Volatile Organic Compounds from Pythium oligandrum Play a Role in Its Parasitism on Plant-Pathogenic Pythium myriotylum.

The oomycete Pythium oligandrum is a soil-inhabiting parasite and predator of both fungi and oomycetes, and uses hydrolytic enzymes extensively to penetrate and hydrolyze its host or prey. Other mechanisms have been studied less, and we investigated the contribution of P. oligandrum-produced volatile organic compounds (VOCs) to parasitism. The growth-inhibiting activity of P. oligandrum VOCs was tested on Pythium myriotylum-a host or prey of P. oligandrum-coupled with electron microscopy, and biochemical and transcriptomic analyses. The P. oligandrum-produced VOCs reduced P. myriotylum growth by 80% and zoospore levels by 60%. Gas chromatography-mass spectrometry (GC-MS) identified 23 VOCs, and methyl heptenone, d-limonene, 2-undecanone, and 1-octanal were potent inhibitors of P. myriotylum growth and led to increased production of reactive oxygen species at a concentration that did not inhibit P. oligandrum growth. Exposure to the P. oligandrum VOCs led to shrinkage of P. myriotylum hyphae and lysis of the cellular membranes and organelles. Transcriptomics of P. myriotylum exposed to the P. oligandrum VOCs at increasing levels of growth inhibition initially showed a strong upregulation of putative detoxification-related genes that was not maintained later. The inhibition of P. myriotylum growth continued immediately after the exposure to the VOCs was discontinued and led to the reduced infection of its plant hosts. The VOCs produced by P. oligandrum could be another factor alongside hydrolytic enzymes contributing to its ecological role as a microbial parasite in particular ecological niches such as in soil, and may also contribute to the biocontrol of diseases using P. oligandrum commercial preparations. IMPORTANCE Microbe-microbe interactions in nature are multifaceted, with multiple mechanisms of action, and are crucial to how plants interact with microbes. Volatile organic compounds (VOCs) have diverse functions, including contributing to parasitism in ecological interactions and potential applications in biocontrol. The microbial parasite P. oligandrum is well known for using hydrolytic enzymes as part of its parasitism. We found that P. oligandrum VOCs reduced the growth of, and caused major damage to, the hyphae of P. myriotylum (a host or prey of P. oligandrum). Transcriptomic analyses of P. myriotylum exposed to the VOCs revealed the upregulation of genes potentially involved in an attempt to detoxify the VOCs. The inhibitory effects of the VOCs had a knock-on effect by reducing the virulence of P. myriotylum toward its plant hosts. The P. oligandrum VOCs could contribute to its ecological role as a microbial parasite. The VOCs analyzed here may also contribute to the biocontrol of diseases using P. oligandrum commercial preparations.

Drawbacks of neural monitoring troubleshooting algorithms in transoral endoscopic thyroidectomy.

INTRODUCTION: The application of intraoperative neural monitoring (IONM) trouble-shooting algorithms procedures in transoral endoscopic thyroidectomy vestibular approach (TOETVA) was investigated. METHODS: Loss of signal (LOS) is defined as a loss of the primary electromyographic (EMG) normal biphasic waveform with reduced amplitude response to less than 100µV with a stimulation level intensity of 1-2mA. A systematic review of the IONM system at LOS was covered methodically: (i) correct endotracheal tube verification, (ii) stimulation of the recurrent laryngeal nerve (RLN) at entry point, (iii) ipsilateral or contralateral vagal nerve (VN) stimulation, and (iv) laryngeal twitch (LT). RESULTS: The function of 223 nerves at risk (NAR) was recorded with IONM. Twenty-seven (12%) NAR experienced a suspected LOS. LT could not be appreciated. In 15/27 (55%) cases, the application of the IONM trouble-shooting algorithm revealed upward displacement of the EMG tube (all orotracheal intubations). In 9 (4%) NAR, VN stimulation was not accomplished. In detail, there were n.5 left and n. 4 right VNs. Two VNs were ipsilateral, and 7 VNs contralateral. For EMG tube displacement, because the oral/nasal area is included in the aseptic field, it is less possible to re-check by the laryngoscope or fiberscope. CONCLUSIONS: A limit for applying the IONM trouble-shooting algorithm to TOETVA is determined by (a) inability to appreciate the LT, (b) difficulty in stimulating the ipsilateral and contralateral VN, and (c) remodeling EMG endotracheal tube position. A modified IONM trouble-shooting algorithm for TOETVA is proposed.

Stimulating and dissecting instrument for transoral endoscopic thyroidectomy: proof of concept investigation.

OBJECTIVES/HYPOTHESIS: Intraoperative neuromonitoring (IONM) is a useful adjunct for recurrent laryngeal nerve (RLN) mapping and identification in transoral endoscopic thyroidectomy vestibular approach (TOETVA). This experimental study aimed to investigate the feasibility, safety, thresholds required of an endoscopic forceps that combine the function of surgical dissection and nerve stimulation. STUDY DESIGN: Prospective experimental research. METHODS: TOETVA was performed in 12 piglets, i.e., 24 RLNs and 24 vagal nerves (VN). RLNs electromyography (EMG) was recorded via endotracheal surface electrodes. Baseline EMG of VN and RLN were recorded and compared by (a) percutaneously placed monopolar stimulator probe (Group I), (b) adapted Maryland endoscopic dissector applied on nerves at its tip-end (Group II) and (c) endoscopic dissector tip-lateral applied (Group III). EMG profiles, amplitude, latency, waveform, thresholds and supra-maximal stimulation (5 mA) were analyzed. RESULTS: Application of the endoscopic device was feasible in all TOETVA and did not result in any morbidity. 24 RLNs and VNs were detected, stimulated and monitored. With increase of stimulation current, the amplitude of EMG increased, showing a dose-response curve. Mean VN stimulation thresholds were: Group I 0.28 mA, Group II 0.56 mA, Group III 0.58 mA (P1 = 0.00, P2 = 0.00, P3 = 0.11). Minimal current to evoked a maximal VN response was: Group I 0.65 mA, Group II 1.07 mA and Group III 1.14 mA (P1 = 0.00, P2 = 0.00, P3 = 0.48). Minimal current to evoke a RLN maximal response was Group I 0.6 mA, Group II 0.95 mA and Group III 1.05 mA (P1 = 0.00, P2 = 0.00, P3 = 0.31). Latency values were similar to each group. Repetitive (> 10 min) supra-maximal (> 5 mA) electrical stimulation was safe. CONCLUSIONS: The application of endoscopic stimulating dissector is simple, effective and safe way to monitor both VN and RLN function during a TOETVA animal model. It provides surgeons with real-time feedback of EMG response and can be applied as a tool for RLN monitoring. Endoscopic instrument required higher current to evoke EMG response compared to hand probe stimulation. Tip-end required less current to evoke EMG response compared to tip-lateral mode of stimulation.

The Association Between Tumor Tissue Calcification, Obesity, and Thyroid Cancer Invasiveness In A Cohort Study.

OBJECTIVE: We examined the relationships between tumor tissue calcifications of papillary thyroid cancer (PTC), body mass index (BMI), and tumor invasiveness. METHODS: This was a retrospective analysis of 13,995 patients with PTC. Comparisons were made between the clinical and pathologic features of the tumor tissue calcifications group and non-tumor tissue calcifications group. Odds ratios (ORs) of tumor tissue calcifications, BMI, and tumor invasiveness features were calculated using a binary logistic regression model. We analyzed the relationship between tumor tissue calcifications and certain characteristics of thyroid cancer based on the pathologic findings. RESULTS: BMI was positively correlated with tumor tissue calcifications in patients with PTC (OR, 1.015; P = .011), and obesity increased the risk of tumor tissue calcifications (OR, 1.374; P = .038). Calcifications were positively correlated with T-size (OR, 1.899; P<.001), multifocality (OR, 1.217; P<.001), extrathyroidal extension (ETE) (OR, 1.287; P<.001), high T-stage (OR, 1.765; P<.001), N+ (OR, 1.763; P<.001), and a higher number of lymph node metastases (OR, 1.985; P<.001). Compared with normal-weight patients with tumor tissue calcifications, obese patients with tumor tissue calcifications had an increased risk of ETE (ORobesity, 1.765 vs. ORnormal, 1.300) and N+ (ORobesity, 1.992 vs. ORnormal, 1.784). CONCLUSION: Tumor tissue calcifications are positively correlated with the invasiveness of PTC. Obesity further promotes the risk of tumor invasiveness in PTC combined with tumor tissue calcifications. These findings suggest that more comprehensive evaluations by trained pathologists may help physicians identify the optimal therapeutic regimens in the postoperative period. ABBREVIATIONS: BMI = body mass index; CI = confidence interval; ETE = extrathyroidal extension; FT3 = free triiodothyronine; OR = odds ratio; PTC = papillary thyroid carcinoma; RET = rearranged during transfection; TTC = tumor tissue calcification; US = ultrasonography; USC = ultrasonography calcification; WHO = World Health Organization.

Comparison of parathyroid hormone kinetics in endoscopic thyroidectomy via bilateral areola with open thyroidectomy.

BACKGROUND: In this study, we aimed to compare the kinetics of intact parathyroid hormone (iPTH) during the perioperative period of endoscopic thyroidectomy via bilateral areola approach (ETBAA) in the same period, following a traditional open thyroidectomy approach (OTA). METHODS: We conducted a prospective observational study of patients who were undergoing thyroidectomy and level VI clearance. Patients who had been affected by papillary thyroid cancer (PTC) were stratified into three groups: those eligible for endoscopic treatment (ETBAA); patients who were eligible for ETBAA but had opted for OTA (OTA-L); and patients who were not suitable for endoscopic intervention (OTA-H). A process for locating parathyroid glands was utilized to stratify gland dissection laboriousness. In Type A, the gland is firmly fixed to thyroid gland. This type can be sub-classified into three subtypes. A1: the parathyroid gland is attached to the inherent thyroid capsule. A2: the gland is partially embedded in the thyroid gland. A3: the gland is located in the thyroid tissue. Type B is defined as a gland which is separated from the thyroid gland. The iPTH was sampled at wound closure. RESULTS: There were 100 patients in each group. We found a significant difference between the ETBAA and OTA-H groups for type A2, as well as a loss of parathyroid glands and a number of parathyroid transplantation procedures. The endoscopic group was treated during an earlier stage of thyroid cancer. The iPTH profile of each group decreased, although this was the most consistent in the OTA-H group. A comparison of ETBAA with OTA-L demonstrates that the iPTH level change is similar. CONCLUSION: There is no advantage of endoscopic treatment for preserving parathyroid function.

New Paradigms for Neural Monitoring in Thyroid Surgery.

Intraoperative neuromonitoring (IONM) in thyroid gland surgery provides real-time feedback to the endocrine surgeon regarding the electrophysiological consequences of surgical manipulation of the laryngeal nerves. The goal of monitoring modalities is to detect surgical or physiological insults to the recurrent laryngeal nerve (RLN) while they are still reversible or, in cases where prevention is not an option, to minimize the damage done to these structures during thyroidectomy. In recent decades, monitoring of the RLN has become a fundamental part of endocrine surgery. IONM is a feasible procedure in both open and endoscopic, robotic thyroidectomy. Experts in IONM have organized a working group of general, endocrine, head and neck ENT surgeons and endocrinologists (International Neural Monitoring Study Group; INMSG) to develop standards for practicing this technique in endoscopic and robotic thyroidectomy. This paper presents recent clinical and research experience with intraoperative neural monitoring for thyroid gland surgery.

Translational Study to Standardize the Safe Use of Bipolar Forceps, LigaSure™, Sonicision™ and PlasmaBlade™ Around the Recurrent Laryngeal Nerve in Thyroid Surgery.

PURPOSE: We investigated the function of the recurrent laryngeal nerve (RLN) in a live porcine model during adjacent activation with bipolar forceps (BF), LigaSure™ small jaw (LSJ), Sonicision™ and PlasmaBlade™ (PB) devices. METHODS: Each of the energy-based devices (EBD) was activated for 3 seconds at different power settings at 5, 3, 2, and 1 mm from the RLN. Nerve root function and thermal spread were measured by continuous intraoperative neuromonitoring and infrared thermal imaging. RESULTS: BF: The EMG amplitude decreased to 87% of baseline at a standardized distance. The highest thermal reading was 120°C at 1 mm (average 80.7°C). LSJ: EMG amplitudes were 99% (5mm), 90% (3mm) and 66% (2mm) of the baseline amplitude. At 1mm, the temperatures of the RLN surface and the LSJ tip reached 80.6°C and 100.8°C, respectively. Sonicision™: Under both the minimum and maximum settings, EMG amplitudes remained above 80% of the baseline amplitude. The highest temperatures of the device tip and RLN surface were 135°C and 117.3°C, respectively, at 1 mm. PB: The temperatures of the device tip and RLN surface increased gradually with an increase in the setting (tip 38.3°C to 163.8°C; nerve 34.8°C to 46.2°C). Loss of nerve function occurred at settings 9 and 10. There were no changes in the latency profile under any of the applications. CONCLUSIONS: RLN roots were exposed to increased temperatures when EBDs were applied at close spacing. The results suggest that these 4 EBDs are unsafe when applied at a distance of 1-3 mm from the RLN due to their effects on both EMG and temperature.

The risk factors for postoperative temporary vocal cord paralysis after thyroid cancer surgery: an observational retrospective cohort study.

OBJECTIVE: To analyze the potential factors influencing new-onset postoperative transient vocal cord paralysis (VCP) in thyroid cancer patients. METHODS: Case information of 8,340 thyroid cancer patients hospitalized at XX from January 2018 to December 2020 was collected retrospectively and analyzed. The possible influencing factors were analyzed using a chi-square test, rank-sum test, and multiple logistic regression analysis. A nomogram was used to construct the clinical prediction model that was validated in the validation set by ROC, calibration curves, and DCA. RESULTS: The STROCSS guideline was followed to conduct a retrospective cohort study. A total of 8,340 patients, including 1,817 (21.8%) men and 6,523 (78.2%) women, were enrolled in this study. The rate of temporary VCP was 3.6% (308/8,340). Based on the results of postoperative laryngoscopy, the patients were divided into VCP group and non-VCP group. Comparative analysis between the groups revealed that potential factors associated with postoperative transient VCP were tumor location on the dorsal side of the gland (P = 0.042), ultrasound showing a maximum nodal diameter > 1 cm (P = 0.002), multifocal carcinoma (P < 0.001), invasion of surrounding tissue (P = 0.005), lymph node metastases in the central compartment (P = 0.034), lateral cervical lymph node metastasis (P < 0.001), and prolonged operation (P < 0.001). A multiple logistic regression analysis showed that the independent risk factors in postoperative transient VCP were T stage (OR = 1.411, P = 0.013, 95% CI: 1.075-1.853), multifocal carcinoma (OR = 1.532, P = 0.013, 95% CI: 1.095-2.144), and duration of surgery (OR = 1.009, P < 0.001, 95% CI: 1.006-1.012). Finally, a clinical prediction model was established via a nomogram and was validated in the validation set, although its diagnostic efficacy needs to be improved further. CONCLUSION: High T stage, multifocal carcinoma, and prolonged operation time may be independent risk factors for the occurrence of postoperative transient VCP in patients undergoing initial surgery for thyroid cancer.

Noticeable effect of lower baseline amplitude on the predictive accuracy of intraoperative amplitude changes for postoperative vocal cord palsy: a prospective cohort study.

BACKGROUND: To explore the effect of lower baseline amplitude on its predictive accuracy of postoperative vocal cord paralysis (VCP) in monitored thyroid surgery. MATERIALS AND METHODS: Clinical and electrophysiological data were collected during thyroid surgeries performed between November and December 2021 at China-Japan Union Hospital. Univariate/multivariate regression analysis were applied to these data to examine a possible correlation. A receiver operating characteristic curve was used to evaluate predictive efficacy. RESULTS: A total of 631 nerves-at-risk (NAR) were identified in 460 patients who were divided into two groups according to postoperative development of VCP. The VCP group included a higher percentage of NAR with V1<1000 (68.2 vs. 40.7%, respectively; P =0.014) and NAR with R1<1400 (77.3 vs. 47.0%, respectively; P =0.005) compared with the non-VCP group. Multivariate regression analysis further identified V1<1000 [odds ratio (OR)=2.688, P =0.038], R1<1400 (OR=3.484, P =0.018) as independent risk factors for postoperative temporary VCP. The receiver operating characteristic curve showed the AUC value of V signal decline for predicting VCP was 0.87. The diagnostic efficiency of R signal decline reached as high as 0.973. A multivariate logistic regression analysis identified independent risk factors for V1<1000 and these included: higher BMI (OR=1.072, P =0.013), hypertension (OR=1.816, P =0.015), smoking (OR=1.814, P =0.031), and male sex (OR=2.016, P =0.027). CONCLUSION: In our cohort, lower baseline amplitude was an independent risk factor for developing transient postoperative VCP. It also affected the predictive efficacy of intraoperative amplitude changes on VCP. Higher BMI, hypertension, smoking, and male sex may also be closely associated with lower initial amplitude. Thus, maintaining a higher initial amplitude is critical for patient safety during thyroid surgery.

Growth, Enzymatic, and Transcriptomic Analysis of xyr1 Deletion Reveals a Major Regulator of Plant Biomass-Degrading Enzymes in Trichoderma harzianum.

The regulation of plant biomass degradation by fungi is critical to the carbon cycle, and applications in bioproducts and biocontrol. Trichoderma harzianum is an important plant biomass degrader, enzyme producer, and biocontrol agent, but few putative major transcriptional regulators have been deleted in this species. The T. harzianum ortholog of the transcriptional activator XYR1/XlnR/XLR-1 was deleted, and the mutant strains were analyzed through growth profiling, enzymatic activities, and transcriptomics on cellulose. From plate cultures, the Δxyr1 mutant had reduced growth on D-xylose, xylan, and cellulose, and from shake-flask cultures with cellulose, the Δxyr1 mutant had ~90% lower ß-glucosidase activity, and no detectable ß-xylosidase or cellulase activity. The comparison of the transcriptomes from 18 h shake-flask cultures on D-fructose, without a carbon source, and cellulose, showed major effects of XYR1 deletion whereby the Δxyr1 mutant on cellulose was transcriptionally most similar to the cultures without a carbon source. The cellulose induced 43 plant biomass-degrading CAZymes including xylanases as well as cellulases, and most of these had massively lower expression in the Δxyr1 mutant. The expression of a subset of carbon catabolic enzymes, other transcription factors, and sugar transporters was also lower in the Δxyr1 mutant on cellulose. In summary, T. harzianum XYR1 is the master regulator of cellulases and xylanases, as well as regulating carbon catabolic enzymes.

Improved Quantitative Analysis Method for Magnetic Particle Imaging Based on Deblurring and Region Scalable Fitting.

PURPOSE: Magnetic particle imaging (MPI) is a technique for imaging magnetic particle concentration distribution. It has the advantages of high sensitivity, no signal attenuation with depth, and no ionizing radiation. Although MPI has been widely used in the biomedical field, accurate image analysis has been challenging due to its anisotropic point spread function (PSF). The purpose of this study is to propose an MPI image restoring and segmentation method to facilitate a more precise quantitative evaluation of the magnetic particle imaging in vivo. PROCEDURES: We proposed a DeRSF method that combined deblurring and region scalable fitting (RSF) to determine the imaging tracer distribution. Then a uniform erosion and scaling criterion was established based on simulation experiments to correct the segmentation results, which was further validated on phantom imaging. Finally, we imaged the MPI tracer at gradient concentrations to establish the calibration curve between the MPI signal and iron mass for iron quantification in phantom and in vivo imaging. RESULTS: The phantom imaging experiments showed that our method achieved improved segmentation performance. The mean value of the dice coefficients for segmentation was up to 0.86, demonstrating that our method can accurately map and quantify the distribution of the tracer. Moreover, the iron quantification on both phantom and in vivo mouse imaging was realized with the minimal error of 5.50%, by our established calibration curve. CONCLUSIONS: Our proposed DeRSF method was successfully used for improved MPI quantitative analysis. More importantly, this method also showed accurate quantitative results on images with different shapes and tracer concentrations in both phantom and in vivo data, which laid the foundation for the biomedical study of MPI.

Recurrent laryngeal never monitoring versus non-monitoring in parathyroid surgery.

Background: Although intraoperative neural monitoring (IONM) is well established in thyroid surgery, it is less commonly analyzed in parathyroid operations. This study presents the results of IONM for primary and secondary hyperparathyroidism surgery. Methods: We retrospectively assessed 270 patients with primary hyperparathyroidism (PHPT), 53 patients with secondary hyperparathyroidism (SHPT), and 300 patients with thyroid cancer from June 2010 to June 2022 in one hospital in China. The follow-up was 12 months. Demographic, electromyography data from IONM, laboratory, and clinical information were collected. Laryngoscopy was collected from 109 patients with PHPT in whom IONM was not used. All groups were assessed by Pearson's chi-square test and Fisher's exact probability method to verify the relationship between parathyroid size and location, duration of surgery, preoperative concordant localization, laryngeal pain, IONM outcomes, cure rate, and RLN injury. Visual analog scale (VAS) assessed laryngeal pain. RLN outcomes were measured according to nerves at risk (NAR). Results: The study comprehended 918 NAR, that is 272, 105, 109, and 432 NAR for PHPT, SHPT with IONM, PHPT without IONM, and thyroid surgery control group, respectively. IONM successfully prevented RLN injury (P<0.001, P=0.012): Fifteen (5.51%) RLNs experienced altered nerve EMG profiles during surgery, and five (1.84%) experienced transient RLN injury in PHPT patients. Five (4.76%) RLNs were found to have altered EMG profiles during surgery, and one (0.95%) RLN had a transient RLN injury in SHPT patients. There was no permanent nerve injury (0.00%) in this series. There was no association between location, gland size, preoperative concordant localization, cure rate, duration of surgery, and IONM (P >0.05). Duration of surgery was associated with postoperative pharyngeal discomfort (P=0.026, P=0.024). Transient RLN injury was significantly lower in patients with PHPT who underwent IONM than in those who did not. Intraoperative neuromonitoring played an effective role in protecting the recurrent laryngeal nerve (P=0.035). Compared with parathyroidectomy, thyroidectomy had a higher rate of RLN injury (5.32%, P<0.001). Conclusion: IONM for SHPT and PHPT offers rapid anatomical gland identification and RLN functional results for effective RLN protection and reduced RLN damage rates.

A Semi-Empirical Damage Model of Helankou Rocks Based on Acoustic Emission.

The Helankou rock as the relics carrier in Ningxia, China, have been suffering from serious weathering caused by variable environmental conditions. To study the freeze-thaw damage characteristics of Helankou relics carrier rocks, three dry-wet conditions (i.e., drying, pH = 2 and pH = 7) together with freeze-thaw experiments have been carried out at 0, 10, 20, 30, and 40 cycles. Additionally, a series of triaxial compression tests have been carried out at four different cell pressures of 4 MPa, 8 MPa, 16 MPa, and 32 MPa in tandem with a non-destructive acoustic emission technique. Subsequently, the rock damage variables were identified based on elastic modulus and acoustic emission ringing counts. It has been revealed that the acoustic emission positioning points reflected that the cracks would be concentrated near the surface of main fracture at higher cell pressures. Notably, the rock samples at 0 freeze-thaw cycles failed in pure shear. However, both shear slip and extension along the tensile cracks were observed at 20 freeze-thaw cycles, while tensile-oblique shear failure occurred at 40 freeze-thaw cycles. Not surprisingly, the decreasing order of deterioration inside the rock was observed to be (drying group) > (pH = 7 group) > (pH = 2 group). The peak values of damage variables in these three groups were also found to be consistent with the deterioration trend observed under freeze-thaw cycles. Finally, the semi-empirical damage model could rigorously ascertain stress and deformation behavior of rock samples, thus providing theoretical basis to establish a protection framework for Helankou relics.

Prediction of central lymph node metastasis in patients with papillary thyroid microcarcinoma by gradient-boosting decision tree model based on ultrasound radiomics and clinical features.

Background: In recent years, the study of radiomics in thyroid diseases has developed rapidly. This study aimed to establish a preoperative radiomics prediction model for central compartment lymph node metastases (CLNMs) in papillary thyroid microcarcinoma (PTMC) patients using gradient-boosting decision tree (GBDT) model and evaluate the performance of the model. Methods: A total of 274 patients with PTMC admitted for thyroid surgery at China-Japan Union Hospital of Jilin University from January 2020 to July 2022 were retrospectively analyzed. Patients were randomized into training and validation cohorts according to a ratio of 8:2. Radiomics features were extracted from the ultrasound (US) images of PTMC lesions. The open-source software Pyradiomics was used to extract radiomics features, and WEKA software was used to select CLNM-related radiomics features. Clinical risk factors for CLNM were screened by statistical methods. The GBDT model was constructed by combining radiomics features and clinical risk factors, and compared with the diagnostic efficacy of US-reported cervical lymph node status. Shapley Additive exPlanations (SHAP) was applied to visualize and analyze the GBDT model globally and locally. Results: A total of seven radiomics features were significantly correlated with central lymph node status in the training and validation cohorts. The predictors in the GBDT model included the radiomics features, sex, age, and body mass index (BMI). The area under the curve (AUC) values of the GBDT model in the training and validation cohorts were 0.946 [95% confidence interval (CI): 0.920-0.972] and 0.845 (95% CI: 0.714-0.976), respectively, compared with 0.583 (95% CI: 0.508-0.659) and 0.582 (95% CI: 0.430-0.736) for US-reported lymph node status alone. The Delong test showed a significant difference between AUS in the training and validation cohorts (P<0.001, respectively). SHAP visual analysis showed the effect of each parameter on the GBDT model globally and locally. Decision curve analysis demonstrated the clinical utility of the GBDT model. Conclusions: The prediction of CLNM by the GBDT model, based on US radiomics features and clinical factors, can be better than that by using US alone in patients with PTMC. Furthermore, the GBDT model may serve a guidance of clinical decision for patient's treatment strategy.

Factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients.

Background: Parathyroidectomy (PTX) is an effective treatment for primary hyperparathyroidism (PHPT) patients. Postoperative hypocalcemia is a common complication after PTX. This study aimed to analyze the factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients. Methods: The retrospective study included 270 PHPT patients treated with PTX and collected their demographic and clinical information and their laboratory indices. Factors influencing serum calcium levels and hypocalcemia after PTX in PHPT patients were analyzed using univariate and multifactorial analyses. Results: First, in patients with normal preoperative serum calcium levels (2.20-2.74 mmol/L), the higher the preoperative alkaline phosphatase and serum phosphorus levels, the lower the postoperative serum calcium levels. Furthermore, the higher the preoperative serum calcium levels and the accompanying clinical symptoms, the higher the postoperative serum calcium levels. Low preoperative serum calcium levels were shown to be a risk factor for postoperative hypocalcemia (OR=0.022), and the optimal preoperative serum calcium threshold was 2.625 mmol/L (sensitivity and specificity were 0.587 and 0.712, respectively). Second, in the mild preoperative hypercalcemia group (2.75-3.00 mmol/L), the older the patient, the higher the preoperative and postoperative serum calcium levels, the higher the postoperative serum calcium; the lower the alkaline phosphatase and calcitonin levels, the higher the postoperative serum calcium levels. On the other hand, the younger the patient was, the more likely hypocalcemia blood was (OR=0.947), with an optimal age threshold of 47.5 years (sensitivity and specificity were 0.543 and 0.754, respectively). Third, in the preoperative moderate to severe hypercalcemia group (>3.0mmol/L), patients undergoing a combined contralateral thyroidectomy and a total thyroidectomy had low postoperative serum calcium levels. Conclusion: Patients with different preoperative serum calcium levels had various factors influencing their postoperative serum calcium levels and postoperative hypocalcemia, which facilitated the assessment of their prognosis.

Volatile Organic Compounds Emitted by the Biocontrol Agent Pythium oligandrum Contribute to Ginger Plant Growth and Disease Resistance.

The oomycete Pythium oligandrum is a potential biocontrol agent to control a wide range of fungal and oomycete-caused diseases, such as Pythium myriotylum-caused rhizome rot in ginger, leading to reduced yields and compromised quality. Previously, P. oligandrum has been studied for its plant growth-promoting potential by auxin production and induction of disease resistance by elicitors such as oligandrin. Volatile organic compounds (VOCs) play beneficial roles in sustainable agriculture by enhancing plant growth and resistance. We investigated the contribution of P. oligandrum-produced VOCs on plant growth and disease suppression by initially using Nicotiana benthamiana plants for screening. P. oligandrum VOCs significantly enhanced tobacco seedling and plant biomass contents. Screening of the individual VOCs showed that 3-octanone and hexadecane promoted the growth of tobacco seedlings. The total VOCs from P. oligandrum also enhanced the shoot and root growth of ginger plants. Transcriptomic analysis showed a higher expression of genes related to plant growth hormones and stress responses in the leaves of ginger plants exposed to P. oligandrum VOCs. The concentrations of plant growth hormones such as auxin, zeatin, and gibberellic acid were higher in the leaves of ginger plants exposed to P. oligandrum VOCs. In a ginger disease biocontrol assay, the VOC-exposed ginger plants infected with P. myriotylum had lower levels of disease severity. We conclude that this study contributes to understanding the growth-promoting mechanisms of P. oligandrum on ginger and tobacco, priming of ginger plants against various stresses, and the mechanisms of action of P. oligandrum as a biocontrol agent. IMPORTANCE Plant growth promotion plays a vital role in enhancing production of agricultural crops, and Pythium oligandrum is known for its plant growth-promoting potential through production of auxins and induction of resistance by elicitors. This study highlights the significance of P. oligandrum-produced VOCs in plant growth promotion and disease resistance. Transcriptomic analyses of leaves of ginger plants exposed to P. oligandrum VOCs revealed the upregulation of genes involved in plant growth hormone signaling and stress responses. Moreover, the concentration of growth hormones significantly increased in P. oligandrum VOC-exposed ginger plants. Additionally, the disease severity was reduced in P. myriotylum-infected ginger plants exposed to P. oligandrum VOCs. In ginger, P. myriotylum-caused rhizome rot disease results in severe losses, and biocontrol has a role as part of an integrated pest management strategy for rhizome rot disease. Overall, growth enhancement and disease reduction in plants exposed to P. oligandrum-produced VOCs contribute to its role as a biocontrol agent.

Metastasis to lymph nodes at the contralateral entrance point to the recurrent laryngeal nerve in unilateral thyroid papillary carcinoma: a case report and literature review.

Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. PTC is slow growing, and prognosis after surgery is excellent. However, PTC is associated with a high incidence of cervical lymph node metastasis, and usually metastasizes from the central lymph nodes to the ipsilateral cervical and mediastinal lymph nodes. Anatomic studies have shown that the thyroid gland and surrounding tissue have an abundant lymphatic network that facilitates tumor dissemination and lymph node metastasis, there may be many ways to connect lymph nodes on both sides of the neck of patients, which needs further research and discussion. Case Description: We report the case of a 45-year-old female who was diagnosed with thyroid cancer of the right lobe and right lateral lymph node metastasis by fine-needle aspiration (FNA). During surgery, 0.2 mL of carbon nanoparticle (CN) suspension was injected into the right lobe of the thyroid gland, which resulted in black staining of a lymph node at the contralateral entrance point to the recurrent laryngeal nerve (LN-epRLN). The black-stained lymph node was resected, and the pathology results revealed lymph node metastasis from thyroid cancer. The left lobe of the thyroid was benign. Conclusions: Retro-tracheal periesophageal lymph node metastasis may be a rare metastatic pathway in thyroid cancer.

Papillary thyroid carcinoma with rare lymph node metastasis between the non-ipsilateral sternocleidomastoid and striate muscles: two case reports and literature review.

Background: Differentiated thyroid cancer (DTC) has a high incidence but a generally good prognosis. However, lymph node metastasis is likely to occur. It usually metastasizes from the central group lymph nodes to the deep cervical lymph nodes and less frequently to the sternocleidomastoid-sternohyoid muscle. The lymph nodes between the sternocleidomastoid and sternohyoid muscles (LNSS) is easily overlook. Ignoring the preoperative assessment and dissection of level LNSS, especially in the contralateral neck level LNSS, may lead to incomplete surgery and thus require reoperation. The metastatic relevant factors and pathway for LNSS remains inconclusive require further investigation. There is a lack of reports of contralateral or bilateral cervical level LNSS metastasis in thyroid cancer. We hope to arouse attention to the level LNSS through our two case reports. Case Description: We report two cases of non-ipsilateral LNSS metastases. The patients were diagnosed with thyroid cancer by fine-needle aspiration (FNA), and ultrasound examination showed enlarged lymph nodes at the LNSS level. After surgical treatment and postoperative paraffin pathology, both patients were diagnosed with papillary thyroid carcinoma (PTC) and LNSS-level lymph node metastasis. Case 1 was a 63-year-old woman admitted to our hospital with a 15-day history of an untreated thyroid nodule and preoperative euthyroidism. This patient underwent total thyroidectomy, central and left neck LNSS dissection. Her prognosis was good, and there were no signs of recurrence at her 6-month follow-up appointment; Case 2 was a 24-year-old woman admitted to our hospital for a physical examination of an anterior cervical mass that had been present for 1 year and preoperative euthyroidism. This patient underwent total thyroidectomy, central and bilateral neck LNSS dissection. Her prognosis was good, and there were no signs of recurrence at her 12-month follow-up appointment. Conclusions: The occurrence of contralateral and bilateral simultaneous LNSS metastasis in thyroid cancer is relatively rare. However, in clinical practice, surgeons should focus on the evaluation and clearance of LNSS, especially in patients with cancer foci located in the lower pole, cancer foci invading the anterior cervical band muscle, extensive metastasis in the lateral cervical lymph nodes or stages T3/4 and to reduce postoperative recurrence.

The feasibility of laryngeal nerve protection during thyroidectomy using sternocleidomastoid intermuscular approach with intraoperative neuromonitoring: a case series and step-by-step description of surgical procedure.

Background: Thyroid surgery is increasingly demanding in terms of cosmetic neck outcomes and protection of anterior neck function, so we have adopted an alternative sternocleidomastoid intermuscular approach (SMIA) for open/conventional thyroidectomy. The protection of recurrent laryngeal nerve (RLN) and external branch of superior laryngeal nerve (EBSLN) is the key and difficult point in thyroid surgery. The aim of this study was to testify the feasibility of RLN and EBSLN functional protection during SMIA thyroidectomy with the intraoperative neuromonitoring. Methods: A total of 39 patients and 39 RLN and EBSLNs who underwent monitored SMIA thyroidectomy were included. Thyroid gland is revealed and excised anterior to the cervical sheath between the sternal and clavicular heads of the sternocleidomastoid muscle. Standardized intraoperative neuromonitoring (IONM) procedures and postoperative laryngeal examination were performed to audit the SMIA. Following the four-step method, V1, R1, R2, and V2 were monitored and the signal values were recorded. Statistical analysis was used to evaluate the change of IONM amplitude of RLN, combined with the results of laryngoscopy before and after operation to determine the status of RLN. EBSLN injuries were identified from changes in cricothyroid muscle (CTM) twitch and EMG. SMIA video vignette is detailed. Results: All RLN and EBSLNs [17 on the left and 22 on the right] were monitored in 39 patients [5 men, 34 women; mean age 34.1±8.7 years; mean body mass index 22.5 (±3.0, 17.0-30.8) kg/m2] undergoing SMIA. For RLN of the affected side, we compared the V2 and V1 (1,236±672 vs. 1,240±428, P=0.973), R2 and R1 (1,676±778 vs. 1,656±765, P=0.849) signals separately, and the results were not statistically different (P>0.05). Comparing the V1 (1,240±428 vs. 1,309±395, P=0.601) signals of the bilateral recurrent laryngeal nerve, there was no statistical difference (P>0.05). CTM twitch and EMG were preserved. Conclusions: The SMIA technique appears feasible. RLN and EBSLN are easier to be exposed during thyroid surgery of SMIA, which is beneficial to the neuroprotection during the operation. At the same time, it can protect the anterior cervical function and improve the cosmetic effect after operation.

Prognostic significance of inflammatory markers LMR, PLR, MPV, FIB in intermediate-and high-risk papillary thyroid carcinoma.

Background: Lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV) and fibrinogen (FIB) have been identified as predictive biomarkers in several malignancies. The aim of this study was to explore the association between inflammatory index with clinicopathologic features as well as recurrence risk in intermediate-to high-risk papillary thyroid carcinoma (PTC). Methods: Retrospective evaluation of 212 patients diagnosed with intermediate-to high-risk PTC who underwent surgery at China-Japan Union Hospital between 2015 and 2016. Logistic regression and receiver operating curves (ROC) were used to explore possible risk factors. Results: LMR was predictive of capsular invasion (AUC=0.595, P=0.017), FIB was predictive of lymph node metastasis (LN) (AUC=0.714, P=0.002), MPV was predictive of largest LN size ≥1cm (AUC=0.639, P=0.002), PLR and MPV were predictive of recurrence (AUC=0.616, P=0.032; AUC=0.626, P=0.020). In addition, FIB ≤ 2.6 (OR=6.440, 95%CI:1.777-23.336, P=0.005) and capsular invasion (OR=3.773, 95%CI:1.171-12.159, P=0.026) were identified as independent risk factors for lymph node metastasis by multivariate analysis. In addition, LN metastasis (P=0.048), largest LN size ≥ 1 cm (P=0.032), MPV > 9.4 (P=0.046), and PLR ≤ 128.1 (P=0.032) were significantly related with recurrence. Further multivariate regression analysis revealed that PLR ≤ 128.1 was a potentially independent risk factor for recurrence. Specifically, the risk of recurrence was 2.951 times higher in patients with a PLR ≤ 128.1 compared with patients with a PLR > 128.1 (OR=2.951, 95% CI:1.238-7.037, P=0.015). Conclusion: In intermediate-to high-risk PTC, LMR, PLR, MPV, and FIB could predict clinicopathologic features and recurrence, with lower PLR being the potential risk factors for recurrence.