Literature Watch

Blood Cell Counts and Inflammatory Indexes in Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis - Tue, 2025-03-04 06:00

Cureus. 2025 Jan 31;17(1):e78319. doi: 10.7759/cureus.78319. eCollection 2025 Jan.

ABSTRACT

Introduction Inflammatory cells play a role in several idiopathic pulmonary fibrosis (IPF) pathogenesis steps. We aimed to evaluate the predictive value of peripheral blood cell (PBC) counts and inflammation indexes in the prognosis and mortality of IPF. Materials and methods A total of 155 patients with IPF followed between 1 January 2016 and 1 January 2023 were evaluated retrospectively. The baseline values and annual changes for pulmonary function tests and the PBC counts, ratios, and inflammation indexes (leukocyte, neutrophil, platelet, monocyte, lymphocyte, red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), Systemic Immune Inflammation (SII) index, Systemic Inflammation Response Index (SIRI), the Aggregate Index of Systemic Inflammation (AISI)) were recorded. The relation between PBC, ratios, and inflammatory indexes with functional parameters (forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), 6-minute walking test (6MWT), Gender, Age, and Physiology (GAP) index, GAP stage) and mortality were examined. Results It was found that baseline RDW and neutrophil count were negatively correlated with survival time. The prognosis was worse in patients who had an RDW>13.6% and a neutrophil count>5.26×109/L (p = 0.0005 and p = 0.037, respectively). Significant correlations were observed between baseline peripheral blood cell counts, ratios, and index values (leukocyte, monocyte, neutrophil, platelet, monocyte, lymphocyte, NLR, PLR, MLR, SII, SIRI, AISI) and functional parameters (FVC, DLCO, 6MWT, GAP index, GAP stage). However, there was no significant correlation between the yearly changes. Conclusions Increased neutrophils and RDW may be related to the poor prognosis in IPF. Peripheral blood cell counts and inflammatory indices may provide useful information in identifying patients with worse functional status.

PMID:40034886 | PMC:PMC11873667 | DOI:10.7759/cureus.78319

Categories: Literature Watch

Genome-wide CRISPR/Cas9 screening identifies key profibrotic regulators of TGF-beta1-induced epithelial-mesenchymal transformation and pulmonary fibrosis

Idiopathic Pulmonary Fibrosis - Tue, 2025-03-04 06:00

Front Mol Biosci. 2025 Feb 17;12:1507163. doi: 10.3389/fmolb.2025.1507163. eCollection 2025.

ABSTRACT

BACKGROUND: The idiopathic pulmonary fibrosis (IPF) is a progressive and lethal interstitial lung disease with high morbidity and mortality. IPF is characterized by excessive extracellular matrix accumulation (ECM) and epithelial-mesenchymal transformation (EMT). To date, few anti-fibrotic therapeutics are available to reverse the progression of pulmonary fibrosis, and it is important to explore new profibrotic molecular regulators mediating EMT and pulmonary fibrosis.

METHODS: Based on our model of TGF-β1-induced EMT in BEAS-2B cells, we performed the genome-wide CRISPR/Cas9 knockout (GeCKO) screening technique, pathway and functional enrichment analysis, loss-of-function experiment, as well as other experimental techniques to comprehensively investigate profibrotic regulators contributing to EMT and the pathogenesis of pulmonary fibrosis.

RESULTS: Utilizing the GeCKO library screening, we identified 76 top molecular regulators. Ten candidate genes were subsequently confirmed by integrating the high-throughput data with findings from pathway and functional enrichment analysis. Among the candidate genes, knockout of COL20A1 and COL27A1 led to decreased mRNA expression of ECM components (Fibronectin and Collagen-I), as well as an increased rate of cell apoptosis. The mRNA expression of Collagen-I, together with the cell viability and migration, were inhibited when knocking out the WNT11. In addition, a decrease in the protein deposition of ECM components was observed by suppressing the expression of COL20A1, COL27A1, and WNT11.

CONCLUSION: Our study demonstrates that the COL20A1, COL27A1, and WNT11 serve as key profibrotic regulators of EMT. Gaining understanding and insights into these key profibrotic regulators of EMT paves the way for the discovery of new therapeutic targets against the onset and progression of IPF.

PMID:40034336 | PMC:PMC11872725 | DOI:10.3389/fmolb.2025.1507163

Categories: Literature Watch

An antisense oligonucleotide targeting the heat-shock protein HSPB5 as an innovative therapeutic approach in pulmonary fibrosis

Idiopathic Pulmonary Fibrosis - Tue, 2025-03-04 06:00

Br J Pharmacol. 2025 Mar 4. doi: 10.1111/bph.17470. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by fibroblast activation and abnormal accumulation of extracellular matrix in the lungs. We previously demonstrated the importance of the heat shock protein αB-crystallin (HSPB5) in TGF-β1 profibrotic signalling, which suggests that HSPB5 could be a new therapeutic target for the treatment of IPF. The purpose of this study was thus to develop antisense oligonucleotides targeting HSPB5 and to study their effects on the development of experimental pulmonary fibrosis.

EXPERIMENTAL APPROACH: Specific antisense oligonucleotides (ASO) were designed and screened in vitro, based on their ability to inhibit human and murine HSPB5 expression. The selected ASO22 was characterized in vitro in human fibroblast CCD-19Lu cells and A549 epithelial pulmonary cells, as well as in vivo using a mouse model of bleomycin-induced pulmonary fibrosis.

KEY RESULTS: ASO22 was selected for its capacity to inhibit TGF-β1-induced expression of HSPB5 and additional key markers of fibrosis such as plasminogen activator inhibitor-1, collagen, fibronectin and α-smooth muscle actin in fibroblastic human CCD-19Lu cells as well as plasminogen activator inhibitor-1 and α-smooth muscle actin in pulmonary epithelial A549 cells. Intra-tracheal or intravenous administration of ASO22 in bleomycin-induced pulmonary fibrotic mice decreased HSPB5 expression and reduced fibrosis, as demonstrated by decreased pulmonary remodelling, collagen accumulation and Acta2 and Col1a1 expression.

CONCLUSION AND IMPLICATIONS: Our results suggest that an antisense oligonucleotide strategy targeting HSPB5 could be of interest for the treatment of IPF.

PMID:40033950 | DOI:10.1111/bph.17470

Categories: Literature Watch

Quality by design for transient RBD-Fc fusion protein production in Chinese hamster ovary cells

Systems Biology - Tue, 2025-03-04 06:00

Biotechnol Rep (Amst). 2025 Feb 9;45:e00882. doi: 10.1016/j.btre.2025.e00882. eCollection 2025 Mar.

ABSTRACT

Quality by design (QbD) is applied to the upstream process to maximize the RBD-Fc fusion protein production in CHO cells. The three factors (culture duration, temperature, and polyethyleneimine to plasmid DNA (PEI-Max/pDNA) ratio) were identified as critical process attributes based on risk analysis (FMEA) and further optimized by response surface to maximize the protein yields. Using a Box-Behnken design, the optimal conditions for RBD-Fc production were determined to be a culture duration of 5 days, a culture temperature of 34.4 °C, and a PEI-Max/pDNA ratio of 4.2:1 (w/w) with a predictive value of 48 mg/L (desirability of 92.8 %). The PEI-Max/pDNA ratio and its interaction with culture duration to express the highest yield (47.78 ± 2.30 mg/l). In addition, the purified CHO-produced RBD-Fc fusion protein was highly pure and strongly bound to its receptor, ACE2. Our finding demonstrated that the QBD tools can identify the critical parameters to facilitate scaling-up production.

PMID:40034964 | PMC:PMC11872631 | DOI:10.1016/j.btre.2025.e00882

Categories: Literature Watch

Identification of the fruit of <em>Brucea javanica</em> as an anti-liver fibrosis agent working via SMAD2/SMAD3 and JAK1/STAT3 signaling pathways

Systems Biology - Tue, 2025-03-04 06:00

J Pharm Anal. 2025 Feb;15(2):101047. doi: 10.1016/j.jpha.2024.101047. Epub 2024 Jul 25.

ABSTRACT

Image 1.

PMID:40034864 | PMC:PMC11874559 | DOI:10.1016/j.jpha.2024.101047

Categories: Literature Watch

A large-scale database of T-cell receptor beta sequences and binding associations from natural and synthetic exposure to SARS-CoV-2

Systems Biology - Tue, 2025-03-04 06:00

Front Immunol. 2025 Feb 17;16:1488851. doi: 10.3389/fimmu.2025.1488851. eCollection 2025.

ABSTRACT

We describe the establishment and current content of the ImmuneCODE™ database, which includes hundreds of millions of T-cell Receptor (TCR) sequences from over 1,400 subjects exposed to or infected with the SARS-CoV-2 virus, as well as over 160,000 high-confidence SARS-CoV-2-associated TCRs. This database is made freely available, and the data contained in it can be used to assist with global efforts to understand the immune response to the SARS-CoV-2 virus and develop new interventions.

PMID:40034696 | PMC:PMC11873104 | DOI:10.3389/fimmu.2025.1488851

Categories: Literature Watch

Bioinformatics-Driven Investigations of Signature Biomarkers for Triple-Negative Breast Cancer

Systems Biology - Tue, 2025-03-04 06:00

Bioinform Biol Insights. 2025 Mar 2;19:11779322241271565. doi: 10.1177/11779322241271565. eCollection 2025.

ABSTRACT

Breast cancer is a highly heterogeneous disorder characterized by dysregulated expression of number of genes and their cascades. It is one of the most common types of cancer in women posing serious health concerns globally. Recent developments and discovery of specific prognostic biomarkers have enabled its application toward developing personalized therapies. The basic premise of this study was to investigate key signature genes and signaling pathways involved in triple-negative breast cancer using bioinformatics approach. Microarray data set GSE65194 from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus was used for identification of differentially expressed genes (DEGs) using R software. Gene ontology and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses were carried out using the ClueGO plugin in Cytoscape software. The up-regulated DEGs were primarily engaged in the regulation of cell cycle, overexpression of spindle assembly checkpoint, and so on, whereas down-regulated DEGs were employed in alteration to major signaling pathways and metabolic reprogramming. The hub genes were identified using cytoHubba from protein-protein interaction (PPI) network for top up-regulated and down-regulated DEG's plugin in Cytoscape software. The hub genes were validated as potential signature biomarkers by evaluating the overall survival percentage in breast cancer patients.

PMID:40034579 | PMC:PMC11873876 | DOI:10.1177/11779322241271565

Categories: Literature Watch

Systems metabolic engineering of <em>Corynebacterium glutamicum</em> for efficient l-tryptophan production

Systems Biology - Tue, 2025-03-04 06:00

Synth Syst Biotechnol. 2025 Feb 8;10(2):511-522. doi: 10.1016/j.synbio.2025.02.002. eCollection 2025 Jun.

ABSTRACT

Corynebacterium glutamicum is a versatile industrial microorganism for producing various amino acids. However, there have been no reports of well-defined C. glutamicum strains capable of hyperproducing l-tryptophan. This study presents a comprehensive metabolic engineering approach to establish robust C. glutamicum strains for l-tryptophan biosynthesis, including: (1) identification of potential targets by enzyme-constrained genome-scale modeling; (2) enhancement of the l-tryptophan biosynthetic pathway; (3) reconfiguration of central metabolic pathways; (4) identification of metabolic bottlenecks through comparative metabolome analysis; (5) engineering of the transport system, shikimate pathway, and precursor supply; and (6) repression of competing pathways and iterative optimization of key targets. The resulting C. glutamicum strain achieved a remarkable l-tryptophan titer of 50.5 g/L in 48h with a yield of 0.17 g/g glucose in fed-batch fermentation. This study highlights the efficacy of integrating computational modeling with systems metabolic engineering for significantly enhancing the production capabilities of industrial microorganisms.

PMID:40034180 | PMC:PMC11872490 | DOI:10.1016/j.synbio.2025.02.002

Categories: Literature Watch

From FAIR to CURE: Guidelines for Computational Models of Biological Systems

Systems Biology - Tue, 2025-03-04 06:00

ArXiv [Preprint]. 2025 Feb 21:arXiv:2502.15597v1.

ABSTRACT

Guidelines for managing scientific data have been established under the FAIR principles requiring that data be Findable, Accessible, Interoperable, and Reusable. In many scientific disciplines, especially computational biology, both data and models are key to progress. For this reason, and recognizing that such models are a very special type of 'data', we argue that computational models, especially mechanistic models prevalent in medicine, physiology and systems biology, deserve a complementary set of guidelines. We propose the CURE principles, emphasizing that models should be Credible, Understandable, Reproducible, and Extensible. We delve into each principle, discussing verification, validation, and uncertainty quantification for model credibility; the clarity of model descriptions and annotations for understandability; adherence to standards and open science practices for reproducibility; and the use of open standards and modular code for extensibility and reuse. We outline recommended and baseline requirements for each aspect of CURE, aiming to enhance the impact and trustworthiness of computational models, particularly in biomedical applications where credibility is paramount. Our perspective underscores the need for a more disciplined approach to modeling, aligning with emerging trends such as Digital Twins and emphasizing the importance of data and modeling standards for interoperability and reuse. Finally, we emphasize that given the non-trivial effort required to implement the guidelines, the community moves to automate as many of the guidelines as possible.

PMID:40034129 | PMC:PMC11875277

Categories: Literature Watch

Dual and spatially resolved drought responses in the Arabidopsis leaf mesophyll revealed by single-cell transcriptomics

Systems Biology - Tue, 2025-03-04 06:00

New Phytol. 2025 Mar 3. doi: 10.1111/nph.20446. Online ahead of print.

ABSTRACT

Drought stress imposes severe challenges on agriculture by impacting crop performance. Understanding drought responses in plants at a cellular level is a crucial first step toward engineering improved drought resilience. However, the molecular responses to drought are complex as they depend on multiple factors, including the severity of drought, the profiled organ, its developmental stage or even the cell types therein. Thus, deciphering the transcriptional responses to drought is especially challenging. In this study, we investigated tissue-specific responses to mild drought (MD) in young Arabidopsis thaliana (Arabidopsis) leaves using single-cell RNA sequencing (scRNA-seq). To preserve transcriptional integrity during cell isolation, we inhibited RNA synthesis using the transcription inhibitor actinomycin D, and demonstrated the benefits of transcriptome fixation for studying mild stress responses at a single-cell level. We present a curated and validated single-cell atlas, comprising 50 797 high-quality cells from almost all known cell types present in the leaf. All cell type annotations were validated with a new library of reporter lines. The curated data are available to the broad community in an intuitive tool and a browsable single-cell atlas (http://www.single-cell.be/plant/leaf-drought). We show that the mesophyll contains two spatially separated cell populations with distinct responses to drought: one enriched in canonical abscisic acid-related drought-responsive genes, and another one enriched in genes involved in iron starvation responses. Our study thus reveals a dual adaptive mechanism of the leaf mesophyll in response to MD and provides a valuable resource for future research on stress responses.

PMID:40033544 | DOI:10.1111/nph.20446

Categories: Literature Watch

Pentosan Polysulfate Sodium and Maculopathy in Patients with Interstitial Cystitis: A Systematic Review and Meta-Analysis

Drug-induced Adverse Events - Tue, 2025-03-04 06:00

World J Mens Health. 2025 Feb 27. doi: 10.5534/wjmh.240295. Online ahead of print.

ABSTRACT

PURPOSE: Pentosan polysulfate sodium (PPS) is the only pharmacological intervention approved by the US Food and Drug Administration for treating interstitial cystitis (IC) to date. However, PPS may induce an adverse event, maculopathy, which can be a significant challenge. To determine the risk of PPS-induced maculopathy in patients with IC.

MATERIALS AND METHODS: PubMed and Embase were systematically searched through July 2024. Two authors also independently and manually searched all relevant studies. We included national level cohort studies using healthcare claim big data or real-world data with the following criteria: (1) patients diagnosed with IC; (2) interventions included PPS as an active treatment; (3) comparisons were specified as non-PPS interventions; and (4) the primary outcome of interest was the risk of maculopathy. The pairwise meta-analysis was performed to compare the PPS treatment group with control used in IC. The primary outcome measure was the hazard ratio (HR), odds ratio (OR), and proportional report ratio (PRR) of maculopathy after receiving the PPS treatment, as compared to non-PPS interventions.

RESULTS: A comprehensive literature search was conducted, and identified 6 studies with 411,098 patients. The pooled risk for maculopathy due to PPS in patients with IC was significant (HR, 1.678; 95% confidence interval [95% CI], 1.066-2.642]). The heterogeneity test produced a Higgins' I-squared statistic, which was 83.6%. In the subgroup analysis of follow-up period of less than 5 years (HR, 1.285; 95% CI, 1.139-1.449) and more (HR, 1.341; 95% CI, 1.307-1.375) were statistically significant, indicating that the patients with IC who had a long-term PPS treatment were more likely to have maculopathy than the control groups.

CONCLUSIONS: This is the first study to investigate the relationship between PPS and its association with the risk of maculopathy in patients with IC through a systematic review and meta-analysis.

PMID:40034025 | DOI:10.5534/wjmh.240295

Categories: Literature Watch

Hyperbolic Geometry-Driven Robustness Enhancement for Rare Skin Disease Diagnosis

Orphan or Rare Diseases - Mon, 2025-03-03 06:00

IEEE J Biomed Health Inform. 2025 Mar;29(3):2161-2171. doi: 10.1109/JBHI.2024.3500094. Epub 2025 Mar 6.

ABSTRACT

The automated diagnosis of rare skin diseases using dermoscopy images, known as a few-shot learning (FSL) problem, remains challenging, since traditional FSL research tends to disregard the intrinsic hierarchical nature of rare diseases and data uncertainty. To address these issues, we propose to conduct rare skin disease diagnosis in hyperbolic space, which facilitates implicit class hierarchical structures and precise uncertainty measurement due to pivotal geometrical properties. We propose a Hyperbolic Geometry-driven Robustness Enhancement (HGRE) framework specifically tailored for diagnosing rare skin diseases. The HGRE framework uses implicit hierarchical relation in the hyperbolic space to better represent the features of rare diseases. Moreover, the framework incorporates an Adversarial Proxy Construction (APC) module to address the problem of data uncertainty. Specifically, the APC module uses the distance to the hyperbolic space origin as an indicator of uncertainty to filter and construct adversarial proxies for each uncertain prototype to achieve adversarial robust training. Leveraging the two unique geometrical properties, our HGRE framework effectively addresses the limitations of insufficient hierarchical relation utilization and data uncertainty in FSL-based rare skin disease diagnosis. This enhancement of the model's robustness in training has been corroborated by extensive empirical validation on two skin lesion datasets, where HGRE's performance notably surpassed existing state-of-the-art FSL methods.

PMID:40030401 | DOI:10.1109/JBHI.2024.3500094

Categories: Literature Watch

CardiOT: Towards Interpretable Drug Cardiotoxicity Prediction Using Optimal Transport and Kolmogorov--Arnold Networks

Drug-induced Adverse Events - Mon, 2025-03-03 06:00

IEEE J Biomed Health Inform. 2025 Mar;29(3):1759-1770. doi: 10.1109/JBHI.2024.3510297. Epub 2025 Mar 6.

ABSTRACT

Investigating the inhibitory effects of compounds on cardiac ion channels is essential for assessing cardiac drug safety. Consequently, researchers have developed computational models to evaluate combined cardiotoxicity (CCT) on cardiac ion channels. However, limitations in experimental data often cause issues like uneven data distribution and scarcity. Additionally, existing models primarily emphasize atomic information flow within graph neural networks (GNNs) while overlooking chemical bonds, leading to inadequate recognition of key structures. Therefore, this study integrates optimal transport (OT), structure remapping (SR), and Kolmogorov-Arnold networks (KANs) into a GNN-based CCT prediction model, CardiOT. First, the proposed CardiOT model employs OT pooling to optimize sample-feature joint distribution using expectation maximization, identifying "important" sample-feature pairs. Additionally, SR technology is used to emphasize the role of chemical bond information in message propagation. KAN technology is integrated to greatly enhance model interpretability. In summary, the model mitigates challenges related to uneven data distribution and scarcity. Multiple experiments on public datasets confirm the model's robust performance. We anticipate that this model will provide deeper insights into compound inhibition mechanisms on cardiac ion channels and reduce toxicity risks.

PMID:40030556 | DOI:10.1109/JBHI.2024.3510297

Categories: Literature Watch

An observational pilot study of an active surveillance tool to enhance pharmacovigilance in Brazil

Drug-induced Adverse Events - Mon, 2025-03-03 06:00

Malar J. 2025 Mar 3;24(1):71. doi: 10.1186/s12936-025-05295-9.

ABSTRACT

BACKGROUND: Active surveillance involves systematically monitoring patients to seek detailed information about the occurrence of adverse events (AEs) following drug administration. The Seta technology was developed to improve active surveillance of AEs or pregnancy in low- and middle-income countries and geographically challenging areas. Seta actively solicits responses from participants via WhatsApp messages. The study aimed to determine whether Seta facilitated reporting of AEs and pregnancies to the Brazilian National Health Surveillance Agency (ANVISA).

METHODS: Malaria patients participating in the Tafenoquine Roll-out STudy (TRuST) in Brazil's Amazon region were invited to participate in this observational pilot study evaluating Seta. The study was conducted at two sites from 27 July 2022 to 28 October 2022. Seta sent messages to all participants on Day 7 and in Week 8 asking if they had experienced an AE or if they had become pregnant during the time since they took the malaria medication. If a participant responded "yes", a pharmacovigilance coordinator (PVC) called them to collect further details, which the PVC was then encouraged to report to ANVISA.

RESULTS: This pilot study included 149 participants, 50 from Manaus and 99 from Porto Velho. On Day 7, 117 (79%) of 149 participants responded to WhatsApp messages generated by Seta asking whether they had experienced an AE or become pregnant; 45 participants responded "yes". At Week 8, 64 (55%) of the Day 7 responders also responded, 10 of whom indicated that they had experienced an AE or become pregnant. A total of 55 follow-up calls were therefore attempted by PVCs, of which, 25 (45%) were answered and allowed for reporting of AEs and pregnancies, as appropriate, to ANVISA.

CONCLUSIONS: This observational pilot study provides insights into how digital reporting tools such as Seta can enhance pharmacovigilance in remote areas and build upon existing signal detection methodologies. Twenty-five AEs or pregnancies were reported to ANVISA that were unlikely to have been reported otherwise.

PMID:40033382 | DOI:10.1186/s12936-025-05295-9

Categories: Literature Watch

Repurposing the anti-parasitic agent pentamidine for cancer therapy; a novel approach with promising anti-tumor properties

Drug Repositioning - Mon, 2025-03-03 06:00

J Transl Med. 2025 Mar 3;23(1):258. doi: 10.1186/s12967-025-06293-w.

ABSTRACT

Pentamidine (PTM) is an aromatic diamidine administered for infectious diseases, e.g. sleeping sickness, malaria, and Pneumocystis jirovecii pneumonia. Due to similarities of cellular mechanisms between human cells and such infections, PTM has also been proposed for repurposing in non-infectious diseases such as cancer. Indeed, by modulating different signaling pathways such as PI3K/AKT, MAPK/ERK, p53, PD-1/PD-L1, etc., PTM has been shown to inhibit different properties of cancer, including proliferation, invasion, migration, hypoxia, and angiogenesis, while inducing anti-tumor immune responses and apoptosis. Given the promising implications of PTM for cancer treatment, however, the clinical translation of PTM in cancer is not without certain challenges. In fact, clinical trials have shown that systemic administration of PTM can be concurrent with serious adverse effects, e.g. hypoglycemia. Therefore, to reduce the administered doses of PTM, lower the risk of adverse effects, and prevent any potential drug resistance, while maintaining the anti-tumor efficacy, two main strategies have been suggested. One is combination therapy that employs PTM in conjunction with other anti-cancer modalities, such as chemotherapy and radiotherapy, and attacks tumor cells with significant additive or synergistic anti-tumor effects. The other is developing PTM-loaded nanocarrier drug delivery systems e.g. pegylated liposomes, chitosan-coated niosomes, squalene-based nanoparticles, hyaluronated lipid-polymer hybrid nanoparticles, etc., that offer enhanced pharmacokinetic characteristics, including increased bioavailability, sit-targeting, and controlled/sustained drug release. This review highlights the anti-tumor properties of PTM that favor its repurposing for cancer treatment, as well as, PTM-based combination therapies and nanocarrier delivery systems which can enhance therapeutic efficacy and simultaneously reduce toxicity.

PMID:40033361 | DOI:10.1186/s12967-025-06293-w

Categories: Literature Watch

Drug Repurposing Tactics in the USA: Known Active Pharmaceutical Ingredients in New Indications

Drug Repositioning - Mon, 2025-03-03 06:00

Pulm Pharmacol Ther. 2025 Mar 1:102348. doi: 10.1016/j.pupt.2025.102348. Online ahead of print.

NO ABSTRACT

PMID:40032240 | DOI:10.1016/j.pupt.2025.102348

Categories: Literature Watch

Expanding Access to Continuous Glucose Monitoring Through Empowering Primary Care: A Joint Endocrinology-Primary Care Quality Improvement Project

Cystic Fibrosis - Mon, 2025-03-03 06:00

J Gen Intern Med. 2025 Mar 3. doi: 10.1007/s11606-025-09449-y. Online ahead of print.

ABSTRACT

BACKGROUND: Despite guideline recommendations to offer continuous glucose monitoring (CGM) to all patients with diabetes using insulin, prescription rates for CGM remain low in primary care.

OBJECTIVE: This quality improvement project aimed to improve access to CGM in primary care for patients with type 2 diabetes on insulin.

DESIGN: This was a quality improvement project conducted by a joint endocrinology/primary care team at a single primary care community health clinic. After defining the problem through process mapping, driver diagrams, and Pareto charts, several interventions were trialed through Plan-Do-Study-Act (PDSA) cycles.

PARTICIPANTS: The study team consisted of four endocrinologists, two primary care providers (MD/NP), the lead primary care nurse, and the primary care population health specialist.

INTERVENTIONS: Interventions included a directory for durable medical equipment (DME) suppliers, nursing education with device company representatives, a new electronic ordering system for DME, and a nursing outreach program to patients eligible for CGM.

MAIN MEASURES: The primary outcome was percentage of eligible patients using CGM. Process measures included the number of CGM orders started weekly. Nursing comfort with CGM, knowledge of CGM, and perceptions of communication with DME suppliers were also measured.

KEY RESULTS: The percentage of eligible patients using CGM increased from 28 to 42%, and the percentage of patients using CGM started in primary care increased from 8 to 14%. Weekly orders increased from 0.3 per week to 2.3 per week. Nursing reported feeling more comfortable and knowledgeable about CGM after the interventions and reported improved communication with DME suppliers.

CONCLUSIONS: CGM is known to improve outcomes for patients with diabetes but is an underutilized tool in primary care. Collaborative quality improvement projects between endocrinology and primary care can rapidly build capacity within primary care to prescribe CGM and expand access for patients with diabetes who do not have endocrinologists.

PMID:40032724 | DOI:10.1007/s11606-025-09449-y

Categories: Literature Watch

Application of Machine Learning in the Diagnosis of Temporomandibular Disorders: An Overview

Deep learning - Mon, 2025-03-03 06:00

Oral Dis. 2025 Mar 3. doi: 10.1111/odi.15300. Online ahead of print.

ABSTRACT

OBJECTIVES: Temporomandibular disorders (TMDs) refer to a group of disorders related to the temporomandibular joint (TMJ), the diagnosis of which is important in dental practice but remains challenging for nonspecialists. With the development of machine learning (ML) methods, ML-based TMDs diagnostic models have shown great potential. The purpose of this review is to summarize the application of ML in TMDs diagnosis, as well as future directions and possible challenges.

METHODS: PubMed, Google Scholar, and Web of Science databases were searched for electronic literature published up to October 2024, in order to describe the current application of ML in the classification and diagnosis of TMDs.

RESULTS: We summarized the application of various ML methods in the diagnosis and classification of different subtypes of TMDs and described the role of different imaging modalities in constructing diagnostic models. Ultimately, we discussed future directions and challenges that ML methods may confront in the application of TMDs diagnosis.

CONCLUSIONS: The screening and diagnosis models of TMDs based on ML methods hold significant potential for clinical application, but still need to be further verified by a large number of multicenter data and longitudinal studies.

PMID:40033467 | DOI:10.1111/odi.15300

Categories: Literature Watch

Machine learning for the rElapse risk eValuation in acute biliary pancreatitis: The deep learning MINERVA study protocol

Deep learning - Mon, 2025-03-03 06:00

World J Emerg Surg. 2025 Mar 3;20(1):17. doi: 10.1186/s13017-025-00594-7.

ABSTRACT

BACKGROUND: Mild acute biliary pancreatitis (MABP) presents significant clinical and economic challenges due to its potential for relapse. Current guidelines advocate for early cholecystectomy (EC) during the same hospital admission to prevent recurrent acute pancreatitis (RAP). Despite these recommendations, implementation in clinical practice varies, highlighting the need for reliable and accessible predictive tools. The MINERVA study aims to develop and validate a machine learning (ML) model to predict the risk of RAP (at 30, 60, 90 days, and at 1-year) in MABP patients, enhancing decision-making processes.

METHODS: The MINERVA study will be conducted across multiple academic and community hospitals in Italy. Adult patients with a clinical diagnosis of MABP, in accordance with the revised Atlanta Criteria, who have not undergone EC during index admission will be included. Exclusion criteria encompass non-biliary aetiology, severe pancreatitis, and the inability to provide informed consent. The study involves both retrospective data from the MANCTRA-1 study and prospective data collection. Data will be captured using REDCap. The ML model will utilise convolutional neural networks (CNN) for feature extraction and risk prediction. The model includes the following steps: the spatial transformation of variables using kernel Principal Component Analysis (kPCA), the creation of 2D images from transformed data, the application of convolutional filters, max-pooling, flattening, and final risk prediction via a fully connected layer. Performance metrics such as accuracy, precision, recall, and area under the ROC curve (AUC) will be used to evaluate the model.

DISCUSSION: The MINERVA study aims to address the specific gap in predicting RAP risk in MABP patients by leveraging advanced ML techniques. By incorporating a wide range of clinical and demographic variables, the MINERVA score aims to provide a reliable, cost-effective, and accessible tool for healthcare professionals. The project emphasises the practical application of AI in clinical settings, potentially reducing the incidence of RAP and associated healthcare costs.

TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT06124989.

PMID:40033414 | DOI:10.1186/s13017-025-00594-7

Categories: Literature Watch

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