SEARCH · Search PubMed

Results for “Liquid Phase Microextraction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

199 records · Page 7Linked to original sources

PubMed2026

Obinutuzumab or Tacrolimus in Primary Membranous Nephropathy.

BACKGROUND: Studies of obinutuzumab, a type II anti-CD20 antibody, have shown efficacy in the treatment of hematologic cancers and autoimmune diseases. An evaluation of the efficacy and safety of obinutuzumab in patients with primary membranous nephropathy is needed. METHODS: In a phase 3 trial, we randomly assigned adults with primary membranous nephropathy in a 1:1 ratio to receive intravenous obinutuzumab or oral tacrolimus. The primary end point was complete remission (defined as a urinary protein-to-creatinine ratio of 0.3 or lower and a stable estimated glomerular filtration rate [eGFR]) at week 104. Key secondary end points were complete or partial remission at week 104, complete remission at week 76, a sustained reduction in the eGFR of at least 30%, duration of complete remission, and change in the Patient-Reported Outcomes Measurement Information System Fatigue T score from baseline to week 104. Fixed-sequence hierarchical testing was performed. Safety was assessed. RESULTS: A total of 142 patients underwent randomization. At week 104, complete remission was observed in 26 of 71 patients in the obinutuzumab group and in 4 of 70 patients in the tacrolimus group (37% vs. 6% with multiple imputation for missing data; adjusted difference, 31 percentage points; 95% CI, 18 to 44; P<0.001). The analyses of complete or partial remission at week 104 and complete remission at week 76 also showed a significant treatment effect. The analysis of a sustained eGFR reduction did not show a significant treatment effect; thus, subsequent end points in the hierarchy were not formally tested for significance. Adverse events of grade 3 or higher were reported in 16 patients (22%) in the obinutuzumab group and in 13 patients (19%) in the tacrolimus group; serious adverse events occurred in 12 (17%) and 10 (14%), respectively. There were 61 and 57 infections per 100 patient-years in the obinutuzumab and tacrolimus groups, respectively; 3 and 4 serious infections per 100 patient-years; and 11 and 14 serious adverse events per 100 patient-years. Adverse drug reactions with obinutuzumab included infusion-related reactions, respiratory tract infections, and neutropenia. One patient in each group died during escape therapy. CONCLUSIONS: Obinutuzumab was superior to tacrolimus in inducing complete remission in patients with primary membranous nephropathy. (Funded by F. Hoffmann-La Roche; MAJESTY ClinicalTrials.gov number, NCT04629248.).

Adult↗

PubMed2026

Osimertinib With or Without Chemotherapy in Advanced Non-Small Cell Lung Cancer With EGFR and Concurrent TP53 Mutations: A Randomized Clinical Trial.

IMPORTANCE: Combination therapy has emerged as a promising therapeutic approach for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, its clinical benefit-risk profile remains a focus of ongoing debate. Identifying patients most likely to derive benefit from such regimens remains an unmet clinical need. OBJECTIVE: To prospectively compare the efficacy and safety of first-line osimertinib plus chemotherapy with osimertinib monotherapy for patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, open-label, phase 3 study conducted at 17 sites in China. Between March 25, 2021, and July 11, 2024, a total of 294 eligible patients with treatment-naive, stage IV or recurrent nonsquamous NSCLC harboring concurrent TP53 and EGFR-sensitizing mutations were enrolled. INTERVENTIONS: Patients were randomized (1:1) to receive osimertinib plus chemotherapy (pemetrexed and carboplatin every 3 weeks for 4 cycles, followed by maintenance therapy of osimertinib plus pemetrexed; n = 146) or osimertinib monotherapy (n = 148). MAIN OUTCOMES AND MEASURES: The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, response, safety, and quality of life. RESULTS: Among 294 enrolled patients, the median age was 57 years (range, 26-79 years), and 159 (54.1%) were female. The data cutoff date was November 11, 2025. At a median follow-up of 25.1 months for the osimertinib-chemotherapy group and 26.1 months for the osimertinib monotherapy group, median progression-free survival was significantly longer with osimertinib plus chemotherapy than with osimertinib monotherapy (34.0 vs 15.6 months; difference, 18.4 months [95% CI, 9.9-22.3]; hazard ratio, 0.44 [95% CI, 0.32-0.60]; P < .001). This benefit was consistent across prespecified subgroups, including those with brain metastases and L858R mutations. The overall survival data remained immature (30.6% maturity); however, a trend toward overall survival benefit with combination therapy was observed. The incidence of grade 3 or higher treatment-related adverse events was higher in the combination group, with no new safety signal identified. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, osimertinib plus chemotherapy significantly increased progression-free survival among patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. These findings provided a clinical rationale for individualized combination strategies in the management of patients with EGFR-mutated NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04695925.

Adult↗

PubMed2026

From prediction to mechanism: Explainable AI uncovers plasma and CSF proteomic signatures of Alzheimer's disease.

Alzheimer's disease (AD) plasma and cerebrospinal fluid (CSF) proteomics can distinguish AD from cognitively normal controls, but the generalizability of machine learning performance and the recurrence of biological signals across datasets require cautious interpretation. We developed an explainable artificial intelligence framework spanning two fluids and four ADNI proteomic datasets, covering 2082 modality specific samples, all analysed internally within ADNI. Phase 1 analysed plasma using a 119 analyte NULISA and targeted UPENN panel (n = 727; 216 CE, 511 controls). Phase 2 extended the analysis to CSF using SOMAscan7k, TMT-MS and targeted SET2, with Elecsys Aβ42, Aβ40, total tau and p-tau181 as anchor biomarkers. Only SOMAscan was subject-independent relative to Phase 1 plasma; TMT-MS and SET2 overlapped with Phase 1 for 96.0% and 97.7% of subjects and therefore are not independent replication cohorts. Under subject-level splits with fold internal preprocessing, we compared Elastic Net, Explainable Boosting Machines and gradient boosted trees with SHAP-based explanations. Among the candidate pipelines, we selected the pipeline with the highest held-out test ROC AUC for each platform; the selected values were 0.927 in plasma and 0.954-0.973 across the three CSF datasets. Because the same held out test performance was used for pipeline selection and headline reporting, these are optimistically selected single-holdout estimates, not unbiased estimates of generalizable or clinical performance. Explanations identified five recurring biological axes within ADNI: cholinergic (ACHE), tau/14-3-3 (YWHAG, YWHAZ, YWHAB, YWHAE), neuro-axonal (NEFL, NEFH), microglial/complement (CHIT1, SMOC1, CHI3L1, C7, CFH) and synaptic (NPTXR, NPTX2, DLG4, SYT5, VSNL1, ELAVL2). CSF analyses showed synaptic vesicle-cycle enrichment (q = 2 × 10-6), and CSF YWHAG correlated strongly with total tau (ρ = 0.87). Cross-fluid directional concordance was modest overall (54-57%) but increased to 73-80% among mapped analyte/protein rows reaching q < 0.05 in CSF. These findings provide hypothesis-generating, internally supported evidence within ADNI. Independent external cohorts with locked pipelines are required to evaluate generalizable performance and biological reproducibility; the overlapping TMT-MS and SET2 analyses should not be interpreted as independent replication.

Alzheimer Disease↗

PubMed2026

Comparative effectiveness of torsemide vs furosemide in the management of heart failure patients: Win-ratio reanalysis of the TRANSFORM-HF trial.

BACKGROUND: Loop diuretics are widely used for managing congestion in patients with heart failure (HF). The TRANSFORM-HF trial is a multicenter randomized study that enrolled heart failure patients, comparing a strategy of torsemide vs furosemide. The time-to-event analysis demonstrated neutral effects on all-cause death at 30 months and the composite of all-cause death and first rehospitalization at 12 months. We evaluated whether a hierarchical win-ratio (WR) framework integrating mortality, recurrent hospitalization, and patient-reported health status provides additional interpretive insight. METHODS: This study is a secondary analysis of the pragmatic, multicenter, open-label, randomized TRANSFORM-HF trial, conducted across 60 US hospitals that randomized 2,859 patients hospitalized with HF to torsemide or furosemide. The primary 12-month hierarchical composite outcome was defined as (1) all-cause mortality, (2) recurrent all-cause hospitalizations, and (3) lack of improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). The primary statistical method was a WR analysis adjusting covariates via inverse probability weighting. Subgroup analyses evaluated potential heterogeneity across patient demographics and clinical characteristics. RESULTS: In the primary 12-month intention-to-treat analysis, the adjusted WR was 1.07 (95% CI, 0.98-1.16; P = .13), indicating no significant difference between torsemide and furosemide. A supplementary 30-month analysis with extended mortality follow-up yielded a similar estimate (adjusted WR, 1.06; 95% CI, 0.98-1.16; P = .14); hospitalization and KCCQ-CSS components were assessed through 12 months. As-treated sensitivity analyses were consistent with the neutral primary findings. Exploratory subgroup analyses were not adjusted for multiplicity and should be considered hypothesis-generating. CONCLUSIONS: The overall WR comparison between torsemide and furosemide showed no statistically significant difference in the primary 12-month analysis. The WR framework provided an interpretive decomposition across outcome domains but did not establish superiority of either loop diuretic strategy. All findings should be considered exploratory. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03296813, https://clinicaltrials.gov/study/NCT03296813.

Aged↗

PubMed2026

High-Dose Intravenous Vitamin C and Mortality and Organ Dysfunction in Severe Burn Injury: The VICTORY Randomized Clinical Trial.

IMPORTANCE: Severe burn injury triggers systemic inflammation that can lead to multiple organ dysfunctions and death. High-dose intravenous vitamin C has been proposed to mitigate these effects, but strong evidence in patients with burn injury is lacking. OBJECTIVE: To evaluate the efficacy of high-dose intravenous vitamin C in patients with severe burn injury. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled phase 3 trial conducted across 24 burn centers in North, Central, and South America; Europe; and Asia. Adults (≥18 years) with deep second- and/or third-degree burns covering 20% or more of total body surface area and requiring skin grafting were enrolled between August 18, 2020, and September 12, 2025. Final follow-up was completed in March 2026. The trial was stopped early after the first prespecified interim analysis for futility/harm. INTERVENTIONS: Patients were randomly assigned (1:1) to receive intravenous vitamin C (50 mg/kg every 6 hours for 96 hours) or matched placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of 28-day mortality and persistent organ dysfunction (defined as dependence on mechanical ventilation, kidney replacement therapy, or vasopressor/inotrope support at day 28). The main secondary outcome was time to discharge alive from hospital within 90 days. RESULTS: Among 238 patients enrolled (mean age, 48.9 [SD, 19.1] years; 79% male; mean total body surface area, 37.0% [SD, 14.6%]), 120 were assigned to vitamin C and 118 to placebo. The primary composite outcome occurred in 49 patients (40.8%) in the vitamin C group and 35 patients (29.7%) in the placebo group (adjusted risk ratio [RR], 1.28 [95% CI, 0.99-1.65]; P = .06), crossing the prespecified futility/harm threshold and prompting early trial termination. Time to discharge alive from hospital within 90 days was not improved (adjusted subdistribution hazard ratio, 0.85 [95% CI, 0.62-1.16]; P = .31). Twenty-eight-day mortality was higher in the vitamin C group (15.0% vs 7.6%; adjusted RR, 1.96 [95% CI, 1.32-2.90]; P = .001), as was hospital mortality (23.3% vs 16.1%; adjusted RR, 1.44 [95% CI, 1.03-2.00]; P = .03). CONCLUSIONS AND RELEVANCE: Among patients with severe burn injury, high-dose intravenous vitamin C did not reduce 28-day mortality and persistent organ dysfunction and is possibly harmful. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04138394.

Humans↗

PubMed2026

Degradation of a graphene-reinforced polyamide by fungi: When culture conditions matter.

The large-scale production, marketing and disposal of polymer-based graphene products can lead to the dispersal of graphene-enriched plastic particles into terrestrial ecosystems, where they might accumulate if not degraded by organisms. The objective of this work is to test the degradability and compatibility of one polyamide-6 polymer reinforced with reduced graphene-oxide (PA6-rGO) and its base constituents (polyamide-6, PA6; reduced graphene oxide, rGO) using mono- and co-cultures of two lignin-degrading fungi (Bjerkandera adusta and Morchella esculenta) grown under different nutrient conditions. Fungal (co-)cultures were exposed to pure rGO or abraded powders of PA6 and PA6-rGO in two different liquid media, and monitored over time for biomass growth, H2O2 production, and activity of two lignolytic enzymes (i.e., Laccase, Lac, and Lignin peroxidase, LiP). The changes in polyamide structure were evaluated by proton nuclear magnetic resonance and mass spectrometry, and changes in rGO were evaluated by Raman spectroscopy. The materials had no effect on fungal growth. PA6 increased Lac secretion only in low nutrient medium, while PA6-rGO slightly suppressed LiP activity. Only M. esculenta promoted polyamides oxidation when cultured in a low nutrient medium, as evidenced by a change in mass distribution values (m/z: 400-420) and the appearance of a new resonance peak (at 5.37 ppm). Lignolytic exudates in co-cultures low in nutrients caused a greater change in rGO, as shown by the increase in the ID/IG ratio. The degradation of rGO, PA6 and PA6-rGO depended on culture conditions.

Graphite↗

PubMed2025

Oral semaglutide for weight loss and liver fibrosis in overweight and obesity: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Obesity is a leading risk factor for fatty liver disease and weight loss has been shown to improve liver parameters. This study evaluates the efficacy of oral semaglutide for weight loss in individuals with overweight or obesity, excluding those with diabetes mellitus. METHODS: A randomized, open-label, controlled trial was conducted at the Asian Institute of Gastroenterology, Hyderabad, from June 2022 to December 2023. Adults (≥ 18 years) with a body mass index (BMI) ≥ 30 or ≥ 27 with comorbidities (pre-diabetes, hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease) were randomized into two groups. Both groups received counselling on a reduced-calorie diet and increased physical activity. Group 1 also received oral semaglutide, starting at 3 mg/day and titrated to 14 mg/day over two to four weeks. The objectives were to assess the effects of semaglutide on weight loss, non-invasive markers of liver fibrosis and cardiometabolic parameters. (ClinicalTrials.gov ID: NCT05442450). RESULTS: Total 116 participants (58 per group) completed the study. At 28 weeks, the mean percentage weight reduction was -10.47% (SD 5.3) in the Semaglutide group vs. -2.4% (SD 4.5) in the control group (p < 0.001). Semaglutide treatment significantly improved alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) levels, along with reductions in the aspartate aminotransferase to platelet ratio index (APRI) score, liver fat content and liver stiffness. However, NFS (NAFLD fibrosis score) and FIB-4 (fibrosis-4 index) did not show significant reductions. Improvements in BMI, waist circumference, HbA1c, fasting insulin and C-reactive protein (CRP) were significantly greater with semaglutide (p < 0.001). Total fat mass decreased by 7.3 kg vs. 1.74 kg (p < 0.0001) in controls, while visceral fat ratings dropped by 3.67 vs. 0.6 (p < 0.0001). CONCLUSIONS: In adults with overweight or obesity without diabetes, oral semaglutide, combined with dietary and lifestyle modifications, led to significant and clinically meaningful weight loss and metabolic improvements compared to lifestyle modifications alone.

Adult↗

PubMed2026

Towards microplastic bioremediation: Fungal degradation of pristine and pretreated high-density polyethylene and polystyrene.

Microplastic (MP) contamination has become a significant ecological issue because of its enduring existence in the ecosystem and its possible negative impacts. Therefore, using degrading strategies to eliminate these stubborn polymers has been a subject of scientific research. However, the currently used degradation methods are relatively inefficient. Given the pervasiveness of High-Density Polyethylene (HDPE) and Polystyrene (PS) and their resistance to biodegradability, disposal strategies are critical and must be addressed. This manuscript examines the biodegradation of pristine and UV-treated HDPE and PS MPs by Aspergillus flavus species in minimal growth media over 70 days. The maximum weight loss observed at 70 days for pristine HDPE and PS in sole carbon source (SCS) media was (29.33 ± 0.28) % and (17.67 ± 0.35) %, respectively. Whereas, for UV-treated HDPE and PS MPs, the % weight reduction was (33 ± 0.21) % and (25 ± 0.19) %, respectively. UV-treated MPs exhibited greater weight reduction, as UV induced oxygenated functional groups enhance polymer susceptibility to enzymes, thereby promoting biodegradation. HDPE MPs typically show a higher proportion of particles in the lower size range compared to PS MPs. This assertion was based on the weight loss, particle size distribution, and SEM analysis. Furthermore, chemical changes were evaluated using Fourier transform Infrared Spectroscopy (FTIR) analysis, which also displayed chemical oxidation occurring during biodegradation. Liquid Chromatography-Mass Spectrometry (LC-MS) results indicate that UV pretreatment enhances biodegradability by promoting chain scission. These findings further suggest that this fungus's natural and ubiquitous occurrence in terrestrial and marine environments may actively contribute to MP biodegradation while requiring few nutrients.

Microplastics↗

PubMed2026

Natural deep eutectic solvent in situ formation-based extraction method coupled to high-performance anion-exchange chromatography with pulsed amperometric detection for multiclass carbohydrates in hot pot bases.

A novel method was developed for the simultaneous extraction of fourteen multiclass carbohydrates from high-fat foods via the in situ formation of deep eutectic adducts from analytes and acetate ions. Different natural deep eutectic solvents (NADESs) composed of fructose and organic acids were tested as extraction solvents. A model NADES formulated with sodium acetate and fructose was characterized using Fourier transform infrared (FTIR) spectroscopy and hydrogen nuclear magnetic resonance (1H-NMR) spectroscopy. The critical extraction parameters were systematically optimized using multi-response surface methodology (MRSM) with a central composite design (CCD). The extract was analyzed using high-performance anion-exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD) using a sodium hydroxide-sodium acetate eluent, which did not require organic solvents. This approach exhibited good linearity over the concentration range of 0.02-10 mg L-1, with correlation coefficients (r) ranging from 0.9994 to 0.9999. The limits of detection and quantification were in the ranges of 0.06-0.42 mg kg-1 and 0.19-1.3 mg kg-1, respectively, which were significantly lower than those of liquid chromatography (LC). The protocol was successfully applied to the determination of fourteen carbohydrates in forty-five hotpot seasoning samples. The recoveries ranged from 86.3% to 104.1%, with relative standard deviations (RSDs) of 0.9-7.1%. By integrating multiple techniques, this strategy simplifies operations, shortens extraction time, and achieves baseline separation of three carbohydrate classes that exhibit poor resolution using a conventional LC method. This study describes an efficient procedure for the simultaneous determination of multiple trace-level carbohydrates in complex samples using HPAEC-PAD.

Journal Article↗

PubMed2026

Clinical and endocrine correlates of genetic etiologies in severe hypospadias: Study from 34 patients.

OBJECTIVE: Hypospadias is a prevalent congenital anomaly (0.3%-1.0%); however, severe hypospadias (defined as proximal cases with the meatus at the penoscrotal junction, scrotum, or perineum) is a rare and clinically challenging entity with a multifactorial etiology. This study aimed to characterize the interrelationships among the clinical, endocrine, and genetic profiles in children with severe hypospadias. MATERIALS AND METHODS: We conducted a comprehensive analysis of 34 male patients with severe hypospadias. Preoperative hormone levels were measured using two methods: chemiluminescent immunoassay for luteinizing hormone and follicle-stimulating hormone, and liquid chromatography-tandem mass spectrometry for testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), 17α-hydroxyprogesterone (17α-OHP), and other steroids. Genetic analysis was conducted via whole exome sequencing. RESULTS: The diagnostic yield of clinically relevant genetic variants (including pathogenic and likely pathogenic, and variants of uncertain significance) in our cohort was 41.2% (14/34) of patients. Patients carrying these variants exhibited a more complex phenotypic profile compared to non-carriers, including a significantly higher rate of patients with ≥3 associated malformations and a greater prevalence of cryptorchidism. Furthermore, the group with clinically relevant variants showed selective elevations in adrenal-derived precursors, specifically 17α-OHP and DHEA. Correlation analysis revealed significant positive associations of both 17α-OHP levels and the T/DHT ratio with the number of associated malformations. CONCLUSION: This study reveals significant genetic heterogeneity in patients with severe hypospadias. Those carrying genetic variants was associated with more severe clinical phenotypes, while certain endocrine variations, including the elevation of adrenal-derived hormones, were also observed in this cohort.

Humans↗

PubMed2026

Empirical Meropenem Versus Piperacillin/Tazobactam for Critically Ill Adults With Sepsis: Feasibility of a Randomised Trial.

BACKGROUND: Meropenem and piperacillin/tazobactam are commonly used empirical antibiotics in critically ill adults with sepsis, but whether one is superior to the other is uncertain. METHODS: The Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial is an ongoing investigator-initiated, randomised, open-label, adaptive clinical trial with an integrated feasibility phase comparing empirical treatment with meropenem versus piperacillin/tazobactam in critically ill adults with sepsis. The integrated feasibility phase enrolled 200 participants across 10 intensive care units (ICUs) in Denmark between 28 June and 12 December 2025. Five pre-specified feasibility criteria were evaluated; if all feasibility criteria were met, the trial would proceed unaltered, whereas failure to meet one or more criteria would require intervention and re-evaluation. RESULTS: We randomised 200 of 284 screened patients (70.4%). The median age was 70 years (interquartile range (IQR): 60-77), 65.5% were males. At randomisation, 80.0% received vasopressors or inotropes, and 43.5% were on invasive mechanical ventilation. Four of five pre-specified feasibility criteria were met: time to completion of the feasibility phase (5.5 months vs. threshold < 12.0 months), recruitment proportion (70.4% vs. threshold ≥ 50.0%), proportion of participants without consent to the continued collection of data (2.5% vs. threshold < 5.0%) and protocol adherence (81.0% vs. threshold ≥ 75.0%). The proportion of participants with timely primary outcome data availability (30-day mortality) within 45 days was 85.5% and below the pre-specified threshold of ≥ 95.0%. The proportions were low in the first 3 months (33.3%, 22.2% and 30.8%, respectively), increasing to 95.8% in the last month of the feasibility phase. All-cause mortality at 30 days was 30.5%, and specific serious adverse reactions occurred in 4.0% of participants. CONCLUSIONS: In this integrated feasibility evaluation of the EMPRESS trial comparing empirical meropenem versus piperacillin/tazobactam in critically ill adults with sepsis, four of five pre-specified feasibility criteria were met. The unmet criterion, timely primary outcome data availability, improved substantially during the feasibility phase. We consider the trial feasible and will proceed without modifications. EDITORIAL COMMENT: This feasibility study assessed recruitment, randomised allocation and data collection for the multicentre EMPRESS trial. For adaptive trials on trial platforms, careful interim checking of trial design functions is an important and necessary process. TRIAL REGISTRATION: Clinical Trials Information System EUCT number: 2023-509703-33-00; ClinicalTrials.gov identifier: NCT06184659; Universal Trial Number: U1111-1301-6379.

Humans↗

PubMed2026

A complete hlyCABD-like RTX operon marks a virulence-associated subset of trh-positive Vibrio parahaemolyticus from Hangzhou Bay, China.

Vibrio parahaemolyticus remains a major cause of seafood-associated gastroenteritis, yet routine surveillance still relies largely on the canonical hemolysin markers thermostable direct hemolysin (tdh) and tdh-related hemolysin (trh). To determine whether this framework overlooks accessory virulence determinants in trh-positive lineages, we analyzed 193 V. parahaemolyticus isolates collected between 2022 and 2025 from clinical, environmental, and seafood-associated sources in the Hangzhou Bay region of China. Serotyping identified 45 serotypes, with O10:K4 predominating among clinical isolates. Both clinical and non-clinical populations showed open pan-genomes, although the non-clinical group carried a larger accessory gene pool. We identified a complete hlyCABD-like RTX operon in 10 trh-positive isolates with T3SS2-associated virulence backgrounds. These RTX-positive isolates were distributed across seven sequence types and three of five phylogenetic groups. This distribution was lineage-restricted but non-clonal. In the representative hybrid-assembled genome, the operon occurred within a mosaic genomic region containing additional virulence- and mobility-associated genes, indicating a composite pathogenicity island-like element. In the tested subset, RTX-positive isolates showed significantly greater hemolytic activity than RTX-negative trh-positive isolates. This significant difference was consistently observed in both plate-based and liquid assays, and within the RTX-positive subset, hlyA expression correlated with hemolytic activity, whereas the trh gene and the tlh (thermolabile hemolysin) gene did not. A complete hlyCABD-like RTX operon therefore identifies a hemolysis-associated subset of trh-positive V. parahaemolyticus and supports its further evaluation as an additional target for food safety surveillance.

Vibrio parahaemolyticus↗

PubMed2026

Improved quality of life and prolonged survival with add-on homeopathic treatment in patients with non-small cell lung cancer: a prospective, randomized, placebo-controlled, double-blind, three-arm, multicenter study.

BACKGROUND: Alongside conventional anticancer treatment, add-on homeopathy might help to alleviate adverse effects of conventional therapy. AIM: The aim of this study was to replicate previous studies on the effect of adjunctive homeopathy on quality of life (QoL) and survival in non-small cell lung cancer (NSCLC) patients. METHOD: In this prospective, randomized, placebo-controlled, double-blind, three-arm multicenter phase III study with quadruple-checked data analysis, we investigated the potential effects of an add-on homeopathic treatment compared to placebo in patients with stage IV NSCLC in terms of QoL. Ninety-eight received either individualized homeopathic medicinal products (HMPs; n = 51) or placebo (n = 47) in a double-blinded fashion. Fifty-two control patients without homeopathic treatment were only observed in terms of their survival rate. The ingredients of the various HMPs were mainly prepared of plant, mineral, or animal origin. The data entry and statistical analysis were subject to an exceptional quadruple-checked data analysis process. The analysis presented in this article was inspired by our earlier report of this trial published in The Oncologist in 2020, which was retracted by that journal in November 2025 after two corrections; a majority of the co-authors disagreed with this decision. The present article is based on the same trial dataset but was deliberately designed to highlight the unique research methodology: design and preparation by a lead statistician, data entry, data clearing and independent statistical evaluation were performed in four mutually independent steps, reporting follows the CONSORT statement, and the interpretation of the findings has been reframed conservatively. RESULTS: Global health status (QoL) was higher in the homeopathy group than in the placebo group after 9 weeks and after 18 weeks (p < 0.001). With the exception of cognitive functioning at 9 weeks and of pain, diarrhea and financial difficulties at 9 weeks, all functional and symptom scales of the EORTC QLQ-C30 favored the homeopathy group (p < 0.001 for the multivariate comparisons), with between-group differences exceeding the threshold of 10 points that is generally regarded as clinically meaningful. Median survival time over the 730-day observation period was 435 days in the homeopathy group, 257 days in the placebo group (p = 0.010), and 228 days in the non-randomized control group (p < 0.001); the corresponding 2-year survival rates were 45.1%, 23.4%, and 13.5% (homeopathy vs. placebo p = 0.020; homeopathy vs. control p < 0.001). The difference between the placebo group and the non-randomized control group was not statistically significant (p = 0.154). CONCLUSION: In this trial, add-on homeopathy was associated with better quality of life across most functional and symptom domains, with clinically meaningful effect sizes congruently to a previous open study. Survival time was significantly longer in the homeopathy group compared to both the placebo and control groups. Independent replication, ideally within contemporary immuno-oncological treatment regimens is required. TRIALS REGISTRATION: ClinicalTrials.gov; No.: NCT01509612; January 7, 2012.

Humans↗

PubMed2026

primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial: Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma.

PURPOSE: Stage IIB/IIC melanoma has a high risk of recurrence after resection. Combined BRAF/MEK inhibitor therapy showed benefit in resected high-risk stage III and advanced melanoma. The objective of this study was to investigate its role in stage IIB/IIC. METHODS: Adult patients with resected stage IIB/IIC cutaneous melanoma which had a BRAF V600E/K mutation were randomized 1:1 to receive encorafenib (enco) 450 mg QD + binimetinib (bini) 45 mg BID orally for one year or placebo. The study planned to randomize 815 patients and was designed to demonstrate superiority regarding recurrence-free survival (RFS). Following a premature termination of accrual, the study was amended with safety as the primary endpoint and RFS as secondary endpoint. RESULTS: Between June 9, 2022, and October 9, 2023, 339 patients were screened for a BRAF mutation and 110 randomized. Data cutoff was 19 Nov. 2024, after the last patient discontinued study participation. Among randomized patients, 87 (79%) had a BRAF V600E mutation, and 39 (35%) AJCC8 stage IIC. Median follow-up was 12 and 7 months for enco/bini and placebo arms, respectively. Among 54 patients who initiated enco + bini, grade ≥ 3 treatment-related adverse events (AE) occurred in 13 (24%) patients, and 18 (33%) patients had an AE leading to permanent treatment discontinuation. RFS at 12 months was 86% (95% CI: 65-95%) in the enco + bini and 70% (95% CI: 46-85%) in the placebo arm, distant metastasis-free survival at 12 months was 92% (95% CI: 77-97%) for enco + bini and 82% (95% CI: 55-93%) for placebo. CONCLUSION: EORTC 2139 - Columbus-AD demonstrated a consistent and manageable safety profile and encouraging efficacy results for the combination of enco and bini in resected stage IIB/C BRAF V600E/K-mutated cutaneous melanomas.

Adult↗

PubMed2026

Design, rationale, and baseline patient characteristics for the Sickle Cell Disease and CardiovAscular Risk-Red cell Exchange (SCD-CARRE) trial.

BACKGROUND: Despite wide utilization of automated red blood cell exchange (RBCX) transfusion in adult patients with sickle cell disease (SCD), no consensus or quality efficacy data exist on its use. The Sickle Cell Disease and CardiovAscular Risk- Red cell Exchange (SCD-CARRE) trial tests the hypothesis that an automated chronic RBCX transfusion strategy reduces acute health care encounters and death while improving quality of life and end-organ function (cardiac, pulmonary and renal) in participants with SCD that are at high risk of death. METHODS: Adult patients with SCD with elevated tricuspid regurgitant jet velocity (TRV) and/or chronic kidney disease were considered to be at high risk of death and were randomly assigned to RBCX plus standard of care vs standard of care alone. Participants assigned to RBCX received 12 months of exchange transfusions to maintain target pretransfusion hemoglobin S% < 30%, post-transfusion hemoglobin S% < 20%, and post-transfusion hemoglobin concentration ≥10 g/dL. All study participants were managed according to NHLBI/ASH/ATS Expert Panel guidelines. The primary endpoint was the number of SCD acute health care encounters or death over 13 months. Secondary endpoints included measures of cardiovascular and renal function, exercise capacity, patient reported outcomes (all collected at baseline, and months 4, 8, and 12), and transfusion-related adverse events (collected monthly). RESULTS: Between 2020 and 2025, the SCD-CARRE trial randomized 173 participants at 23 sites across 3 countries. Enrolled participants had mean (SD) age of 45.8 (11.8) years and 54% were female. At baseline, participants had average TRV of 2.8 (0.5) m/s such that 45.9% had a TRV between 2.5 to 2.9 m/sec and 28.1% had a TRV ≥ 3.0 m/sec. The median (Q1, Q3) eGFR in this cohort was 60 (36, 110) mL/min/1.73 m2. The median (Q1, Q3) 6-minute walk test distance was 375 meters (309, 439), the median daily steps were 3,728 (2,187, 5,821), and participants experienced a median (Q1, Q3) of 2 (1, 5) pain episodes in the year prior to randomization. The trial results are pending. CONCLUSIONS: The SCD-CARRE trial successfully enrolled a cohort of n = 173 adults with SCD. This study highlights a rationale to evaluate the effect of automated chronic RBCX transfusion strategy plus standard of care as compared to standard of care alone in SCD patients at high risk of death with a focus on patient centered outcomes, preservation of cardiovascular function, end-organ complications and death. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT04084080, https://clinicaltrials.gov/study/NCT04084080.

Adult↗

PubMed2026

Quality assessment, prognostic factors, and biomarkers for brain tumor analysis: a comprehensive systematic review.

The brain tumors possess different causative factors and properties, making their diagnosis and treatment difficult. Growth of these cancers usually leads to compression of the adjacent nerves and obstruction of the flow of cerebrospinal fluid, thus leading to increase in intracranial pressure. This affects the working of brain in many ways; thus, the difficulty involved in its treatment. With the improvements in technology in neuroimaging, including Diffusion Tensor Imaging (DTI), Positron Emission Tomography (PET), and multiparametric Magnetic Resonance Imaging (mpMRI), the diagnosis process has become easy. The effectiveness of any form of therapy in such patients depends primarily on their prognosis. While it is a common practice that physicians determine the prognosis of the disease by considering the age of the patient, histological grade of the tumor, and resection status, now this method has become more comprehensive by adding molecular signature and genetic analyses to the list of criteria. Next-generation sequencing (NGS) allows a reliable molecular classification. It increases the level of risk stratification, facilitating the application of therapies tailored to individual patients. Thus, molecular oncology has greatly changed our views on brain tumors' pathology and prognosis while neoadjuvant treatments aim at increasing the survival rate. On the other hand, radiogenomics is a field of study that combines non-invasive imaging phenotypes and genomic information in order to find unique molecular signatures of tumors without collecting samples from tumors. Molecular biomarkers are absolutely essential in the diagnosis of cancer, treatment monitoring, and recurrence of cancer. Advances in liquid biopsy technology, particularly the methods for circulating tumor DNA (ctDNA) and Extracellular Vesicle (EV) based analysis, have enabled the possibility of non-invasive monitoring of the progression of the tumors over time. This review highlights key studies and important scientific works about imaging technologies, biomarkers, and prognostic factors of malignant brain tumors.

Humans↗

PubMed2026

Interface-dependent V. parahaemolyticus biofilm under varying temperatures, media, and oxygen conditions: implications for seafood safety.

Vibrio parahaemolyticus biofilms play a critical role in pathogen persistence in marine and seafood-processing environments, where oxygen availability, temperature, and surface interfaces vary widely. This study investigated biofilm development by three strains on partially submerged stainless-steel coupons under gas-liquid-wall (GLW) and fully submerged (SM) interfaces. Viable cell counts (log₁₀CFU/cm2) along with normalized protein concentration per viable cell (nProt) and normalized polysaccharide concentration per viable cell (nPol) were measured, under aerobic and anaerobic conditions across a temperature range of 15-30 °C, using tryptic soy broth with 3% NaCl (TSB) and seawater-based medium (SW). GLW biofilms consistently exhibited higher cell counts (6.4-7.3 log₁₀CFU/cm2) compared to SM biofilms (5.9-6.3 log₁₀CFU/cm2), suggesting that enhanced oxygen diffusion promotes bacterial proliferation. Conversely, SM biofilms exhibited significantly higher nProt and nPol levels (p < 0.001), indicating increased production of the extracellular polymeric substance (EPS) matrix under low-oxygen, high-nutrient conditions. Microscopy and three-dimensional surface plot analyses revealed relatively uniform biofilm layers at the GLW interface, whereas SM biofilms formed heterogeneous, tower-like structures. EPS production was further influenced by medium composition, oxygen, and temperature. SM biofilms grown in SW exhibited significantly higher nProt and nPol than those in TSB under aerobic conditions (p < 0.001), indicating enhanced matrix stabilization. Under anaerobic conditions at 15 °C, nProt and nPol were higher, whereas under aerobic conditions, peak nProt and nPol occurred at elevated temperatures. These findings highlight a trade-off between bacterial growth and matrix production and provide insight into biofilm adaptation and persistence in seafood-processing environments. These insights may help develop improved biofilm control and seafood safety management.

Biofilms↗

PubMed2026

Identification and formation pathways of oxidation products of chlorinated paraffins during ozonation in municipal wastewater.

Chlorinated paraffins (CPs) cannot be efficiently removed by conventional water treatment processes and are continually discharged into the aqueous environment. Ozonation can effectively remove lipophilic and persistent pollutants. However, the degradation behaviors of short-chain CPs (SCCPs), medium-chain CPs (MCCPs), and long-chain CPs (LCCPs) in wastewater during the ozonation process remained unknown. In this study, ozonation treatment achieved removal efficiencies of 61 % for SCCPs, 66 % for MCCPs, and 51 % for LCCPs from wastewater within 30 min. Approximately 147 oxidative products of SCCPs, MCCPs, and LCCPs were non-targeted identified through Ph4PCl-enhanced ionization with ultra-high performance liquid chromatography-Orbitrap mass spectrometry. These oxidation products were structurally classified into three categories: carbon chain breakage (53 products), HCl-elimination (27 products), and hydroxylation (67 products). Twenty-three di-hydroxylated CPs were newly identified among the products. Hydroxylation was the predominant pathway for SCCPs, producing di-hydroxylated SCCPs ((OH)₂-SCCPs) with a higher generation rate constant (KG = 22.28 × 10⁻² min⁻¹) compared to other products. MCCPs and LCCPs mainly underwent carbon chain breakage and hydroxylation, generating shorter carbon chain congeners, (OH)2-SCCPs, and di-hydroxylated MCCPs ((OH)2-MCCPs). The KG values of (OH)2-SCCPs (10.56 × 10-2 min-1) and (OH)2-MCCPs (12.05 × 10-2 min-1) generated from the MCCPs were the highest, and the KG values of MCCPs (6.49 × 10-2 min-1), SCCPs (6.27 × 10-2 min-1), and (OH)2-SCCPs (4.74 × 10-2 min-1) generated from the LCCPs were higher than those of other products. These results comprehensively clarify the oxidation efficiencies and pathways of CPs during ozonation. Future studies must explore the potential risks associated with the oxidation products.

Water Pollutants, Chemical↗