Search

Recently, nanovaccine-based immunotherapy has been robustly investigated due to its potential in governing the immune response and generating long-term protective immunity. However, the presentation of a tumor peptide-major histocompatibility complex to T lymphocytes is still a challenge that needs to be addressed for eliciting potent antitumor immunity. Type 1 conventional dendritic cell (cDC1) subset is of particular interest due to its pivotal contribution in the cross-presentation of exogenous antigens to CD8+ T cells. Here, the DC-derived nanovaccine (denoted as Si9GM) selectively targets cDC1s with marginal loss of premature antigen release for effective stimulator of interferon genes (STING)-mediated antigen cross-presentation. Bone marrow dendritic cell (BMDC)-derived membranes, conjugated to cDC1-specific antibody (αCLEC9A) and binding to tumor peptide (OVA257-264), are coated onto dendrimer-like polyethylenimine (PEI)-grafted silica nanoparticles. Distinct molecular weight-cargos (αCLEC9A-OVA257-264 conjugates and 2′3′-cGAMP STING agonists) are loaded in hierarchical center-radial pores that enables lysosome escape for potent antigen-cross presentation and activates interferon type I, respectively. Impressively, Si9GM vaccination leads to the upregulation of cytotoxic T cells, a reduction in tumor regulatory T cells (Tregs), M1/M2 macrophage polarization, and immune response that synergizes with αPD-1 immune checkpoint blockade. This nanovaccine fulfills a dual role for both direct T cell activation as an artificial antigen-presenting cell and DC subset maturation, indicating its utility in clinical therapy and precision medicine.

While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs, the outcomes often exhibit suboptimal particle size distribution and large particle sizes, limiting their effectiveness. In this study, we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs, enabling the fabrication of nanoparticles with fine and uniform particle size distribution. Regorafenib (1 g), as a model drug, copovidone (5 g), and sodium dodecyl sulfate (0.1 g) were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer. The electrostatic spray-dried nanoparticles (ESDN) showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles (CSDN). ESDN demonstrated significantly enhanced solubility and rapid release in water. In vitro studies revealed that ESDN induced apoptosis in HCT-116 cells to a greater extent, exhibiting superior cytotoxicity compared to CSDN. Furthermore, ESDN substantially improved oral bioavailability and antitumor efficacy compared to CSDN. These findings suggest that ESD shows potential in developing enhanced drug delivery systems for poorly water-soluble drugs, effectively addressing the limitations associated with CSD methods.

Plants are treasure trove of novel compounds that have potential for antifungal chemicals and drugs. In our previous study, we had screened plant extracts obtained from more than eight hundred plant materials collected in Korea, and found that butanol fraction of the Actinostemma lobatum were most potent in suppressing growth of diverse fungal pathogens of plants. Here in this study, we describe further analysis of the butanol fraction, and summarize the results of subsequent antifungal activity test for the sub-fractions against a selected set of plant pathogenic fungi. This line of analyses allowed us to identify the sub-fractions that could account for a significant proportion of observed antifungal activity of initial butanol fraction from A. lobatum. Further analysis of these sub-fractions and determination of structure would provide the shortlist for novel compounds that can be a lead to new agrochemicals.

In Korea, most drivers equip their vehicles with a black box camera, used to estimate the speed of the vehicle in case of traffic accidents such as car-to-car collisions, single-car accidents, and car-to-pedestrian accidents. Traditionally, speed estimation using the camera video has been done by using the distance between the road lane, surrounding structures, etc.However, when the following vehicle collides with a stationary leading vehicle or barrier, and no road lanes or structures are visible around the driving path in the black box camera video of the following vehicle, the speed of the following vehicle could be just estimated according the deformations on the collided vehicles or objects.Therefore, in this study, when a vehicle collision occurs, a virtual parallel line is drawn between the leading vehicle and the following vehicle in the black box camera image of the following vehicle and analyzed geometrically to estimate the distance and the speed of the following vehicle.After the vehicle collision experiment, the speed was estimated using the method proposed in this study using the captured black box video. As a result, it was confirmed that the accuracy was high when the collision speed was low. So The method proposed in this study is expected to be used to estimate collision speed in the cases of low impact speed in the rear end collisions.

Abstract Background Exercise stimulates the activation of muscle satellite cells, which facilitate the maintenance of stem cells and their myogenic conversion during muscle regeneration. However, the underlying mechanism is not yet fully understood. This study shows that the transcriptional co‐activator with PDZ‐binding motif (TAZ) stimulates muscle regeneration via satellite cell activation. Methods Tazf/f mice were crossed with the paired box gene 7 (Pax7)creERT2 mice to generate muscle satellite cell‐specific TAZ knockout (sKO) mice. Mice were trained in an endurance exercise programme for 4 weeks. Regenerated muscles were harvested and analysed by haematoxylin and eosin staining. Muscle tissues were also analysed by immunofluorescence staining, immunoblot analysis and quantitative reverse transcription PCR (qRT‐PCR). For the in vitro study, muscle satellite cells from wild‐type and sKO mice were isolated and analysed. Mitochondrial DNA was quantified by qRT‐PCR using primers that amplify the cyclooxygenase‐2 region of mitochondrial DNA. Quiescent and activated satellite cells were stained with MitoTracker Red CMXRos to analyse mitochondria. To study the p38 mitogen‐activated protein kinase (MAPK)–TAZ signalling axis, p38 MAPK was activated by introducing the MAPK kinase 6 plasmid into satellite cells and also inhibited by treatment with the p38 MAPK inhibitor, SB203580. Results TAZ interacts with Pax7 to induce Myf5 expression and stimulates mammalian target of rapamycin signalling for satellite cell activation. In sKO mice, TAZ depletion reduces muscle satellite cell number by 38% (0.29 ± 0.073 vs. 0.18 ± 0.034, P = 0.0082) and muscle regeneration. After muscle injury, TAZ levels (2.59‐fold, P

Acute kidney injury (AKI) constitutes a severe condition characterized by a sudden decrease in kidney function. Utilizing lineage-restricted stem/progenitor cells, directly reprogrammed from somatic cells, is a promising therapeutic option in personalized medicine for serious and incurable diseases such as AKI. The present study describes the therapeutic potential of induced nephron progenitor cell-sourced molecules (iNPC-SMs) as a cell-free strategy against cisplatin (CP)-induced nephrotoxicity, employing hyaluronic acid (HA) hydrogel-mediated local delivery to minimize systemic leakage and degradation. iNPC-SMs exhibited anti-apoptotic effects on HK-2 cells by inhibiting CP-induced ROS generation. Additionally, the localized biodistribution facilitated by hydrogel-mediated iNPC-SM delivery contributed to enhanced renal function, anti-inflammatory response, and renal regeneration in AKI mice. This study could serve as a ‘proof of concept’ for injectable hydrogel-mediated iNPC-SM delivery in AKI and as a model for further exploration of the development of cell-free regenerative medicine strategies.

Acanthamoeba keratitis (AK) is a sight-threatening and difficult-to-treat ocular infection. The significant side effects of current AK treatments highlight the urgent need to develop a safe and effective AK medication. In this study, the amoebicidal activity of Iris setosa Pall. ex Link extract (ISE) against Acanthamoeba was examined and its specific amoebicidal mechanism was explored. ISE induced significant morphological changes in Acanthamoeba trophozoites and exhibited amoebicidal activity against A. castellanii and A. polyphaga. ISE was further fractionated into five subfractions by sequential extraction with n-hexane, chloroform, ethyl acetate, n-butanol, and water, and their amoebicidal activities and underlying amoebicidal mechanisms were investigated. The n-butanol subfraction of ISE (ISE-BuOH) displayed selective amoebicidal activity against the Acanthamoeba species with minimal cytotoxicity in human corneal cells (HCE-2). ISE-BuOH triggered apoptosis-like programmed cell death (PCD) in amoebae, characterized by DNA fragmentation, increased ROS production, and caspase-3 activity elevation. ISE-BuOH also demonstrated a partial cysticidal effect against the amoeba species. ISE-BuOH could be a promising candidate in the development of therapeutic drugs for AK.

Abstract Background Polymeric clips are easy to apply, but whether they present more advantages than endoloops is unclear. This single-center, open-label, randomized controlled trial study was conducted to compare the advantages of using a polymeric clip versus an endoloop in terms of the surgical time. Methods Adult patients who were diagnosed with acute appendicitis without perforation on preoperative abdominal computed tomography and underwent laparoscopic appendectomy between August 6, 2019, and December 26, 2022, were included. Single-blinded randomization was performed in a 1:1 ratio between the endoloop and polymeric clip groups. The primary endpoint was the difference in surgery time between the polymeric clip and endoloop groups. The secondary endpoints were the difference in the application time of each instrument, difference in operation and anesthesia fees, as well as the frequency of complications. Results The completed trial included 104 and 103 patients in the polymeric clip and endoloop groups, respectively. The median surgery time with a polymeric clip was shorter than that with an endoloop; however, the difference was not significant (18 min 56 s vs 19 min 49 s, p = 0.426). Interestingly, the median time from applying the instrument to appendiceal cutting in the polymeric clip group was significantly shorter than that in the endoloop group (49.0 s vs 84.5 s, p 0.999). Conclusion A polymeric clip is a safe instrument that can reduce the time from applying the instrument to appendiceal cutting, although it does not affect the overall surgical time and operation fee when performing laparoscopic appendectomy for uncomplicated appendicitis. Trial registration: KCT0004154.

Extracellular vesicles (EVs) are membrane-enclosed particles secreted by a variety of cell types. These vesicles encapsulate a diverse range of molecules, including proteins, nucleic acids, lipids, metabolites, and even organelles derived from their parental cells. While EVs have emerged as crucial mediators of intercellular communication, they also hold immense potential as both biomarkers and therapeutic agents for numerous diseases. A thorough understanding of EV biogenesis is crucial for the development of EV-based diagnostic developments since the composition of EVs can reflect the health and disease status of the donor cell. Moreover, when EVs are taken up by target cells, they can exert profound effects on gene expression, signaling pathways, and cellular behavior, which makes these biomolecules enticing targets for therapeutic interventions. Yet, despite decades of research, the intricate processes underlying EV biogenesis by donor cells and subsequent uptake by recipient cells remain poorly understood. In this review, we aim to summarize current insights and advancements in the biogenesis and uptake mechanisms of EVs. By shedding light on the fundamental mechanisms governing EV biogenesis and delivery, this review underscores the potential of basic mechanistic research to pave the way for developing novel diagnostic strategies and therapeutic applications.

Inspired by erythrocytes that contain oxygen-carrying hemoglobin (Hb) and that exhibit photo-driven activity, we introduce homogenous-sized erythrocyte-like Hb microgel (μGel) systems (5–6 μm) that can (i) emit heat, (ii) supply oxygen, and (iii) generate reactive oxygen species (ROS; 1O2) in response to near-infrared (NIR) laser irradiation. Hb μGels consist of Hb, bovine serum albumin (BSA), chlorin e6 (Ce6) and erbium@lutetium upconverting nanoparticles (UCNPs; ∼35 nm) that effectively convert 808 nm NIR light to 660 nm visible light. These Hb μGels are capable of releasing oxygen to help generate sufficient reactive oxygen species (1O2) from UCNPs/Ce6 under severely hypoxic condition upon NIR stimulation for efficient photodynamic activity. Moreover, the Hb μGels emit heat and increase surface temperature due to NIR light absorption by heme (iron protoporphyrin IX) and display photothermal activity. By changing the Hb/UCNP/Ce6 ratio and controlling the amount of NIR laser irradiation, it is possible to formulate bespoke Hb μGels with either photothermal or photodynamic activity or both in the context of combined therapeutic effect. These Hb μGels effectively suppress highly hypoxic 4T1 cell spheroid growth and xenograft mice tumors in vivo.

Background and Objectives Epistaxis is one of the most common emergencies in otolaryngology, and the recently developed Rapid Rhino nasal pack, a balloon-type nasal packing device, is widely used in emergency departments. Rebleeding after initial treatment increases patients’ discomfort and medical costs. The aim of this study was to investigate risk factors for rebleeding in patients treated with Rapid Rhino packing. Methods In this retrospective study, 93 patients with epistaxis treated with Rapid Rhino from January 2020 to November 2022 were divided into the well-controlled group (39 patients) and the rebleeding group (54 patients), and the baseline characteristics, management methods, and complications were compared between these groups. The rebleeding group was divided according to whether patients experienced a single episode of rebleeding (38 patients) or multiple rebleeding episodes (16 patients), and the differences between these two groups were compared. Results Oral anticoagulation therapy was associated with a higher risk of rebleeding after Rapid Rhino packing (odds ratio [OR]=8.41, p=0.047). A history of nasal surgery was associated with multiple rebleeding (OR=22.55, p=0.009). Age, sex, the management method, complications, and the site of bleeding were not found to be related to rebleeding. Conclusion Patients with rebleeding after Rapid Rhino nasal packing had a higher rate of concurrent oral anticoagulation therapy. A history of nasal surgery was strongly associated with multiple episodes of rebleeding. A detailed medical history can be important for assessing the risk of rebleeding in epistaxis patients treated with Rapid Rhino packing.

COVID-19: Corticosteroids counteract inflammation by interferon The ability of corticosteroid drugs to alleviate extreme inflammation in severe cases of COVID-19 is linked to their reduction of the gene expression that is stimulated by interferon, an immunological cytokine protein. Interferon is crucial for a healthy immune response, but when produced in excess it can play a central role in causing damaging inflammation. Hyun-Woo Jeong at the Max Planck Institute for Molecular Biomedicine, Münster, Germany, and colleagues in South Korea compared the activity of genes involved in the inflammatory response in blood cells from COVID-19 patients and healthy donors. The results provided insights into the role of altered gene activity in both aggravation and improvement of COVID-19. Of particular interest was the ability of corticosteroids to downregulate the activity of a gene called STAT1, involved in mediating interferon signals.

This paper presents a method for measuring human respiration using a thermal camera. Respiration, being a commonly monitored biomedical signal, has traditionally been measured using contact-based methods, which can cause discomfort and skin damage to patients. With the need for non-contact respiration measurement to prevent infection in the post-COVID-19 era, previous studies encountered challenges in applying non-contact methods in clinical settings due to the distortion of respiratory signals caused by high-dimensional filters. To address these limitations, this paper proposes the use of a thermal camera for non-contact data acquisition and accurate respiratory rate (RR) prediction, even in the presence of noisy respiratory signals. The proposed method leverages a multi-resolution window (MW) and phase-sensitive (PS) processing. Specifically, thermal images are captured using an infrared (IR) thermal camera, and the respiratory signal is extracted from the series of thermal images. The MW method, employing three windows of different sizes in the time domain, is then applied to the extracted respiratory signal. The resulting MW output is transformed into the frequency domain using the Fourier synchro-squeezed transform (FSST). The PS processing involves the multiplication of the converted signal, which is in polar form after a phasor operation. The processed data is utilized to train two bidirectional Long Short-Term Memory (bi-LSTM) networks, and the RR is calculated based on the trained model. To validate the proposed model, a total of 37 surgical patients were involved, with 20 patients used for training and 17 patients for testing. Six deep learning models were designed and their performances were compared. The results indicate that the proposed model outperformed the others, achieving a test classification accuracy of 98.06% and a root mean square error (RMSE) of 0.381. Despite being non-invasive and non-contact, our method demonstrates high accuracy in predicting RR, attributed to the utilization of MW and PS processing. Therefore, it holds potential for application in clinical environments, such as monitoring patients with pulmonary diseases or in intensive care units (ICUs).

Breathing can be measured in a non-contact method using a thermal camera. The objective of this study investigates non-contact breathing measurements using thermal cameras, which have previously been limited to measuring the nostril only from the front where it is clearly visible. The previous method is challenging to use for other angles and frontal views, where the nostril is not well-represented. In this paper, we defined a new region called the breathing-associated-facial-region (BAFR) that reflects the physiological characteristics of breathing, and extract breathing signals from views of 45 and 90 degrees, including the frontal view where the nostril is not clearly visible. Experiments were conducted on fifteen healthy subjects in different views, including frontal with and without nostril, 45-degree, and 90-degree views. A thermal camera (A655sc model, FLIR systems) was used for non-contact measurement, and biopac (MP150, Biopac-systems-Inc) was used as a chest breathing reference. The results showed that the proposed algorithm could extract stable breathing signals at various angles and views, achieving an average breathing cycle accuracy of 90.9% when applied compared to 65.6% without proposed algorithm. The average correlation value increases from 0.587 to 0.885. The proposed algorithm can be monitored in a variety of environments and extract the BAFR at diverse angles and views.

Plants produce chemicals of immense diversity that provide great opportunities for development of new antifungal compounds. In search for environment-friendly alternatives to the fungicide of current use, we screened plant extracts obtained from more than eight hundred plant materials collected in Korea for their antifungal activity against the model plant pathogenic fungus, Magnaporthe oryzae. This initial screening identified antifungal activities from the eleven plant extract samples, among which nine showed reproducibility in the follow-up screening. These nine samples were able to suppress not only M. oryzae but also other fungal pathogens. Interestingly, the plant extracts obtained from Actinostemma lobatum comprised five out of eight samples, and were the most effective in their antifungal activity. We found that butanol fraction of the A. lobatum extract is the most potent. Identification and characterization of antifungal substances in the A. lobatum extracts would provide the promising lead compounds for new fungicide.

Skeletal progenitors provide a reservoir for bone-forming osteoblasts. However, the major energy source for their osteogenesis remains unresolved. Here, the authors demonstrate that ESCIT-mediated regulation of mitochondrial metabolism is required for osteogenesis.

Recent studies indicate that signaling molecules traditionally associated with central nervous system function play critical roles in cancer. Dopamine receptor signaling is implicated in various cancers including glioblastoma (GBM) and it is a recognized therapeutic target, as evidenced by recent clinical trials with a selective dopamine receptor D2 (DRD2) inhibitor ONC201. Understanding the molecular mechanism(s) of the dopamine receptor signaling will be critical for development of potent therapeutic options. Using the human GBM patient-derived tumors treated with dopamine receptor agonists and antagonists, we identified the proteins that interact with DRD2. DRD2 signaling promotes glioblastoma (GBM) stem-like cells and GBM growth by activating MET. In contrast, pharmacological inhibition of DRD2 induces DRD2-TRAIL receptor interaction and subsequent cell death. Thus, our findings demonstrate a molecular circuitry of oncogenic DRD2 signaling in which MET and TRAIL receptors, critical factors for tumor cell survival and cell death, respectively, govern GBM survival and death. Finally, tumor-derived dopamine and expression of dopamine biosynthesis enzymes in a subset of GBM may guide patient stratification for DRD2 targeting therapy.

Soluble epoxide hydrolase (sEH) is an important enzyme for metabolic and cardiovascular health. sEH converts FFA epoxides (EpFAs), many of which are regulators of various cellular processes, to biologically less active diols. In human studies, diol (sEH product) to EpFA (sEH substrate) ratios in plasma or serum have been used as indices of sEH activity. We previously showed these ratios profoundly decreased in rats during acute feeding, possibly reflecting decreases in tissue sEH activities. The present study was designed to test which tissue(s) these measurements in the blood represent and if factors other than sEH activity, such as renal excretion or dietary intake of EpFAs and diols, significantly alter plasma EpFAs, diols, and/or their ratios. The results show that postprandial changes in EpFAs and diols and their ratios in plasma were very similar to those observed in the liver but not in other tissues, suggesting that the liver is largely responsible for these changes in plasma levels. EpFAs and diols were excreted into the urine, but their levels were not significantly altered by feeding, suggesting that renal excretion of EpFAs and diols may not play a major role in postprandial changes in circulating EpFAs, diols, or their ratios. Diet intake had significant impacts on circulating EpFA and diol levels but not on diol-to-EpFA (D-to-E) ratios, suggesting that these ratios, reflecting sEH activities, may not be significantly affected by the availability of sEH substrates (i.e., EpFAs). In conclusion, changes in FFA D-to-E ratios in plasma may reflect those in the liver, which may in turn represent sEH activities in the liver, and they may not be significantly affected by renal excretion or the dietary intake of EpFAs and diols.

Natural light continuously changes its correlated color temperature (CCT) from sunrise to sunset, providing the best color reproducibility and healthy light. In the lighting field, efforts have been made to improve the Color Rendering Index (CRI) to provide light quality at the same level as natural light. A unique light source technology that mixes and controls multiple LED light sources with different spectral or CCT characteristics or provides a high color rendering index has been introduced. However, the characteristics of natural light, which provide high CRI light while changing color temperature every moment, could not be reproduced as they were. Therefore, in this paper, we propose a CRI-based smart lighting system that reproduces natural light characteristics, provides light with high color reproducibility, and maintains homeostasis even under the changing environment of natural light CCT. After extracting the CCT for each day from the characteristics of measured natural light, the light with the highest CRI under the CCT condition for each hour was provided through a CRI-based CCT matching algorithm. Performance evaluation was conducted for four-channel LED experimental lighting. For each clear and cloudy day, daily natural light was reproduced with a light quality higher than average CRI 98 within the MAE range of CCT 6.78 K.

A typical deep geological repository (DGR) design consists of a multi-barrier system, including the natural host rock and the engineered barrier system. Understanding the swelling behavior of bentonite-based sealing materials (BBSM), as a candidate material for the engineered barrier system, is crucial for DGR’s long-term safety. In this study, a hydromechanical (HM) column-type test was designed to model the hydration of BBSM from the underground water and determine the resulting swelling pressure in vertical and radial directions. Five hydration tests were carried out on identical compacted samples of 70% bentonite and 30% sand (70-30 bentonite-sand) mixtures with a dry density of 1.65 g/cm3 for varied durations of hydration, between 1 day and 120 days. The experiments were performed parallel to the compaction direction. Following each HM column-type test, the advancement of the wetting front was determined for each test. After 120 days, 56,339 mm3 of water infiltrated the sample and the wetting front reached over 50% of the sample height. The evolution of axial swelling pressure revealed an initial increase in swelling pressure with time in all tests, followed by a reduction in the rate at later times. After early stages of swelling, radial sensors showed an increase in swelling pressure. After 120 days, the radial pressure sensor closest to the hydration front showed 52% more radial pressure than the axial swelling pressure.

Background/Aims The study investigated the incidence of thromboembolic events (TEE) in head and neck (H&N) cancer patients who received concurrent chemoradiotherapy (CCRT) with cisplatin, and analyzed the factors affecting TEE occurrence Methods Two hundred and fifty-seven patients who started CCRT with cisplatin for H&N cancer from January 2005 to December 2019 were analyzed. Results TEE occurred in five patients, an incidence rate of 1.9%. The 2-, 4-, and 6-month cumulative incidences of TEE were 0.8%, 1.6%, and 1.9%, respectively. Khorana score was the only factor associated with TEE occurrence (p = 0.010). Conclusions The incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low when compared to other types of cancer. However, patients with a high Khorana score require more careful surveillance for possible TEE occurrence.

Persicaria maackiana (Regel) Nakai ex T. Mori (1922), a species of the Polygonaceae family, is an annual plant widely distributed in Northeast Asia. We aimed to sequence the complete chloroplast genome of P. maackiana using Illumina HiSeq paired-end sequencing. The chloroplast genome was determined to be 160,635 bp. The complete chloroplast genome contained 129 genes, including 84 protein-coding genes, 37 tRNA, and eight rRNA genes. Phylogenetic analysis of the chloroplast genome sequences of 15 Polygonaceae plants revealed that P. maackiana was most closely related to P. perfoliata. Our findings might be useful for future phylogenetic studies of Polygonaceae.

Background/Aims The optimal treatment (Tx) for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains to be determined. Methods A retrospective review was conducted on 77 NSCLC patients with synchronous BM who underwent first-line EGFR-tyrosine kinase inhibitor (TKI) Tx. The outcomes of patients were analyzed according to the clinicopathological characteristics including local Tx modalities. Results Fifty-nine patients underwent local Tx for BM (gamma knife surgery [GKS], 37; whole brain radiotherapy [WBRT], 18; others, four) concurrently or sequentially with EGFR-TKI. Patients treated with TKI alone showed significantly lower incidence of central nervous system (CNS) symptoms. The median progression-free survival (PFS) and overall survival (OS) after the initiation of EGFR-TKI for all patients were 9 and 19 months, respectively. In 60 patients with follow-up brain imaging, the median time to CNS progression was 15 months. Patients with EGFR exon 19 deletion had a significantly longer median OS than those with other mutations including L858R (23 months vs. 17 months). Other clinical characteristics, including CNS symptoms, number of BM, and the use of local Tx were not associated with OS, as well as PFS. In terms of the local optimal Tx modality, no difference was found between GKS and WBRT in the OS and PFS. Conclusions This study suggests that EGFR-TKI may result in a favorable outcome in NSCLC patients with synchronous BM, especially in deletion 19 mutant, regardless of the extent of BM lesions or local Tx modalities. Patients with asymptomatic BM can be treated with EGFR-TKI and careful surveillance.

Mitochondrial biogenesis is stimulated to meet energy requirements in response to extracellular signals including exercise. TAZ is revealed as a novel stimulator for mitochondrial biogenesis and facilitates exercise-induced muscle adaptation.

BackgroundSmall circular staplers possess the advantage of being relatively easy to use when compared to larger circular staplers. However, there is some contention as to whether the use of small circular staples in colorectal surgery increases the incidence of anastomotic strictures. This study aimed to determine whether the frequency of anastomosis site stricture formation differs depending on stapler size when performing anastomosis in colorectal surgery.MethodsPatients who underwent surgery for colon or rectal disease between June 1, 2009, and December 31, 2021, and who had circular staplers used for the formation of intestinal anastomoses post colectomy were included in our study. Propensity score matching with a 1:1 ratio using logistic regression was performed. The primary outcome was the anastomotic stricture rate, and the secondary outcome was total anastomotic complications.ResultsA total of 875 patients who were operated on by surgeons using 28/29-mm and 25-mm circular staplers were included. After propensity score matching, 106 patients were assigned to each group. Anastomotic strictures occurred in two cases (1.9%) from the 25-mm group and in four cases (3.8%) from the 28/29-mm group. There were no statistically significant differences between the two groups (p = 0.683). Anastomotic complications were observed in two cases (1.9%) from the 25-mm group and in six cases (5.7%) from the 28/29-mm group; no statistically significant differences were found (p = 0.280).ConclusionCircular stapler size does not influence anastomotic stricture formation in colorectal surgery.

BackgroundAlthough the advantages of laparoscopic Hartmann reversal (LHR) compared to open Hartmann reversal (OHR) have been reported in the literature, the number of multicenter studies with good matching investigating this topic is rare. In the present study, we aimed to confirm the advantages of LHR in terms of short-term outcomes through propensity score matching of LHR and OHR groups, using data collected from multiple institutions.MethodsPatients who underwent Hartmann reversal at six institutions under the Catholic Medical Center of the Catholic University of Korea between January 1, 2005, and December 31, 2021, were included. The patients were divided into the LHR and OHR groups based on the technique used. The two groups were matched using propensity score matching (1:1 ratio, logistic regression with the nearest-neighbor method). The primary outcome was postoperative ileus (POI) frequency, and secondary outcomes were time to solid diet (days) and length of stay (days).ResultsAmong 337 patients, propensity score matching was performed on 322, after excluding 15 who had undergone open conversion. Of these, 63 patients were assigned to each group through propensity score matching. There was no difference in the frequency of adhesiolysis (77.8% vs. 82.5%, p = 0.503) or the operation time. (210 (IQR 159-290) vs. 233 (IQR 160-280), p = 0.718) between the two groups. As the primary outcome, the LHR group showed significantly lower POI frequency than the OHR group. (4.8% vs. 22.2%, p = 0.0041) Regarding the secondary outcomes, the LHR group showed a shorter period to solid diet than the OHR group. The length of hospital stay was also significantly shorter in the LHR group (4 vs. 6, p < 0.0001; 9 vs. 12, pConclusionLHR is an effective method to ensure faster recovery of patients after surgery compared to OHR.

Abstract In this study, strong electron-withdrawing fluorine (F) and cyano (CN) substituents are selectively incorporated into the quinoxaline unit of two-dimensional (2D) D–A-type polymers to investigate their effects on the photovoltaic properties of the polymers. To construct the 2D polymeric structure, electron-donating benzodithiophene and methoxy-substituted triphenylamine are directly linked to the horizontal and vertical directions of the quinoxaline acceptor, respectively. After analyzing the structural, optical, and electrochemical properties of the resultant F- and CN-substituted polymers, labeled as PBCl-MTQF and PBCl-MTQCN, respectively, inverted-type polymer solar cells with a non-fullerene Y6 acceptor are fabricated to investigate the photovoltaic performances of the polymers. It is discovered that the maximum power conversion efficiency of PBCl-MTQF is 7.48%, whereas that of PBCl-MTQCN is limited to 3.52%. This significantly reduced PCE of the device based on PBCl-MTQCN is ascribed to the formation of irregular, large aggregates in the active layer, which can readily aggravate the charge recombination and charge transport kinetics of the device. Therefore, the photovoltaic performance of 2D quinoxaline-based D–A-type polymers is significantly affected by the type of electron-withdrawing substituent.

Objectives: This study aims to describe the utilization of herbal formulas from Wenrejingwei by using network analysis and understand the treatment of acute exogenous febrile diseases.Methods: We constructed a matrix of high-frequency herbal combinations (HCs) from Wenrejingwei and Shang Han Lun and cluster networks based on cohesive analysis. Network analysis was performed to compare the results.Results: The results of the high-frequency HC network in Wenrejingwei showed cohesive patterns in three categories corresponding to dampness-heat and warm-fever treatment. Compared to the Shang Han Lun network, the Wenrejingwei network indicated a careful approach in the use of pungent and warm herbs such as Guizhitang. Moreover, the combination of Scutellaria baicalensis and Coptis chinensis along with the use of herbs strengthening yin, such as Ginseng Radix and Liriopes Radix, provide evidence of a holistic approach in the treatment of exogenous febrile diseases by considering the balance of the human body damaged by heat.Conclusion: The results of this study could help select appropriate herbal formulas and treatment methods for treating Onbyeong and modern acute febrile infectious diseases.

BackgroundEarly morning behaviors between waking up and beginning daily work can develop into productive habits. However, sleep inertia limits the level of human ability immediately after waking, lowering a person’s motivation and available time for productive morning behavior. ObjectiveThis study explores a design for morning behavior change using a wake-up task, a simple assignment the user needs to finish before alarm dismissal. Specifically, we set two research objectives: (1) exploring key factors that relate to morning behavior performance, including the use of wake-up tasks in an alarm app and (2) understanding the general practice of affecting morning behavior change by implementing wake-up tasks. MethodsWe designed and implemented an apparatus that provides wake-up task alarms and facilities for squat exercises. We recruited 36 participants to perform squat exercises in the early morning using the wake-up tasks for 2 weeks. First, we conducted a generalized estimating equation (GEE) analysis for the first research objective. Next, we conducted a thematic analysis of the postsurvey answers to identify key themes about morning behavior change with the wake-up tasks for the second objective. ResultsThe use of wake-up tasks was significantly associated with both the completion of the target behavior (math task: P=.005; picture task: P

This study evaluated the effects of Rorippa cantoniensis (Lour.) ohwi extract (RCE) on factors associated with inflammation-related skin lesions in RAW 264.7 and HaCaT cells. RCE inhibited the levels of proinflammatory mediators and cytokines such as nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In addition, RCE significantly inhibited the expression of chemokines and cytokines such as MDC/CCL22, TARC/CCL17, RANTES/CCL5, CTSS, IL-6, IL-1β, and TNF-α in HaCaT cells costimulated by TNF-α and interferon (IFN)-γ in a concentration-dependent manner. These results suggest that RCE attenuated the TNF-α- and IFN-γ-induced release of proinflammatory chemokines and cytokines probably by suppressing the activation of MAPK (JNK and p38), NF-κB, and STAT1 signaling. Moreover, RCE significantly increased the expression of skin components such as hyaluronic acid and aquaporin, which play important roles in the physical and chemical barriers of the skin. These results suggest that RCE has significant anti-inflammatory and antiatopic activities, which may be beneficial for the topical treatment of inflammatory skin disorders.

Oxylipins, oxidation products of unsaturated free fatty acids (FFAs), are involved in various cellular signaling systems. Among these oxylipins, FFA epoxides are associated with beneficial effects in metabolic and cardiovascular health. FFA epoxides are metabolized to diols, which are usually biologically less active, by soluble epoxide hydrolase (sEH). Plasma epoxide-diol ratios have been used as indirect measures of sEH activity. This study was designed to examine the effects of acute elevation of individual plasma FFAs on a variety of oxylipins, particularly epoxides, diols, and their ratios. We tested if FFA epoxide-diol ratios are altered by circulating FFA levels (i.e., substrate availability) independent of sEH activity. Wistar rats received a constant intravenous infusion of olive (70% oleic acid (OA)), safflower seed (72% linoleic acid (LA)), and fish oils (rich in ω-3 FFAs) as emulsions to selectively raise OA, LA, and ω-3 FFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), respectively. As expected, olive, safflower seed, and fish oil infusions selectively raised plasma OA (57%), LA (87%), EPA (70%), and DHA (54%), respectively (p < 0.05 for all). Raising plasma FFAs exerted substrate effects to increase hepatic and plasma epoxide and diol levels. These increases in epoxides and diols occurred to similar extents, resulting in no significant changes in epoxide-diol ratios. These data suggest that epoxide-diol ratios, often used as indices of sEH activity, are not affected by substrate availability or altered plasma FFA levels and that epoxide-diol ratios may be used to compare sEH activity between conditions of different circulating FFA levels.

Abstract Background Considering the limited accessibility of amyloid position emission tomography (PET) in patients with dementia, we proposed a deep learning (DL)-based amyloid PET positivity classification model from PET images with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (2-[18F]FDG). Methods We used 2-[18F]FDG PET datasets from the Alzheimer's Disease Neuroimaging Initiative and Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer’s disease for model development. Moreover, we used an independent dataset from another hospital. A 2.5-D deep learning architecture was constructed using 291 submodules and three axes images as the input. We conducted the voxel-wise analysis to assess the regions with substantial differences in glucose metabolism between the amyloid PET-positive and PET-negative participants. This facilitated an understanding of the deep model classification. In addition, we compared these regions with the classification probability from the submodules. Results There were 686 out of 1433 (47.9%) and 50 out of 100 (50%) amyloid PET-positive participants in the training and internal validation datasets and the external validation datasets, respectively. With 50 times iterations of model training and validation, the model achieved an AUC of 0.811 (95% confidence interval (CI) of 0.803–0.819) and 0.798 (95% CI, 0.789–0.807) on the internal and external validation datasets, respectively. The area under the curve (AUC) was 0.860 when tested with the model with the highest value (0.864) on the external validation dataset. Moreover, it had 75.0% accuracy, 76.0% sensitivity, 74.0% specificity, and 75.0% F1-score. We found an overlap between the regions within the default mode network, thus generating high classification values. Conclusion The proposed model based on the 2-[18F]FDG PET imaging data and a DL framework might successfully classify amyloid PET positivity in clinical practice, without performing amyloid PET, which have limited accessibility.

Abstracts: Background: Reducing postoperative pain with less opioid is critical in postoperative care. Author developed our multimodal perioperative pain management protocol and it consists of preoperative medication, intraoperative ultrasound-guided laparoscopic transverse abdominis plane (LTAP) block and postoperative medication. This study aimed to evaluate the clinical effect of the multimodal perioperative pain management protocol for minimally invasive colorectal cancer surgery. Methods: Of 596 colorectal surgery cases for colorectal cancer, 133 patients managed with multimodal perioperative pain protocol (group 1) and 463 patients managed without multimodal perioperative pain protocol (group 2) were enrolled in this study. To adjust for baseline differences and selection bias, operative outcomes and complications were compared after propensity score matching (PSM). Results: After 1:1 propensity score matching, well-matched 133 patients in each group were evaluated. The median VAS scores on post-operative day 1 (2.1 ± 1.1 vs. 3.9 ± 1.8, p

Abstract Background Routine colonoscopy is recommended to determine the coexistence of colon cancer after medical treatment for colon diverticulitis. However, in the case of uncomplicated diverticulitis diagnosed by computed tomography, the clinical relevance of routine follow-up colonoscopy has recently been debated. Yet, the role of follow-up colonoscopy for right colon diverticulitis, which tends to develop at a younger age than left colon diverticulitis, has not been specifically evaluated. Therefore, we aimed to evaluate the incidence of right colon cancer or colonic adenomatous polyps, detected by routine colonoscopy, after conservative management of acute uncomplicated right colon diverticulitis. Methods Patients with uncomplicated right colon diverticulitis (modified Hinchey stage Ia) diagnosed by computed tomography imaging, between 2011 and 2017, and who underwent follow-up colonoscopy surveillance after treatment were included. The primary outcome was the incidence of colon cancer, with the detection rate of adenoma being the secondary outcome. Information for analysis was retrieved retrospectively from patients’ medical records. Results The study group included 330 consecutive patients, with a mean age of 41.9 years, and 51.9% being men. For the primary outcome, the rate of colon cancer on follow-up colonoscopy was 0.3% (1/330 cases). The rate of adenoma detection was 20.9% (69/330 cases) and advanced adenoma (> 10 mm in diameter; or exhibiting a > 25% villous component or severe dysplasia), including colon cancer, was observed in 9 patients (2.7%). Conclusions In patients with acute uncomplicated right colonic diverticulitis, routine colonoscopy after conservative treatment may be necessary because although the colon cancer detection rate is low, it is possible to detect advanced colon adenoma.

Polypropylene (PP) is used as a housing material in automotive headlamps but can cause fogging as a result of absorbed moisture and temperature differences between the exterior and interior of the housing. In this study, PP was combined with a graphene/montmorillonite hybrid (MMT-G) to yield a nanocomposite with reduced moisture absorption. Crucially, the modified nanofiller had low hydrophilicity and good compatibility with the PP matrix. Notably, the water contact angle of the MMT-G improved by 676%. Furthermore, the maximum moisture absorption of the PP/MMT-G nanocomposites was reduced by up to 11.22% compared to that of commercial PP composites, and the weight of the headlamp housing was decreased by 3.6%. Therefore, the designed nanocomposites are expected to help mitigate headlamp fogging while slightly reducing the housing weight.

Patients discharged from hospitals after an inpatient course of medical treatment for any ailment or traumatic injury that results in disabling conditions and are rendered mobility impaired require ongoing systematic sports and exercise programs to maintain healthy lifestyles. Under such circumstances, a rehabilitation exercise and sports center, accessible throughout local communities, is critical for promoting beneficial living and community participation for these individuals with disabilities. An innovative data-driven system equipped with state-of-the-art smart and digital equipment, set up in architecturally barrier-free infrastructures, is essential for these individuals to promote health maintenance and overcome secondary medical complications following an acute inpatient hospitalization or suboptimal rehabilitation. A federally funded collaborative research and development (R&D) program proposes to build a multi-ministerial data-driven system of exercise programs using a smart digital living lab as a platform to provide pilot services in physical education and counseling with exercise and sports programs for this patient population. We describe the social and critical aspects of rehabilitating such a population of patients by presenting a full study protocol. A modified sub-dataset of the previously generated 280-item full dataset is applied using a data-collecting system—“The Elephant”—as an example of how data acquisition will be achieved to assess the effects of lifestyle rehabilitative exercise programs for people with disabilities.