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.

Emulating trial to evaluate the effectiveness of routine supportive care on mortality among cancer patients experiencing distress at the time of diagnosis.

INTRODUCTION: Few studies have evaluated the effectiveness of interventions for distress during cancer diagnosis on clinical outcomes in a real-world setting. We aimed to evaluate whether routine information and psychosocial support to patients experiencing distress at the time of diagnosis could decrease the risk of mortality within 1 and 3 years after diagnosis. MATERIAL AND METHODS: We conducted a retrospective cohort study of 4880 newly diagnosed cancer patients who reported distress scores of ≥4 using the tablet or kiosk-based screening between July 2014 and December 2017 at a university-affiliated cancer center in Seoul, South Korea. We performed an emulated target trial with two groups: those that received information and psychosocial support and those that did not. Cox proportional hazards models were used to identify the associations between information and psychosocial support and all-cause mortality. RESULTS: Of all the patients, 16.6 % had routine information and psychosocial support. The hazard ratio (HR) for one-year mortality comparing participants with information and psychosocial support to those without it were 0.73 (95 % confidence interval (CI) = 0.54, 0.99). Age < 50 and 50 - <60 group had a stronger effect of information and psychosocial support on reducing mortality within one-year than these in age ≥ 60 (p for interaction = 0.03). In terms of three-year mortality, the HR comparing participants with information and psychosocial support to those without it was 0.93 (95 % CI = 0.76, 1.14). CONCLUSION: This large-scale real-world study suggests that timely psychosocial care benefits newly diagnosed cancer patients who had distress during pre-treatment period.

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.

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.

The Prognostic Impact of Coronary Artery Disease and Aortic Aneurysm: Insights From CT Protocol for Simultaneous Evaluation of Coronary Artery and Aorta.

BACKGROUND: There is a strong correlation between risk factors for coronary artery disease (CAD) and aortic aneurysm (AA). We aimed to investigate the prevalence and prognostic impact of CAD and AA in patients who underwent coronary aorta computed tomography (CACT) protocol, which allowed simultaneous evaluation of coronary artery and aorta. METHODS: Between 2010 and 2021, 1,553 patients who underwent CACT were enrolled from a tertiary center. The presence and location of AA and the presence of CAD were identified from CT. The primary outcome was a composite of cardiovascular death, acute coronary syndrome requiring urgent revascularization, and stroke at 3 years after the index CT scan. RESULTS: Out of 1,553 enrolled patients, 179 (11.5%) had AA. The prevalence of CAD was significantly higher in patients with AA than those without (47.5% vs. 18.3%, P < 0.001). Among patients with AA, the prevalence of comorbid CAD was higher in those with abdominal AA than thoracic AA (57.3% vs. 37.8%, P = 0.014), respectively. In multivariable analysis, the presence of CAD was an independent predictor of primary outcome at 3 years (hazard ratio [HR], 2.58; 95% CI, 1.47-4.51; P = 0.001), while AA was not (HR, 1.00; 95% CI, 0.48-2.07; P = 0.993). CONCLUSION: In this cohort of patients undergoing simultaneous evaluation of coronary artery and aorta using CACT protocol, patients with AA had an increased risk of comorbid CAD compared to those without AA. CAD was independently associated with adverse clinical outcomes at 3 years.

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.

Cellular Efficacy of Fattigated Nanoparticles and Real-Time ROS Occurrence Using Microfluidic Hepatocarcinoma Chip System: Effect of Anticancer Drug Solubility and Shear Stress.

The objective of this study was to evaluate the effectiveness of organ-on-chip system investigating simultaneous cellular efficacy and real-time reactive oxygen species (ROS) occurrence of anticancer drug-loaded nanoparticles (NPs) using hepatocarcinoma cells (HepG2) chip system under static and hepatomimicking shear stress conditions (5 dyne/cm2). Then, the role of hepatomimetic shear stress exposed to HepG2 and drug solubility were compared. The highly soluble doxorubicin (DOX) and poorly soluble paclitaxel (PTX) were chosen. Fattigated NPs (AONs) were formed via self-assembly of amphiphilic albumin (HSA)-oleic acid conjugate (AOC). Then, drug-loaded AONs (DOX-AON or PTX-AON) were exposed to a serum-free HepG2 medium at 37 °C and 5% carbon dioxide for 24 h using a real-time ROS sensor chip-based microfluidic system. The cellular efficacy and simultaneous ROS occurrence of free drugs and drug-loaded AONs were compared. The cellular efficacy of drug-loaded AONs varied in a dose-dependent manner and were consistently correlated with real-time of ROS occurrence. Drug-loaded AONs increased the intracellular fluorescence intensity and decreased the cellular efficacy compared to free drugs under dynamic conditions. The half-maximal inhibitory concentration (IC50) values of free DOX (13.4 µg/mL) and PTX (54.44 µg/mL) under static conditions decreased to 11.79 and 38.43 µg/mL, respectively, under dynamic conditions. Furthermore, DOX- and PTX-AONs showed highly decreased IC50 values of 5.613 and 21.86 µg/mL, respectively, as compared to free drugs under dynamic conditions. It was evident that cellular efficacy and real-time ROS occurrence were well-correlated and highly dependent on the drug-loaded nanostructure, drug solubility and physiological shear stress.

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.

Structure-based drug discovery of a corticotropin-releasing hormone receptor 1 antagonist using an X-ray free-electron laser.

Thus far, attempts to develop drugs that target corticotropin-releasing hormone receptor 1 (CRF1R), a drug target in stress-related therapy, have been unsuccessful. Studies have focused on using high-resolution G protein-coupled receptor (GPCR) structures to develop drugs. X-ray free-electron lasers (XFELs), which prevent radiation damage and provide access to high-resolution compositions, have helped accelerate GPCR structural studies. We elucidated the crystal structure of CRF1R complexed with a BMK-I-152 antagonist at 2.75 Å using fixed-target serial femtosecond crystallography. The results revealed that two unique hydrogen bonds are present in the hydrogen bond network, the stalk region forms an alpha helix and the hydrophobic network contains an antagonist binding site. We then developed two antagonists-BMK-C203 and BMK-C205-and determined the CRF1R/BMK-C203 and CRF1R/BMK-C205 complex structures at 2.6 and 2.2 Å, respectively. BMK-C205 exerted significant antidepressant effects in mice and, thus, may be utilized to effectively identify structure-based drugs against CRF1R.

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.

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.

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.

Clinical outcomes of a CT protocol for simultaneous examination of the aorta and coronary artery in patients with aortic aneurysm.

Objectives: In patients with aortic aneurysm (AA), coronary artery disease (CAD) increases the risk of perioperative complications and even asymptomatic CAD is associated with adverse clinical outcomes. We aimed to compare coronary-aorta CT (CACT) with thoracoabdominal CT angiography (Aorta CT) for CAD management and clinical outcomes in these patients. Methods: We enrolled 479 patients undergoing CACT and 693 patients undergoing Aorta CT as an initial CT scan for AA. The primary outcome was a composite of all-cause death or myocardial infarction (MI) at 3 years after CT. The secondary outcomes were subsequent CAD management and invasive coronary angiography (CAG). Results: After index CT scan, the CACT group had a significantly higher rate of coronary revascularization compared with the Aorta CT group (10.7% vs. 3.8%, p < 0.001) but a lower probability of diagnostic CAG among total invasive CAG (32% vs. 55%, p < 0.001). At 3 months after the CT scan, the prescription rates of statins (65.8% vs. 44.6%, p < 0.001) and antiplatelet agents (57.6% vs. 43.9%, p < 0.001) were higher in the CACT group. During follow-up, the CACT group had a significantly lower incidence of the composite outcome of all-cause death or MI (adjusted HR 1.72, 95% CI 1.07-2.78, p = 0.027) than the Aorta CT group. Conclusion: Among patients with AA, CACT was associated with a higher rate of subsequent CAD management and a lower risk of all-cause death or MI compared to Aorta CT. When evaluating with AA using CT, simultaneous coronary and aortic evaluation using CACT would be recommended over Aorta CT.

Efficacy of a novel remotely-generated ultrasonic root canal irrigation system for removing biofilm-mimicking hydrogel from a simulated isthmus model.

AIM: To evaluate the efficacy of a novel ultrasonic irrigation device, remotely-generated irrigation with a non-invasive sound field enhancement (RINSE) system, in removing biofilm-mimicking hydrogel from a simulated isthmus model and compare it with sonically- and ultrasonically-activated irrigation systems. METHODOLOGY: A polycarbonate root canal model containing two standardized root canals (apical diameter of 0.20 mm, 4% taper, 18 mm long with a coronal reservoir) connected by three isthmuses (0.40 mm deep, 2 mm high, 4 mm long) was used as the test model. The isthmuses were filled with a hydroxyapatite powder-containing hydrogel. The canals were filled with irrigant, and the models were randomly assigned to the following activation groups (n = 15): EndoActivator (EA), ultrasonically activated irrigation (UAI), and RINSE system (RS). Syringe irrigation (SI) with a 30G needle served as the control. Standardized images of the isthmuses were taken before and after irrigation, and the amount of hydrogel removed was determined using image analysis software and compared across groups using anova (p < .05). RESULTS: Hydrogel removal was significantly higher with the RS (83.7%) than with UAI, EA, or SI (p ≤ .01). UAI (69.2%) removed significantly more hydrogel than SI and EA (p < .05), while there was no significant difference between SI (24.3%) and EA (25.7%) (p = .978). CONCLUSIONS: RINSE system resulted in the most hydrogel removal, performing better than UAI or EA. The effect of RS was also not reliant on the insert or tip entering the pulp chamber or root canal, making it particularly useful in conservative endodontics.

A method for non-destructive microwave focusing for deep brain and tissue stimulation.

Non-invasive stimulation of biological tissue is highly desirable for several biomedical applications. Of specific interest are methods for tumor treatment, endometrial ablation, and neuro-modulation. In traditional neuro-modulation, single- and multi-coil transcranial stimulation techniques in low oscillation frequencies are utilized to non-invasively penetrate the skull and elicit action potentials in cortical neurons. Although these methods have been proven effective, tightly focusing these signals to localized regions is difficult. In recent years, microwave (MW) methods have seen an increase usage as a minimally invasive treatment modality for ablation and neuro-stimulation. Unlike low frequency signals, MW signals can be focused to localized sub-centimeter regions. In this work we demonstrate that a three-dimensional array of MW antennas can be used to tightly focus signals to a localized region in space within the human body with MW frequencies. Assuming an array of small MW loop antennas are placed around the body, the optimal amplitude and phase of each array element can be accurately determined to match an arbitrary desired field profile. The major innovation of the presented method is that the fields that penetrate the biological region are determined via computing numerical Green's functions (NGF) that are then used to drive an optimization algorithm. Using simplified models of regions in the human body, it is shown that the MW fields at 1 GHz can be focused to sub-centimeter sized "hot spots" at depths of several centimeters. The algorithm can be easily extended to more realistic models of the human body or for non-biological applications.

Plant cell-like tip-growing polymer precipitate with structurally embedded multistimuli sensing ability.

Soft systems that respond to external stimuli, such as heat, magnetic field, and light, find applications in a range of fields including soft robotics, energy harvesting, and biomedicine. However, most of the existing systems exhibit nondirectional, nastic movement as they can neither grow nor sense the direction of stimuli. In this regard, artificial systems are outperformed by organisms capable of directional growth in response to the sense of stimuli or tropic growth. Inspired by tropic growth schemes of plant cells and fungal hyphae, here we report an artificial multistimuli-responsive tropic tip-growing system based on nonsolvent-induced phase separation of polymer solution, where polymer precipitates as its solvent dissolves into surrounding nonsolvent. We provide a theoretical framework to predict the size and velocity of growing precipitates and demonstrate its capability of sensing the directions of gravity, mechanical contact, and light and adjusting its growing direction in response. Exploiting the embedded physical intelligence of sensing and responding to external stimuli, our soft material system achieves multiple tasks including printing 3D structures in a confined space, bypassing mechanical obstacles, and shielded transport of liquids within water.

U-IMPACT: a universal 3D microfluidic cell culture platform.

The development of organs-on-a-chip has resulted in advances in the reconstruction of 3D cellular microenvironments. However, there remain limitations regarding applicability and manufacturability. Here, we present an injection-molded plastic array 3D universal culture platform (U-IMPACT) for various biological applications in a single platform, such as cocultures of various cell types, and spheroids (e.g., tumor spheroids, neurospheres) and tissues (e.g., microvessels). The U-IMPACT consists of three channels and a spheroid zone with a 96-well plate form factor. Specifically, organoids or spheroids (~500 µm) can be located in designated areas, while cell suspensions or cell-laden hydrogels can be selectively placed in three channels. For stable multichannel patterning, we developed a new patterning method based on capillary action, utilizing capillary channels and the native contact angle of the materials without any modification. We derived the optimal material hydrophilicity (contact angle of the body, 45-90°; substrate, <30°) for robust patterning through experiments and theoretical calculations. We demonstrated that the U-IMPACT can implement 3D tumor microenvironments for angiogenesis, vascularization, and tumor cell migration. Furthermore, we cultured neurospheres from induced neural stem cells. The U-IMPACT can serve as a multifunctional organ-on-a-chip platform for high-content and high-throughput screening.

Postherpetic Trigeminal Trophic Syndrome: A Case Report.

Trigeminal trophic syndrome (TTS) is a rare condition characterized by anesthesia, paresthesia, and facial ulceration involving the trigeminal dermatome secondary to self-manipulation of the skin after a peripheral or central injury to the trigeminal nerve or its branches. Differential diagnosis of TTS includes conditions presenting with chronic facial ulceration, such as various infectious diseases, malignancy, vasculitis, pyoderma gangrenosum and dermatitis artefacta. We report a case of postherpetic TTS and highlight the importance of early diagnosis and prompt treatment of this condition, which may commonly be misdiagnosed.