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It has been demonstrated that a reward-associated stimulus feature captures attention involuntarily. The present study tested whether spatial attentional orienting is biased via reinforcement learning. Participants were to identify a target stimulus presented in one of two placeholders, preceded by a non-informative arrow cue at the center of the display. Importantly, reward was available when the target occurred at a location cued by a reward cue, defined as a specific color (experiments 1 and 3) or a color–direction combination (experiment 2). The attentional bias of the reward cue was significantly increased as trials progressed, resulting in a greater cue-validity effect for the reward cue than the no-reward cue. This attentional bias was still evident even when controlling for the possibility that the incentive salience of the reward cue color modulates the cue-validity effect (experiment 2) or when the reward was withdrawn after reinforcement learning (experiment 3). However, it disappeared when the reward was provided regardless of cue validity (experiment 4), implying that the reinforcement contingency between reward and attentional orienting is a critical determinant of reinforcement learning-based spatial attentional modulation. Our findings highlight that a spatial attentional bias is shaped by value via reinforcement learning.

Abstract Background Increased Galectin 3‐binding protein (LGALS3BP) serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma (HCC). Considering the crucial role of transforming growth factor‐β1 (TGF‐β1) in the emergence of these diseases, the present study tested the hypothesis that LGALS3BP regulates the TGF‐β1 signaling pathway. Methods The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction‐associated steatohepatitis (MASH) and HCC. Multiple omics techniques, such as RNA‐sequencing, transposase‐accessible chromatin‐sequencing assay, and liquid chromatography‐tandem mass spectrometry proteomics, were used to identify the regulatory mechanisms for the LGALS3BP‐TGF‐β1 axis. The effects of altered TGF‐β1 signaling by LGALS3BP were investigated in conditional LGALS3BP‐knockin and LGALS3BP‐knockout mice. Results In patients with MASH and HCC, the levels of LGALS3BP and TGFB1 exhibited positive correlations. Stimulation of LGALS3BP by the inflammatory cytokine interferon α in HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of TGFB1. Aggravated fibrosis was observed in the livers of hepatocyte‐specific LGALS3BP‐knockin mice, with increased TGFB1 levels. LGALS3BP directly bound to and assembled integrin αV, an integral mediator required for releasing active TGF‐β1 from extracellular latent complex with the rearranged F‐actin cytoskeleton. The released TGF‐β1 activated JunB transcription factor, which in turn promoted the TGF‐β1 positive feedback loop. LGALS3BP deletion in the hepatocytes downregulated TGF‐β1 signaling and CCl4 induced fibrosis. Moreover, LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF‐β1. Conclusion LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF‐β1 signaling pathway, making it a promising therapeutic target in TGF‐β1‐related diseases.

This paper presents a seismic analysis method that can evaluate a very large number of cases for the free standing dry storage cask by proposing a methodology that has short analysis time as well as accuracy. This study also performed a seismic analysis of a dry storage facility with multiple casks to show a tip-over phenomenon from earthquake accident conditions. The earthquake accident condition is long-term event that occur during about 20 s long, and lots of seismic analysis cases should be performed to consider various real conditions because the free-standing spent-fuel dry storage cask has many nonlinear responses. The soil–concrete pad–cask interaction was considered in the seismic analysis and finite element model was made using concrete pad, soil and cask models. In the reinforced concrete pad, the rebar was excluded to reduce the analysis time, but the thickness was corrected to maintain the bending rigidity. Additionally, the analysis time reduced by modeling the cask as a rigid body rather than a flexible body. 35-cases of seismic analysis were performed to determine a tip-over phenomenon from each earthquake. The analysis revealed that no tip-over phenomenon of the cask was observed in all analyses from 0.2 g to 0.6 g, however the tip-over of the cask were observed from 0.8 g with friction coefficients of 0.8 and 1.0.

Background: Hanwoo cattle farmers aim to improve calf production and reproductive efficiency. Recovery of the reproductive tract postpartum is a critical factor influencing the postpartum period and conception of breeding cows. This study aimed to precisely analyze the recovery process of the reproductive tract in primiparous Hanwoo postpartum and to establish recovery criteria. Methods: Ten primiparous Hanwoo cows were used in this study. After parturition, estrus was examined daily using visual observations and estrus detection patches. Ovarian recovery, cervical diameter, and uterine horn diameter were examined using ultrasonography four times per week. Results: The analysis revealed that the first estrus occurred at 19.1 ± 6.5 days postpartum, the first ovulation at 27.1 ± 4.5 days, and the first normal estrus cycle at 39.2 ± 6.4 days. The ovulation rate during the first estrus was 40%. A normal estrus cycle occurred in 11.1% of patients at the first ovulation. The cervix diameter recovered to 42.0 ± 3.5 mm and the uterine horn diameter to 34.4 ± 7.1 mm by 24 days postpartum, with the difference in uterine horn diameter recovering to 2.6 ± 1.2 mm by 31 days postpartum. Conclusions: This study can aid in determining the optimal breeding time for postpartum primiparous Hanwoo cow and provide foundational data for Hanwoo breeding studies.

Abstract Preclinical drug efficacy and tumor microenvironment (TME) investigations often utilize humanized xenograft mouse models, yet these models typically fall short in replicating the intricate TME. We developed a humanized liver metastasis (LM) model by transplanting human peripheral blood mononuclear cells (PBMCs) and assessed it against the conventional subcutaneous (SC) xenograft model, focusing on immune cell dynamics post-transplantation and immunotherapy response. NOD-scid IL2Rgammanull(NSG) were inoculated with PBMCs to create humanized models. We induced SC and LM models using HCT116 cells, to investigate and compare the distributions and transformations of immune cell subsets, respectively. Both models were subjected to anti-PD-L1 therapy, followed by an analysis the TME analysis. The LM model demonstrated enhanced central tumor infiltration by tumor-infiltrating lymphocytes (TILs) compared to the peripheral pattern of SC model. TIL subpopulations in the LM model showed a progressive increase, contrasting with an initial rise and subsequent decline in the SC model. Post-anti-PD-L1 therapy, the LM model exhibited a significant rise in central and effector memory T cells, a response absents in the SC model. Our study highlights differential TME responses between SC and LM models and introduces a robust humanized LM model that swiftly indicates the potential efficacy of immunotherapies. These insights could streamline the preclinical evaluation of TME-targeting immunotherapeutic agents.

Abstract Background Computed tomography (CT) body compositions reflect age‐related metabolic derangements. We aimed to develop a multi‐outcome deep learning model using CT multi‐level body composition parameters to detect metabolic syndrome (MS), osteoporosis and sarcopenia by identifying metabolic clusters simultaneously. We also investigated the prognostic value of metabolic phenotyping by CT model for long‐term mortality. Methods The derivation set (n = 516; 75% train set, 25% internal test set) was constructed using age‐ and sex‐stratified random sampling from two community‐based cohorts. Data from participants in the individual health assessment programme (n = 380) were used as the external test set 1. Semi‐automatic quantification of body compositions at multiple levels of abdominal CT scans was performed to train a multi‐layer perceptron (MLP)‐based multi‐label classification model. External test set 2 to test the prognostic value of the model output for mortality was built using data from individuals who underwent abdominal CT in a tertiary‐level institution (n = 10 141). Results The mean ages of the derivation and external sets were 62.8 and 59.7 years, respectively, without difference in sex distribution (women 50%) or body mass index (BMI; 23.9 kg/m2). Skeletal muscle density (SMD) and bone density (BD) showed a more linear decrement across age than skeletal muscle area. Alternatively, an increase in visceral fat area (VFA) was observed in both men and women. Hierarchical clustering based on multi‐level CT body composition parameters revealed three distinctive phenotype clusters: normal, MS and osteosarcopenia clusters. The L3 CT‐parameter‐based model, with or without clinical variables (age, sex and BMI), outperformed clinical model predictions of all outcomes (area under the receiver operating characteristic curve: MS, 0.76 vs. 0.55; osteoporosis, 0.90 vs. 0.79; sarcopenia, 0.85 vs. 0.81 in external test set 1; P

Wire and arc additive manufacturing (WAAM) technique has introduced a novel approach for producing complex Ti–6Al–4V parts with metric dimensions. However, the produced part leads to the development of a strong texture and anisotropic mechanical properties due to the formation of large columnar β grains. To resolve this issue, the plastic deformation of each deposited track through hammer peening was developed as a means to refine these large β grains. In this study, we have investigated an innovative approach to further enhance the efficiency of β grain refinement by minimizing the arc heat input associated with previous deposited layer, which is achieved by employing a C-type filler wire. Our findings reveal a notable enhancement in grain refinement efficiency through the utilization of a C-type filler wire with peening process, as compared to available conventional commercial round shape filler wire. Specifically, the employment of the C-type filler wire results in a reduced melt pool penetration depth of WAAM Ti–6Al–4V (3.3 mm), compared to the commercially available round shape (R-Type) filler wire (4.48 mm). Within the plastically deformed region by peening, fine and randomly oriented β grains are observed, extending to a depth of deformation reaching 844 ± 32.65 μm. Peening WAAM Ti–6Al–4V with the C-type filler wire leads to the development of isotropic mechanical properties in both horizontal and vertical directions, offering high strength due to the presence of small equiaxed β grains and thin α laths (0.56 ± 0.18 μm), in contrast to the use of conventional commercial round shape filler wire.

As the number of offshore wind-power installations increases, collision accidents with vessels occur more frequently. This study investigates the risk of collision damage with operating vessels that may occur during the operation of an offshore wind turbine. The floater used in the collision study is a 15 MW UMaine VolturnUS-S (semi-submersible type), and the colliding ships are selected as multi-purpose vessels, service operation vessels, or anchor-handling tug ships based on their operational purpose. Collision analysis is performed using ABAQUS and substantiation is performed via a drop impact test. The collision analyses are conducted by varying the ship velocity, displacement, collision angle, and ship shape. By applying this numerical model, the extent of damage and deformation of the collision area is confirmed. The analysis results show that a vessel with a bulbous bow can cause flooding, depending on the collision conditions. For damage caused by collision, various collision angles must be considered based on the internal stiffener arrangement. Additionally, the floater can be flooded with relatively small collision energy when the colliding vessel has a bulbous bow.

Abstract Glioblastoma (GBM) is a highly aggressive and deadly brain cancer. Temozolomide (TMZ) is the standard chemotherapeutic agent for GBM, but the majority of patients experience recurrence and invasion of tumor cells. We investigated whether TMZ treatment of GBM cells regulates matrix metalloproteinases (MMPs), which have the main function to promote tumor cell invasion. TMZ effectively killed GL261, U343, and U87MG cells at a concentration of 500 µM, and surviving cells upregulated MMP9 expression and its activity but not those of MMP2. TMZ also elevated levels of MMP9 mRNA and MMP9 promoter activity. Subcutaneous graft tumors survived from TMZ treatment also exhibited increased expression of MMP9 and enhanced gelatinolytic activity. TMZ-mediated MMP9 upregulation was specifically mediated through the phosphorylation of p38 and JNK. This then stimulates AP-1 activity through the upregulation of c-Fos and c-Jun. Inhibition of the p38, JNK, or both pathways counteracted the TMZ-induced upregulation of MMP9 and AP-1. This study proposes a potential adverse effect of TMZ treatment for GBM: upregulation of MMP9 expression potentially associated with increased invasion and poor prognosis. This study also provides valuable insights into the molecular mechanisms by which TMZ treatment leads to increased MMP9 expression in GBM cells.

Introduction Technetium thyroid uptake (TcTU) measured by single-photon emission CT/CT (SPECT/CT) is an important diagnostic tool for the differential diagnosis of Graves’ disease and destructive thyroiditis. Artificial intelligence (AI) may reduce CT-induced radiation exposure by substituting the role of CT in attenuation correction (AC) and thyroid segmentation, thus realising CT-free SPECT. This study aims to compare the diagnostic accuracy for the differential diagnosis of thyrotoxicosis between CT-free SPECT and SPECT/CT.Methods and analysis The AI-based CT-free SPECT is a single-blind, multicentre, prospective, non-inferiority, clinical trial with a paired design conducted in the Republic of Korea. Eligible participants are adult (≥19 years old) thyrotoxicosis patients without a previous history of hyperthyroidism or hypothyroidism. Approximately 160 subjects will be screened for quantitative thyroid SPECT/CT using Tc-99m pertechnetate. CT-free thyroid SPECT will be realised using only SPECT data by the trained convolutional neural networks. TcTU will be calculated by SPECT/CT and CT-free SPECT in each subject. The primary endpoint is the accuracy of diagnosing Graves’ disease using TcTU. The trial will continue until 152 completed datasets have been enrolled to assess whether the 95% (two-sided) lower confidence limit of the accuracy difference (CT-free SPECT accuracy—SPECT/CT accuracy) for Graves’ disease is greater than −0.1. The secondary endpoints include the accuracy of diagnosing destructive thyroiditis and predicting the need for antithyroid drug prescription within 1 month of the SPECT/CT.Ethics and dissemination The study protocol has been approved by the institutional review board of Seoul National University Bundang Hospital (IRB No. B-2304-824-301), Konkuk University Medical Center (IRB No. 2023-05-022-006) and Chonnam National University Hospital (IRB No. CNUH-2023-108). Findings will be disseminated as reports, presentations and peer-reviewed journal articles.Trial registration number KCT0008387, Clinical Research Information Service of the Republic of Korea (CRIS).

Viral vectors are agents enabling gene transfer and genome editing and have widespread utility across the healthcare and biotechnology sectors. In January 2023, the International Bureau for Weights and Measures’ Consultative Committee for Amount of Substance (CCQM) held a workshop on Metrology for Viral systems as molecular tools. The workshop brought together international leaders from across regulatory, industry, government science, and metrology sectors to better understand key challenges for the community: Exploring current limitations in the measurement of virus-derived, virus-based, and virus-like systems in terms of quantification and characterisation; surveying the state-of-the-art in analytical methods and reference material provision for these entities; and initiating a dialog for the strategic development and implementation of suitable standardisation approaches for this sector. This article presents the workshop background and rationale, presentation summaries, conclusions, and recommendations.

Abstract ISG15 is an interferon-stimulated ubiquitin-like protein (UBL) with multifaceted roles as a posttranslational modifier in ISG15 conjugation (ISGylation). However, the mechanistic consequences of ISGylation in cancer have not been fully elucidated, largely due to a lack of knowledge on the ISG15 target repertoire. Here, we identified SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, as a new target for ISGylation. SIRT1 ISGylation impairs the association of SIRT1 with its negative regulator, deleted in breast cancer 1 (DBC1), which unleashes SIRT1 from its inactive state and leads to an increase in its deacetylase activity. Importantly, SIRT1 ISGylation promoted lung cancer progression and limited lung cancer cell sensitivity to DNA damage-based therapeutics in vivo and in vitro models. The levels of ISG15 mRNA and protein were significantly higher in lung cancer tissues than in adjacent normal tissues. Accordingly, elevated expression of SIRT1 and ISG15 was associated with poor prognosis in lung cancer patients, a finding that could be translated for lung cancer patient stratification and disease outcome evaluation. Taken together, our findings provide a mechanistic understanding of the regulatory effect of SIRT1 ISGylation on tumor progression and therapeutic efficacy in lung cancer.

Background: Sperm quality and the number of sperm introduced into the uterus during artificial insemination (AI) are pivotal factors influencing pregnancy outcomes. However, there have been no reports on the relationship between sperm concentration at AI and sperm quality in Hanwoo cattle. In this study, we examined sperm quality and pregnancy rates after AI using sperm inseminated at different concentrations. Methods: We evaluated the motility, viability, and acrosomal membrane integrity of sperm at different concentrations (10, 15, 18, and 20 million sperm/straw) in 0.5-mL straws. Subsequently, we compared the pregnancy rates after AI with different sperm concentrations. Results: After freeze-thawing, sperm at the assessed concentrations showed similar viability and acrosomal membrane integrity. After AI, cattle in the 10 million group had significantly lower pregnancy rates compared to those in the 18 and 20 million groups. Conversely, there were no statistically significant variances observed between cattle in the 10 and 15 million groups. Conclusions: Sperm at concentrations of 10, 15, 18 and 20 million per straw exhibited comparable motility, viability, and acrosomal membrane integrity. However, a concentration of at least 18 million sperm per straw is required to achieve a consistent rate of pregnancy rate in Hanwoo cattle after AI.

IntroductionSchistosomiasis is a neglected tropical disease that puts over 200 million people at risk, and prevention options are sparse with no approved vaccine. Our vaccine candidate, SchistoShield®, is based on an approximately 87 kDa large subunit of calcium activated neutral protease - termed Sm-p80 - combined with a potent TLR4 agonist-based adjuvant. SchistoShield® has been shown to prevent disease throughout the parasitic life cycle - including egg, juvenile, and adult worm stages - in numerous animal models up to and including baboons. SchistoShield® has been shown safe in both preclinical toxicology studies in rabbits and in a Phase 1 clinical trial in the USA. A Phase 1b trial was initiated in 2023 in endemic regions of Africa, and to date no serious safety signals have been reported.MethodsIn preparation for large-scale Phase 2 clinical trials and eventual vaccine deployment, the Sm-p80 antigen production process has been transferred to a manufacturing organization, Quratis Corporation in South Korea, which specializes in preparation of vaccines for large-scale European and African trials. The process of scaling from our current production level of ~ 2000 vaccine doses, to a process that will generate more than 100 million doses has required multiple improvement steps in the process including fermentation, downstream purification of the protein antigen, lyophilization, and fill and finish.ResultsIn this study, we detail the large-scale production process of the SchistoShield® protein product by Quratis. In addition, an effort was made to analyze and compare the Quratis-made lot of Sm-p80, referred to as QTP-105, to the cGMP lot of Sm-p80 which is in use in human trials in the USA and Africa, referred to as Sm-p80 DP (made in USA). We show that QTP-105 demonstrates excellent potency, purity, identity, and endotoxin levels compared to our Phase 1 Sm-p80 DP and is suitable for use in Phase 2 studies and beyond.

Major countries around the world are leveraging information and communications technology (ICT), such as artificial intelligence, big data, cloud computing and cybersecurity, to strengthen their militaries. These technological advancements are driving the changes in weapon systems, strategies, and tactics. In 2021, the South Korean Ministry of National Defense introduced the concept of “military meta power” to describe the power generated in the cognitive military domain utilizing ICT. This concept is significant in that it differentiates between cognitive and physical military power, emphasizing the importance of the cognition-based power in future warfare. Additionally, the concept consolidates various cognitive military capabilities, including AI capability, cyber capability, space capability, and C4ISR (Command, Control, Communications, Computers, Intelligence, Surveillance, and Reconnaissance), into a unified ICT-generated power. This study aims to contribute to the literature on “military meta power” by providing a comprehensive overview of its characteristics, composition, and attributes. To achieve this objective, the research begins with an exploration of the philosophical insights on technology related to ICT, followed by a comprehensive review of the perspectives of existing academic papers. Finally, this study provides an in-depth analysis of various military strategies.

Abstract Trastuzumab is used to treat HER2-amplified metastatic gastric cancer; however, most patients become trastuzumab-resistant within a year. Knowledge of the mechanisms underlying trastuzumab resistance is required to overcome this limitation. Here, we aimed to elucidate this resistance mechanism using four trastuzumab-resistant (TR) cell lines and investigate the efficacy of HER2-targeted therapies to overcome treatment resistance. Each TR cell line had different phenotypic characteristics. Interestingly, HER2 expression remained as high as the parental cell lines in TR cell lines, suggesting that HER2-targeted agents were still useful. As expected, three tyrosine kinase inhibitors (lapatinib, neratinib, and tucatinib) and one antibody–drug conjugate (trastuzumab deruxtecan: T-DXd) exhibited good antitumor effects against TR cell lines. We further investigated the potential biological mechanism of T-DXd. When treated with trastuzumab or T-DXd, HER2 or its downstream signals were disrupted in parental cell lines, but not in TR cell lines. Moreover, T-DXd induced the expression of pH2A.X and cPARP and caused cell cycle arrest in the S or G2-M phase in TR cell lines. T-DXd showed promising antitumor activity in both parental and TR cell lines, suggesting that it is a potential candidate for overcoming trastuzumab resistance.

Background: Fluoroscopy-guided PTNB for fluoroscopy-identifiable lung lesions has been suggested as a useful method for the pathological diagnosis of lung lesions; however, it is lacking in accuracy and safety compared to CT-guided PTNB. Thus, we aimed to investigate the diagnostic accuracy and complications of fluoroscopy-guided percutaneous transthoracic needle biopsy (PTNB) with the aid of pre-procedural planning cone-beam computed tomography (CBCT) in order to take advantage of their respective strengths. Methods: A total of 255 fluoroscopy-guided PTNBs with the aid of planning CBCT were performed. Pre-procedural planning CBCT was conducted to calculate the shortest length from the skin puncture site to the margin of the target lesion for the needle trajectory. No intra-procedural CBCT was performed. The diagnostic performance of fluoroscopy-guided PTNB with the aid of planning CBCT was calculated. The prognostic factors for diagnostic failures and complications were evaluated using logistic regression analysis. Results: The accuracy, sensitivity, specificity, PPV, and NPV were 97.3%, 88.0%, 90.9%, 100%, and 62.5%, respectively. There were 29 diagnostic failures (11.8%), and the multivariable analysis showed that a longer lesion depth on CBCT and a shorter specimen length were each associated with diagnostic failure (p = 0.010 and 0.012, respectively). Complications occurred in 34 PTNBs (13.3%). The multivariable analysis showed that an increased total number of biopsies per lesion, a longer length of lung aeration via needle insertion, a smaller lesion size on CT imaging (≤20 mm), and the presence of an air bronchogram were associated with the occurrence of complications (p = 0.027, Conclusions: Excellent diagnostic accuracy was obtained by fluoroscopy-guided PTNB with the aid of planning CBCT. Compared to that of CT- or CBCT-guided PTNB, the procedure-related complication rate was acceptably low, but the radiation dose to patients could be potentially reduced.

Superovulation is a technique used to increase the number of oocytes released for fertilization. This study investigated the effects of short-term differences in concentrate feed intake on in vivo embryo production through superovulation in indigenous Korean (Hanwoo) cows. The cows were given fresh water and hay ad libitum and randomly divided into three groups (control (CON, n = 9): 2.0 kg/day (unchanged diet); low concentrate (LC, n = 10): 0 kg/day; and high concentrate (HC, n = 8): 4.0 kg/day) according to the amount of formula they were fed. This feeding treatment began seven days before the start of the hormonal treatment for superovulation. From the results, the LC group had the greatest weight change and the lowest body condition score at harvest, followed by the CON and HC groups (p < 0.05). The LC group had the highest number of harvesting embryos, followed by the HC and CON groups (p < 0.05). Estradiol, progesterone, glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, total protein, and blood urea nitrogen concentrations did not differ between the groups, except for a temporary increase in the HC group on day 0. These findings suggest that more embryos may be harvested when short-term changes in concentrate intake are made during superovulatory responses in Hanwoo cows.

Abstract Changes in dopamine and fronto-striato-thalamic (FST) circuit functional connectivity are prominent in schizophrenia. Dopamine is thought to underlie connectivity changes, but experimental evidence for this hypothesis is lacking. Previous studies examined the association in some of the connections using positron emission tomography (PET) and functional MRI (fMRI); however, PET has disadvantages in scanning patients, such as invasiveness. Excessive dopamine induces neuromelanin (NM) accumulation, and NM-MRI is suggested as a noninvasive proxy measure of dopamine function. We aimed to investigate the association between NM and FST circuit connectivity at the network level in patients with schizophrenia. We analysed substantia nigra NM-MRI and resting-state fMRI data from 29 schizophrenia patients and 63 age- and sex-matched healthy controls (HCs). We identified the FST subnetwork with abnormal connectivity found in schizophrenia patients compared to that of HCs and investigated the relationship between constituting connectivity and NM-MRI signal. We found a higher NM signal (t = −2.12, p = 0.037) and a hypoconnected FST subnetwork (FWER-corrected p = 0.014) in schizophrenia patients than in HCs. In the hypoconnected subnetwork of schizophrenia patients, lower left supplementary motor area-left caudate connectivity was associated with a higher NM signal (β = −0.38, p = 0.042). We demonstrated the association between NM and FST circuit connectivity. Considering that the NM-MRI signal reflects dopamine function, our results suggest that dopamine underlies changes in FST circuit connectivity, which supports the dopamine hypothesis. In addition, this study reveals implications for the future use of NM-MRI in investigations of the dopamine system.

Abstract Objective To understand the physician perspective on the barriers and facilitators of implementing nine different opioid risk mitigation strategies (RMS) when prescribing opioid medications. Methods We created and dispersed a cross-sectional online survey through the Qualtrics© data collection platform among a nationwide sample of physicians licensed to practice medicine in the United States who have prescribed an opioid medication within the past year. The responses were analyzed using a deductive thematic analysis approach based on the Consolidated Framework for Implementation Research (CFIR) to ensure a holistic approach to identifying the barriers and facilitators for each RMS assessed. In concordance with this method, the themes and codes for the thematic analysis were defined prior to the analysis. The five domains within the CFIR were used as themes and the 39 nested constructs were treated as the codes. Two members of the research team independently coded the transcripts and discussed points of disagreement until consensus was reached. All analyses were conducted in ATLAS.ti© V7. Results The completion rate for this survey was 85.1% with 273 participant responses eligible for analysis. Intercoder reliability was calculated to be 82%. Deductive thematic analysis yielded 2,077 descriptions of factors affecting implementation of the nine RMS. The most salient code across all RMS was Knowledge and Beliefs about the Intervention, which refers to individuals’ attitudes towards and value placed on the intervention. Patient Needs and Resources, a code referring to the extent to which patient needs are known and prioritized by the organization, also emerged as a salient code. The physicians agreed that the patient perspective on the issue is vital to the uptake of each of the RMS. Conclusions This deductive thematic analysis identified key points for actionable intervention across the nine RMS assessed and established the importance of patient concordance with physicians when deciding on a course of treatment.

Abstract Sarcopenia is a progressive loss of muscle mass and strength that is associated with increasing the risk of falls, musculoskeletal diseases, and chronic metabolic diseases. However, the animal models adopted to study sarcopenia face limitations since the functional tests conducted on human cannot be directly adapted to animals because the animals do not follow instructions. Moreover, current preclinical research tools for muscle function assessment, such as the rotarod, grip strength, and treadmill, have limitations, including low-intensity simple movements, evaluator subjectivity, and limited power indicators. Hence, in this study, we present a new jumping-power assessment tool in a preclinical rodent model to demonstrate muscle functions. To overcome the light weight and command issues in the rodent model, we developed an electrical stimulation-assisted jump power assessment device. Precisely, the device utilizes a load cell with a 0.1 g resolution and a 50 points/s data acquisition rate to capture the short period of the mouse jump. Additionally, interdigitated electrodes are used to electrically stimulate the mice and make them jump. While our primary focus in this article is the validation of the newly developed jump power assessment device, it is worth noting that this tool has several potential utilities. These include the phenotypic comparison of sarcopenia models, the exploration of muscle function reduction mechanisms, muscle function-related blood biomarkers, and the evaluation of drug intervention effects.

Offshore structures and ships can be progressively damaged due to repeated mass impacts induced by contacts with ships, ice floes, and dropped and/or floating other objects while in service. This paper aims to predict the residual deflection evolution of the marine structures under such impact repetitions. The side hull structures of the general ice-class vessels were selected for this study. The numerical simulations were performed to predict the deflection response of repeatedly impacted stiffened plates by using the software package Abaqus 6.13. For the simulations, the strain hardening of the relevant ice-class steel grade was adopted using the proposed constitutive equations, and the strain-rate hardening effects were taken into account by employing the existing formulations. The developed numerical model was substantiated against tests available in the open literature. Based on the validated model, a parametric study on various stiffened plates was performed. The evolution of the residual deflection of the repeatedly impacted plates with actual scantlings and various impact scenarios was investigated. A practical formula for the prediction of the residual deflection evolution of the plates under repeated mass impacts was proposed based on the regression analysis of the parametric study results. The reliability and accuracy of the proposed formula were confirmed through comparisons with numerical simulations and existing analytical formulations. It is expected that the proposed formula can be efficiently employed as a quick-hand tool for the reliable prediction of the residual deflection evolution incurred by repeated mass impacts.

Background: The elderly population is increasing rapidly worldwide. Muscle mass, usual walking speed (UWS), knee extension strength (KES), hand grip strength (HGS), peak expiratory flow (PEF), and depression is used for sarcopenia diagnosis. All four of these factors (KES, HGS, PEF, and depression) correlated with UWS and also to muscle mass. But, many studies have suggested that no correlation exists between muscle mass and UWS. Objects: This study aimed: 1) to investigate whether muscle mass reduction affected UWS, as mediated by KES, HGS, PEF and depression, and 2) to explored whether significant changes in these mediators varied by the body segment in which muscle mass evaluated in elderly female aged 65–80 years. Methods: A total of 100 female aged 65–80 years were surveyed. Muscle mass was measured by body segment (upper and lower segment), and KES, HGS, PEF, depression, and UWS were also assessed. Median analyses were progressed in IBM SPSS software (ver. 23.0, IBM Co.) using a downloaded INDIRECT macro. Results: The direct effect of the KES and PEF were significant, and the indirect effect of KES and PEF were not significant. Thus, KES and PEF served as full mediators of the effect of muscle mass on UWS. Regardless of bodily region, KES and PEF combined with muscle mass were significant mediators of UWS, with similar indirect effect sizes. Conclusion: KES and PEF are the only mediators regardless of body part. Therefore, mediating the KES and PEF may prevent sarcopenia progression in elderly female. Also, sarcopenia can be readily assessed by evaluating either the upper or lower body; it is not necessary to measure total muscle mass.

Corrosion damage to submarine pressure hulls is a crucial consideration during the structural design phase because it diminishes the structural strength of a submarine, reducing its operational depth and posing a severe risk to the life of the crew. This necessitates using a validated analytical method to estimate the residual strength and assess the safety of corrosion-affected pressure hulls. This paper presents an experimental and numerical investigation of the residual strength of corroded ring-stiffened cylinders, which are typical components of submarine pressure hulls, the main legs of semi-submersibles, and Floating Offshore Wind Turbine (FOWT) foundations. Four steel ring-stiffened cylinder models were fabricated: two remained intact, whereas the other two were artificially corroded by machining. Hydrostatic collapse tests were conducted in a pressure chamber. To evaluate the effect of initial shape imperfections caused by welding fabrication on the strength of the structure, the initial shape imperfections were measured using a three-dimensional coordinate measuring machine. The experimental results illustrate a significant reduction in the residual strengths of the two damaged models compared with those of the intact models. The collapse processes simulated using the Abaqus software package are presented, demonstrating a close agreement between the experimental results and numerical predictions.

ABSTRACT Potato virus Y (PVY) is one of the foremost plant viruses affecting potato plants and production. Many diagnostic and detection techniques are available to detect and prevent the spread of this virus. Serological analyses, such as enzyme-linked immunosorbent assay (ELISA), are widely used in laboratories as well as in the field. In addition, recently, serological methods using whole or recombinant antibodies have been developed. However, these antibodies are unstable under certain chemical conditions and can be easily degraded by exposure to enzymes. M13KO7, a derivative of bacteriophage M13, with a filamentous structure similar to PVY, was used for antibody screening. We found that PVY and “bald” M13KO7 had binding activity similar to that of antigen-antibody in ELISA analyses. The binding interactions between PVY and M13KO7 were highly specific. A new method for detecting PVY using ELISA analysis with M13KO7 was developed in this study. These results provide new insights into two virus-binding interactions and novel systems for the detection of plant viruses. IMPORTANCE In this study, we confirmed the binding of M13KO7 to Potato virus Y (PVY) using enzyme-linked immunosorbent assay. M13KO7 is a “bald” bacteriophage in which no recombinant antibody is displayed. M13KO7 is easy to propagate by using Escherichia coli, making this method more reasonable in economic perspective. Based on this study, we suggest that M13KO7 detection system has applicability as a novel biological tool for the detection of PVY

Metformin is a widely used drug for treatment of diabetes mellitus, due to its safety and efficacy. In addition to its role as an antidiabetic drug, numerous beneficial effects of metformin have enabled its use in various diseases. Considering the anti-androgenic, anti-angiogenic, anti-fibrotic and antioxidant properties of metformin, it may have the potential to improve chronic inflammatory skin diseases. However, further evidence is needed to confirm the efficacy of metformin in dermatological conditions, This review focuses on exploring the therapeutic targets of metformin in acne vulgaris, hidradenitis suppurativa and rosacea, by studying their pathogeneses.

Abstract Introduction This randomized, double-blind, placebo-controlled, phase 2a trial was conducted to evaluate the safety and immunogenicity of the ID93 + glucopyranosyl lipid adjuvant (GLA)-stable emulsion (SE) vaccine in human immunodeficiency virus (HIV)-negative, previously Bacillus Calmette–Guérin (BCG)-vaccinated, and QuantiFERON-TB-negative healthy adults in South Korea. Methods Adults (n = 107) with no signs or symptoms of tuberculosis were randomly assigned to receive three intramuscular injections of 2 μg ID93 + 5 μg GLA-SE, 10 μg ID93 + 5 μg GLA-SE, or 0.9% normal saline placebo on days 0, 28, and 56. For safety assessment, data on solicited adverse events (AEs), unsolicited AEs, serious AEs (SAEs), and special interest AEs were collected. Antigen-specific antibody responses were measured using serum enzyme-linked immunosorbent assay. T-cell immune responses were measured using enzyme-linked immunospot and intracellular cytokine staining. Results No SAEs, deaths, or AEs leading to treatment discontinuation were found. The solicited local and systemic AEs observed were consistent with those previously reported. Compared with adults administered with the placebo, those administered with three intramuscular vaccine injections exhibited significantly higher antigen-specific antibody levels and Type 1 T-helper cellular immune responses. Conclusion The ID93 + GLA-SE vaccine induced antigen-specific cellular and humoral immune responses, with an acceptable safety profile in previously healthy, BCG-vaccinated, Mycobacterium tuberculosis-uninfected adult healthcare workers. Trial Registration This clinical trial was retrospectively registered on 16 January 2019 at Clinicaltrials.gov (NCT03806686).

R&D strategies of companies with low and high technological levels are discussed based on the concept of technology convergence and divergence. However, empirically detecting enterprise technology convergence in the distribution of enterprise technology (total productivity increase) over time and identifying key change factors are challenging. This study used a novel statistical indicator that captures the internal technology distribution change with a single number to clearly measure the technology distribution peak as a change in critical bandwidth for enterprise technology convergence and presented it as evidence of each technology convergence or divergence. Furthermore, this study applied the quantitative technology convergence identification method. Technology convergence appeared from the separation of total corporate productivity distribution of 69 IT companies in Korea in 2019-2020 rather than in 2015-2016. Results indicated that when the total technological level was separated from the technology leading and technology catch-up, IT companies were found to be pursuing R&D strategies for technol ogy catch-up.

Abstract Transforming growth factor-β-activated kinase 1 (TAK1), which is highly expressed and aberrantly activated in triple-negative breast cancer (TNBC), plays a pivotal role in metastasis and progression. This makes it a potential therapeutic target for TNBC. Previously, we reported lectin galactoside-binding soluble 3 binding protein (LGALS3BP) as a negative regulator of TAK1 signaling in the inflammatory response and inflammation-associated cancer progression. However, the role of LGALS3BP and its molecular interaction with TAK1 in TNBC remain unclear. This study aimed to investigate the function and underlying mechanism of action of LGALS3BP in TNBC progression and determine the therapeutic potential of nanoparticle-mediated delivery of LGALS3BP in TNBC. We found that LGALS3BP overexpression suppressed the overall aggressive phenotype of TNBC cells in vitro and in vivo. LGALS3BP inhibited TNF-α-mediated gene expression of matrix metalloproteinase 9 (MMP9), which encodes a protein crucial for lung metastasis in TNBC patients. Mechanistically, LGALS3BP suppressed TNF-α-mediated activation of TAK1, a key kinase linking TNF-α stimulation and MMP9 expression in TNBC. Nanoparticle-mediated delivery enabled tumor-specific targeting and inhibited TAK1 phosphorylation and MMP9 expression in tumor tissues, suppressing primary tumor growth and lung metastasis in vivo. Our findings reveal a novel role of LGALS3BP in TNBC progression and demonstrate the therapeutic potential of nanoparticle-mediated delivery of LGALS3BP in TNBC.

Abstract Background Predicting the survival of cancer patients provides prognostic information and therapeutic guidance. However, improved prediction models are needed for use in diagnosis and treatment. Objective This study aimed to identify genomic prognostic biomarkers related to colon cancer (CC) based on computational data and to develop survival prediction models. Methods We performed machine‐learning (ML) analysis to screen pathogenic survival‐related driver genes related to patient prognosis by integrating copy number variation and gene expression data. Moreover, in silico system analysis was performed to clinically assess data from ML analysis, and we identified RABGAP1L, MYH9, and DRD4 as candidate genes. These three genes and tumor stages were used to generate survival prediction models. Moreover, the genes were validated by experimental and clinical analyses, and the theranostic application of the survival prediction models was assessed. Results RABGAP1L, MYH9, and DRD4 were identified as survival‐related candidate genes by ML and in silico system analysis. The survival prediction model using the expression of the three genes showed higher predictive performance when applied to predict the prognosis of CC patients. A series of functional analyses revealed that each knockdown of three genes reduced the protumor activity of CC cells. In particular, validation with an independent cohort of CC patients confirmed that the coexpression of MYH9 and DRD4 gene expression reflected poorer clinical outcomes in terms of overall survival and disease‐free survival. Conclusions Our survival prediction approach will contribute to providing information on patients and developing a therapeutic strategy for CC patients.

IntroductionTo investigate the effects of hepatic arterial infusion chemotherapy (HAIC) with or without systemic chemotherapy compared to systemic chemotherapy alone in patients with locally advanced hepatocellular carcinoma (HCC).MethodsFollowing a registered protocol (PROSPERO 2023 CRD42023386780 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023386780), a comprehensive search was performed using reputable databases and registries up to December 26, 2022, with no language, publication date, or status restrictions. Only randomized controlled trials (RCTs) investigating the effects of HAIC with or without systemic chemotherapy versus systemic therapy alone were included. The primary outcomes were overall survival (OS), progression-free survival (PFS), and adverse events. The secondary outcomes included the objective response rate (ORR) and disease control rate (DCR). A random-effects model was used, and the certainty of the evidence was rated using GRADE.ResultsSeven RCTs involving 1,010 patients were included. All trials utilized sorafenib as the comparator. Five trials (690 patients) compared HAIC plus sorafenib to sorafenib alone, while two trials (320 patients) compared HAIC to sorafenib. The results indicate that HAIC, with or without sorafenib, may increase OS, PFS, and ORR compared with sorafenib alone. HAIC may enhance DCR, but the evidence is very uncertain. Adverse events were comparable between HAIC plus sorafenib and sorafenib alone. However, adverse events might be decreased in HAIC alone.DiscussionHAIC with or without systemic chemotherapy may improve survival outcomes and response rates of patients with HCC. Since the current body of evidence is moderate to very low, more robust randomized trials are needed to confirm the efficacy of HAIC.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=386780, identifier CRD42023386780.

Background: Rosacea is a common chronic skin condition. To manage rosacea long-term and prevent further flare-ups, patients need to be aware of the disease and have sound knowledge of the condition. However, few related studies have been conducted on this subject. Objectives: The aim of this study was to identify rosacea awareness and knowledge among Korean rosacea patients and their means of gathering information on the disease. Methods: A prospective multicenter cross-sectional study recruited a total of 201 outpatients who were diagnosed with rosacea by a dermatologist. All were asked to complete a questionnaire asking about their demographic characteristics, rosacea awareness, and knowledge. Results: Among 201 rosacea patients, 146 (72.6%) were unaware of the disease before their diagnosis. The median number of questions the patients correctly answered was 6 of a total of 13 questions (46%) on rosacea knowledge, implying relatively shallow knowledge on rosacea. Better understanding of rosacea was negatively associated with age (odds ratio [OR] 0.965; 95% confidence interval [CI]: 0.941 – 0.989) and positively associated with a higher education level (OR = 2.896; 95% CI: 1.379–6.082). Individuals with rosacea felt that they were getting reliable information from doctors (n = 189, 94%), followed by the Internet (n = 38, 18.9%). Conclusion: Overall, rosacea awareness and knowledge among Korean rosacea patients were relatively low. Detailed education, especially targeting elderly patients and those with low education levels, is necessary for better disease outcomes.

Adaptive laboratory evolution (ALE) has long been used as the tool of choice for microbial engineering applications, ranging from the production of commodity chemicals to the innovation of complex phenotypes. With the advent of systems and synthetic biology, the ALE experimental design has become increasingly sophisticated. For instance, implementation of in silico metabolic model reconstruction and advanced synthetic biology tools have facilitated the effective coupling of desired traits to adaptive phenotypes. Furthermore, various multi-omic tools now enable in-depth analysis of cellular states, providing a comprehensive understanding of the biology of even the most genomically perturbed systems. Emerging machine learning approaches would assist in streamlining the interpretation of massive and multiplexed datasets and promoting our understanding of complexity in biology. This review covers some of the representative case studies among the 700 independent ALE studies reported to date, outlining key ideas, principles, and important mechanisms underlying ALE designs in bioproduction and synthetic cell engineering, with evidence from literatures to aid comprehension.

A novel displacement ventilation system (DVS) was designed using a four-way cassette fan coil unit (FCU) and air purifiers (APs) for supplying clean air. The proposed DVS in this study involved drawing indoor air through the FCU and diffusers installed in the ceiling, controlling air temperature using the FCU, and then discharging it back into the office through the APs placed on the floor. The comparative ventilation system considered was the typical mixing ventilation system (MVS) that intakes and exhausts indoor air using diffusers installed on the ceiling. The local mean age of air was used as an index to compare indoor air quality between DVS and MVS under winter heating conditions. It was found that the DVS was more effective in improving indoor air quality in winter than the MVS. Moreover, compared to the MVS, utilizing the DVS designed in this study resulted in the advantage of a much more uniform air temperature variation in the office space. Therefore, it is anticipated that modifying the structure of an indoor space with an FCU installed in the ceiling and APs on the floor to use the DVS designed in this study would greatly assist in enhancing indoor air quality.

Background The current conventional drug susceptibility test (DST) for Mycobacterium tuberculosis (Mtb) takes several weeks of incubation to obtain results. As a rapid method, molecular DST requires only a few days to get the results but does not fully cover the phenotypic resistance. A new rapid method based on the ability of viable Mtb bacilli to hydrolyze fluorescein diacetate to free fluorescein with detection of fluorescent mycobacteria by flow cytometric analysis, was recently developed. Methods To evaluate this cytometric method, we tested 39 clinical isolates which were susceptible or resistant to isoniazid (INH) or rifampin (RIF), or ethambutol (EMB) by phenotypic or molecular DST methods and compared the results. Results The susceptibility was determined by measuring the viability rate of Mtb and all the isolates which were tested with INH, RIF, and EMB showed susceptibility results concordant with those by the phenotypic solid and liquid media methods. The isolates having no mutations in the molecular DST but resistance in the conventional phenotypic DST were also resistant in this cytometric method. These results suggest that the flow cytometric DST method is faster than conventional agar phenotypic DST and may complement the results of molecular DST. Conclusion In conclusion, the cytometric method could provide quick and more accurate information that would help clinicians to choose more effective drugs.

Abstract Background The mainstay of endometrial cancer treatment is surgical resection of tumors and postoperative adjuvant treatment is recommended if necessary. However, there is no consensus on the management of unresectable metastatic endometrial cancer. This study aimed to assess the feasibility and effectiveness of neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS) in unresectable, metastatic endometrial cancer. Methods From the endometrial cancer cohorts of four institutions in Korea, we identified patients with International Federation of Gynecology and Obstetrics stages IIIC–IVB endometrial cancer who received NAC-IDS between January 2008 and December 2020. Through a medical record review, we collected patients’ clinicopathological data. Progression-free survival (PFS), overall survival (OS), and the factors affecting survival outcomes were analyzed. Results Overall, 32 patients were included with endometrioid (n = 18), serous (n = 5), carcinosarcoma (n = 6), and other histological types (n = 3). Among them, 28 (87.5%) patients had stage IVB disease. The most common neoadjuvant chemotherapy (NAC) regimen was paclitaxel-carboplatin (n = 25, 78.1%), which was administered for a median of six cycles. While 26 (81.3%) patients showed an objective response, two (6.3%) progressed despite NAC. At the time of interval debulking surgery (IDS), 23 (71.9%) patients achieved complete cytoreduction. During 31.0 months of the median follow-up, there were 23 recurrences and 11 deaths, corresponding to a median PFS of 19.7 months and a 3-year OS rate of 69.7%. In multivariate analyses, non-endometrioid histology and residual tumor after IDS were identified as independent poor prognostic factors for PFS (adjusted hazard ratio [HR], 7.322; P

The Custom Alveolar Ridge Splitting (CARS) technique was recently reported as a less-invasive treatment option for augmentation of the maxillary anterior area in cases where alveolar width deficiency exists due to bone resorption and remodeling. This technique creates an intraosseous defect to improve success when horizontal ridge augmentation is attempted. The purpose of the present case report was to demonstrate implant placement in an atrophic posterior mandibular site using the CARS technique. This technique was used in the mandibular right second premolar area, followed by placement of a single implant. The restored implant showed stable soft and hard tissue outcomes at 6 months postloading. [ABSTRACT FROM AUTHOR]

IntroductionAlthough most cases of myocardial bridge (MB) are clinically benign, sometimes it can be one of potential threats of myocardial infarction (MI) and life-threatening arrhythmia. In the present study, we present a case of ST-segment elevation MI caused by MB and concomitant vasospasm.Case PresentationA 52-year-old woman was brought to our tertiary hospital due to resuscitated cardiac arrest. Because the 12-lead electrocardiogram indicated ST-segment elevation MI, coronary angiogram was promptly commenced, which showed near-total occlusion at the middle portion of left anterior descending coronary artery (LAD). After intracoronary nitroglycerin administration, this occlusion was dramatically relieved, however, systolic compression at this site remained, indicative of myocardial bridge (MB). Intravascular ultrasound also showed eccentric compression with a “half-moon” sign, which is consistent with MB. Coronary computed tomography also showed a bridged coronary segment surrounded by myocardium at the middle portion of LAD. To assess the severity and extent of myocardial damages and ischemia, myocardial single photon emission computed tomography (SPECT) was additionally conducted, showing a moderate fixed perfusion defect around the cardiac apex, suggesting MI. After receiving optimal medical therapy, the patient's clinical symptoms and signs were improved then the patient was discharged from the hospital successfully and uneventfully.ConclusionWe demonstrated a case of MB-induced ST-segment elevation MI which was confirmed with its perfusion defects via myocardial perfusion SPECT. There have been proposed a number of diagnostic modalities to examine its anatomic and physiologic significance. Among them, myocardial perfusion SPECT can be available as one of useful modalities to evaluate the severity and extent of myocardial ischemia in patients with MB.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with bimodal incidence peaks in early childhood and middle-aged and older adults. Few studies have focused on the risk of dementia in AD. The aims of this study were to analyse the incidence, and risk factors for dementia in patients with AD. This nationwide population-based retrospective cohort study enrolled 38,391 adults ≥ 40 years of age with AD and 2,643,602 controls without AD from the Korean National Health Insurance System (NHIS) database from 2009 to 2016. The cumulative incidence probability of all-cause dementia, Alzheimer’s disease, or vascular dementia at 8 years was 50, 39, and 7 per 1,000 person-years in patients with AD, respectively. The adjusted risks of all-cause dementia (hazard ratio (HR), 1.072; 95% confidence interval (95% CI) 1.026–1.120), and Alzheimer’s disease (HR 1.051; 95% CI 1.000–1.104) were increased in patients with AD. The effect of AD on the development of all-cause dementia and Alzheimer’s dementia varied according to age and diabetes mellitus (all p for interaction,

OBJECTIVES Elevated C-reactive protein (CRP) levels are associated with an increased risk for colorectal cancer (CRC), as well as a poor prognosis, but it remains unclear whether these associations are causal. This study examined the potential causality between CRP levels and CRC survival using 2-sample Mendelian randomization (MR). METHODS From the Korean Genome and Epidemiology Study, a genome-wide association study (n=59,605), 7 single-nucleotide polymorphisms (SNPs) related to log2-transformed CRP levels were extracted as instrumental variables for CRP levels. The associations between the genetically predicted CRP and CRC-specific and overall mortality among CRC patients (n=6,460) were evaluated by Aalen’s additive hazard model. The sensitivity analysis excluded a SNP related to the blood lipid profile. RESULTS During a median of 8.5 years of follow-up, among 6,460 CRC patients, 2,676 (41.4%) CRC patients died from all causes and 1,622 (25.1%) died from CRC. Genetically predicted CRP levels were not significantly associated with overall or CRC-specific mortality in CRC patients. The hazard difference per 1,000 person-years for overall and CRC-specific mortality per 2-fold increase in CRP levels was -2.92 (95% confidence interval [CI], -14.05 to 8.21) and -0.76 (95% CI, -9.61 to 8.08), respectively. These associations were consistent in a subgroup analysis according to metastasis and a sensitivity analysis excluding possible pleiotropic SNPs. CONCLUSIONS Our findings do not support a causal role for genetically predisposed CRP levels in CRC survival.

Apple (Malus domestica (Suckow) Borkh., 1803) is economically important horticultural fruit crop in the world. In this study, the complete chloroplast genome of Korean apple cultivar ‘Kamhong’ was characterized through the de novo assembly of Illumina sequencing data. The chloroplast genome is a circular molecule of 161,069 bp length with 36.55% GC content and has a total of 112 genes including 78 protein-coding genes, 30 transfer RNA genes, and 4 ribosomal RNA genes. Phylogenetic analysis with protein-coding sequences of chloroplast genome revealed that ‘Kamhong’ was closely grouped with M. domestica cultivars reported in China. The genomic data generated in this study can extend a molecular basis for phylogenetic relationships of Korean cultivar ‘Kamhong’ with other M. domestica cultivars bred in other countries.

Background/Aims Despite the increasing need for geriatric assessment prior to chemotherapy, the method for this assessment remains inadequate for older cancer patients. We aimed to propose a simple assessment method to predict the performance of adjuvant chemotherapy in older patients after colon cancer surgery. Methods This prospective study included patients over 65 years of age who were scheduled for adjuvant chemotherapy after colon cancer surgery. Before initiating chemotherapy, their functional status was assessed on the basis of activities of daily living (ADL)/instrumental activities of daily living (IADL). These parameters were analyzed with clinical characteristics and the patterns of adjuvant chemotherapy. The focus was on the completion rate of adjuvant chemotherapy. Results A total of 89 patients with a median age of 72 years were analyzed. Among them, 54 (61%) were non-impaired and 35 (39%) were impaired regarding their ADL/IADL classification. Low body mass index and impairment of ADL/IADLs were significantly associated with chemotherapy interruption. Among toxicities, fatigue and hand-foot syndrome were independent prognostic factors for chemotherapy interruption. Impairments of ADL/IADL were significantly associated with fatigue regardless of age. Based on age and ADL/IADL stratification, younger patients (≤ 72 years) and/or those who were ADL/IADL non-impaired were significantly more likely to complete adjuvant chemotherapy than older patients (> 72 years) and ADL/IADL impaired patients (p = 0.038). This was regardless of the chemotherapy regimen. Conclusions Functional assessment using ADL/IADL is a convenient method to predict chemotherapy toxicity and performance. These results suggested that routine screening for ADL/IADLs could guide appropriate patient selection for the completion of adjuvant chemotherapy and predict expected outcomes.

Direct and real-time observation of the excess holes in an element-specific and energylevel-specific manner is a challenging task. Here the authors present a complete hole dynamics of photo-excited anatase TiO2 with 100 femto-second resolution.

Purpose This study aimed to compare the clinical outcomes of laparoscopic appendectomy (LA) according to the method of appendiceal stump closure. Methods Patients who underwent LA for appendicitis between 2010 and 2020 were retrospectively reviewed. Patients were classified into locking polymeric clip (LPC) and loop ligature (LL) groups. Clinical outcomes were compared between the groups. Results LPC and LL were used in 188 (56.6%) and 144 patients (43.4%), respectively for appendiceal stump closure. No significant differences were observed in sex, age, comorbidities, and the severity of appendicitis between the groups. The median operative time was shorter in the LPC group than in the LL group (64.5 minutes vs. 71.5 minutes, P=0.027). The median hospital stay was longer in the LL group than in the LPC group (4 days vs. 3 days, P=0.020). Postoperative incidences of intraabdominal abscess and ileus were higher in the LL group than in the LPC group (4.2% vs. 1.1%, P=0.082 and 2.8% vs. 0%, P=0.035; respectively). The readmission rate was higher in the LL group than that in the LPC group (6.3% vs. 1.1%, P=0.012). Conclusion Using LPC for appendiceal stump closure during LA for appendicitis was associated with lower postoperative complication rate, shorter operative time, and shorter hospital stay compared to the use of LL. Operative time above 60 minutes and the use of LL were identified as independent risk factors for postoperative complications in LA. Therefore, LPC could be considered a more favorable closure method than LL during LA for appendicitis.