Nevin Manimala

Anal Methods. 2025 Oct 20. doi: 10.1039/d5ay01304f. Online ahead of print.

ABSTRACT

Breath analysis by direct mass spectrometry faces significant challenges due to the inherent complexities in sample collection, low analyte concentrations, and accurate compound identification. While current breath analysis primarily focuses on volatile organic compounds (VOCs) for disease research, non-volatile organic compounds (nVOCs) remain largely unexplored despite their diagnostic potential. Here, we present a novel breath analysis method for lung cancer diagnosis based on nVOCs, integrating non-invasive breath analysis with machine learning algorithms for comprehensive characterization of 98 clinical breath samples. This study leverages a machine learning-driven database docking methodology to overcome the bottleneck of metabolite direct mass spectrometry conventional identification. This approach enables rapid and precise screening of non-volatile differential metabolites while effectively excluding exogenous confounders (e.g., pharmacological or environmental interference), enhancing nVOC detection in breath. The approach identified 29 statistically significant nVOC biomarkers, including fatty acids and amino acids, achieving a 0.9878 prediction accuracy for lung cancer detection. For distinguishing between NSCLC and SCLC, the area under the curve (AUC) value can reach 0.9, and the out-of-bag error of random forest is 0.00402. Notably, specific nVOCs including fatty acids and amino acids have high diagnostic potential, with an AUC of up to 0.67 of individual metabolites for the differentiation of SCLC from NSCLC. Finally, significantly altered metabolic pathways were explored by metabolite pathway and transcriptome analysis, showing that the fatty acid metabolism is a potentially regulatable pathway. Our approach facilitates rapid, non-invasive discrimination of NSCLC and SCLC in metabolic analysis, showing promise as an efficient, low-cost clinical test.

PMID:41111388 | DOI:10.1039/d5ay01304f

Arch Esp Urol. 2025 Sep;78(8):1092-1100. doi: 10.56434/j.arch.esp.urol.20257808.142.

ABSTRACT

INTRODUCTION: Emerging studies have indicated that obstructive sleep apnea (OSA) is an independent risk factor for erectile dysfunction (ED). However, the results are inconsistent. By leveraging aggregated statistical data from genome-wide association studies (GWAS), we performed a bidirectional mendelian randomization (MR) analysis to further investigate the potential causal link between OSA and ED.

MATERIALS AND METHODS: We chose single nucleotide polymorphisms (SNPs) as instrumental variables based on rigorous criteria. Our research adopted five advanced two-sample MR analysis approaches, specifically encompassing inverse-variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode. Additionally, we conducted several sensitivity analyses to evaluate heterogeneity, horizontal pleiotropy, and stability, including Cochrane’s Q test, MR-Egger intercept test, MR-pleiotropy residual sum and outlier (MR-PRESSO) global test, and leave-one-out analysis.

RESULTS: The study included one dataset related to ED (Bovijn et al.) and two datasets related to OSA (Finngen and Sakaue et al.). The MR study results using the IVW method showed no significant causal association between OSA and ED in two datasets related to OSA. (IVW, odds ratio (OR): 1.01, 95% confidence interval (CI): 0.82-1.24, p = 0.954; 1.07, 0.87-1.30, p = 0.532, respectively). The results of other four MR analysis methods were consistent with IVW. In the reverse MR analyses, there was no causal effect of ED on OSA according to IVW method (IVW, OR: 1.01, 95% CI: 0.96 to 1.06, p = 0.708; 0.95, 0.87-1.05, p = 0.319, respectively). Moreover, sensitivity analysis showed that the study results remain highly consistent, with no indication of multi-collinearity or heterogeneity.

CONCLUSIONS: Our MR analysis revealed no clear bidirectional causal link between OSA and ED.

PMID:41111381 | DOI:10.56434/j.arch.esp.urol.20257808.142

Arch Esp Urol. 2025 Sep;78(8):1045-1055. doi: 10.56434/j.arch.esp.urol.20257808.137.

ABSTRACT

BACKGROUND: We aimed to determine which parameters other than the time until torsion surgery can predict orchiectomy risk in acute testicular torsion (TT).

METHODS: The medical records of acute TT who applied to five different health centres in Turkey between 2016 and 2023 were analysed retrospectively. Patients who underwent orchiectomy because blood flow cannot be detected were defined as Group I, and patients with testicles preserved and fixed were defined as Group II. The differences between the two groups and potential predictors of testicular salvage were analysed.

RESULTS: Eighty-three patients with TT were included in the study. Amongst them, 44 (53.01%) were included in Group I and 39 patients (46.99%) in Group II. Time from the onset of pain to surgery and mean platelet volume (MPV) were significantly higher in Group I (p < 0.05). In Group II, the ipsilateral Prehn’s sign negativity rates, the rate of normal ipsilateral testicular echogenicity, and the rate of normal volume on ultrasonography were significantly higher than those in Group I (p < 0.05). We created a new scoring system named Time, MPV, Prehn’s sign, Echogenicity, and Volume (TMPEV) that can predict the risk of orchiectomy in TT by using the parameters that differed statistically between Groups I and II.

CONCLUSIONS: The time until surgery may not be the only factor affecting the possibility of testicular recovery in acute TT. MPV, positivity of Prehn’s sign, differentiations in ipsilateral testicular echogenicity and volume changes on ultrasonography, may have significant value in predicting the possibility of orchiectomy after open detorsion surgery. If more comprehensive and clear nomograms similar to our new TMPEV scoring system can be created, more proactive algorithms can also be developed for predicting orchiectomy after TT and managing TT.

PMID:41111376 | DOI:10.56434/j.arch.esp.urol.20257808.137

Arch Esp Urol. 2025 Sep;78(8):986-994. doi: 10.56434/j.arch.esp.urol.20257808.129.

ABSTRACT

BACKGROUND: Alpha blockers (ARBs) are important agents in treating benign prostatic hyperplasia (BPH). Although multiple ARBs are available, comparative data on their early and mid-term effects are limited. This study aimed to evaluate and compare the early clinical efficacy of three ARBs (alfuzosin, tamsulosin and silodosin) in patients with lower urinary tract symptoms due to BPH.

METHODS: This retrospective study was conducted using a 1:1:1 matched design on the basis of age, prostate-specific antigen level and prostate volume. Eligible patients were subsequently grouped for comparison. Patients received 10 mg of alfuzosin, 0.4 mg of tamsulosin or 8 mg of silodosin once daily for 3 months. Uroflowmetry parameters, including maximum urinary flow rate (Qmax), average urinary flow rate (Qave) and post-void residual volume (PVR), were assessed at baseline, 6 h after the first dose and at the first and third months. The International Prostate Symptom Score (IPSS) and quality of life (QoL) scores were evaluated at baseline and the first and third months. Repeated-measure analysis of variance (ANOVA) and Bonferroni post-hoc tests were applied.

RESULTS: A total of 117 patients were included in the final analysis, with 38 in the alfuzosin group, 40 in the tamsulosin group and 39 in the silodosin group. Repeated-measure ANOVA revealed that all groups showed significant improvements over time in Qmax, IPSS and QoL scores (p < 0.001). Silodosin provided a significantly greater increase in Qmax at 6 h than alfuzosin (p = 0.013) and tamsulosin (p = 0.044), though no statistically significant differences were observed between groups at the first or third month (p = 1.000). PVR values decreased in all groups over time, but intergroup differences were not statistically significant (p > 0.05).

CONCLUSIONS: Silodosin provided the most rapid symptomatic improvement following initial administration, likely due to its high α1A-receptor selectivity. However, by the third month, all three agents showed similar clinical efficacy, supporting their use as viable treatment options tailored to patient-specific needs.

PMID:41111368 | DOI:10.56434/j.arch.esp.urol.20257808.129

Diabetes Obes Metab. 2025 Oct 20. doi: 10.1111/dom.70204. Online ahead of print.

ABSTRACT

AIMS: We aimed at comparing different approved strategies (obesity management medications-OMM, endoscopic bariatric procedures-EBP, and metabolic bariatric surgery-MBS) with lifestyle intervention/placebo/no therapy (LSI/Pbo/NT) for the treatment of different BMI-based classes of obesity (i.e., overweight-BMI: 25-29.9 kg/m²; class I-BMI: 30-34.9 kg/m²; class II-BMI: 35-39.9 kg/m²; class III-BMI >39.9 kg/m²).

MATERIALS AND METHODS: This systematic review (SR) and network meta-analysis (NMA) included randomised clinical trials (RCTs) comparing OMM, EBP, and MBS versus either LSI/Pbo/NT or active comparators in individuals with overweight or obesity. A Medline and Embase search was performed up to 31st January 2025 for RCTs on EMA (European Medicines Agency)-approved weight-loss interventions in adults with overweight/obesity. The primary endpoint was total body weight loss (TBWL%), analysed at different time points: 26-52, 53-104, 105-156, and ≥156 weeks. Secondary endpoints included all-cause mortality, quality of life, and serious adverse events (SAE). Weighted mean difference and 95% confidence intervals (WMD, 95% CI) for continuous variables and Mantel-Haenszel odds ratio (MH-OR, 95% CI) for categorical variables were calculated using random effect models. The study was registered on the PROSPERO website (CRD42024625338).

RESULTS: In trials enroling subjects in class I of obesity, tirzepatide resulted in equal effectiveness to both OAGB and RYGB, and it was significantly superior to all the other comparisons. In trials on class II of obesity, tirzepatide was significantly superior to all the other comparisons and inferior to both OAGB and RYGB. Semaglutide was associated with a higher TBWL% than the other OMMs (with the notable exception of tirzepatide), and it was equally effective to EBP, GCP, and LAGB. In trials enroling patients with a mean BMI >40 kg/m², the procedure with the highest estimated weight loss was BPD. Semaglutide was statistically less effective than SG and gastric bypass, but not inferior to GCP and LAGB. Both RYGB and OAGB were superior to SG.

CONCLUSION: In patients affected by mild to moderate obesity, newer OMMs (i.e., tirzepatide and semaglutide) appear to be valid alternatives to EBP and MBS. They could be preliminarily chosen as a first-line option based on similar efficacy and greater safety and tolerability. Higher degrees of obesity could be more effectively treated with MBS, the efficacy of which, with the notable exception of LAGB and GCP, appears superior to other treatments, especially in the long term.

PMID:41111360 | DOI:10.1111/dom.70204

Pharm Stat. 2025 Nov-Dec;24(6):e70044. doi: 10.1002/pst.70044.

ABSTRACT

The initiation of dose optimization has driven a paradigm shift in oncology clinical trials to determine the optimal biological dose (OBD). Early-phase trials with randomized doses can facilitate additional investigation of the identified OBD in targeted populations by incorporating safety, efficacy, and biomarker data. To support dose comparison in such settings, we propose to extend the utility score-based approach (U-MET) to account for multiple endpoints and doses. The utility-based dose optimization approach for multiple-dose randomized trial designs accounting for multiple (≤ 3) endpoints and doses (U-MET-m) extends the U-MET, using a utility score to account for multiple endpoints jointly (e.g., toxicity-efficacy trade-off). When there are > 3 endpoints, assigning weights jointly is quite complicated; therefore, we suggest an alternative approach with CUI-MET (clinical utility index dose optimization approach for multiple-dose randomized trial designs), which uses a utility index to account for multiple endpoints marginally. We demonstrate the relationship between U-MET-m and CUI-MET to offer a guide in weight selection for U-MET-m when there are up to three endpoints. U-MET-m and (extended) CUI-MET use Bayesian inference within a hypothesis framework to compare utility metrics across doses to identify the OBD. Here we describe simulation studies and present examples to compare both the U-MET-m and CUI-MET designs with the empirical design. The U-MET-m design and CUI-MET were shown to have satisfactory operating characteristics for selecting the OBD. Based on these findings, we recommend the U-MET-m with ≤ 3 endpoints and CUI-MET with > 3 endpoints as the primary dose comparison approach to select the OBD.

PMID:41111350 | DOI:10.1002/pst.70044

Cancer. 2025 Nov 1;131(21):e70067. doi: 10.1002/cncr.70067.

ABSTRACT

BACKGROUND: There are suspected disparities in clinical research (CR) development among low- and middle-income countries (LMICs). This study investigated differences in number and complexity of clinical trials (CTs) and how economic growth (EG) might contribute to these disparities.

METHODS: For countries classified as LMICs in 2000, number, proportion of phase 1-2/3 and independent/pharma-sponsored CTs were documented. For correlations with EG, correlation coefficients (CC) were produced, indicating very weak, weak, moderate, strong, and very strong correlation.

RESULTS: A total of 16,977 CTs were identified. Asian countries China and South Korea experienced strong EG and increases in CTs (very strong CC). South/Southeast Asian countries had strong EG but modest increases in CTs (variable CC). Most East European countries and West Asian/Southeast European Turkey experienced robust EG and increases in CTs (moderate to strong and very strong CC, respectively). South/North American Argentina, Brazil, and Mexico had inconsistent EG but increases in CTs (weak to moderate CC). Among African countries, Egypt showed strong EG with a corresponding increase in CTs (strong CC), whereas South Africa had a weak CC. Most LMICs, except for China and South Korea, relied heavily on pharma-sponsored CTs, with a persistently low proportion of early-phase (1-2) compared to late-phase (3) CTs.

CONCLUSION: CR development has been unequal among LMICs. Strong EG could be a contributing factor but only to some extent. Only China and South Korea meaningfully developed independent and high-complexity CR. These data reinforce the need for initiatives to support cancer research in LMICs.

PMID:41111348 | DOI:10.1002/cncr.70067

Disaster Med Public Health Prep. 2025 Oct 20;19:e299. doi: 10.1017/dmp.2025.10218.

ABSTRACT

BACKGROUND: Preparation for mass casualty incidents (MCIs) requires knowledge of the number of victims to be treated on site and transferred to hospitals. The objective was to collect this information for MCIs with hospital admissions in Europe over the last 30 years.

METHOD: This was a scoping review of MCIs with hospital admissions in Europe between 1991 and 2023. The study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Scoping Review (PRISMA-ScR) guidelines with PubMed, the Web of Science, Industrial and Transport Accident Reports, and two global databases on terrorism and disasters. Events with ten victims transferred to hospitals were included.

RESULTS: In total, 2,498 documents were identified, and 82 documents covering 62 MCIs were selected. In Europe, there was a median of 73 MCI: 9 victims died on site (12%), 48 were transferred to hospitals (66%), and 13 with serious casualties (17%). MCI is divided into 7 categories: explosion, ballistic, fire, road, ram raid, railway, and industrial accident.

CONCLUSIONS: By improving our knowledge of past MCIs and their casualty figures, we can now train more realistically and be better prepared to respond to future MCIs.

PMID:41111321 | DOI:10.1017/dmp.2025.10218

Ren Fail. 2025 Dec;47(1):2570817. doi: 10.1080/0886022X.2025.2570817. Epub 2025 Oct 20.

ABSTRACT

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy in severe respiratory and/or cardiovascular failure. Acute kidney injury (AKI) is a frequent complication of ECMO that increases morbidity and mortality. We report the outcomes of patients with AKI who received ECMO.

METHODS: Clinical, management, and 30-d kidney and patient outcome data of adult inpatients with AKI who received ECMO in seven public hospitals in Kuwait from 1 January to 31 December 2021, were prospectively collected and analyzed.

RESULTS: There were 3,744 AKI referrals to nephrology during study period, of which 121 received ECMO (3.2%). Patients with AKI on ECMO had a mean age of 56.3 years and a mean baseline eGFR of 81.6 mL/min. Preexisting chronic kidney disease was reported in 21.5% of patients, diabetes in 58.7%, and hypertension in 48%. COVID-19 infection contributed to AKI in 69% of the cases. AKI developed before ECMO initiation in 62% of cases. ECMO was veno-venous in 90% of cases. Dialysis was performed in 92% of cases, 97% of which was continuous modality. Mechanical ventilation was required in 94.2% of patients (all on inotropic support). At 30 d, 86.8% of the cohort died (91% of the deceased were on dialysis), 5% remained on dialysis, and only 3.3% recovered kidney function completely.

CONCLUSIONS: AKI in patients receiving ECMO was associated with a high need for dialysis, and a high mortality rate. COVID-19 pandemic may have contributed to this outcome. ECMO modality, and whether AKI was pre or post ECMO did not affect the outcome.

PMID:41111310 | DOI:10.1080/0886022X.2025.2570817

SAR QSAR Environ Res. 2025 Oct 20:1-25. doi: 10.1080/1062936X.2025.2569865. Online ahead of print.

ABSTRACT

Enhancer of Zeste Homolog 2 (EZH2) inhibitors have demonstrated selective efficacy, but their broader therapeutic potential remains limited, highlighting the need to clarify the structural basis of their activity. The central aim of our study is to systematically analyse the structural diversity and activity patterns of known EZH2 inhibitors to provide insights that may guide incremental scaffold optimization. We examined 531 potential EZH2 inhibitors retrieved from ChEMBL through a cheminformatics workflow encompassing clustering, scaffold identification, activity cliff detection, and chemical space visualization. Using RDKit and NetworkX, 94 clusters were generated, of which 13 contained ten or more compounds. Notably, clusters 6, 16, 20, 21, and 31 exhibited favourable balances of structural homogeneity and enrichment scores, suggesting chemical cohesiveness and biological relevance for structure – activity relationship (SAR) prioritization. Statistical analyses revealed significant differences in mean pIC₅₀ values across clusters, underscoring distinct activity distributions linked to structural groups. Scaffold analysis highlighted pyrrole – benzamide derivatives, particularly those incorporating morpholine and piperidine motifs, as enriched among potent inhibitors. Substructure evaluation further indicated that aromatic rings and aromatic amine groups were positively correlated with bioactivity. These findings delineate key SAR features of EZH2 inhibitors and provide guidance for scaffold refinement, hit identification, and lead optimization.

PMID:41111308 | DOI:10.1080/1062936X.2025.2569865