focus groups (ONZ-2022-0470). Ethical approval for dissemination of the PRMs and psychometric testing will be sought at the Ghent University Hospital Ethics Committee at the start of Phase 6. Results will be disseminated through peer-reviewed journals and professional conferences.

PMID:39806694 | DOI:10.1136/bmjopen-2024-087798

Categories: Literature Watch

Respiratory rehabilitation techniques for patients with cystic fibrosis: a protocol for a systematic review and network meta-analysis

Cystic Fibrosis - Tue, 2025-01-14 06:00

BMJ Open. 2024 Dec 20;14(12):e092747. doi: 10.1136/bmjopen-2024-092747.

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, primarily affecting the respiratory and digestive systems. Respiratory rehabilitation techniques play a crucial role in managing pulmonary symptoms and maintaining lung function in CF patients. Although various techniques have been developed and applied, there is currently no globally recognised optimal respiratory rehabilitation regimen. This study intends to conduct a network meta-analysis to comprehensively evaluate and compare the effectiveness of different respiratory rehabilitation techniques in CF patients.

METHODS AND ANALYSIS: The following key electronic bibliographic databases will be searched from inception to September 2024: Medline, Embase, Cochrane Library, Web of Science, CINAHL and Physiotherapy Evidence Database. We will include randomised controlled trials (RCTs) and quasi-RCTs that compare the efficacy of various respiratory rehabilitation techniques in CF patients, such as airway clearance techniques, exercise training and inspiratory muscle training. The primary outcomes will be lung function (forced expiratory volume in 1 s and forced vital capacity) and exercise capacity (VO2 max and 6 min walk test). Secondary outcomes will include quality of life, frequency of pulmonary exacerbations, hospitalisation rates and adverse events. If permitted, data will be synthesised using traditional pairwise meta-analysis and network meta-analysis, with the quality of evidence assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

ETHICS AND DISSEMINATION: Ethical approval will not be required for this protocol. The results of the final review will be disseminated via peer-reviewed journals and conference presentations.

PROSPERO REGISTRATION NUMBER: CRD42024574551.

PMID:39806674 | DOI:10.1136/bmjopen-2024-092747

Categories: Literature Watch

Sleep stages classification based on feature extraction from music of brain

Deep learning - Tue, 2025-01-14 06:00

Heliyon. 2024 Dec 12;11(1):e41147. doi: 10.1016/j.heliyon.2024.e41147. eCollection 2025 Jan 15.

ABSTRACT

Sleep stages classification one of the essential factors concerning sleep disorder diagnoses, which can contribute to many functional disease treatments or prevent the primary cognitive risks in daily activities. In this study, A novel method of mapping EEG signals to music is proposed to classify sleep stages. A total of 4.752 selected 1-min sleep records extracted from the capsleep database are applied as the statistical population for this assessment. In this process, first, the tempo and scale parameters are extracted from the signal according to the rules of music, and next by applying them and changing the dominant frequency of the pre-processed single-channel EEG signal, a sequence of musical notes is produced. A total of 19 features are extracted from the sequence of notes and fed into feature reduction algorithms; the selected features are applied to a two-stage classification structure: 1) the classification of 5 classes (merging S1 and REM-S2-S3-S4-W) is made with an accuracy of 89.5 % (Cap sleep database), 85.9 % (Sleep-EDF database), 86.5 % (Sleep-EDF expanded database), and 2) the classification of 2 classes (S1 vs. REM) is made with an accuracy of 90.1 % (Cap sleep database),88.9 % (Sleep-EDF database), 90.1 % (Sleep-EDF expanded database). The overall percentage of correct classification for 6 sleep stages are 88.13 %, 84.3 % and 86.1 % for those databases, respectively. The other objective of this study is to present a new single-channel EEG sonification method, The classification accuracy obtained is higher or comparable to contemporary methods. This shows the efficiency of our proposed method.

PMID:39807512 | PMC:PMC11728888 | DOI:10.1016/j.heliyon.2024.e41147

Categories: Literature Watch

AxonFinder: Automated segmentation of tumor innervating neuronal fibers

Deep learning - Tue, 2025-01-14 06:00

Heliyon. 2024 Dec 15;11(1):e41209. doi: 10.1016/j.heliyon.2024.e41209. eCollection 2025 Jan 15.

ABSTRACT

Neurosignaling is increasingly recognized as a critical factor in cancer progression, where neuronal innervation of primary tumors contributes to the disease's advancement. This study focuses on segmenting individual axons within the prostate tumor microenvironment, which have been challenging to detect and analyze due to their irregular morphologies. We present a novel deep learning-based approach for the automated segmentation of axons, AxonFinder, leveraging a U-Net model with a ResNet-101 encoder, based on a multiplexed imaging approach. Utilizing a dataset of whole-slide images from low-, intermediate-, and high-risk prostate cancer patients, we manually annotated axons to train our model, achieving significant accuracy in detecting axonal structures that were previously hard to segment. Our method achieves high performance, with a validation F1-score of 94 % and IoU of 90.78 %. Besides, the morphometric analysis that shows strong alignment between manual annotations and automated segmentation with nerve length and tortuosity closely matching manual measurements. Furthermore, our analysis includes a comprehensive assessment of axon density and morphological features across different CAPRA-S prostate cancer risk categories revealing a significant decline in axon density correlating with higher CAPRA-S prostate cancer risk scores. Our paper suggests the potential utility of neuronal markers in the prognostic assessment of prostate cancer in aiding the pathologist's assessment of tumor sections and advancing our understanding of neurosignaling in the tumor microenvironment.

PMID:39807499 | PMC:PMC11728976 | DOI:10.1016/j.heliyon.2024.e41209

Categories: Literature Watch

An empirical study of LLaMA3 quantization: from LLMs to MLLMs

Deep learning - Tue, 2025-01-14 06:00

Vis Intell. 2024;2(1):36. doi: 10.1007/s44267-024-00070-x. Epub 2024 Dec 30.

ABSTRACT

The LLaMA family, a collection of foundation language models ranging from 7B to 65B parameters, has become one of the most powerful open-source large language models (LLMs) and the popular LLM backbone of multi-modal large language models (MLLMs), widely used in computer vision and natural language understanding tasks. In particular, LLaMA3 models have recently been released and have achieved impressive performance in various domains with super-large scale pre-training on over 15T tokens of data. Given the wide application of low-bit quantization for LLMs in resource-constrained scenarios, we explore LLaMA3's capabilities when quantized to low bit-width. This exploration can potentially provide new insights and challenges for the low-bit quantization of LLaMA3 and other future LLMs, especially in addressing performance degradation issues that suffer in LLM compression. Specifically, we comprehensively evaluate the 10 existing post-training quantization and LoRA fine-tuning (LoRA-FT) methods of LLaMA3 on 1-8 bits and various datasets to reveal the low-bit quantization performance of LLaMA3. To uncover the capabilities of low-bit quantized MLLM, we assessed the performance of the LLaMA3-based LLaVA-Next-8B model under 2-4 ultra-low bits with post-training quantization methods. Our experimental results indicate that LLaMA3 still suffers from non-negligible degradation in linguistic and visual contexts, particularly under ultra-low bit widths. This highlights the significant performance gap at low bit-width that needs to be addressed in future developments. We expect that this empirical study will prove valuable in advancing future models, driving LLMs and MLLMs to achieve higher accuracy at lower bit to enhance practicality.

PMID:39807379 | PMC:PMC11728678 | DOI:10.1007/s44267-024-00070-x

Categories: Literature Watch

Advances in modeling cellular state dynamics: integrating omics data and predictive techniques

Deep learning - Tue, 2025-01-14 06:00

Anim Cells Syst (Seoul). 2025 Jan 10;29(1):72-83. doi: 10.1080/19768354.2024.2449518. eCollection 2025.

ABSTRACT

Dynamic modeling of cellular states has emerged as a pivotal approach for understanding complex biological processes such as cell differentiation, disease progression, and tissue development. This review provides a comprehensive overview of current approaches for modeling cellular state dynamics, focusing on techniques ranging from dynamic or static biomolecular network models to deep learning models. We highlight how these approaches integrated with various omics data such as transcriptomics, and single-cell RNA sequencing could be used to capture and predict cellular behavior and transitions. We also discuss applications of these modeling approaches in predicting gene knockout effects, designing targeted interventions, and simulating organ development. This review emphasizes the importance of selecting appropriate modeling strategies based on scalability and resolution requirements, which vary according to the complexity and size of biological systems under study. By evaluating strengths, limitations, and recent advancements of these methodologies, we aim to guide future research in developing more robust and interpretable models for understanding and manipulating cellular state dynamics in various biological contexts, ultimately advancing therapeutic strategies and precision medicine.

PMID:39807350 | PMC:PMC11727055 | DOI:10.1080/19768354.2024.2449518

Categories: Literature Watch

Assessment of the Accuracy of a Deep Learning Algorithm- and Video-based Motion Capture System in Estimating Snatch Kinematics

Deep learning - Tue, 2025-01-14 06:00

Int J Exerc Sci. 2024 Dec 1;17(1):1629-1647. doi: 10.70252/PRVV4165. eCollection 2024.

ABSTRACT

In weightlifting, quantitative kinematic analysis is essential for evaluating snatch performance. While marker-based (MB) approaches are commonly used, they are impractical for training or competitions. Markerless video-based (VB) systems utilizing deep learning-based pose estimation algorithms could address this issue. This study assessed the comparability and applicability of VB systems in obtaining snatch kinematics by comparing the outcomes to an MB reference system. 21 weightlifters (15 Male, 6 Female) performed 2-3 snatches at 65%, 75%, and 80% of their one-repetition maximum. Snatch kinematics were analyzed using an MB (Vicon Nexus) and VB (Contemplas along with Theia3D) system. Analysis of 131 trials revealed that corresponding lower limb joint center positions of the systems on average differed by 4.7 ± 1.2 cm, and upper limb joint centers by 5.7 ± 1.5 cm. VB and MB lower limb joint angles showed highest agreement in the frontal plane (root mean square difference (RMSD): 11.2 ± 5.9°), followed by the sagittal plane (RMSD: 13.6 ± 4.7°). Statistical Parametric Mapping analysis revealed significant differences throughout most of the movement for all degrees of freedom. Maximum extension angles and velocities during the second pull displayed significant differences (p < .05) for the lower limbs. Our data showed significant differences in estimated kinematics between both systems, indicating a lack of comparability. These differences are likely due to differing models and assumptions, rather than measurement accuracy. However, given the rapid advancements of neural network-based approaches, it holds promise to become a suitable alternative to MB systems in weightlifting analysis.

PMID:39807293 | PMC:PMC11728585 | DOI:10.70252/PRVV4165

Categories: Literature Watch

Glomerular and Nephron Size and Kidney Disease Outcomes: A Comparison of Manual Versus Deep Learning Methods in Kidney Pathology

Deep learning - Tue, 2025-01-14 06:00

Kidney Med. 2024 Nov 28;7(1):100939. doi: 10.1016/j.xkme.2024.100939. eCollection 2025 Jan.

NO ABSTRACT

PMID:39807248 | PMC:PMC11728938 | DOI:10.1016/j.xkme.2024.100939

Categories: Literature Watch

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