Search Results (2,253)

Background: Metabolite identification and annotation remain major bottlenecks in untargeted metabolomics because mass spectral features often lack sufficient specificity. High-confidence annotation requires experimental validation using authentic standards analyzed under matched chromatographic and ionization conditions, providing greater reliability than in silico predictions or database matching alone. This study aimed to develop a practical and scalable workflow for constructing a high-quality mass spectral library using a commercially available analytical standards kit. Methods: A total of 603 metabolites from the MSMLS kit were organized into 42 mixtures, each containing approximately 15 compounds. Mixture design was based on molecular mass and distribution coefficient values, specifically logD at pH 3.1, with a minimum logD spacing of 0.15 to improve chromatographic separation and reduce co-elution. This strategy was used to minimize the total number of injections while maintaining spectral quality. The resulting spectra were evaluated against online spectral resources and in silico fragmentation predictions. A preliminary proof-of-concept analysis was also performed using human serum samples. Results: Using this workflow, 471 metabolites, corresponding to approximately 78% of the standards, were successfully detected and incorporated into the spectral library. Comparison with online resources and in silico fragmentation predictions demonstrated improved spectral quality and reliability. The proof-of-concept serum analysis enabled identification of endogenous metabolites using the constructed library. In addition, the robustness and applicability of the workflow were further supported by a method validation study using metabolites derived from this library. Conclusions: This workflow provides a scalable strategy for constructing mass spectral libraries that balances spectral quality with analytical throughput. By using rational mixture design and authentic standards analyzed under matched experimental conditions, the approach enables substantial metabolite coverage while maintaining data reliability and minimizing experimental effort. Full article

Background/Objectives: There is limited data on treatment outcomes under immune checkpoint inhibitor (ICI) administration in solid organ transplant recipients (sOTRs). This study aims to evaluate cancer outcome and allograft rejection risk in sOTRs receiving ICI. Methods: This is a retrospective multicenter study. The data had been collected within the Swiss Transplant Cohort Study (STCS) database. We searched for matching individuals from May 2008 up to the end of 2024. The primary outcomes were treatment response and survival; the secondary outcome was allograft rejection. Additional analyses included associated factors such as tumor, transplant, and treatment characteristics. Results: We identified ten patients, six of whom received a kidney allograft, while the remaining four received a liver, lung, pancreas, or combined kidney–pancreas transplant. Treatment response was achieved in half of the sOTRs, with a complete response (CR) in three and prolonged stable disease (SD) in two patients. CR was achieved in all three patients after only a few infusions. At the time of data analysis, four out of ten patients were still alive. Graft rejection occurred in six out of ten cases, five of which occurred after the first cycle of ICI administration. Conclusions: Data is limited and definitive conclusions from this study cannot be drawn given the limited sample size. However, ICI displays promising effects on cancer outcomes in sOTRs with advanced malignancies. The study’s findings demonstrate an overall response in half of sOTRs, but with graft rejection occurring in a similar number of patients. We propose initiating immunotherapy as early as possible, given the promising results, particularly in patients with kidney transplants. We further suggest that in sOTRs, a few ICI infusions could potentially be a cautious option, pending further evidence. Full article

Snake envenomation causes acute cerebrovascular complications, but its long-term effect on stroke risk remains unclear. This study suggests that snake envenomation may be associated with long-term stroke risk. Using the Korean National Health Insurance Service database, we conducted a nationwide population-based cohort study to evaluate the long-term risk of stroke following snake envenomation. A total of 764 adult patients diagnosed with snake envenomation and treated with antivenom were identified and matched with 3056 control patients (1:4) by age, sex, and socioeconomic status, excluding those with prior cerebrovascular disease. Stroke outcomes were defined using ICD-10 diagnostic codes and healthcare utilization criteria. After a 1-year lag period was applied to minimize reverse causation, multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios for total, ischemic, and hemorrhagic strokes. During 10 years of follow-up, snake envenomation was associated with a significantly increased risk of total stroke (aHR 1.42 (95% CI 1.01–1.99)), particularly hemorrhagic stroke (aHR 2.55 (95% CI 1.12–5.80)), whereas no significant association was observed with ischemic stroke. Interaction analyses showed a stronger association among men with diabetes mellitus, particularly for hemorrhagic stroke. In addition, severe envenomation with disseminated intravascular coagulation or requiring transfusion was associated with a higher long-term risk of hemorrhagic stroke. These findings highlight the need for further investigations of long-term cerebrovascular complications of snake envenomation, particularly hemorrhagic stroke in vulnerable populations. Full article

Background: Diabetic peripheral neuropathy (DPN) is a progressive complication of type 2 diabetes mellitus (T2DM) for which no approved disease-modifying therapy exists. Palmitoylethanolamide/Baicalin (PEA/Bai; Neuridase^®) is a nutraceutical formulation with anti-neuroinflammatory and antioxidant properties; however, real-world evidence on its associations with objective neuropathy biomarkers remains limited; nutraceutical approaches to DPN remain exploratory and adjunctive in the absence of randomised controlled trial evidence of disease modification. Methods: We conducted a single-centre, retrospective, 1:1 matched-cohort study at an Internal Medicine outpatient clinic. Forty-eight T2DM patients with clinically diagnosed DPN who received PEA/Bai supplementation (Neuridase^® group) were matched to 48 untreated controls drawn from a large institutional database, using age, sex, BMI, and diabetes duration as matching variables. Acknowledged a priori limitations include baseline imbalance in neuropathy severity (VAS and ESC) and SGLT2 inhibitor use, reflecting real-world prescribing patterns (confounding by indication) and constituting potential sources of residual confounding that preclude causal inference. The primary outcome was change in VAS neuropathic pain score from baseline (T0) to 6-month follow-up (T6). Secondary outcomes were changes in electrochemical skin conductance (ESC, µS) in hands, feet, and four-limb sum measured by Sudoscan. Results: At baseline, the Neuridase^® group exhibited significantly greater neuropathic burden: higher VAS scores (median 5.5 [IQR 3.8–7.2] vs. 2.0 [0.0–5.0]; p < 0.001) and lower ESC in both hands (53.0 vs. 72.2 µS; p < 0.001) and feet (74.5 vs. 81.0 µS; p < 0.001), reflecting real-world prescribing patterns. Over 6 months, VAS decreased significantly in the Neuridase^® group (5.5→3.0; p < 0.0001; median Δ = −2.5 points, exceeding the clinically important difference), with no change in controls (2.0→2.0; p = 0.85). Differential Sudoscan trajectories were observed: the Neuridase^® group showed significant improvement in hand ESC (53.0→60.0 µS; p = 0.035) and preservation of foot ESC (p = 0.888), while controls exhibited significant deterioration across all three sudomotor indices (hand p = 0.038; foot p = 0.008; four-limb sum p = 0.004). In a complementary categorical pain trajectory analysis, VAS worsening occurred in 31.3% of controls compared with 0% of Neuridase^®-treated patients (p = 0.00022). Among patients with pathological hand ESC at baseline (<60 µS), 27.8% of Neuridase^® patients (n = 36) transitioned to non-pathological values at T6 versus 0% of controls (n = 32; p = 0.001). Conclusions: In a real-world matched cohort, PEA/Baicalin supplementation was associated with clinically meaningful pain reduction and with differential longitudinal sudomotor trajectories compared to matched untreated controls. These exploratory, hypothesis-generating findings from a retrospective non-randomised design are consistent with possible modulatory effects of PEA/Baicalin on objective sudomotor autonomic biomarkers in DPN. Confounding by indication, baseline severity imbalance, and residual confounders including SGLT2 inhibitor use preclude causal interpretation. These observations provide a rationale for adequately powered, prospective, randomised placebo-controlled trials with extended follow-up and structural neuropathy endpoints. Full article

Background: The study aims to compare the short-term clinical outcomes of transcatheter aortic valve implantation (TAVI) with the novel self-expandable, intra-annular Navitor valve (NAV) and the balloon-expandable, intra-annular Sapien 3 Ultra valve (S3U). Methods: From a single-center TAVI database, patients receiving NAV and S3U were identified. We applied 1:2 propensity score matching for the selected variables (gender, age, aortic valve perimeter, area, diameter, mean aortic valve gradient, EuroScore2, coronary artery disease (CAD), previous stroke and previous pacemaker implantation), resulting in 153 patients. Results: Clinical outcomes at 30 days of 51 patients with NAV [mean age: 80.4 ± 6.7 years; 51% female; mean annulus diameter: 24.1 ± 1.40 mm; EuroScore2: 3.4 ± 3.1%] and 102 patients with S3U [mean age: 79.9 ± 6.5 years (p = 0.7); 51% female (p > 0.99); mean annulus diameter: 24.1 ± 1.4 mm (p > 0.99); EuroScore2: 3.2 ± 2.7 (p = 0.7)] were analyzed according to VARC-3 recommendations. Post-TAVI aortic valve mean (S3U: 11.0 [3–27] mmHg; NAV: 7 [3–15] mmHg; p < 0.001) and maximum (S3U: 22 [6–44] mmHg; NAV: 12 [5–28] mmHg; p < 0.001) gradients at discharge were significantly lower with NAV, whereas the effective orifice area (EOA) of the aortic valve measured significantly larger with NAV (S3U: 1.5 [0.8–3.8] cm²; NAV: 2.1 [0.9–3.5] cm²; p < 0.001). Rates of no to mild paravalvular regurgitation (PVL) were 92.1% after NAV and 91.2% after S3U implantation (p = 0.15), mild to moderate PVL were 2.0% after NAV vs. 2.9% after S3U (p = 0.1) and moderate PVL were 2% after NAV and 1% after S3U (p = 0.07). None of the patients had a severe regurgitation. Severe patient–prosthesis mismatch (PPM) occurred significantly less with NAV (S3U: 14.7%; NAV: 7.8%; p = 0.002). One (1%) non-disabling stroke occurred within the S3U group and none occurred within the NAV group (p = 0.1). Life-threatening (S3U: 2.9%; NAV= 1%; p > 0.99) and major (S3U: n = 2.9; NAV: 0%; p = 0.55) bleeding events were comparable between both groups. The incidence of major (S3U: 2.9%; NAV: 2.0%; p > 0.99) vascular complications and the need for permanent pacemaker implantation (S3U: 9.8%; NAV: 11.8%; p = 0.8) were comparable in both groups. The 30-day mortality rate was 0.7% [1 in NAV group (2%), none in S3U; p = 0.3]. Conclusions: In conclusion, at 30-day follow-up, the self-expanding intra-annular Navitor valve demonstrated excellent acute safety and superior early hemodynamic performance, characterized by significantly lower transvalvular gradients and lower rates of severe PPM compared to the balloon-expandable Sapien 3 Ultra. However, whether these acute hemodynamic advantages translate into superior long-term clinical outcomes remains to be determined in long-term follow-up studies. Full article

Background/Objectives: To compare the incidence of postoperative acute urinary retention (AUR) between traditional open laminectomy and percutaneous endoscopic lumbar surgery (PELS) using a large-scale real-world database, with specific stratification by urologic status, age, and sex. Methods: A retrospective, propensity score-matched analysis was conducted using the TriNetX Global Health Research Network (2015–2024). Adult patients undergoing PELS were compared to those undergoing open laminectomy. To rule out the confounding effect of routine intraoperative catheterization, the primary outcome was defined as de novo AUR occurring between 24 h and 3 months postoperatively. Subgroup analyses were performed for patients with benign prostatic hyperplasia (BPH), females, and age-stratified cohorts (<70 vs. ≥70 years). This study was approved by the Institutional Review Board (IRB/REC: CE25727C) and conducted under a waiver of informed consent. Results: In the matched cohorts of non-BPH males, females, and patients aged < 70 years, PELS was associated with a statistically significant reduction in AUR risk (Hazard Ratios: 0.445, 0.649, and 0.403, respectively) compared to open surgery. However, in males with BPH, the protective benefit of the endoscopic technique was attenuated and did not reach statistical significance (p = 0.0744), suggesting the study was underpowered for this subgroup or that baseline obstruction remains a dominant risk factor. Conclusions: Percutaneous endoscopic lumbar surgery was associated with a significantly lower risk of postoperative AUR compared to open laminectomy, particularly in patients without preexisting urologic obstruction. This benefit is likely attributable to minimized tissue trauma and the anti-inflammatory effects of continuous saline irrigation. However, in patients with BPH, baseline pathology outweighs surgical factors, necessitating medical prophylaxis regardless of the surgical approach. Full article

Background/Objectives: People with non-ST-segment elevation myocardial infarction (NSTEMI) with an occluded culprit vessel represent a unique subset of patients; however, their long-term outcomes remain unclear. This study aimed to compare 5-year mortality between NSTEMI patients treated with percutaneous coronary intervention (PCI) based on TIMI flow states in the culprit vessel on presentation (TIMI 0-1 compared to TIMI 2-3). Methods: A retrospective analysis of prospectively collected data of all NSTEMI patients who underwent PCI from 2012 to 2019 at a tertiary cardiac center (The Freeman Hospital, Newcastle-Upon-Tyne, UK) with follow up for 5 years until January 2024. Patients were identified from the database and categorized based on pre-procedural TIMI flow in the culprit vessel. A propensity score was used to pair TIMI 0-1 patients with a matched cohort of TIMI 2-3 patients. The primary outcome was 5-year all-cause mortality. Results: A total of 775 patients with TIMI 0-1 flow were matched with 750 patients who had TIMI 2-3 flow. Patients with TIMI 0-1 flow were more likely to have transient ST elevation (24% vs. 18%, p < 0.001) or Q waves (4% vs. 1%, p < 0.001) compared with patients who had TIMI 2-3 flow. They were also more likely to have moderately to severely impaired left ventricular systolic function compared with patients with TIMI 2-3 flow (21% vs. 16%, p = 0.01). In-hospital mortality (1.2% vs. 1.2%, p = NS), 1-year mortality (5% vs. 6.9%, p = NS), and 5-year mortality (16% vs. 18%, p = 0.34) were not significantly different between the two groups. The use of glycoprotein IIb/IIIa antagonists was associated with lower mortality, HR 0.64 (0.46 to 0.87). Conclusions: NSTEMI patients with occluded culprit vessels who underwent PCI had similar in-hospital and long-term outcomes to patients with patent culprit vessels. The use of glycoprotein IIb/IIIa inhibitors appears to be associated with lower mortality. Full article

Background: The rapid expansion of functional ready-to-drink (RTD) beverages—formulated with prebiotic fibers, botanical extracts, and reduced sugar—has outpaced systematic characterization of their small-molecule composition. Methods: We applied dual-mode untargeted high-resolution liquid chromatography–tandem mass spectrometry (LC–MS/MS), integrating hydrophilic interaction (HILIC) and reversed-phase C18 separations, to profile five commercial RTD beverages spanning distinct formulation categories: Coca-Cola^®, Poppi^® Orange, OLIPOP^® Cream Soda, Pure Leaf^® Unsweetened Black Tea, and BeePop™ Peach + Orange Blossom Honey. Results: Across all products, 478 compounds were structurally annotated at Metabolomics Standards Initiative (MSI) Levels 1 and 2, of which 42 matched compounds with reported bioactivity in a curated literature-based reference database. Seventeen compounds—including the NAD+ precursor trigonelline and multiple B vitamins—were detected across all five products. The number and diversity of compounds with reported bioactivity varied substantially by product and correlated with botanical ingredient complexity. Conclusions: This work presents a qualitative molecular survey of the RTD beverage category using standardized, dual-mode untargeted metabolomics, providing a reference dataset for future targeted quantitation studies. Full article

Background and Objectives: The use of presbyopia-correcting intraocular lenses (IOLs) has become an integral part of modern cataract surgery. Trifocal IOLs are designed to provide functional vision at multiple distances but may be associated with dysphotopsia and reduced contrast sensitivity. In contrast, extended depth-of-focus (EDOF) IOLs offer a smoother defocus profile and fewer photic phenomena; however, they often provide insufficient uncorrected near visual acuity. To overcome the limitations of each design, a mix-and-match implantation strategy, involving implantation of a trifocal IOL in one eye and an EDOF IOL in the fellow eye, has been proposed. The objective of this systematic review was to evaluate whether mix-and-match implantation can maintain high visual acuity at near, intermediate, and distance ranges in the early postoperative period. Materials and Methods: A systematic literature search was conducted in five electronic databases, including PubMed, Scopus, Web of Science, Google Scholar, and ScienceDirect, following PRISMA guidelines. Studies reporting outcomes of mix-and-match implantation with a trifocal IOL in one eye and an EDOF IOL in the fellow eye were included. Only studies presenting binocular uncorrected visual acuity (UCVA) at a distance, intermediate, and near ranges, expressed in logMAR units, were considered. Visual outcomes assessed at approximately 3 months postoperatively were extracted. Results: Five studies involving 225 patients were included. The pooled mean logMAR UDVA at 3 months was 0.05 (95% CI: 0.03–0.07), with substantial heterogeneity (I² = 80.1%). The pooled mean logMAR UNVA was 0.09 (95% CI: 0.05–0.14), with high heterogeneity (I² = 87.9%). For intermediate vision, the pooled mean logMAR UIVA was 0.03 (95% CI: −0.00 to 0.06), with moderate heterogeneity (I² = 72.5%). Meta-regression analyses did not show statistically significant associations between publication year and visual outcomes for UDVA (p = 0.695), UNVA (p = 0.469), or UIVA (p = 0.099). Sensitivity analyses confirmed the robustness of the pooled estimates. Conclusions: Mix-and-match implantation of a trifocal IOL in one eye and an EDOF IOL in the fellow eye provides favorable early binocular visual acuity across distance, intermediate, and near ranges. However, substantial heterogeneity across studies and very low certainty of evidence warrant cautious interpretation of these findings. Full article

Globalization and international trade have increased the importance of customs authorities in ensuring national security. However, regulatory differences regarding substances such as cannabis derivatives, the emergence of new psychoactive substances (NPSs), and the limitations of detection technology challenge customs in identifying suspicious cross-border goods. Traditional attribute extraction methods struggle with professional terminology and cross-sentence reasoning, making it difficult to regulate unknown or emerging substances. To address this, we propose a generative question answering (QA) framework based on inverse reinforcement learning (IRL) that converts attribute extraction into natural language QA tasks. Our approach, CAESAR (Chemical-Attribute Extraction with Sub-rewArd Reinforcement), uses a customs database to match known profiles and cross-references extracted attributes with benchmarks to enhance detection. It integrates the BioBART model with multi-objective reward optimization, using QA templates to capture implicit attributes. IRL automates the learning of reward weights from expert annotations. Experiments show that CAESAR achieves a competitive F1 score of 77.82 on explicit attributes and obtains the highest BLEU score and the lowest perplexity among the compared generative methods. For implicit attributes, ROUGE-L and BLEU scores are 43.08 and 44.46, respectively, with a perplexity of 11.3. These results are obtained in an open-ended generative QA setting rather than a closed-set classification setting, indicating that the proposed framework can provide practically useful attribute-level evidence for customs-oriented risk pre-screening and expert-assisted prioritization. This study offers an efficient solution for mining implicit knowledge in chemical texts and provides insights into multi-objective generative tasks. Full article

Methanolic bee pollen extracts from Xyris spp. and Mimosa spp. were evaluated for proximate composition, extraction yield, total phenolic content (TPC), total flavonoid content (TFC), antioxidant activity, erythrocyte oxidative hemolysis protection, HRBC membrane stabilization, and LC-QToF-MS-based phytochemical annotation. Mimosa spp. pollen showed higher crude protein content than Xyris spp. pollen (29.54% vs. 18.38%, dry basis), whereas Xyris spp. pollen showed higher crude fat and nitrogen-free extract. The methanolic extraction yield was higher for Xyris spp. than Mimosa spp. (44.26% vs. 34.63%). Mimosa spp. extract exhibited higher TPC (17.07 ± 0.19 mg GAE/g dry pollen) and TFC (8.89 ± 0.59 mg QE/g dry pollen) than Xyris spp. extract, which contained 10.39 ± 0.27 mg GAE/g dry pollen and 6.94 ± 0.22 mg QE/g dry pollen, respectively. Mimosa spp. also showed lower DPPH and ABTS IC₅₀ values and higher FRAP activity. LC-QToF-MS results were reported as putatively annotated compounds based on accurate mass and database matching. These findings suggest that botanical origin influences the chemical composition and in vitro bioactivity of bee pollen; however, further targeted compound confirmation, toxicity assessment, and in vivo studies are required. Full article

Similar to a web search engine, we have developed a computer-based acoustic search engine tailored for the critical scenario of high-speed aircraft ground explosion monitoring, addressing the long-standing challenge of real-time localization for such high-impact events. Unlike conventional acoustic source localization techniques, our method uniquely resolves the separation and localization of multiple aliasing events, which are prevalent in high-speed aircraft explosion scenarios due to complex shock wave propagation and overlapping signatures. We first calculate the waveforms of all possible acoustic sources over 2D grids. Then, a dimensionality reduction method and fast search technology are applied to the database. Once a high-speed aircraft ground explosion occurs, the real-time system returns detection feedback by matching real-time data with the pre-established search database. Different from other artificial intelligence (AI)-based approaches, the acoustic search engine can handle multiple aliased acoustic events in real time and does not require any prior information or input parameters—a key advantage for emergency response to high-speed aircraft explosions where predefined parameters are often unavailable. Both synthetic tests and field data applications (using actual acoustic records from high-speed aircraft ground explosion experiments) demonstrate the method’s credibility in detecting and localizing multiple acoustic sources. Full article

During the pre-Omicron phases of the COVID-19 pandemic, patients with hematological neoplasms were characterized by very high morbidity and mortality rates. Remdesivir, a viral RNA-polymerase inhibitor, interferes with key SARS-CoV-2 enzymes, preventing the virus from multiplying. The use of convalescent plasma (CP) in treating patients with COVID-19 has been shown to be beneficial in patients with an impaired humoral response to infection, including most of those on active treatment for hematologic malignancies. This retrospective, non-interventional study was performed using the Croatian Cooperative Group for Hematological Diseases database of patients with hematological malignancies infected with SARS-CoV-2. Patients treated with remdesivir and/or CP were matched to those untreated according to age, disease type, and antineoplastic therapy. We identified 119 patients treated with remdesivir and/or CP fulfilling entry criteria and matched 116 according to our established criteria to one of the 374 untreated patients. Treatment significantly reduced COVID-19 mortality. The beneficial effect of antiviral therapy was limited to those who started antiviral treatment within 7 days of the onset of symptoms. Due to the exclusive enrolment of hematological patients with COVID-19, our study provides unique insights into the benefits of early application of both antiviral and CP therapy. It emphasizes the need for early administration before the infection has transformed into the hyperinflammatory phase. Full article

Background: The rapid emergence of immune-evasive SARS-CoV-2 variants necessitates the identification of accessible, low-cost prophylactic strategies. While drug repurposing offers a time-efficient alternative to novel drug development, clinical evidence for existing medications in the general population remains limited. The PharmLines Initiative provided us with unique data linkage for this study to assess the associations between 42 candidate drugs and COVID-19 infection. Potential effect modification by dominant SARS-CoV-2 strain and COVID-19 vaccination status was addressed. Methods: We conducted a test-negative case–control study using data from the Lifelines cohort and University of Groningen IADB.nl dispensing database. Cases were adults with self-reported reverse transcription polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 and controls had only negative results. Cases and controls were matched in age, sex, and testing date. The 42 candidate drugs were identified through a systematic review of prior publications. The primary outcome was SARS-CoV-2 infection. We applied multivariable conditional logistic regression to estimate the associations, with subgroup analyses for variant and vaccination effects. Significance levels were corrected for multiple testing. Results: From November 2020 to October 2022, we included 2019 test-positive cases and 4089 matched test-negative controls with a mean age of 57 years and 67% female. After adjustments for confounders, none of the studied drugs were associated with SARS-CoV-2 infection. When stratified by SARS-CoV-2 variants, chronic use of calcium channel blockers (adjusted odds ratio 2.13; 95% CI 1.45–3.13), diuretics (2.23; 95% CI 1.50–3.32), and metformin (4.31; 95% CI 1.91–9.69) were associated with increased risks of original strain SARS-CoV-2 infection. No significant associations were found in the vaccination status subgroup analysis. Conclusions: Despite limited statistical power for some drugs, none of the studied drugs showed protective associations against SARS-CoV-2 infection. Antihypertensives and metformin were associated with increased risk. These findings do not support the off-label use of these drugs as COVID-19 prophylaxis in the general population. Full article

Background/Objectives: Aged garlic extract (AGE), produced by aging raw garlic in an aqueous ethanol solution for over 10 months, exhibits multiple pharmacological activities, including antioxidant and anti-inflammatory effects. However, because AGE has a complex composition and many constituents remain insufficiently characterized, the chemical basis underlying its broad activities is not fully understood. This study aimed to investigate these previously overlooked compounds in AGE to better understand its chemical complexity. Methods: AGE was fractionated using bioactivity assays to select target fractions for detailed chemical analysis. Metabolomics profiling was performed using liquid chromatography-mass spectrometry (LC-MS). Compounds were tentatively identified through database matching, fragmentation pattern analysis, and comparison with authentic standards. Results: Thirteen compounds not previously reported in AGE were tentatively identified. Citric acid was present at high levels. Citrulline and galacturonic acid were detected in AGE but not in raw garlic, suggesting that they are formed during the aging process. Trigonelline was detected and tentatively identified in the AGE sample used in this study. The remaining compounds included choline, 5-oxoproline, malic acid, gluconic acid, adenine, succinic acid, mucic acid, pipecolinic acid, and caffeic acid. These compounds may contribute to the diverse biological activities of AGE. Conclusions: These findings expand the chemical characterization of AGE and provide a foundation for understanding its broad pharmacological activities. They may also support future studies on functional food development and the health benefits of AGE. Full article