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1.
Anal Bioanal Chem ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39254691

ABSTRACT

The proteome serves as the primary basis for identifying targets for treatment. This study conducted proteomic range two-sample Mendelian randomization (MR) analysis to pinpoint potential protein markers and treatment targets for ankylosing spondylitis (AS). A total of 4907 data points on circulating protein expression were collected from a large-scale protein quantitative trait locus investigation involving 35,559 individuals. Using data from a Finnish study on AS as the outcome, the dataset comprised 166,144 individuals of European ancestry (1462 cases and 164,682 controls), and causal relationships were determined through bidirectional Mendelian randomization of two samples. Proteins were further validated and identified through single-cell expression analysis, certain cells showing enriched expression levels were detected, and possible treatment targets were optimized. Increased HERC5 expression predicted by genes was related to increased AS risk, whereas the expression of the remaining five circulating proteins, AIF1, CREB3L4, MLN, MRPL55, and SPAG11B, was negatively correlated with AS risk. For each increase in gene-predicted protein levels, the ORs of AS were 2.11 (95% CI 1.44-3.09) for HERC5, 0.14 (95% CI 0.05-0.41) for AIF1, 0.48 (95% CI 0.34-0.68) for CREB3L4, 0.54 (95% CI 0.42-0.68) for MLN, 0.23 (95% CI 0.13-0.38) for MRPL55, and 0.26 (95% CI 0.17-0.39) for SPAG11B. The hypothesis of a reverse causal relationship between these six circulating proteins and AS is not supported. Three of the six protein-coding genes were expressed in both the AS and healthy control groups, while CREB3L4, MLN, and SPAG11B were not detected. Increased levels of HERC5 predicted by genes are related to increased AS risk, whereas the levels of the remaining five circulating proteins, AIF1, CREB3L4, MLN, MRPL55, and SPAG11B, negatively correlate with AS risk. HERC5, AIF1, and MRPL55 are potential therapeutic targets for AS. This study advanced the field by employing a novel combination of proteomic range two-sample MR analysis and single-cell expression analysis to identify potential protein markers and therapeutic targets for AS. This approach enabled a comprehensive understanding of the causal relationships between circulating proteins and AS, which has not been extensively explored in previous studies.

2.
Front Pediatr ; 12: 1387626, 2024.
Article in English | MEDLINE | ID: mdl-39105160

ABSTRACT

Background: Congenital pyriform sinus fistula (CPSF) is uncommon congenital abnormality, and the optimal definitive treatment has not yet been established. The aim of the present study was to comparatively evaluate patients with CPSF regarding the indications and outcomes of treatment with open surgical excision (OSE) vs. endoscopic Radiofrequency Ablation (RA), and the advantages of both therapeutic procedures were also analyzed. Methods: An observational, longitudinal, retrospective, analytical and comparative study was conducted on 166 consecutive pediatric patients with CPSF treated at Shanghai Children's Hospital between December 2018 and September 2023. Results: In this study, there were 79 males and 87 females. The median age at operation was 4.8 years (8 days to 15 years). OSE and Endoscopic RA were respectively performed in 48 and 118 children. The gastric tube retention time after RA was longer (3 days vs. 14 days) than after OSE. Patients with a history of incision and drainage (I&D) tended to choose OSE (75.0% vs. 39.0%, P < 0.01). There were no significant differences in postoperative complications and recurrence rates between these two groups (P > 0.05), but the hospitalization duration was shorter for RA group compared to OSE group [2 (2-3) vs. 4 (3-5), P < 0.01]. Conclusions: Both OSE and RA are recognized as first-line treatment options for CPSF, which show no significant differences in prognosis, except hospitalization duration and the gastric tube retention time. Nevertheless, the indications for OSE and RA differ, which are influenced by factors such as the inflammatory stage, specific typing, previous treatments, and the surgeon's expertise. The selection of surgical approach should be carefully determined based on individual circumstances.

3.
iScience ; 27(8): 110545, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39165842

ABSTRACT

Both mental health and mental illness unfold in complex and unpredictable ways. Novel artificial intelligence approaches from the area of dynamical systems reconstruction can characterize such dynamics and help understand the underlying brain mechanisms, which can also be used as potential biomarkers. However, applying deep learning to model dynamical systems at the individual level must overcome numerous computational challenges to be reproducible and clinically useful. In this study, we performed an extensive analysis of these challenges using generative modeling of brain dynamics from fMRI data as an example and demonstrated their impact on classifying patients with schizophrenia and major depression. This study highlights the tendency of deep learning models to identify functionally unique solutions during parameter optimization, which severely impacts the reproducibility of downstream predictions. We hope this study guides the future development of individual-level generative models and similar machine learning approaches aimed at identifying reproducible biomarkers of mental illness.

4.
J Clin Ultrasound ; 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39189701

ABSTRACT

OBJECTIVE: To discuss the usefulness of ultrasonography (US) in the diagnosis and management of pediatric head and neck lymphatic malformations (HNLMs). METHODS: We conducted a retrospective analysis of 140 children who were referred to our hospital for the treatment of HNLMs. RESULTS: The median age at presentation was 12 months (1 day-171 months; 66.4% under 2 years old; 35.7% neonatus). The majority clinical presentations were asymptomatic mass (65.7%, 92/140) and cosmetic deformity (25.7%, 36/140). HNLMs involved the neck accounting for 65.7% (92/140), especially posterior cervical trigone (22.1%, 31/140), and submandibular (20.0%, 28/140). The US diagnostic accuracy was 91.4% (128/140). Their boundary with the surrounding tissues was usually clear (87.9%, 123/140), whereas the shape was mostly irregular (97.1%, 136/140). Based on surgical findings, there were 67 pure HNLMs and 73 intracystic hemorrhage. Between the two groups, there were statistical differences in capsule contents (χ2 = 7.8299, p = 0.0051), flocculent echo floating (χ2 = 21.2964, p < 0.0001), overlying skin (χ2 = 9.0498, p = 0.0026), and palpation (χ2 = 13.4058, p = 0.0003). CONCLUSIONS: US typically reveals the lesion with clear boundary, irregular morphology, anechoic contents, no blood flow signal, and echoic intracapsular septum with blood flow signal. In contrast, bluish appearance, tensional palpation, and capsule contents with low/mixed echo or flocculent echo floating may indicate intracystic hemorrhage.

5.
Org Lett ; 26(33): 6966-6971, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39145601

ABSTRACT

A novel kind of S-alkynylthio sulfonate, which can be directly activated under visible-light irradiation, has been developed for the radical addition of multiple bond systems and radical coupling with diazonium salts under photocatalyst-free conditions. This strategy features a broad substrate scope, high regioselectivity, excellent tolerance of functional groups, and the late-stage modification of drugs. Experimental and theoretical mechanistic investigations gave reasonable insight into the photolysis of S-alkynylthio sulfonates and C-S bond formation.

6.
J Orthop Surg Res ; 19(1): 468, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39118178

ABSTRACT

OBJECTIVE: This study aims to investigate the anatomical structure of the C6 pedicle and lateral mass in children aged 0-14 years using CT imaging, providing detailed insights into their growth and development. METHODS: We conducted a comprehensive measurement of C6. Measurements included width, length, and height of the pedicles, as well as the length, width, and thickness of the lateral masses, and several angular metrics. Regression analysis was performed to understand the growth trends, and statistical analyses were carried out to identify differences between age groups, genders, and sides. RESULTS: In children younger than four years, the pedicle width exceeds its height, influencing the diameter of the pedicle screws. By age two to three, the pedicle height and lateral mass thickness reaches 3.0 mm, allowing for the use of 3.0 mm diameter screws. The pedicle transverse angle remains stable. Most parameters showed no significant differences between the left and right sides. Size parameters exhibited significant larger in males than females at ages 0-1, 3-7, and 10-12 years. Regression analysis revealed that the growth trends of size parameters follow cubic or polynomial curves. Most angular metrics follow cubic fitting curves without a clear trend of change with age. CONCLUSION: This study provides a detailed analysis of the anatomical development of the C6 pedicle and lateral masses in children, offering valuable insights for pediatric cervical spine surgeries. The findings highlight the importance of considering age-specific anatomical variations when planning posterior surgical fixation, specifically at C6. It is necessary for us to perform thin-layer CT scans on children and carefully measure various indicators before surgery.


Subject(s)
Cervical Vertebrae , Tomography, X-Ray Computed , Humans , Male , Female , Infant , Child , Child, Preschool , Adolescent , Tomography, X-Ray Computed/methods , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/anatomy & histology , Cervical Vertebrae/surgery , Cervical Vertebrae/growth & development , Infant, Newborn , Pedicle Screws , Age Factors
7.
Br J Radiol ; 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39152999

ABSTRACT

OBJECTIVES: Telomerase reverse transcriptase promoter (pTERT) mutation status plays a key role in making decisions and predicting prognoses for patients with WHO grade IV glioma. This study was conducted to assess the value of diffusion-weighted imaging (DWI) for predicting pTERT mutation status in WHO grade IV glioma. METHODS: Magnetic resonance (MR) imaging (MRI) data and molecular information were obtained for 266 patients with WHO grade IV glioma at the Hospital and divided into training, validation sets. The ratio of training to validation set was approximately 10:3. We trained the same residual convolutional neural network (ResNet) for each MR modality, including structural MRIs (T1-weighted, T2-weighted, and contrast-enhanced T1-weighted) and DWI*, to compare the predictive capacities between DWI and conventional structural MRI. We also explored the effects of different regions of interest (ROIs) on pTERT mutation status prediction outcomes. RESULTS: Structural MRI modalities poorly predicted the pTERT mutation status (accuracy = 51%-54%; area under the curve [AUC]=0.545-0.571), whereas DWI combined with its ADC maps yielded the best predictive performance (accuracy = 85.2%, AUC = 0.934). Including the radiological and clinical characteristics did not further improve the performance for predicting pTERT mutation status. The entire tumor volume yielded the best prediction performance. CONCLUSIONS: DWI technology shows promising potential for predicting pTERT mutations in WHO grade IV glioma and should be included in the MRI protocol for WHO grade IV glioma in clinical practice. ADVANCES IN KNOWLEDGE: This is the first large-scale model study to validate the predictive value of DWI for pTERT in WHO grade IV glioma.

8.
Int Immunopharmacol ; 142(Pt A): 113027, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39216119

ABSTRACT

OBJECTIVE: This study aimed to elucidate the causal relationships between antibodies and autoimmune diseases using Mendelian randomization (MR). METHODS: Data on 46 antibodies were obtained from genome-wide association studies (GWAS). Autoimmune disease data were sourced from the FinnGen consortium and the IEU OpenGWAS project. Inverse-variance weighted (IVW) analysis was the primary method, supplemented by heterogeneity and sensitivity analyses. We also examined gene expression near significant SNPs and conducted drug sensitivity analyses. RESULTS: Antibodies and autoimmune diseases exhibit diverse interactions. Antibodies produced after Polyomavirus infection tend to increase the risk of several autoimmune diseases, while those following Human herpesvirus 6 infection generally reduce it. The impact of Helicobacter pylori infection varies, with different antibodies affecting autoimmune diseases in distinct ways. Overall, antibodies significantly influence the risk of developing autoimmune diseases, whereas autoimmune diseases have a lesser impact on antibody levels. Gene expression and drug sensitivity analyses identified multiple genes and drugs as potential treatment options for ankylosing spondylitis (AS), with the AIF1 gene being particularly promising. CONCLUSIONS: Bidirectional MR analysis confirms complex causal relationships between various antibodies and autoimmune diseases, revealing intricate patterns of post-infection antibody interactions. Several drugs and genes, notably AIF1, show potential as candidates for AS treatment, offering new avenues for research. Further exploration of the underlying mechanisms is necessary.

9.
Front Public Health ; 12: 1370076, 2024.
Article in English | MEDLINE | ID: mdl-39131569

ABSTRACT

Background: As alternative replacement products for tobacco-derived nicotine, synthetic nicotine products have recently emerged and gained increasing popularity. This study analyzes public perception and discussion of synthetic nicotine products on Twitter (now "X"). Methods: Through Twitter streaming API (Application Programming Interface), we have collected 2,764 Twitter posts related to synthetic nicotine from December 12, 2021, to October 17, 2022, using keywords related to synthetic nicotine. By applying an inductive approach, two research assistants manually determined the relevance of tweets to synthetic nicotine products and assessed the attitude of tweets as positive, negative, and neutral of tweets toward synthetic nicotine, and the main topics. Results: Among 1,007 tweets related to synthetic nicotine products, the proportion of negative tweets (383/1007, 38.03%) toward synthetic nicotine products was significantly higher than that of positive tweets (218/1007, 21.65%) with a p-value <0.05. Among negative tweets, major topics include the concern about addiction and health risks of synthetic nicotine products (44.91%) and synthetic nicotine as a policy loophole (31.85%). Among positive tweets, top topics include alternative replacement for nicotine (39.91%) and reduced health risks (31.19%). Conclusion: There are mixed attitudes toward synthetic nicotine products on Twitter, resulting from different perspectives. Future research could incorporate demographic information to understand the attitudes of various population groups.


Subject(s)
Nicotine , Social Media , Humans , Public Opinion
10.
BMC Nurs ; 23(1): 452, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961494

ABSTRACT

BACKGROUND: The central component in impactful healthcare decisions is evidence. Understanding how nurse leaders use evidence in their own managerial decision making is still limited. This mixed methods systematic review aimed to examine how evidence is used to solve leadership problems and to describe the measured and perceived effects of evidence-based leadership on nurse leaders and their performance, organizational, and clinical outcomes. METHODS: We included articles using any type of research design. We referred nurses, nurse managers or other nursing staff working in a healthcare context when they attempt to influence the behavior of individuals or a group in an organization using an evidence-based approach. Seven databases were searched until 11 November 2021. JBI Critical Appraisal Checklist for Quasi-experimental studies, JBI Critical Appraisal Checklist for Case Series, Mixed Methods Appraisal Tool were used to evaluate the Risk of bias in quasi-experimental studies, case series, mixed methods studies, respectively. The JBI approach to mixed methods systematic reviews was followed, and a parallel-results convergent approach to synthesis and integration was adopted. RESULTS: Thirty-one publications were eligible for the analysis: case series (n = 27), mixed methods studies (n = 3) and quasi-experimental studies (n = 1). All studies were included regardless of methodological quality. Leadership problems were related to the implementation of knowledge into practice, the quality of nursing care and the resource availability. Organizational data was used in 27 studies to understand leadership problems, scientific evidence from literature was sought in 26 studies, and stakeholders' views were explored in 24 studies. Perceived and measured effects of evidence-based leadership focused on nurses' performance, organizational outcomes, and clinical outcomes. Economic data were not available. CONCLUSIONS: This is the first systematic review to examine how evidence is used to solve leadership problems and to describe its measured and perceived effects from different sites. Although a variety of perceptions and effects were identified on nurses' performance as well as on organizational and clinical outcomes, available knowledge concerning evidence-based leadership is currently insufficient. Therefore, more high-quality research and clinical trial designs are still needed. TRAIL REGISTRATION: The study was registered (PROSPERO CRD42021259624).

11.
J Chem Inf Model ; 64(15): 6174-6189, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39008832

ABSTRACT

Anticancer peptides (ACPs) are promising future therapeutics, but their experimental discovery remains time-consuming and costly. To accelerate the discovery process, we propose a computational screening workflow to identify, filter, and prioritize peptide sequences based on predicted class probability, antitumor activity, and toxicity. The workflow was applied to identify novel ACPs with potent activity against colorectal cancer from the genome sequences of Candida albicans. As a result, four candidates were identified and validated in the HCT116 colon cancer cell line. Among them, PCa1 and PCa2 emerged as the most potent, displaying IC50 values of 3.75 and 56.06 µM, respectively, and demonstrating a 4-fold selectivity for cancer cells over normal cells. In the colon xenograft nude mice model, the administration of both peptides resulted in substantial inhibition of tumor growth without causing significant adverse effects. In conclusion, this work not only contributes a proven computational workflow for ACP discovery but also introduces two peptides, PCa1 and PCa2, as promising candidates poised for further development as targeted therapies for colon cancer. The method as a web service is available at https://app.cbbio.online/acpep/home and the source code at https://github.com/cartercheong/AcPEP_classification.git.


Subject(s)
Antineoplastic Agents , Candida albicans , Peptides , Candida albicans/drug effects , Candida albicans/genetics , Animals , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Peptides/chemistry , Peptides/pharmacology , Mice, Nude , Genome, Fungal , Computer Simulation , Mice , HCT116 Cells , Xenograft Model Antitumor Assays
12.
Orthop Surg ; 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39056377

ABSTRACT

OBJECTIVE: The C4 is the transition point between the upper and lower cervical vertebrae and plays a pivotal role in the middle of the cervical spine. Currently, there are limited reports on large-scale sample studies regarding C4 anatomy in children, and a scarcity of experience exists in pediatric cervical spine surgery. The current study addresses the dearth of anatomical measurements of the C4 vertebral arch and lateral mass in a substantial sample of children. This study aims to measure the imaging anatomy of the C4 vertebral arch and lateral mass in children under 14 years of age across various age groups, investigate the growth and development of these structures. METHODS: We measured 12 indicators, including the size (D1, D2, D3, D4, D5, D6, D7, and D8) and angle (A, C, D, and E) of the C4 vertebral arch and lateral mass, in 513 children who underwent cervical CT examinations at our hospital. We employed the aggregate function for statistical analysis, conducted t-tests for difference statistics, and utilized the least squares method for regression analysis. RESULTS: Overall, as age increased, there was a gradual increase in the size of the vertebral arch and lateral mass. Additionally, the medial inclination angle of the vertebral arch decreased, and the lateral mass flattened gradually. The rate of change decreased gradually with age. The mean value of D1 increased from 2.31 mm to 3.88 mm, of D2 from 16.75 mm to 29.2 mm, of D3 from 2.21 mm to 4.92 mm, and of D4 from 7.34 mm to 11.84 mm. Meanwhile, the mean value of D5 increased from 5.2 mm to 9.71 mm, of D6 from 10.19 mm to 16.16 mm, of D7 from 2.53 mm to 5.67 mm, and of D8 from 6.11 mm to 11.45 mm. Angle A ranged from 49.12° to 54.97°, angle C from 15.28° to 19.83°, angle D from 39.91° to 53.7°, and angle E from 18.63° to 28.08°. CONCLUSION: Prior to cervical spine surgery in children, meticulous CT imaging anatomical measurements is essential. The imaging data serves as a reference for posterior C4 internal fixation, aids in designing posterior cervical screws for pediatric patients, and offer morphological anatomical references for posterior cervical spine surgery and screw design in pediatric patients.

13.
Small ; : e2400641, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38989690

ABSTRACT

Li-rich manganese-based cathode (LRMC) has attracted intense attention to developing advanced lithium-ion batteries with high energy density. However, LRMC is still plagued by poor cyclic stability, undesired rate capacity, and irreversible oxygen release. To address these issues, herein, a feasible polyvinylidene fluoride (PVDF)-assisted interface modification strategy is proposed for modulating the surface architecture and electronic conductivity of LRMC by intruding the F-doped carbon coating, spinel structure, and oxygen vacancy on the LRMC, which can greatly enhance the cyclic stability and rate capacity, and restrain the oxygen release for LRMC. As a result, the modified material delivers satisfactory cyclic performance with a capacity retention of 90.22% after 200 cycles at 1 C, an enhanced rate capacity of 153.58 mAh g-1 at 5 C and 126.32 mAh g-1 at 10 C, and an elevated initial Coulombic efficiency of 85.63%. Moreover, the thermal stability, electronic conductivity, and structure stability of LRMC are also significantly improved by the PVDF-assisted interface modification strategy. Therefore, the strategy of simultaneously modulating the surface architecture and the electronic conductivity of LRMC provides a valuable idea to improve the comprehensive electrochemical performance of LRMC, which offers a promising reference for designing LRMC with high electrochemical performance.

14.
ACS Appl Mater Interfaces ; 16(27): 34880-34891, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38949126

ABSTRACT

Lithium-rich manganese-based layered oxides (LRMOs) have recently attracted enormous attention on account of their remarkably big capacity and high working voltage. However, some inevitable inherent drawbacks impede their wide-scale commercial application. Herein, a kind of Cr-containing Co-free LRMO with a topical spinel phase (Li1.2Mn0.54Ni0.13Cr0.13O2) has been put forward. It has been found that the high valence of Cr6+ can reduce the Li+ ion content and induce the formation of a local spinel phase by combining more Li+ ions, which is beneficial to eliminate the phase boundary between the spinel phase and the bulk phase of the LRMO material, thus dramatically avoiding phase separation during the cycling process. In addition, the introduction of Cr can also expand the layer spacing and construct a stronger Cr-O bond compared with Mn-O, which enables to combine the transition metal (TM) slab to prevent the migration of TM ions and the transformation of the bulk phase to the spinel phase. Simultaneously, the synergistic effect of the successfully constructed spinel-layered biphase interface and the strong Cr-O bond can effectively impede the escape of lattice oxygen during the initial activation process of Li2MnO3 and provide the fast diffusion path for Li+ ion transmission, thus further reinforcing the configurable stability. Besides, Cr-LRMO presents an ultrahigh first discharge specific capacity of 310 mAh g-1, an initial Coulombic efficiency of as high as 92.09%, a good cycling stability (a capacity retention of 94.70% after 100 cycles at 1C), and a small voltage decay (3.655 mV per cycle), as well as a good rate capacity (up to 165.88 mAh g-1 at 5C).

15.
Front Pediatr ; 12: 1297831, 2024.
Article in English | MEDLINE | ID: mdl-38884103

ABSTRACT

Objective: This study aims to evaluate the efficacy of a novel surgical procedure for pyriform sinus fistulas in children via the external cervical approach through the hypopharynx. Methods: A retrospective analysis was conducted on 71 pediatric patients with pyriform sinus fistula (PSF) who underwent treatment at the Department of Otolaryngology Head and Neck Surgery, Shanghai Children's Hospital, from 2012 July to 2022 July. Surgical treatment of PSF was performed via the external cervical approach through the hypopharynx, with dye instilled through the internal opening to serve as a guide for tract identification. Results: All the internal orifices were found in the pyriform sinus by direct laryngoscopy in all 71 patients under general anesthesia. Two patients had a postoperative temporary hoarseness that resolved after 3 months. The other patients had no complications such as parapharyngeal abscess and incision infection. All patients were followed up for 23 months-70 months, and no recurrence was found. Conclusion: The novel surgical procedure of PSF performed via the hypopharynx has advantages such as a short operation path, quick recovery, fewer complications, and a low recurrence rate. This method is a better choice for managing recurrence cases after repeated cauterization endoscopic surgeries, as well as for patients with visible cervical surgical scars or masses.

16.
Eur J Pharm Sci ; 199: 106807, 2024 08 01.
Article in English | MEDLINE | ID: mdl-38797440

ABSTRACT

Ustekinumab (UST), a fully human immunoglobulin G1 κ monoclonal antibody, exhibiting high affinity for the p40 subunit shared by IL-12 and IL-23, which play key roles in the pathogenesis of inflammatory bowel disease (IBD). By scaling the physiologically-based pharmacokinetic modeling (PBPK) model of UST in adult patients with IBD, we aim to predict effective dosages for UST in pediatric patients, thereby offering a more practical dosing regimen for real-world applications. In this work, a PBPK model for UST in adult patients with IBD has been developed using PK-Sim and Mobi. Advanced ontogeny model has been incorporated to extrapolate the model to pediatric patients. The simulation results showed that the fold errors of the predicted and observed values of the area under the curve (AUC) and peak plasma concentration (Cmax) were between 0.79 and 1.73. For children aged 6-18, it is recommended to administer the drug per kilogram of body weight, at the model-recommended dose, to achieve a median AUC similar to that of the adult reference population post-administration. This comprehensive model construction enables us to comprehensively and extensively explore the pharmacokinetic characteristics of UST in pediatric patients of different age groups, providing robust support for clinical applications and personalized drug therapy.


Subject(s)
Inflammatory Bowel Diseases , Models, Biological , Ustekinumab , Humans , Ustekinumab/pharmacokinetics , Ustekinumab/administration & dosage , Child , Adolescent , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/metabolism , Male , Female , Area Under Curve , Adult , Computer Simulation
18.
J Org Chem ; 89(10): 6694-6703, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38695196

ABSTRACT

An excellent compatible and cost-effective dynamic kinetic resolution (DKR) protocol has been developed by combining a novel immobilized oxovanadium racemization catalyst onto cheap diatomite (V-D) with an immobilized lipase LA resolution catalyst onto a macroporous resin (LA-MR). V-D was prepared via grinding immobilization, which may become a promising alternative for the immobilization of metals, especially precious metals due to its low cost, high efficiency, easy separation, and large reaction interface. The DKR afforded high yield (96.1%), e.e. (98.67%), and Sel (98.28%) under optimal conditions established using response surface methodology as follows: the amount of V-D 10.83 mg, reaction time 51.2 h, and temperature 48.1 °C, respectively, indicating that all the reactions in the DKR were coordinated very well. The DKR protocol was also found to have high stability up to six reuses. V-D exhibited excellent compatibility with LA-MR because the lipase immobilized onto MR did not physically contact with the vanadium species immobilized onto diatomite, thus avoiding inactivation. Considering that lipase, oxovanadium, diatomite, and MR used are relatively inexpensive, and the adsorption or grinding immobilization is simple, the LA-V-MD DKR by coupling LA-MR with V-D is a cost-effective and promising protocol for chiral secondary alcohols.

19.
PLoS One ; 19(5): e0303404, 2024.
Article in English | MEDLINE | ID: mdl-38713733

ABSTRACT

The development of urbanization has brought new challenges to the ecological environment, and the promotion of green technology innovation and development is widely recognized as an essential method to achieve cities' economic benefits and environmental protection. This paper examines whether the new urbanization pilot policies (NUP) increase green technology innovation (GTI) from both theoretical and empirical perspectives. This paper examines the impact of new urbanization on GTI by analyzing data from 285 cities in China between 2010 and 2021, using the multi-period DID model with the implementation of NUP as an exogenous policy shock. The study results indicate that NUP significantly affects GTI, and the conclusion still holds after the parallel trend test, placebo test, and other robustness tests. Heterogeneity analysis shows that the NUP significantly enhances GTI in low environmental pollution, non-resource-based, Medium-sized, and Central Region cities. The test of moderating effect shows that NUP has a "linkage effect" with the government's environmental attention, financial investment in innovation, and regional talent pooling. The findings of this paper provide empirical evidence and decision-making reference for promoting NUP and sustainable development of cities.


Subject(s)
Cities , Urbanization , China , Humans , Pilot Projects , Inventions , Technology , Sustainable Development/trends , Conservation of Natural Resources/methods
20.
Sci Rep ; 14(1): 7691, 2024 04 02.
Article in English | MEDLINE | ID: mdl-38565845

ABSTRACT

Spinal cord injury (SCI) is a prevalent and serious complication among patients with spinal tuberculosis (STB) that can lead to motor and sensory impairment and potentially paraplegia. This research aims to identify factors associated with SCI in STB patients and to develop a clinically significant predictive model. Clinical data from STB patients at a single hospital were collected and divided into training and validation sets. Univariate analysis was employed to screen clinical indicators in the training set. Multiple machine learning (ML) algorithms were utilized to establish predictive models. Model performance was evaluated and compared using receiver operating characteristic (ROC) curves, area under the curve (AUC), calibration curve analysis, decision curve analysis (DCA), and precision-recall (PR) curves. The optimal model was determined, and a prospective cohort from two other hospitals served as a testing set to assess its accuracy. Model interpretation and variable importance ranking were conducted using the DALEX R package. The model was deployed on the web by using the Shiny app. Ten clinical characteristics were utilized for the model. The random forest (RF) model emerged as the optimal choice based on the AUC, PRs, calibration curve analysis, and DCA, achieving a test set AUC of 0.816. Additionally, MONO was identified as the primary predictor of SCI in STB patients through variable importance ranking. The RF predictive model provides an efficient and swift approach for predicting SCI in STB patients.


Subject(s)
Spinal Cord Injuries , Tuberculosis, Spinal , Humans , Prospective Studies , Tuberculosis, Spinal/complications , Spinal Cord Injuries/complications , Algorithms , Machine Learning , Retrospective Studies
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