Comparative Study on Simulated Outdoor Navigation for Agricultural Robots.

This research presents a comprehensive comparative analysis of SLAM algorithms and Deep Neural Network (DNN)-based Behavior Cloning (BC) navigation in outdoor agricultural environments. The study categorizes SLAM algorithms into laser-based and vision-based approaches, addressing the specific challenges posed by uneven terrain and the similarity between aisles in an orchard farm. The DNN-based BC navigation technique proves efficient, exhibiting reduced human intervention and providing a viable alternative for agricultural navigation. Despite the DNN-based BC navigation approach taking more time to reach its target due to a constant throttle limit for steady speed, the overall performance in terms of driving deviation and human intervention is notable compared to conventional SLAM algorithms. We provide comprehensive evaluation criteria for selecting optimal techniques for outdoor agricultural navigations. The algorithms were tested in three different scenarios: Precision, Speed, and Autonomy. Our proposed performance metric, P, is weighted and normalized. The DNN-based BC algorithm showed the best performance among the others, with a performance of 0.92 in the Precision and Autonomy scenarios. When Speed is more important, the RTAB-Map showed the best score with 0.96. In a case where Autonomy has a higher priority, Gmapping also showed a comparable performance of 0.92 with the DNN-based BC.

Prediction of the efficacy of proton-pump inhibitors in patients with contact granuloma using 24-hour combined dual channel pH/impedance monitoring.

OBJECTIVES: We aimed to evaluate the treatment outcomes of proton-pump inhibitors (PPIs) in patients with contact granuloma (CG) and to investigate the parameters of 24 h combined dual channel pH/impedance (24 h pH/MII) monitoring, which are reliable for predicting the response to PPI of CG patients. METHODS: We reviewed the medical records of patients with CG who had been treated with PPIs and had completed more than 6 months of follow-up. We classified the patients into two groups (cured vs. persistent), according to their PPI treatment outcomes. Reflux events were categorized into three groups based on pharyngeal pH during reflux: 1) acid reflux (pH < 4), 2) weak acid reflux (4 < pH < 7), and 3) weak alkaline reflux (pH >7), as detected by a proximal probe. We compared the results of 24h-pH/MII between the two groups and used receiver operating characteristic curve (ROC) analysis to determine the cutoff values of significant parameters for predicting responses to PPIs. RESULTS: Among 22 patients who completed at least 6 months of PPI treatment and follow-up, weak acid reflux events were more frequently observed in persistent group than in the cured group (p = 0.046), and the proportion of weak acid reflux was also higher in the persistent group (p = 0.031) than in the cured group. Reliable parameters predictive of a poor response to PPIs were a number of weak acid reflux events ≥ 11 (area under the curve [AUC], 0.775; p = 0.03) and a proportion of weak acid reflux events ≥ 56.7 % (AUC, 0.763; p = 0.038) in ROC analyses. CONCLUSION: Weak acid reflux was identified as a significant factor associated with the treatment outcomes of PPIs in patients with CG. A number of weak acid reflux events ≥ 11 is considered to be the most reliable predictor of a poor response to PPIs in patients with CG.

Self-Assembled Skin-Penetrating Peptides with Controlled Supramolecular Properties for Enhanced Transdermal Delivery.

The use of nanocarriers decorated with penetration-enhancing agents (PEAs) is considered to be a promising approach for efficient transdermal delivery. In this study, we developed short amphiphilic skin-penetrating peptides (17 amino acids) that functioned not only as PEAs but also as building blocks of nanocarriers without the incorporation of additional macromolecules for self-assembly and guest molecule encapsulation. Interestingly, varying only two amino acids in the hydrophobic moiety of the peptides resulted in significantly different self-assembly behavior, thermal stability, protease resistance, and skin-penetration efficiency in a human skin model. The analysis of the peptide secondary structure revealed that such characteristic changes arose due to the sequence variation-mediated conformational change in the hydrophobic block. These findings hold significant promise for the development of simple and effective delivery systems exhibiting controllable supramolecular properties.

Self-assembling biomolecules for biosensor applications.

Molecular self-assembly has received considerable attention in biomedical fields as a simple and effective method for developing biomolecular nanostructures. Self-assembled nanostructures can exhibit high binding affinity and selectivity by displaying multiple ligands/receptors on their surface. In addition, the use of supramolecular structure change upon binding is an intriguing approach to generate binding signal. Therefore, many self-assembled nanostructure-based biosensors have been developed over the past decades, using various biomolecules (e.g., peptides, DNA, RNA, lipids) and their combinations with non-biological substances. In this review, we provide an overview of recent developments in the design and fabrication of self-assembling biomolecules for biosensing. Furthermore, we discuss representative electrochemical biosensing platforms which convert the biochemical reactions of those biomolecules into electrical signals (e.g., voltage, ampere, potential difference, impedance) to contribute to detect targets. This paper also highlights the successful outcomes of self-assembling biomolecules in biosensor applications and discusses the challenges that this promising technology needs to overcome for more widespread use.

Tailoring tumor-recognizable hyaluronic acid-lipid conjugates to enhance anticancer efficacies of surface-engineered natural killer cells.

Natural killer (NK) cells have clinical advantages in adoptive cell therapy owing to their inherent anticancer efficacy and their ability to identify and eliminate malignant tumors. However, insufficient cancer-targeting ligands on NK cell surfaces often inhibit their immunotherapeutic performance, especially in immunosuppressive tumor microenvironment. To facilitate tumor recognition and subsequent anticancer function of NK cells, we developed hyaluronic acid (HA, ligands to target CD44 overexpressed onto cancer cells)-poly(ethylene glycol) (PEG, cytoplasmic penetration blocker)-Lipid (molecular anchor for NK cell membrane decoration through hydrophobic interaction) conjugates for biomaterial-mediated ex vivo NK cell surface engineering. Among these major compartments (i.e., Lipid, PEG and HA), optimization of lipid anchors (in terms of chemical structure and intrinsic amphiphilicity) is the most important design parameter to modulate hydrophobic interaction with dynamic NK cell membranes. Here, three different lipid types including 1,2-dimyristoyl-sn-glycero-3-phosphati-dylethanolamine (C14:0), 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE, C18:0), and cholesterol were evaluated to maximize membrane coating efficacy and associated anticancer performance of surface-engineered NK cells (HALipid-NK cells). Our results demonstrated that NK cells coated with HA-PEG-DSPE conjugates exhibited significantly enhanced anticancer efficacies toward MDA-MB-231 breast cancer cells without an off-target effect on human fibroblasts specifically via increased NK cell membrane coating efficacy and prolonged surface duration of HA onto NK cell surfaces, thereby improving HA-CD44 recognition. These results suggest that our HALipid-NK cells with tumor-recognizable HA-PEG-DSPE conjugates could be further utilized in various cancer immunotherapies.

PSMD1 as a prognostic marker and potential target in oropharyngeal cancer.

BACKGROUND: Despite the diverse genetic mutations in head and neck cancer, the chemotherapy outcome for this cancer has not improved for decades. It is urgent to select prognostic factors and therapeutic targets for oropharyngeal cancer to establish precision medicine. Recent studies have identified PSMD1 as a potential prognostic marker in several cancers. We aimed to assess the prognostic significance of PSMD1 expression in oropharyngeal squamous cell carcinoma (OPSCC) patients using immunohistochemistry. METHODS: We studied 64 individuals with OPSCC tissue from surgery at Seoul National University Bundang Hospital between April 2008 and August 2017. Immunostaining analysis was conducted on the tissue microarray (TMA) sections (4 µm) for p16 and PSMD1. H-score, which scale from 0 to 300, was calculated from each nucleus, cytoplasm, and cellular expression. Clinicopathological data were compared with Chi-squared test, Fisher's exact test, t-test, and logistic regression. Survival data until 2021 were achieved from national statistical office of Korea. Kaplan-Meier method and cox-regression model were used for disease-specific survival (DSS) analysis. RESULTS: H-score of 90 in nucleus was appropriate cutoff value for 'High PSMD1 expression' in OPSCC. Tonsil was more frequent location in low PSMD1 group (42/52, 80.8%) than in high PSMD1 group (4/12, 33.3%; P = .002). Early-stage tumor was more frequent in in low PSMD1 group (45/52, 86.5%) than in high PSMD1 group (6/12, 50%; P = .005). HPV was more positive in low PSMD1 group (43/52, 82.7%) than in high PSMD1 group (5/12, 41.7%; P = .016). Patients with PSMD1 high expression showed poorer DSS than in patients with PSMD1 low expression (P = .006 in log rank test). In multivariate analysis, PSMD1 expression, pathologic T staging, and specimen age were found to be associated with DSS (P = .011, P = .025, P = .029, respectively). CONCLUSIONS: In our study, we established PSMD1 as a negative prognostic factor in oropharyngeal squamous cell carcinoma, indicating its potential as a target for targeted therapy and paving the way for future in vitro studies on drug repositioning.

Ex Vivo Peptide Decoration Strategies on Stem Cell Surfaces for Augmenting Endothelium Interaction.

Ischemic vascular diseases remain leading causes of disability and death. Although various clinical therapies have been tried, reperfusion injury is a major issue, occurring when blood recirculates at the damaged lesion. As an alternative approach, cell-based therapy has emerged. Mesenchymal stem cells (MSCs) are attractive cellular candidates due to their therapeutic capacities, including differentiation, safety, angiogenesis, and tissue repair. However, low levels of receptors/ligands limit targeted migration of stem cells. Thus, it is important to improve homing efficacy of transplanted MSCs toward damaged endothelium. Among various MSC modulations, ex vivo cell surface engineering could effectively augment homing efficiency by decorating MSC surfaces with alternative receptors/ligands, thereby facilitating intercellular interactions with the endothelium. Especially, exogenous decoration of peptides onto stem cell surfaces could provide appropriate functional signaling moieties to achieve sufficient MSC homing. Based on their protein-like functionalities, high modularity in molecular design, and high specific affinities and multivalency to target receptors, peptides could be representative surface-presentable moieties. Moreover, peptides feature a mild synthetic process, enabling precise control of amino acid composition and sequence. Such ex vivo stem cell surface engineering could be achieved primarily by hydrophobic interactions of the cellular bilayer with peptide-conjugated anchor modules and by covalent conjugation between peptides and available compartments in membranes. To this end, this review provides an overview of currently available peptide-mediated, ex vivo stem cell surface engineering strategies for enhancing MSC homing efficiency by facilitating interactions with endothelial cells. Stem cell surface engineering techniques using peptide-based bioconjugates have the potential to revolutionize current vascular disease treatments while addressing their technical limitations.

Portable Colorimetric Hydrogel Beads for Point-of-Care Antimicrobial Susceptibility Testing.

Sepsis is a life-threatening condition with systemic inflammatory responses caused by bacterial infections. Considering the emergence of antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), sepsis is a great threat to public health. The gold standard methods for antimicrobial susceptibility testing (AST), however, take at least approximately 3 days to implement the entire blood culture, pure culture, and AST processes. To overcome the time-consuming nature of conventional AST, a method employing a chromatic biosensor composed of poly(diacetylene), alginate, and LB broth (PAL) is introduced in this study. Compared to the gold standards, AST with PAL biosensors can be completed within a time frame as short as 16 h. Such a significant reduction in time is possible because the consecutive cultures and AST are carried out simultaneously by encapsulating the bacterial nutrients and detection molecules into a single component. The bead-like hydrogel sensors were used in their freeze-dried form, which endows them with portability and stability, thus making them adequate for point-of-care testing. The PAL biosensor yields minimum inhibitory concentrations comparable to those from the Clinical and Laboratory Standards Institute, and the applicability of the biosensor is further shown in MRSA-infected mice.

Single-Walled Carbon Nanotube-Guided Topical Skin Delivery of Tyrosinase to Prevent Photoinduced Damage.

When the skin is exposed to ultraviolet radiation (UV), it leads to the degradation of the extracellular matrix (ECM) and results in inflammation. Subsequently, melanocytes are triggered to induce tyrosinase-mediated melanin synthesis, protecting the skin. Here, we introduce a proactive approach to protect the skin from photodamage via the topical delivery of Streptomyces avermitilis-derived tyrosinase (SaTy) using single-walled carbon nanotube (SWNT). Utilizing a reverse electrodialysis (RED) battery, we facilitated the delivery of SaTy-SWNT complexes up to depths of approximately 300 µm, as analyzed by using confocal Raman microscopy. When applied to ex vivo porcine skin and in vivo albino mouse skin, SaTy-SWNT synthesized melanin, resulting in 4-fold greater UV/vis absorption at 475 nm than in mice without SaTy-SWNT. The synthesized melanin efficiently absorbed UV light and alleviated skin inflammation. In addition, the densification of dermal collagen, achieved through SaTy-mediated cross-linking, reduced photoinduced wrinkles by 66.3% in the affected area. Our findings suggest that SWNT-mediated topical protein delivery holds promise in tissue engineering applications.

Modulating the folding and binding of peptides using a stimuli-responsive molecular tweezer.

This study presents the development of a ß-hairpin (tryptophan zipper, Trpzip)-based molecular tweezer (MT) that can control the folding and binding of α-helical peptides. When an α-helix isolated from the p53 protein was conjugated with Trpzip in an optimized macrocyclic structure, the folded ß-hairpin stabilized the helix conformation through the side chain-to-side chain stapling strategy, which notably enhanced target (hDM2) affinity of the peptide. On the other hand, the helicity and binding affinity were significantly reduced when the hairpin was unfolded by a redox stimulus. This stimulus-responsive property was translated into the effective capture and release of model multivalent biomaterials, hDM2-gold nanoparticle conjugates. Since numerous protein interactions are mediated by α-helical peptides, these results suggest that the ß-hairpin-based MT holds great potential to be utilized in various biomedical applications, such as protein interaction inhibition and cancer biomarker (e.g., circulating tumor cells and exosomes) detection.

Revisiting Loré's retrograde thyroidectomy from the perspective of preserving the external branch of the superior laryngeal nerve.

Background: Injury to the external branches of the superior laryngeal nerve (EBSLN) is the main reported cause of inexplicable post-thyroidectomy dysphonia (PTD) without recurrent laryngeal nerve (RLN) injury. Loré proposed a retrograde thyroidectomy (RT) technique in which the superior pole is dissected as a final step after the Berry ligament division, making this approach advantageous for protecting the EBSLN. However, evidence of this protective effect remains insufficient. We aimed to evaluate EBSLN function following RT and conventional thyroidectomy (CT) using postoperative electromyography (EMG). Methods: This is a retrospective cohort study conducted at a single tertiary center. Consecutive patients who had undergone CT or RT were included. Bilateral EMG of the cricothyroid muscle was performed 2-3 months postoperatively in all patients. Patient characteristics, postoperative findings of bleeding events, drain amount, hypocalcemia, calcium replacement, RLN function, and EBSLN function were thoroughly reviewed and compared between the two surgical approaches. Abnormalities in the EMG findings were reported based on the wave configuration, and the results were graded into four categories. Results: Seven hundred and thirty-one consecutive patients who underwent CT (n=341), or RT (n=390) were included, and a total of 1,179 RLNs and EBSLNs were at risk in CT (n=601) and RT (n=578). The CT and RT groups had similar clinical characteristics and surgical data. Two groups presented similar postoperative results for bleeding incidence, drain amount, and hypocalcemia. All RLNs were identified in both groups and their permanent function was preserved. EBSLN was significantly less frequently identified in the surgical field during RT than it was during CT (0.3% vs. 4.2%, respectively; P<0.001). Abnormal rates of postoperative EMG on the EBSLN were significantly lower in the RT group than in the CT group (1.7% vs. 7.8%, respectively; P<0.001), while the CT group presented with a higher grade of abnormal EMG (P<0.001). Conclusions: The RT technique may be beneficial for preserving EBSLN function. Meticulous capsular dissection and appropriate traction of the upper pole facilitated by RT are crucial for decreasing the risk of EBSLN injury, which can be achieved without directly identifying the nerve.

Incidence and Clinicopathological Features of Differentiated High-Grade Thyroid Carcinomas: An Institutional Experience.

Differentiated high-grade thyroid carcinoma (DHGTC) is a new entity in the 2022 WHO classification. We aimed to investigate the incidence and clinicopathological features of differentiated HG thyroid carcinoma (DHGTC) and compare the clinicopathological parameters of DHGTC, DTC without HG features, and poorly differentiated thyroid carcinoma (PDTC). A total of 1069 DTCs including papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs) were included in this study. Consecutive 22 PDTCs were also included for comparative purposes. There were a total of 14 (1.3%) cases of DHGTCs, with 13 HGPTCs (1.2% of PTCs) and one HGFTC (6.7% of FTCs). Compared to DTCs without HG features, DHGTCs were associated with larger tumor size, presence of blood vessel invasion, gross extrathyroidal extension, distant metastasis at the time of diagnosis, higher American Joint Committee on Cancer stage, high American Thyroid Association risk, and TERT promoter mutations. DHGTC and PDTC showed a significantly shorter recurrence-free survival (RFS) than DTC without HG features. Multivariate Cox regression analysis revealed that blood vessel invasion, lateral node metastasis, TERT promoter mutations, and HG features were independent prognostic factors (all p < 0.05). When tumor necrosis and increased mitotic count were evaluated separately, tumor necrosis, but not increased mitotic counts, was found to be an independent prognostic factor (p = 0.006). This study confirmed that DHGTC is significantly associated with aggressive clinicopathological features and poor clinical outcomes, similar to PDTC. Although the incidence is low, careful microscopic examination of HG features in DTC is required.

Cholesterol sulfate inhibits osteoclast differentiation and survival by regulating the AMPK-Sirt1-NF-κB pathway.

Cholesterol sulfate (CS) is an activator of retinoic acid-related orphan receptor α (RORα). CS treatment or RORα overexpression attenuates osteoclastogenesis in a collagen-induced arthritis mouse model. However, the mechanism by which CS and RORα regulate osteoclast differentiation remains largely unknown. Thus, we aimed to investigate the role of CS and RORα in osteoclastogenesis and their underlying mechanism. CS inhibited osteoclast differentiation, but RORα deficiency did not affect osteoclast differentiation and CS-mediated inhibition of osteoclastogenesis. CS enhanced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and sirtuin1 (Sirt1) activity, leading to nuclear factor-κB (NF-κB) inhibition by decreasing acetylation at Lys310 of p65. The NF-κB inhibition was restored by AMPK inhibitor, but the effects of CS on AMPK and NF-κB were not altered by RORα deficiency. CS also induced osteoclast apoptosis, which may be due to sustained AMPK activation and consequent NF-κB inhibition, and the effects of CS were significantly reversed by interleukin-1ß treatment. Collectively, these results indicate that CS inhibits osteoclast differentiation and survival by suppressing NF-κB via the AMPK-Sirt1 axis in a RORα-independent manner. Furthermore, CS protects against bone destruction in lipopolysaccharide- and ovariectomy-mediated bone loss mouse models, suggesting that CS is a useful therapeutic candidate for treating inflammation-induced bone diseases and postmenopausal osteoporosis.

Superior Laryngeal Nerve Block in Transcutaneous Vocal Fold Injection: A Pilot Study.

OBJECTIVES: Topical lidocaine remains the mainstay for anesthesia in transcutaneous vocal fold injection (VFI). While using topical lidocaine, laryngologists sometimes encounter uncontrolled reflexes or poor compliance. Superior laryngeal nerve block (SLNB) provides deep and rapid anesthesia on the larynx above the vocal folds and abolishes the glottic closure reflex. Herein, we present a pilot study to evaluate the feasibility and safety of SLNB for transcutaneous VFI and explored its usefulness. METHODS: Fifty-nine patients were prospectively anesthetized with SLNB during transcutaneous VFI for unilateral vocal fold paralysis. In the SLNB group, 0.5 to 1 mL of 2% lidocaine was infiltrated on bilateral SLNs through the thyrohyoid membrane. As the control group, we included previous 47 patients who underwent VFI with topical lidocaine. In the control group, 10% lidocaine spray was applied to the laryngopharyngeal mucosa. Demographic data, laryngeal exposure, patient compliance, procedural interruption, and complications were investigated. Patient compliance was evaluated based on the frequency of cough and swallowing during VFI procedures. RESULTS: SLNB enabled endoscopic contact on the epiglottis and pharyngeal wall without gag reflex and provided good exposure of the procedure field on the vocal folds. In the SLNB group, the laryngeal exposure is significantly better than in the control (P = 0.005). The frequency of cough and swallowing was significantly lower in the SLNB group than in the control (P < 0.001). The number of procedural interruptions was lower in the SLNB group than in the control (P < 0.001). There was no acute or delayed complication related to SLNB such as bleeding, hematoma, delayed sensory/swallowing problems, or unscheduled hospital visits. CONCLUSIONS: SLNB might be safe and effective for anesthesia in transcutaneous VFI. SLNB could be a good anesthetic option for patients with poor compliance despite the sufficient application of topical lidocaine.

Adjuvant radiotherapy in node-negative salivary malignancies of the parotid gland: A multi-institutional analysis.

BACKGROUND AND PURPOSE: To determine the role of adjuvant radiotherapy (ART) in parotid gland cancer without nodal metastasis, we evaluated the survival outcomes, prognostic factors, and dose-response relationships in patients with node-negative parotid gland cancer patients. MATERIALS AND METHODS: Patients who underwent curative parotidectomy and were pathologically diagnosed with parotid gland cancer without regional or distant metastases between 2004 and 2019 were reviewed. The benefit of ART in terms of locoregional control (LRC) and progression-free survival (PFS) were evaluated. RESULTS: In total, 261 patients were included in the analysis. Of them, 45.2 % received ART. The median follow-up period was 66.8 months. Multivariate analysis revealed that histological grade and ART were independent prognostic factors for LRC and PFS (all p <.05). For patients with high-grade histology, ART was associated with a significant improvement in 5-year LRC (p =.005) and PFS (p =.009). Among patients with high-grade histology who completed RT, higher biologic effective dose (≥77 Gy10) significantly increased PFS (adjusted hazard ratio [HR], 0.10 per 1-Gy increase; 95 % confidence interval [CI], 0.02-0.58; p =.010). ART significantly improved LRC (p =.039) in patients with low-to-intermediate histological grade as well per multivariate analysis, and subgroup analyses revealed patients with T3-4 stage and close/positive resection margins (<1 mm) would benefit from ART. CONCLUSION: ART should be strongly recommended for patients with node-negative parotid gland cancer with high-grade histology in terms of disease control and survival. In patients with low-to-intermediate-grade disease, those with high T stage and incomplete resection margin benefit with ART.

Cumulative sum analysis of the learning curve for robotic retroauricular thyroidectomy.

Background: Remote-access robotic thyroid surgery enables avoiding a visible scar on the neck and allows precise manipulation through a magnified surgical view. The retroauricular approach has many advantages. This study aimed to evaluate the learning curve for robotic retroauricular thyroidectomy using cumulative sum analysis. Methods: The medical records of 36 patients who underwent robotic retroauricular thyroidectomy between 2018 and 2021 were retrospectively reviewed. The clinical features and surgical outcomes were analyzed; the learning curve was evaluated using the cumulative sum analysis. Results: The learning curve using cumulative sum analysis was divided into two phases based on 15 cases: phase I (first 15 cases) and phase II (remaining 21 cases). The total operation time was significantly shorter in phase II than that in phase I (161.9±23.4 vs. 199±41.0 min, P=0.002). The flap dissection and docking time (77.1±14.3 vs. 90.0±21.5 min, P=0.037) and console time (36.5±16.2 vs. 50.3±17.8 min, P=0.020) were significantly shorter in phase II than that in phase I. There was no significant difference between the two phases in the total amount of drainage, duration of hospital stay, and complications after the surgery. Conclusions: The learning curve for robotic retroauricular thyroidectomy demonstrates that the operation time decreased rapidly after 15 cases. Proficiency in docking and manipulating the instruments accelerate the learning curve.

BRAFV600E and TERT promoter C228T mutations on ThyroSeq v3 analysis of delayed skin metastasis from papillary thyroid cancer: a case report and literature review.

BACKGROUND: Skin metastasis from papillary thyroid cancer (PTC) is a rare entity that can occur up to decades after treatment of the primary tumor. Here, we present a patient who developed skin metastasis 10 years after treatment of her primary tumor and describe the molecular findings of the metastatic lesion. CASE PRESENTATION: A 44-year-old female with a history of PTC who underwent a total thyroidectomy and radioactive iodine (RAI) treatment 10 years ago presented with a 1.3-cm skin lesion along the prior thyroidectomy scar. A biopsy revealed metastatic PTC, and the patient underwent surgical excision of the lesion. ThyroSeq molecular testing showed the copresence of BRAFV600E mutation and TERT promoter C228T mutation. The patient subsequently received one round of adjuvant RAI therapy. CONCLUSIONS: A high index of suspicion is warranted in patients with a history of PTC who develop a skin lesion, even several years after remission of the primary disease. In patients with high-risk mutations, such as BRAFV600E and TERT promoter C228T mutations, long-term surveillance of disease recurrence is particularly important.

Dendrimer-Peptide Conjugates for Effective Blockade of the Interactions between SARS-CoV-2 Spike Protein and Human ACE2 Receptor.

The coronavirus disease 2019 (COVID-19) pandemic has threatened the stability of global healthcare, which is becoming an endemic issue. Despite the development of various treatment strategies to fight COVID-19, the currently available treatment options have shown varied efficacy. Herein, we have developed an avidity-based SARS-CoV-2 antagonist using dendrimer-peptide conjugates (DPCs) for effective COVID-19 treatment. Two different peptide fragments obtained from angiotensin-converting enzyme 2 (ACE2) were integrated into a single sequence, followed by the conjugation to poly(amidoamine) (PAMAM) dendrimers. We hypothesized that the strong multivalent binding avidity endowed by dendrimers would help peptides effectively block the interaction between SARS-CoV-2 and ACE2, and this antagonist effect would be dependent upon the generation (size) of the dendrimers. To assess this, binding kinetics of the DPCs prepared from generation 4 (G4) and G7 PAMAM dendrimers to spike protein of SARS-CoV-2 were quantitatively measured using surface plasmon resonance. The larger dendrimer-based DPCs exhibited significantly enhanced binding strength by 3 orders of magnitude compared to the free peptides, whereas the smaller one showed a 12.8-fold increase only. An in vitro assay using SARS-CoV-2-mimicking microbeads also showed the improved SARS-CoV-2 blockade efficiency of the G7-peptide conjugates compared to G4. In addition, the interaction between the DPCs and SARS-CoV-2 was analyzed using molecular dynamics (MD) simulation, providing an insight into how the dendrimer-mediated multivalent binding effect can enhance the SARS-CoV-2 blockade. Our findings demonstrate that the DPCs having strong binding to SARS-CoV-2 effectively block the interaction between ACE2 and SARS-CoV-2, providing a potential as a high-affinity drug delivery system to direct anti-COVID payloads to the virus.

Early Postoperative Injections of Polydeoxyribonucleotide Prevent Hypertrophic Scarring After Thyroidectomy: A Randomized Controlled Trial.

Objective: Polydeoxyribonucleotide (PDRN) is known to enhance wound healing, but there has been no clinical trial investigating the effect of PDRN on scar prevention in surgical wounds. This study aimed to evaluate the efficacy of PDRN administration in preventing postoperative scars. Approach: In this randomized controlled trial (NCT05149118), 44 patients who underwent open thyroidectomy were randomly assigned to the PDRN treatment or untreated control group. Only patients in the treatment group received two consecutive injections of PDRN 1 and 2 days after surgery. The modified Vancouver Scar Scale (mVSS), patients' subjective symptoms, erythema index (EI), melanin index (MI), and scar height were assessed 3 months after surgery. Results: Patients in the treatment group had lower mVSS scores (1.619 ± 1.244 vs. 2.500 ± 1.540, respectively; p = 0.059) and a significantly lower vascularity subscore (0.476 ± 0.512 vs. 0.900 ± 0.447, respectively; p = 0.010) than those in the control group at the 3-month follow-up. Compared with the control group, the level of subjective symptoms, EI, and scar height were all significantly lowered in the PDRN injection group. No specific side effects related to PDRN injection were observed. Innovation: This is the first clinical study that demonstrated that PDRN injections rapidly decreased postsurgical wound erythema and as a result, significantly reduced both excessive scar formation and accompanying symptoms. Conclusion: Early postoperative injection of PDRN is an effective and safe treatment to prevent hypertrophic scars and improve scar outcomes.

Antioxidant Constituents and Activities of the Pulp with Skin of Korean Tomato Cultivars.

Tomato is a widely distributed, cultivated, and commercialized vegetable crop. It contains antioxidant constituents including lycopene, tocopherols, vitamin C, γ-aminobutyric acid, phenols, and flavonoids. This study determined the contents of the antioxidant components and activities of the pulp with skin of ten regular, six medium-sized, and two small cherry tomato cultivars at red ripe (BR + 10) stage cultivated in Korea. The relationships among the Hunter color coordinates, the content of each component, and antioxidant activities were measured by Pearson's correlation coefficients. As the a* value increased, the carotenoid and vitamin C contents increased, while the L* value, hue angle and tocopherol content decreased. As the b* value increased, the lycopene and total carotenoid contents decreased, and the flavonoid content in the hydrophilic extracts increased. The contents of vitamin C and total carotenoids including lycopene showed high positive correlations with the DPPH radical scavenging activities of both the lipophilic and hydrophilic extracts. Tocopherols and total phenolics in the hydrophilic and lipophilic extracts were not major positive contributors to the antioxidant activity. These findings suggest the quality standards for consumer requirements and inputs for on-going research for the development of better breeds.