J Med Eng Technol. 2025 Feb 12:1-14. doi: 10.1080/03091902.2025.2462310. Online ahead of print.

ABSTRACT

This research aimed to develop an algorithm for classifying scalogram images generated from electromyography data of patients with Rheumatoid Arthritis and Prolapsed Intervertebral Disc. Electromyography is valuable for assessing muscle function and diagnosing neurological disorders, but limitations, such as background noise, cross-talk, and inter-subject variability complicate the interpretation and assessment. To mitigate this, the present study uses scalogram images and attention-network architecture. The algorithm utilises a combination of features extracted from an attention module and a convolution feature module, followed by classification using a Convolutional Neural Network classifier. A comparison of eight alternative architectures, including individual implementations of attention and convolution filters and a Convolutional Neural Network-only model, shows that the hybrid Convolutional Neural Network model proposed in this study outperforms the others. The model exhibits excellent discriminatory ability between gait abnormalities with an accuracy of 96.7%, a precision of 95.2%, a recall of 94.8%, and an Area Under Curve of 0.99. These findings suggest that the proposed model is highly accurate in classifying scalogram images of electromyography signals and may have significant clinical implications for early diagnosis and treatment planning.

PMID:39936825 | DOI:10.1080/03091902.2025.2462310

Rev Soc Bras Med Trop. 2025 Feb 7;58:e004012024. doi: 10.1590/0037-8682-0178-2024. eCollection 2025.

ABSTRACT

BACKGROUND: Emerging infections have posed persistent threats to humanity throughout history. Rapid and unprecedented anthropogenic, behavioral, and social transformations witnessed in the past century have expedited the emergence of novel pathogens, intensifying their impact on the global human population.

METHODS: This study aimed to comprehensively analyze and compare the genomic sequences of four distinct viruses: SARS-CoV-2, SARS, MERS, and Ebola. Advanced genomic sequencing techniques and a Gated Recurrent Unit-based deep learning model were used to examine the intricate genetic makeup of these viruses. The proposed study sheds light on their evolutionary dynamics, transmission patterns, and pathogenicity and contributes to the development of effective diagnostic and therapeutic interventions.

RESULTS: This model exhibited exceptional performance as evidenced by accuracy values of 99.01%, 98.91%, 98.35%, and 98.04% for SARS-CoV-2, SARS, MERS, and Ebola respectively. Precision values ranged from 98.1% to 98.72%, recall values consistently surpassed 92%, and F1 scores ranged from 95.47% to 96.37%.

CONCLUSIONS: These results underscore the robustness of this model and its potential utility in genomic analysis, paving the way for enhanced understanding, preparedness, and response to emerging viral threats. In the future, this research will focus on creating better diagnostic instruments for the early identification of viral illnesses, developing vaccinations, and tailoring treatments based on the genetic composition and evolutionary patterns of different viruses. This model can be modified to examine a more extensive variety of diseases and recently discovered viruses to predict future outbreaks and their effects on global health.

PMID:39936709 | DOI:10.1590/0037-8682-0178-2024

Curr Neuropharmacol. 2025 Feb 6. doi: 10.2174/011570159X327908241121062335. Online ahead of print.

ABSTRACT

Neurodegenerative diseases represent a prevalent category of age-associated diseases. As human lifespans extend and societies become increasingly aged, neurodegenerative diseases pose a growing threat to public health. The lack of effective therapeutic drugs for both common and rare neurodegenerative diseases amplifies the medical challenges they present. Current treatments for these diseases primarily offer symptomatic relief rather than a cure, underscoring the pressing need to develop efficacious therapeutic interventions. Drug repositioning, an innovative and data-driven approach to research and development, proposes the re-evaluation of existing drugs for potential application in new therapeutic areas. Fueled by rapid advancements in artificial intelligence and the burgeoning accumulation of medical data, drug repositioning has emerged as a promising pathway for drug discovery. This review comprehensively examines drug repositioning for neurodegenerative diseases through the lens of translational informatics, encompassing data sources, computational models, and clinical applications. Initially, we systematized drug repositioning-related databases and online platforms, focusing on data resource management and standardization. Subsequently, we classify computational models for drug repositioning from the perspectives of drug-drug, drug-target, and drug-disease interactions into categories such as machine learning, deep learning, and networkbased approaches. Lastly, we highlight computational models presently utilized in neurodegenerative disease research and identify databases that hold potential for future drug repositioning efforts. In the artificial intelligence era, drug repositioning, as a data-driven strategy, offers a promising avenue for developing treatments suited to the complex and multifaceted nature of neurodegenerative diseases. These advancements could furnish patients with more rapid, cost-effective therapeutic options.

PMID:39936420 | DOI:10.2174/011570159X327908241121062335

J Surg Res. 2025 Jan;305:295-303. doi: 10.1016/j.jss.2024.11.002. Epub 2024 Dec 27.

ABSTRACT

INTRODUCTION: Due to parenchymal fibrosis and chest wall contraction in idiopathic pulmonary fibrosis (IPF), donor lung allografts are generally undersized to accommodate smaller diseased chest cavities. We hypothesized that transplanting oversized allografts (OAs) in recipients with IPF would be associated with thoracic cavity expansion.

METHODS: A single center retrospective study of IPF patients who underwent lung transplant between 2014 and 2022 was conducted. Size matching was determined by comparing donor and recipient lung height on chest radiographs, measured from lung apex to middiaphragm on donor and recipient inspiratory anterior to posterior chest radiographs. Allografts that were ≥10% larger on chest radiograph compared to corresponding recipient lungs were deemed OAs, or not oversized allografts. Allograft lung height and pulmonary function tests were collected at 1, 6, and 12 mo and a comparative analysis was performed.

RESULTS: The OA group had a significant increase in change of height in the left lung at 1 mo and both lungs at 6 mo (P < 0.05). There were no significant differences in change of forced expiratory volume in 1 s at 1, 6, 12 mo between the two groups. The change in forced vital capacity was significantly increased in the OA group at 6 mo (P < 0.05). The degree of donor to recipient allograft size mismatch and resultant recipient pleural cavity expansion was significantly correlated at 1 and 6 mo (P < 0.05).

CONCLUSIONS: Transplanting larger allografts into IPF patients was associated with pleural cavity expansion, without an associated change in pulmonary function tests. Thus, larger allografts potentially can be used in IPF patients, thereby increasing donor availability for these patients.

PMID:39937562 | DOI:10.1016/j.jss.2024.11.002

Cells. 2025 Feb 5;14(3):222. doi: 10.3390/cells14030222.

ABSTRACT

Idiopathic Pulmonary Fibrosis (IPF) is an epithelial-driven interstitial lung disease of unknown etiology characterized by the excessive proliferation of fibroblast populations that synthesize large amounts of extracellular matrix. In this devastating disorder, all aging hallmarks appear prematurely or are altered. This review highlights key findings about IPF characteristics recently recognized as hallmarks of aging, including mechanical alterations, inflammaging, dysbiosis, alternative splicing, and disabled macroautophagy. It also revisits the classic hallmarks of aging, which encompass stem cell exhaustion, cellular senescence, and altered intercellular communication. Enhancing our understanding of the fundamental processes that underlie the altered hallmarks of aging in IPF may facilitate the development of innovative experimental strategies to improve therapeutic outcomes.

PMID:39937013 | DOI:10.3390/cells14030222

Mol Biol Rep. 2025 Feb 12;52(1):226. doi: 10.1007/s11033-025-10341-5.

ABSTRACT

Microsomal cytochromes P450 (micCYPs) are monooxygenases located in the endoplasmic reticulum and other endomembranes of human cells. micCYPs receive electrons from specific redox partners and perform enzymatic transformations of drugs and different endogenous substrates. The large biodiversity of micCYPs leads to the idea that protein-protein interactions (PPIs) involving micCYPs are not limited to classical redox partners. This review aims to perform a systems biology analysis of the complete set of PPIs for all 33 micCYPs studied, as well as to examine the subinteractome of each micCYP. We have retrieved 287 PPIs from interactomic databases, involving 246 unique protein interactors that share a similar profile of subcellular localization with micCYPs. The number of protein interactors per micCYP unevenly varies from one to 47. Interactors of micCYPs are involved in cellular metabolism, signal transduction, cell-cell junctions, cytoskeleton organization, and intracellular or transmembrane transport. Notably, up to one-third of all interactors belong to the latter group, half of which consists of membrane transporters of compounds, metabolites, and ions (e.g., CACNA2D1, ORAI1, SCN3B, SLC7A2, SLC19A3, and SLC11A2). The CYP2C8 subinteractome is enriched with proteins involved in autophagy; CYP2S1- ERBB2 and EPH-Ephrin signaling; CYP3A4- glucuronidation. Proteins UBC, PGRMC1, and FANCG are the most frequent common interactors across various micCYPs. Nine and 12 interactors of micCYPs are involved in phosphorylation and ubiquitination, respectively; 20 interactors are 'moonlighting' proteins that are represented in the CYP3A4 subinteractome. Furthermore, micCYPs such as CYP2C9, 3A5, 2E1, 2A6, 4F2, and 4A11 may be involved in potentially binary interactions with other micCYPs. The functional implication of these CYP-CYP pairs is likely associated with modulation of their activity. Analysis of transcriptomic data revealed that some micCYP/interactor pairs exhibit tissue-, time-, and disease-specific gene expression patterns. Drugs that are metabolized by micCYPs in some cases can influence the expression of corresponding interactors at the gene or protein levels. These findings suggest that micCYPs may play roles in functions beyond their monooxygenase activity, as indicated by the spectrum of PPIs analyzed.

PMID:39937310 | DOI:10.1007/s11033-025-10341-5

Microb Biotechnol. 2025 Feb;18(2):e70096. doi: 10.1111/1751-7915.70096.

ABSTRACT

The DnaK (Hsp70) protein is an essential ATP-dependent chaperone foldase and holdase found in most organisms. In this study, combining multiple experimental approaches we determined FliC as major interaction partner of DnaK in the opportunistic bacterial pathogen Pseudomonas aeruginosa. Implementing immunofluorescence microscopy and electron microscopy techniques DnaK was found extracellularly associated to the assembled filament in a regular pattern. dnaK repression led to intracellular FliC accumulation and motility impairment, highlighting DnaK essentiality for FliC export and flagellum assembly. SPOT-membrane peptide arrays coupled with artificial intelligence analyses suggested a highly dynamic DnaK-FliC interaction landscape involving multiple domains and transient complexes formation. Remarkably, in vitro fast relaxation imaging (FReI) experiments mimicking ATP-deprived extracellular environment conditions exhibited DnaK ATP-independent holdase activity, regardless of its co-chaperone DnaJ and its nucleotide exchange factor GrpE. We present a model for the DnaK-FliC interactions involving dynamic states throughout the flagellum assembly stages. These results expand the classical view of DnaK chaperone functioning and introduce a new participant in the Pseudomonas flagellar system, an important trait for bacterial colonisation and virulence.

PMID:39937155 | DOI:10.1111/1751-7915.70096

Cells. 2025 Jan 21;14(3):152. doi: 10.3390/cells14030152.

ABSTRACT

Calcium (Ca2+) signalling is a fundamental cellular process, essential for a wide range of physiological functions. It is regulated by various mechanisms, including a diverse family of Ca2+-binding proteins (CaBPs), which are structurally and functionally similar to calmodulin (CaM). The CaBP family consists of six members (CaBP1, CaBP2, CaBP4, CaBP5, CaBP7, and CaBP8), each exhibiting unique localisation, structural features, and functional roles. In this review, we provide a structure-function analysis of the CaBP family, highlighting the key similarities and differences both within the family and in comparison to CaM. It has been shown that CaBP1-5 share similar structural and interaction characteristics, while CaBP7 and CaBP8 form a distinct subfamily with unique properties. This review of current CaBP knowledge highlights the critical gaps in our understanding, as some CaBP members are less well characterised than others. We also examine pathogenic mutations within CaBPs and their functional impact, showing the need for further research to improve treatment options for associated disorders.

PMID:39936944 | DOI:10.3390/cells14030152

Microbiol Resour Announc. 2025 Feb 12:e0094124. doi: 10.1128/mra.00941-24. Online ahead of print.

ABSTRACT

Sneathia vaginalis, a fastidious pathogen of the female reproductive tract, is implicated in obstetric and gynecologic pathologies, including spontaneous preterm birth and bacterial vaginosis. Here, we report the successful cultivation and genomic sequencing of three Sneathia vaginalis isolates collected via a vaginal swab from a patient with bacterial vaginosis.

PMID:39936913 | DOI:10.1128/mra.00941-24

ACS Synth Biol. 2025 Feb 12. doi: 10.1021/acssynbio.4c00881. Online ahead of print.

ABSTRACT

1,6-Hexamethylenediamine (HMD) and 1,6-hexanediol (HDO) are pivotal C6 platform chemicals with extensive applications as key monomers in the synthesis of nylons, polyurethanes, and polyesters. The biological production of HMD and HDO from cheap and renewable bioresources represents an environmentally benign strategy for the sustainable chemical industry. Herein, we report the development of a novel biocatalytic route for the direct conversion of d-glucose to HMD and HDO in Escherichia coli. This was achieved through the integration of an adipic acid synthesis module with conversion modules tailored for HMD and HDO production. The study entailed a comprehensive optimization of pathway enzymes, protein expression, and precursor supply. Furthermore, a co-culture fermentation strategy was employed to enhance the efficiency of labor division, resulting in a two-strain cocultivation process that yielded 16.62 mg/L of HMD and 214.93 mg/L of HDO using glucose as the sole carbon source. This study establishes a foundational framework for the advancement of sustainable biological production processes for HMD and HDO from renewable resources.

PMID:39936844 | DOI:10.1021/acssynbio.4c00881

Bioinformatics. 2025 Feb 12:btaf070. doi: 10.1093/bioinformatics/btaf070. Online ahead of print.

ABSTRACT

MOTIVATION: The Open Targets Platform (https://platform.opentargets.org) is a unique, comprehensive, open-source resource supporting systematic identification and prioritisation of targets for drug discovery. The Platform combines, harmonises and integrates data from >20 diverse sources to provide target-disease associations, covering evidence derived from genetic associations, somatic mutations, known drugs, differential expression, animal models, pathways and systems biology. An in-house target identification scoring framework weighs the evidence from each data source and type, contributing to an overall score for each of the 7.8M target-disease associations. However, the old infrastructure did not allow user-led dynamic adjustments in the contribution of different evidence types for target prioritisation, a limitation frequently raised by our user community. Furthermore, the previous Platform user interface did not support navigation and exploration of the underlying target-disease evidence on the same page, occasionally making the user journey counterintuitive.

RESULTS: Here, we describe "Associations on the Fly" (AOTF), a new Platform feature-developed with a user-centred vision-that enables the user to formulate more flexible therapeutic hypotheses through dynamic adjustment of the weight of contributing evidence from each source, altering the prioritisation of targets.

AVAILABILITY AND IMPLEMENTATION: The codebases that power the Platform-including our pipelines, GraphQL API, and React UI-are all open source and licensed under the APACHE LICENSE, VERSION 2.0.You can find all of our code repositories on GitHub at https://github.com/opentargets and on Zenodo at https://zenodo.org/records/14392214.This tool was implemented using React v18 and its code is accessible here: [https://github.com/opentargets/ot-ui-apps].The tools are accessible through the Open Targets Platform web interface [https://platform.opentargets.org/] and GraphQL API (https://platform-docs.opentargets.org/data-access/graphql-api).Data is available for download here: [https://platform.opentargets.org/downloads] and from the EMBL-EBI FTP: [https://ftp.ebi.ac.uk/pub/databases/opentargets/platform/].

CONTACT: Annalisa Buniello, European Molecular Biology Laboratory (EMBL-EBI), buniello@ebi.ac.uk.

SUPPLEMENTARY INFORMATION: Features walkthrough video: https://youtu.be/2A9bksboAag, https://www.youtube.com/watch?v=WQwQn6I4jkwExtensive documentation: https://platform-docs.opentargets.org/web-interface/associations-on-the-fly https://platform-docs.opentargets.org/target-prioritisation.

PMID:39936578 | DOI:10.1093/bioinformatics/btaf070

Psychiatry Clin Neurosci. 2025 Feb 12. doi: 10.1111/pcn.13800. Online ahead of print.

ABSTRACT

AIM: Vafidemstat is a brain-penetrant, orally bioavailable, small molecule irreversible inhibitor of the histone lysine-specific demethylase KDM1A (also known as LSD1), which corrects memory deficits and behavior alterations including aggression and social interaction deficits in preclinical models.

METHODS: Here, we report the results of REIMAGINE, a phase IIa, single-center, open-label, one-arm basket trial that evaluated the safety and efficacy of vafidemstat on aggression in adult patients with borderline personality disorder (BPD), attention-deficit/hyperactivity disorder (ADHD), and autistic spectrum disorder (ASD). Participants received 1.2 mg/day of vafidemstat for 8 weeks.

RESULTS: Vafidemstat was shown to be safe and well tolerated, and no drug-related clinically significant adverse events were observed. Furthermore, all neuropsychiatric scales assessed showed notable efficacy signals, whether assessing agitation/aggression (Clinical Global Impression for Severity [CGI-S] and Clinical Global Impression for Improvement [CGI-I] and Neuropsychiatric Inventory [NPI] questionnaire for Agitation-Aggression [NPI-AA]), overall patient functioning (total NPI), or disease-specific features (Attention-Deficit/Hyperactivity Disorder Rating Scale [ADHD-RS] and Borderline Personality Disorder Checklist [BPDCL]). Statistically significant improvements were observed in the aggregated data (all participants) and for each of the three disease groups independently. Changes were evident within the first 2 weeks of treatment.

CONCLUSION: In summary, the REIMAGINE study supports that vafidemstat is safe, well tolerated, and causes a significant and consistent reduction in agitation/aggression and nonaggression features in BPD, ADHD, and ASD. These data support continuing the development of vafidemstat as a new treatment option for these psychiatric disorders.

PMID:39936839 | DOI:10.1111/pcn.13800

HIV Res Clin Pract. 2025 Dec;26(1):2456890. doi: 10.1080/25787489.2025.2456890. Epub 2025 Feb 12.

ABSTRACT

BACKGROUND: BICtegravir Single Tablet Regimen (BICSTaR) is an observational cohort study evaluating the effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in treatment-naïve (TN) and treatment-experienced (TE) people with HIV.

OBJECTIVE: To present final pooled 24-month outcomes for the full cohort.

METHODS: Prospective data were pooled from TN and TE adults with HIV initiating B/F/TAF in routine clinical practice across 14 countries (data collection: 25/06/2018-29/12/2023). Outcomes at 24 months included virologic suppression (HIV-1 RNA <50 copies/mL), immunologic effectiveness (change in CD4 cell count and CD4/CD8 ratio), persistence, and safety. Outcomes were also analysed in key populations.

RESULTS: Of 2,074 (483 TN, 1,591 TE) participants included, most were male (85%), White (70%), and had ≥1 comorbidity (66%). Median (Q1, Q3) age was 45 (35, 54) years. At 24 months, 94% of TN and 96% of TE participants had HIV-1 RNA <50 copies/mL (missing = excluded analysis). These values were 88% and 86%, respectively, in a discontinuation = failure analysis. Effectiveness remained high across all key populations at 24 months. Median (Q1, Q3) CD4 count increased by 257 (127, 447) cells/µL in TN and 40 (-70, 153) cells/µL in TE participants (both p < 0.001). There was no reported treatment-emergent resistance to B/F/TAF. Persistence was high at 24 months (TN, 95%; TE, 91%). Drug-related adverse events occurred in 11% of TN and 12% of TE participants, leading to B/F/TAF discontinuation in 5%.

CONCLUSIONS: B/F/TAF was generally well tolerated over 24 months, with high effectiveness and persistence observed among a broad range of people with HIV.

PMID:39936702 | DOI:10.1080/25787489.2025.2456890

Hum Vaccin Immunother. 2025 Dec;21(1):2465161. doi: 10.1080/21645515.2025.2465161. Epub 2025 Feb 12.

ABSTRACT

In light of the widespread use of rotavirus vaccines, there is a pressing need to perform thorough, large-scale surveillance to actively monitor safety. This study aimed to identify potential adverse events following rotavirus vaccination in infants. Using a nationwide linked database of the national immunization registry and health insurance claims data, we identified infants vaccinated with the first dose of rotavirus vaccine between January 2016 and October 2022. The self-controlled tree-temporal scan statistics method analyzed all incident diagnoses recorded within 56 days post-vaccination and evaluated all temporal risk windows. Among 1,720,778 rotavirus vaccine recipients 64,752 infants contributed to the analysis, yielding 72,970 incident diagnoses. Of these, 28 clusters were categorized as known adverse drug reactions (ADRs), including infection following immunization (Days 1-2, p<.001), viral infection (Days 1-5, p<.001), urticaria and erythema (Days 3-9, p<.001), acute upper respiratory infections (Days 28-42, p<.001), and pneumonia (Days 9-19 or 28-42, p<.001). Seventeen clusters were classified as ADR-related events, such as the ones clinically related to ADR or lower-level diagnostic codes of ADR. The remaining 26 clusters were classified as signals, including sepsis (Days 1-20, p<.001), meningitis (Days 1-23, p<.001), liver disease (Days 4-11, p<.001), and tubulo-interstitial nephritis (Days 11-38, p<.001). A cluster of intussusceptions was only found in monovalent vaccine-stratified analysis (Days 5-8, p = 0.005). This study confirmed known ADRs following rotavirus vaccination, while identifying potential safety signals requiring further investigation. These findings emphasize the importance of active vaccine surveillance and underscore the need for epidemiological studies with validated outcome definitions to confirm causal relationships between rotavirus vaccination and the detected outcomes.

PMID:39936376 | DOI:10.1080/21645515.2025.2465161

Front Med (Lausanne). 2025 Jan 28;12:1492709. doi: 10.3389/fmed.2025.1492709. eCollection 2025.

ABSTRACT

OBJECTIVE: To systematically map the knowledge landscape and development trends in artificial intelligence (AI) applications for antimicrobial resistance (AMR) research through bibliometric analysis, providing evidence-based insights to guide future research directions and inform strategic decision-making in this dynamic field.

METHODS: A comprehensive bibliometric analysis was performed using the Web of Science Core Collection database for publications from 2014 to 2024. The analysis integrated multiple bibliometric approaches: VOSviewer for visualization of collaboration networks and research clusters, CiteSpace for temporal evolution analysis, and quantitative analysis of publication metrics. Key bibliometric indicators including co-authorship patterns, keyword co-occurrence, and citation impact were analyzed to delineate research evolution and collaboration patterns in this domain.

RESULTS: A collection of 2,408 publications was analyzed, demonstrating significant annual growth with publications increasing from 4 in 2014 to 549 in 2023 (22.7% of total output). The United States (707), China (581), and India (233) were the leading contributors in international collaborations. The Chinese Academy of Sciences (53), Harvard Medical School (43), and University of California San Diego (26) were identified as top contributing institutions. Citation analysis highlighted two major breakthroughs: AlphaFold's protein structure prediction (6,811 citations) and deep learning approaches to antibiotic discovery (4,784 citations). Keyword analysis identified six enduring research clusters from 2014 to 2024: sepsis, artificial neural networks, antimicrobial resistance, antimicrobial peptides, drug repurposing, and molecular docking, demonstrating the sustained integration of AI in antimicrobial therapy development. Recent trends show increasing application of AI technologies in traditional approaches, particularly in MALDI-TOF MS for pathogen identification and graph neural networks for large-scale molecular screening.

CONCLUSION: This bibliometric analysis shows the importance of artificial intelligence in enhancing the progress in the discovery of antimicrobial drugs especially toward the fight against AMR. From enhancing the fast, efficient and predictive performance of drug discovery methods, current AI capabilities have revealed observable potential to be proactive in combating the ever-growing challenge of AMR worldwide. This study serves not only an identification of current trends, but also, and especially, offers a strategic approach to further investigations.

PMID:39935800 | PMC:PMC11810743 | DOI:10.3389/fmed.2025.1492709

Clin Pharmacol Ther. 2025 Feb 11. doi: 10.1002/cpt.3583. Online ahead of print.

ABSTRACT

We evaluated whether drugs approved for other indications that also target metabolic drivers of Alzheimer's disease and related dementia (ADRD) pathogenesis are associated with delayed onset of ADRD. Using routinely collected healthcare data from two population-based data sources from the US (Medicare) and UK (CPRD), we conducted active comparator, new-user cohort studies. Four alternate analytic and design specifications were implemented: (1) an as-treated follow-up approach, (2) an as-started follow-up approach incorporating a 6-month induction period, (3) incorporating a 6-month symptom to diagnosis period to account for misclassification of ADRD onset, and (4) identifying ADRD through symptomatic prescriptions and diagnosis codes. Of the 10 drug pairs evaluated, hydrochlorothiazide vs. dihydropyridine CCBs showed meaningful reductions in 3 out of 4 analyses that addressed specific biases including informative censoring, reverse causality, and outcome misclassification (pooled hazard ratios [95% confidence intervals] across Medicare and CPRD: 0.81 [0.75-0.88] in Analysis 1, 0.98 [0.92-1.06] in Analysis 2, 0.83 [0.75-0.91] in Analysis 3, 0.75 [0.65-0.85] in Analysis 4). Amiloride vs. triamterene, although less precise, also suggested a potential reduction in risk in 3 out of 4 analyses (0.86 [0.66-1.11] in Analysis 1, 0.98 [0.79-1.23] in Analysis 2, 0.74 [0.54-1.00] in Analysis 3, 0.61 [0.36-1.05] in Analysis 4). Other analyses suggested likely no major differences in risk (probenecid, salbutamol, montelukast, propranolol/carvedilol, and anastrozole) or had limited precision precluding a definitive conclusion (semaglutide, ciloztozol, levetiracetam). Future replication studies should be considered to validate our findings.

PMID:39935003 | DOI:10.1002/cpt.3583

Rom J Ophthalmol. 2024 Oct-Dec;68(4):466-469. doi: 10.22336/rjo.2024.84.

ABSTRACT

BACKGROUND: Stevens-Johnson syndrome (SJS) is a life-threatening condition resulting from a severe reaction to the use of certain drugs, with the highest incidence found in children. It manifests as a triad of skin, orifice, and ocular mucosa lesions. Ocular manifestations most commonly involve the conjunctiva and eyelids. This case report further discusses symblepharon as an ocular manifestation of SJS.

METHOD: A case report.

CASE REPORT: A 10-year-old boy came with decreased vision and an inability to produce tears. On examination, pseudomembranous conjunctivitis was found in both eyes, granulation tissue in the right eye, and erosion of the corneal epithelium in the left eye. The posterior segment could not be assessed due to symblepharon. It was known that the patient previously experienced SJS in early 2023. Symblepharectomy was carried out with the indication of separate adhesions caused by symblepharon.

DISCUSSION: Symblepharon is a rare, severe ocular manifestation of SJS (Stevens-Johnson syndrome). Previous studies found that severe ocular occurred in around 4% and 11.1% of cases. This happened because of ongoing chronic inflammation due to SJS. Symblepharon is an adhesion of eyelids and bulbar conjunctiva, which can harm the eye because it can cause cicatricial then disruption of the tear film meniscus, limit eye mobility, and cause visual disturbances.

CONCLUSION: Symblepharon occurs due to prolonged inflammation, which can structurally and functionally disrupt the eye. Early discovery of symblepharon, especially in severe manifestations of SJS, can help prevent further damage to the eye.

PMID:39936062 | PMC:PMC11809831 | DOI:10.22336/rjo.2024.84

J Pediatr Pharmacol Ther. 2025 Feb;30(1):146-148. doi: 10.5863/1551-6776-30.1.146. Epub 2025 Feb 10.

NO ABSTRACT

PMID:39935567 | PMC:PMC11809527 | DOI:10.5863/1551-6776-30.1.146

Front Immunol. 2025 Jan 28;16:1486784. doi: 10.3389/fimmu.2025.1486784. eCollection 2025.

ABSTRACT

BACKGROUND: CFTR modulator therapies have positive clinical outcomes, yet chronic inflammation and bacterial infections persist in people with CF (pwCF). How elexacaftor-tezacaftor-ivacaftor (ETI) fails to improve innate immune signaling responsible for bacterial clearance and inflammation resolution remains unknown.

METHODS: We used an unbiased proteomics approach to measure the effect of ETI on inflammatory proteins. Plasma from 20 pediatric pwCF and 20 non-CF (NCF) was collected during routine examination and 3 months after ETI initiation. Protein screening was performed with an inflammation panel (Target 96, Olink®). Bioinformatics analysis was used to determine changes in protein expression.

RESULTS: There were significantly fewer pulmonary exacerbations after ETI initiation, along with sustained improvement in lung function and reduced bacterial colonization. Unpaired analysis of CF pre-ETI and NCF resulted in 34 significantly different proteins. Of these, CCL20, MMP-10, EN-RAGE, and AXIN1 had a log2 fold change of 1.2 or more. There was a modest shift in overall CF protein profiles post-ETI toward the NCF cluster. Unpaired analysis of protein differential expression between NCF and CF post-ETI identified a total of 24 proteins significantly impacted by ETI therapy (p-value ≤ 0.05), with only CCL20 having a log2 fold change higher than 1.2. Paired analysis (CF pre- and CF post-ETI) of differential protein expression demonstrated significant expression changes of MMP-10, EN-RAGE, and IL-17A. Pathway analysis identified significantly impacted pathways such as the NF-κB pathway.

CONCLUSION: This study showed that ETI in a pediatric cohort had a modest effect on several inflammatory proteins with potential as biomarkers. Pathways significantly impacted by ETI can be further studied for future therapies to combat persistent inflammation and dysregulated immunity.

PMID:39935472 | PMC:PMC11811078 | DOI:10.3389/fimmu.2025.1486784

Pediatr Pulmonol. 2025 Feb;60(2):e27505. doi: 10.1002/ppul.27505.

ABSTRACT

BACKGROUND: People with CF (pwCF) are often treated with prolonged courses of aminoglycosides (AGs), for which known adverse effects include ototoxicity as a subset of hearing impairment (HI).

METHODS: The PIANO-CF trial was a single-center study conducted at The Royal Children's Hospital where 28 pediatric patients aged < 7 years underwent sequential hearing tests at increased range up to 12,500 Hz in relation to receiving intravenous (IV) AGs. More than 85% of the cohort (n = 24) participated in the follow-up hearing testing up to 1 year.

RESULTS: HI was defined by degree (dB) and frequency (Hz) on the audiogram. This was further reviewed to determine if the type of HI was consistent with ototoxicity as there are frequently other causes of HI in this age group. At baseline the prevalence of HI and ototoxicity were 11% and 7%, respectively. Over a period of 1 year, HI was identified in 12.5% and that of ototoxicity in 6%. No correlation was found between degree of IV AG exposure and HI or ototoxicity.

DISCUSSION: The finding of HI in young children with CF, including in those with minimal IV AG exposure, has implications for CF services to proactively screen for HI. Undetected HI may compromise learning outcomes and given the age of children studied, this is not insignificant during the acquisition and development of language skills.

CONCLUSION: Routine audiometric testing for pwCF up to 12,500 Hz or beyond may increase sensitivity in detection of ototoxicity and should be considered for use in screening, monitoring, and future research.

PMID:39935234 | DOI:10.1002/ppul.27505