Machine Learning-Driven Design Optimization of Buckling-Induced Quasi-Zero Stiffness Metastructures for Low-Frequency Vibration Isolation.

Metastructures, artificial arrangements of micro/macrostructures, possess unique properties and are of significant interest in aerospace, stealth technology, and various other applications. Recent studies have focused on quasi-zero stiffness metastructures, providing an outstanding vibration isolation capability. However, existing methods are constrained to low preloads and lack the consideration of structural analysis, despite their intended use in practical structures. This study introduces metastructures with quasi-zero stiffness characteristics under high preloads by inducing local buckling. An optimization framework combining deep reinforcement learning and finite-element analysis is employed to derive an optimal model that considers both structural safety and quasi-zero stiffness characteristics. To validate the optimization results, quasi-zero stiffness metastructures are fabricated via 3D printing, and compression and vibration experiments are conducted. The fabricated metastructures exhibit quasi-zero stiffness characteristics under a high target preload along with outstanding vibration reduction performance, even in the low-frequency range.

Reducing Bonding Temperature and Energy Consumption in Electronic Packaging Using Flash Electro-Thermal Carbon Fiber Heating Elements.

Semiconductor packaging based on an epoxy molding compound (EMC) currently has several disadvantages including warpage, limited processing area, and variability that all negatively affect cost and production yield. We propose a facile EMC molding process method using a flash electro-thermal carbon fiber heating (FE-CH) device based on carbon fiber-based papers to manufacture an EMC molded to a copper substrate (EMC/Cu bi-layer package) via Joule heating, and using this device, a modified cure cycle that combines the conventional cure cycle (CCC) with rapid cooling was performed using FE-CH to reduce the curvature of the EMC/Cu bi-layer package. Compared to the conventional hot press process, which uses 3.17 MW of power, the FE-CH process only uses 32.87 kW, resulting in a power consumption reduction of over 100 times when following the CCC. Furthermore, the FE-CH-cured EMC/Cu bi-layer package exhibits mechanical properties equivalent to those of a hot press-cured specimen, including the degree of cure, elastic modulus, curvature, bonding temperature, residual strain, and peel strength. The modified cure cycle using the FE-CH results in a 31% reduction in residual strain, a 32% reduction in curvature, and a 47% increase in peel strength compared to the CCC, indicating that this new process method is very promising for reducing a semiconductor package's price by reducing the process cost and warpage.

Improving the Deformability and Recovery Moment of Shape Memory Polymer Composites for Bending Actuators: Multiple Neutral Axis Skins and Deployable Core.

Shape memory polymer composite (SMPC) actuators have received significant attention for applications in space deployable structures because of their light weight and simple actuating process without any additional components. However, conventional SMPC actuators exhibit limited deformation owing to damages caused by the slight elongation of fibers and microbuckling. In this study, we designed a sandwich-structured SMPC bending actuator to increase deformability and the recovery moment with two novel features: multiple neutral axis (MNA) skins and a deployable core. The MNA skins were fabricated as layered structures of a soft layer (the polydimethylsiloxane/ethoxylated polyethylenimine layer) and hard layers (the SMPC layer) based on the MNA effect derived from the large modulus difference between the soft and hard layers. Under the bending deformation, the large shear strain in the soft layer significantly decreases the axial strain in SMPC layers and increases deformability. Applying the deployable core on the sandwich-structured SMPC bending actuator increases the recovery moment owing to the deploying force of the core. To the best of our knowledge, the sandwich-structured SMPC bending actuator composed of two MNA skins and a deployable core yielded the world's largest width-normalized recovery moment of 51.2 N·m/m with the smallest bending radius of 15 mm.

Electronic Packaging Enhancement Engineered by Reducing the Bonding Temperature via Modified Cure Cycles.

Semiconductor packaging continues to reduce in thickness following the overall thinning of electronic devices such as smartphones and tablets. As the package becomes thinner, the warpage of the semiconductor package becomes more important due to the reduced bending stiffness and driven by thermal residual stresses and thermal expansion mismatch during the epoxy molding compound (EMC) curing to create the package. To address this packaging reliability issue, in this study, we developed a modified cure cycle that adds a rapid cooling step to the conventional cure cycle (CCC) to enhance the reliability of the EMC molded to a copper substrate (EMC/Cu bi-layer package) by lowering the bonding temperature of the EMC/Cu bi-layer package. Modeling of the package via Timoshenko theory including effective cure shrinkage allowed the rapid cooling step to be quantified and confirmed via experiments. The modified cure cycle resulted in a 26% reduction in residual strain, a 27% reduction in curvature, and a 40% increase in peel strength compared to the CCC, suggesting that this is an effective new method for managing warping effects in such packaged structures.

Pediatricians' perception of factors concerning the clinical application of blockchain technology to pediatric health care: a questionnaire survey.

BACKGROUND: Interest in digital medical information has increased because it allows doctors to easily access a patient's medical records and provide appropriate medical care. Blockchain technology ensures data safety, reliability, integrity, and transparency by distributing medical data to all users over a peer-to-peer network. This study attempted to assess pediatricians' thoughts and attitudes toward introducing blockchain technology into the medical field. METHODS: This study used a questionnaire survey to examine the thoughts and attitudes of 30- to 60-year-old pediatricians regarding the introduction of blockchain technology into the medical field. Responses to each item were recorded on a scale ranging from 1 (never agree) to 7 (completely agree). RESULTS: The scores for the intentions and expectations of using blockchain technology were 4.0 to 4.6. Pediatricians from tertiary hospitals responded more positively (4.5-4.9) to the idea of using blockchain technology for hospital work relative to the general population (4.3-4.7). However, pediatricians working in primary and secondary hospitals had a slightly negative view of the application of blockchain technology to hospital work (p=0.018). CONCLUSION: When introducing the medical records of related pediatric and adolescent patients using blockchain technology in the future, it would be better to conduct a pilot project that prioritizes pediatricians in tertiary hospitals. The cost, policy, and market participants' perceptions are essential factors to consider when introducing technology in the medical field.

Unilateral Internuclear Ophthalmoplegia Following Minor Head Injury.

A lesion in the medial longitudinal fasciculus (MLF) causes internuclear ophthalmoplegia (INO). Many intracranial lesions, such as multiple sclerosis or vascular disorders may be associated with INO; however, INO is a rare complication of minor head injury. The mechanism underlying injury to the MLF may be shear force on the brain stem during head trauma. The shear force can tear or stretch the fibers of the MLF and can also lead to compromise or rupture of the perforating branches of the basilar artery. We present an unusual case of unilateral INO after minor head injury in a patient with a small site of hemorrhage in the midline of the pontomesencephalic junction, confirmed by brain magnetic resonance imaging using susceptibility-weighted imaging.

Customizable, conformal, and stretchable 3D electronics via predistorted pattern generation and thermoforming.

Recently, three-dimensional electronics (3DE) is attracting huge interest owing to the increasing demands for seamless integration of electronic systems on 3D curvilinear surfaces. However, it is still challenging to fabricate 3DE with high customizability, conformability, and stretchability. Here, we present a fabrication method of 3DE based on predistorted pattern generation and thermoforming. Through this method, custom-designed 3DE is fabricated through the thermoforming process. The fabricated 3DE has high 3D conformability because the thermoforming process enables the complete replication of both the overall shape and the surface texture of the 3D mold. Furthermore, the usage of thermoplastic elastomer and a liquid metal­based conductive electrode allows for high thermoformability during the device fabrication as well as high stretchability during the device operation. We believe that this technology can enable a wide range of new functionalities and multiscale 3D morphologies in wearable electronics.

N2O dynamics in the western Arctic Ocean during the summer of 2017.

The western Arctic Ocean (WAO) has experienced increased heat transport into the region, sea-ice reduction, and changes to the WAO nitrous oxide (N2O) cycles from greenhouse gases. We investigated WAO N2O dynamics through an intensive and precise N2O survey during the open-water season of summer 2017. The effects of physical processes (i.e., solubility and advection) were dominant in both the surface (0-50 m) and deep layers (200-2200 m) of the northern Chukchi Sea with an under-saturation of N2O. By contrast, both the surface layer (0-50 m) of the southern Chukchi Sea and the intermediate (50-200 m) layer of the northern Chukchi Sea were significantly influenced by biogeochemically derived N2O production (i.e., through nitrification), with N2O over-saturation. During summer 2017, the southern region acted as a source of atmospheric N2O (mean: + 2.3 ± 2.7 µmol N2O m-2 day-1), whereas the northern region acted as a sink (mean - 1.3 ± 1.5 µmol N2O m-2 day-1). If Arctic environmental changes continue to accelerate and consequently drive the productivity of the Arctic Ocean, the WAO may become a N2O "hot spot", and therefore, a key region requiring continued observations to both understand N2O dynamics and possibly predict their future changes.

RNA interference-mediated suppression of TNF-α converting enzyme as an alternative anti-TNF-α therapy for rheumatoid arthritis.

Excessive tumor necrosis factor-α (TNF-α) is associated with the pathogenesis of rheumatoid arthritis (RA). Approximately 90% of patients with RA, who have inadequate response to methotrexate, follow anti-TNF-α therapy as the first-line immuno-treatment. However, ineffective long-term anti-TNF-α antibody cycling for 40% of non-responders to anti-TNF-α antibodies is costly and associated with various side effects, which needs alternative mechanism of action therapies. In the present study, a novel strategy to down-regulate TNF-α level was developed by using an alternative method of suppressing TNF-α converting enzyme (TACE), a transmembrane enzyme involved in cleaving and releasing bioactive soluble TNF-α. TACE suppression can be an effective remedy to block the production of soluble TNF-α, leading to an increased sensitivity to anti-TNF-α non-responders. A disease site-targeted RNA interference system was developed by forming non-viral complex between shRNA against TACE (shTACE) and bone resorption site-specific peptide carrier composed of aspartate repeating and arginine repeating sequences. The shTACE/peptide carrier complex alleviated arthritic symptoms in collagen induced arthritis (CIA) models by demonstrating enhanced anti-inflammatory and anti-osteoclastogenic effects. Similar results were obtained with human primary synovial cells and osteoclast precursor isolated from tissues and synovial fluids of RA patients. Taken together, the shTACE/targeting peptide complex provides a strong potential as an alternative anti-TNF-α therapeutic for RA treatment.

Studies on Pre-Modern Medical History in Korea, 2010-2019: Increased Study Areas and Diversified Approaches.

The goal of this article is to summarize the current status of medical history research conducted from 2010 to 2019, following Shin Dongwon's research covering 2000-2010 regarding the current status of Korean pre-modern medical history. The list of references is organized according to several principles. The representative subjects of the Korean Society for the History of Medicine and the Korean Society of Medical history are Korean Journal of Medical History and The Journal of Korean Medical History, and Yonsei Journal of Medical History of the Yonsei University Medical History Institute. Subsequently, "Reviews and Prospects" of the History Journal and "Korean History Research Report" of the National History Compilation Committee are also summarized, and "Medical History Company Research," which was recently published by the Medical History Research Society, is also included. Unlike previous periods, many studies have been conducted on the topic, and the characteristics of the system are largely classified. Most notably, the medical data related to carriers that were concentrated in the early 2010s. It is also worth noting that the research on the agenda, including Lee Soo-gi's newly discovered agenda, is also increasing. In addition, studies that combine the history of medicine with women's history and intellectual history as interdisciplinary studies have been increasing. As such, this is an opportunity for future medical history research to expand the horizon.

Heme Oxygenase 1-Targeted Hybrid Nanoparticle for Chemo- and Immuno-Combination Therapy in Acute Myelogenous Leukemia.

Acute myelogenous leukemia (AML) is a fatal blood cancer with high patient mortality. Daunorubicin and cytarabine are first-line chemotherapy for AML, with bone marrow transplantation in most cases. Recently, cancer immunotherapy has been challenged in AML and leukemia-niche myeloid cells are promising targets for the AML immunotherapy. Heme oxygenase 1 (HO1) is an antioxidative and cytoprotective enzyme inducing chemo-resistant AML and has been focused as an immune checkpoint molecule in tumor microenvironments. Herein, lipid-polymer hybrid nanoparticle (hNP) is loaded with tin mesoporphyrin (SnMP), a HO1-inhibitor, and non-covalently modified with an engineered antibody for leukemic cell-targeted delivery. HO1-inhibiting T-hNP (T-hNP/SnMP) enhances chemo-sensitivity in human leukemia cells. In a human AML-bearing orthotopic mouse model, intravenously injected T-hNP not only actively targets to human leukemia cells but passively targets to CD11b+ myeloid cells in a bone marrow niche. The T-hNP/SnMP enhances the chemo-therapeutic effect of daunorubicin and boosts immune response by reprogramming bone marrow myeloid cells resulting from the recruitment of the monocyte-lineage and induction of inflammatory genes. The ex vivo study demonstrates an enhanced immune response of HO1-inhibited bone marrow CD11b+ myeloid cells against apoptotic leukemia cells. Collectively, HO1-inhibiting dual cell-targeted T-hNP/SnMP has a strong potential as a novel therapeutic in AML.

Pharmacokinetic Evaluation by Modeling and Simulation Analysis of a Donepezil Patch Formulation in Healthy Male Volunteers.

INTRODUCTION: This study characterized the pharmacokinetics (PKs) of a donepezil patch formulation currently under development, using mixed effect modeling analysis, and explored optimal patch dosing regimens in comparison with the donepezil oral formulation. METHODS: PK data used in this analysis were from 60 healthy Korean male subjects participating in two Phase I studies, where subjects received single or multiple doses of donepezil of 43.75, 87.5, and 175 mg via patches, and 12 of them received a single oral dose of 10 mg of donepezil, followed by a single dose of donepezil via a patch. Donepezil PKs were analyzed by nonlinear mixed effect modeling using NONMEM software. RESULTS: A well-stirred model with two-compartment distribution and delayed absorption was chosen as the best model for the oral formulation. The PKs of donepezil after the patch applications were best described by a two-compartment linear model with zero-order absorption (D2) and absorption delay. The relative bioavailability (BA) of donepezil after the patch application compared with oral dosing was described to be affected by the duration of patch application. CONCLUSION: PK simulations based on the chosen PK models suggested that, overall, donepezil exposure in plasma is similar whether with 10 mg of oral donepezil every 24 h or a 175 mg patch every 72 h, and likewise with 5 mg of oral donepezil every 24 h or an 87.5 mg patch every 72 h.

CD64-targeted HO-1 RNA interference enhances chemosensitivity in orthotopic model of acute myeloid leukemia and patient-derived bone marrow cells.

Acute myeloid leukemia is the most frequent and life-threatening blood cancer. The main treatment is chemotherapy, sometimes followed by stem cell transplant. Resistance to chemotherapy and hepatotoxicity of the CD33-targeted therapy require an alternative therapeutic strategy. Here, we report CD64-targeted RNA interference as a novel AML therapy, which was delivered by a recombinant fusion protein of CD64-binding antibody and nona-arginine (sR9). The sR9-mediated heme oxygenase-1 siRNA (siHO-1) delivery efficiently enhanced apoptotic response to daunorubicin of AML cells and AML-targeted HO-1 silencing improved chemotherapy and prolonged survival in orthotopic myeloid leukemia model. CD64 expression was verified and HO-1-silencing-mediated chemo-sensitization was also validated in leukemic blast cells originated from AML M4/M5 patient's bone marrow. Collectively, CD64-targeted RNA interference could be a promising strategy for AML therapy and AML-targeted HO-1 suppression is expected to improve the chemotherapeutic effect in future clinical trials.

Latitudinal Distributions and Controls of Bacterial Community Composition during the Summer of 2017 in Western Arctic Surface Waters (from the Bering Strait to the Chukchi Borderland).

The western Arctic Ocean is experiencing some of the most rapid environmental changes in the Arctic. However, little is known about the microbial community response to these changes. Employing observations from the summer of 2017, this study investigated latitudinal variations in bacterial community composition in surface waters between the Bering Strait and Chukchi Borderland and the factors driving the changes. Results indicate three distinctive communities. Southern Chukchi bacterial communities are associated with nutrient rich conditions, including genera such as Sulfitobacter, whereas the northern Chukchi bacterial community is dominated by SAR clades, Flavobacterium, Paraglaciecola, and Polaribacter genera associated with low nutrients and sea ice conditions. The frontal region, located on the boundary between the southern and northern Chukchi, is a transition zone with intermediate physical and biogeochemical properties; however, bacterial communities differed markedly from those found to the north and south. In the transition zone, Sphingomonas, with as yet undetermined ecological characteristics, are relatively abundant. Latitudinal distributions in bacterial community composition are mainly attributed to physical and biogeochemical characteristics, suggesting that these communities are susceptible to Arctic environmental changes. These findings provide a foundation to improve understanding of bacterial community variations in response to a rapidly changing Arctic Ocean.

Construction of the safe neutralizing assay system using pseudotyped Nipah virus and G protein-specific monoclonal antibody.

Nipah virus (NiV) is a recently emerged paramyxovirus that causes acute respiratory illness and fatal encephalitis in a broad spectrum of vertebrates, including humans. Due to its high pathogenicity and mortality rates, NiV requires handling in biosafety level-4 (BSL-4) containment facilities and no effective vaccines or therapeutic agents are currently available. Since current diagnostic tests for detecting serum neutralizing antibodies against NiV mainly employ live viruses, establishment of more safe and robust alternative diagnostic methods is an essential medical requirement. Here, we have developed a pseudotyped NiV and closely related Hendra virus (HeV) expressing envelope attachment (G) and fusion (F) glycoproteins using the Moloney murine leukemia virus (MuLV) packaging system. We additionally generated polyclonal antibodies (pAbs) against NiV-G and HeV-G and assessed their neutralizing activities for potential utilization in the pseudovirus-based neutralization assay and further application in the serum diagnostic test. To enhance the specificity of neutralizing antibody and sensitivity of the serological diagnostic test, monoclonal antibodies (mAbs) against NiV-G were generated, and among which four out of six mAb clones showed significant reactivity. Specifically, the 7G9 clone displayed the highest sensitivity. The selected mAb clones showed no cross-reactivity with HeV-G and efficient neutralizing activities against pseudotyped NiV. These results validate the safety and specificity of neutralization assays against NiV and HeV and present a useful tool to design effective vaccines and serological diagnosis.

Effect of fentanyl nasal packing treatment on patients with acute postoperative pain after closed reduction of nasal bone fracture: a randomized double-blind controlled trial.

PURPOSE: Nasal bone fracture reduction surgery is normally followed by nasal packing to control bleeding. Yet, patients suffer from pain and require further analgesic treatments following nasal packing and removal. This study aimed to evaluate the effect of fentanyl-soaked packing as a method of controlling pain after nasal surgeries in a prospective, randomized, double-blind controlled trial. METHODS: Sixty-five patients that have undergone closed nasal bone fracture reduction surgery were included in this study. Thirty-two patients were treated postoperatively with 50 mcg fentanyl-soaked Merocel®, a biodegradable synthetic polyurethane foams packing, and the other 33 patients were treated with saline-soaked packings. To analyze the relative nasal pain control effect of fentanyl, Numeric Rating Scale, patient satisfaction and Ramsay Sedation Scale were used. Patients were closely monitored to record relevant cardiopulmonary indicators and degree of adverse symptoms such as headache or sore throat. RESULTS: Fentanyl group had a significantly lower Numeric Rating Scale and higher patient satisfaction for most of the time periods after operation (p < .05). Symptoms of headache and sore throat were also significantly reduced. Ramsay Sedation Scale scores improved compared to the control group (p < .05). No significant differences in cardiopulmonary relevant indicators between the two experimental groups were observed (p > .05). CONCLUSION: Fentanyl-soaked packing significantly decreased postoperative pain with no observable adverse effects. Our results demonstrate that topical fentanyl application to nasal packing is an effective method of postoperative pain control after closed nasal bone fracture reduction surgery.

The effects of adjuvant intrathecal fentanyl on postoperative pain and rebound pain for anorectal surgery under saddle anesthesia.

BACKGROUND: Intrathecal opioid has been known to enhance the quality and prolong the duration of spinal anesthesia, as well as to reduce postoperative pain. The purpose of this study was to evaluate postoperative analgesic characteristics of intrathecal fentanyl for the first 48 hours after anorectal surgery under saddle anesthesia. METHODS: Eighty patients were recruited in our study. Forty patients were randomly allocated to group B that received 0.5% bupivacaine 5 mg with 0.3 ml normal saline. The other 40 patients were assigned to group BF which was given 0.5% bupivacaine 5 mg with fentanyl 15 µg. The primary outcome variable was a numeric rating scale (NRS) at six hours postoperatively. Secondary outcomes included changes in the NRS score between one and 48 hours postoperatively, consumption of rescue analgesics, and the frequency of rebound pain. RESULTS: Group BF exhibited a lower mean NRS score at postoperative six hours compared to group B (P < 0.001). However, the mean NRS score was not different after postoperative six hours between the two groups. The median consumption of rescue analgesics in group BF was less than that of group B (P = 0.028) and the frequency of rebound pain decreased in group BF when compared to group B (P = 0.021). The levels of sensory block were S1 dermatome and motor block scores were 0 for both groups. There was no significant difference in adverse effects between the groups. CONCLUSIONS: Intrathecal fentanyl 15 µg for anorectal surgery under saddle anesthesia led to an improved pain score for the first six hours after surgery and decreased postoperative analgesic use. Rebound pain diminished with intrathecal fentanyl and adverse effects did not increase.

Effect of Fentanyl Nasal Packing Treatment on Patients With Acute Postoperative Pain After Nasal Operation: A Randomized Double-Blind Controlled Trial.

PURPOSE: Nasal packing is an option for bleeding control after endoscopic sinus surgery and septoplasty. Although new packing materials have been developed, patients still suffer from pain and require additional analgesics treatments. In this study, a prospective, randomized, and double-blind controlled trial was designed to evaluate the effect of fentanyl-soaked packing on pain after endoscopic sinus surgery and septoplasty. METHODS: One hundred fifty-two patients who underwent nasal surgeries due to chronic rhinosinusitis or nasal septal deviation were enrolled in this study. At the end of operation, 50 mcg fentanyl-soaked biodegradable synthetic polyurethane foams packing Nasopore or Merocel were applied to a group of 79 patients, and saline-soaked ones were applied to another group of 73 patients. To evaluate the influence of fentanyl on postoperative nasal pain, patients' conditions were assessed via means of Numeric Rating Scale, patient satisfaction, and Ramsay Sedation Scale. In addition, symptoms of headache or sore throat and any signs of cardiopulmonary-relevant indicators were monitored. RESULTS: The fentanyl group had significantly decreased Numeric Rating Scale and increased patient satisfaction in every operation type for the majority of postoperative time periods ( P < .05) with reduced postoperative headache and sore throat compared to the control group. The fentanyl group showed a higher score on Ramsay Sedation Scale than the control group ( P < .05 in group including endoscopic sinus surgery). There were no significant differences in cardiopulmonary-relevant indicators between the 2 groups ( P > .05). CONCLUSION: Fentanyl group showed significantly reduced postoperative pain without serious adverse effects. We suggest that topical fentanyl application to nasal packs can be a useful method to reduce pain during the early postoperative period after endoscopic sinus surgery and septoplasty.

From Woohwang Cheongsimwon* to Ginseng - The History of Medicine Use in the Joseon Era -*.

In Korean traditional medicine, though herbal decoction, acupuncture, and moxibustion are all used to treat diseases, restorative medicines are the most widely preferred treatment method. This paper explores the historical background of restorative herbal medicines and ginseng among the Korean public and Korean traditional medicine practice. It also seeks to clarify how social and cultural perspectives on drug use have changed since restorative medicine became mainstream during the Joseon era. Drug use tendencies were affected by the medical system of the Joseon Dynasty, patients' desires for reliable treatment, and perceptions of the human body and the causes of disease. In the late Joseon Dynasty, medicine, an industry originally monopolized by the government, began to be manufactured and traded on the free market, and medical personnel began to participate in medical activities on a large scale. As the health preserving theory became more popular and medical personnel became more accessible, medicinal preferences also changed. Specifically, whereas preference was first given to common medicines, such as Cheongsimwon, which are effective for various symptoms, restorative medicines, such as ginseng, gradually became more popular. These restorative medicines were faithful to the basic tenet of East Asian traditional medicine: to avoid disease by making the body healthy before the onset of illness. Patients' desires for safe treatment and growing competition among commercial doctors who wanted stable profits further increased the popularity of milder medicines. Ultimately, as ginseng cultivation was realized, its use expanded even further in a wave of commercialization.