Nat Commun. 2025 Jan 20;16(1):837. doi: 10.1038/s41467-025-56049-9.

ABSTRACT

Accurate gametogenesis requires the establishment of the telomere bouquet, an evolutionarily conserved, 3D chromosomal arrangement. In this spatial configuration, telomeres temporarily aggregate at the nuclear envelope during meiotic prophase, which facilitates chromosome pairing and recombination. The mechanisms governing the assembly of the telomere bouquet remain largely unexplored, primarily due to the challenges in visualizing and manipulating the bouquet. Here, using Schizosaccharomyces pombe as a model system to elucidate telomere bouquet function, we reveal that centromeres, traditionally perceived as playing a passive role in the chromosomal reorganization necessary for bouquet assembly, play a key role in the initiation of telomere bouquet formation. We demonstrate that centromeres are capable to induce telomere mobilization, which is sufficient to trigger the first stages of bouquet assembly and the meiotic transcription program in mitotic cells. This discovery highlights the finely tuned control exerted over long-distance heterochromatic regions and underscores a pivotal step in the mechanism of eukaryotic telomere bouquet formation and meiotic transcriptional rewiring.

PMID:39833200 | DOI:10.1038/s41467-025-56049-9

Nat Commun. 2025 Jan 20;16(1):872. doi: 10.1038/s41467-025-56192-3.

ABSTRACT

Knowledge about how and where proteins interact provides a pillar for cell biology. Protein proximity-labeling has emerged as an important tool to detect protein interactions. Biotin-related proximity labeling approaches are by far the most commonly used but may have labeling-related drawbacks. Here, we use pupylation-based proximity labeling (PUP-IT) as a tool for protein interaction detection in plants. We show that PUP-IT readily confirmed protein interactions for several known protein complexes across different types of plant hosts and that the approach increased detection of specific interactions as compared to biotin-based proximity labeling systems. To further demonstrate the power of PUP-IT, we used the system to identify protein interactions of the protein complex that underpin cellulose synthesis in plants. Apart from known complex components, we identified the ARF-GEF BEN1 (BFA-VISUALIZED ENDOCYTIC TRAFFICKING DEFECTIVE1). We show that BEN1 contributes to cellulose synthesis by regulating both clathrin-dependent and -independent endocytosis of the cellulose synthesis protein complex from the plasma membrane. Our results highlight PUP-IT as a powerful proximity labeling system to identify protein interactions in plant cells.

PMID:39833163 | DOI:10.1038/s41467-025-56192-3

Redox Biol. 2025 Jan 19:103496. doi: 10.1016/j.redox.2025.103496. Online ahead of print.

NO ABSTRACT

PMID:39833011 | DOI:10.1016/j.redox.2025.103496

Acta Pharmacol Sin. 2025 Jan 20. doi: 10.1038/s41401-024-01452-z. Online ahead of print.

ABSTRACT

The bromodomain (BRD) represents a highly conserved structural module that provides BRD proteins with fundamental functionality in modulating protein-protein interactions involved in diverse biological processes such as chromatin-mediated gene transcription, DNA recombination, replication and repair. Consequently, dysregulation of BRD proteins has been implicated in the pathogenesis of numerous human diseases. In recent years, considerable scientific endeavors have focused on unraveling the molecular mechanisms underlying BRDs and developing inhibitors that target these domains. While these inhibitors compete for binding with the acetylated lysine binding site of BRDs, achieving inhibition of BRD proteins via competitive pocket binding has proven challenging due to the conserved nature of these pockets. To address this limitation, the present study employed dynamic simulations for a comprehensive analysis, leading to the identification of a non-conserved pocket in CECR2 for achieving BRD family inhibition through allosteric modulation. Subsequently, the compound BAY 11-7085 was proven capable of covalently binding to C494 of this pocket after covalent docking and biological verification in vitro. The allosteric inhibition strategy of CECR2 was further verified by the structurally optimized compound LC-CE-7, which is an allosteric covalent CECR2 inhibitor with anti-cancer effects in MDA-MB-231 cells.

PMID:39833305 | DOI:10.1038/s41401-024-01452-z

Biosens Bioelectron. 2025 Jan 13;273:117142. doi: 10.1016/j.bios.2025.117142. Online ahead of print.

ABSTRACT

Food allergies affect millions of individuals worldwide, significantly impacting personal health and the economy. While avoiding allergenic foods remains the primary management strategy, consumers lack reliable means for immediate allergen detection in everyday dining settings. Here, we present iEAT2 (integrated Exogenous Allergen Test 2), an advanced electrochemical sensing system for rapid, on-site food allergen detection. Building upon our previous assay system, the iEAT2 features technical breakthroughs: i) a complete kit for sample processing, including a torsion device for food grinding, and ii) a new strategy for multi-electrode measurements, which enables the simultaneous detection of multiple allergens in a simplified electronic architecture. We designed a compact iEAT2 prototype capable of 16 electrochemical reactions. Experimental validation confirmed the independent electrochemical measurements in a simultaneous operation. Furthermore, the entire testing protocol was completed within 15 min, from allergen extraction to detection. The platform detected three common food allergens (gliadin, Ara h1, and ovalbumin) at concentrations below established allergic reaction thresholds. It also effectively identified cross-contamination events in real-world food samples. This technology may empower consumers to monitor food safety and improve its management.

PMID:39832405 | DOI:10.1016/j.bios.2025.117142

BMC Psychiatry. 2025 Jan 20;25(1):52. doi: 10.1186/s12888-025-06493-0.

ABSTRACT

OBJECTIVE: Paliperidone palmitate is a second-generation antipsychotic that has undergone extensive investigation in clinical trials. However, real-world studies assessing its safety in large populations are lacking. As such, this study aimed to comprehensively evaluate real-world adverse drug events (ADEs) linked to paliperidone palmitate by employing data mining techniques on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database and the Japanese Adverse Drug Event Report (JADER) database.

METHODS: The study retrieved ADE reports from the FAERS database covering the period from 2009 through the third quarter of 2024, and from the JADER database covering the period from 2013 through the second quarter of 2024. Utilizing disproportionality analyses such as the reporting odds ratios (ROR), proportional reporting ratios (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item Poisson shrinkage (MGPS), significant associations between ADEs and paliperidone palmitate were evaluated.

RESULTS: A total of 27,672 ADE reports related to paliperidone palmitate were identified in FAERS, with 285 significantly disproportionate preferred terms (PTs) identified by all four algorithms. Paliperidone palmitate-associated ADEs encompassed 27 System Organ Classes (SOCs). The top three PTs with the highest reported cases were off-label use, drug ineffective, and hospitalization. Common ADEs included increased blood prolactin, galactorrhea, and schizophrenia, which was consistent with drug label. Noteworthy, unexpected signals not listed in the drug label were also identified, such as psychosexual disorders, prolactin-producing pituitary tumors, suicide attempt, and sudden death. The median onset time for all ADEs was 40 days. Furthermore, gender-based difference in risk signals was detected. Females are more likely to experience elevated blood prolactin and weight increase, whereas males are more prone to sexual dysfunction. Among the 1,065 ADE reports from the JADER database, we identified 51 positive signals, 35 of which overlapped with those found in FAERS, including schizophrenia, hyperprolactinemia, and erectile dysfunction.

CONCLUSION: The study findings from two independent databases serve as crucial references for ensuring the safe of paliperidone palmitate. Additionally, the gender-specific monitoring references provided can enhance clinical surveillance efforts and facilitate more effective risk identification.

PMID:39833706 | DOI:10.1186/s12888-025-06493-0

bioRxiv [Preprint]. 2025 Jan 9:2025.01.09.632114. doi: 10.1101/2025.01.09.632114.

ABSTRACT

In vertebrates, germ layer specification represents a critical transition where pluripotent cells acquire lineage-specific identities. We identify the maternal transcription factors Foxi2 and Sox3 to be pivotal master regulators of ectodermal germ layer specification in Xenopus . Ectopic co-expression of Foxi2 and Sox3 in prospective endodermal tissue induces the expression of ectodermal markers while suppressing mesendodermal markers. Transcriptomics analyses reveal that Foxi2 and Sox3 jointly and independently regulate hundreds of ectodermal target genes. During early cleavage stages, Foxi2 and Sox3 pre-bind to key cis-regulatory modules (CRMs), marking sites that later recruit Ep300 and facilitate H3K27ac deposition, thereby shaping the epigenetic landscape of the ectodermal genome. These CRMs are highly enriched within ectoderm-specific super-enhancers (SEs). Our findings highlight the pivotal role of ectodermal SE-associated CRMs in precise and robust ectodermal gene activation, establishing Foxi2 and Sox3 as central architects of ectodermal lineage specification.

HIGHLIGHTS: Foxi2 and Sox3 are master regulators for the ectodermal germ layer and sub-lineagesFive ectodermal cell states of early gastrulae are regulated by Foxi2 and Sox3Foxi2 and Sox3 binding sites in the genome are enriched in ectoderm super-enhancersSE-associated genes show high expression levels, low noise, stabilizing ectodermal regulation.

PMID:39829826 | PMC:PMC11741269 | DOI:10.1101/2025.01.09.632114

J Pharm Pharmacol. 2025 Jan 20:rgaf002. doi: 10.1093/jpp/rgaf002. Online ahead of print.

ABSTRACT

OBJECTIVES: Chronic kidney disease (CKD) is a serious health issue with rising morbidity and mortality rates. Despite advances in understanding its pathophysiology, effective therapeutic options are limited, necessitating innovative treatment approaches. Also, current frontline treatments that are available against CKD are not uniformly effective and often come with significant side effects. Therefore, identifying new therapeutic targets or improving existing treatments for CKD is crucial. Drug repurposing is a promising strategy in the drug discovery process that involves screening existing approved drugs for new therapeutic applications.

KEY FINDINGS: This review discusses the pharmacological mechanisms and clinical evidence that support the efficacy of these repurposed drugs. Various drugs classes such as inodilators, endothelin-1 type A (ET-1A) receptor antagonists, bisphosphonates, mineralocorticoid receptor (MR) antagonists, DNA demethylating agents, nuclear factor erythroid 2-related factor 2 (NRF2) activators, P2X7 inhibitors, autophagy modulators, hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHI) are discussed that could remarkably contribute against CKD.

SUMMARY: The review critically examines the potential for repurposing well-established drugs to slow the progression of CKD and enhance patient outcomes. This review emphasizes the importance of a multidisciplinary approach in advancing the field of drug repurposing, ultimately paving the way for innovative and effective therapies for patients suffering from CKD.

PMID:39832316 | DOI:10.1093/jpp/rgaf002

medRxiv [Preprint]. 2025 Jan 9:2025.01.08.25320199. doi: 10.1101/2025.01.08.25320199.

ABSTRACT

BACKGROUND: Analyzing disease-linked genetic variants via expression quantitative trait loci (eQTLs) is important for identifying potential disease-causing genes. Previous research prioritized genes by integrating Genome-Wide Association Study (GWAS) results with tissue- level eQTLs. Recent studies have explored brain cell type-specific eQTLs, but they lack a systematic analysis across various Alzheimer's disease (AD) GWAS datasets, nor did they compare effects between tissue and cell type levels or across different cell type-specific eQTL datasets. In this study, we integrated brain cell type-specific eQTL datasets with AD GWAS datasets to identify potential causal genes at the cell type level.

METHODS: To prioritize disease-causing genes, we used Summary Data-Based Mendelian Randomization (SMR) and Bayesian Colocalization (COLOC) to integrate AD GWAS summary statistics with cell-type-specific eQTLs. Combining data from five AD GWAS, three single-cell eQTL datasets, and one bulk tissue eQTL meta-analysis, we identified and confirmed both novel and known candidate causal genes. We investigated gene regulation through enhancer activity using H3K27ac and ATAC-seq data, performed protein-protein interaction and pathway enrichment analyses, and conducted a drug/compound enrichment analysis with the Drug Signatures Database (DSigDB) to support drug repurposing for AD.

RESULTS: We identified 27 candidate causal genes for AD using cell type-specific eQTL datasets, with the highest numbers in microglia, followed by excitatory neurons, astrocytes, inhibitory neurons, oligodendrocytes, and oligodendrocyte precursor cells (OPCs). PABPC1 emerged as a novel astrocyte-specific gene. Our analysis revealed protein-protein interaction (PPI) networks for these causal genes in microglia and astrocytes. We found the "regulation of aspartic-type peptidase activity" pathway being the most enriched among all the causal genes. AD-risk variants associated with candidate causal gene PABPC1 is located near or within enhancers only active in astrocytes. We classified the genes into three drug tiers and identified druggable interactions, with imatinib mesylate emerging as a key candidate. A drug-target gene network was created to explore potential drug targets for AD.

CONCLUSIONS: We systematically prioritized AD candidate causal genes based on cell type- specific molecular evidence. The integrative approach enhances our understanding of molecular mechanisms of AD-related genetic variants and facilitates the interpretation of AD GWAS results.

PMID:39830273 | PMC:PMC11741481 | DOI:10.1101/2025.01.08.25320199

J Clin Nurs. 2025 Jan 20. doi: 10.1111/jocn.17664. Online ahead of print.

ABSTRACT

AIM: To cross-culturally adapt a framework for person-centred leadership in residential care for older people in Sweden.

DESIGN: This study has an exploratory and descriptive design.

METHODS: The translation procedure followed a cyclic process of translation into Swedish and back-translation into English by two independent bilingual linguists. An evaluation of conceptual and semantic equivalence and comprehensiveness between the original English version and the translated Swedish version was performed by an expert committee. The translated version of the framework was validated by leaders (n = 34) in residential care, who assessed its relevance through a web form. The adaptation of the framework followed recommended guidelines for cross-cultural adaptation.

RESULTS: The translation procedure resulted in two minor changes related to the wording in two descriptors. The results of the validation procedure showed that the framework is relevant for leaders in Swedish residential care for older people.

CONCLUSION: The cross-culturally adapted framework is useful and suitable for leaders in Swedish residential care for older people. The framework clarifies the leader's role and identifies leadership attributes and requirements for person-centred leadership in residential care, thereby providing support to leaders by framing person-centred leadership.

IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The framework can be used as a guide for leadership training and/or development initiatives in residential care. It can be further extended to nursing curriculums, leadership development programs, and organisational performance and development processes. It may also provide a foundation for policy and guidelines by establishing the activities required for leaders to promote person-centredness in the care of older people.

REPORTING METHOD: This study followed the STROBE checklist for cross-sectional studies.

PATIENT AND PUBLIC CONTRIBUTION: There was no patient or public contribution.

PMID:39831575 | DOI:10.1111/jocn.17664

Pharmacogenet Genomics. 2025 Jan 21. doi: 10.1097/FPC.0000000000000558. Online ahead of print.

ABSTRACT

Ibrutinib treatment is often complicated by cardiovascular side effects (CVSEs). The objective of this retrospective pharmacogenetic study is to replicate a previously reported association of 'high-risk' patients, who are homozygous carriers of at least two of GATA4 rs804280 AA, KCNQ1 rs163182 GG, and KCNQ1 rs2237895 AA, with increased risk of hypertension or atrial fibrillation, and explore associations for other pharmacogenes (e.g. CYP3A4, CYP3A5, CYP2D6, and ABCB1) with ibrutinib CVSEs. Univariate associations with P < 0.05 were adjusted for significant pretreatment cardiovascular conditions. In total 57 patients were included in the analysis. In the primary analysis, 'high-risk' patients were not more likely to experience hypertension or atrial fibrillation (70 vs. 41%, chi-square P value = 0.06). In secondary analyses, 'high-risk' patients were more likely to experience any CVSE during treatment (75 vs. 41%, P = 0.013), develop a cardiac rhythm or function disorder (65 vs. 24%, P = 0.008), and have a treatment modification due to CVSE (45 vs. 8%, P = 0.004). Additionally, high-risk homozygous variant genotypes of KCNQ1 rs163182 GG and rs2237895 AA were each associated with an increased likelihood of treatment modifications due to CVSE (40 vs. 11%, P = 0.021 and 45 vs. 9%, P = 0.004, respectively) and cardiac rhythm or function disorders (60 vs. 27%, P = 0.037 and 60 vs. 27%, P = 0.037). This study found supportive evidence that 'high-risk' genotype was associated with increased ibrutinib CVSEs. Validation of these associations is necessary before prospective trials testing whether personalized ibrutinib treatment approaches improve clinical outcomes.

PMID:39832190 | DOI:10.1097/FPC.0000000000000558

Eur J Clin Pharmacol. 2025 Jan 17. doi: 10.1007/s00228-025-03805-x. Online ahead of print.

ABSTRACT

OBJECTIVE: The study aims to verify the usage of mathematical modeling in predicting patients' medication doses in association with their genotypes versus real-world data.

METHODS: The work relied on collecting, extracting, and using real-world data on dosing and patients' genotypes. Drug metabolizing enzymes, i.e., cytochrome CYP 450, were the focus. A total number of 1914 subjects from 26 studies were considered, and CYP2D6 and CYP2C19 gene polymorphisms were used for the verification.

RESULTS: Results show that the mathematical model was able to predict the reported optimal dosing of the values provided in the considered studies. Predicting patients' optimal doses circumvents trial and error in patients' treatments.

DISCUSSION: The authors discussed the advantages of using a mathematical model in patients' dosing and identified multiple issues that would hinder the usability of raw data in the future, especially in the era of artificial intelligence (AI). The authors recommend that researchers and healthcare professionals use simple descriptive metabolic activity terms for patients and use allele activity scores for drug dosing rather than phenotype/genotype classifications.

CONCLUSION: The authors verified that a mathematical model could assist in providing data for better-informed decision-making in clinical settings and drug research and development.

PMID:39832006 | DOI:10.1007/s00228-025-03805-x

Front Pharmacol. 2025 Jan 3;15:1540478. doi: 10.3389/fphar.2024.1540478. eCollection 2024.

NO ABSTRACT

PMID:39830351 | PMC:PMC11739166 | DOI:10.3389/fphar.2024.1540478

Front Pharmacol. 2025 Jan 3;15:1526101. doi: 10.3389/fphar.2024.1526101. eCollection 2024.

ABSTRACT

INTRODUCTION: The field of pharmacogenetics (PGx) is experiencing significant growth, with increasing evidence to support its application in psychiatric care, suggesting its potential to personalize treatment plans, optimize medication efficacy, and reduce adverse drug reactions. However, the perceived utility and practicability of PGx for psychiatric treatment in youth remains underexplored. This study investigated perceived barriers and attitudes in Australian young adults towards the implementation of PGx testing to guide antidepressant treatment in primary care.

METHODS: Semi-structured focus groups and interviews were conducted with 17 participants aged between 18 and 24 years. These sessions were recorded and transcribed before thematic analysis was used to identify collective themes.

RESULTS: Three key themes were identified, including attitudes towards the medication prescription process, concerns and attitudes towards PGx testing, and perceived barriers to its clinical implementation. Although PGx testing was positively perceived by most participants, all participants shared concerns about PGx testing. Participants voiced concerns about the financial impact of PGx testing, the potential for treatment delays, and the accuracy of PGx testing in guiding antidepressant treatment. Additionally, participants noted that the low awareness and willingness of general practitioners to incorporate PGx testing into routine practice could hinder successful clinical implementation.

DISCUSSION: Prior to the implementation of PGx testing into Australian primary practices, it is essential to acknowledge patient perspectives and ensure that clinical practices remain patient-focused. This study highlights important considerations for integrating PGx testing into antidepressant pharmacotherapy and emphasizes the need for future research to address and mitigate the perceived barriers of young adults.

PMID:39830342 | PMC:PMC11739104 | DOI:10.3389/fphar.2024.1526101

Clin Pharmacol Ther. 2025 Jan 20. doi: 10.1002/cpt.3557. Online ahead of print.

ABSTRACT

Tuberculosis (TB) is a major health burden in Africa. Although TB is treatable, anti-TB drugs are associated with adverse drug reactions (ADRs), which are partly attributed to pharmacogenetic variation. The distribution of star alleles (haplotypes) influencing anti-TB drug metabolism is unknown in many African populations. This presents challenges in implementing genotype-guided therapy in Africa to decrease the occurrence of ADRs and enhance the efficacy of anti-TB drugs. In this study, we used StellarPGx to call variants and star alleles in NAT1, NAT2, GSTM1, GSTT1, GSTP1, and CYP2E1, from 1079 high-depth African whole genomes. We present the distribution of common, rare, and potential novel star alleles across various Sub-Saharan African (SSA) populations, in comparison with other global populations. NAT1*10 (53.6%), GSTT1*0 (65%), GSTM1*0 (48%), and NAT2*5 (17.5%) were among the predominant functionally relevant star alleles. Additionally, we predicted varying phenotype distributions for NAT1 and NAT2 (acetylation) and the glutathione-S-transferase (GST) enzymes (detoxification activity) between SSA and other global populations. Forty-seven potentially novel haplotypes were identified computationally across the genes. This study provides insight into the distribution of key variants and star alleles potentially relevant to anti-TB drug metabolism and other drugs prescribed across various African populations. The high number of potentially novel star alleles exemplifies the need for pharmacogenomics studies in the African context. Overall, our study provides a foundation for functional pharmacogenetic studies and potential implementation of pharmacogenetic testing in Africa to reduce the risk of ADRs related to treatment of TB and other diseases.

PMID:39829327 | DOI:10.1002/cpt.3557

Pharmacogenomics. 2025 Jan 19:1-5. doi: 10.1080/14622416.2025.2454217. Online ahead of print.

ABSTRACT

BACKGROUND: Macrolides are widely used antibiotics, but adverse drug reactions (ADRs), particularly in genetically predisposed individuals, can compromise their safety. This study examines the impact of pharmacogenetic markers on macrolide safety in participants with bacterial complications of influenza.

OBJECTIVE: To evaluate how polymorphisms in genes encoding transporter proteins (ABCB1) and enzymes (CYP3A4, CYP3A5) influence ADR risk during macrolide therapy.

METHODS: A prospective study included 100 participants with lower respiratory tract bacterial complications of influenza treated with azithromycin or erythromycin for five days. Genotyping targeted ABCB1 (3435C>T), CYP3A4 (C>T intron 6), and CYP3A5 (6986A>G) polymorphisms. ADRs were monitored daily and correlated with genetic markers.

RESULTS: The ABCB1 (3435C>T) polymorphism was associated with higher rates of abdominal pain and diarrhea in CT and TT genotypes (OR = 2.12, p = 0.043). The CYP3A4 (C>T intron 6) polymorphism increased ADR risk in erythromycin-treated participants (OR = 24.0, p = 0.0339). No significant effects were observed for CYP3A5 (6986A>G).

CONCLUSION: Genetic polymorphisms in ABCB1 and CYP3A4 genes predict macrolide-related ADRs. Pharmacogenetic screening could improve macrolide safety, particularly for genetically susceptible individuals.

PMID:39829075 | DOI:10.1080/14622416.2025.2454217

J Particip Med. 2025 Jan 20;17:e49941. doi: 10.2196/49941.

ABSTRACT

BACKGROUND: Adolescents and young adults (AYA) with cystic fibrosis (CF) are at risk for deviating from their daily treatment regimen due to significant time burden, complicated daily therapies, and life stressors. Developing patient-centric, effective, engaging, and practical behavioral interventions is vital to help sustain therapeutically meaningful self-management.

OBJECTIVE: This study aimed to devise and refine a patient-centered telecoaching intervention to foster self-management in AYA with CF using a combination of intervention development approaches, including an evidence- and theory-based approach (ie, applying existing theories and research evidence for behavior change) and a target population-centered approach (ie, intervention refinement based on the perspectives and actions of those individuals who will use it).

METHODS: AYA with CF, their caregivers, and health professionals from their CF care teams were recruited to take part in focus groups (or individual qualitative interviews) through a video call interface to (1) obtain perspectives on the overall structure and logistics of the intervention (ie, Step 1) and (2) refine the overall framework of the intervention and obtain feedback on feasibility, content, materials, and coach training (ie, Step 2). Qualitative data were analyzed using a reflexive thematic analysis process. Results were used to create and then modify the intervention structure and content in response to community partner input.

RESULTS: For Step 1, a total of 31 AYA and 20 clinicians took part in focus groups or interviews, resulting in 2 broad themes: (1) video call experience and (2) logistics and content of intervention. For Step 2, a total of 22 AYA, 18 clinicians, and 11 caregivers completed focus groups or interviews, yielding 3 major themes: (1) intervention structure, (2) intervention materials, and (3) session-specific feedback. Our Step 1 qualitative findings helped inform the structure (eg, telecoaching session frequency and duration) and approach of the telecoaching intervention. Step 2 qualitative results generally suggested that community partners perceived the feasibility and practicality of the proposed telecoaching intervention in promoting self-management in the face of complex treatment regimens. Extensive specific feedback was used to refine our telecoaching intervention before its efficacy testing in subsequent research. The diverse community partner input was critical in optimizing and tailoring our telecoaching intervention.

CONCLUSIONS: This study documents the methods and results for engaging key community partners in creating an evidence-based behavioral intervention to promote self-management in AYA with CF. Incorporating the lived experiences and perspectives of community partners is essential when devising tailored and patient-centered interventions.

PMID:39832355 | DOI:10.2196/49941

Cochrane Database Syst Rev. 2025 Jan 20;1:CD009730. doi: 10.1002/14651858.CD009730.pub3.

ABSTRACT

BACKGROUND: Cystic fibrosis is a multisystem disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. Intravenous (IV) antibiotics are commonly used in the treatment of acute deteriorations in symptoms (pulmonary exacerbations); however, recently the assumption that exacerbations are due to increases in bacterial burden has been questioned. This is an update of a previously published review.

OBJECTIVES: To establish whether IV antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis improve short-term and long-term clinical outcomes.

SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews and ongoing trials registers. Date of last search of Cochrane Trials Register: 19 June 2024.

SELECTION CRITERIA: Randomised controlled trials and the first treatment cycle of cross-over studies comparing IV antibiotics (given alone or in an antibiotic combination) with placebo, or inhaled or oral antibiotics for people with cystic fibrosis experiencing a pulmonary exacerbation. Studies comparing different IV antibiotic regimens were also eligible.

DATA COLLECTION AND ANALYSIS: We assessed studies for eligibility and risk of bias, and extracted data. Using GRADE, we assessed the certainty of the evidence for the outcomes lung function % predicted (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)), time to next exacerbation and quality of life.

MAIN RESULTS: We included 45 studies involving 2810 participants. The included studies were mostly small, and inadequately reported, many of which were quite old. The certainty of the evidence was mostly low. Combined intravenous antibiotics versus placebo Data reported for absolute change in % predicted FEV1 and FVC suggested a possible improvement in favour of IV antibiotics, but the evidence is very uncertain (1 study, 12 participants; very low-certainty evidence). The study did not measure time to next exacerbation or quality of life. Intravenous versus nebulised antibiotics Five studies (122 participants) reported FEV1, with analysable data only from one study (16 participants). We found no difference between groups (moderate-certainty evidence). Three studies (91 participants) reported on FVC, with analysable data from only one study (54 participants). We are very uncertain on the effect of nebulised antibiotics (very low-certainty evidence). In one study, the 16 participants on nebulised plus IV antibiotics had a lower mean number of days to next exacerbation than those on combined IV antibiotics (low-certainty evidence), but we found no difference in quality of life between groups (low-certainty evidence). Intravenous versus oral antibiotics Three studies (172 participants) reported no difference in different measures of lung function. We found no difference in analysable data between IV and oral antibiotic regimens in either FEV1 % predicted or FVC % predicted (1 study, 24 participants; low-certainty evidence) or in the time to the next exacerbation (1 study, 108 participants; very low-certainty evidence). No study measured quality of life. Intravenous antibiotic regimens compared One study (analysed as two data sets) compared the duration of IV antibiotic regimens between two groups (split according to initial antibiotic response). The first part was a non-inferiority study in 214 early treatment responders to establish whether 10 days of IV antibiotic treatment was as effective as 14 days. Second, investigators looked at whether 14 or 21 days of IV antibiotics were more effective in 705 participants who did not respond early to treatment. We found no difference in FEV1 % predicted with any duration of treatment (919 participants; high-certainty evidence) or the time to next exacerbation (information later taken from registry data). Investigators did not report FVC or quality of life. Other comparisons We also found little or no difference in lung function when comparing single IV antibiotic regimens to placebo (2 studies, 70 participants), or in lung function and time to next exacerbation when comparing different single antibiotic regimens (2 studies, 95 participants). There may be a greater improvement in lung function in participants receiving combined IV antibiotics compared to single IV antibiotics (6 studies, 265 participants; low- to very low-certainty evidence), but probably no difference in the time to next exacerbation (1 study, 34 participants; low-certainty evidence). Four studies compared a single IV antibiotic plus placebo to a combined IV antibiotic regimen with high levels of heterogeneity in the results. We are very uncertain if there is any difference between groups in lung function (4 studies, 214 participants) and there may be little or no difference to being re-admitted to hospital for an exacerbation (2 studies, 104 participants). Nine studies (417 participants) compared combined IV antibiotic regimens with a great variation in drugs. We identified no differences in any measure of lung function or the time to next exacerbation between different regimens (low- to very low-certainty evidence). There were mixed results for adverse events across all comparisons; common adverse effects included elevated liver function tests, gastrointestinal events and haematological abnormalities. There were limited data for other secondary outcomes, such as weight, and there was no evidence of treatment effect.

AUTHORS' CONCLUSIONS: The evidence of benefit from administering IV antibiotics for pulmonary exacerbations in cystic fibrosis is often poor, especially in terms of size of studies and risk of bias, particularly in older studies. We are not certain whether there is any difference between specific antibiotic combinations, and neither is there evidence of a difference between the IV route and the inhaled or oral routes. There is limited evidence that shorter antibiotic duration in adults who respond early to treatment is not different to a longer period of treatment. There remain several unanswered questions regarding optimal IV antibiotic treatment regimens.

PMID:39831540 | DOI:10.1002/14651858.CD009730.pub3

World Allergy Organ J. 2024 Dec 27;18(1):101016. doi: 10.1016/j.waojou.2024.101016. eCollection 2025 Jan.

ABSTRACT

BACKGROUND: This study aimed to evaluate the impact of severe asthma (SA) treatments after 12 months in achieving clinical remission (CR) within the context of the Severe Asthma Network in Italy (SANI) using the recent SANI definition of CR on treatment.

METHODS: CR has been defined by SANI as complete, partial, and no CR. Complete CR is defined by the absence of oral corticosteroids (OCS), no symptoms, no exacerbations, and stable lung function, and partial CR requires the absence of OCS and the fulfillment of 2 out of the other 3 criteria. Patients who do not meet the previous criteria do not reach CR.

RESULTS: After 12 months of treatment, 283 patients were selected to evaluate the effectiveness of biologics (225 patients) and inhaled therapy (58 patients) in achieving CR. Among patients treated with biologic agents, 45.8% reached complete CR, 23.1% partial CR, and 31.1% no CR. Differences in CR achievement according to type of biologic agent administered were observed. Interesting results were found when assessing the inhaled therapy (ICS/LABA/LAMA and no biologics) effectiveness: 34.5% patients reached complete CR, 34.5% partial CR, and 31.0% did not reach CR. This finding is noteworthy since it further supports the efficacy of inhaled treatment in certain SA patients and highlights the relevance of using CR as a modern outcome of SA treatments. Chronic rhinosinusitis with nasal polyps (CRSwNP) comorbidity was associated, though not significantly, with CR achievement in patients treated with biologics. Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) scores significantly impacted CR (p = 0.003 and p = 0.027, respectively), while biomarkers, namely IgE, blood eosinophils, or fractional exhaled nitric oxide (FeNO), were not associated with CR achievement.

CONCLUSIONS: This study confirmed the effectiveness of biologics in reaching CR and demonstrated also inhaled therapies able to achieve CR. These innovative findings should encourage post hoc analysis of randomized clinical trials or even retrospective analysis of SA patient cohorts to evaluate CR with different inhaled treatments and further define the populations eligible for each treatment.

TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT06625216; Central Ethics Committee: Comitato Etico Area Vasta Nord-Ovest Toscana (study number 1245/2016, protocol number:73714).

PMID:39829953 | PMC:PMC11741032 | DOI:10.1016/j.waojou.2024.101016

Biomed Phys Eng Express. 2025 Jan 20. doi: 10.1088/2057-1976/adabea. Online ahead of print.

ABSTRACT

Deep learning has emerged as a powerful tool in medical imaging, particularly for corneal topographic map classification. However, the scarcity of labeled data poses a significant challenge to achieving robust performance. This study investigates the impact of various data augmentation strategies on enhancing the performance of a customized convolutional neural network model for corneal topographic map classification. We propose a hybrid data augmentation approach that combines traditional transformations, generative adversarial networks, and specific generative models. Experimental results demonstrate that the hybrid data augmentation method, achieves the highest accuracy of 99.54%, significantly outperforming individual data augmentation techniques. This hybrid approach not only improves model accuracy but also mitigates overfitting issues, making it a promising solution for medical image classification tasks with limited data availability.

PMID:39832385 | DOI:10.1088/2057-1976/adabea