Int J Tuberc Lung Dis. 2025 May 25;29(5):199-201. doi: 10.5588/ijtld.25.0157.

ABSTRACT

Until relatively recently, bronchiectasis (not due to cystic fibrosis) was considered an orphan disease, lacking clinical and commercial interest, and was rarely diagnosed. Since the 2000s, several working groups have emerged in Europe and the US - with the first register for bronchiectasis launching in Spain - and these have demonstrated the impact bronchiectasis has on health. Today, bronchiectasis is considered the third most common chronic inflammatory disease of the airways, after COPD and asthma, and represents a significant economic burden. We make the case for further characterization of these registries to better understand the heterogeneous epidemiology of bronchiectasis.

PMID:40281677 | DOI:10.5588/ijtld.25.0157

Sensors (Basel). 2025 Apr 8;25(8):2362. doi: 10.3390/s25082362.

ABSTRACT

Traditional farming has evolved from standalone computing systems to smart farming, driven by advancements in digitalization. This has led to the proliferation of diverse information systems (IS), such as IoT and sensor systems, decision support systems, and farm management information systems (FMISs). These systems often operate in isolation, limiting their overall impact. The integration of IS into connected smart systems is widely addressed as a key driver to tackle these issues. However, it is a complex, multi-faceted issue that is not easily achievable. Previous studies have offered valuable insights, but they often focus on specific cases, such as individual IS and certain integration aspects, lacking a comprehensive overview of various integration dimensions. This systematic review of 74 scientific papers on IS integration addresses this gap by providing an overview of the digital technologies involved, integration levels and types, barriers hindering integration, and available approaches to overcoming these challenges. The findings indicate that integration primarily relies on a point-to-point approach, followed by cloud-based integration. Enterprise service bus, hub-and-spoke, and semantic web approaches are mentioned less frequently but are gaining interest. The study identifies and discusses 27 integration challenges into three main areas: organizational, technological, and data governance-related challenges. Technologies such as blockchain, data spaces, AI, edge computing and microservices, and service-oriented architecture methods are addressed as solutions for data governance and interoperability issues. The insights from the study can help enhance interoperability, leading to data-driven smart farming that increases food production, mitigates climate change, and optimizes resource usage.

PMID:40285052 | DOI:10.3390/s25082362

Clin Pharmacokinet. 2025 Apr 26. doi: 10.1007/s40262-025-01502-7. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Metoprolol is primarily metabolized via the polymorphic cytochrome P450-2D6 (CYP2D6) enzyme, which underlies interindividual variation in conversion rates and may benefit from pharmacogenetics-driven therapy personalization. However, the field relies heavily on knowledge of a drug's metabolism, often originating from early-phase clinical trials with single-dose administration in small samples of healthy volunteers. Pharmacogenetics could thus benefit from real-world drug metabolism studies.

METHODS: We conducted a real-world drug metabolism study for metoprolol in 18 (potential) living kidney donors and 374 kidney transplant recipients from the Transplant Lines Food and Nutrition Biobank and Cohort Study (NCT02811835) using existing liquid chromatography-high resolution mass spectrometry pharmacometabolomic data.

RESULTS: In both groups, we confirmed the presence of seven expected metabolites, including the high-abundance substances metoprolol acid and hydroxymetoprolol. We were unable to detect deisopropylmetoprolol and a metabolite known as "H 119/68". However, we did find putative further oxidized forms, namely the expected variant of deisopropylmetoprolol in which the primary amine is removed and the leftover methyl group is oxidized into a carboxylic acid ("H 104/83") and an unknown/unreported metoprolol metabolite that we refer to as "metoprolol benzoic acid". Moreover, we found nine other previously unknown/unreported metabolites, putatively reflecting N-glucuronidated metoprolol, four glucuronidated versions of hydroxymetoprolol, and a formylated, a glucuronidated, and two hydroxylated versions of metoprolol acid. Interestingly, the same metabolites were detected in potential living kidney donors and kidney transplant recipients, and metabolite profiles did not differ between both groups in principal component analysis.

CONCLUSION: We found more metoprolol metabolites than previously reported, calling for replication studies and evaluation of pharmacogenetic testing approaches to realize safer, more effective metoprolol therapy.

PMID:40285825 | DOI:10.1007/s40262-025-01502-7

Drug Dev Res. 2025 May;86(3):e70093. doi: 10.1002/ddr.70093.

ABSTRACT

Recent advances in pharmacology are revolutionizing drug discovery and treatment strategies through personalized medicine, pharmacogenomics, and artificial intelligence (AI). The objective of the present study is to review the role of personalized medicine, pharmacogenomics, and AI-based strategies in optimizing patient outcomes with improved drug efficacy and reduced side effects. A comprehensive review was performed to debate the utility of pharmacogenomics in the prediction of drug response, the role of AI in drug discovery, and the utility of personalized medicine in the clinic. This review highlights how drug discovery and treatment techniques are evolving with the aid of personalized medicine, pharmacogenomics, and AI. Personalized medicine makes the treatment fit the DNA pattern for higher efficacy and minimal side effects. Pharmacogenomics forecasts the action of a drug in terms of genetic difference. AI speeds up drug discovery to enhance the effectiveness and accuracy of finding and evaluating drug leads. Studies show that customized medicine charts therapy to an individual patient's individual genetic profile, resulting in better therapy. Pharmacogenomics facilitates precise drug selection by considering genetic variations, reducing adverse reactions. AI speeds up drug discovery by applying predictive modeling and data-driven evaluation to propel optimized drug development pathways. Together, these advances are enabling more efficient and safer treatment practices across medical disciplines. The combination of pharmacology, genomics, and AI is revolutionizing contemporary healthcare through the personalization of treatments, improved drug safety, and therapeutic outcomes. The future of research should be on optimizing these techniques and overcoming ethical and regulatory issues to facilitate broader clinical implementation.

PMID:40285487 | DOI:10.1002/ddr.70093

Clin Transl Sci. 2025 May;18(5):e70239. doi: 10.1111/cts.70239.

ABSTRACT

Previous pharmacogenetic findings for beta-blocker pharmacodynamic candidate genes (ADRB1, ADRB2, ADRA2C, GRK4, and GRK5) have been inconsistent. Therefore, the purpose of this study was to determine whether interactions of pharmacodynamic variants with beta-blocker exposure significantly associated with survival in patients with heart failure with reduced ejection (HFrEF). The 893 patients were 51% self-reported African American and 49% self-reported White race, 36% female, and 240 died (27%) over a median follow-up of 2.8 years. The primary outcome was all-cause mortality. Using Cox proportional hazards models with time-varying beta-blocker exposure and adjusted for clinical risk factors and ancestry, interactions of ADRB1 Arg389Gly, ADRB1 Ser49-Arg389Gly haplotype, ADRA2C Del322-325, and GRK4 Ala486Val with beta-blocker exposure were significant before correction for multiple comparisons (p < 0.1), but only GRK4 Ala486Val remained significant in African Americans after correction for multiple comparisons using the adaptive Hochberg method (p = 0.022). Beta-blocker exposure only associated with a significant reduction in the risk of mortality in the African American HFrEF patients with the GRK4 Ala486/Ala486 genotype (HR = 0.44; 95% CI = 0.20-0.96; p = 0.04). In conclusion, the interaction of GRK4 Ala486Val with beta-blocker exposure significantly associated with survival in African American HFrEF patients. Larger sample sizes or meta-analyses are needed to have more statistical power to better assess beta-blocker pharmacogenetic interactions for ADRB1 Arg389Gly, ADRB1 Ser49-Arg389Gly haplotype, and ADRA2C Del322-325 in the future.

PMID:40285373 | DOI:10.1111/cts.70239

Brief Bioinform. 2025 Mar 4;26(2):bbaf195. doi: 10.1093/bib/bbaf195.

ABSTRACT

The rapidly emerging large-scale data in diverse biological research fields present valuable opportunities to explore the underlying mechanisms of tissue development and disease progression. However, few existing methods can simultaneously capture common and condition-specific association between different types of features across different biological conditions, such as cancer types or cell populations. Therefore, we developed the sparse tensor-based partial least squares (sTPLS) method, which integrates multiple pairs of datasets containing two types of features but derived from different biological conditions. We demonstrated the effectiveness and versatility of sTPLS through simulation study and three biological applications. By integrating the pairwise pharmacogenomic data, sTPLS identified 11 gene-drug comodules with high biological functional relevance specific for seven cancer types and two comodules that shared across multi-type cancers, such as breast, ovarian, and colorectal cancers. When applied to single-cell data, it uncovered nine gene-peak comodules representing transcriptional regulatory relationships specific for five cell types and three comodules shared across similar cell types, such as intermediate and naïve B cells. Furthermore, sTPLS can be directly applied to tensor-structured data, successfully revealing shared and distinct cell communication patterns mediated by the MK signaling pathway in coronavirus disease 2019 patients and healthy controls. These results highlight the effectiveness of sTPLS in identifying biologically meaningful relationships across diverse conditions, making it useful for multi-omics integrative analysis.

PMID:40285361 | DOI:10.1093/bib/bbaf195

Pharmaceuticals (Basel). 2025 Apr 7;18(4):539. doi: 10.3390/ph18040539.

ABSTRACT

Background: Studying single-nucleotide polymorphisms (SNPs) in xenobiotic-transporting and metabolizing enzyme genes before administering the doxorubicin hydrochloride and cyclophosphamide (AC) regimen may help optimize breast cancer (BC) treatment for individual patients. Objective: Genotyping specific SNPs on genes encoding for the transport and metabolism of the AC regimen and study their association with its chemotherapeutic toxicity. Method: This prospective cohort study was conducted in two hospitals in Egypt. Before receiving AC therapy, venous blood was collected from female patients with BC for DNA extraction and the genotyping of four SNPs: rs2228100 in ALDH3A1 gene, rs12248560 in CYP2C19 gene, rs1045642 in ABCB1 gene, and rs6907567 in SLC22A16 gene. Patients were then prospectively monitored for hematological, gastrointestinal, and miscellaneous toxicities throughout the treatment cycles. Results: The ALDH3A1 gene polymorphism demonstrated a significant increase in nausea, stomachache, and peripheral neuropathy among patients carrying the GC+CC genotype, compared to those with the GG genotype (p = 0.023, 0.036, and 0.008, respectively). Conversely, patients with the GG genotype exhibited significantly higher fever grades after cycles 1, 2, and 3 of the AC regimen compared to those with the GC+CC genotype (p = 0.009, 0.017, and 0.018, respectively). Additionally, fatigue severity was significantly increased among patients with the GG genotype compared to those with the GC+CC genotype following AC administration (p = 0.008). Conclusions: The SNP variation of ALDH3A1 (rs2228100) gene significantly influenced AC regimen toxicity in female BC patients. Meanwhile, SNPs in CYP2C19 (rs12248560), ABCB1 (rs1045642), and SLC22A16 (rs6907567) genes showed a significant influence on the recurrence rate of certain toxicities.

PMID:40283974 | DOI:10.3390/ph18040539

Pharmaceuticals (Basel). 2025 Apr 1;18(4):515. doi: 10.3390/ph18040515.

ABSTRACT

Background/Objectives: Fluoropyrimidine derivatives, 5-fluorouracil (5-FU) and its prodrugs (capecitabine and tegafur), are widely used in patients suffering from colorectal cancer. The enzyme responsible for their metabolization, dihydropyrimidine dehydrogenase (DPD), is encoded by the DPYD gene, which is highly polymorphic and may contain polymorphisms which could severely compromise its function. This article aims to describe the prevalence of the four main DPYD polymorphisms in the Galician population (Spain) and to compare these frequencies with data obtained from European cohorts in genetic databases and a Spanish study. Methods: Galician data frequencies for the four main DPYD polymorphisms recommended by the European Medicine Agency (EMA) and the Spanish Agency for Medicines and Health Products (AEMPS) (rs3918290 (c.1905+1G>A), rs55886062 (c.1679T>G), rs56038477 (c.1236G>A) and rs67376798 (c.2846A>T)) were collected, as well as data from the genomic databases 1000 Genomes and gnomAD. Additionally, the results from a Spanish DPYD study were included. Results: Significant differences in DPYD variant allele frequencies were observed in the Galician population compared to the frequencies reported in the European population, as well as in the Spanish PhotoDPYD study. Specifically, the rs56038477-T variant (most prevalent) along with the rs3918290-T variant, exhibited significantly lower frequencies than anticipated in the Galician cohort, with a high degree of statistical significance. Conclusions: Observed allele frequencies for the four DPYD variants suggest that Europeans and Spanish frequencies may not be fully applicable to the Galician population. These results emphasize the emerging need for incorporating the genetic information of populations that might be underrepresented into populational databases available worldwide.

PMID:40283950 | DOI:10.3390/ph18040515

Pharmaceuticals (Basel). 2025 Mar 29;18(4):499. doi: 10.3390/ph18040499.

ABSTRACT

Lysergic acid diethylamide (LSD) is gaining renewed interest as a potential treatment for anxiety, depression, and alcohol use disorder, with clinical trials reporting significant symptom reductions and long-lasting effects. LSD modulates serotonin (5-HT2A) receptors, which, in turn, influence dysfunctional brain networks involved in emotional processing and cognition. It has also shown promise in psychedelic-assisted psychotherapy, where mystical-type experiences are linked to improved psychological well-being. This review examines LSD's pharmacokinetics, neurobiological mechanisms, and safety considerations, including cardiovascular risks, emotional vulnerability, and the potential for hallucinogen-persisting perception disorder (HPPD). Challenges such as small sample sizes, variable dosing protocols, and regulatory restrictions limit large-scale trials. Future research should focus on standardization, pharmacogenetic influences, and personalized treatment strategies to ensure its safe and effective integration into clinical practice.

PMID:40283936 | DOI:10.3390/ph18040499

Genes (Basel). 2025 Apr 15;16(4):453. doi: 10.3390/genes16040453.

ABSTRACT

BACKGROUND/OBJECTIVES: Lung cancer has a high mortality rate worldwide, with non-small cell lung cancer (NSCLC) being the most prevalent. Carboplatin and paclitaxel are key treatments for NSCLC; however, adverse drug reactions (ADRs) pose significant challenges. This study examined the impact of genetic variations in ABCB1 and ABCC2 genes on the incidence of ADRs and survival in NSCLC patients treated with carboplatin and paclitaxel.

METHODS: Variants were identified using RT-PCR, and ADRs classified according to the Common Toxicity Criteria for Adverse Events, Version 4.03.

RESULTS: The ABCB1 rs1128503 (c.1236C>T) CC genotype was associated with a higher chance of nausea (OR: 3.5, 95% CI 1.367-9.250, p = 0.0093), vomiting (OR: 13.553, 95% CI 1.705-107.723, p = 0.0137), and a higher risk of death in CT or TT genotypes (HR: 1.725, 95% CI 1.036-2.871, p = 0.0361). The ABCC2 rs717620 (c.-24C>T) TT genotype was associated with increased ALP levels (OR: 14.6, 95% CI 1.234-174.236, p = 0.0335). The ABCB1 rs2032582 non-CC genotypes (TT+AA+TA+CA+CT) were associated with an increased risk of death (HR: 1.922, 95% CI 1.093-3.377, p = 0.0232). Patients with hypocalcemia (HR: 2.317, 95% IC 1.353-3.967, p = 0.022), vomiting (HR: 3.047, 95% IC 1.548-5.997, p = 0.0013), and diarrhea (HR: 2.974, 95% IC 1.590-5.562, p = 0.0006) were associated with lower overall survival.

CONCLUSIONS: The data suggest that ABCB1 variants may influence gastrointestinal ADRs and patient survival, highlighting the importance of pharmacogenomics in predicting ADRs and drug resistance. This approach offers more precise pharmacotherapy, reduces ADRs, and enhances the patients' quality of life and survival.

PMID:40282412 | DOI:10.3390/genes16040453

Genes (Basel). 2025 Mar 30;16(4):403. doi: 10.3390/genes16040403.

ABSTRACT

BACKGROUND/OBJECTIVES: This review examines the role of pharmacogenomics in individual responses to the pharmacotherapy of various drugs of abuse, including alcohol, cocaine, and opioids, to identify genetic variants that contribute to variability in substance use disorder treatment outcomes. In addition, it explores the pharmacomicrobiomic aspects of substance use, highlighting the impact of the gut microbiome on bioavailability, drug metabolism, pharmacodynamics, and pharmacokinetics.

RESULTS: Research on pharmacogenetics has identified several promising genetic variants that may contribute to the individual variability in responses to existing pharmacotherapies for substance addiction. However, the interpretation of these findings remains limited. It is estimated that genetic factors may account for 20-95% of the variability in individual drug responses. Therefore, genetic factors alone cannot fully explain the differences in drug responses, and factors such as gut microbiome diversity may also play a significant role. Drug microbial biotransformation is produced by microbial exoenzymes that convert low molecular weight organic compounds into analogous compounds by oxidation, reduction, hydrolysis, condensation, isomerization, unsaturation, or by the introduction of heteroatoms. Despite significant advances in pharmacomicrobiomics, challenges persist including the lack of standardized methodologies, inter-individual variability, limited understanding of drug biotransformation mechanisms, and the need for large-scale validation studies to develop microbiota-based biomarkers for clinical use.

CONCLUSIONS: Progress in the pharmacogenomics of substance use disorders has provided biological insights into the pharmacological needs associated with common genetic variants in drug-metabolizing enzymes. The gut microbiome and its metabolites play a pivotal role in various stages of drug addiction including seeking, reward, and biotransformation. Therefore, integrating pharmacogenomics with pharmacomicrobiomics will form a crucial foundation for significant advances in precision and personalized medicine.

PMID:40282363 | DOI:10.3390/genes16040403

Genes (Basel). 2025 Mar 24;16(4):372. doi: 10.3390/genes16040372.

ABSTRACT

BACKGROUND/OBJECTIVES: The CYP2C9 enzyme is involved in the metabolism of warfarin. The CYP2C9 gene harbors several single-nucleotide polymorphisms (SNPs), including CYP2C9*2 (rs1799853), which is known to affect warfarin's therapeutic response. So, it is important to develop analytical tools capable of genotyping these SNPs to adjust warfarin's therapeutic outcomes. In this work, an electrochemical DNA-based sensor was constructed and optimized for the detection of the CYP2C9*2 polymorphism.

METHODS: Using bioinformatic database platforms, two 71 base pair DNA target probes with the polymorphic variants A and G were chosen and designed. A DNA-based sensor was composed by mercaptohexanol and the CYP2C9*2 DNA capture probe in a self-assembled monolayer connected to screen-printed gold electrodes. Two independent hybridization events of the CYP2C9*2 allele were designed using complementary fluorescein-labeled DNA signaling to improve selectivity and avoid secondary structures. Three human samples with the homozygous variant (G/G) and non-variant (A/A) and heterozygous (G/A) genotypes were amplified by PCR and then applied to the developed genosensor.

RESULTS: Chronoamperometry measurements were performed for both polymorphic probes. A calibration curve in the 0.25 to 2.50 nM (LOD of 13 pM) and another in the 0.15 to 5.00 nM range (LOD of 22.6 pM) were obtained for the homozygous non-variant and variant probes, respectively. This innovative tool was capable of identifying the hybridization reaction between two complementary strands of immobilized DNA, representing a genotyping alternative to the classical PCR methodology.

CONCLUSIONS: The developed electrochemical DNA-based sensor was able to discriminate two synthetic SNP target sequences (Target-A and Target-G) and detect, with specificity, the three patients' genotypes (G/G, G/A, and A/A). This tool is therefore a promising, sensitive, and cost-effective analytical way to determine and discriminate an individual's genotype and predict the appropriate warfarin dose.

PMID:40282332 | DOI:10.3390/genes16040372

Genes (Basel). 2025 Mar 24;16(4):371. doi: 10.3390/genes16040371.

ABSTRACT

Neuropsychiatric disorders are complex conditions with multifactorial etiologies, in which genetics play a pivotal role. Despite significant advancements in psychiatric research, traditional treatment options remain largely symptomatic, focusing on clinical signs without fully addressing the underlying biological causes. However, recent developments in precision medicine-an approach that tailors treatments based on genetic, environmental, and lifestyle factors-hold great promise for transforming the treatment of these disorders. By identifying specific genetic markers and understanding gene-environment interactions, precision medicine can offer more personalized and effective treatments, leading to better patient outcomes. Our primary aim was to explore how integrating genetic data with environmental factors could enhance the understanding and treatment of neuropsychiatric conditions such as schizophrenia, bipolar disorder, and depression. The secondary aim was to examine the potential of pharmacogenomics and gene therapy in improving therapeutic strategies. The results indicate that while significant progress has been made, challenges remain, including the complexity of genetic interactions and the need for more granular phenotypic data. In conclusion, precision medicine has the potential to revolutionize neuropsychiatric treatment by providing individualized care that considers genetic makeup, environmental influences, and lifestyle factors, paving the way for more effective therapies and improved patient outcomes.

PMID:40282331 | DOI:10.3390/genes16040371

Microorganisms. 2025 Mar 24;13(4):730. doi: 10.3390/microorganisms13040730.

ABSTRACT

This study examines the impact of inhaled tobramycin therapy on the within-host changes in P. aeruginosa strains isolated from Bulgarian patients with CF prior to and post treatment. Genotypic comparison by RAPD-PCR indicated that most of the pre-treatment isolates had a high similarity and were genetically comparatively close to strains from other countries with known increased morbidity or treatment requirements. Most of the post-treatment isolates were, however, genetically distant from their pre-treatment counterparts, showing genotypic diversification after the treatment. Phenotypic comparisons showed a lower ODmax reached during groswth and an increased lag-time in the post-treatment isolates. All strains were capable of invasion and intracellular reproduction within A549 cultured cells. The addition of sub-inhibitory amounts (1/4 or 1/2 MIC) of tobramycin during growth showed the higher relative fitness (as a percentage of the untreated control) of the post-treatment strains. The effects of sub-MICs on biofilm growth did not show such a pronounced trend. However, when a resazurin-based viability test was applied, the advantage of the post-treatment strains was confirmed for both broth and biofilm cultures. In spite of that, according to the determined MIC values, all isolates were tobramycin-sensitive, and the data from this study imply the development of tolerance to the antibiotic in the strains that survived the treatment.

PMID:40284567 | DOI:10.3390/microorganisms13040730

J Clin Med. 2025 Apr 18;14(8):2807. doi: 10.3390/jcm14082807.

ABSTRACT

Background/Objective: Cystic fibrosis (CF) is a chronic genetic disease affecting multiple body systems and having a significant impact on mental health and sleep. Patients with CF frequently suffer from anxiety, depression, and sleep disturbances, but non-pharmacological strategies are understudied. Although progressive muscle relaxation (PMR) has recognized benefits, its impact on CF remains insufficiently explored. The study aimed to analyze the effect of integrating PMR into a standard pulmonary rehabilitation (PR) program on mental health, sleep quality, and quality of life in adults with CF. Methods: A total of 22 adult patients with CF were randomly assigned to either the intervention group (PR + PMR) or the control group (PR only). Assessments were performed at baseline, after 21 days of intervention, and at the 48-day follow-up. Outcome measures included the CFQ-R for quality of life, the HADS for mental health, and the PSQI for sleep. Results: Compared to the control group, participants who practiced PMR experienced significant reductions in anxiety (p = 0.05) and depression (p = 0.02) at the final assessment. A significant improvement in sleep quality was also observed (p < 0.01). No relevant differences were found in pulmonary function or performance on the six-minute walk test. Conclusions: Integrating PMR into pulmonary rehabilitation programs may be an effective strategy for improving mental health and sleep in patients with CF. Due to its accessibility and ease of implementation, PMR could be adopted as a complementary method in the holistic care of these patients.

PMID:40283637 | DOI:10.3390/jcm14082807

J Clin Med. 2025 Apr 9;14(8):2583. doi: 10.3390/jcm14082583.

ABSTRACT

Background/Objectives: Olfactory dysfunction (OD) is a common symptom among people with cystic fibrosis (PwCF) and contributes to environmental safety concerns, nutritional challenges, and an overall diminished quality of life. OD is perceived to progress along the lifespan in PwCF, often due to worsening sinonasal disease. Among children with cystic fibrosis (CwCF), OD is poorly characterized as limited resources and tolerance contribute to challenges in psychophysical olfactory evaluation among pediatric populations. The Children's Personal Significance of Olfaction (ChiPSO) questionnaire was recently proposed as a tool to assess olfaction and the importance of olfactory stimulation among children. This pilot study aimed to evaluate the utility of ChiPSO among a cohort of ethnically diverse CwCF. Methods: Individuals aged 7-17 with physician-diagnosed CF were asked to complete questionnaires, including ChiPSO and the brief questionnaire on olfactory dysfunction (bQOD-NS), prior to undergoing psychophysical olfactory evaluation with the U-Sniff Identification test. Potential associations between questionnaires and olfactory performance, pulmonary function, and demographic characteristics were evaluated using Pearson and Spearman correlations, independent-sample t-tests, Wilcoxon rank sum tests, and multiple linear regression. Results: U-Sniff Identification score positively correlated with the overall ChiPSO total score [r(13) = 0.640, p = 0.010] and its environmental subdomain score [r(13) = 0.774, p < 0.001], though not with the food subdomain [r(13) = 0.450, p = 0.093], the social subdomain [r(13) = 0.343, p = 0.2], or bQOD-NS score [r(11) = -0.125, p = 0.7]. Hispanic ethnicity is associated with ChiPSO (p = 0.041). Conclusions: In this preliminary study, olfactory importance increases with olfactory function among an ethnically diverse sample of CwCF, with a preferential influence of olfactory function on personal importance of environmental olfactory information. While these results should be interpreted with limitations imposed by the pilot nature of our sample size, our pilot data highlights associations with early adolescent development of importance of olfaction that can be disrupted in the setting of progressive disease among CwCF.

PMID:40283411 | DOI:10.3390/jcm14082583

Medicina (Kaunas). 2025 Apr 2;61(4):653. doi: 10.3390/medicina61040653.

ABSTRACT

Background and Objectives: In the present systematic review and meta-analysis, we aimed to discover the overall efficacy of azithromycin in children with cystic fibrosis (CF) and with or without Pseudomonas aeruginosa infection, specifically regarding its effect on respiratory parameters such as forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in addition to its effect on exacerbations and the need to use additional antibiotics. Materials and Method: We conducted this systematic review and meta-analysis by searching for all eligible articles on PubMed, Web of Science, and Scopus published between inception and September 2024. We used the following search strategy for our searching process: "Cystic fibrosis" AND "Azithromycin" and "Children" OR "Pediatric" OR "Infant". We conducted the meta-analysis by pooling the mean difference (MD) and comparing the continuous variables and odds ratio (OR) for dichotomous variables at 95% confidence intervals (CI), at a p-value of 0.05. Results: Azithromycin was observed to be associated with increased FEV1 compared with the control, showing an MD of 1.91 (95% CI: 1.09, 2.74, p < 0.00001) and non-significant heterogeneity. However, no significant difference was observed between azithromycin and control groups regarding FVC with MD = 0.62 (95% CI: -0.01, 1.25, p = 0.06). Compared with the control group, azithromycin was significantly associated with lower risk and a lower number of exacerbations, with OR = 0.48 (95% CI: 0.34, 0.67, p < 0.0001) and MD = -0.82 (95% CI: -1.32, -0.33, p = 0.001), respectively, with non-significant heterogeneity. Regarding the need for new antibiotic usage, azithromycin showed a significantly lower need, with OR = 0.35 (95% CI: 0.13, 0.94, p = 0.04), I2 = 75%, p = 0.02. No significant difference was observed between both groups regarding hospitalization rate, with OR = 0.88 (95% CI: 0.55, 1.4, p = 0.59). Conclusions: This systematic review and meta-analysis showed the efficacy of azithromycin in pediatric patients with CF, as it improved lung function by increasing FEV1, reduced exacerbations of CF, which is the most common symptom of CF that leads to mortality, and reduced the number of antibiotics that needed to be administered to patients with CF, which reduces the risk of antibiotic resistance. Therefore, the long-term use of azithromycin is recommended for pediatric patients with CF as part of their treatment regimen.

PMID:40282944 | DOI:10.3390/medicina61040653

Genes (Basel). 2025 Apr 7;16(4):439. doi: 10.3390/genes16040439.

ABSTRACT

BACKGROUND: Psychosis, particularly schizophrenia (SZ), is influenced by genetic and environmental factors. The neurodevelopmental hypothesis suggests that genetic factors affect neuronal circuit connectivity during perinatal periods, hence causing the onset of the diseases. In this study, we performed a genome-wide association study (GWAS) in a sample of the first episode of psychosis (FEP).

METHODS: A sample of 147 individuals diagnosed with non-affective psychosis and 102 controls were recruited and assessed. After venous blood and DNA extraction, the samples were genotyped. Genetic data underwent quality controls, genotype imputation, and a case-control genome-wide association study (GWAS). After the GWAS, results were investigated using an in silico functional mapping and annotation approach.

RESULTS: Our GWAS showed the association of 27 variants across 13 chromosomes at genome-wide significance (p < 1 × 10-7) and a total of 1976 candidate variants across 188 genes at suggestive significance (p < 1 × 10-5), mostly mapping in non-coding or intergenic regions. Gene-based tests reported the association of the SUFU (p = 4.8 × 10-7) and NCAN (p = 1.6 × 10-5) genes. Gene-sets enrichment analyses showed associations in the early stages of life, spanning from 12 to 24 post-conception weeks (p < 1.4 × 10-3) and in the late prenatal period (p = 1.4 × 10-3), in favor of the neurodevelopmental hypothesis. Moreover, several matches with the GWAS Catalog reported associations with strictly related traits, such as SZ, as well as with autism spectrum disorder, which shares some genetic overlap, and risk factors, such as neuroticism and alcohol dependence.

CONCLUSIONS: The resulting genetic associations and the consequent functional analysis displayed common genetic liability between the non-affective psychosis, related traits, and risk factors. In sum, our investigation provided novel hints supporting the neurodevelopmental hypothesis in SZ and-in general-in non-affective psychoses.

PMID:40282399 | DOI:10.3390/genes16040439

Genes (Basel). 2025 Mar 30;16(4):402. doi: 10.3390/genes16040402.

ABSTRACT

Cystic fibrosis (CF), a genetic disorder characterized by mutations in the CFTR gene, has seen significant advances in treatment through cutting-edge approaches such as gene therapy and personalized medicine. This review examines the current and emerging strategies shaping CF care, focusing on novel therapies that target the root cause of CF and optimize patient outcomes. CFTR modulators have transformed cystic fibrosis management by enhancing protein function for specific mutations, leading to improved lung function and quality of life. Concurrently, gene therapy offers transformative potential by aiming to correct CFTR mutations using tools like CRISPR/Cas9 or prime editing, though challenges remain in delivery and long-term efficacy. The integration of precision medicine, facilitated by genomic and computational technologies, allows for personalized treatment plans that account for genetic variability and disease severity. Complementing these approaches, holistic management emphasizes the importance of psychological support and nutritional optimization, acknowledging CF's multi-system impact. Future directions include exploring anti-inflammatory agents and microbiome modulation to further mitigate disease morbidity. However, global disparities in treatment access continue to challenge equitable healthcare delivery, underscoring the need for policy reform and international cooperation. By synthesizing these developments, this review highlights the transformative potential of modern CF treatments, advocating for continued innovation and global healthcare equity, with the ultimate goal of dramatically improving life expectancy and quality of life for individuals with CF.

PMID:40282362 | DOI:10.3390/genes16040402

Healthcare (Basel). 2025 Apr 17;13(8):923. doi: 10.3390/healthcare13080923.

ABSTRACT

Pediatric gastroenterology is entering a pivotal phase marked by significant challenges and emerging opportunities in treating conditions like celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH) pose significant clinical hurdles, but new therapeutic avenues are emerging. Advances in precision medicine, particularly proteomics, are reshaping care by tailoring treatments to individual patient characteristics. For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent. Immunotherapy and microbiota modulation, including probiotics and fecal microbiota transplantation (FMT), are also under exploration, with potential benefits in symptom management. Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated. These therapies require more pediatric-specific research to optimize their use. For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments. New medications for individuals with refractory or steroid-dependent AIH have been explored. Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric IBD management. This narrative review explores recent breakthroughs in treating CeD, EoE, IBD, and AIH, with a focus on pediatric studies when available, and discusses the growing role of proteomics in advancing personalized gastroenterological care.

PMID:40281872 | DOI:10.3390/healthcare13080923