APLNR inhibited nasopharyngeal carcinoma growth and immune escape by downregulating PD-L1.

BACKGROUND: APLNR is a G protein-coupled receptor and our previous study had revealed that APLNR could inhibit nasopharyngeal carcinoma (NPC) growth and metastasis. However, the role of APLNR in regulating PD-L1 expression and immune escape in NPC is unknown. METHODS: We analyzed the expression and correlation of APLNR and PD-L1 in NPC tissues and cells. We investigated the effect of APLNR on PD-L1 expression and the underlying mechanism in vitro and in vivo. We also evaluated the therapeutic potential of targeting APLNR in combination with PD-L1 antibody in a nude mouse xenograft model. RESULTS: We found that APLNR was negatively correlated with PD-L1 in NPC tissues and cells. APLNR could inhibit PD-L1 expression by binding to the FERM domain of JAK1 and blocking the interaction between JAK1 and IFNGR1, thus suppressing IFN-γ-mediated activation of the JAK1/STAT1 pathway. APLNR could also inhibit NPC immune escape by enhancing IFN-γ secretion and CD8+ T-cell infiltration and reducing CD8+ T-cell apoptosis and dysfunction. Moreover, the best effect was achieved in inhibiting NPC growth in nude mice when APLNR combined with PD-L1 antibody. CONCLUSIONS: Our study revealed a novel mechanism of APLNR regulating PD-L1 expression and immune escape in NPC and suggested that APLNR maybe a potential therapeutic target for NPC immunotherapy.

A comparative study of transcervical, endoscope-assisted transcervical, and endoscope-assisted transoral resection of retrostyloid space schwannomas.

BACKGROUND: The aim of this retrospective study was to compare the efficacy of transcervical (TC), endoscope-assisted transoral (TO), and endoscope-assisted TC for resection of retrostyloid space schwannomas. METHODS: The study included patients who underwent complete resection of schwannomas by only one surgical approach. The data we collected included tumor size, estimated blood loss, postoperative complications, and so on. Statistical analysis was performed using one-way analysis of variance and Fisher's exact test. RESULTS: The study collected 85 patients with tumors mostly located at the oropharyngeal level who were followed up 6 months at least. The results showed that endoscope-assisted TO had certain advantages over others. Additionally, the endoscope-assisted TO set the lowest incidence of neurological complications. CONCLUSION: Our findings demonstrate that for team with rich experience in the skull base surgery, endoscope-assisted TO is a superior option compared to the other two groups for resection of retrostyloid space schwannomas, with the better preservation of neurological function.

Predictors of Difficult Laryngeal Exposure in Suspension Laryngoscopy: A Systematic Review and Meta-Analysis.

OBJECTIVES: Considerable research has been focused on independent predictors of difficult laryngeal exposure (DLE) during suspension laryngoscopy. However, previous studies have yielded inconsistent results and conclusions. Consequently, we performed a meta-analysis of the existing literature with the aim of identifying significant parameters for a standardized preoperative DLE prediction system. METHODS: We systematically retrieved articles from the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang databases up to October 2022. Data from eligible studies were extracted and analyzed using the R programming language. The effect measures included odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous variables and mean differences (MDs) with 95% CIs for continuous variables. RESULTS: The search yielded 1,574 studies, of which 18 (involving a total of 2,263 patients) were included. Pooled analysis demonstrated that patients with DLE during microsurgery tended to be male (OR, 1.73; 95% CI, 1.16-2.57); were older (MD, 5.47 years, 95% CI, 2.44-8.51 years); had a higher body mass index (BMI; MD, 1.19 kg/m2; 95% CI, 0.33-2.05 kg/m2); had a greater neck circumference (MD, 2.50 cm; 95% CI, 1.56-3.44 cm); exhibited limited mouth opening (MD, -0.52 cm; 95% CI, -0.88 to -0.15 cm); had limited neck flexibility (MD, -10.05 cm; 95% CI, -14.10 to -6.00 cm); displayed various other anatomical characteristics; and had a high modified Mallampati index (MMI) or test score (OR, 3.37; 95% CI, 2.07-5.48). CONCLUSION: We conducted a comprehensive and systematic analysis of the factors relevant to DLE. Ultimately, we identified sex, age, BMI, neck circumference, MMI, inter-incisor gap, hyomental distance, thyromental distance, sternomental distance, and flexion-extension angle as factors highly correlated with DLE.

Multi-systemic melioidosis in a patient with type 2 diabetes in non-endemic areas: A case report and review of literature.

BACKGROUND: Melioidosis, an infectious disease caused by Burkholderia pseudomallei (B. pseudomallei), occurs endemically in Southeast Asia and Northern Australia and is a serious opportunistic infection associated with a high mortality rate. CASE SUMMARY: A 58-year-old woman presented with scattered erythema on the skin of her limbs, followed by fever and seizures. B. pseudomallei was isolated successively from the patient's urine, blood, and pus. Magnetic resonance imaging showed abscess formation involving the right forehead and the right frontal region. Subsequently, abscess resection and drainage were performed. The patient showed no signs of relapse after 4 months of follow-up visits post-treatment. CONCLUSION: We present here a unique case of multi-systemic melioidosis that occurs in non-endemic regions in a patient who had no recent travel history. Hence, it is critical to enhance awareness of melioidosis in non-endemic regions.

Diet-derived circulating antioxidants, periodontitis and dental caries: A Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Given the potential association between oxidative stress, periodontitis and dental caries, whether dietary supplementation with antioxidants is beneficial for periodontitis and dental caries has been widely reported, but remains controversial. This study aims to clarify these relationships through two-sample Mendelian randomization (MR) analysis. METHODS: Circulating antioxidants (copper, selenium, zinc, ascorbate, ß-carotene, lycopene, retinol and vitamin E) were derived from absolute circulating antioxidants and circulating antioxidant metabolites. Summary data of periodontitis and dental caries were obtained from two separate databases, respectively. We performed inverse-variance weighted (IVW) analysis separately in different databases, followed by meta-analysis. The robustness of results was examined by sensitivity analyses, including three complementary MR methods, heterogeneity and pleiotropy tests, and PhenoScanner query. RESULTS: IVW analysis showed that elevated levels of absolute circulating retinol reduced the risk of periodontitis (GLIDE: OR = 0.41, 95% CI = 0.18-0.95, p = .038, power = 100%; FinnGen: OR = 0.15, 95% CI = 0.04-0.54, p = .004, power = 100%). The pooled OR for periodontitis risk per unit increase of retinol is 0.30 (95% CI = 0.15-0.61, p = .001, I2 = 40.3%, power = 100%). No significant associations were noted for genetically predicted circulating antioxidants and dental caries risk. The sensitivity analyses yielded similar estimates. CONCLUSION: This study demonstrates that a negative causality between circulating retinol and periodontitis risk, and null linkage between circulating antioxidants and dental caries risk, suggesting potential strategies for the prevention and control of periodontitis.

Periodontitis and thyroid function: A bidirectional Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Previous studies suggest interaction between periodontitis and thyroid function, while the causality has not yet been established. We applied the Mendelian randomization (MR) method to assess bidirectional causal association between periodontitis and thyroid-related traits, including free thyroxine (FT4), thyroid stimulating hormone (TSH), hypothyroidism, hyperthyroidism and autoimmune thyroid disease (AITD). METHODS: Genetic instruments were extracted from large-scale genome-wide association studies on normal-range FT4 (N = 49 269) and TSH (N = 54 288) levels, TSH in full range (N = 119 715); hypothyroidism (discovery/replication cohorts: N = 53 423/334 316), hyperthyroidism (discovery/replication cohorts: N = 51 823/257 552), AITD (N = 755 406) and periodontitis (N = 45 563). Here, the inverse variance weighted (IVW) method was applied as the primary analysis, and robustness of results were assessed by several pleiotropic-robust methods. Results were adjusted for Bonferroni correction thresholds with significant p < .004 (0.05/13) and suggestive p between .004 and .05. RESULTS: The IVW analysis revealed a suggestively causal linkage between genetic predisposition to periodontitis and the increased risk of hypothyroidism (discovery cohort: odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.05-1.46, p = .012; replication cohort: OR = 1.06, 95% CI = 1.01-1.11, p = .011). No evidence was found for supporting the impact of periodontitis on hyperthyroidism and AITD risks (associated p ≥ .209), as well as thyroid-related traits on periodontitis risk (associated p ≥ .105). These findings were robust and consistent through sensitivity analysis with other MR models. CONCLUSION: This bidirectional MR reveals periodontitis should not be attributed to variations in thyroid function but it has potential causal effect on hypothyroidism risk, which provides a better understanding of the relationship between periodontitis and thyroid function, and potential evidence for the clinical intervention of hypothyroidism. Further investigations are warranted to elucidate the nature and underlying mechanisms of this finding.

Allergic Diseases and Chronic Adenotonsillar Diseases: A Mendelian Randomization Study.

OBJECTIVE: The existing epidemiological evidence regarding the intricate relationship between allergic diseases and chronic adenotonsillar diseases (CATD) remains inconclusive. Herein, the objective of our study is to explore the causal association using Mendelian randomization (MR). METHODS: Employing data from large genome-wide association studies, a comprehensive two-sample bidirectional MR study was conducted. The studied traits encompassed allergic rhinitis (cases n = 9707, controls n = 331173), allergic asthma (cases n = 8525, controls n = 193857), allergic conjunctivitis (cases n = 18321, controls n = 324178), atopic dermatitis (cases n = 11964, controls n = 306909), and CATD (cases n = 38983, controls n = 258553). All the patients were of European descent and participants in cohort studies. The primary analysis was executed using inverse-variance-weighted MR. Furthermore, six additional MR methods (MR-Egger, weighted median, simple mode, weighted mode, MR pleiotropy residual sum and outlier, MR robust adjusted profile score) were employed to ensure the reliability and detect potential horizontal pleiotropy within the results. The estimates obtained from the MR analysis were factored into the overall effect calculation. RESULTS: Genetically anticipated outcomes demonstrated a significant association between CATD risk and allergic rhinitis (OR = 1.141, p = 6.30E-06), allergic asthma (OR = 1.115, p = 8.31E-05), allergic conjunctivitis (OR = 1.197, p = 8.69E-07), and a suggestive association with atopic dermatitis (OR = 1.053, p = 0.040). However, no substantial correlation was observed in the reverse direction. CONCLUSIONS: Findings of our study provide evidence supporting a causal role of allergic diseases in the development of CATD, whereas the converse relationship does not appear to hold true. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2653-2658, 2024.

Total thyroidectomy versus unilateral lobectomy for unilateral multifocal papillary thyroid carcinoma: systematic review and meta­analysis.

The optimal surgical procedure(s) for unilateral multifocal papillary thyroid carcinomas is currently controversial. As such, the present study aimed to compare the efficacies of total thyroidectomy and lobectomy in patients with unilateral multifocal papillary thyroid carcinoma. A literature search of the PubMed/Medline, Embase, Web of Science, Cochrane Library, Wan Fang, and Zhi Wang databases for relevant studies, published from inception to October 31, 2022, was performed. Two researchers independently extracted data from the included studies. Lymph node metastasis, vocal fold paralysis, parathyroid injury, postoperative recurrence, and disease-free survival were evaluated. The meta-analysis included 7 studies comprising 1540 patients, of whom 496 and 1044 underwent lobectomy and total thyroidectomy, respectively. Compared with lobectomy, total thyroidectomy resulted in more vocal cord paralysis (odds ratio [OR] 0.35 [95% confidence interval (CI) 0.13 to 0.96]; P = 0.04) and parathyroid injury (OR 0.11 [95% CI 0.03-0.39]; P = 0.001) but with better disease-free survival (OR 0.21 [95% CI 0.09-0.49]; P = 0.000), although vocal cord paralysis and parathyroid injury, in large part, resolved within 1 year after surgery. In addition, there was no difference in postoperative lymph nodes metastasis (OR 0.74 [95% CI 0.13-4.21]; P = 0.737) and postoperative recurrence (OR 2.37 [95% CI 0.42-13.38]; P = 0.33). Excluding studies that deviated from the general trend, total thyroidectomy was beneficial in reducing recurrence. Compared with lobectomy, total thyroidectomy was beneficial in reducing recurrence and disease-free survival and may be considered a more optimal approach for unilateral multifocal papillary thyroid carcinoma.

Bioinspired High-Strength Borate Cross-Linked Microfibrillated Cellulose Composite Laminate with Self-Extinguishing Flame Retardance and Superhydrophobicity for Self-Cleaning.

The cross-linking of borates enhances the intercellular structural connection, resulting in the creation of a mechanically superior structural material composed of lignocellulose and borate. This is accomplished by employing a mechanical pretreatment procedure and a binder-free hot-pressing method. Nevertheless, these materials frequently encounter constraints in humid environments, making it challenging to simultaneously achieve the desired performance objectives. Here, the prepressed bulk of microfibrillated cellulose is modified and subjected to hot pressing, while ensuring that the enhanced physical and mechanical properties of lignocellulosic recombinant materials are maintained. This modified material is termed the microfibrillated cellulose composite laminate (MCCL). These findings indicate that the application of compression, shear, and friction forces during hot-pressing results in the formation of a compact laminated structure using pine lignocellulose. The self-cleaning MCCL exhibits significantly improved mechanical properties compared with untreated lignocellulose materials (ULM). Specifically, the flexural strength (MOR), modulus of elasticity (MOE), and internal bonding strength (IB) of self-cleaning MCCL are found to be 5 times, 2.5 times, and 4.1 times higher, respectively, than those of ULM. This improvement in the pine lignocellulose can be attributed to the enhanced layering and branching that occurs during mechanical milling. This results in a higher proportion of ester and hydrogen bonds, as well as an increased exposure of hydroxyl groups. As a result, the modified MCCL exhibits self-cleaning properties, as evidenced by its surface water contact angle (WCA) of 152°. The rolling/jumping water droplets, which contain pollutants, effectively remove graphite powder from the surface, leaving it clean. Moreover, MCCL demonstrates exceptional dimensional stability and flame-retardant self-extinguishing properties, making it highly promising as a structural material in engineering technology.

Identification of biomarkers in laryngeal cancer by weighted gene co-expression network analysis. / åº”ç”¨åŠ æƒåŸºå› å ±è¡¨è¾¾ç½‘ç»œåˆ†æžæŽ¢ç´¢å–‰ç™Œæ ‡å¿—ç‰©ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Laryngeal cancer (LC) is a globally prevalent and highly lethal tumor. Despite extensive efforts, the underlying mechanisms of LC remain inadequately understood. This study aims to conduct an innovative bioinformatic analysis to identify hub genes that could potentially serve as biomarkers or therapeutic targets in LC. METHODS: We acquired a dataset consisting of 117 LC patient samples, 16 746 LC gene RNA sequencing data points, and 9 clinical features from the Cancer Genome Atlas (TCGA) database in the United States. We employed weighted gene co-expression network analysis (WGCNA) to construct multiple co-expression gene modules. Subsequently, we assessed the correlations between these co-expression modules and clinical features to validate their associations. We also explored the interplay between modules to identify pivotal genes within disease pathways. Finally, we used the Kaplan-Meier plotter to validate the correlation between enriched genes and LC prognosis. RESULTS: WGCNA analysis led to the creation of a total of 16 co-expression gene modules related to LC. Four of these modules (designated as the yellow, magenta, black, and brown modules) exhibited significant correlations with 3 clinical features: The age of initial pathological diagnosis, cancer status, and pathological N stage. Specifically, the yellow and magenta gene modules displayed negative correlations with the age of pathological diagnosis (r=-0.23, P<0.05; r=-0.33, P<0.05), while the black and brown gene modules demonstrated negative associations with cancer status (r=-0.39, P<0.05; r=-0.50, P<0.05). The brown gene module displayed a positive correlation with pathological N stage. Gene Ontology (GO) enrichment analysis identified 77 items, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified 30 related signaling pathways, including the calcium signaling pathway, cytokine-cytokine receptor interaction, neuro active ligand-receptor interaction, and regulation of lipolysis in adipocytes, etc. Consequently, central genes within these modules that were significantly linked to the overall survival rate of LC patients were identified. Central genes included CHRNB4, FOXL2, KCNG1, LOC440173, ADAMTS15, BMP2, FAP, and KIAA1644. CONCLUSIONS: This study, utilizing WGCNA and subsequent validation, pinpointed 8 genes with potential as gene biomarkers for LC. These findings offer valuable references for the clinical diagnosis, prognosis, and treatment of LC.

Transoral robotic surgery vs. non-robotic surgeries for oropharyngeal squamous cell carcinoma: systematic review and meta-analysis.

To compare the effectiveness of transoral robotic surgery (TORS) and non-robotic surgeries (NRES) in patients with oropharyngeal squamous cell carcinoma (OPSCC), medical databases were searched including PubMed, Web of Science, Medline, Embase, and Cochrane Library up to January 2023. The methodology follows PRISMA guidelines, including the PRISMA flow diagram. Data from the included studies were extracted independently by two researchers. Seven studies involving five hundred seventy-seven patients were included. Of these, 275 underwent TORS and 302 underwent NRES. The disease-free survival rate was significantly higher in the TORS group than in the NRES group (OR = 3.43, 95% CI 1.92-6.15, P < 0.0001). However, there were no significant differences in positive surgical margins, hospital stays, operation time, blood loss, postoperative bleeding rate, perioperative tracheostomy, perioperative feeding tube, and overall survival rate. These findings can initially guide the preoperative counseling of TORS in patients with OPSCC, and preliminarily confirm that the adoption of TORS deserves careful consideration.

PHF5A regulates the expression of the DOCK5 variant to promote HNSCC progression through p38 MAPK activation.

BACKGROUND: Previously, we identified an oncogenic splicing variant of DOCK5 in head and neck squamous cell carcinoma (HNSCC); however, the mechanism for the generation of this specific DOCK5 variant remains unknown. This study aims to explore the potential spliceosome genes involved in the production of the DOCK5 variant and validate its role in regulating the progression of HNSCC. METHODS: The differentially expressed spliceosome genes involved in the DOCK5 variant were analysed in The Cancer Genome Atlas (TCGA), and the correlation between the DOCK5 variant and the potential spliceosome gene PHF5A was verified by qRT-PCR. The expression of PHF5A was detected in HNSCC cells, TCGA data and a separate primary tumour cohort. The functional role of PHF5A was examined using CCK-8, colony formation, cell scratch and Transwell invasion assays in vitro and validated in vivo in xenograft models of HNSCC. Western blot analysis was used to explore the potential mechanism of PHF5A in HNSCC. RESULTS: PHF5A was one of the top upregulated spliceosome genes in TCGA HNSCC samples with highly expressed DOCK5 variants. Knockdown or overexpression of PHF5A in HNSCC cells correspondingly altered the level of the DOCK5 variant. PHF5A was highly expressed in tumour cells and tissues and correlated with a worse prognosis of HNSCC. Loss- and gain-of-function experiments demonstrated that PHF5A could promote the proliferation, migration and invasion of HNSCC cells in vitro and in vivo. Moreover, PHF5A inhibition reversed the oncogenic effect of the DOCK5 variant in HNSCC. Western blot analysis showed that PHF5A activated the p38 MAPK pathway, and inhibition of p38 MAPK further reversed the effect of PHF5A on the proliferation, migration and invasion of HNSCC cells. CONCLUSION: PHF5A regulates the alternative splicing of DOCK5 to promote HNSCC progression through p38 MAPK activation, which provides potential therapeutic implications for HNSCC patients.

Modifiable factors for benign salivary gland neoplasms: A Mendelian randomization study.

BACKGROUND: Observational studies have found associations between smoking, alcohol, radiation, body mass index (BMI), periodontitis, and the hazard of benign salivary gland neoplasms (BSGNs). Nevertheless, the etiology of BSGNs remains unclear. This study aims to assess the causal association between these modifiable factors and the BSGNs. METHODS: Genetic instruments associated with exposures at the genome-wide significance level were selected from corresponding genome-wide association studies. The summary statistics for BSGNs were obtained from the FinnGen consortium (2445 cases and 340,054 controls). The inverse variance-weighted method was used as the primary analysis, and several sensitivity analyses were performed to test the reliability. RESULTS: Genetically predicted higher lifetime smoking index (odds ratio [OR] = 2.10, p = 0.012) and BMI (OR = 1.58, p = 2.29 × 10-5 ) were associated with elevated risk of BSGNs, whereas other exposures do not. Sensitivity analyses showed consistency. The causal effect of the lifetime smoking index became more significant after adjusting for BMI (OR = 2.89, p = 0.005) and alcohol consumption (OR = 2.49, p = 0.002). A slight negative association emerged for alcohol consumption with adjustment for cigarettes per day (OR = 0.53, p = 0.034) but disappeared when adjusting for cigarettes per day and BMI. CONCLUSION: This study supports the independent causal role of lifetime smoking index and BMI in BSGNs risk.

Comparison of Remimazolam and Propofol for Drug-Induced Sleep Endoscopy: A Randomized Clinical Trial.

OBJECTIVE: To compare the efficacy and safety of remimazolam with those of propofol for drug-induced sleep endoscopy (DISE) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). STUDY DESIGN: A prospective, single-center, randomized clinical trial. SETTING: Xiangya Hospital of Central South University. METHODS: Patients with OSAHS receiving DISE were randomly assigned to either the remimazolam or propofol group. The primary outcome was the incidence of hypoxemia (pulse oxygen saturation [SpO2 ] < 90%) during DISE. The secondary outcomes were the incidence of severe hypoxemia (SpO2 < 80%), the minimal value of SpO2 , sedation success rate (completion of DISE according to the medication regimen), and incidence of events of interest (including injection pain, bradycardia, and decreased respiratory rate). RESULTS: Sixty-four patients were included in this study. The incidence of hypoxemia was significantly lower in the remimazolam than in the propofol group (25.00% vs 62.50%, respectively; relative risk, 0.40; 95% confidence interval [CI], 0.20-0.74; p < .01). There was no significant difference in the sedation success rate between the remimazolam and propofol groups (96.88% vs 81.25%, respectively; relative risk, 1.19; 95% CI, 1.01-1.50; p = .10). The incidence of at least 1 event of interest was lower in the remimazolam than in the propofol group (43.75% vs 96.88%, respectively; relative risk, 0.45; 95% CI, 0.29-0.63; p < .01). CONCLUSION: Remimazolam can present satisfactory sedative efficacy in DISE, with a lower incidence of hypoxemia and a higher safety profile than propofol.

MRI-based radiomics analysis for preoperative evaluation of lymph node metastasis in hypopharyngeal squamous cell carcinoma.

Objective: To investigate the role of pre-treatment magnetic resonance imaging (MRI) radiomics for the preoperative prediction of lymph node (LN) metastasis in patients with hypopharyngeal squamous cell carcinoma (HPSCC). Methods: A total of 155 patients with HPSCC were eligibly enrolled from single institution. Radiomics features were extracted from contrast-enhanced axial T-1 weighted (CE-T1WI) sequence. The most relevant features of LN metastasis were selected by the least absolute shrinkage and selection operator (LASSO) method. Univariate and multivariate logistic regression analysis was adopted to determine the independent clinical risk factors. Three models were constructed to predict the LN metastasis status: one using radiomics only, one using clinical factors only, and the other one combined radiomics and clinical factors. Receiver operating characteristic (ROC) curves and calibration curve were used to evaluate the discrimination and the accuracy of the models, respectively. The performances were tested by an internal validation cohort (n=47). The clinical utility of the models was assessed by decision curve analysis. Results: The nomogram consisted of radiomics scores and the MRI-reported LN status showed satisfactory discrimination in the training and validation cohorts with AUCs of 0.906 (95% CI, 0.840 to 0.972) and 0.853 (95% CI, 0.739 to 0.966), respectively. The nomogram, i.e., the combined model, outperformed the radiomics and MRI-reported LN status in both discrimination and clinical usefulness. Conclusions: The MRI-based radiomics nomogram holds promise for individual and non-invasive prediction of LN metastasis in patients with HPSCC.

Indole-3-Carboxylic Acid From the Endophytic Fungus Lasiodiplodia pseudotheobromae LPS-1 as a Synergist Enhancing the Antagonism of Jasmonic Acid Against Blumeria graminis on Wheat.

The discovery of natural bioactive compounds from endophytes or medicinal plants against plant diseases is an attractive option for reducing the use of chemical fungicides. In this study, three compounds, indole-3-carbaldehyde, indole-3-carboxylic acid (3-ICA), and jasmonic acid (JA), were isolated from the EtOAc extract of the culture filtrate of the endophytic fungus Lasiodiplodia pseudotheobromae LPS-1, which was previously isolated from the medicinal plant, Ilex cornuta. Some experiments were conducted to further determine the antifungal activity of these compounds on wheat powdery mildew. The results showed that JA was much more bioactive than indole-3-carbaldehyde and 3-ICA against Blumeria graminis, and the disease severity caused by B. graminis decreased significantly with the concentration increase of JA treatment. The assay of the interaction of 3-ICA and JA indicated that there was a significant synergistic effect between the two compounds on B. graminis in each of the ratios of 3-ICA to JA (3-ICA:JA) ranging from 1:9 to 9:1. When the compound ratio of 3-ICA to JA was 2:8, the synergistic coefficient was the highest as 22.95. Meanwhile, a histological investigation indicated that, under the treatment of JA at 500 µg/ml or 3-ICA:JA (2:8) at 40 µg/ml, the appressorium development and haustorium formation of B. graminis were significantly inhibited. Taken together, we concluded that JA plays an important role in the infection process of B. graminis and that 3-ICA as a synergist of JA enhances the antagonism against wheat powdery mildew.

Machine learning-based radiomics for histological classification of parotid tumors using morphological MRI: a comparative study.

OBJECTIVES: To evaluate the effectiveness of machine learning models based on morphological magnetic resonance imaging (MRI) radiomics in the classification of parotid tumors. METHODS: In total, 298 patients with parotid tumors were randomly assigned to a training and test set at a ratio of 7:3. Radiomics features were extracted from the morphological MRI images and screened using the Select K Best and LASSO algorithm. Three-step machine learning models with XGBoost, SVM, and DT algorithms were developed to classify the parotid neoplasms into four subtypes. The ROC curve was used to measure the performance in each step. Diagnostic confusion matrices of these models were calculated for the test cohort and compared with those of the radiologists. RESULTS: Six, twelve, and eight optimal features were selected in each step of the three-step process, respectively. XGBoost produced the highest area under the curve (AUC) for all three steps in the training cohort (0.857, 0.882, and 0.908, respectively), and for the first step in the test cohort (0.826), but produced slightly lower AUCs than SVM in the latter two steps in the test cohort (0.817 vs. 0.833, and 0.789 vs. 0.821, respectively). The total accuracies of XGBoost and SVM in the confusion matrices (70.8% and 59.6%) outperformed those of DT and the radiologist (46.1% and 49.2%). CONCLUSION: This study demonstrated that machine learning models based on morphological MRI radiomics might be an assistive tool for parotid tumor classification, especially for preliminary screening in absence of more advanced scanning sequences, such as DWI. KEY POINTS: • Machine learning algorithms combined with morphological MRI radiomics could be useful in the preliminary classification of parotid tumors. • XGBoost algorithm performed better than SVM and DT in subtype differentiation of parotid tumors, while DT seemed to have a poor validation performance. • Using morphological MRI only, the XGBoost and SVM algorithms outperformed radiologists in the four-type classification task for parotid tumors, thus making these models a useful assistant diagnostic tool in clinical practice.

Diagnosis of lymph node metastasis in head and neck squamous cell carcinoma using deep learning.

BACKGROUND: To build an automatic pathological diagnosis model to assess the lymph node metastasis status of head and neck squamous cell carcinoma (HNSCC) based on deep learning algorithms. STUDY DESIGN: A retrospective study. METHODS: A diagnostic model integrating two-step deep learning networks was trained to analyze the metastasis status in 85 images of HNSCC lymph nodes. The diagnostic model was tested in a test set of 21 images with metastasis and 29 images without metastasis. All images were scanned from HNSCC lymph node sections stained with hematoxylin-eosin (HE). RESULTS: In the test set, the overall accuracy, sensitivity, and specificity of the diagnostic model reached 86%, 100%, and 75.9%, respectively. CONCLUSIONS: Our two-step diagnostic model can be used to automatically assess the status of HNSCC lymph node metastasis with high sensitivity. LEVEL OF EVIDENCE: NA.

The prognosis of HPV-associated metastatic pharyngeal patients by primary and distant site.

OBJECTIVES: Human papillomavirus (HPV) positivity is a favorable prognostic factor in the general population of head and neck squamous cell carcinoma (HNSCC) patients. However, its impact on the survival of metastatic HNSCC of pharynx (mHNSC-P) patients is unclear. This study aims to investigate the associations between HPV status and survival in mHNSC-P patients. METHODS: 735 mHNSC-P patients diagnosed at first presentation from 2010 to 2016 were retrieved from the Surveillance, Epidemiology and End Result database (SEER). Chi-Squared test, univariate and multivariate cox proportional hazards model, Kaplan-Meier analysis, and log-rank test were applied to compare HPV-positive and -negative mHNSC-P patients. RESULT: Using univariate cox proportional hazards analysis, HPV status, primary site, T stage, treatment and distant metastatic site correlate with the overall survival (OS) and disease-specific survival (DSS) in mHNSC-P patients. Multivariate cox regression analysis shows that HPV-positive mHNSC-P patients experienced significantly better OS (HR: 0.62 CI: 0.51-0.76, p < 0.001) and DSS (HR: 0.73 CI: 0.58-0.91, p < 0.01) as compared to HPV-negative mHNSC-P patients. Subgroup analysis indicates that HPV-associated OS and DSS benefits exist in patients with metastatic HNSCC of oropharynx (mHNSC-OP) but not in patients with metastatic HNSCC of non-oropharynx (mHNSC-non-OP). Among mHNSC-OP patients, HPV positivity confers disease-specific survival benefit in patients with oligometastatic rather than polymetastatic patients. Furthermore, HPV associated OS and DSS advantages in mHNSC-OP with lung metastasis was observed. CONCLUSION: HPV-positive mHNSC-OP patients with lung metastasis show better survival than HPV-negative mHNSC-OP patients, providing key information to guide patient treatment approaches.

Modified Arytenoid Adduction Operation for the Treatment of Unilateral Vocal Fold Paralysis.

INTRODUCTION: Unilateral vocal fold paralysis (UVFP) was a relative common glottic insufficiency disease; however, a completely satisfactory treatment of UVFP was elusive. This study was aimed to evaluate the surgical efficacy of modified arytenoid adduction with fenestration of the thyroid cartilage in the management of patients with UVFP, including voice and aspiration outcomes, and to summarize the postoperative complications. METHODS: A retrospective analysis was performed on a total of 21 patients who underwent modified arytenoid adduction operation with fenestration of the thyroid cartilage for UVFP from July 2012 to June 2017. The scores of Grade, Roughness, Breathiness, Asthenia, Strain scale (GRBAS), voice self-satisfaction, dynamic laryngoscopy and the voice acoustic data (fundamental frequency [F0], fundamental frequency perturbation [jitter], loudness, amplitude perturbation [shimmer], and maximal phonatory time [MPT], etc.) were statistically analyzed preoperatively and 3-6 months postoperatively. The occurrence of postoperative complications was also summarized. RESULTS: The voice subjective perception of 21 patients was significantly improved after operation. The rate of voice self-satisfaction was 90.5%. The mean values of voice acoustics parameters were significantly improved. The MPT was significantly longer (p < 0.001), and the ratings of postoperative aspiration were significantly decreased compared with the preoperation. Among the 21 patients, 15 cases had sense of laryngeal obstruction, 8 cases had of 1-2° laryngemphraxis (recovered after 10-15 days). There were 2 cases of laryngeal stridor, 1 case of incision infection, 1 case of pharyngeal fistula, and 1 case of falsetto (corrected by voice training). No patient had laryngeal hematoma, neck hematoma, or laryngospasm. CONCLUSION: The modified arytenoid adduction operation with fenestration of the thyroid cartilage can significantly improve the vocal function of patients with UVFP and effectively reduce the aspiration, with fewer postoperative complications, less trauma, and more convenient advantages.