Study on the Mechanism of Nd:YAG Laser-Assisted Therapy on the Changes of Subgingival Flora in Periodontitis.

PURPOSE: This study evaluated the therapeutic efficacy of combining Neodymium-doped Yttrium Aluminum Garnet (Nd:YAG) laser with subgingival curettage and root planing (SRP) in generalised stage III/grade C periodontitis patients and its effects on cytokine dynamics and microbial community. MATERIALS AND METHODS: Fifteen patients diagnosed with stage III/grade C periodontitis were included in the cohort. The right and left sides of the mouth were randomly assigned either the conventional SRP (control) group or the SRP supplemented with Nd:YAG laser group (experimental group, 160 mJ, 4 W) in a split-mouth design. Clinical periodontal indices were recorded at baseline and at the 6-week follow-up post-treatment. ELISA was utilised to measure IL-1ß and TNF-α levels in gingival crevicular fluid. The subgingival microbiota's composition and variations were characterised using 16S rDNA amplicon sequencing, while quantitative real-time polymerase chain reaction (qRT-PCR) was employed to analyse the changes in the red-complex bacteria in subgingival plaque. RESULTS: The SRP+Nd group exhibited a statistically significant reduction in record probing depth (PD) and bleeding on probing (BOP) compared to the SRP group after treatment (p0.05). The SRP+Nd group showed a markedly lower IL-1ß level than the SRP group (p0.05). Furthermore, there was no statistically significant difference in the dominant subgingival microbiota composition and level of the red-complex bacteria between the two groups (p>0.05). CONCLUSION: The adjunctive use of Nd:YAG laser with SRP demonstrates promising short-term therapeutic benefits for patients with extensive stage III/grade C periodontitis. Both SRP as a standalone treatment and its combination with Nd:YAG laser effectively facilitate a transition in the dominant bacterial community from periodontitis-associated to periodontal health-associated microbiota.

Pentacam and Corvis ST findings in myopic Chinese patients with different corneal diameters in Singapore.

PURPOSE: To study the effect of corneal white-to-white diameter on Pentacam Scheimpflug cornea tomography and Corvis ST corneal visualization Scheimpflug technology parameters in myopic eyes. METHODS: In this retrospective cross-sectional study, 190 eyes of 190 Chinese myopic patients (spherical equivalent range: -1.25 D to -11.00 D) assessed for refractive surgery using Pentacam and Corvis ST devices were included. Patients were divided into groups based on corneal diameter: group A <12 mm, and group B ≥12 mm. Age, gender, spherical equivalent, Pentacam variables, and Corvis ST variables were collected. Statistical analysis was performed using IBM SPSS Statistics (Version 28.0). RESULTS: There were 110 patients in group A and 80 patients in group B, with no statistically significant difference in age, gender, or spherical equivalence. For Pentacam data, group A had significantly higher Belin/Ambrosio Enhanced Ectasia Display (BAD-D) scores than group B (0.88 vs. 0.44) and pachymetric progression index (minimum, average, and maximum), and steeper front keratometric values, whereas group B had larger anterior chamber depth and maximum Ambrosio-relational thickness (ARTmax) (462.54 vs. 503.93). BAD-D indices, pachymetric progression indices, and front keratometric values had negative correlations with corneal diameter, whereas ARTmax and back keratometric values had positive correlations. For Corvis ST data, group A had a significantly higher corneal biomechanical index (CBI) (negatively correlated) while group B had a higher Ambrosio relational thickness to the horizontal profile (ARTh) (473.60 vs. 570.78) (positively correlated). CONCLUSION: Corneal diameter influences both Pentacam and Corvis ST parameters, with smaller corneal diameters having a higher BAD-D and a lower ARTmax and ARTh. In addition, this is the first study to report a correlation between posterior surface corneal power and corneal diameter. As refractive surgery evaluation relies on these parameters, taking corneal diameter into account would improve both sensitivity and specificity in pre-refractive surgery screening for ectasia/keratoconus.

Effects of bile acids on the growth, composition and metabolism of gut bacteria.

Bile acids (BAs) exert a profound influence on the body's pathophysiology by intricately shaping the composition of gut bacteria. However, the complex interplay between BAs and gut microbiota has impeded a systematic exploration of their impact on intestinal bacteria. Initially, we investigated the effects of 21 BAs on the growth of 65 gut bacterial strains in vitro. Subsequently, we examined the impact of BAs on the overall composition of intestinal bacteria, both in vivo and in vitro. The results unveiled distinct effects of various BAs on different intestinal strains and their diverse impacts on the composition of gut bacteria. Mechanistically, the inhibition of intestinal strains by BAs occurs through the accumulation of these acids within the strains. The intracellular accumulation of deoxycholic acid (DCA) significantly influenced the growth of intestinal bacteria by impacting ribosome transcription and amino-acid metabolism. The metabolomic analysis underscores the pronounced impact of DCA on amino-acid profiles in both in vivo and in vitro settings. This study not only elucidates the effects of BAs on a diverse range of bacterial strains and their role in shaping the gut microbiota but also reveals underlying mechanisms essential for understanding and maintaining a healthy gut microbiota.

Light-modulated van der Waals force microscopy.

Atomic force microscope generally works by manipulating the absolute magnitude of the van der Waals force between tip and specimen. This force is, however, less sensitive to atom species than to tip-sample separations, making compositional identification difficult, even under multi-modal strategies or other atomic force microscopy variations. Here, we report the phenomenon of a light-modulated tip-sample van der Waals force whose magnitude is found to be material specific, which can be employed to discriminate heterogeneous compositions of materials. We thus establish a near-field microscopic method, named light-modulated van der Waals force microscopy. Experiments discriminating heterogeneous crystalline phases or compositions in typical materials demonstrate a high compositional resolving capability, represented by a 20 dB signal-to-noise ratio on a MoTe2 film under the excitation of a 633 nm laser of 1.2 mW, alongside a sub-10 nm lateral spatial resolution, smaller than the tip size of 20 nm. The simplicity of the light modulation mechanism, minute excitation light power, broadband excitation wavelength, and diversity of the applicable materials imply broad applications of this method on material characterization, particularly on two-dimensional materials that are promising candidates for next-generation chips.

Accuracy and validation of a point-of-care blood glucose monitoring system for use in horses.

Abnormal blood glucose (BG) levels often seen in critically ill horses are significantly associated with adverse patient outcomes and increased mortality. Rapid and accurate BG monitoring is now considered an essential component of evidence-based equine practice and can provide critical information quickly for treatment. Although several point-of-care (POC) BG monitoring hand-held devices are commercially available for veterinary use, none contains a unique algorithm validated for use in horses. The AlphaTrak 3 (AT3) BG monitoring system is a first-of-its-kind device with an equine-specific algorithm that allows stall-side clinical decision making, and frequent monitoring at minimal cost. As such, AT3 is potentially a preferred alternative to more costly and time-consuming standard diagnostic reference laboratory methods. The objective of this study was to determine the accuracy of the AT3 device in measuring BG levels in equine whole blood samples in comparison to results obtained by the Beckman Coulter AU480 reference analyzer per ISO15197:2013 specifications. Accuracy of the AT3 equine algorithm were initially verified by testing equine blood samples with artificially adjusted blood glucose levels followed by its validation in a field study. Testing with artificially adjusted equine samples (n = 129) showed that 98.9% of glucose measurements ranging from 29 to 479 mg/dL fell within ISO accuracy threshold of ±15 mg/dL or ±15% of the average reference value. In addition, 100% of the AT3 measurements fell in consensus error grid (CEG) zone A, which indicates that test outcomes have a minimal likelihood of adverse clinical impact. In a follow-up field study involving 96 horses, 98.4% of AT3 measurements met the ISO accuracy threshold and 99.2% of AT3 measurements fell in CEG zone A. These results demonstrate that the AT3 glucometer has a high degree of accuracy in horses and is a dependable, convenient, and cost-effective device for accurately monitoring equine BG levels in farm or clinical settings.

Joint Beamforming Design and User Clustering Algorithm in NOMA-Assisted ISAC Systems.

To enhance the performance of non-orthogonal multiple access (NOMA)-assisted integrated sensing and communication (ISAC) systems in multi-user distributed scenarios, an improved Gaussian Mixture Model (GMM)-based user clustering algorithm is proposed. This algorithm is tailored for ISAC systems, significantly improving bandwidth reuse gains and reducing serial interference. First, using the Sum of Squared Errors (SSE), the algorithm reduces sensitivity to the initial cluster center locations, improving clustering accuracy. Then, direction weight factors are introduced based on the base station position and a penalty function involving users' Euclidean distances and sensing power. Modifications to the EM algorithm in calculating posterior probabilities and updating the covariance matrix help align user clusters with the characteristics of NOMAISAC systems. This improves users' interference resistance, lowers decoding difficulty, and optimizes the system's sensing capabilities. Finally, a fractional programming (FP) approach addresses the non-convex joint beamforming design problem, enhancing power and channel gains and achieving co-optimizing sensing and communication signals. The simulation results show that, under the improved GMM user clustering algorithm and FP optimization, the NOMA-ISAC system improves user spectral efficiency by 4.3% and base station beam intensity by 5.4% compared to traditional ISAC systems.

Feasibility of double nitrite supply through partial nitrification and partial denitrification driven by sludge fermentation.

Challenges in obtaining stable nitrite have impeded the use of anammox in municipal wastewater treatment. This study explored the feasibility of using sludge fermentation products as carbon source and selective nitrification inhibitor to supply nitrite via partial nitrification (PN) and partial denitrification (PD). PD was initiated within 15 days, achieving nitrite transformation rate of over 90 % with a C/N ratio of 3 and a reaction time of 0.75 h. The dominant genus, Romboutsia, increased in relative abundance from 4.1 to 35 %. Organic acids in sludge fermentation products, like acetate (200 mg/L) and propionate (400 mg/L), selectively suppressed nitrite-oxidizing bacteria (NOB) more than ammonia-oxidizing bacteria (AOB), leading to PN. Combining anaerobic exposure with sludge fermentation products addition achieved PN with over 80.0 % nitrite accumulation. AOB increased tenfold in the long term, significantly outpacing NOB growth. This strategy simplifies difficulty of anammox application and shows broad application potential in municipal wastewater treatment.

Hepatic ectopic pregnancy with hemorrhage secondary diaphragmatic adhesion: A case report.

BACKGROUND: Primary abdominal pregnancy is an extremely rare form of ectopic pregnancy. Ectopic pregnancies that occur in the liver and diaphragm are even rarer, limited case reports are available in the literature. CASE SUMMARY: A woman of childbearing age was transferred to the emergency department due to lumbar and abdominal pain radiating to the back toward the lower right. After a series of physical and auxiliary examinations, she was clinically diagnosed with hepatic ectopic pregnancy. Laparoscopic surgery was performed to remove the pregnancy tissue and achieve hemostasis. After a period of follow-up, the patient was successfully cured. CONCLUSION: Paying attention to the patient's signs and utilizing imaging examination methods can help avoid missed diagnoses of liver pregnancy.

Establishment of national standards of SARS-CoV-2 variants in Taiwan.

Objectives: In response to the pandemic, the Taiwan Food and Drug Administration (TFDA) established an initial SARS-CoV-2 RNA national standard based on the original Wuhan strain. However, with the depletion of the first national standard and continued mutation of the virus, the establishment of new national standards was imminent. Methods: Hence, new candidate national standards were established by heat-inactivation for 30 min for six representative strains of SARS-CoV-2, comprising the original strain and five variants with anticipated concentrations of 7.70 Log10 international units (IU)/mL each. To enhance the credibility of these national standards, the TFDA extended invitations to both domestic and international institutions to participate in a collaborative study. A total of eight participants contributed eleven datasets, incorporating two methods and targeting four distinct genes. Results: Based on these collective findings, the quantified viral RNA concentrations for each SARS-CoV-2 national standard strain are 7.69, 7.70, 7.69, 7.44, 7.52, and 7.29 Log10 IU/mL with Wuhan, alpha, beta, gamma, delta, and omicron strain, respectively. Conclusions: These newly established national standards will continue to be made available to the industry, serving as a fundamental reference for the development and quality control of nucleic acid in vitro diagnostic (IVD) reagents in Taiwan.

Predicting aeration time and nitrite accumulation rate variations for Partial Nitritation: A model incorporating nitrogen oxidation rate dynamics.

This study aimed to develop a two-step nitrification model to predict variations in aeration time and nitrite accumulation rate (NAR) under fluctuating operational conditions in mainstream partial nitritation (PN) processes. Lab-scale sequencing batch reactors (SBRs) were used to evaluate the ammonia oxidation rate (AOR) and nitrite oxidation rate (NOR) under different solids retention times (SRT) (10, 15, 20, 30, and 50 days) and total volumetric nitrogen loadings (TVNL) (20-60 mg N/L per cycle). A static model was developed to predict consistent AOR and NOR values in the steady state, whereas a dynamic model was established to capture the growth dynamics of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) under unsteady-state conditions. The static model accurately predicted the AOR, NOR, and aeration time at steady state. The dynamic model quantified the relationship between specific growth rates (µ) and food-to-microorganism ratios (F/M) through exponential fitting, successfully capturing AOB and NOB growth dynamics. Validation experiments (SRT = 10 d, TVNL = 60 mg/L per cycle) demonstrated the ability of the dynamic model to predict trends in NAR and aeration time accurately. This study emphasizes the importance of accurately modeling AOR and NOR variations to predict aeration time and NAR, thereby providing valuable insights for aeration control and precise management of AOB and NOB populations in mainstream PN processes.

Hyperparathyroidism presented as multiple pulmonary nodules in hemodialysis patient status post parathyroidectomy: A case report.

BACKGROUND: Primary hyperparathyroidism is typically caused by a single parathyroid adenoma. Ectopic parathyroid adenomas occur as well, with cases involving various sites, including the mediastinum, presenting in varying frequencies. Secondary hyperparathyroidism develops in the context of chronic kidney disease, primarily due to vitamin D deficiency, hypocalcemia, and hyperphosphatemia. It is frequently diagnosed in patients undergoing dialysis. This article presents a rare case of hyperparathyroidism involving multiple hyperplastic parathyroid glands with pulmonary seeding in a 50-year-old female patient undergoing hemodialysis (HD). CASE SUMMARY: The patient had a history of parathyroidectomy 10 years prior but developed recurrent hyperparathyroidism with symptoms of pruritus and cough with sputum during a period of routine dialysis. Radiographic imaging revealed multiple nodules in both lungs, with the largest measuring approximately 1.35 cm. Surgical histopathology confirmed the presence of hyperplastic parathyroid glands within the pulmonary tissue. After tumor resection surgery via video-assisted thoracic surgery with wedge resection, the patient was discharged in stable condition and in follow-up her symptoms showed improvement. CONCLUSION: This article describes hyperparathyroidism presenting as pulmonary nodules in a patient undergoing post-parathyroidectomy HD, highlighting diagnostic challenges and a positive outcome from tumor resection surgery.

Relationship between left atrial isolated surface area and early-term recurrence in patients with persistent atrial fibrillation after cryoballoon ablation.

OBJECTIVE: To investigate the effect of pulmonary vein antrum enlargement combined with left atrial roof cryoballoon ablation in patients with persistent atrial fibrillation (PeAF) by analyzing the relationship between left atrial isolation area surface area (ISA) and early postoperative recurrence. METHODS: 93 patients with PeAF were classified into recurrence and non-recurrence groups according to the results of the 1-year follow-up. Three-dimensional electroanatomical labeling map was constructed and merged with that of the left atrial pulmonary vein CTA, and the ISA and the left atrial surface area (LASA) were measured and analyzed to determine the relationship between ISA/LASA in relation to early postoperative recurrence. RESULTS: 93 patients were included and followed up for 1 year with AF-free recurrence rate of 75.3%. The ISA of the recurrence group was lower than that of the non-recurrence group. Left atrial internal diameter (LAD), left common pulmonary vein, the ISA, the ISA/LASA and early-term recurrence had statistical significance in both groups. The factors that significantly predicted early-term recurrence were left common pulmonary vein and the ISA/LASA. ISA/LASA (HR 0, 95% CI 0-0.005, P = 0.008) and left common pulmonary vein trunk (HR 7.754, 95% CI 2.256-25.651, P = 0.001) were the independent risk factors for early recurrence. ROC curve analysis showed that ISA/LASA predicted the best early recurrence after operation with a cut-off value of 15.2%. CONCLUSION: A greater ISA/LASA reduces early recurrence after cryoablation in patients with PeAF. An ISA/LASA of 15.2% may be the best cut-off value for predicting early recurrence after cryoablation for PeAF.

The Efficacy of High-Fidelity Telesimulation in Preparing Nursing Students for Emergency and Critical Patient Care: A Prospective Study.

BACKGROUND: High-fidelity telesimulation can address the gap in nursing education caused by the pandemic by providing a simulated environment for students to practice skills that closely mimic real-life scenarios. PURPOSE: This study was designed to determine the effect of a high-fidelity telesimulation teaching program on emergency and critical patient care-related knowledge, self-confidence, and critical thinking skills in nursing students. METHODS: This randomized, single-blind controlled study was conducted on a sample of 84 nursing students who were evaluated using pretest and posttest measurements. The participants were randomized into a control group ( n = 43) and an experimental group ( n = 41). The control group received an in-person traditional teaching program, and the experimental group was taught using a high-fidelity telesimulation program. During the high-fidelity telesimulation, synchronous online tutorial learning and telesimulation were conducted every 100 and 300 minutes. The experimental group program included a lecture, simulation teaching videos, and demonstrations related to endotracheal intubation, 12-lead electrocardiography, protective clothing, and hybrid telesimulation learning. In each subgroup, the students executed a single high-fidelity telesimulation scenario in which they were assigned individual roles. The students in the other subgroups served as observers and engaged in the synchronous online debriefing. Teaching efficacy was evaluated using an objective structured clinical examination and a questionnaire designed for emergency and critical patient care. RESULTS: In the experimental group, levels of knowledge and self-confidence as well as critical thinking skills related to emergency and critical patient care were significantly higher than in the control group ( p < .05). CONCLUSIONS: High-fidelity telesimulation teaching is a feasible and reliable alternative to conventional in-person simulation for nursing students, particularly in situations where traditional clinical experiences are not possible.

Novel temperature responsive polymer based sealant for embolization.

A sealant has been developed that improves upon current catheter-based treatments in the following ways: 1) Efficient delivery system, 2) No in situ polymerization, 3) No harmful byproducts, and 4) Cost-effective formulation. During the development process, particular attention was given to materials that were tunable, safe, and effective sealant agents. The thermo-responsive properties of poly(N-isopropylacrylamide) (PNIPAM) provides an ideal foundation to develop an optimized solution. Through a combination of model-based and material testing, a hydrogel was developed that balances conformational factors to achieve a customized transition temperature, radiopacity suitable for visualization, mechanical properties suitable for delivery via 3Fr catheter, sufficient cohesion once applied to resist migration under physiological pressures and an improved safety profile. Two applications, embolization of lymphatic leakage and exclusions of the left atrial appendage (LAA), to eliminate LAA dead space to reduce the risk of thromboembolic events, were considered. The material and benchtop results for this product demonstrate the suitability of this new material not only for these applications but also for other potential healthcare applications.

A sealant has been developed that improves upon current catheter-based treatments in the following ways: 1) Efficient delivery system, 2) No in situ polymerization, 3) No harmful byproducts, and 4) Cost-effective formulation.

Building a Chinese ancient architecture multimodal dataset combining image, annotation and style-model.

In this rapidly evolving era of multimodal generation, diffusion models exhibit impressive generative capabilities, significantly enhancing the realm of creative image synthesis by intricately textual prompts. Yet, their effectiveness is limited in certain niche sectors, like depicting Chinese ancient architecture. This limitation is primarily due to the insufficient data that fails to encompass the unique architectural features and corresponding text information. Hence, we build an extensive multimodal dataset capturing the essence of Chinese architectures mostly from the Tang to the Yuan Dynasties. The dataset is categorized on the types, including image&text, video, and style models. In details, images and videos are methodically categorized based on locations. All images are annotated at two levels: initial annotations and descriptive terms based on distinctive characteristics and official information. Moreover, seven artistic styles fine-tuning models are provided in our dataset for further innovations. Significantly, this is the first Chinese ancient architecture dataset and the instance of using the Pinyin system to annotate unique terms related to Chinese architectural styles.

The Adverse Effects of Anxiety and Depression on Pregnant Women with Hypothyroidism in Late Pregnancy.

BACKGROUND: Maternal depression and anxiety during pregnancy are significant public health concerns commonly reported worldwide among pregnant women. This study aimed to investigate the impact of anxiety and depression on thyroid function, pregnancy outcomes, and sleep quality among pregnant women with hypothyroidism in the later stages of pregnancy. METHODS: Eighty cases of pregnant women with hypothyroidism in late pregnancy who were treated at Zhangjiakou First Hospital from January 2021 to October 2023 were selected for this retrospective study. The pregnant women in late pregnancy were divided into four groups according to the scores on the Hospital Anxiety and Depression Scale (HADS): control group with 20 cases, anxiety group with 18 cases, depression group with 22 cases, and anxiety-depression group with 20 cases. A comparison was made among the four groups regarding general information of pregnant women in late pregnancy, HADS scale scores, levels of free thyroxine (FT4, FT3), thyroid-stimulating hormone (TSH), occurrence of adverse pregnancy outcomes, and sleep quality at different time periods. RESULTS: There was no statistically significant difference in comparing general information among the four groups of pregnant women in late pregnancy (p > 0.05). There were statistically significant differences in HADS depression and HADS anxiety scores (p < 0.05), levels of FT4, FT3, TSH in pregnant women in late pregnancy postpartum (p < 0.05), occurrence of adverse pregnancy outcomes (p < 0.05), and comparison of sleep quality of pregnant women in late pregnancy at 1, 3, and 5 months of follow-up among the groups (F = 5.735, 23.930, 11.573, p < 0.05). CONCLUSION: Anxiety and depression significantly impact thyroid function, pregnancy outcomes, and sleep quality in pregnant women with hypothyroidism in late pregnancy, which is detrimental to the health of pregnant women in late pregnancy. Therefore, necessary interventions are needed.

Emerging insights into the application of metal-organic framework (MOF)-based materials for electrochemical heavy metal ion detection.

Heavy metal ions are one of the main sources of water pollution, which has become a major global problem. Given the growing need for heavy metal ion detection, electrochemical sensor stands out for its high sensitivity and efficiency. Metal-organic frameworks (MOFs) have garnered much interest as electrode modifiers for electrochemical detection of heavy metal ions owing to their significant specific surface area, tailored pore size, and catalytic activity. This review summarizes the progress of MOF-based materials, including pristine MOFs and MOF composites, in the electrochemical detection of various heavy metal ions. The synthetic methods of pristine MOFs, the detection mechanisms of heavy metal ions and the modification strategies of MOFs are introduced. Besides, the diverse applications of MOF-based materials in detecting both single and multiple heavy metal ions are presented. Furthermore, we present the current challenges and prospects for MOF-based materials in electrochemical heavy metal ion detection.

Recent Developments in the Fabrication and Application of Superhydrophobic Suraces.

A superhydrophobic surface is defined as having a contact angle exceeding 150 °C, indicating a remarkable ability to repel water. Generally, superhydrophobicity originates from the utilization of low-surface-energy materials with unique micro- and nanostructures. Superhydrophobic surfaces have gained considerable recognition and are widely employed in diverse areas for anti-icing, oil-water separation, anticorrosion, self-cleaning, blood-repellent, and antibacterial applications. These surfaces can greatly enhance industrial processes by yielding significant performance improvements. In this review, we introduce the basic theories that provide a foundation for understanding the hydrophobic properties of superhydrophobic surfaces. We then discuss current techniques for fabricating superhydrophobic coatings, critically analyzing their strengths and limitations. Furthermore, we provide an overview of recent progress in the application of superhydrophobic materials. Finally, we summarize the challenges in developing superhydrophobic materials and future trends in this field. The insights provided by this review can help researchers understand the basic knowledge of superhydrophobic surfaces and obtain the latest progress and challenges in the application of superhydrophobic surfaces. It provides help for further research and practical application of superhydrophobic surfaces.

The effect of anionic emulsifiers' diversity and manufacturing processes on the stability and mechanical properties of the water-based epoxy-emulsified asphalt.

Emulsified asphalt mixtures' cold mix and paving features facilitate asphalt pavements in fulfilling dual-carbon and energy-saving demands. Anionic emulsifiers can enhance emulsion stability, ensure uniform dispersion of oil and water, possess good decompression viscosity, thickening, and lubricating properties, and maintain good stability under acidic conditions. Nevertheless, anionic emulsified asphalt is restricted in engineering applications due to problems like its storage stability. In this paper, eight anionic emulsifiers and two preparation procedures were chosen for stability tests. Through static tests, storage tests, sieve residue tests, and laser particle size tests, the impacts of emulsifiers on the storage stability and dispersion of asphalt were analyzed. Waterborne epoxy resin exhibits excellent adhesive properties, mechanical properties, chemical resistance, and heat stability. A fluorescence microscope test, static and storage test, laser particle size test, and cementation test were employed to explore the effects of different preparation processes and waterborne epoxy mixing ratios on emulsified asphalt's storage stability, dispersion stability, and structural stability. The results showed that: (1) the emulsified asphalt prepared with the BWH-02 emulsifier exhibits the best storage stability, and blending with 20% of the waterborne epoxy modifier can notably enhance the bonding properties; (2) the shear strength of the BWH-02 waterborne epoxy emulsified asphalt prepared can reach 1.543 MPa, and the tensile viscosity can reach 0.848 MPa; (3), The emulsified asphalt prepared by the process of modification has better storage stability than that prepared by the side of the emulsification process. Moreover, the storage stability of emulsified asphalt prepared by emulsification and modification is superior to that of the emulsification and modification process. This research provides theoretical and technical support for popularizing and applying cold-mixed cold-paving asphalt mixtures.

Extrapolation of Upadacitinib Efficacy in Juvenile Idiopathic Arthritis Leveraging Pharmacokinetics, Exposure-Response Models, and Real-World Patient Data.

Juvenile idiopathic arthritis (JIA) is the most prevalent pediatric rheumatic disease. While disease-modifying antirheumatic drugs (DMARDs), especially biologics, have greatly transformed the management of JIA, there remain some unmet medical needs that require new treatment options. The objective of this work was to describe and apply a modeling and simulation approach to extrapolate upadacitinib efficacy from the adult diseases, rheumatoid arthritis (RA) and psoriatic arthritis (PsA), to their respective pediatric diseases, polyarticular course JIA (pcJIA), and juvenile PsA (JPsA). A population pharmacokinetic model characterized upadacitinib pharmacokinetics in pediatric patients using data from two phase I studies in pediatric patients with pcJIA (N = 51) or atopic dermatitis (N = 33). Efficacy simulations were conducted using previously developed exposure-response models in adults with RA and PsA. Real-world pcJIA and JPsA patient databases were leveraged to construct representative patient profiles for the targeted population. Following administration of the proposed weight-based dosing regimen, the model-predicted median upadacitinib plasma exposures in pediatric patients were within 20% of those in adult RA and PsA patients receiving the approved adult regimen. Simulations demonstrate that upadacitinib efficacy in pcJIA and JPsA is predicted to be non-inferior to that in adults with RA or PsA, respectively. The results of this work enabled recent approvals of upadacitinib for the treatment of polyarticular JIA and JPsA in the United States. Upadacitinib safety in pediatrics is being further evaluated in ongoing clinical trials.