A Self-supervised Learning-Based Fine-Grained Classification Model for Distinguishing Malignant From Benign Subcentimeter Solid Pulmonary Nodules.

RATIONALE AND OBJECTIVES: Diagnosing subcentimeter solid pulmonary nodules (SSPNs) remains challenging in clinical practice. Deep learning may perform better than conventional methods in differentiating benign and malignant pulmonary nodules. This study aimed to develop and validate a model for differentiating malignant and benign SSPNs using CT images. MATERIALS AND METHODS: This retrospective study included consecutive patients with SSPNs detected between January 2015 and October 2021 as an internal dataset. Malignancy was confirmed pathologically; benignity was confirmed pathologically or via follow-up evaluations. The SSPNs were segmented manually. A self-supervision pre-training-based fine-grained network was developed for predicting SSPN malignancy. The pre-trained model was established using data from the National Lung Screening Trial, Lung Nodule Analysis 2016, and a database of 5478 pulmonary nodules from the previous study, with subsequent fine-tuning using the internal dataset. The model's efficacy was investigated using an external cohort from another center, and its accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined. RESULTS: Overall, 1276 patients (mean age, 56 ± 10 years; 497 males) with 1389 SSPNs (mean diameter, 7.5 ± 2.0 mm; 625 benign) were enrolled. The internal dataset was specifically enriched for malignancy. The model's performance in the internal testing set (316 SSPNs) was: AUC, 0.964 (95% confidence interval (95%CI): 0.942-0.986); accuracy, 0.934; sensitivity, 0.965; and specificity, 0.908. The model's performance in the external test set (202 SSPNs) was: AUC, 0.945 (95% CI: 0.910-0.979); accuracy, 0.911; sensitivity, 0.977; and specificity, 0.860. CONCLUSION: This deep learning model was robust and exhibited good performance in predicting the malignancy of SSPNs, which could help optimize patient management.

Predicting epidermal growth factor receptor mutations in non-small cell lung cancer through dual-layer spectral CT: a prospective study.

OBJECTIVE: To determine whether quantitative parameters of detector-derived dual-layer spectral computed tomography (DLCT) can reliably identify epidermal growth factor receptor (EGFR) mutation status in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with NSCLC who underwent arterial phase (AP) and venous phase (VP) DLCT between December 2021 and November 2022 were subdivided into the mutated and wild-type EGFR groups following EGFR mutation testing. Their baseline clinical data, conventional CT images, and spectral images were obtained. Iodine concentration (IC), iodine no water (INW), effective atomic number (Zeff), virtual monoenergetic images, the slope of the spectral attenuation curve (λHU), enhancement degree (ED), arterial enhancement fraction (AEF), and normalized AEF (NAEF) were measured for each lesion. RESULTS: Ninety-two patients (median age, 61 years, interquartile range [51, 67]; 33 men) were evaluated. The univariate analysis indicated that IC, normalized IC (NIC), INW and ED for the AP and VP, as well as Zeff and λHU for the VP were significantly associated with EGFR mutation status (all p < 0.05). INW(VP) showed the best diagnostic performance (AUC, 0.892 [95% confidence interval {CI}: 0.823, 0.960]). However, neither AEF (p = 0.156) nor NAEF (p = 0.567) showed significant differences between the two groups. The multivariate analysis showed that INW(AP) and NIC(VP) were significant predictors of EGFR mutation status, with the latter showing better performance (p = 0.029; AUC, 0.897 [95% CI: 0.816, 0.951] vs. 0.774 [95% CI: 0.675, 0.855]). CONCLUSION: Quantitative parameters of DLCT can help predict EGFR mutation status in patients with NSCLC. CRITICAL RELEVANCE STATEMENT: Quantitative parameters of DLCT, especially NIC(VP), can help predict EGFR mutation status in patients with NSCLC, facilitating appropriate and individualized treatment for them. KEY POINTS: Determining EGFR mutation status in patients with NSCLC before starting therapy is essential. Quantitative parameters of DLCT can predict EGFR mutation status in NSCLC patients. NIC in venous phase is an important parameter to guide individualized treatment selection for NSCLC patients.

Correlation between different points on the face and the width of maxillary anterior teeth.

Statement of problem: There is currently no consensus on the relationship between maxillary anterior teeth and different facial anthropometric measurements. Additionally, whether these relationships vary by age and sex remains unreported. Purpose: This clinical study aimed to investigate the relationship between the intercanine distance (ICaD) and intercanthal distance (ICD), interpupillary distance (IPD), interalar width (IAW), and intercommissural width (ICW), and to compare whether these relationships differ between different age and sex populations. Material and methods: Participants (n = 409) were enrolled according to the inclusion criteria, and their standardized digital images were taken to measure facial and oral segments through an image processing program. The differences between ICaD and four facial measurements and the sexual differences for all measurements were compared using the 1-sample t-test. The differences among different age groups for all measurements were compared using the one-way analysis of variance (ANOVA) test, and a least significant difference (LSD) test was used for multiple comparisons. The association between ICaD and the four facial measurements was evaluated using Pearson correlation analysis. The correlation between ICaD and four facial measurements was evaluated using linear regression. Differences in regression equations among the subgroups were evaluated through subgroup regression analysis and the significance test of the difference between the two regression coefficients. Tests of significance were two-sided, with alpha level of 0.05. The reliability of the results was evaluated by calculating intraclass correlation coefficients. Results: The ICD, IPD, ICW, and IAW significantly differed from the ICaD in both sexes (P < 0.01). All measurements were significantly greater in men than in women (P < 0.01). The differences among the age groups were statistically significant for all measurements except IPD (P < 0.05). A significant positive correlation was found between all facial measurements (r = 0.258 [ICD], r = 0.334 [IPD], r = 0.389 [ICW], and r = 0.393 [IAW]) and the ICaD in both sexes. The highest correlation was found between ICW(r = 0.345) and ICAD in men and IAW (r = 0.285) and ICAD in women. Except for the 20-29 and 50-59 age groups, the mathematical equations of ICaD and facial anthropometric measurements differed among the other age groups and sexes. Conclusions: ICD, IPD, ICW, and IAW cannot be directly used to determine ICaD in both sexes. Nevertheless, when observed from the frontal aspect, by the use of digital images, all facial measurements correlated to the intercanine distance, with a high probability. The mathematical formulae combined with facial anthropological measurements can help ensure the combined width of the six maxillary anterior teeth, but the effects of sex and age differences should be considered.

Radiological and clinical features of large consolidative-type pulmonary invasive mucinous adenocarcinoma.

BACKGROUND: This study aimed to investigate the radiological, pathological, and prognostic characteristics of large consolidative-type pulmonary invasive mucinous adenocarcinomas (IMA). METHODS: We retrospectively reviewed 738 patients who confirmed IMA between January 2010 and August 2022, and two radiologists reviewed imaging data to determine subtypes. We included 41 patients with pathologically large consolidative-type IMA. We analyzed their radiological, pathological, and prognostic characteristics. The recurrence-free survival (RFS) and overall survival (OS) were determined using the Kaplan-Meier method. RESULTS: Most lesions were located in the lower lobe, with 46.3% patients showing multiple lesions. Halo, angiogram, vacuole, air bronchogram, and dead branch sign were observed in 97.6%, 73.2%, 63.4%, 61.0%, and 61.0% of the cases, respectively. Unevenly low enhancement was observed in 88.89% of patients. T3 and T4 pathological stages were observed in 50.0% and 30.6% of patients, respectively. Lymph node metastasis was observed in 16.7% patients, with no distant metastasis. Spread-through air spaces and intrapulmonary dissemination were observed in 27.8% and 19.4% patients, respectively. Moreover, Kirsten rat sarcoma viral oncogene mutations were found in 68.6% of cases, and no epidermal growth factor receptor mutations were seen. Among all mutation sites, G12V mutation is the most common, accounting for 40%. The average RFS and OS were 19.4 and 66.4 months, respectively, with 3-year RFS and OS rates of 30.0% and 75.0%, respectively. Pleural invasion and lymph node metastasis were independent risk factors for diagnosis. CONCLUSION: Halo, vacuole, angiogram, and dead branch signs were frequently observed in consolidative-type IMA. Kirsten rat sarcoma viral oncogene mutations are common in consolidative-type IMA, especially site G12V, whereas epidermal growth factor receptor mutations were rare; therefore, gene immunotherapy was more difficult. Most patients were in stage T3-T4; however, lymph node metastasis was rare.

Development of a combined radiomics and CT feature-based model for differentiating malignant from benign subcentimeter solid pulmonary nodules.

BACKGROUND: We aimed to develop a combined model based on radiomics and computed tomography (CT) imaging features for use in differential diagnosis of benign and malignant subcentimeter (≤ 10 mm) solid pulmonary nodules (SSPNs). METHODS: A total of 324 patients with SSPNs were analyzed retrospectively between May 2016 and June 2022. Malignant nodules (n = 158) were confirmed by pathology, and benign nodules (n = 166) were confirmed by follow-up or pathology. SSPNs were divided into training (n = 226) and testing (n = 98) cohorts. A total of 2107 radiomics features were extracted from contrast-enhanced CT. The clinical and CT characteristics retained after univariate and multivariable logistic regression analyses were used to develop the clinical model. The combined model was established by associating radiomics features with CT imaging features using logistic regression. The performance of each model was evaluated using the area under the receiver-operating characteristic curve (AUC). RESULTS: Six CT imaging features were independent predictors of SSPNs, and four radiomics features were selected after a dimensionality reduction. The combined model constructed by the logistic regression method had the best performance in differentiating malignant from benign SSPNs, with an AUC of 0.942 (95% confidence interval 0.918-0.966) in the training group and an AUC of 0.930 (0.902-0.957) in the testing group. The decision curve analysis showed that the combined model had clinical application value. CONCLUSIONS: The combined model incorporating radiomics and CT imaging features had excellent discriminative ability and can potentially aid radiologists in diagnosing malignant from benign SSPNs. RELEVANCE STATEMENT: The model combined radiomics features and clinical features achieved good efficiency in predicting malignant from benign SSPNs, having the potential to assist in early diagnosis of lung cancer and improving follow-up strategies in clinical work. KEY POINTS: • We developed a pulmonary nodule diagnostic model including radiomics and CT features. • The model yielded the best performance in differentiating malignant from benign nodules. • The combined model had clinical application value and excellent discriminative ability. • The model can assist radiologists in diagnosing malignant from benign pulmonary nodules.

Gastrodin improves osteoblast function and adhesion to titanium surface in a high glucose environment.

Objective: To investigate the effects of gastrodin on the biological behavior of osteoblasts and osseointegration on the surface of the titanium plate in a high glucose environment, and to explore the possible regulatory mechanisms involved. Methods: A high glucose-induced oxidative damage model of MC3T3-E1 cells was established in vitro to observe the effects of gastrodin on cellular oxidative stress, cell viability, osteogenic differentiation, mineralization, migration, and adhesion ability on the titanium surface. Results: High glucose environment can cause oxidative stress damage to MC3T3-E1 cells, leading to a decrease in cell viability, osteogenesis, migration, adhesion and other functions. Gastrodin can upregulate the expression of antioxidant enzymes (Nrf2 and HO-1) and osteogenic differentiation related proteins (RUNX2 and BMP2) in MC3T3-E1 cells in high glucose environment, thereby inhibiting the excessive production of intracellular reactive oxygen species (ROS), reversing the decrease in cell viability, and improving the osteogenic differentiation and mineralization ability of osteoblasts. And gastrodin alleviated the decline in cell migration ability, improved the morphology of the cytoskeleton and increased the adhesion ability of osteoblasts on the surface of titanium plates in high glucose environment. However, gastrodin itself did not affect the cell viability, osteogenic differentiation and mineralization ability of osteoblasts in normal environment. Conclusions: Gastrodin may protect MC3T3-E1 cells osteogenesis and osseointegration on the surface of the titanium plate in vitro by upregulating antioxidant enzymes expression, and attenuating high glucose-induced oxidative stress. Therefore, gastrodin may be a potential drug to address the problem of poor implant osseointegration in patients with diabetes.

Genome-Wide Identification and Expression Profiling of Potato (Solanum tuberosum L.) Universal Stress Proteins Reveal Essential Roles in Mechanical Damage and Deoxynivalenol Stress.

Universal stress proteins (USPs) play an important regulatory role in responses to abiotic stress. Most of the research related to USPs so far has been conducted on plant models such as Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa L.), and cotton (Gossypium hirsutum L.). The potato (Solanum tuberosum L.) is one of the four major food crops in the world. The potato is susceptible to mechanical damage and infection by pathogenic fungi during transport and storage. Deoxynivalenol (DON) released by Fusarium can seriously degrade the quality of potatoes. As a result, it is of great significance to study the expression pattern of the potato StUSP gene family under abiotic stress conditions. In this study, a total of 108 USP genes were identified from the genome of the Atlantic potato, divided into four subgroups. Based on their genetic structure, the physical and chemical properties of their proteins and other aspects of their biological characteristics are comprehensively analyzed. Collinear analysis showed that the homologous genes of StUSPs and four other representative species (Solanum lycopersicum, Arabidopsis, Oryza sativa L., and Nicotiana attenuata) were highly conserved. The cis-regulatory elements of the StUSPs promoter are involved in plant hormones, environmental stress, mechanical damage, and light response. RNA-seq analysis showed that there are differences in the expression patterns of members of each subgroup under different abiotic stresses. A Weighted Gene Coexpression Network Analysis (WGCNA) of the central gene showed that the differential coexpression gene is mainly involved in the plant-pathogen response process, plant hormone signal transduction, and the biosynthesis process of secondary metabolites. Through qRT-PCR analysis, it was confirmed that StUSP13, StUSP14, StUSP15, and StUSP41 may be important candidate genes involved in the response to adversity stress in potatoes. The results of this study provide a basis for further research on the functional analysis of StUSPs in the response of potatoes to adversity stress.

Diagnostic performance of a deep learning-based method in differentiating malignant from benign subcentimeter (≤10 mm) solid pulmonary nodules.

Background: This study assessed the diagnostic performance of a deep learning (DL)-based model for differentiating malignant subcentimeter (≤10 mm) solid pulmonary nodules (SSPNs) from benign ones in computed tomography (CT) images compared against radiologists with 10 and 15 years of experience in thoracic imaging (medium-senior seniority). Methods: Overall, 200 SSPNs (100 benign and 100 malignant) were retrospectively collected. Malignancy was confirmed by pathology, and benignity was confirmed by follow-up or pathology. CT images were fed into the DL model to obtain the probability of malignancy (range, 0-100%) for each nodule. According to the diagnostic results, enrolled nodules were classified into benign, malignant, or indeterminate. The accuracy and diagnostic composition of the model were compared with those of the radiologists using the McNemar-Bowker test. Enrolled nodules were divided into 3-6-, 6-8-, and 8-10-mm subgroups. For each subgroup, the diagnostic results of the model were compared with those of the radiologists. Results: The accuracy of the DL model, in differentiating malignant and benign SSPNs, was significantly higher than that of the radiologists (71.5% vs. 38.5%, P<0.001). The DL model reported more benign or malignant deterministic results and fewer indeterminate results. In subgroup analysis of nodule size, the DL model also yielded higher performance in comparison with that of the radiologists, providing fewer indeterminate results. The accuracy of the two methods in the 3-6-, 6-8-, and 8-10-mm subgroups was 75.5% vs. 28.3% (P<0.001), 62.0% vs. 28.2% (P<0.001), and 77.6% vs. 55.3% (P=0.001), respectively, and the indeterminate results were 3.8% vs. 66.0%, 8.5% vs. 66.2%, and 2.6% vs. 35.5% (all P<0.001), respectively. Conclusions: The DL-based method yielded higher performance in comparison with that of the radiologists in differentiating malignant and benign SSPNs. This DL model may reduce uncertainty in diagnosis and improve diagnostic accuracy, especially for SSPNs smaller than 8 mm.

A review: Mechanism and prospect of gastrodin in prevention and treatment of T2DM and COVID-19.

Gastrodin is an extract from the dried tuber of the Chinese herb Gastrodia elata (Tian ma), with anti-inflammatory, antioxidant, and antiviral properties. Recent studies have shown that, compared to commonly used diabetes drugs, gastrodin has antidiabetic effects in multiple ways, with characteristics of low cost, high safety, less side effects, protection of ß-cell function, relieving insulin resistance and alleviating multiple complications. In addition, it is confirmed that gastrodin can protect the function of lung and other organs, enhance antiviral activity via upregulating the type I interferon (IFN-I), and inhibit angiotensin II (AngII), a key factor in "cytokine storm" caused by COVID-19. Therefore, we reviewed the effect and mechanism of gastrodin on type 2 diabetes mellitus (T2DM), and speculated other potential mechanisms of gastrodin in alleviating insulin resistance from insulin signal pathway, inflammation, mitochondrial and endoplasmic reticulum and its potential in the prevention and treatment of COVID-19. We hope to provide new direction and treatment strategy for basic research and clinical work: gastrodin is considered as a drug for the prevention and treatment of diabetes and COVID-19.

Hemolysin from Aeromonas hydrophila enhances the host's serum enzyme activity and regulates transcriptional responses in the spleen of Cyprinus rubrofuscus.

Aeromonas hydrophila is a conditional pathogen impacting public hygiene and safety. Hemolysin is a virulence factor of Aeromonas hydrophila that causes erythrocyte hemolysis, yet its transcriptional response to Cyprinus rubrofuscus remains unknown. Our investigation confirmed the hemolysis of hemolysin from A. hydrophila. Serum enzyme activity was evaluated weekly after C. rubrofuscus were immunized with hemolysin Ahh1. The results showed that the hemolysin enhances the serum superoxide dismutase (SOD), lysozyme (LZM), and catalase (CAT) activity, which reached a maximum on day 14. To elucidate the molecular interaction between hemolysin from A. hydrophila and the host, we performed transcriptome sequencing on the spleen of C. rubrofuscus 14 days post hemolysin infection. The total number of clean reads was 41.37 Gb, resulting in 79,832 unigenes with an N50 length of 1863 bp. There were 1982 significantly differentially expressed genes (DEGs), including 1083 upregulated genes and 899 downregulated genes. Transcript levels of the genes, such as LA6BL, CD2, and NLRC5, were significantly downregulated, while those of IL11, IL1R2, and IL8 were dramatically upregulated. The DEGs were mainly enriched in the immune disease, viral protein interaction with cytokine and cytokine receptor, and toll-like receptor pathways, suggesting that hemolysin stimulation can activate the transcriptional responses. RT-qPCR experiments results of seven genes, IL-8, STAT2, CTSK, PRF1, CXCL9, TLR5, and SACS, showed that their expression was highly concordant with RNA-seq data. We clarified for the first time the key genes and signaling pathways response to hemolysin from A. hydrophila, which offers strategies for treating and preventing diseases.

Fully digital workflow for duplicating clasp-retained removable partial dentures using three-dimensional printing: A clinical report.

This clinical report describes a fully digital workflow for replicating removable partial dentures (RPDs). The artificial teeth and denture base of existing dentures were duplicated and applied to new dentures with a redesigned framework. After the components of RPDs had been separated from the scan data of the existing dentures, they were fabricated using 3-dimensional printing and assembled to create a new denture.

Iva xanthiifolia leaf extract reduced the diversity of indigenous plant rhizosphere bacteria.

BACKGROUND: Iva xanthiifolia, native to North America, is now widely distributed in northeastern China and has become a vicious invasive plant. This article aims to probe the role of leaf extract in the invasion of I. xanthiifolia. METHODS: We collected the rhizosphere soil of Amaranthus tricolor and Setaria viridis in the invasive zone, the noninvasive zone and the noninvasive zone treated with extract from I. xanthiifolia leaf, and obtained I. xanthiifolia rhizosphere soil in the invasive zone. All wild plants were identified by Xu Yongqing. I. xanthiifolia (collection number: RQSB04100), A. tricolor (collection number: 831,030) and S. viridis (collection number: CF-0002-034) are all included in Chinese Virtual Herbarium ( https://www.cvh.ac.cn/index.php ). The soil bacterial diversity was analyzed based on the Illumina HiSeq sequencing platform. Subsequently, taxonomic analysis and Faprotax functional prediction were performed. RESULTS: The results showed that the leaf extract significantly reduced the diversity of indigenous plant rhizosphere bacteria. A. tricolor and S. viridis rhizobacterial phylum and genus abundances were significantly reduced under the influence of I. xanthiifolia or its leaf extract. The results of functional prediction showed that bacterial abundance changes induced by leaf extracts could potentially hinder nutrient cycling in native plants and increased bacterial abundance in the A. tricolor rhizosphere related to aromatic compound degradation. In addition, the greatest number of sensitive Operational Taxonomic Units (OTUs) appeared in the rhizosphere when S. viridis was in response to the invasion of I. xanthiifolia. It can be seen that A. tricolor and S. viridis have different mechanisms in response to the invasion of I. xanthiifolia. CONCLUSION: I. xanthiifolia leaves material has potential role in invasion by altering indigenous plant rhizosphere bacteria.

Genome-Wide Identification of the NPR1-like Gene Family in Solanum tuberosum and Functional Characterization of StNPR1 in Resistance to Ralstonia solanacearum.

The NPR1 (nonexpressor of pathogenesis-related genes 1) gene is an activator of the systemic acquisition of resistance (SAR) in plants and is one of the central factors in their response to pathogenic bacterial infestation, playing an important role in plant disease resistance. Potato (Solanum tuberosum) is a crucial non-grain crop that has been extensively studied. However, the identification and analysis of the NPR1-like gene within potato have not been understood well. In this study, a total of six NPR1-like proteins were identified in potato, and phylogenetic analysis showed that the six NPR1-like proteins in Solanum tuberosum could be divided into three major groups with NPR1-related proteins from Arabidopsis thaliana and other plants. Analysis of the exon-intron patterns and protein domains of the six NPR1-like genes from potato showed that the exon-intron patterns and protein domains of the NPR1-like genes belonging to the same Arabidopsis thaliana subfamily were similar. By performing quantitative real-time PCR (qRT-PCR) analysis, we found that six NPR1-like proteins have different expression patterns in different potato tissues. In addition, the expression of three StNPR1 genes was significantly downregulated after being infected by Ralstonia solanacearum (RS), while the difference in the expression of StNPR2/3 was insignificant. We also established potato StNPR1 overexpression lines that showed a significantly increased resistance to R. solanacearum and elevated activities of chitinase, ß-1,3-glucanase, and phenylalanine deaminase. Increased peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) activities, as well as decreased hydrogen peroxide, regulated the dynamic balance of reactive oxygen species (ROS) in the StNPR1 overexpression lines. The transgenic plants activated the expression of the genes associated with the Salicylic acid (SA) defense response but suppressed the expression of the genes associated with Jasmonic acid (JA) signaling. This resulted in resistance to Ralstonia solanacearum.

Longitudinal assessment of cardiac parameters through MRI in breast cancer patients treated with anti-HER2 therapy.

BACKGROUND: We evaluated the early changes in left ventricular (LV) volumetric, functional, and tissue characteristics in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with trastuzumab and/or pertuzumab at cardiac magnetic resonance imaging (MRI). METHODS: HER2-positive breast cancer patients undergoing planned anti-HER2 therapy and nonanthracycline-based chemotherapy were enrolled and subdivided into dual anti-HER2 (trastuzumab plus pertuzumab) group and trastuzumab group. Cardiac MRI was performed before treatment and three months after starting, covering ventricular volumes, cardiac function, systolic myocardial strain, myocardial oedema, and T1 and T2 relaxation times. Cardiac dysfunction was primarily defined as a > 10% reduction in LV ejection fraction (LVEF) to < 55% and/or a > 15% global longitudinal strain (GLS) change at the follow-up MRI examination. RESULTS: Twenty-four HER2-positive patients were evaluated (16 in the dual anti-HER2 group, 8 in the trastuzumab group). Six patients developed cardiac dysfunction at follow-up, five of them in the dual anti-HER2 group. One patient developed symptomatic heart failure, and five patients developed asymptomatic cardiac dysfunction. Patients displayed significantly decreased systolic function and increased T1 and T2 relaxation time at follow-up (p ≤ 0.031). Systolic dysfunction remained significant in the dual anti-HER2 group. The decrease in GLS in the trastuzumab group was not significant (p = 0.169). T1 and T2 relaxation times tended to increase, but this was not significant at subgroup analysis. CONCLUSIONS: Cardiac MRI scans showed frequent signs of subclinical cardiotoxicity after short-term anti-HER2 therapy and nonanthracycline-based chemotherapy; the effect was slightly stronger in patients treated with dual therapy. KEY POINTS: • A frequent subclinical cardiotoxicity was detected by cardiac magnetic resonance imaging after short-term anti-human epidermal growth factor receptor 2 (HER2) therapy. • The change in myocardial strain was more marked in patients treated with dual (trastuzumab plus pertuzumab) than with trastuzumab only anti-HER2 therapy. • Cardiotoxicity surveillance through MRI is an interesting option particularly in patients treated with dual anti-HER2 therapy.

Combined Transcriptome and Metabolome Analysis Reveals Adaptive Defense Responses to DON Induction in Potato.

Phytophthora infestans poses a serious threat to potato production, storage, and processing. Understanding plant immunity triggered by fungal elicitors is important for the effective control of plant diseases. However, the role of the potato stress response to Fusarium toxin deoxynivalenol (DON)-induced stress is still not fully understood. In this study, the metabolites of DON-treated potato tubers were studied for four time intervals using UPLC-MS/MS. We identified 676 metabolites, and differential accumulation metabolite analysis showed that alkaloids, phenolic acids, and flavonoids were the major differential metabolites that directly determined defense response. Transcriptome data showed that differentially expressed genes (DEGs) were significantly enriched in phenylpropane and flavonoid metabolic pathways. Weighted gene co-expression network analysis (WGCNA) identified many hub genes, some of which modulate plant immune responses. This study is important for understanding the metabolic changes, transcriptional regulation, and physiological responses of active and signaling substances during DON induction, and it will help to design defense strategies against Phytophthora infestans in potato.

Effect of build orientation and layer thickness on manufacturing accuracy, printing time, and material consumption of 3D printed complete denture bases.

OBJECTIVES: To evaluate the influence of build orientation and layer thickness on manufacturing accuracy, material consumption, and printing time of complete denture (CD) bases fabricated using digital light processing (DLP). METHODS: The CD base was designed on the basis of a standard maxillary edentulous model. Seventy CD bases were fabricated using a DLP 3D printer (Pro95, SprintRay, USA) and printable CD base material (DENTCA Denture Base II, Dentca, USA) at seven build orientations (0°, labial 45°, labial 90°, posterior 45°, posterior 90°, buccal 45°, and buccal 90°) and two types of layer thicknesses (50- and 100 µm) (n = 5). All test CD bases were digitalized and superimposed on the reference cast by section-based best-fit alignment. For evaluating manufacturing accuracy, deviation analysis was performed to compare the test data with the reference cast using the "3D Compare" in the 3D metrology software. The printing time and material consumption were calculated using slicing software and recorded, respectively. The two-way ANOVA test was used for accuracy evaluation, and the non-parametric test was used to evaluate printing time and material consumption (α = 0.05). RESULTS: Statistically significant differences were found in the manufacturing accuracy (p < 0.001), printing time (p < 0.001), and material consumption (p < 0.001) among the build orientation groups. The labial 45° and labial 90° groups showed the best accuracy. The 90° build orientations required the least material consumption and longest printing time; the labial 45° group consumed the most printing materials; the 0° group required the shortest printing time to fabricate a CD base. Moreover, the layer thickness influenced the printing time (p < 0.001) rather than the accuracy (p = 0.560) and material consumption (p = 1.000). CONCLUSIONS: When DLP was used to fabricate the CD bases, the build orientation influenced the manufacturing accuracy, material consumption, and printing time. However, the layer thickness only affected the printing time. CLINICAL SIGNIFICANCE: This study suggests that optimizing the build orientation can improve the manufacturing accuracy and reduce the material consumption and printing time of a DLP-printed CD base. The fast-printing setting (100 µm layer thickness) can reduce the printing time without compromising the manufacturing accuracy of the CD base.

Comparison of maxillary anterior mathematical proportions among 3 dental arch forms.

STATEMENT OF PROBLEM: Race and sex differences in the mathematical proportions of maxillary anterior teeth have been evaluated. However, studies exploring the relationship between the mathematical proportion of maxillary anterior teeth and maxillary dental arch form are lacking. PURPOSE: The purpose of this clinical study was to determine if a correlation exists between the mathematical proportions of maxillary anterior teeth and 3 dental arch forms. MATERIAL AND METHODS: Three hundred young participants were recruited according to predefined criteria, and images and maxillary casts were obtained. The perceived width and length of the maxillary anterior teeth were measured on the images by using a software program, and mathematical proportions, including width ratios and width-to-length ratios, were calculated for each. The casts were used to categorize each specimen into tapered, ovoid, or square groups by using a specific classification method, and the width ratios and width-to-height ratios of the 3 dental arch forms were compared. Statistical analysis was performed by using analysis of variance (ANOVA) or the Kruskal-Wallis H test to compare the mathematical proportions of maxillary anterior teeth among the 3 dental arch forms (α=.05). The intraclass correlation coefficient (ICC) was used to test the reliability of the investigators. RESULTS: Except for the width-to-length ratios of the central incisor, mathematical proportions were affected by the dental arch form. The perceived width ratios of the maxillary lateral incisor-to-central incisor gradually increased from the tapered arch to the ovoid arch and from the ovoid arch to the square arch, with mean ±standard deviation values of 0.71 ±0.04, 0.73 ±0.05, and 0.79 ±0.06, respectively. For the maxillary perceived width ratios of canine-to-lateral incisor, the ovoid arch had the maximum perceived width ratios (0.86 ±0.10), followed by the tapered (0.82 ±0.10) and square arches (0.77 ±0.11). The width-to-length ratios of the central incisor were not affected by the arch form (P=.075), and the width-to-length ratios of the lateral incisor increased as the arch form became flat, with respective values of 0.70 ±0.10, 0.74 ±0.10, and 0.76 ±0.10. For the width-to-length ratios of the canine, the ovoid arch had the maximum perceived width ratios (0.58 ±0.10), followed by the tapered (0.53 ±0.10) and square arches (0.52 ±0.10). CONCLUSIONS: The mathematical proportions varied among the 3 dental arch forms, and the dental arch form should be considered during the prosthodontic design of maxillary anterior teeth.

Dynamics of heavy metals during the development and decomposition of leaves of Avicennia marina and Kandelia obovata in a subtropical mangrove swamp.

In mangrove wetlands, leaves make up a high proportion of the plant biomass and can accumulate heavy metals from contaminated sediment. Despite this, it is still unclear how heavy metal concentrations in leaves change as they develop and how metals in senescence leaves are recycled back into the mangrove ecosystems during decomposition. The present study aims to investigate the dynamics of six heavy metals (Cu, Zn, Cr, Ni, Cd, and Pb) in leaves of two common mangrove plants, Avicennia marina and Kandelia obovata, at different stages of development (young, mature, and senescent) and leaf litter decomposition (from 0 to 20 weeks). Based on litterbag experiments in a subtropical mangrove swamp, both plant species showed similar trends in alternations of the six heavy metals during leaf development, that was, decreased in Cu and Zn but increased in Pb, while Cr, Ni, and Cd remained steady. All heavy metals in litter gradually increased in concentration during decomposition. By the end of the 20-weeks decomposition, the concentrations of Cu, Zn, and Cd in decayed leaves were comparable to those in sediment, with Cu, Zn, and Cd at approximately 18, 75, and 0.2 mg·kg-1, respectively, while Cr (66 mg·kg-1), Ni (65 mg·kg-1), and Pb (55 mg·kg-1) were lower than those in sediment, indicating that metals were not retained in litter but recycled back to the sediment. Tannins in mangrove leaf litter might chelate heavy metals, affecting their migration and transformation of heavy metals in estuarine mangrove wetlands. The findings of our study provide insight into the interactions between toxic heavy metals and mangrove plant species during leaf development, representing the first example of how most metals would be retained in leaf litter during decomposition, thereby reducing their release to estuarine and marine ecosystems.

Mechanism and Prospect of Gastrodin in Osteoporosis, Bone Regeneration, and Osseointegration.

Gastrodin, a traditional Chinese medicine ingredient, is widely used to treat vascular and neurological diseases. However, recently, an increasing number of studies have shown that gastrodin has anti-osteoporosis effects, and its mechanisms of action include its antioxidant effect, anti-inflammatory effect, and anti-apoptotic effect. In addition, gastrodin has many unique advantages in promoting bone healing in tissue engineering, such as inducing high hydrophilicity in the material surface, its anti-inflammatory effect, and pro-vascular regeneration. Therefore, this paper summarized the effects and mechanisms of gastrodin on osteoporosis and bone regeneration in the current research. Here we propose an assumption that the use of gastrodin in the surface loading of oral implants may greatly promote the osseointegration of implants and increase the success rate of implants. In addition, we speculated on the potential mechanisms of gastrodin against osteoporosis, by affecting actin filament polymerization, renin-angiotensin system (RAS) and ferroptosis, and proposed that the potential combination of gastrodin with Mg2+, angiotensin type 2 receptor blockers or artemisinin may greatly inhibit osteoporosis. The purpose of this review is to provide a reference for more in-depth research and application of gastrodin in the treatment of osteoporosis and implant osseointegration in the future.

Co-Delivery of Dihydroartemisinin and Indocyanine Green by Metal-Organic Framework-Based Vehicles for Combination Treatment of Hepatic Carcinoma.

Dihydroartemisinin (DHA), a widely used antimalarial agent, has clinical potential for the treatment of hepatic carcinoma. Although chemotherapy is indispensable for tumor therapy, it is generally limited by poor solubility, low efficiency, rapid clearance, and side effects. As an emerging treatment method, photothermal therapy (PTT) has many outstanding properties, but suffers from poor photostability of photosensitizer and incomplete ablation. Multimodal therapies could combine the advantages of different therapy methods to improve antitumor efficiency. Hence, we designed a nano-delivery system (ICG&DHA@ZIF-8) using zeolitic imidazolate framework-8 (ZIF-8) with a high porous rate and pH sensitivity property, to co-load DHA and indocyanine green (ICG). Dynamic light scattering and transmission electron microscopy were used to characterize the prepared nanoparticles. The photothermal conversion and drug release performances of ICG&DHA@ZIF-8 were investigated. In vitro antitumor efficacy and cellular uptake were studied. The mechanism of the combination treatment was studied by reactive oxygen species level detection and western blot assays. In vivo antitumor assays were then studied with the guidance of ex vivo imaging. The results showed that the ICG&DHA@ZIF-8 based combination therapy could efficiently kill hepatic carcinoma cells and suppress tumor growth. This research provides a potential nanodrug for the treatment of hepatic carcinoma.