Predictive and prognostic value of aurora kinase A combined with tumor-infiltrating lymphocytes in medullary thyroid carcinoma.

Background: Aurora kinase A (AURKA) and tumor-infiltrating lymphocytes (TILs) are both known to play an essential role in tumorigenesis. However, the expression and prognostic value of the AURKA and TILs in medullary thyroid carcinoma (MTC) have not yet been investigated. Patients and methods: Surgical specimens and clinical data of 137 patients diagnosed with MTC were collected. AURKA expression and TILs infiltration were quantified by immunohistochemistry and hematoxylin-eosin staining. Subsequently, the prognostic value of AURKA expression and TIL infiltration in MTC was evaluated. Results: AURKA was highly expressed in patients with multifocal tumor, cervical lymph node metastasis, and an advanced TNM stage, indicating a high probability of recurrence. AURKA further exhibited a positive correlation with TILs (R = 0.44, P < 0.001). High expression of AURKA combined with a low numbers of TILs (AURKAhigh/TILslow) was identified as an independent prognostic factor for biochemical recurrence (odds ratio: 4.57, 95% confidence interval: 1.54-14.66, P < 0.01) and recurrence-free survival (hazard ratio: 3.64, 95% confidence interval: 1.52-8.71, P < 0.001). The combination of AURKA and TILs apparently improves the prognostic value for biochemical recurrence (area under the curve: 0.751) and structural recurrence (area under the curve: 0.836) of MTC. Notably, AURKAhigh/TILslow demonstrated a high value for prediction of distant or unresectable locoregional recurrence, with an overall accuracy of 86.9%. Conclusion: AURKAhigh is associated with the MTC malignancy. The combination of AURKAhigh/TILslow was identified as novel independent prognostic marker in MTC, predicting incurable disease recurrence with high accuracy.

Quantitative Characterization of Protein N-Linked Core-Fucosylation by an Efficient Glycan Truncation Strategy.

Dysregulation of protein core-fucosylation plays a pivotal role in the onset, progression, and immunosuppression of cancer. However, analyzing core-fucosylation, especially the accurate determination of the core-fucosylation (CF) site occupancy ratio, remains challenging. To address these problems, we developed a truncation strategy that efficiently converts intact glycopeptides with hundreds of different glycans into two truncated forms, i.e., a monosaccharide HexNAc and a disaccharide HexNAc+core-fucose. Further combination with data-independent analysis to form an integrated platform allowed the measurement of site-specific core-fucosylation abundances and the determination of the CF occupancy ratio with high reproducibility. Notably, three times CF sites were identified using this strategy compared to conventional methods based on intact glycopeptides. Application of this platform to characterize protein core-fucosylation in two breast cancer cell lines, i.e., MDA-MB-231 and MCF7, yields a total of 1615 unique glycosites and about 900 CF sites from one single LC-MS/MS analysis. Differential analysis unraveled the distinct glycosylation pattern for over 201 cell surface drug targets between breast cancer subtypes and provides insights into developing new therapeutic strategies to aid precision medicine. Given the robust performance of this platform, it would have broad application in discovering novel biomarkers based on the CF glycosylation pattern, investigating cancer mechanisms, as well as detecting new intervention targets.

A finite element analysis of periodontal ligament fluid mechanics response to occlusal loading based on hydro-mechanical coupling model.

OBJECTIVE: Considering fluid stimulation is one of the essential biomechanical signals for periodontal tissues, this study aims to characterizing fluid mechanics response during occlusal loading by a hydro-mechanical coupling model for periodontal ligament. DESIGN: Models simulating periodontium with normal bone height and with intraosseous defects were built with three mechanical modules: tooth, periodontal ligament and alveolar bone. Tooth was modeled as linear elastic, and periodontal ligament and alveolar bone as a hydro-mechanical coupling model. Transient analyses under dynamic occlusal loading were performed. Fluid dynamics within periodontal ligament space was simulated and visualized by post-processing module. RESULTS: Reciprocating oscillatory flow occurred within the periodontal ligament under occlusal loading. Higher pore pressure and fluid velocity were observed in furcation and apical regions compared to mid-root and cervical regions. Intraosseous defects increased pore pressure and fluid velocity within the periodontal ligament, most significantly near the defect. CONCLUSION: Based on the results of the hydro-mechanical coupling model, significant oscillatory fluid motion is observed within the periodontal ligament under occlusal loading. Particularly, higher fluid velocity is evident in the furcation and apical areas. Additionally, Intraosseous defects significantly enhance fluid motion within the periodontal ligament.

Time Kinetics and prognosis roles of calcitonin after surgery for medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time kinetic and risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) are yet to be elucidated. METHODS: A retrospective study was conducted for 190 MTC patients. Risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) were analyzed. The predictors of calcitonin normalization time (CNT) and biochemical persistent/recurrent time (BPT) were identified. Further, the prognostic roles of CNT and BPT were also demonstrated. RESULTS: The 5- and 10-year DFS were 86.7% and 70.2%, respectively. The 5- and 10-year OS were 97.6% and 78.8%, respectively. CN was achieved in 120 (63.2%) patients, whereas BP was presented in 76 (40.0%) patients at the last follow up. After curative surgery, 39 (32.5%) and 106 (88.3%) patients achieved CN within 1 week and 1 month. All patients who failed to achieve CN turned to BP over time and 32/70 of them developed structural recurrence. The median time of CNT and BPT was 1 month (1 day to 84 months) and 6 month (3 day to 63months), respectively. LNR > 0.23 and male gender were independent predictors for CN and BP. LNR > 0.23 (Hazard ratio (HR), 0.24; 95% CI,0.13-0.46; P < 0.01) and male gender (HR, 0.65; 95% CI, 0.42-0.99; P = 0.045) were independent predictors for longer CNT. LNR > 0.23 (HR,5.10; 95% CI,2.15-12.11; P < 0.01) was still the strongest independent predictor followed by preoperative serum Ctn > 1400ng/L (HR,2.34; 95% CI,1.29-4.25; P = 0.005) for shorter BPT. In survival analysis, primary tumor size > 2 cm (HR, 5.81; 95% CI,2.20-15.38; P < 0.01), CNT > 1 month (HR, 5.69; 95% CI, 1.17-27.61; P = 0.031) and multifocality (HR, 3.10; 95% CI, 1.45-6.65; P = 0.004) were independent predictor of DFS. CONCLUSION: Early changes of Ctn after curative surgery can predict the long-term risks of biochemical and structural recurrence, which provide a useful real-time prognostic information. LNR significantly affect the time kinetic of biochemical prognosis. Tumor burden and CNT play a crucial role in MTC survival, the intensity of follow-up must be tailored accordingly.

A Narrative Review of the Reciprocal Relationship Between Sleep Deprivation and Chronic Pain: The Role of Oxidative Stress.

Sleep is crucial for human health, insufficient sleep or poor sleep quality may negatively affect sleep function and lead to a state of sleep deprivation. Sleep deprivation can result in various health problems, including chronic pain. The intricate relationship between sleep and pain is complex and intertwined, with daytime pain affecting sleep quality and poor sleep increasing pain intensity. The article first describes the influence of sleep on the onset and development of pain, and then explores the impact of daytime pain intensity on nighttime sleep quality and subsequent pain thresholds. However, the primary emphasis is placed on the pivotal role of oxidative stress in this bidirectional relationship. Although the exact mechanisms underlying sleep and chronic pain are unclear, this review focuses on the role of oxidative stress. Numerous studies on sleep deprivation have demonstrated that it can lead to varying degrees of increased pain sensitivity, while chronic pain leads to sleep deprivation and further exacerbates pain. Further research on the role of oxidative stress in the mechanism of sleep deprivation-induced pain sensitization seems reasonable. This article comprehensively reviews the current research on the interrelationship between sleep deprivation, pain and the crucial role of oxidative stress.

Energy-storing DNA-based hydrogel remodels tumor microenvironments for laser-free photodynamic immunotherapy.

Photodynamic therapy (PDT) is a promising modality for cancer treatment. However, limited tissue penetration of external radiation and complicated tumor microenvironments (TMEs) restrict the antitumor efficiency of PDT. Herein, we report an energy-storing DNA-based hydrogel, which enables tumor-selective PDT without external radiation and regulates TMEs to achieve boosted PDT-mediated tumor immunotherapy. The system is constructed with two ultralong single-stranded DNA chains, which programmed partial complementary sequences and repeated G-quadruplex forming AS1411 aptamer for photosensitizer loading via hydrophobic interactions and π-π stacking. Then, energy-storing persistent luminescent nanoparticles are incorporated to sensitize PDT selectively at tumor site without external irradiation, generating tumor antigen to agitate antitumor immune response. The system catalytically generates O2 to alleviate hypoxia and releases inhibitors to reverse the IDO-related immunosuppression, synergistically remodeling the TMEs. In the mouse model of breast cancer, this hydrogel shows a remarkable tumor suppression rate of 78.3 %. Our study represents a new paradigm of photodynamic immunotherapy against cancer by combining laser-free fashion and TMEs remodeling.

Sustainable biochar application in anammox process: Unveiling novel pathways for enhanced nitrogen removal and efficient start-up at low temperature.

This study explored the use of biochar to accelerate the establishment of anaerobic ammonium oxidation (anammox) reactors operating at 15 ± 1℃. Incorporating 10 g/L bamboo charcoal in S1 accelerated the start-up of anammox in 87 days, which was significantly shorter than 103 days in S0 (without biochar). After 140 days, S1 exhibited a 10.9 % increase in nitrogen removal efficiency due to a 28.9 % elevation in extracellular polymeric substances, bolstering anammox bacterial resilience. Predominant anammox bacteria (Cadidatus Brocadia and Cadidatus Jettenia) showed relative abundances of 3.19 % and 0.38 % in S1, respectively, which were significantly higher than 0.40 % and 0.05 % in S0. Biochar provides favorable habitats for the enrichment of anammox bacteria and accelerates the establishment of anammox at low temperatures. This finding holds promise for enhancing the efficiency of anammox in cold climates and advancing sustainable wastewater nitrogen removal.

MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.

Exploring the Median Effective Dose of Ciprofol for Anesthesia Induction in Elderly Patients: Impact of Frailty on ED50.

Purpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients. Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS≥4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. Results: The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.

Prediction of Potential Suitable Areas and Priority Protection for Cupressus gigantea on the Tibetan Plateau.

Cupressus gigantea (C. gigantea) is an endemic endangered species on the Tibetan Plateau; its potential suitable areas and priority protection in the context of global climate change remain poorly predicted. This study utilized Biomod2 and Marxan to assess the potential suitable areas and priority protection for C. gigantea. Our study revealed that the suitable areas of C. gigantea were concentrated in the southeastern Tibetan Plateau, with the center in Lang County. Temperature was identified as a crucial environmental factor influencing the distribution of C. gigantea. Over the coming decades, the suitable range of C. gigantea expanded modestly, while its overall distribution remained relatively stable. Moreover, the center of the highly suitable areas tended to migrate towards Milin County in the northeast. Presently, significant areas for improvement are needed to establish protected areas for C. gigantea. The most feasible priority protected areas were located between the Lang and Milin counties in Tibet, which have more concentrated and undisturbed habitats. These results provide scientific guidance for the conservation and planning of C. gigantea, contributing to the stability and sustainability of ecosystems.

Distribution Pattern of Suitable Areas and Corridor Identification of Endangered Ephedra Species in China.

The suitable habitat of endangered Ephedra species has been severely threatened and affected by climate change and anthropogenic activities; however, their migration trends and restoration strategies are still relatively understudied. In this study, we utilized the MaxEnt model to simulate the suitable habitats of five endangered Ephedra species in China under current and future climate scenarios. Additionally, we identified significant ecological corridors by incorporating the minimum cumulative resistance (MCR) model. Under the current climate scenario, the suitable area of Ephedra equisetina Bunge, Ephedra intermedia Schrenk ex Mey, Ephedra sinica Stapf, and Ephedra monosperma Gmel ex Mey comprised 16% of the area in China, while Ephedra rhytidosperma Pachom comprised only 0.05%. The distribution patterns of these five Ephedra species were primarily influenced by altitude, salinity, temperature, and precipitation. Under future climate scenarios, the suitable areas of E. equisetina, E. intermedia, and E. sinica are projected to expand, while that of E. monosperma is expected to contract. Notably, E. rhytidosperma will lose its suitable area in the future. Our identified ecological corridors showed that the first-level corridors encompassed a wider geographical expanse, incorporating E. equisetina, E. intermedia, E. sinica, and E. monosperma, while that of E. rhytidosperma exhibited a shorter length and covered fewer geographical areas. Overall, our study provides novel insights into identifying priority protected areas and protection strategies targeting endangered Ephedra species.

The influence of WeChat education and care program on anxiety, depression, insomnia, and general state of health in parents of pediatric acute lymphoblastic leukemia patients.

PURPOSE: WeChat-based education and care program serves as a promising nursing method for relieving mental stress in parents of pediatric patients. This study purposed to explore the influence of the WeChat education and care program (WECP) on mental health, insomnia, and general state of health in parents of pediatric acute lymphoblastic leukemia (ALL) patients. METHODS: Totally, 146 parents of 73 primary pediatric ALL patients were randomized into the WECP group (74 parents of 37 patients) and standard care (SC) group (72 parents of 36 patients) to receive a 6-month corresponding intervention. Self-rating anxiety scale (SAS), self-rating depression scale (SDS), Athens insomnia scale (AIS), and 12-item general health questionnaire (GHQ-12) were assessed in parents of patients. RESULTS: SAS scores at the third month (M3) (P = 0.041) and M6 (P = 0.032) were reduced in WECP group versus SC group. SAS-defined anxiety rate at M6 (P = 0.035) was declined in WECP group versus SC group. SDS score at M6 was descended in WECP group versus SC group (P = 0.024). However, there was no discrepancy in SDS-defined depression rate at any time point between groups (all P > 0.05). AIS scores at M1 (P = 0.015) and M6 (P = 0.021), as well as GHQ-12 scores at M3 (P = 0.007) and M6 (P = 0.001) were decreased in WECP group versus SC group. By subgroup analyses, WECP exhibited good effects at M6 in mothers, but not in fathers. CONCLUSION: WECP is a feasible and efficacy intervention to improve mental stress and health status among parents of pediatric ALL patients, especially in mothers.

Preliminary genetic parameter estimates of meat quality traits in Hu sheep.

Because substantial numbers of Chinese consumers are prepared to pay for tender and quality lamb, meat quality traits are becoming more relevant for breeding programs for Chinese sheep breeds. The current study estimated heritabilities and genetic correlations for 13 meat quality traits recorded on lamb loins from Hu sheep. Heritability estimates ranged from 0.04 ± 0.06 for meat redness at 45 min to 0.57 ± 0.10 for drip loss, with most of the meat quality traits having moderate heritabilities. Positive genetic correlations were observed among meat color traits. Intramuscular fat (IMF) was genetically correlated with most meat quality traits, indicating that increasing IMF can favor meat pH, color, and tenderness, but would lead to increased cooking loss. Direct selection to increase IMF of loins is recommended to be included in breeding programs for Hu sheep, as it was more efficient than indirect selection on the other meat quality traits. The genetic parameters presented in this preliminary study provide valuable genetic information needed to design a breeding program aimed at improving the quality of lamb meat from Hu sheep.

Linkage of CDC42 and T-helper cell ratio with anxiety, depression and quality of life in ST-elevation myocardial infarction.

Objective: To investigate the correlations between CDC42 and T-cell subsets concerning anxiety, depression and quality of life in ST-elevation myocardial infarction patients undergoing percutaneous coronary intervention. Methods: Sera from 156 participants were analyzed for CDC42 levels and Th1, Th2, Th17 and Treg cells. Results: CDC42 correlated with reduced Th1/Th2 and Th17/Treg ratios, lower anxiety and depression, and higher EuroQol visual analog scale (EQ-VAS) score. The Th17/Treg ratio correlated with elevated anxiety, depression, EuroQol-5 dimensions score and decreased EQ-VAS score. The Th1/Th2 ratio was positively related to the EQ-VAS score. Conclusion: CDC42 correlates with reduced Th1/Th2 and Th17/Treg ratios, reduced anxiety and depression, and improved quality of life in ST-elevation myocardial infarction patients undergoing percutaneous coronary intervention.

CDC42 is a protein that regulates immune cells and negative mood. This study enrolled 156 patients with ST-elevation myocardial infarction (a severe type of coronary artery disease) who had percutaneous coronary intervention (a treatment that improves coronary blood flow). Their blood was collected for detecting CDC42 and specific immune cells, including Th1, Th2, Th17 and Treg cells. Their feelings of anxiety, depression and quality of life (QoL) were assessed using relevant questionnaires. The results showed that if a patient presented with reduced CDC42, they would have a high probability of anxiety and depression and poor QoL, as well as increased Th1 and Th17 cells. The study also found that patients with increased Th17 cells or decreased Treg cells would have a high possibility of anxiety and depression, as well as bad QoL. In addition, if a patient had increased Th2 cells, they would have a high probability of poor QoL. In summary, the detection of CDC42 can help ST-elevation myocardial infarction patients who have percutaneous coronary intervention better observe anxiety and depression.

The Spatiotemporal Dynamics of Insect Predator-Prey System Incorporating Refuge Effect.

The insect predator-prey system mediates several feedback mechanisms which regulate species abundance and spatial distribution. However, the spatiotemporal dynamics of such discrete systems with the refuge effect remain elusive. In this study, we analyzed a discrete Holling type II model incorporating the refuge effect using theoretical calculations and numerical simulations, and selected moths with high and low growth rates as two exemplifications. The result indicates that only the flip bifurcation opens the routes to chaos, and the system undergoes four spatiotemporally behavioral patterns (from the frozen random pattern to the defect chaotic diffusion pattern, then the competition intermittency pattern, and finally to the fully developed turbulence pattern). Furthermore, as the refuge effect increases, moths with relatively slower growth rates tend to maintain stability at relatively low densities, whereas moths with relatively faster growth rates can induce chaos and unpredictability on the population. According to the theoretical guidance of this study, the refuge effect can be adjusted to control pest populations effectively, which provides a new theoretical perspective and is a feasible tool for protecting crops.

A Smart DNA Hydrogel Enables Synergistic Immunotherapy and Photodynamic Therapy of Melanoma.

Immunotherapy faces insufficient immune activation and limited immune effectiveness. Herein, we report a smart DNA hydrogel that enables the release of multivalent functional units at the tumor site to enhance the efficacy of immunotherapy. The smart DNA hydrogel was assembled from two types of ultra-long DNA chains synthesized via rolling circle amplification. One DNA chain contained immune adjuvant CpG oligonucleotides and polyaptamers for loading natural killer cell-derived exosomes; the other chain contained multivalent G-quadruplex for loading photodynamic agents. DNA chains formed DNA hydrogel through base-pairing. HhaI restriction endonuclease sites were designed between functional units. Upon stimuli in the tumor sites, the hydrogel was effectively cleaved by the released HhaI and disassembled into functional units. Natural killer cell-derived exosomes played an anti-tumor role, and the CpG oligonucleotide activated antigen-presenting cells to enhance the immunotherapy. Besides the tumor-killing effect of photodynamic therapy, the generated cellular debris acted as an immune antigen to further enhance the immunotherapeutic effect. In a mouse melanoma orthotopic model, the smart DNA hydrogel as a localized therapeutic agent, achieved a remarkable tumor suppression rate of 91.2 %. The smart DNA hydrogel exhibited enhanced efficacy of synergistic immunotherapy and photodynamic therapy, expanding the application of DNA materials in biomedicine.

Effectiveness of perioperative low-dose esketamine infusion for postoperative pain management in pediatric urological surgery: a prospective clinical trial.

BACKGROUND: Postoperative pain is common in pediatric urological surgery. The study assess the impact of perioperative intravenous infusion of low-dose esketamine on postoperative pain in pediatric urological surgery. METHODS: Pediatric patients (n = 80) undergoing urological surgery were randomized into four groups. Patients in the control group were administered an analgesic pump containing only hydromorphone at a dose of 0.1 mg/kg (Hydromorphone Group 1, H1) or 0.15 mg/kg (Hydromorphone Group 2, H2). Patients in the experimental group were injected intravenously with 0.3 mg/kg of esketamine (Esketamine group 1, ES1) or equal volume of saline (Esketamine Group 2, ES2) during anesthesia induction. Esketamine 1.0 mg/kg and hydromorphone 0.1 mg/kg were added to the analgesic pump. Face, Leg, Activity, Crying, and Comfort (FLACC) scale or the Numerical Rating Scale (NRS) and adverse effects were recorded at 2, 6, 24, and 48 h postoperatively. Additionally, total and effective PCA button presses were recorded. RESULTS: In comparison to the H1 group, the pain scores were notably reduced at all postoperative time points in both the ES1 and H2 groups. The ES2 group exhibited lower pain scores only at 24 and 48 h postoperatively. When compared to the H2 group, there were no significant differences in pain scores at various postoperative time points in the ES2 group. However, the ES1 group demonstrated significantly lower pain scores at 6, 24 and 48 h postoperatively, and these scores were also significantly lower than those observed in the ES2 group. The total and effective number of PCA button presses in the ES1, ES2 and H2 group were lower than that in the H1 group (P < 0.001). The incidence of adverse effects within 48 h after surgery was 15% in ES1, 22% in ES2, 58% in H1, and 42% in H2, respectively (P = 0.021). CONCLUSIONS: The use of low-dose esketamine infusion in analgesia pump can effectively alleviates postoperative pain in pediatric urological patients, leading to a significant reduction in the number of analgesic pump button press. The combined approach of perioperative anesthesia induction and analgesia pump administration is recommended for optimal pain management in these patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry- ChiCTR2300073879 (24/07/2023).

Identification of high-risk population of pneumoconiosis using deep learning segmentation of lung 3D images and radiomics texture analysis.

OBJECTION: The aim of this study is to develop an early-warning model for identifying high-risk populations of pneumoconiosis by combining lung 3D images and radiomics lung texture features. METHODS: A retrospective study was conducted, including 600 dust-exposed workers and 300 confirmed pneumoconiosis patients. Chest computed tomography (CT) images were divided into a training set and a test set in a 2:1 ratio. Whole-lung segmentation was performed using deep learning models for feature extraction of radiomics. Two feature selection algorithms and five classification models were used. The optimal model was selected using a 10-fold cross-validation strategy, and the calibration curve and decision curve were evaluated. To verify the applicability of the model, the diagnostic efficiency and accuracy between the model and human interpretation were compared. Additionally, the risk probabilities for different risk groups defined by the model were compared at different time intervals. RESULTS: Four radiomics features were ultimately used to construct the predictive model. The logistic regression model was the most stable in both the training set and testing set, with an area under curve (AUC) of 0.964 (95 % confidence interval [CI], 0.950-0.976) and 0.947 (95 %CI, 0.925-0.964). In the training and testing sets, the Brier scores were 0.092 and 0.14, respectively, with threshold probability ranges of 2 %-99 % and 2 %-85 %. These results indicate that the model exhibits good calibration and clinical benefit. The comparison between the model and human interpretation showed that the model was not inferior in terms of diagnostic efficiency and accuracy. Additionally, the high-risk population identified by the model was diagnosed as pneumoconiosis two years later. CONCLUSION: This study provides a meticulous and quantifiable method for detecting and assessing the risk of pneumoconiosis, building upon accurate diagnosis. Employing risk scoring and probability estimation, not only enhances the efficiency of diagnostic physicians but also provides a valuable reference for controlling the occurrence of pneumoconiosis.

Multimodal Model to Predict Tissue-to-Blood Partition Coefficients of Chemicals in Mammals and Fish.

Tissue-to-blood partition coefficients (Ptb) are key parameters for assessing toxicokinetics of xenobiotics in organisms, yet their experimental data were lacking. Experimental methods for measuring Ptb values are inefficient, underscoring the urgent need for prediction models. However, most existing models failed to fully exploit Ptb data from diverse sources, and their applicability domain (AD) was limited. The current study developed a multimodal model capable of processing and integrating textual (categorical features) and numerical information (molecular descriptors/fingerprints) to simultaneously predict Ptb values across various species, tissues, blood matrices, and measurement methods. Artificial neural network algorithms with embedding layers were used for the multimodal modeling. The corresponding unimodal models were developed for comparison. Results showed that the multimodal model outperformed unimodal models. To enhance the reliability of the model, a method considering categorical features, weighted molecular similarity density, and weighted inconsistency in molecular activities of structure-activity landscapes was used to characterize the AD. The model constrained by the AD exhibited better prediction accuracy for the validation set, with the determination coefficient, root mean-square error, and mean absolute error being 0.843, 0.276, and 0.213 log units, respectively. The multimodal model coupled with the AD characterization can serve as an efficient tool for internal exposure assessment of chemicals.