In vitro characterization of [125I]HY-3-24, a selective ligand for the dopamine D3 receptor.

Introduction: Dopamine D3 receptor (D3R) ligands have been studied for the possible treatment of neurological and neuropsychiatric disorders. However, selective D3R radioligands for in vitro binding studies have been challenging to identify due to the high structural similarity between the D2R and D3R. In a prior study, we reported a new conformationally-flexible benzamide scaffold having a high affinity for D3R and excellent selectivity vs. D2R. In the current study, we characterized the in vitro binding properties of a new radioiodinated ligand, [125I]HY-3-24. Methods: In vitro binding studies were conducted in cell lines expressing D3 receptors, rat striatal homogenates, and rat and non-human primate (NHP) brain tissues to measure regional brain distribution of this radioligand. Results: HY-3-24 showed high potency at D3R (Ki = 0.67 ± 0.11 nM, IC50 = 1.5 ± 0.58 nM) compared to other D2-like dopamine receptor subtypes (D2R Ki = 86.7 ± 11.9 nM and D4R Ki > 1,000). The Kd (0.34 ± 0.22 nM) and Bmax (38.91 ± 2.39 fmol/mg) values of [125I]HY-3-24 were determined. In vitro binding studies in rat striatal homogenates using selective D2R and D3R antagonists confirmed the D3R selectivity of [125I]HY-3-24. Autoradiography results demonstrated that [125I]HY-3-24 specifically binds to D3Rs in the nucleus accumbens, islands of Calleja, and caudate putamen in rat and NHP brain sections. Conclusion: These results suggest that [125I]HY-3-24 appears to be a novel radioligand that exhibits high affinity binding at D3R, with low binding to other D2-like dopamine receptors. It is anticipated that [125I]HY-3-24 can be used as the specific D3R radioligand.

Dynamics of self-propelled particles in vibrated dense granular media.

We study a system consisting of a few self-propelled particles (SPPs) placed among a crowd of densely packed granular particles that are vertically vibrated in a two-dimensional circular confinement. Our experiments reveal two important findings. First, an SPP exhibits a fractal renewal process within the dense granular medium, which induces a superdiffusive behavior whose diffusion exponent increases with its aspect ratio. Second, the SPPs eventually reach the boundary and form a moving cluster, which transitions from the moving state to the static state as the number of SPPs is increased. These results suggest a simple and effective method of modulating the fluidity and directionality of granular systems via controlling the shape and the number of SPPs.

Magnetic particle image scanner based on asymmetric core-filled electromagnetic actuator.

Monitoring the distribution of magnetic nanoparticles (MNPs) in the vascular system is an important task for the advancement of precision therapeutics and drug delivery. Despite active targeting using active motilities, it is required to visualize the position and concentration of carriers that reach the target, to promote the development of this technology. In this work, a feasibility study is presented on a tomographic scanner that allows monitoring of the injected carriers quantitatively in a relatively short interval. The device is based on a small-animal-scale asymmetric magnetic platform integrated with magnetic particle imaging technology. An optimized isotropic field-free region (FFR) generation method using a magnetic manipulation system (MMS) is derived and numerically investigated. The in-vitro and in-vivo tracking performances are demonstrated with a high position accuracy of approximately 1 mm. A newly proposed tracking method was developed, specialized in vascular system, with quick scanning time (about 1s). In this paper, the primary function of the proposed system is to track magnetic particles using a magnetic manipulation system. Through this, proposed method enables the conventional magnetic actuation systems to upgrade the functionalities of both manipulation and localization of magnetic objects.

The flow behavior and sealing ability of calcium silicate root canal cement containing dimethyl sulfoxide: An in vitro study.

INTRODUCTION: To develop a calcium silicate (CaSi)-based cement containing dimethyl sulfoxide (DMSO) and cement deliver device for new root canal filling technique, and to assess the flow behavior, leakage, and root canal filling quality of CaSi containing DMSO. METHODS: CaSi containing DMSO (CSC-DMSO) and CaSi containing PEG (CSC-PEG) were prepared, and the flow characteristics of both cements were compared in gypsum and resin channels using a high-speed camera. Eight root canals were obturated by CSC-DMSO or CSC-PEG using a cement delivery device, and root canal filling quality was assessed in terms of filling length using periapical radiographs. The filling length was evaluated by 'apico-coronal extension,' measuring length in reference to apical constriction. Microleakage was measured for thirty human molars that were randomly filled with CSC-DMSO, CSC-PEG, or gutta-percha and AH plus. Preliminary obturation of CSC-DMSO with cement delivery device in human teeth was analyzed in terms of filling length and void, using periapical radiographs. Statistical analysis was performed with the Kruskal Wallis test for simulated root canal fillings and one-way ANOVA for leakage test. RESULTS: The flow speed of CSC-DMSO reduced in gypsum channels compared to resin channels, but CSC-PEG did not exhibit significant differences in the channels. The median absolute value of apico-coronal extension was significantly lower in CSC-DMSO compared to CSC-PEG (p < 0.05). Microleakage did not statistically differ between the groups (p > 0.05). In the preliminary obturation, the mean apico-coronal extension of CSC-DMSO was -0.297 ± 0.724 mm, while CSC-PEG was not feasible due to excess apical extrusions. CONCLUSIONS: CSC-DMSO could be considered as an alternative filling material for root canal obturation.

Precise and selective macroscopic assembly of a dual lock-and-key structured hydrogel.

Macroscopic assembly offers immense potential for constructing complex systems due to the high design flexibility of the building blocks. In such assembly systems, hydrogels are promising candidates for building blocks due to their versatile chemical compositions and ease of property tuning. However, two major challenges must be addressed to facilitate application in a broader context: the precision of assembly and the quantity of orthogonally matching pairs must both be increased. Although previous studies have attempted to address these challenges, none have successfully dealt with both simultaneously. Here, we propose topology-based design criteria for the selective assembly of hydrogel building blocks. By introducing the dual lock-and-key structures, we demonstrate highly precise assembly exclusively between the matching pairs. We establish principles for selecting multiple orthogonally matching pairs and achieve selective assembly involving simple one-to-one matching and complex assemblies with multiple orthogonal matching points. Moreover, by harnessing hydrogel tunability and the abundance of matching pairs, we synthesize complementary single-stranded structures for programmable assembly and successfully assemble them in the correct order. Finally, we demonstrate a hydrogel-based self-assembled logic gate system, including a YES gate, an OR gate, and an AND gate. The output is generated only when the corresponding inputs are provided according to each logic.

3D microprinting of inorganic porous materials by chemical linking-induced solidification of nanocrystals.

Three-dimensional (3D) microprinting is considered a next-generation manufacturing process for the production of microscale components; however, the narrow range of suitable materials, which include mainly polymers, is a critical issue that limits the application of this process to functional inorganic materials. Herein, we develop a generalised microscale 3D printing method for the production of purely inorganic nanocrystal-based porous materials. Our process is designed to solidify all-inorganic nanocrystals via immediate dispersibility control and surface linking-induced interconnection in the nonsolvent linker bath and thereby creates multibranched gel networks. The process works with various inorganic materials, including metals, semiconductors, magnets, oxides, and multi-materials, not requiring organic binders or stereolithographic equipment. Filaments with a diameter of sub-10 µm are printed into designed complex 3D microarchitectures, which exhibit full nanocrystal functionality and high specific surface areas as well as hierarchical porous structures. This approach provides the platform technology for designing functional inorganics-based porous materials.

Swelling kinetics of constrained hydrogel spheres.

A cross-linked polymer network immersed in a solvent will absorb molecules from its surroundings, leading to transient swelling. Under the constraint of a semi-permeable membrane, the system will swell less and generate a larger internal pressure in return, a system rarely analyzed to date. We use a nonlinear poroelastic theory to model the kinetics of swelling under mechanical constraint. We find the simulation results agree well with our experimental data using hydrogel beads made of a mixture of 3-sulfopropyl acrylate potassium salt and acrylamide, bathed in water. Understanding and predicting the response speed and the actuation stress developed during the swelling of constrained hydrogels can guide the design of polymer-based soft actuators with unusually high strength.

Health-related quality of life in long-term early-stage breast cancer survivors compared to general population in Korea.

PURPOSE: This study assessed health-related quality of life (HRQoL) of long-term breast cancer (BC) survivors diagnosed at early stages and compare with cancer-free, age-matched women. METHODS: The study population included BC survivors diagnosed with ductal carcinoma in situ (DCIS) or breast cancer stages I-II, who had undergone lumpectomy/mastectomy, with time since diagnosis ranging from 9 to 16 years. Survey was conducted at two tertiary hospitals in 2020. Data for cancer-free female controls was randomly drawn from a population-based survey and age-, education-matched with 1 case: 3 controls ratio. Self-reported HRQoL was assessed using EQ-5D with five dimentions. EQ-5D utility index score was calculated. Difference in EQ-5D score was evaluated using the Tobit regression model with adjustment for other covariates. RESULTS: Of 273 survivors. 88% and 12% underwent mastectomy and lumpectomy, respectively. The mean (standard deviation, SD) age at survey was 57.3 (8.5) years old. BC survivors reported significantly more problems performing daily activities (11% vs. 5%, p < 0.001), pain/discomfort (46% vs. 23%, p < 0.001), and anxious/depressed feelings (44% vs. 8%, p < 0.001) relative to the controls. Difference in EQ-5D score between BC survivors and the general population was higher in older age groups. The overall EQ-5D score of BC survivors was statistically lower than that of the control subjects (adjusted [Formula: see text]=0.117, p < 0.001). CONCLUSION: Long-term BC survivors who survived beyond ten years post-diagnosis experience more pain, anxiety, and distress, leading to an overall poorer HRQoL. IMPLICATIONS FOR CANCER SURVIVORS: This study suggest the importance of follow-up care, particularly focusing on pain, anxiety, and distress management to enhance the HRQoL of long-term BC survivors.

Snap-through inversion of elastic shells swelling via solvent diffusion.

Snap-through buckling instability of elastic shells can provide a variety of biological and artificial mechanical systems with an efficient strategy to generate rapid and powerful actuation. However, snapping spherical shells studied to date have typically been shallow and thus are dominantly prone to axisymmetric inversions. Here, we study diffusion-swelling stimulated snap-through inversion of bilayer shells of a wide range of depth to cover non-axisymmetric as well as axisymmetric modes. We first establish an analytical model of strain energy stored in axisymmetrically swelling shells, in order to predict the snap-through conditions based on energy minimization. Confirming that the strain energy can indicate the critical conditions for snap-through, we compare the conditions of axisymmetric and non-axisymmetric snap-through inversion using both experiments and numerical simulations. We find that differentially swelling bilayer shells snap-through with a time-lagged but increased energy release during inversion when buckled non-axisymmetrically rather than axisymmetrically.

Hierarchical Capillarity-Assisted Liquid Invasion in Multilayered Paper Channels for Nanoelectrokinetic Preconcentration.

A nanoelectrokinetic phenomenon called ion concentration polarization (ICP) has been recently applied to microfluidic paper-based devices for the high fold preconcentration of low-abundant analytes. The inherent microstructural characteristics of cellulose papers can sufficiently stabilize the chaotic electroconvection of ICP, which is a significant annoyance for typical engineered microfluidic channels. However, a high electrical voltage to induce ICP in a paper-fluidic channel can increase unavoidable electrophoretic forces over drag forces so that the preconcentrated plug is rapidly receded with severe dispersion. In order to enhance the hydraulic drag force that helps the preconcentration of analytes, here we introduce a multilayered paper structure into paper-fluidic channel. We theoretically and experimentally demonstrate that a hierarchical capillary structure in a multilayered paper-fluidic channel can effectively increase the hydraulic drag force. For the practical utility in the field of diagnostics, the mechanism is verified by a simple example of the immunoassay using biotin-streptavidin complexation.

Development of rapid and effective oil-spill response system integrated with oil collection, recovery and storage devices for small oil spills at initial stage: From lab-scale study to field-scale test.

In the present study, through the laboratory-to-field scale experiments and trials, we report the development and evaluation of an integrated oil-spill response system capable of oil collection, recovery (separation), and storage, for a timely and effective response to the initial stage of oil-spill accidents. With the laboratory-scale experiments, first, we evaluate that the water-surface waves tend to abate the oil recovery rate below 80% (it is above 95% for the optimized configuration without the waves), which is overcome by installing the hydrophilic (and oleophobic) porous structures at the inlet and/or near the water outlet of the separator. In the follow-up meso-scale towing tank tests with a scaled-up prototype, (i) we optimize the maneuverability of the assembled system depending on the speed and existence of waves, and (ii) evaluate the oil recovery performance (more than 80% recovery for the olive oil and Bunker A fuel oil). Although more thorough investigations and improvements are needed, a recovery rate of over 50% can be achieved for the newly enforced marine fuel oil (low sulfur fuel oil, LSFO) that was not targeted at the time of development. Finally, we perform a series of field tests with a full-scale system, to evaluate the rapid deployment and operational stability in the real marine environment. The overall floating balance and coordination of each functional part are sustained to be stable during the straight and rotary maneuvers up to the speed of 5 knots. Also, the collection of the floating debris (mimicking the spilled oil) is demonstrated in the field test. The present system is now being tested by the Korea Coast Guard and we believe that it will be very powerful to prevent the environmental damage due to the oil spills.

A Novel Brain PET Radiotracer for Imaging Alpha Synuclein Fibrils in Multiple System Atrophy.

Abnormal α-synuclein (α-syn) aggregation characterizes α-synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy (MSA). However, no suitable positron emission tomography (PET) radiotracer for imaging α-syn in PD and MSA exists currently. Our structure-activity relationship studies identified 4-methoxy-N-(4-(3-(pyridin-2-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)phenyl)benzamide (4i) as a PET radiotracer candidate for imaging α-syn. In vitro assays revealed high binding of 4i to recombinant α-syn fibrils (inhibition constant (Ki) = 6.1 nM) and low affinity for amyloid beta (Aß) fibrils in Alzheimer's disease (AD) homogenates. However, [3H]4i also exhibited high specific binding to AD, progressive supranuclear palsy, and corticobasal degeneration tissues as well as PD and MSA tissues, suggesting notable affinity to tau. Nevertheless, the specific binding to pathologic α-syn aggregates in MSA post-mortem brain tissues was significantly higher than in PD tissues. This finding demonstrated the potential use of [11C]4i as a PET tracer for imaging α-syn in MSA patients. Nonhuman primate PET studies confirmed good brain uptake and rapid washout for [11C]4i.

Two different jumping mechanisms of water striders are determined by body size.

Current theory for surface tension-dominant jumps on water, created for small- and medium-sized water strider species and used in bioinspired engineering, predicts that jumping individuals are able to match their downward leg movement speed to their size and morphology such that they maximize the takeoff speed and minimize the takeoff delay without breaking the water surface. Here, we use empirical observations and theoretical modeling to show that large species (heavier than ~80 mg) could theoretically perform the surface-dominated jumps according to the existing model, but they do not conform to its predictions, and switch to using surface-breaking jumps in order to achieve jumping performance sufficient for evading attacks from underwater predators. This illustrates how natural selection for avoiding predators may break the theoretical scaling relationship between prey size and its jumping performance within one physical mechanism, leading to an evolutionary shift to another mechanism that provides protection from attacking predators. Hence, the results are consistent with a general idea: Natural selection for the maintenance of adaptive function of a specific behavior performed within environmental physical constraints leads to size-specific shift to behaviors that use a new physical mechanism that secure the adaptive function.

Treatment outcomes of advanced/metastatic extramammary Paget's disease in Korean patients: KCSG-RC20-06.

BACKGROUND: Extramammary Paget's disease (EMPD) is rare. There are no standard treatments due to its rarity and few clinical trials. METHODS: The objective of this multicenter study was to investigate treatment outcomes of Korean patients with advanced/metastatic EMPD. Data were collected retrospectively from 14 institutions participating in Korean Cancer Study Group (KCSG) Rare Cancer Committee. RESULTS: A total of 37 patients were identified. Of these 37 patients, 6 received locoregional therapy as a first-line treatment. In 31 patients who received systemic chemotherapy as a first-line treatment, platinum-based chemotherapy (n = 22) achieved an objective response rate (ORR) of 45.5% and a median progression-free survival (PFS) of 7.89 months. Taxane-based chemotherapy (n = 8) achieved an objective response rate of 62.5% and median PFS of 9.73 months. In second-line chemotherapy, platinum-based chemotherapy (n = 4) had a disease control rate (DCR) of 75.0% and median PFS of 3.45 months. Taxane-based chemotherapy (n = 8) had a DCR of 75.0% and a median PFS of 8.67 months. Six patients received anti-human epidermal growth factor receptor 2 (HER2) antibody during first- and second-line chemotherapy. Overall, systemic chemotherapy combined with anti-HER2 antibody had an ORR of 100% and a median PFS of 13.31 months. The ORR and PFS with systemic chemotherapy combined with trastuzumab was better than platinum- and taxane-based chemotherapy only. CONCLUSIONS: Due to its rarity, advanced or metastatic EMPD still has no established standard treatment. Results of our study indicate that the combination of trastuzumab with taxane has longer survival than trastuzumab monotherapy or conventional platinum- or taxane-based chemotherapy.

Sequential Multimodal Morphing of Single-Input Pneu-Nets.

Soft actuators provide an attractive means for locomotion, gripping, and deployment of those machines and robots used in biomedicine, wearable electronics, automated manufacturing, etc. In this study, we focus on the shape-morphing ability of soft actuators made of pneumatic networks (pneu-nets), which are easy to fabricate with inexpensive elastomers and to drive with air pressure. As a conventional pneumatic network system morphs into a single designated state, achieving multimodal morphing has required multiple air inputs, channels, and chambers, making the system highly complex and hard to control. In this study, we develop a pneu-net system that can change its shape into multiple forms as a single input pressure increases. We achieve this single-input and multimorphing by combining pneu-net modules of different materials and geometry, while harnessing the strain-hardening characteristics of elastomers to prevent overinflation. Using theoretical models, we not only predict the shape evolution of pneu-nets with pressure change but also design pneu-nets to sequentially bend, stretch, and twist at distinct pressure points. We show that our design strategy enables a single device to carry out multiple functions, such as grabbing-turning a light bulb and holding-lifting a jar.

The Risk of Venous Thromboembolism in Korean Patients with Breast Cancer: A Single-Center Experience.

The relationship between cancer and venous thromboembolism (VTE) has long been described. The risk of VTE in Asian patients with breast cancer remains largely unknown. This study described the incidence and risk factors of VTE in Korean patients with breast cancer. Data were collected from a retrospective database of patients who underwent breast cancer surgery between 2011 and 2020 at a single institution. The Cox proportional-hazards model was used to identify factors associated with VTE occurrences. Among the 2246 patients with breast cancer, 48 (2.1%) developed VTE during a median follow-up period of 53 months. The average incidence of VTE was 459 per 100,000 person-years. Age ≥ 60 years, male sex, chronic kidney disease, reconstructive procedures, and stage II or higher were independent predictive factors for VTE. VTE was associated with poor disease-free survival (hazard ratio (HR), 6.140; 95% confidence interval (CI), 3.480-10.835), and overall survival (HR, 8.842; 95% CI 4.386-17.824). Most VTE events were manageable with anticoagulation; three (6.3%) patients died of VTE, despite intensive care. The incidence of VTE was significantly elevated in Korean patients with breast cancer. Since VTE has a negative effect on oncologic outcomes of breast cancer, clinicians should manage its risk throughout their lifetime.

Hygromachines: Humidity-Powered Wheels, Seesaws, and Vehicles.

Hygroscopic soft actuators offer an attractive means to convert environmental energy to mechanical motions as they use water vapor, a ubiquitous substance in the atmosphere. To overcome the limits of existing hygroactuators, such as simplistic actuation mode, slow response, and low efficiency, here we present three kinds of humidity-powered soft machines adopting directionally electrospun hygroresponsive nanofibrous sheets. The wheels, seesaws, and vehicles developed in this work utilize spatial humidity gradient naturally established near moist surfaces such as human skin, so that they operate spontaneously, realizing energy scavenging or harvesting. We also constructed a theoretical framework to mechanically analyze their dynamics, which allowed us to optimize their design to obtain the highest motion speed physically possible.

Intermetallic Nanoarchitectures for Efficient Electrocatalysis.

Intermetallic structures whose regular atomic arrays of constituent elements present unique catalytic properties have attracted considerable attention as efficient electrocatalysts for energy conversion reactions. Further performance enhancement in intermetallic catalysts hinges on constructing catalytic surfaces possessing high activity, durability, and selectivity. In this Perspective, we introduce recent endeavors to boost the performance of intermetallic catalysts by generating nanoarchitectures, which have well-defined size, shape, and dimension. We discuss the beneficial effects of nanoarchitectures compared with simple nanoparticles in catalysis. We highlight that the nanoarchitectures have high intrinsic activity owing to their inherent structural factors, including controlled facets, surface defects, strained surfaces, nanoscale confinement effects, and a high density of active sites. We next present notable examples of intermetallic nanoarchitectures, namely, facet-controlled intermetallic nanocrystals and multidimensional nanomaterials. Finally, we suggest the future research directions of intermetallic nanoarchitectures.

A Multicenter, Prospective, Observational Study to Evaluate Ethanol-Induced Symptoms in Patients Receiving Docetaxel Chemotherapy.

PURPOSE: Several previous studies and case reports have reported ethanol-induced symptoms in patients receiving anticancer drugs containing ethanol. Most docetaxel formulations contain ethanol as a solvent. However, there are insufficient data on ethanol-induced symptoms when docetaxel-containing ethanol is administered. The primary purpose of this study was to investigate the frequency and pattern of ethanol-induced symptoms during and after docetaxel administration. The secondary purpose was to explore the risk factors for ethanol-induced symptoms. MATERIALS AND METHODS: This was a prospective, multicenter, observational study. The participants filled out ethanol-induced symptom questionnaire on the day of chemotherapy and the following day. RESULTS: Data from 451 patients were analyzed. The overall occurrence rate of ethanol-induced symptoms was 44.3% (200/451 patients). The occurrence rate of facial flushing was highest at 19.7% (89/451 patients), followed by nausea in 18.2% (82/451 patients), and dizziness in 17.5% (79/451 patients). Although infrequent, unsteady walking and impaired balance occurred in 4.2% and 3.3% of patients, respectively. Female sex, presence of underlying disease, younger age, docetaxel dose, and docetaxel-containing ethanol amount were significantly associated with the occurrence of ethanol-induced symptoms. CONCLUSION: The occurrence of ethanol-induced symptoms was not low in patients receiving docetaxel-containing ethanol. Physicians need to pay more attention to the occurrence of ethanol-induced symptoms and prescribe ethanol-free or low-ethanol-containing formulations to high-risk patients.