Nevin Manimala

J Breath Res. 2026 Mar 2. doi: 10.1088/1752-7163/ae4bfd. Online ahead of print.

ABSTRACT

Melioidosis is a life-threatening infectious disease caused by Burkholderia pseudomallei (Bp). Rapid diagnosis and appropriate antimicrobial treatment are critical to reduce mortality, yet diagnosis is hindered by diverse clinical manifestations, mimicry with other diseases, and reliance on slow culture-based methods. Detecting volatile compounds offers a non-invasive approach for rapid infection detection. In this study, we aim to identify volatile compounds in patients’ breath that can aid in diagnosing melioidosis and indicating response to treatment.
Methods: Breath samples were collected from 17 patients with culture-confirmed melioidosis and eight patients with other febrile illnesses. Longitudinal samples were collected from five of the 17 melioidosis patients over approximately one month of antibiotic treatment. Breath samples were analyzed using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. Data analysis involved statistical comparison and machine learning-based feature selection. 
Results: We identified three breath markers -camphene, 1-butanol, and 3-methylheptyl acetate -that discriminated melioidosis (n=7) from febrile controls (n=6) with an area under the receiver operating characteristic curve of 1.00. These three markers correctly classified 11 additional samples from 11 melioidosis patients, with one febrile control misclassified. Separately, we selected four breath markers, three of which were hydrocarbons, that differentiated samples associated with a positive Bp culture from those with a negative Bp culture, with a random forest model developed upon these four markers showing a sensitivity of 98% and specificity of 95%. Moreover, we identified a set of 16 volatile compounds that significantly correlated (correlation coefficient > 0.6) with blood C-reactive protein levels. Lastly, a panel of 144 volatile compounds was identified that corresponded to treatment time, indicating that the breath profile may reflect treatment response or shifts in disease severity.
Conclusion: This pilot study reports candidate breath-based markers for diagnosing melioidosis and assessing treatment outcome, supporting further validation in larger studies. &#xD.

PMID:41771178 | DOI:10.1088/1752-7163/ae4bfd

J Radiol Prot. 2026 Mar 2. doi: 10.1088/1361-6498/ae4be9. Online ahead of print.

ABSTRACT

Ionizing radiation elicits complex cellular responses that are influenced by both total dose and delivery rate. Understanding how dose rate modulates molecular outcomes is important for accurate risk assessment. In this study, we apply an integrative multi-omics approach combining transcriptomic and proteomic profiling, adjusting for covariates, to investigate how differential dose rates alter gene and protein expression in human lymphocytes, with emphasis on alterations in key molecular pathways.&#xD;Methods: Peripheral blood from 14 healthy donors (8 males, 6 females) was irradiated ex vivo with X-rays at 0.05 Gy/minute (DR1) and 1.0 Gy/minute (DR2) across a dose range 0-6 Gy. Gene expression was assessed using TempO-Seq™, and relative protein abundance was determined by mass spectrometry. Differential expression analysis was conducted using edgeR and limma, adjusting for sex, age, and leukocyte counts (false discovery rate (FDR) < 0.05). Multi-omics integration was performed using regularized canonical correlation analysis (rCCA) implemented in mixOmics, followed by Reactome pathway enrichment analysis.&#xD;Results: We identified 2,477 and 2,612 differentially expressed genes at DR1 and DR2, respectively, and 368 and 386 differentially expressed proteins. Using canonical variates from rCCA, we show that covariate adjustment improved dose discrimination, particularly above 0.5 Gy. Using a correlation cut-off threshold of 0.5 in rCCA, 212 (DR1) and 276 (DR2) highly correlated gene-protein pairs were identified. DR2 exposure was associated with stronger enrichment of stress-related pathways, including unfolded protein response, senescence and oncogenic kinase signaling. In contrast, DR1 induced enrichment of pathways associated with immune engagement, including antigen presentation. At both dose rates, transcriptomic changes highlighted upstream regulatory processes (chromatin modeling) and proteomic changes captured downstream functional pathways such as immune activity and apoptosis. &#xD;Conclusion: Multi-omics approach with covariate adjustment revealed key radiation-responsive pathways and dose-rate-dependent molecular differences, highlighting the value of integrating transcriptomic and proteomic data to better understand radiation effects.

PMID:41771177 | DOI:10.1088/1361-6498/ae4be9

Thorac Cancer. 2026 Mar;17(5):e70255. doi: 10.1111/1759-7714.70255.

ABSTRACT

BACKGROUND: Pleural mesothelioma is a highly aggressive malignancy with a poor prognosis due to the limited efficacy of currently available therapies. Macroautophagy (hereafter “autophagy”) is a lysosome-mediated degradation pathway involved in cellular homeostasis that can either support or inhibit cancer progression depending on context. In this study, we investigated the effects of SAR405, an inhibitor of vacuolar protein-sorting 34 (VPS34), which is important for regulating the early stage of autophagy, on pleural mesothelioma.

METHODS: Human pleural mesothelioma cell lines H28, H2452, and 211H were cultured with SAR405. The effects of SAR405 on protein expression, cell viability, colony formation, cell invasion, and the cell cycle were investigated, as were its synergistic effects with cisplatin. Autophagy induction was evaluated in mesothelioma cells transfected with the pMRX-IP-GFP-LC3-RFP-LC3ΔG plasmid, which was developed for the quantitative and statistical estimation of autophagy.

RESULTS: SAR405 treatment alone significantly reduced cell viability, colony formation, and cell invasion, and increased G₂/M cell cycle arrest. In addition, SAR405 induced apoptosis in the H2452 cell line. Although cisplatin weakly induced autophagy in mesothelioma cells, its combination with SAR405 did not result in additive or synergistic effects on cell viability.

CONCLUSIONS: Based on these results, inhibition of VPS34 by SAR405 effectively suppressed cell viability in all mesothelioma cell lines and induced apoptosis in H2452 cells. The findings of this study indicate the potential for VPS34 inhibition as a new strategy for the treatment of mesothelioma and provide insights into the complex role of autophagy in this malignancy.

PMID:41771171 | DOI:10.1111/1759-7714.70255

Eur J Heart Fail. 2026 Jan 14:xuag009. doi: 10.1093/ejhf/xuag009. Online ahead of print.

ABSTRACT

AIMS: Cardiogenic shock (CS) is often treated with catecholamines titrated to an adequate target mean arterial pressure (MAP) while minimizing adverse effects. We aim to assess the optimal catecholamine dose/MAP balance in heart failure-associated CS (HF-CS).

METHODS: Patients with HF-CS were retrospectively enrolled from 16 tertiary centres in 5 European countries (2016-2021; NCT03313687). Dosage was quantified by inotropic scores (epinephrine, norepinephrine, and dobutamine). Associations of baseline and seven-day summarized dosage with intensive care unit (ICU) discharge (mixed-effects logistic regression) and 30-day mortality (Cox regression) were analysed. Potential catecholamine/MAP target ratios for optimized outcomes were assessed in models adjusted for age, sex, pH, lactate and prior resuscitation, stratified by centre.

RESULTS: N = 704 patients: median age 63 years, 74% male, 34% post-resuscitation, median lactate 5.2 mmol/l. Of these, 53% were discharged from ICU, 48% died within 30 days. Higher inotropic scores independently predicted a lower probability of ICU discharge (baseline score: OR 0.78 [95%-CI 0.69-0.88]; summarized score: OR 0.46 [0.38-0.56]; both P < .001) and higher risk of 30-day mortality (baseline score: HR 1.27 [1.15-1.40], summarized score HR 1.83 [1.60-2.09]; both P < .001). A score/MAP ratio <0.403 µg/kg/min/mmHg was associated with higher ICU discharge odds (ceiling effect); a < 0.426 µg/kg/min/mmHg with lower 30-day mortality hazards (no ceiling effect). Lowering catecholamine doses by accepting reduced MAP targets was linked to better outcomes.

CONCLUSION: In HF-CS, higher catecholamine support independently associates with worse outcomes. Accepting lower blood pressure targets to reduce catecholamine dosage may improve outcomes. Validation in randomized controlled trials is urgently needed.

PMID:41771117 | DOI:10.1093/ejhf/xuag009

Eur J Heart Fail. 2026 Jan 12:xuaf025. doi: 10.1093/ejhf/xuaf025. Online ahead of print.

ABSTRACT

AIMS: In patients with heart failure (HF) influenza vaccination has shown beneficial effects in preventing cardiac decompensations. However, no conclusive results have been achieved in the few studies that have evaluated the impact of vaccination during episodes of acute HF (AHF) decompensation. We conducted a systematic review and meta-analysis to determine the possible effects of influenza vaccination on all-cause mortality in patients diagnosed with AHF.

METHODS: PubMed, Medline, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews databases were searched for longitudinal studies comparing patients with AHF vaccinated against influenza with unvaccinated patients. The primary outcome selected for meta-analysis was 1-year all-cause mortality, and secondary outcomes consisted of other outcomes reported in at least in two different studies. Statistical heterogeneity was determined by calculating the I² statistic. Individual adjusted results were pooled using a random effects model. Sensitivity analysis was run for the primary outcome by removing each individual study and then re-doing the meta-analysis.

RESULTS: Up to 30 June 2025, five observational cohort studies examining the effect of influenza vaccination on 1-year all-cause mortality in AHF patients had been published. Statistical heterogeneity was low (I2 = 33.7%), meaning that between-study results were consistent. Pooled analysis of confounder-adjusted hazard ratio (HR) for all-cause mortality in vaccinated patients was 0.89 (95% CI 0.83-0.96) compared with unvaccinated patients. All sensitivity analyses rendered very similar results. In-hospital and 90-day mortality were reported in three and two studies and showed similar reductions in risk, with an adjusted odds ratio of 0.85, 95% CI 0.70-1.01, and adjusted HR of 0.86, 95% CI 0.76-0.96; respectively. Isolated data from single studies suggest no effect on hospitalization following discharge after the AHF episode.

CONCLUSIONS: Influenza vaccination is associated with a lower short- and long-term all-cause mortality in patients with decompensated HF; however, as all the studies included in this meta-analysis were observational, these results could be subject to residual confounding and causality cannot be directly inferred from them.

PMID:41771112 | DOI:10.1093/ejhf/xuaf025

Eur J Heart Fail. 2026 Jan 8:xuaf001. doi: 10.1093/ejhf/xuaf001. Online ahead of print.

ABSTRACT

AIMS: To evaluate whether circulating N-terminal pro-B type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) can stage hypertensive heart disease (HHD), by assessing their association with adverse cardiac remodelling and cardiovascular outcomes in individuals with essential hypertension.

METHODS AND RESULTS: The REMODEL study prospectively enrolled 1054 asymptomatic individuals with essential hypertension and no prior cardiovascular diseases (59 ± 11 years old; systolic blood pressure 131 ± 14 mmHg; left ventricular ejection fraction 60 ± 7%). All participants underwent cardiovascular magnetic resonance (CMR) and blood sampling for NT-proBNP and hsTnT. The primary outcome was a composite of acute coronary syndromes, heart failure hospitalization, stroke and all-cause mortality. Median follow-up was 53 (23, 72) months. Maximal log-rank statistic identified thresholds of 152 pg/ml for NT-proBNP and 12.7 pg/ml for hsTnT. Individuals with elevations in both biomarkers (high-risk) were older, had the highest 24-h systolic blood pressure and more diabetes mellitus. They showed the most adverse CMR phenotype, with increased myocardial mass, greater diffuse and replacement fibrosis, impaired left ventricular strain and higher left atrial volumes. Event rates differed significantly across biomarker strata (log-rank P < .001). High-risk individuals had the greatest hazard of cardiovascular events [hazard ratio (HR) 17.11; 95% confidence interval (CI) 8.12-36.09), while intermediate-risk individuals showed intermediate risk (HR 3.44; 95% CI 1.71-6.94).

CONCLUSION: NT-proBNP and hsTnT are complementary biomarkers that not only predict cardiovascular outcomes and but also reflect the severity of cardiac remodelling in HHD. Their combined use enables effective staging of disease severity and may support stage-specific management strategies in patients with hypertension.

PMID:41771092 | DOI:10.1093/ejhf/xuaf001

Eur J Heart Fail. 2026 Jan 14:xuag008. doi: 10.1093/ejhf/xuag008. Online ahead of print.

ABSTRACT

AIMS: The association between heart rate (HR) and clinical outcomes is well understood in patients with heart failure with reduced ejection fraction (HFrEF) but less clear in those with HFmrEF/HFpEF, especially among individuals with atrial fibrillation (AF). In a prespecified analysis of the FINEARTS-HF trial, we examined the association between baseline HR and clinical outcomes by heart rhythm and evaluated finerenone’s effect across the spectrum of HR.

METHODS: The primary outcome was a composite of cardiovascular death and total (first and recurrent) HF events. Heart rhythm (sinus rhythm or AF) was determined from the baseline ECG. Patients with pacemaker rhythm or missing HR/rhythm data were excluded.

RESULTS: Among patients with sinus rhythm (SR n = 3497; 62%), higher baseline HR was associated with a higher incidence rate for the primary outcome. In patients with AF (n = 2190; 38%), no association between HR and outcomes was observed. The effect of finerenone on the primary outcome was consistent across the HR spectrum, regardless of rhythm (P for interaction = 0.96 in SR; 0.49 in AF). In patients with SR, there was no significant HR change with finerenone versus placebo. In AF patients, finerenone led to a small but statistically significant HR reduction: a placebo-corrected decrease of 1.35 bpm (95% CI: 0.41-2.29) from baseline to 12 months.

CONCLUSIONS: Among patients with HFpEF/HFmrEF in FINEARTS-HF, higher baseline HR was associated with a higher risk of the primary outcome in patients with SR but not in those with AF. Finerenone’s effect on the primary outcome was consistent across the HR spectrum, irrespective of rhythm.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04435626.

PMID:41771075 | DOI:10.1093/ejhf/xuag008

Eur J Heart Fail. 2026 Jan 21:xuag010. doi: 10.1093/ejhf/xuag010. Online ahead of print.

NO ABSTRACT

PMID:41771072 | DOI:10.1093/ejhf/xuag010

Eur J Heart Fail. 2026 Jan 12:xuaf023. doi: 10.1093/ejhf/xuaf023. Online ahead of print.

ABSTRACT

AIMS: For many years, fluid and sodium restriction have been considered an essential strategy for achieving effective decongestion in acute heart failure (AHF), but this paradigm has recently been questioned. This analysis aims to evaluate and compare the effectiveness of three different fluid strategies for decongestion: no fluid, fluid with sodium/chloride, and fluid without sodium/chloride in AHF.

METHODS: This post-hoc analysis of two prospective, single-centre, mechanistic studies included 55 patients with AHF and fluid overload. All patients received standardized furosemide dosing. A total of 21 patients received a continuous infusion of 0.9% NaCl (83 mL/h), 19 patients received 5% glucose (83 mL/h), and 15 did not receive any fluids. The primary outcome is urine volume and natriuresis at 6 h after loop diuretic administration.

RESULTS: There was a significant difference in cumulative (6 h) net natriuresis between patients receiving fluid therapy (n = 40) and those without fluid therapy (n = 15) (139 [66-264] mmol vs. 79 [15-144] mmol, P = .043). There was no significant difference in cumulative net diuresis between these groups (1170 [880-1890] mL vs. 1010 [475-1270] mL, P = .078), respectively. The NaCl group had a better diuretic response when compared with the glucose and no-fluids groups (absolute: 1980 [1620-3150] mL vs. 1510 [1075-2175] mL vs. 1010 [475-1270] mL, P < .001, net: 1480 [1120-2650] mL vs. 1010 [575-1675] mL vs. 1010 [475-1270] mL, P = .019, respectively) but the difference in natriuresis did not meet statistical significance (P = .126).

CONCLUSION: Intravenous fluid replacement during decongestion in patients with AHF was associated with increased net natriuresis and a trend towards higher urine output, with a significant augmentation of diuresis with sodium chloride supplementation.

PMID:41771069 | DOI:10.1093/ejhf/xuaf023

J Phys Chem B. 2026 Mar 2. doi: 10.1021/acs.jpcb.5c07449. Online ahead of print.

ABSTRACT

A molecular understanding of the solvation and dynamics of ions under static electric fields is crucial for modeling a wide range of natural and technological processes. Yet, traditional simulation methods suffer from a trade-off that has to be made between accuracy and statistical convergence. To bridge this gap, herein, we extend our recently introduced perturbed neural network potential molecular dynamics (PNNP MD) approach to investigate the solvation structures and ionic transport mechanisms of electrified alkali cationic solutions. We obtain ionic conductivities for Li⁺, Na⁺, and Cs⁺ from the field dependence of the ionic current density in good agreement with experiment. Surprisingly, the migration mechanism is found to be strikingly different for the three ions, despite their similar ionic conductivities. While Li⁺ conducts predominantly through vehicular migration of a stable 4-fold coordinated ion at all field strengths, Cs⁺ conducts strictly through a structural diffusion mechanism, where 9-12 transient first shell water coordination bonds are continuously broken and reformed. Notably, aqueous Na⁺ emerges as a “Goldilocks” ion: its ion-water interactions are strong enough to maintain distinct 5-6-fold coordination shells at zero field (unlike Cs⁺) yet labile enough to be strongly perturbed by electric fields (unlike Li⁺). As a consequence, we observe an electric-field-induced transition from vehicular to structural ionic transport for Na⁺ that is accompanied by a marked increase in ionic current density. Our results imply that the conductance mechanism of ions with moderate ion-solvent interactions can be effectively tuned by external electric fields.

PMID:41771043 | DOI:10.1021/acs.jpcb.5c07449