Thyroid Cancer Incidence Among Korean Individuals: A Comparison of South Korea and the United States.

OBJECTIVE: To compare thyroid cancer incidence rates and trends between Korean, non-Korean Asian, and non-Hispanic White populations in the United States, and between the US Korean population and the South Korean population. METHOD: Population-based analysis of cancer incidence data. Cases of thyroid cancer diagnosed during 1999-2014 from the Korean Central Cancer Registry (KCCR) and the Surveillance, Epidemiology, and End Results (SEER) 9 detailed Asian/Pacific Islander subgroup incidence and population dataset were included. Incidence rates were obtained from the datasets, and annual percent change (APC) of the incidence rates was calculated using Joinpoint regression analysis. RESULTS: Thyroid cancer incidence rate for 1999-2014 was significantly higher for South Korea (48.05 [95% CI 47.89-48.22] per 100,000 person-years) than for the US Korean population (11.12 [95% CI 10.49-11.78] per 100,000 person-years), which was slightly higher than the Non-Korean Asian population (10.23 [95% CI 10.02-10.43] per 100,000 person-years), and slightly lower than the Non-Hispanic White population (12.78 [95% CI 12.69-12.87] per 100,000 person-years). Incidence rates in South Korea increased dramatically (average APC 17.9, 95% CI 16.0-19.9), significantly higher than the US Korean population (average APC 5.0, 95% CI 3.1-6.8), which was similar to the non-Korean Asian (average APC 2.5, 95% CI 0.9-4.2) and the non-Hispanic White (average APC 5.1, 95% CI 4.7-5.6) populations. CONCLUSIONS: South Korea's high thyroid cancer incidence rates cannot be attributed to genetic factors, but are likely due to health care system factors. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

A mitochondrial NAD/NADH kinase governs fungal virulence through an oxidative stress response and arginine biosynthesis in Fusarium graminearum.

NADP/NADPH plays an indispensable role in cellular metabolism, serving as a pivotal cofactor in numerous enzymatic processes involved in anabolic pathways, antioxidant defense, and the biosynthesis of essential cellular components. NAD/NADH kinases (NADKs) phosphorylate NAD/NADH, constituting the sole de novo synthetic pathway for NADP/NADPH generation. Despite the pivotal role of NADP/NADPH in cellular functions, the physiological role of NADK remains largely unexplored in filamentous fungi. In this study, we identified three putative NADKs in Fusarium graminearum-FgNadk1, FgNadk2, and FgNadk3-responsible for NAD/NADH phosphorylation. NADK-mediated formation of intracellular NADPH proved crucial for vegetative growth, sexual reproduction, and virulence. Specifically, FgNadk2, the mitochondrial NADK, played a role in oxidative stress resistance and the maintenance of mitochondrial reactive oxygen species levels. Moreover, the deletion of FgNADK2 resulted in arginine auxotrophy, contributing to the reduced fungal virulence. These findings underscore the necessity of mitochondrial NADK in fungal virulence in F. graminearum, revealing its involvement in mitochondrial redox homeostasis and the arginine biosynthetic pathway. This study provides critical insights into the interconnectedness of metabolic pathways essential for fungal growth, stress response, and pathogenicity.

Defect Passivation of 2D Semiconductors by Fixating Chemisorbed Oxygen Molecules via h-BN Encapsulations.

Hexagonal boron nitride (h-BN) is a key ingredient for various 2D van der Waals heterostructure devices, but the exact role of h-BN encapsulation in relation to the internal defects of 2D semiconductors remains unclear. Here, it is reported that h-BN encapsulation greatly removes the defect-related gap states by stabilizing the chemisorbed oxygen molecules onto the defects of monolayer WS2 crystals. Electron energy loss spectroscopy (EELS) combined with theoretical analysis clearly confirms that the oxygen molecules are chemisorbed onto the defects of WS2 crystals and are fixated by h-BN encapsulation, with excluding a possibility of oxygen molecules trapped in bubbles or wrinkles formed at the interface between WS2 and h-BN. Optical spectroscopic studies show that h-BN encapsulation prevents the desorption of oxygen molecules over various excitation and ambient conditions, resulting in a greatly lowered and stabilized free electron density in monolayer WS2 crystals. This suppresses the exciton annihilation processes by two orders of magnitude compared to that of bare WS2 . Furthermore, the valley polarization becomes robust against the various excitation and ambient conditions in the h-BN encapsulated WS2 crystals.

Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease.

Human embryonic stem cell (hESC)-derived midbrain dopaminergic (mDA) cell transplantation is a promising therapeutic strategy for Parkinson's disease (PD). Here, we present the derivation of high-purity mDA progenitors from clinical-grade hESCs on a large scale under rigorous good manufacturing practice (GMP) conditions. We also assessed the toxicity, biodistribution, and tumorigenicity of these cells in immunodeficient rats in good laboratory practice (GLP)-compliant facilities. Various doses of mDA progenitors were transplanted into hemi-parkinsonian rats, and a significant dose-dependent behavioral improvement was observed with a minimal effective dose range of 5,000-10,000 mDA progenitor cells. These results provided insights into determining a low cell dosage (3.15 million cells) for human clinical trials. Based on these results, approval for a phase 1/2a clinical trial for PD cell therapy was obtained from the Ministry of Food and Drug Safety in Korea, and a clinical trial for treating patients with PD has commenced.

Does body mass index affect outcomes following arthroscopic superior capsular reconstruction using fascia lata autograft for massive irreparable rotator cuff tear?

PURPOSE: This study aimed to evaluate the effect of increased body mass index (BMI) on patient-reported outcomes (PROs) and clinically significant outcomes (CSOs) obtained > two years postoperatively following arthroscopic superior capsular reconstruction (ASCR). METHODS: A retrospective study was conducted on patients who underwent ASCR with a minimum two year follow-up. All patients were divided into normal (BMI < 25.0), overweight (BMI 25-30.0), and obese (BMI ≥ 30) according to preoperative BMI. Patients were assessed using the PROs preoperatively and at six months, one year, and two years postoperatively, including the visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES), and Constant-Murley scores. The time required to achieve each CSO was analyzed and compared. Multivariate analyses evaluated the predictor variables and time required to achieve CSOs. RESULTS: This study included 63 patients with a mean age of 64.8 ± 8.6 years, including 31 normal BMI, 25 overweight, and seven obese patients. Significant improvements in VAS and ASES scores after ASCR were observed in all three groups. Normal and overweight patients had significant improvements in the Constant score; however, no difference was observed in obese patients. No significant difference was observed in the probability distributions of CSOs between the BMI groups. Similarly, no significant differences were observed in the probability distributions of the CSOs, ASES, and Constant scores at each time point, among the BMI groups. CONCLUSION: Patients in the normal and overweight groups had significant improvements in the VAS, ASES, and Constant scores after ASCR. Patients in the obese group had a significant improvement in VAS score; however, there is no difference for the ASES and Constant scores in the obese group. However, no differences were observed in all PROMs and the likelihood of achieving CSOs among the different BMI groups.

Runx3 Restoration Regresses K-Ras-Activated Mouse Lung Cancers and Inhibits Recurrence.

Oncogenic K-RAS mutations occur in approximately 25% of human lung cancers and are most frequently found in codon 12 (G12C, G12V, and G12D). Mutated K-RAS inhibitors have shown beneficial results in many patients; however, the inhibitors specifically target K-RASG12C and acquired resistance is a common occurrence. Therefore, new treatments targeting all kinds of oncogenic K-RAS mutations with a durable response are needed. RUNX3 acts as a pioneer factor of the restriction (R)-point, which is critical for the life and death of cells. RUNX3 is inactivated in most K-RAS-activated mouse and human lung cancers. Deletion of mouse lung Runx3 induces adenomas (ADs) and facilitates the development of K-Ras-activated adenocarcinomas (ADCs). In this study, conditional restoration of Runx3 in an established K-Ras-activated mouse lung cancer model regressed both ADs and ADCs and suppressed cancer recurrence, markedly increasing mouse survival. Runx3 restoration suppressed K-Ras-activated lung cancer mainly through Arf-p53 pathway-mediated apoptosis and partly through p53-independent inhibition of proliferation. This study provides in vivo evidence supporting RUNX3 as a therapeutic tool for the treatment of K-RAS-activated lung cancers with a durable response.

Real-time driver monitoring system with facial landmark-based eye closure detection and head pose recognition.

This paper introduces a real-time Driver Monitoring System (DMS) designed to monitor driver behavior while driving, employing facial landmark estimation-based behavior recognition. The system utilizes an infrared (IR) camera to capture and analyze video data. Through facial landmark estimation, crucial information about the driver's head posture and eye area is extracted from the detected facial region, obtained via face detection. The proposed method consists of two distinct modules, each focused on recognizing specific behaviors. The first module employs head pose analysis to detect instances of inattention. By monitoring the driver's head movements along the horizontal and vertical axes, this module assesses the driver's attention level. The second module implements an eye-closure recognition filter to identify instances of drowsiness. Depending on the continuity of eye closures, the system categorizes them as either occasional drowsiness or sustained drowsiness. The advantages of the proposed method lie in its efficiency and real-time capabilities, as it solely relies on IR camera video for computation and analysis. To assess its performance, the system underwent evaluation using IR-Datasets, demonstrating its effectiveness in monitoring and recognizing driver behavior accurately. The presented real-time Driver Monitoring System with facial landmark-based behavior recognition offers a practical and robust approach to enhance driver safety and alertness during their journeys.

Roles of Heterojunction and Cu Vacancies in the Au@Cu2-xSe for the Enhancement of Electrochemical Nitrogen Reduction Performance.

The utilization of hydrogen (H2) as a fuel source is hindered by the limited infrastructure and storage requirements. In contrast, ammonia (NH3) offers a promising solution as a hydrogen carrier due to its high energy density, liquid storage capacity, low cost, and sustainable manufacturing. NH3 has garnered significant attention as a key component in the development of next-generation refueling stations, aligning with the goal of a carbon-free economy. The electrochemical nitrogen reduction reaction (ENRR) enables the production of NH3 from nitrogen (N2) under ambient conditions. However, the low efficiency of the ENRR is limited by challenges such as the electron-stealing hydrogen evolution reaction (HER) and the breaking of the stable N2 triple bond. To address these limitations and enhance ENRR performance, we prepared Au@Cu2-xSe electrocatalysts with a core@shell structure using a seed-mediated growth method and a facile hot-injection method. The catalytic activity was evaluated using both an aqueous electrolyte of KOH solution and a nonaqueous electrolyte consisting of tetrahydrofuran (THF) solvent with lithium perchlorate and ethanol as proton donors. ENRR in both aqueous and nonaqueous electrolytes was facilitated by the synergistic interaction between Au and Cu2-xSe (copper selenide), forming an Ohmic junction between the metal and p-type semiconductor that effectively suppressed the HER. Furthermore, in nonaqueous conditions, the Cu vacancies in the Cu2-xSe layer of Au@Cu2-xSe promoted the formation of lithium nitride (Li3N), leading to improved NH3 production. The synergistic effect of Ohmic junctions and Cu vacancies in Au@Cu2-xSe led to significantly higher ammonia yield and faradaic efficiency (FE) in nonaqueous systems compared to those in aqueous conditions. The maximum NH3 yields were approximately 1.10 and 3.64 µg h-1 cm-2, with the corresponding FE of 2.24 and 67.52% for aqueous and nonaqueous electrolytes, respectively. This study demonstrates an attractive strategy for designing catalysts with increased ENRR activity by effectively engineering vacancies and heterojunctions in Cu-based electrocatalysts in both aqueous and nonaqueous media.

GLUT3 promotes macrophage signaling and function via RAS-mediated endocytosis in atopic dermatitis and wound healing.

The facilitative GLUT1 and GLUT3 hexose transporters are expressed abundantly in macrophages, but whether they have distinct functions remains unclear. We confirmed that GLUT1 expression increased after M1 polarization stimuli and found that GLUT3 expression increased after M2 stimulation in macrophages. Conditional deletion of Glut3 (LysM-Cre Glut3fl/fl) impaired M2 polarization of bone marrow-derived macrophages. Alternatively activated macrophages from the skin of patients with atopic dermatitis showed increased GLUT3 expression, and a calcipotriol-induced model of atopic dermatitis was rescued in LysM-Cre Glut3fl/fl mice. M2-like macrophages expressed GLUT3 in human wound tissues as assessed by transcriptomics and costaining, and GLUT3 expression was significantly decreased in nonhealing, compared with healing, diabetic foot ulcers. In an excisional wound healing model, LysM-Cre Glut3fl/fl mice showed significantly impaired M2 macrophage polarization and delayed wound healing. GLUT3 promoted IL-4/STAT6 signaling, independently of its glucose transport activity. Unlike plasma membrane-localized GLUT1, GLUT3 was localized primarily to endosomes and was required for the efficient endocytosis of IL-4Rα subunits. GLUT3 interacted directly with GTP-bound RAS in vitro and in vivo through its intracytoplasmic loop domain, and this interaction was required for efficient STAT6 activation and M2 polarization. PAK activation and macropinocytosis were also impaired without GLUT3, suggesting broader roles for GLUT3 in the regulation of endocytosis. Thus, GLUT3 is required for efficient alternative macrophage polarization and function, through a glucose transport-independent, RAS-mediated role in the regulation of endocytosis and IL-4/STAT6 activation.

Micellized protein transduction domain-bone morphogenetic protein-2 accelerates bone healing in a rat tibial distraction osteogenesis model.

The clinical application of growth factors such as recombinant human bone morphogenetic protein-2 (rh-BMP-2), for functional bone regeneration remains challenging due to limited in vivo efficacy and adverse effects of previous modalities. To overcome the instability and short half-life of rh-BMP-2 in vivo, we developed a novel osteogenic supplement by fusing a protein transduction domain (PTD) with BMP-2, effectively creating a prodrug of BMP-2. In this study, we first created an improved PTD-BMP-2 formulation using lipid nanoparticle (LNP) micellization, resulting in downsizing from micrometer to nanometer scale and achieving a more even distribution. The micellized PTD-BMP-2 (mPTD-BMP-2) demonstrated improved distribution and aggregation profiles. As a prodrug of BMP-2, mPTD-BMP-2 successfully activated Smad1/5/8 and induced mineralization with osteogenic gene induction in vitro. In vivo pharmacokinetic analysis revealed that mPTD-BMP-2 had a much more stable pharmacokinetic profile than rh-BMP-2, with a 7.5-fold longer half-life. The in vivo BMP-responsive element (BRE) reporter system was also successfully activated by mPTD-BMP-2. In the in vivo rat tibia distraction osteogenesis (DO) model, micro-computed tomography (micro-CT) scan findings indicated that mPTD-BMP-2 significantly increased bone volume, bone surface, axis moment of inertia (MOI), and polar MOI. Furthermore, it increased the expression of osteogenesis-related genes, and induced bone maturation histologically. Based on these findings, mPTD-BMP-2 could be a promising candidate for the next-generation osteogenesis drug to promote new bone formation in DO surgery. STATEMENT OF SIGNIFICANCE: This study introduces micellized bone morphogenetic protein-2 (mPTD-BMP-2), a next-generation osteogenic supplement that combines protein transduction domain (PTD) and nano-sized micelle formulation technique to improve transduction efficiency and stability. The use of PTD represents a novel approach, and our results demonstrate the superiority of mPTD-BMP-2 over rh-BMP-2 in terms of in vivo pharmacokinetic profile and osteogenic potential, particularly in a rat tibial model of distraction osteogenesis. These findings have significant scientific impact and potential clinical applications in the treatment of bone defects that require distraction osteogenesis. By advancing the field of osteogenic supplements, our study has the potential to contribute to the development of more effective treatments for musculoskeletal disorders.

Effective Healing of Staphylococcus aureus-Infected Wounds in Pig Cathelicidin Protegrin-1-Overexpressing Transgenic Mice.

Antimicrobial peptides (AMPs) are promising alternatives to existing treatments for multidrug-resistant bacteria-infected wounds. Therefore, the effect of protegrin-1 (PG1), a potent porcine AMP with broad-spectrum activity, on wound healing was evaluated. PG1-overexpressing transgenic mice were used as an in vivo model to evaluate its healing efficiency against Staphylococcus aureus-infected (106 colony forming units) wounds. We analyzed the wounds under four specific conditions in the presence or absence of antibiotic treatment. We observed the resolution of bacterial infection and formation of neo-epithelium in S. aureus-infected wounds of the mice, even without antibiotic treatment, whereas all wild-type mice with bacterial infection died within 8 to 10 days due to uncontrolled bacterial proliferation. Interestingly, the wound area on day 7 was smaller (p < 0.01) in PG1 transgenic mice than that in the other groups, including antibiotic-treated mice, suggesting that PG1 exerts biological effects other than bactericidal effect. Additionally, we observed that the treatment of primary epidermal keratinocytes with recombinant PG1 enhanced cell migration in in vitro scratch and cell migration assays. This study contributes to the understanding of broad-spectrum endogenous cathelicidins with potent antimicrobial activities, such as PG1, on wound healing. Furthermore, our findings suggest that PG1 is a potent therapeutic candidate for wound healing.

Correlation between 10-meter walking speed and exercise capacity in patients with surgical resection for lung cancer.

Surgical resection for lung cancer adversely impacts exercise capacity. The 6-minute walk test (6MinWT) and cardiopulmonary exercise test (CPET) are commonly used to assess exercise capacity. However, these tests are difficult to use clinically because they must be performed by a trained technician using specialized equipment according to a prescribed method. This study aims to analyze correlations between walking speed in a 10-meter walk test and exercise capacity measured by the 6MinWT or CPET in patients with lung resection for lung cancer. A total of 50 patients who were diagnosed with lung cancer and underwent lung resection were included in the analysis. The 6MinWT and CPET were performed to measure exercise capacity, and the 10-meter walk test was used to evaluate the short-duration walking speed. The population was divided into 2 groups -low and high exercise capacity - based on threshold values (6MinWT, 500 m; CPET, 20 mL·kg-1·min-1); we analyzed the correlation according to the level of exercise capacity. In the correlation analysis between the 10-meter walking speed and exercise capacity, the 10-meter walking speed showed a strong correlation (R = 0.70, P < .001) with the 6MinWT and a moderate correlation (R = 0.47, P < .001) with the CPET, respectively. The low exercise capacity group showed a significant correlation (6MinWT, ρ = 0.70; CPET, ρ = 0.54) between the 10-meter walking speed and exercise capacity, while the high exercise capacity group did not. In patients who underwent lung resection for lung cancer, the 10-meter walking speed was significantly correlated with exercise capacity, especially in subjects with low exercise capacity that require pulmonary rehabilitation.

Synergistic effect of Polydopamine incorporated Copper electrocatalyst by dopamine oxidation for efficient hydrogen production.

Tuning the metal-support interaction in electrocatalysts has been proposed as a viable method for manipulating the electronic structure and catalytic activity. In this work, inspired by natural hydrogenase enzyme, electrocatalysts with a hybrid metal-matrix complex using polydopamine (PDA) as a supporting matrix were synthesized for efficient green hydrogen production. Among the various Metal-PDA electrocatalysts, Cu-PDA shows outstanding catalytic activity (low overpotential (ƞ) of 104 mV at 10 mA cm-2 and small Tafel slope of 60.67 mV dec-1) with high stability at neutral pH. Also, the electrochemical impedance spectroscopy analysis verified the fast charge transfer properties of Cu-PDA (2.8 Ω cm2) than PDA (26 Ω cm2), indicating a faster proton-coupled electron transfer process in Cu-PDA electrocatalyst. Therefore, emerging nature inspired organic ligand-transition metal ion complexes can be extensively encouraged as a prospective HER electrocatalyst under neutral conditions.

Scaffolds for drug delivery and tissue engineering: The role of genetics.

Scaffolds are implants commonly used to deliver cells, drugs, and genes into the body. Their regular porous structure ensures the proper support for cell attachment, proliferation, differentiated function, and migration. Techniques to fabricate a scaffold include leaching, freeze-drying, supercritical fluid technology, thermally induced phase separation, rapid prototyping, powder compaction, sol-gel, and melt molding. Gene delivery from the scaffold represents a versatile approach to influence the environment for managing cell function. Scaffolds can be used for various tissue engineering purposes, e.g. bone formation, periodontal regeneration, cartilage development, artificial corneas, heart valves, tendon repair, or ligament replacement. Moreover, they are also instrumental in cancer therapy, inflammation, diabetes, heart disease, and wound dressings. Scaffolds provide a platform to extend the delivery of drugs and genetic materials at a controlled timeframe, besides potentially being used to prevent infection upon surgery and other chronic diseases, provided that they can be formulated with specific medicines. This review discusses the need to design advanced functional scaffolds with the potential for modified drug delivery and tissue engineering in a synergistic approach. Special attention is given to works published in 2023 to generate the bibliometric map.

Orbitally Controlled Quantum Hall States in Decoupled Two-Bilayer Graphene Sheets.

The authors report on integer and fractional quantum Hall states in a stack of two twisted Bernal bilayer graphene sheets. By exploiting the momentum mismatch in reciprocal space, the single-particle tunneling between both bilayers is suppressed. Since the bilayers are spatially separated by only 0.34 nm, the stack benefits from strong interlayer Coulombic interactions. These interactions can cause the formation of a Bose-Einstein condensate. Indeed, such a condensate is observed for half-filling in each bilayer sheet. However, only when the partially filled levels have orbital index 1. It is absent for partially filled levels with orbital index 0. This discrepancy is tentatively attributed to the role of skyrmion/anti-skyrmion pair excitations and the dependence of the energy of these excitations on the orbital index. The application of asymmetric top and bottom gate voltages enables to influence the orbital nature of the electronic states of the graphene bilayers at the chemical potential and to navigate in orbital mixed space. The latter hosts an even denominator fractional quantum Hall state at total filling of -3/2. These observations suggest a unique edge reconstruction involving both electrons and chiral p-wave composite fermions.

Fresnel-type solid immersion lens for efficient light collection from quantum defects in diamond.

Quantum defects in diamonds have been studied as a promising resource for quantum science. The subtractive fabrication process for improving photon collection efficiency often require excessive milling time that can adversely affect the fabrication accuracy. We designed and fabricated a Fresnel-type solid immersion lens using the focused ion beam. For a 5.8 µm-deep Nitrogen-vacancy (NV-) center, the milling time was highly reduced (1/3 compared to a hemispherical structure), while retaining high photon collection efficiency (> 2.24 compared to a flat surface). In numerical simulation, this benefit of the proposed structure is expected for a wide range of milling depths.

The Uncomfortable Truth: Open Thoracotomy versus Minimally Invasive Surgery in Lung Cancer: A Systematic Review and Meta-Analysis.

For decades, lung surgery in thoracic cancer has evolved in two ways: saving more parenchyma and being minimally invasive. Saving parenchyma is a fundamental principle of surgery. However, minimally invasive surgery (MIS) is a matter of approach, so it has to do with advances in surgical techniques and tools. For example, MIS has become possible with the introduction of VATS (video-assisted thoracic surgery), and the development of tools has extended the indication of MIS. Especially, RATS (robot-assisted thoracic surgery) improved the quality of life for patients and the ergonomics of doctors. However, the dichotomous idea that the MIS is new and right but the open thoracotomy is old and useless may be inappropriate. In fact, MIS is exactly the same as a classic thoracotomy in that it removes the mass/parenchyma containing cancer and mediastinal lymph nodes. Therefore, in this study, we compare randomized-controlled trials about open thoracotomy and MIS to find out which surgical method is more helpful.