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1.
Proc Natl Acad Sci U S A ; 121(30): e2405160121, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38976765

ABSTRACT

Due to the scarcity of rock samples, the Hadean Era predating 4 billion years ago (Ga) poses challenges in understanding geological processes like subaerial weathering and plate tectonics that are critical for the evolution of life. The Jack Hills zircon from Western Australia, the primary Hadean samples available, offer valuable insights into magma sources and tectonic genesis through trace element signatures. However, a consensus on these signatures has not been reached. To address this, we developed a machine learning classifier capable of deciphering the geochemical fingerprints of zircon. This allowed us to identify the oldest detrital zircon originating from sedimentary-derived "S-type" granites. Our results indicate the presence of S-type granites as early as 4.24 Ga, persisting throughout the Hadean into the Archean. Examining global detrital zircon across Earth's history reveals consistent supercontinent-like cycles from the present back to the Hadean. These findings suggest that a significant amount of Hadean continental crust was exposed, weathered into sediments, and incorporated into the magma sources of Jack Hills zircon. Only the early operation of both subaerial weathering and plate subduction can account for the prevalence of S-type granites we observe. Additionally, the periodic evolution of S-type granite proportions implies that subduction-driven tectonic cycles were active during the Hadean, at least around 4.2 Ga. The evidence thus points toward an early Earth resembling the modern Earth in terms of active tectonics and habitable surface conditions. This suggests the potential for life to originate in environments like warm ponds rather than extreme hydrothermal settings.

2.
J Environ Manage ; 366: 121587, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38981272

ABSTRACT

Nutrient loads in lakes are spatially heterogeneous, but current spatial analysis method are mainly zonal, making them subjective and uncertain. This study proposes a high-resolution model for assessing spatial differences in nutrient loads based on the lattice Boltzmann method. The model was applied to Dongping Lake in China. Firstly, the contribution rates of four influencing factors, including water transfer, inflow, wind, and internal load, were calculated at different locations in the lake. Then, their proportionate contributions during different intervals to the whole lake area were calculated. Finally, the cumulative load could be calculated for any location within the lake. The validation showed that the model simulated hydrodynamics and water quality well, with relative errors between the simulated and measured water quality data smaller than 0.45. Wind increased the nutrient loads in most parts of the lake. The loads tended to accumulate in the east central area where high-frequency circulation patterns were present. Overall, the proposed water quality model based on the lattice Boltzmann method was able to simulate seven indexes. Therefore, this model represents a useful tool for thoroughly assessing nutrient load distributions in large shallow lakes and could help refine lake restoration management.

3.
BMC Infect Dis ; 24(1): 676, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971751

ABSTRACT

BACKGROUND: Recent studies on the association between Helicobacter pylori (H. pylori) infection and obesity have reported conflicting results. Therefore, the purpose of our study was to investigate the association of obesity, abdominal obesity, and metabolic obesity phenotypes with H. pylori infection. METHODS: A cross-sectional study of 1568 participants aged 20 to 85 was conducted using the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000. Logistic regression models were employed to evaluate the association of general obesity as defined by body mass index (BMI), abdominal obesity as defined by waist circumference (WC) and waist-height ratio (WHtR), and metabolic obesity phenotypes with H. pylori seropositivity. Subgroup analyses stratified by age were conducted to explore age-specific differences in this association. RESULTS: After grouping individuals according to their WHtR, the prevalence rate of WHtR ≥ 0.5 in H. pylori-seropositive participants was significantly higher than that in H. pylori-seronegative participants (79.75 vs. 68.39, P < 0.001). The prevalence of H. pylori seropositivity in non-abdominal obesity and abdominal obesity defined by WHtR was 24.97% and 31.80%, respectively (P < 0.001). In the subgroup analysis, the adjusted association between abdominal obesity, as defined by the WHtR, and H. pylori seropositivity was significant in subjects aged < 50 years (OR = 2.23; 95% CI, 1.24-4.01; P = 0.01) but not in subjects aged ≥ 50 years (OR = 0.84; 95% CI, 0.35-1.99; P = 0.66). Subjects older than 50 years old had an OR (95% CI) for metabolically healthy obesity of 0.04 (0.01-0.35) compared with the control group. H. pylori seropositivity was consistently not associated with obesity as defined by BMI. CONCLUSIONS: Abdominal obesity, as defined by the WHtR, was associated with H. pylori infection in subjects aged ≤ 50 years.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Nutrition Surveys , Obesity, Abdominal , Obesity , Humans , Helicobacter Infections/epidemiology , Helicobacter Infections/microbiology , Helicobacter Infections/complications , Middle Aged , Adult , Male , Female , Cross-Sectional Studies , Aged , Obesity/microbiology , Obesity/epidemiology , Aged, 80 and over , Young Adult , Obesity, Abdominal/epidemiology , Obesity, Abdominal/microbiology , Prevalence , Phenotype , Body Mass Index
4.
New Phytol ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992951

ABSTRACT

Drought, especially terminal drought, severely limits wheat growth and yield. Understanding the complex mechanisms behind the drought response in wheat is essential for developing drought-resistant varieties. This study aimed to dissect the genetic architecture and high-yielding wheat ideotypes under terminal drought. An automated high-throughput phenotyping platform was used to examine 28 392 image-based digital traits (i-traits) under different drought conditions during the flowering stage of a natural wheat population. Of the i-traits examined, 17 073 were identified as drought-related. A genome-wide association study (GWAS) identified 5320 drought-related significant single-nucleotide polymorphisms (SNPs) and 27 SNP clusters. A notable hotspot region controlling wheat drought tolerance was discovered, in which TaPP2C6 was shown to be an important negative regulator of the drought response. The tapp2c6 knockout lines exhibited enhanced drought resistance without a yield penalty. A haplotype analysis revealed a favored allele of TaPP2C6 that was significantly correlated with drought resistance, affirming its potential value in wheat breeding programs. We developed an advanced prediction model for wheat yield and drought resistance using 24 i-traits analyzed by machine learning. In summary, this study provides comprehensive insights into the high-yielding ideotype and an approach for the rapid breeding of drought-resistant wheat.

5.
Nat Prod Res ; : 1-7, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992980

ABSTRACT

Two new aromatic compounds, namely gastupdin A (1), and gastupdin B (2), together with three known compounds, arundin(3), phomosines B (4) and monocillin IV (5), were isolated from the aerial parts of Gastrodia elata Blume. The structures of the new compounds were confirmed through spectral analyses including NMR, HR-ESI-MS, ECD, UV, and IR. All isolated compounds were evaluated for their neuroprotective effects against 6-hydroxydopamine-induced cell death in Human Neuroblastoma Cells, with curcumin as the positive control, however, the activity of all compounds was weaker than the positive control, showing no significant activity.

6.
Aesthetic Plast Surg ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995348

ABSTRACT

BACKGROUND: In Asia, the demand for cosmetic facial treatments has surged due to technological advancements, increased social acceptability, and affordability. Poly-L-lactic acid (PLLA) fillers, known for their biocompatibility and biodegradability, have emerged as a popular choice for facial contouring, yet studies specifically addressing their use in Asian populations are scarce. METHODS: This retrospective study examined 30 Chinese patients who underwent facial contouring with PLLA fillers, focusing on product composition, injection techniques, and safety measures. A comprehensive clinical evaluation was performed, including the Global Aesthetic Improvement Scale (GAIS) and Global Impression of Change Scale (GICS) for effectiveness and patient satisfaction, respectively. RESULTS: No significant difference in GAIS scores was observed between injectors and blinded evaluators over a 12-month period, indicating consistent effectiveness. Patient satisfaction remained high, with GICS scores reflecting positive outcomes. The safety profile was favorable, with no serious adverse events reported. The study highlighted the importance of anatomical knowledge to avoid complications, particularly in areas prone to blindness. CONCLUSIONS: PLLA fillers offer a safe, effective option for facial contour correction in the Asian population, achieving high patient satisfaction and maintaining results over time. The study underscores the need for tailored approaches in cosmetic procedures for Asians, considering their unique facial structures and aesthetic goals. Further research with larger, multicenter cohorts is recommended to validate these findings and explore long-term effects. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

7.
Biomed Pharmacother ; 177: 117129, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39018874

ABSTRACT

Atopic dermatitis (AD) is a chronic inflammatory skin condition with complex causes involving immune factors. The presence of essential trace elements that support immune system function can influence the development of this condition. This study investigated how serum trace elements impact the pathogenesis of atopic dermatitis. Upon analyzing serum microelements in AD patients and control subjects, it was observed that patients with AD had notably lower zinc levels. Genomic analysis of AD skin revealed distinct gene expression patterns, specifically the increased expression of CXCL10 in the epidermis. The heightened levels of CXCL10 in AD skin lesions were found to correlate with reduced serum zinc levels. Treatment with zinc gluconate showed reduced chemotactic response and CXCL10 release, suggesting its potential to regulate CXCL10 expression of keratinocytes in AD. The mechanism behind this involved the downregulation of STAT phosphorylation through activating PPARα. In the AD-like dermatitis mouse model, zinc gluconate therapy decreased serum IgE levels, alleviated skin lesion severity, reduced skin thickness, and lowered CXCL10 expression, demonstrating its efficacy in managing AD-like skin conditions. These findings indicate that zinc gluconate can reduce inflammation in keratinocytes by activating PPARα, inhibiting STAT signaling, and decreasing CXCL10 release, thus highlighting its potential as a therapeutic target for AD.

9.
Nature ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39020177

ABSTRACT

Measurements of gene expression or signal transduction activity are conventionally performed using methods that require either the destruction or live imaging of a biological sample within the timeframe of interest. Here we demonstrate an alternative paradigm in which such biological activities are stably recorded to the genome. Enhancer-driven genomic recording of transcriptional activity in multiplex (ENGRAM) is based on the signal-dependent production of prime editing guide RNAs that mediate the insertion of signal-specific barcodes (symbols) into a genomically encoded recording unit. We show how this strategy can be used for multiplex recording of the cell-type-specific activities of dozens to hundreds of cis-regulatory elements with high fidelity, sensitivity and reproducibility. Leveraging signal transduction pathway-responsive cis-regulatory elements, we also demonstrate time- and concentration-dependent genomic recording of WNT, NF-κB and Tet-On activities. By coupling ENGRAM to sequential genome editing via DNA Typewriter1, we stably record information about the temporal dynamics of two orthogonal signalling pathways to genomic DNA. Finally we apply ENGRAM to integratively record the transient activity of nearly 100 transcription factor consensus motifs across daily windows spanning the differentiation of mouse embryonic stem cells into gastruloids, an in vitro model of early mammalian development. Although these are proof-of-concept experiments and much work remains to fully realize the possibilities, the symbolic recording of biological signals or states within cells, to the genome and over time, has broad potential to complement contemporary paradigms for how we make measurements in biological systems.

10.
Sci Total Environ ; 947: 174593, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38997038

ABSTRACT

Artificial reefs (ARs) are widespread globally and play a positive role in enhancing fish communities and restoring habitat. However, the effect of ARs on phytoplankton, which are fundamental to the marine food chain, remains inconclusive. Conducting a literature review and meta-analysis, this study investigates how ARs influence phytoplankton community dynamics by comparing the biomass, density, and diversity of phytoplankton between ARs and natural water bodies across varying deployment durations, constituent materials, and climatic zones. The study findings suggest that, overall, ARs enhance the biomass, density, and diversity of phytoplankton communities, with no significant differences observed compared to natural water bodies. The enhancement effect of ARs on phytoplankton communities becomes progressively more pronounced with increasing deployment time, with the overall status of phytoplankton communities being optimal when artificial reefs are deployed for 5 years or longer. Concrete and stone ARs can significantly enhance the biomass and diversity of phytoplankton, respectively. The effect of ARs on phytoplankton diversity is unrelated to climatic zones. However, deploying ARs in temperate waters significantly enhances phytoplankton biomass, while in tropical waters, it significantly reduces phytoplankton density. The research findings provide practical implications for the formulation of artificial reef construction strategies tailored to the characteristics of different aquatic ecosystems, emphasizing the need for long-term deployment and appropriate material selection. This study offers a theoretical basis for optimizing AR design and deployment to achieve maximum ecological benefits.

11.
Cancer Lett ; 598: 217120, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39002691

ABSTRACT

Recent research has underscored the significance of circular RNAs (circRNAs) in various cancers, including neuroblastoma (NB). Specifically, circ-SHPRH, a unique circRNA, has been revealed to inhibit tumor growth by sequestering miRNAs or producing the SHPRH-146aa protein. To explore circ-SHPRH's involvement in NB and its potential application in gene therapy, this study examined circ-SHPRH expression in 94 NB tissues and cell lines (SK-N-BE(2), SH-SY5Y) using real-time PCR and fluorescence in situ hybridization (FISH). Functional assays encompassing both overexpression and knockdown experiments in NB cell lines, as well as in vivo investigations, were conducted. RNA-seq analysis revealed a correlation between circ-SHPRH and the pathway of P21 (CDKN1A), a pivotal cell cycle regulator. Validation through PCR and other techniques confirmed that circ-SHPRH upregulated P21 expression. Furthermore, the regulatory role of circ-SHPRH in the P21-CDK pathway was corroborated through SHPRH-146aa expression analysis. Notably, adenovirus-mediated circ-SHPRH overexpression effectively curbed NB tumor growth in NSG mice, while combining circ-SHPRH with everolimus exhibited potential for NB treatment. This study elucidates the remarkable significance of circ-SHPRH in NB and its prospective utility in gene therapy, thereby paving the way for innovative therapeutic approaches.

12.
Chem Commun (Camb) ; 60(58): 7447-7450, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38946686

ABSTRACT

I+ hydrolysis, sluggish iodine redox kinetics and the instability of Zn anodes are the primary challenges for aqueous four-electron zinc-iodine batteries (4eZIBs). Herein, the OTf- anion chemistry in aqueous electrolyte is essential for developing advanced 4eZIBs. It is elucidated that OTf- anions establish weak hydrogen bonds (H bonds) with water to stabilize I+ species while optimizing a water-lean Zn2+ coordination structure to mitigate Zn dendrites and corrosion. Moreover, the interaction of the OTf- anions with the iodine species results in an increased equilibrium average intermolecular bond length of the iodine species, facilitating the 4e redox kinetics of iodine with improved reversibility.

13.
Nat Commun ; 15(1): 5896, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39003311

ABSTRACT

Outstanding overall mechanical properties are essential for the successful utilization of hydrogels in advanced applications such as human-machine interfaces and soft robotics. However, conventional hydrogels suffer from fracture toughness-stiffness conflict and fatigue threshold-stiffness conflict, limiting their applicability. Simultaneously enhancing the fracture toughness, fatigue threshold, and stiffness of hydrogels, especially within a homogeneous single network structure, has proven to be a formidable challenge. In this work, we overcome this challenge through the design of a loosely cross-linked hydrogel with slight dehydration. Experimental results reveal that the slightly-dehydrated, loosely cross-linked polyacrylamide hydrogel, with an original/current water content of 87%/70%, exhibits improved mechanical properties, which is primarily attributed to the synergy between the long-chain structure and the dense dehydration-induced entanglements. Importantly, the creation of these microstructures does not require intricate design or processing. This simple approach holds significant potential for hydrogel applications where excellent anti-fracture and fatigue-resistant properties are necessary.

14.
Front Public Health ; 12: 1377135, 2024.
Article in English | MEDLINE | ID: mdl-38947348

ABSTRACT

Objective: This study aimed to determine the risk factors associated with fluctuations in nucleic acid CT values in patients infected with the Omicron variant during an outbreak at a hospital in Changchun city. Methods: A retrospective analysis was conducted on general information, medical history, vaccination history, and laboratory test data of COVID-19 patients infected with the Omicron variant and admitted to the hospital in Changchun from March 2022 to April 2022. The study aimed to explore the factors influencing nucleic acid CT value fluctuations in COVID-19 patients infected with the Omicron variant in Changchun city. Results: Fluctuations in nucleic acid CT values were significantly correlated with occupation composition (p = 0.030), hospital stay duration (p = 0.000), heart rate (p = 0.026), creatinine (p = 0.011), platelet count (p = 0.000), glutamic-pyruvic transaminase (p = 0.045), and glutamic oxaloacetic transaminase (p = 0.017). Binary logistic regression analysis revealed significant correlations between hospital stay duration (p = 0.000), platelet count (p = 0.019), heart rate (p = 0.036), and nucleic acid CT value fluctuations (p < 0.05), indicating that they were independent risk factors. Red blood cell count was identified as a factor influencing nucleic acid CT value fluctuations in Group A patients. Occupation composition, direct bilirubin, and platelet count were identified as factors influencing nucleic acid CT value fluctuations in Group B patients. Further binary logistic regression analysis indicated that occupational composition and direct bilirubin are significant independent factors for nucleic acid CT value fluctuations in Group B patients, positively correlated with occupational risk and negatively correlated with direct bilirubin. Conclusion: Therefore, enhancing patients' immunity, increasing physical exercise to improve myocardial oxygen consumption, reducing the length of hospital stays, and closely monitoring liver function at the onset of hospitalization to prevent liver function abnormalities are effective measures to control fluctuations in nucleic acid CT values.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/diagnostic imaging , Retrospective Studies , Male , Female , Middle Aged , China/epidemiology , Adult , Risk Factors , Aged
15.
Semin Ophthalmol ; : 1-12, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949222

ABSTRACT

OBJECTIVE: To dynamically track the publications on central serous chorioretinopathy (CSC) and depict the research status and hot spots to guide future research. METHODS: Gather all papers published in this area between 2004 and 2024 in the WOSCC databases comprehensively, assess their trends, and characterize the contributions of various nations, authors, institutions, and journals. In addition, VOSviewer, CiteSpace, and R software are used to obtain the most popular keywords for the topic. RESULTS: A total of 2,203 papers were published across 1,863 institutions in 59 countries. Among these, 6,907 authors contributed to publications in 300 journals and generated a total of 35,638 citations. The number of publications continues to grow steadily. Notably, Jay Chhablani's team/Lab stands out as the leading contributor with ownership of 84 publications. Through keyword network analysis and clustering techniques, risk factor-related clustering, imaging-related clustering, pathogenesis-related clustering, and treatment-related clustering were identified. Furthermore, keyword analysis has unveiled emerging frontier areas including pachychoroid disease, choroidal vasculature abnormalities, PDT therapy, and optical coherence tomography that have garnered increasing interest. CONCLUSION: This study presents a comprehensive review of central serous retinopathy research conducted in the past two decades, highlighting key trends and exploring emerging research frontiers within this field. As such, it provides valuable references and suggestions for researchers engaged in studying this topic.

16.
Phys Rev Lett ; 132(24): 246501, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38949356

ABSTRACT

Electrons residing in a flat-band system can play a vital role in triggering spectacular phenomenology due to relatively large interactions and spontaneous breaking of different degeneracies. In this work, we demonstrate chirally twisted triple bilayer graphene, a new moiré structure formed by three pieces of helically stacked Bernal bilayer graphene, as a highly tunable flat-band system. In addition to the correlated insulators showing at integer moiré fillings, commonly attributed to interaction induced symmetry broken isospin flavors in graphene, we observe abundant insulating states at half-integer moiré fillings, suggesting a longer-range interaction and the formation of charge density wave insulators which spontaneously break the moiré translation symmetry. With weak out-of-plane magnetic field applied, as observed half-integer filling states are enhanced and more quarter-integer filling states appear, pointing toward further quadrupling moiré unit cells. The insulating states at fractional fillings combined with Hartree-Fock calculations demonstrate the observation of a new type of correlated charge density wave insulators in graphene and points to a new accessible twist manner engineering correlated moiré electronics.

17.
Materials (Basel) ; 17(13)2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38998436

ABSTRACT

The catalytic capabilities of metals in degrading azo dyes have garnered extensive interest; however, selecting highly efficient metals remains a significant challenge. We have developed a Zn-Ca-based metallic glass composite which shows outstanding degradation efficiency for Direct Blue 6. This alloy comprises a Zn2Ca crystalline phase and an amorphous matrix, allowing for the degradation of azo dyes within minutes in a wide temperature range of 0-60 °C. Kinetic calculations reveal an exceptionally low activation energy of 8.99 kJ/mol. The rapid degradation is attributed to the active element Ca and the unique amorphous structure of the matrix, which not only facilitates abundant redox conditions but also minimizes the hydrolysis of the active element. The newly developed metallic glass composite exhibits a notably higher azo dye degradation rate compared to those of general metallic glasses, offering a new avenue for the rapid degradation of azo dyes. This paper holds significant importance for the development of novel azo dye wastewater treatment agents.

18.
Nanomaterials (Basel) ; 14(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38998723

ABSTRACT

This study focuses on improving human thermal comfort in a high-temperature outdoor environment using vests with a radiative cooling coating. The effects of coating thickness on the radiative cooling performance were first evaluated, and an optimal thickness of 160 µm was achieved. Then, six subjects were recruited to evaluate the thermal comfort in two scenarios: wearing the vest with radiative cooling coatings, and wearing the standard vest. Compared with the standard vest, the coated vest decreases the maximum temperature at the vest inner surface and the outer surface by 5.54 °C and 4.37 °C, respectively. The results show that thermal comfort is improved by wearing radiative cooling vests. With an increase of wet bulb globe temperature (WBGT), the improving effects tend to decline. A significant improvement in human thermal comfort is observed at a WBGT of 26 °C. Specifically, the percentage of thermal sensation vote (TSV) wearing the cooling vest in the range of 0 to 1 increases from 29.2% to 66.7% compared with that of the untreated vest. At the same time, the average value of thermal comfort vote (TCV) increases from -0.5 to 0.2.

19.
Cancer Invest ; 42(6): 527-537, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38965994

ABSTRACT

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Rectal Neoplasms/immunology , Male , Female , Middle Aged , Neoadjuvant Therapy/methods , Aged , Chemoembolization, Therapeutic/methods , Prognosis , Treatment Outcome , Adult , Chemoradiotherapy/methods
20.
Cancer Cytopathol ; 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39003588

ABSTRACT

BACKGROUND: This study evaluated the diagnostic effectiveness of the AIxURO platform, an artificial intelligence-based tool, to support urine cytology for bladder cancer management, which typically requires experienced cytopathologists and substantial diagnosis time. METHODS: One cytopathologist and two cytotechnologists reviewed 116 urine cytology slides and corresponding whole-slide images (WSIs) from urology patients. They used three diagnostic modalities: microscopy, WSI review, and AIxURO, per The Paris System for Reporting Urinary Cytology (TPS) criteria. Performance metrics, including TPS-guided and binary diagnosis, inter- and intraobserver agreement, and screening time, were compared across all methods and reviewers. RESULTS: AIxURO improved diagnostic accuracy by increasing sensitivity (from 25.0%-30.6% to 63.9%), positive predictive value (PPV; from 21.6%-24.3% to 31.1%), and negative predictive value (NPV; from 91.3%-91.6% to 95.3%) for atypical urothelial cell (AUC) cases. For suspicious for high-grade urothelial carcinoma (SHGUC) cases, it improved sensitivity (from 15.2%-27.3% to 33.3%), PPV (from 31.3%-47.4% to 61.1%), and NPV (from 91.6%-92.7% to 93.3%). Binary diagnoses exhibited an improvement in sensitivity (from 77.8%-82.2% to 90.0%) and NPV (from 91.7%-93.4% to 95.8%). Interobserver agreement across all methods showed moderate consistency (κ = 0.57-0.61), with the cytopathologist demonstrating higher intraobserver agreement than the two cytotechnologists across the methods (κ = 0.75-0.88). AIxURO significantly reduced screening time by 52.3%-83.2% from microscopy and 43.6%-86.7% from WSI review across all reviewers. Screening-positive (AUC+) cases required more time than negative cases across all methods and reviewers. CONCLUSIONS: AIxURO demonstrates the potential to improve both sensitivity and efficiency in bladder cancer diagnostics via urine cytology. Its integration into the cytopathological screening workflow could markedly decrease screening times, which would improve overall diagnostic processes.

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