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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&#x2009;=&#x2009;146) or osimertinib monotherapy (n&#x2009;=&#x2009;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&#x2009;<&#x2009;.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

Assessment of the role and effectiveness of nurse-led multimodal intervention in the rehabilitation of dysphagia in patients with brain tumors.

BACKGROUND: Dysphagia is a common complication in patients with brain tumors, which has a profound adverse impact on patients' health status and quality of life. However, there is a relative lack of research on the rehabilitation of dysphagia in brain tumor patients, especially regarding the role and effectiveness of nurse-led multimodal interventions in the rehabilitation of dysphagia in brain tumor patients, which lacks systematic assessment and in-depth discussion. AIM: This study aimed to evaluate the role and effectiveness of a nurse-led multimodal intervention in improving swallowing function and quality of life in brain tumor patients with dysphagia. METHODS: In this study, a randomized controlled trial (RCT) design was used to select 120 dysphagia patients among brain tumor patients admitted to our hospital during the period of January 2024 to May 2024 as the study subjects, and they were stratified and randomly divided into an intervention group (n&#x2009;=&#x2009;60) and a control group (n&#x2009;=&#x2009;60). While the control group received conventional nursing care and treatment protocols, the intervention group received a nurse-led multimodal intervention program, including personalized swallowing training, nutritional support, psychological care, and a family-participatory rehabilitation program, which was developed and dynamically adjusted by nurses, rehabilitation therapists, and dietitians. Differences in data before and after the intervention were analyzed using the paired t-test or Wilcoxon signed-rank test, and between-group comparisons were made using the independent samples t-test or Mann-Whitney U test. RESULTS: Both the intervention and control groups showed improvement in swallowing function among the patients. The Kubota drinking test score, Saito's swallowing function grading, and the quality of life scores for patients in the intervention group showed a significant enhancement compared to those in the control group (P&#x2009;<&#x2009;0.05), indicating that the intervention was more effective than the control. When compared within groups, all scores in both the intervention and control groups improved gradually with the time of intervention (P&#x2009;<&#x2009;0.05). The improvement was significantly higher in the intervention group than in the control group. CONCLUSION: This study demonstrates that a nurse-led multimodal intervention is significantly effective in improving swallowing function and quality of life in patients with brain tumors. The intervention provides comprehensive rehabilitation support for patients through multidisciplinary collaboration and personalized care and has certain clinical promotion value.

Humans

Development and Crossover Evaluation of an Artificial Intelligence-Assisted System for Solid Pancreatic Lesion Detection and Pancreatic Parenchyma Recognition in Endoscopic Ultrasonography (With Video).

BACKGROUND AND STUDY AIMS: Pancreatobiliary endoscopic ultrasonography (EUS) is technically demanding, and supervised training opportunities are limited. We developed an artificial intelligence (AI) overlay system for detecting solid pancreatic lesions (SPL) and recognizing pancreatic parenchyma (PP) and evaluated its effect on reader performance. PATIENTS AND METHODS: Across six centers, two deep learning-based models were trained using expert-annotated EUS frames. We then conducted a randomized, two-sequence, two-period crossover reader study in which eight endosonographers (five novices and three experts) interpreted image sets with and without AI assistance. The primary endpoint was superiority of sensitivity for SPL detection among novices; key secondary endpoints included specificity and PP recognition. RESULTS: From 118 patients, 120 SPL-positive/negative image sets and 160 PP-positive/negative image sets were constructed. Among novices, AI assistance improved SPL detection sensitivity (88.7% vs. 76.8%, p&#x2009;<&#x2009;0.001) and accuracy (86.4% vs. 78.7%), while specificity met the predefined noninferiority criterion (84.2% vs. 80.5%, p&#x2009;<&#x2009;0.001). For PP recognition, sensitivity increased numerically (86.3% vs. 83.3%) but did not meet the predefined superiority criterion (p&#x2009;=&#x2009;0.095); specificity met the noninferiority criterion (87.8% vs. 81.0%), and accuracy increased from 82.1% to 87.0%. Among experts, sensitivity was maintained for both tasks, whereas specificity increased with AI assistance. CONCLUSIONS: AI assistance improved SPL detection among novice endosonographers. For PP recognition, sensitivity increased without reaching statistical superiority, whereas specificity met the predefined noninferiority criterion. These findings support a potential adjunctive role for AI in EUS interpretation.

Humans

Ultrasound protocols used to detect vascular gas emboli in divers: a systematic review.

INTRODUCTION: Venous gas emboli (VGE) detected via ultrasound can be used as a surrogate marker for decompression stress. While Doppler ultrasound is the historical gold standard, two-dimensional (2D) ultrasonography offers advantages for on-site monitoring, including a wider field of view and reduced dependence on noise-free environments. This systematic review evaluates 2D ultrasonography protocols used in decompression research since the 2015 International Meeting on Ultrasound for Diving Research, identifying methodological similarities, differences, and adherence to consensus recommendations. METHODS: A search of PubMed and Scopus identified studies using 2D ultrasound to detect VGE in divers. Inclusion criteria were: (1) use of 2D ultrasound, (2) detection of VGE or monitoring of decompression stress, (3) inclusion of a diver cohort, and (4) publication after 2015. Data extraction focused on VGE scoring systems, ultrasound hardware, measurement protocols, and operator experience. Risk of bias was assessed using ROBINS-I-V2, and compliance with the 2015 consensus recommendations was evaluated. RESULTS: Twenty studies were included. The Eftedal-Brubakk scale was most commonly used (n = 15), with cardiac ultrasound as the primary imaging modality; one study assessed a peripheral vessel. Common shortcomings included post-dive measurements lasting less than two hours, underreporting of operator experience and hardware specifications, limited individual-level data, and inappropriate use of parametric statistics for ordinal bubble grade data. No study fully complied with all consensus recommendations. CONCLUSIONS: This review demonstrates that, although two-dimensional ultrasound is widely used for post-dive VGE assessment, methodological heterogeneity with multiple shortcomings remain. Furthermore, nearly all studies restricted imaging to the heart, thus leaving peripheral vessel assessment largely unexplored.

Embolism, Air

Artificial intelligence for dental caries detection: An umbrella review.

Artificial intelligence (AI) has been proposed as a tool to improve dental caries detection across imaging modalities; however, its clinical value remains uncertain. This umbrella review aimed to synthesize and critically appraise systematic reviews evaluating AI for caries detection and diagnosis. An umbrella review was conducted following PRIOR guidance (PROSPERO CRD420261340728). Searches were performed in MEDLINE, Embase, Scopus, Web of Science, and Google Scholar up to 15 March 2026. Methodological quality was assessed using AMSTAR 2, and overlap of primary studies was quantified using the corrected covered area (CCA). Seventeen systematic reviews were included, of which five reported diagnostic test accuracy meta-analyses using bivariate or HSROC models. Across these meta-analyses, pooled sensitivity ranged from 0.76 to 0.94 and specificity from 0.85 to 0.91. Most systems were based on deep learning models applied to bitewing radiographs and intraoral photographs. However, substantial heterogeneity was observed in imaging modalities, lesion thresholds, analytical tasks, and evaluation metrics. In addition, a high degree of overlap across reviews and recurrent methodological limitations, including reliance on retrospective datasets, limited external validation, and inconsistent reporting, substantially weaken the reliability of the evidence. Although AI models demonstrate high diagnostic performance under experimental conditions, current evidence does not support their use as stand-alone diagnostic tools. Their clinical applicability remains limited, and implementation should be restricted to decision-support contexts until robust prospective validation demonstrates meaningful impact on clinical decision-making and patient outcomes.

Dental Caries

Unraveling the c-Myc-CASC19/HDAC1-NPM1 epigenetic axis: A novel regulatory circuitry and therapeutic target in gastric carcinogenesis.

Mounting evidence implicates long non-coding RNA cancer susceptibility candidate 19 (CASC19) in the pathogenesis of diverse malignancies. However, its functional role and molecular mechanisms in gastric cancer (GC) remain elusive. Herein, we identified a novel 717-bp transcript isoform of CASC19 in GC cells. This study aimed to delineate the biological functions and underlying mechanisms of this novel CASC19 transcript in GC pathogenesis. CASC19 was significantly upregulated in GC tissues and cell lines, correlating with adverse clinicopathological features and poor prognosis in GC patients. Functional investigations demonstrated that CASC19 overexpression potentiated GC cell proliferation, metastasis, and epithelial-mesenchymal transition, whereas CASC19 knockdown attenuated these malignant phenotypes and suppressed tumorigenesis in xenograft models. Mechanistically, CASC19 functioned as a molecular scaffold by recruiting histone deacetylase 1 (HDAC1) to the nucleophosmin 1 (NPM1) promoter. This recruitment sustained H3K27 deacetylation, thereby transcriptionally repressing NPM1 promoter activity and accelerating gastric carcinogenesis. Crucially, Depletion of HDAC1 or NPM1 partial rescued CASC19-mediated oncogenic effects. Intriguingly, the transcription factor c-Myc was found to transcriptionally activate CASC19 through direct binding to its promoter region. Collectively, our findings indicate that the c-Myc-CASC19/HDAC1-NPM1 axis acts as a potential prognostic biomarker candidate for GC and may represent a therapeutic vulnerability worthy of future investigation.

Humans

RR-interval-based atrial fibrillation detection and burden estimation: cross-dataset validation and calibration-aware probability analysis.

Objective.Atrial fibrillation (AF) burden has become an increasingly important endpoint in long-duration rhythm monitoring, but reliable burden estimation requires more than accurate AF detection alone. In particular, when burden is derived by aggregating predicted AF probabilities over time, probability calibration may directly affect burden validity under external dataset shift.Approach.This study developed an interpretable-interval feature model for AF detection and evaluated it using record-wise cross-validation on a development cohort and independent cross-dataset external validation on public Holter electrocardiographic databases. Window-level performance was assessed using the area under the receiver operating characteristic curve (ROC-AUC), area under the precision-recall curve (PR-AUC), Brier score, expected calibration error (ECE), and calibration intercept and calibration slope. Recording-level AF burden was estimated using both probability-based and hard-label aggregation and evaluated using mean absolute error (MAE) and agreement analyses.Main results.The model showed high discrimination in both development and external evaluation, with external ROC-AUC ofand PR-AUC of. However, external calibration deteriorated despite preserved ranking performance, with Brier score of, ECE(15) of, calibration intercept of, and calibration slope of. In the external cohort, probability-based burden estimation preserved strong association with reference burden but showed weaker raw agreement than hard-label aggregation, with MAE ofversus, consistent with systematic probability underprediction. Repeated external recalibration across record-level splits substantially improved probability quality and probability-based burden estimation. Median probability-burden MAE decreased fromwithout recalibration toafter Platt recalibration andafter isotonic recalibration, while median ECE(15) decreased fromtoand, respectively.Significance.These findings indicate that-interval-based AF detection maintained strong ranking performance in the tested external cohort, but probability calibration should be evaluated explicitly when predicted probabilities are aggregated into AF-burden estimates.

Atrial Fibrillation

Metal-organic frameworks nanozyme-integrated portable microneedle patch for visual bacterial monitoring in meat.

Foodborne microbial contamination is a major global health concern, with conventional methods often being time-consuming and complex. Herein, we developed a novel portable biosensor by integrating microneedle patch technology and a metal-organic framework (Fe/Cu-NBDC MOF) nanozyme, enabling rapid, on-site, visual detection of bacteria in meat. The sensing system works by encapsulating aptamer-functionalized MOF nanozymes within a hydrogel patch, where their catalytic sites are initially blocked by the aptamer. In the presence of Staphylococcus aureus (S. aureus) as the target, the specific aptamer's binding to bacteria exposes numerous catalytic sites, further activating the chromogenic reaction of the tetramethylbenzidine&#x2011;hydrogen peroxide (TMB-H&#x2082;O&#x2082;) system, enabling visual detection of S. aureus. The biosensor demonstrates a detection limit of 82&#xa0;CFU/mL with excellent specificity to successfully apply to commercial mutton. By integrating sampling, enrichment, and visual detection into a single compact device, this platform offers a practical, efficient solution for rapid on-site screening of foodborne pathogens.

Biosensing Techniques

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

Tripled-Stranded Antisense Oligonucleotide for Biomarker-Activated Suppression of Essential Genes.

Conditional activation of antisense oligonucleotides (ASOs) is a promising strategy for selective suppression of cancer cells without affecting normal cells. In this study, we developed a tripled-stranded ASO (tsASO) that is rendered inactive through complexation with two additional oligonucleotides. The key innovation is the use of partial overlap between the parent ASO and the biomarker sequence, combined with toehold-mediated strand displacement, enabling precise conditional activation. The tsASO effectively triggered RNase H-mediated degradation of DYNC1I2 and DARS1 RNAs exclusively in the presence of the ERBB2 sequence. In cell-free systems, the tsASO demonstrated high cleavage efficiency (up to 81%), comparable to the parent ASO efficiency, with minimal background activity in the absence of the biomarker sequence, validating the concept at the molecular level. However, in cells using lipid-based transfection, the tsASO exhibited nonspecific cytotoxicity that did not correlate with biomarker presence or target gene expression. Detailed analysis showed no clear support for known sequence-driven toxicity mechanisms (CpG/TLR9, G-quadruplexes) in the nonimmune cell lines, suggesting that the primary limitation is intracellular delivery rather than the tsASO design. Future work should focus on optimizing delivery platforms to achieve controlled cellular uptake and biomarker-dependent release, unlocking the therapeutic potential of this conditional gene silencing approach.

Oligonucleotides, Antisense

Enhancing Hemoglobin Bart's hydrops fetalis syndrome prevention: a single-tube multiplex real-time PCR assay for the comprehensive detection of four significant &#x3b1;0-thalassemia deletions (--SEA, --THAI, --CR, and --SA) found in Thailand.

BACKGROUND: Hemoglobin (Hb) Bart's hydrops fetalis is a major public health concern in Southeast Asia, particularly in Thailand. Current screening strategies target the two most common &#x3b1;0 -thalassemia deletions (--SEA and --THAI). METHOD: In this study, we developed a single-tube multiplex real-time PCR assay for the simultaneous detection of four clinically relevant &#x3b1;0-thalassemia deletions (--SEA, --THAI, --CR, and --SA). The assay was validated using 538 clinical samples with diverse thalassemia genotypes and compared against conventional gap-PCR as the reference method. Analytical performance, including sensitivity, specificity, and limit of detection (LOD), was evaluated. In addition, clinical utility was assessed in 22 prenatal diagnosis cases at risk of Hb Bart's hydrops fetalis. RESULTS: The study cohort demonstrated substantial genetic heterogeneity, comprising 43 distinct genotypes. The developed assay achieved 100% sensitivity and specificity for all targeted deletions, with complete concordance with gap-PCR results. No cross-reactivity was observed with &#x3b1;+-thalassemia. The assay demonstrated a high analytical sensitivity with a LOD of 9.76&#x2009;&#xd7;&#x2009;10-3&#x2009;ng per reaction. Whereas in prenatal diagnosis, all 22 fetal genotypes were accurately identified, including five cases of homozygous --SEA and one rare compound heterozygous --SEA/--CR fetus. CONCLUSIONS: This study presents a rapid, accurate, and cost-effective multiplex real-time PCR assay capable of detecting both common and rare &#x3b1;0-thalassemia deletions in a single reaction. The assay demonstrates strong potential for implementation in routine clinical laboratories and large-scale population screening, contributing to improved prevention and control of severe thalassemia syndromes in high-prevalence regions.

Humans

UNCX/SIN3A-Mediated H4K8 decrotonylation suppresses FOXO3 to drive TNBC progression and docetaxel resistance.

Triple-negative breast cancer (TNBC) remains a clinically challenging subtype characterized by aggressive behavior and limited treatment options. Though docetaxel remains a cornerstone chemotherapy for TNBC, the frequent emergence of resistance highlights the urgent need to identify novel therapeutic targets. In this study, we report that uncoordinated homeobox (UNCX) is upregulated in docetaxel-resistant breast cancer cells, genomically amplified in breast cancer, and associated with poor survival in breast carcinoma patients. Functional studies revealed that UNCX promotes breast cancer cell proliferation, migration and reduces the docetaxel sensitivity. Mechanistically, UNCX functions as a transcriptional repressor by recruiting the SIN3A complex. Genome-wide profiling indicated that the UNCX/SIN3A complex directly binds to the promoters of tumor-suppressor genes including FOXO3, and represses their transcription by removing histone H4K8 crotonylation (H4K8cr). Additionally, the UNCX/SIN3A complex enhances FOXO3 phosphorylation and inhibits its nuclear translocation, further inhibiting its activity. Notably, SIN3A knockdown, FOXO3 overexpression, or crotonylation restoration effectively reverses UNCX-induced malignant phenotypes. These findings collectively establish the UNCX/SIN3A-H4K8cr-FOXO3 axis as a pivotal epigenetic regulator of TNBC progression and chemoresistance, revealing new avenues for targeted therapeutic development against this aggressive breast cancer subtype.

Humans

Feasibility and Efficacy of Lorlatinib in Japanese Patients With Relapsed/Refractory ALK-Aberrant Neuroblastoma.

Lorlatinib, a third-generation ALK inhibitor, was administered off-label to five heavily pretreated patients with relapsed or refractory ALK-aberrant neuroblastoma. ALK alterations included F1174L, R1275Q, BEND5::ALK fusion, and ALK amplification; three patients had MYCN amplification. Best responses were three partial responses and two disease progressions. The longest progression-free survival (6.7 months) occurred in a patient with F1174L and non-amplified MYCN, whereas rapid progression was observed in two MYCN-amplified cases. Lorlatinib was generally well tolerated with manageable adverse events. These findings suggest that lorlatinib is a feasible therapeutic option in ALK-aberrant neuroblastoma and that clinical heterogeneity in treatment response warrants further investigation.

Humans

Pathway incompatibility between NF-&#x3ba;B and RAS signaling constrains oncogenicity in B-cell leukemia.

Oncogenic pathways do not always cooperate; in some contexts, their co-activation is antagonistic and suppresses tumorigenesis, a phenomenon we termed pathway incompatibility. However, the mechanisms underlying this antagonism and the role of receptor context in shaping these interactions remain unclear. During normal B-cell development, precursor B-cell receptor (pre-BCR) signaling supports survival and proliferation of early B-cell precursors before transition to expression of the mature B-cell receptor (BCR). B-cell acute lymphoblastic leukemia (B-ALL), the most common childhood cancer, is characterized by developmental arrest prior to BCR expression, and approximately 35% of cases harbor activating RAS-ERK mutations that mimic pre-BCR-dependent survival signaling. NF-&#x3ba;B plays context-dependent roles in B-cell malignancies, but whether it influences the compatibility between oncogenic RAS signaling and BCR expression remains poorly understood. Activation of canonical NF-&#x3ba;B induced apoptotic depletion of RAS-driven B-ALL cells. Mechanistically, NF-&#x3ba;B suppressed pre-BCR-dependent survival signaling while promoting expression of BCR components. Consistent with this shift, oncogenic RAS signaling was poorly tolerated in BCR-positive cells unless BCR expression was disrupted. Pharmacologic activation of NF-&#x3ba;B reduced ERK signaling and selectively impaired viability of RAS-driven B-ALL cells, with enhanced effects in combination with ERK inhibition. Together, these findings show that canonical NF-&#x3ba;B signaling promotes BCR expression, which constrains oncogenic RAS activity, and establish pathway incompatibility as a mechanism through which receptor context can limit oncogenic potential.

Cancer biology

Single-slice Functional Lung MRI During Metronome-Paced Tachypnea Detects Changes in Regional Ventilation Dynamics After a Single Dose of Dual Bronchodilator Treatment in COPD.

Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p&#x2009;<&#x2009;0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p&#x2009;<&#x2009;0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.

Humans

Evaluating the need for late angiography for complete obliteration of AVMs after endovascular treatment: collaborative AVM center experience and a systematic review.

Brain arteriovenous malformations (bAVMs) can be treated curatively by endovascular embolization. However, limited data exist on late recanalization rates. We investigated the rate of late bAVM recanalization following complete endovascular obliteration, confirmed by primary control angiography.We performed a single-center retrospective cohort study on late recurrences in adult patients with bAVMs after complete endovascular obliteration at a Radboud - Isala - MUMC+ (RIM) collaborative AVM center in the Netherlands between 2014 and 2022.Additionally, we conducted a systematic review to evaluate the rate of late recanalization following complete endovascular obliteration, confirmed on primary control angiography, in adults with bAVMs. The protocol for this review was registered in PROSPERO (CRD42024546875).Our retrospective study revealed 42 adult patients treated by endovascular means only; 90.5% (38 patients with mean age of 48.1 years) had confirmed complete obliteration. Both primary (6 months post-treatment) and secondary (more than 1 year post-treatment) angiographic control confirmed complete obliteration in 21 of 23 patients with complete follow-up. Mean follow-up was 47.8 months. Two late recurrences (9.5%) were detected at 5- and 6-years' follow-up imaging.Our systematic review included two studies encompassing a total of 19 patients with mean angiographical follow-up of 20.8 months. There were no late recurrences.Late bAVM recurrence after endovascular treatment with proven complete obliteration may be underestimated owing to limited long-term follow-up. Our findings suggest that after a 6-month angiographic confirmed obliteration, a 5-year angiographic imaging control is justified.

Humans

Effectiveness of STK Spray&#xae; for semen stain localization on solid surfaces: A specificity and sensitivity study.

Semen identification is a crucial step in sexual assault cases. The aim of this study was to assess STK Spray&#xae;, a presumptive test for semen, under controlled conditions including, simulated crime scene stains detection. Easy to use, it can be sprayed directly onto different surfaces and visualized under UV light. Several tests were performed on five different substrates (ceramic tile, drywall, metal, wood, and faux leather). The spray was able to enhance semen fluorescence, especially in diluted samples, with characteristic "globular" spots. Although it showed good specificity, false positives could be obtained with 10% bleach. The fluorescence signals were quantified using ImageJ&#x2122; and showed a statistically significant substrate-dependent variability. Mixture analysis indicated that saliva did not interfere with detection of semen, while urine partially suppressed the signal and blood markedly affected its interpretation. Simulation tests with UV lamp comparisons confirmed the importance of choosing the right detection method and the utility of this presumptive test in combination with additional immunochromatographic tests. A preliminary signal retention test showed stable fluorescence for up to two years when stains were stored appropriately. Finally, complete DNA profiles (100% of alleles) were obtained from all samples (n&#xa0;=&#xa0;24) after exposure to the reagent and UV light. Because of its ability to enhance semen signal, especially on specific surfaces, and its rapidity of use and detection, STK Spray&#xae; may represent a useful aid in the preliminary screening phase.

Humans

Orange juice and hesperidin increase flavanone exposure without detectable short-term vascular benefits: a randomized crossover trial.

Orange juice is a major dietary source of hesperidin, a citrus flavanone with vascular protective effects in experimental models. However, whether nutritionally realistic intake levels induce measurable benefits in humans remains unclear. We investigated the effects of orange juice and hesperidin supplementation, at realistic dietary doses, on vascular function, flavanone bioavailability, and molecular responses. Thirty-seven centrally overweight men completed a randomized, double-blind, controlled, three-period crossover trial with three 6-week interventions separated by washout periods. Participants consumed daily 330 mL of 100% orange juice (OJ), an isoenergetic control beverage (CON), or a hesperidin-enriched control beverage (HESP, 210 mg day-1). Fasting vascular, metabolic and anthropometric parameters were assessed before and after each intervention, with flow-mediated dilation (FMD) as the primary endpoint. Postprandial FMD, circulating flavanone metabolites and oxylipin profiles were evaluated following a standardized high-fat meal challenge, and flavanone bioavailability was assessed by 24 h urinary excretion. Whole-blood transcriptomics were performed in a subset (n = 9). Plasma exposure to phase II hesperetin metabolites (AUC0-6 h) and 24 h urinary excretion were comparable after OJ and HESP, indicating effective hesperidin delivery and limited matrix effects on bioavailability. Neither intervention significantly affected fasting or postprandial FMD, vascular, metabolic or anthropometric parameters, or oxylipin profiles versus CON. Marked interindividual variability was observed in vascular responses and flavanone bioavailability, although treatment effects were unrelated to baseline endothelial function or flavanone exposure. Exploratory transcriptomic analyses suggested modulation of pathways involved in vascular biology following OJ and HESP. Under nutritionally realistic conditions, orange juice and hesperidin induced measurable biological engagement without detectable short-term vascular benefits, highlighting the complexity of linking flavanone exposure to functional vascular outcomes in humans.

Humans