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This exploratory study evaluated the effects of self-regulated strategy development (SRSD) on students' written expression when asked to solve a word problem and explain reasoning. A secondary question evaluated potential for differential effects based on determination of having mathematics difficulty (MD). We implemented a quasi-experimental design with 163 students with and without MD in grade 4. Results indicated that students in the treatment group (n = 83) significantly outperformed students in the comparison group (n = 80) on measures of mathematical writing involving subtraction and division word problems. For the subtraction problems, students in the treatment group improved their overall written expression of mathematics scores (g = 0.688), yielding a medium effect. The intervention differentially benefited students without MD. Our findings call for greater integration of systematic writing opportunities in mathematics and highlight the importance of explicitly teaching students how to approach the written expression of their mathematical reasoning.

To enable machines to understand human-centric images and videos, they need the capability to detect human–object interactions. This capability has been studied using various approaches, but previous research has mainly focused only on recognition accuracy using widely used open datasets. Given the need for advanced machine-learning systems that provide spatial analysis and services, the recognition model should be robust to various changes, have high extensibility, and provide sufficient recognition speed even with minimal computational overhead. Therefore, we propose a novel method that combines the skeletal method with object detection to accurately predict a set of $ \langle $ human, verb, object $ \rangle $ triplets in a video frame considering the robustness, extensibility, and lightweight of the model. Training a model with similar perceptual elements to those of humans produces sufficient accuracy for advanced social systems, even with only a small training dataset. The proposed model is trained using only the coordinates of the object and human landmarks, making it robust to various situations and lightweight compared with deep-learning methods. In the experiment, a scenario in which a human is working on a desk is simulated and an algorithm is trained on object-specific interactions. The accuracy of the proposed model was evaluated using various types of datasets.

Background The P1 method in prosthetic breast reconstruction has the advantage of preventing rippling and ensuring a smooth upper pole contour. This study presents our experience with using an ultrasonic dissection device instead of a monopolar electrocautery device for the P1 method. Methods Patients who underwent prepectoral breast reconstruction at our institution between June and September 2021 were retrospectively reviewed. Among the 39 breasts analyzed, 17 underwent the P1 procedure using an ultrasonic dissection device for the superior slip of the pectoralis major muscle, while 22 underwent P0 prepectoral breast reconstruction. We compared surgical outcomes, including operative time, presence of rippling, capsular contracture, and animation deformities, and complications such as seroma, hematoma, and mastectomy skin flap necrosis. Results Patient demographics were comparable between the groups, except for chemotherapy exposure. Rippling occurred more frequently in the P0 group (36.4% vs. 23.5%); however, capsular contracture was absent in the P1 group. Despite these observations, the differences lacked statistical significance. The average operative time was longer in the P1 group than in the P0 group (104.35 minutes vs. 90.05 minutes), although this difference was not statistically significant (P=0.095). There were no instances of postoperative hematoma, infection, implant exchange, animation deformity, or implant explantation in either group. Conclusions Using an ultrasonic energy device for additional dissection in the P1 method was non-inferior in terms of complications such as bleeding, infection, or animation deformity. The ultrasonic device can facilitate safe and effective dissection when elevating the superior pectoralis muscle slip, despite requiring additional operative time.

The management of chronic kidney disease (CKD) includes nutritional interventions aimed at slowing disease progression and mitigating complications. This review examines various dietary approaches for CKD treatment, focusing on carbohydrate intake modulation, ketogenic diets, and plant-based diets. Standard guidelines recommend carbohydrate intake within 45% to 65% of total calories, but there is growing interest in reducing carbohydrate consumption to preserve kidney function. Low-carbohydrate diets (

As computing systems become increasingly larger, high-performance comput-ing (HPC) is gaining importance. In particular, as hyperscale artificial intelli-gence (AI) applications, such as large language models emerge, HPC has become important even in the field of AI. Important operations in hyperscale AI and HPC are mainly linear algebraic operations based on tensors. An AB21 supercomputing AI processor has been proposed to accelerate such applica-tions. This study proposes a XEM accelerator to accelerate linear algebraic operations in an AB21 processor effectively. The XEM accelerator has outer product-based parallel floating-point units that can efficiently process tensor operations. We provide hardware details of the XEM architecture and intro-duce new instructions for controlling the XEM accelerator. Additionally, hard-ware characteristic analyses based on chip fabrication and simulator-based functional verification are conducted. In the future, the performance and func-tionalities of the XEM accelerator will be verified using an AB21 processor.

Abstract Cyclic guanosine-adenosine monophosphate synthase (cGAS) is a key cytosolic DNA sensor that plays a pivotal role in the innate immune response. Although a decade of research on the cGAS has advanced our understanding of inflammasome formation, cytokine production, and signaling pathways, the role of cGAS in the nucleus remains unclear. In this study, we found that the nuclear localization of endogenous and stably expressed cGAS differed from transiently expressed cGAS, which mainly localized in the cytosol. In the nucleus, cGAS is tightly bound to chromatin DNA. The chromatin DNA binding of cGAS was dependent on RSK2. Our molecular mechanism study indicated that the N-lobe of RSK2 harboring 1–323 interacted with the NTase domain of cGAS harboring residues 213–330. This interaction increased RSK2-induced cGAS phosphorylation at Ser120 and Thr130, resulting in the tightly binding of cGAS to chromatin. Importantly, epidermal growth factor (EGF)-induced cell transformation and anchorage-independent colony growth showed an increase in growth factors, such as EGF or bFGF, in cGAS stable expression compared to mock expression. Notably, the cGAS-S120A/T130A mutant abolished the increasing effect of cell transformation of JB6 Cl41 cells and colony growth of SK-MEL-2 malignant melanoma cells. The results suggested that cGAS’s chromatin DNA binding, which is indispensable to RSK2-dependent phosphorylation of cGAS at Ser120/Thr130, provides the first clue to how cGAS may participate in chromatin remodeling in the nucleus.

Abstract This study aimed to explore the clinical applicability of the shade-matching function in intraoral scanners. This study measured the tooth colors of maxillary anterior dentitions of 83 adults using visual matching, a spectrophotometer, and a scanner according to two color systems: VITA Classical (VC) and VITA 3D-Master (V3D). Agreement between each method was assessed by weighted Cohen’s kappa coefficient (K W , α = 0.05). For V3D, the overall agreement between the scanner and spectrophotometer (K W = 0.498) was higher than that between the scanner and visual matching (K W = 0.473). Similarly, the agreement between the scanner and spectrophotometer (K W = 0.283) was higher than that between a scanner and visual matching (K W = 0.140) for VC. Regarding tooth position, the highest agreement between the scanner and spectrophotometer was observed on the right central incisor (K W = 0.542) for V3D. Tooth color measurement with a scanner was comparable to that with a spectrophotometer, especially on the central incisors when using the VITA 3D-Master system. A scanner could serve as an alternative to a spectrophotometer for shade selection. However, color matching should still be visually verified.

Abstract Background Toothbrushing is the most commonly used method to physically remove dental plaque. However, there are many areas of the mouth that are difficult to reach with a toothbrush. The type of toothbrush is a critical factor influencing the effectiveness of oral care. The purpose of the study was to evaluate a toothbrush with a thin head, slender-neck and super-tapered bristles to target hard-to-reach areas in the oral cavity for reducing dental plaque and gingivitis. Methods This crossover study included 58 adults aged 20 years and older. All participants were randomly assigned to use test and control toothbrushes (the latter had a normal head and round bristles) for two 4-week phases. Participants brushed their teeth twice daily in their habitual manner. At the start and end of each phase the Silness-Lӧe plaque index (PI), Lӧe -Silness gingival index (GI) and bleeding-on-probing index (BOP) were assessed and performed plaque fluorescence tests using quantitative light-induced fluorescence technology. Results After using the test toothbrush, PI, GI and BOP decreased by 25%, 30% and 48%, respectively (P

Abstract Aims This study evaluated how well serial pulse pressure (PP) and PP adjusted by the vasoactive inotropic score (VIS) predicted venoarterial extracorporeal membrane oxygenation (VA‐ECMO) weaning success and clinical outcomes in acute myocardial infarction complicated by cardiogenic shock (AMI‐CS) patients. Methods and results A total of 213 patients with AMI‐CS who received VA‐ECMO between January 2010 and August 2021 were enrolled in the institutional ECMO registry. Serial PP and VIS were measured immediately, 12, 24, and 48 h after VA‐ECMO insertion. PP adjusted by VIS was defined as PP/√VIS. The primary outcome was successful VA‐ECMO weaning. Successful weaning from VA‐ECMO was observed in 151 patients (70.9%). Immediately after VA‐ECMO insertion, PP [successful vs. failed weaning, 26.0 (15.5–46.0) vs. 21.0 (12.5–33.0), P = 0.386] and PP/√VIS [11.1 (5.1–25.0) vs. 6.0 (3.1–14.2), P = 0.118] did not differ between the successful and failed weaning groups. Serial PP and PP adjusted by VIS at 12, 24, and 48 h after VA‐ECMO insertion were significantly higher in patients with successful weaning than those with failed weaning [successful vs. failed weaning, 24.0 (4.0–38.0) vs. 12.5 (6.0–25.5), P = 0.007 for 12 h PP, and 10.1 (5.7–22.0) vs. 2.9 (1.7–5.9), P 7). Conclusions PP adjusted by VIS taken 12 h following VA‐ECMO initiation can predict weaning from VA‐ECMO more successfully than PP alone, and its low value was associated with a higher risk of mortality in AMI‐CS patients.

The current study investigated the effectiveness of an intensive writing intervention focusing on mathematical reasoning through written expression. A group pretest--intervention--posttest comparison experimental design was used to implement a 12-lesson intervention, delivered through a combination of Google Classroom and in-person classroom teacher support, to fifth-grade students with specific learning disabilities (n = 19). Although underpowered, our results indicated the intensive writing intervention led to all students in the intervention group (n = 11) significantly outperforming the students in the control group (n = 8) on subtraction and division word problems requiring an explanation of their solution in written form. Additionally, student treatment interviews revealed the strategy was both enjoyable and helpful in solving and explaining their word problem solutions and the teacher provided insight into potential additional scaffolds to support the most intensive students. Lessons learned and implications for research and practice are presented.

Abstract Strabismus is prevalent among preterm infants of low gestational age and birth weight in Southeast Asian countries, with intermittent exotropia (IXT) being the most common type in South Korea. In this retrospective, cross-sectional study, we investigated the differences between full-term and premature infants with IXT. IXT patients with available childbirth history were divided into two groups: preterm vs. full-term and low birth weight (LBW) vs. normal birth weight (NBW). Parameters related to exotropia including parental heredity, surgical history, and treatment options were investigated. In univariate regression for gestational age, a result of ≥ 100 s in the Titmus test was 1.352 times more frequent in preterm than in full-term infants. When birth weight was considered instead, a result of ≥ 100 s in the Titmus test was 1.412 times more frequent in the LBW compared to the NBW group. In multivariate regression for birth weight, the frequency of a result of ≥ 100 s in the Titmus test for the LBW group was 2.032 times higher than that for the NBW group. It is particularly important to examine stereopsis in preterm and LBW patients affected by IXT to ensure timely surgical planning and avoid potential recurrence after surgery.

Abstract Astronauts wear liquid perfused garments inside their outer spacesuits for regulating body temperature. The present study explored relationships between local heat production from the upper arm and body morphology while wearing liquid perfused sleeve. Heat extraction from the upper arm of 19 subjects (8 males and 11 females) during three different exercise modes (running at 6–8 km∙h−1, cycling at 40–55 W, and arm ergometer at 10–20 W) and rest has been investigated. The total body fat (27.5 ± 7.2%), body mass index (24.4 ± 2.7 kg·m−2), arm surface area (589 ± 90 cm2), and arm volume (1300 ± 300 mL) were considered as covariates. Subjects wore a liquid perfused sleeve over the upper arm (left) with the water inlet temperature of 24.0 ± 0.3 °C and the heat extraction was calculated using the water flow rate and temperature differences. Heat extraction from the upper arm showed no significant differences among the three exercises. During cycling, there was a negative relationship between heat extraction and total body fat (r = − 0.527, P

Although percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) has been increasing in recent years, CTO PCI is still one of the most challenging procedures with relatively higher rates of procedural complications and adverse clinical events after PCI. Due to the innate limitations of invasive coronary angiography, intravascular imaging (IVI) has been used as an adjunctive tool to complement PCI, especially in complex coronary artery disease. Considering the complexity of CTO lesions, the role of IVI is particularly important in CTO intervention. IVI has been a useful adjunctive tool in every step of CTO PCI including assisted wire crossing, confirmation of wire location within CTO segment, and stent optimization. The meticulous use of IVI has been one of the greatest contributors to recent progress of CTO PCI. Nevertheless, studies evaluating the role of IVI during CTO PCI are limited. The current review provides a comprehensive overview of the mechanistic advantages of IVI in CTO PCI, summarizes previous studies and trials, and presents future perspective of IVI in CTO PCI.

Abstract The SARS-CoV-2 pandemic has had an unprecedented impact on global public health and the economy. Although vaccines and antivirals have provided effective protection and treatment, the development of new small molecule-based antiviral candidates is imperative to improve clinical outcomes against SARS-CoV-2. In this study, we identified UNI418, a dual PIKfyve and PIP5K1C inhibitor, as a new chemical agent that inhibits SARS-CoV-2 entry into host cells. UNI418 inhibited the proteolytic activation of cathepsins, which is regulated by PIKfyve, resulting in the inhibition of cathepsin L-dependent proteolytic cleavage of the SARS-CoV-2 spike protein into its mature form, a critical step for viral endosomal escape. We also demonstrated that UNI418 prevented ACE2-mediated endocytosis of the virus via PIP5K1C inhibition. Our results identified PIKfyve and PIP5K1C as potential antiviral targets and UNI418 as a putative therapeutic compound against SARS-CoV-2.

Abstract We investigated the long-term patterns and effects of transfusion on the clinical outcome of patients undergoing percutaneous coronary intervention (PCI) using a nationwide registry. Five-year clinical outcome of all Koreans undergoing PCI using stent in year 2011 (n = 48,786) was investigated. Primary outcome was the incidence density of transfusion. The association of transfusion with major adverse clinical event (MACE) consisting all-cause death, revascularization, critically ill cardiovascular status, or stroke was assessed after adjusting the propensity of each patient for transfusion. The 5-year incidence density of transfusion was 4.74 (95% confidence interval [CI] 4.70–4.79) per 100 person-year. Patients who received transfusion were older and had higher frequency of clinical risk factors (p

Using the intermediate frequency (IF) substitution method, this study establishes a low-frequency attenuation measurement standard operating in the 9 kHz to 10 MHz frequency range. We designed and fabricated a low-frequency attenuation measuring instrument using a mixer that converts the input radio frequency signal into an output IF of 1 kHz. When varying the attenuation of a variable attenuator under test, an attenuation of up to 100 dB was measured. The IF output of the mixer was measured using a spectrum analyzer as the receiver. The receiver’s performance was evaluated using an inductive voltage divider whose measurement capability is traceable to the electrical measurement standard. The measurement uncertainty, which accounts for uncertainty sources such as the performance of the receiver, mismatch, and mixer nonlinearity, was evaluated to be 0.005 dB to 0.058 dB (k = 2) in the attenuation range of 10 dB to 100 dB.

Abstract Background Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are found in 1% of gliomas across children and adults. TRK inhibitors are promising therapeutic agents for NTRK-fused gliomas because they are tissue agnostic and cross the blood–brain barrier (BBB). Methods We investigated twelve NGS-verified NTRK-fused gliomas from a single institute, Seoul National University Hospital. Results The patient cohort included six children (aged 1–15 years) and six adults (aged 27–72 years). NTRK2 fusions were found in ten cerebral diffuse low-grade and high-grade gliomas (DLGGs and DHGGs, respectively), and NTRK1 fusions were found in one cerebral desmoplastic infantile ganglioglioma and one spinal DHGG. In this series, the fusion partners of NTRK2 were HOOK3, KIF5A, GKAP1, LHFPL3, SLMAP, ZBTB43, SPECC1L, FKBP15, KANK1, and BCR, while the NTRK1 fusion partners were TPR and TPM3. DLGGs tended to harbour only an NTRK fusion, while DHGGs exhibited further genetic alterations, such as TERT promoter/TP53/PTEN mutation, CDKN2A/2B homozygous deletion, PDGFRA/KIT/MDM4/AKT3 amplification, or multiple chromosomal copy number aberrations. Four patients received adjuvant TRK inhibitor therapy (larotrectinib, repotrectinib, or entrectinib), among which three also received chemotherapy (n = 2) or proton therapy (n = 1). The treatment outcomes for patients receiving TRK inhibitors varied: one child who received larotrectinib for residual DLGG maintained stable disease. In contrast, another child with DHGG in the spinal cord experienced multiple instances of tumour recurrence. Despite treatment with larotrectinib, ultimately, the child died as a result of tumour progression. An adult patient with glioblastoma (GBM) treated with entrectinib also experienced tumour progression and eventually died. However, there was a successful outcome for a paediatric patient with DHGG who, after a second gross total tumour removal followed by repotrectinib treatment, showed no evidence of disease. This patient had previously experienced relapse after the initial surgery and underwent autologous peripheral blood stem cell therapy with carboplatin/thiotepa and proton therapy. Conclusions Our study clarifies the distinct differences in the pathology and TRK inhibitor response between LGG and HGG with NTRK fusions.

Background/Aims Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. Methods This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. Results This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P

African swine fever (ASF), a contagious and lethal haemorrhagic disease of domestic pigs and wild boars, poses a significant threat to the global pig industry. Although experimental vaccine candidates derived from naturally attenuated, genetically engineered, or cell culture-adapted ASF virus have been tested, no commercial vaccine is accepted globally. We developed a safe and effective cell-adapted live attenuated vaccine candidate (ASFV-MEC-01) by serial passage of a field isolate in CA-CAS-01-A cells. ASFV-MEC-01, isolated via repeated plaque purification using next-generation sequencing analysis, was obtained at passage 18 and showed significant attenuation in 4- and 6-week-old pigs. ASFV-MEC-01 conferred 100% protection against challenge with lethal parental ASFV, which correlated with high ASFV-specific humoral and cellular immune responses. Additionally, ASFV-MEC-01 was not detected in blood until 28 days post-inoculation. Global transcriptome analysis showed that ASFV-MEC-01 lacking 12 genes triggered stronger innate antiviral responses than the parental virus, as exemplified by high levels of mRNA encoding interferon regulatory and inflammatory genes in PAM cells. Ectopic expression of most deleted genes increased replication of DNA viruses by suppressing production of interferons and pro-inflammatory cytokines. Among the genes deleted from ASFV-MEC-01, MGF100-1R interacted specifically with the scaffold dimerization domain of TBK1, thereby preventing TBK1 dimerization and impairing TBK1-mediated type I IFN and NF-κB signalling. These results suggest that attenuation of ASFV-MEC-01 may be mediated by induction of stronger type I IFN and NF-κB signalling within the host innate immune system. Thus, ASFV-MEC-01 could be a safe and effective live attenuated ASFV vaccine candidate with commercial potential.

Background: Survival rates following percutaneous coronary intervention (PCI) show variability across studies, particularly regarding sex-specific outcomes. Relative survival analysis, which considers survival patterns in sex- and age-matched general populations, could help explain this variability. Methods: In a 2011 nationwide South Korean PCI cohort study with 48,783 patients, all-cause death was assessed as the primary outcome over 5 years. Observed and relative survival rates at 5 years conditional on surviving 0 days, 30 days, 1 year, and 2 years were assessed. Sex-specific differences in clinical characteristics were adjusted using propensity score-matching. Results: In the unadjusted analyses, 15,710 females had more cardiovascular risk factors than 33,073 males. Both observed survival (HR 1.28; 95% CI [1.22–1.34]) and relative survival (HR 1.21; 95% CI [1.16–1.27]) were lower in females than males (all p

Early-life experiences play a crucial role in the development of the fronto-limbic regions, influencing both macro- and microstructural changes in the brain. These alterations profoundly impact cognitive, social-emotional functions. Recently, early limbic structural alterations have been associated with numerous neurological and psychiatric morbidities. Although identifying normative developmental trajectories is essential for determining brain alterations, only a few studies have focused on examining the normative trajectories in the fronto-limbic regions during preschool-aged children. The aim of this study was to investigate the structural-developmental trajectory of the fronto-limbic regions using the cortical thickness, volume, and subcortical volume in 57 healthy and typical preschool-aged children between 1 and 5 years and examined the early lateralization patterns during the development of the fronto-limbic regions. Regarding brain lateralization, remarkable asymmetry was detected in the volume of thalamus and the cortical regions excluding the lateral orbitofrontal cortex in the fronto-limbic regions. This study of preschool-aged children may fill the knowledge gaps regarding the developmental patterns and hemispheric asymmetries of the fronto-limbic regions between newborns and adolescents.

Study region: The Juam Dam area in Suncheon, Jeollanam-do, South Korea Study focus: This study aims to analyze drought propagation characteristics using time-lagged correlation analysis based on daily drought index, determining the lag time from meteorological drought to propagation into hydrological drought. The target period for correlation analysis is the onset date of the dry spell preceding the occurrence of hydrological drought and the termination date of the dry spell following the termination of the drought for each drought event. The Standardized Precipitation Index (SPI) at various time-scales for meteorological drought and the Standardized Reservoir Supply Index (SRSI) for hydrological drought were applied. New hydrological insights for the region: This study presents the objectivity and accuracy of drought onset and termination date for drought propagation analysis through daily lagged correlation analysis. Through ROC analysis, SPI90, SPI180, and SPI365 are shown to increase by an average of 16.0 %, 8.8 %, and 6.0 %, respectively. From 1993–2023, long-term hydrological droughts lasting 2 years occurred 5 times, with a maximum duration of 408 days, magnitude −629, and severity −1.76. The daily lag between the multi-scale SPIs and SRSI of individual drought events presents the possibility of predicting hydrological drought through multiple regression analysis. This research provides insights for improving hydrological drought monitoring, prediction, and response strategies through results of individual propagation characteristics of drought events.

Abstract Image-based lineage tracing enables tissue turnover kinetics and lineage potentials of different adult cell populations to be investigated. Previously, we reported a genetic mouse model system, Red2Onco, which ectopically expressed mutated oncogenes together with red fluorescent proteins (RFP). This system enabled the expansion kinetics and neighboring effects of oncogenic clones to be dissected. We now report Red2Flpe-SCON: a mosaic knockout system that uses multicolor reporters to label both mutant and wild-type cells. We develop the Red2Flpe mouse line for red clone-specific Flpe expression, as well as the FRT-based SCON (Short Conditional IntrON) method to facilitate tunable conditional mosaic knockouts in mice. We use the Red2Flpe-SCON method to study Sox2 mutant clonal analysis in the esophageal epithelium of adult mice which reveal that the stem cell gene, Sox2, is less essential for adult stem cell maintenance itself, but rather for stem cell proliferation and differentiation.

Abstract Mouse models expressing human ACE2 for coronavirus disease 2019 have been frequently used to understand its pathogenesis and develop therapeutic strategies against SARS-CoV-2. Given that human TMPRSS2 supports viral entry, replication, and pathogenesis, we established a double-transgenic mouse model expressing both human ACE2 and TMPRSS2 for SARS-CoV-2 infection. Co-overexpression of both genes increased viral infectivity in vitro and in vivo. Double-transgenic mice showed significant body weight loss, clinical disease symptoms, acute lung injury, lung inflammation, and lethality in response to viral infection, indicating that they were highly susceptible to SARS-CoV-2. Pretreatment with the TMPRSS2 inhibitor, nafamostat, effectively reduced virus-induced weight loss, viral replication, and mortality in the double-transgenic mice. Moreover, the susceptibility and differential pathogenesis of SARS-CoV-2 variants were demonstrated in this animal model. Together, our results demonstrate that double-transgenic mice could provide a highly susceptible mouse model for viral infection to understand SARS-CoV-2 pathogenesis and evaluate antiviral therapeutics against coronavirus disease 2019.

Abstract Background Preoperative prism adaptation (PPA) simulates postoperative status and possibly can predict postoperative undercorrection before surgery in esotropia. The present study aimed to assess the effect of 4-week PPA in preventing postoperative residual esotropia. Methods Seventy-five (75) esotropes who had undergone surgery at a single strabismus center were retrospectively enrolled. They included 25 basic, 31 acute comitant, 10 partially accommodative, and 9 recurrent esotropia patients. The preoperative deviation angle, which had been determined using the alternating prism and cover test, was fully corrected with press-on prisms 4 weeks before surgery. If there was an increase of 5 PD or more of esodeviation, the prisms were changed accordingly at 2 weeks. The deviation angle measured at 4 weeks was determined as the surgical target angle. Patients were then divided into increase (≥ 5 PD increase of angle during 4-week PPA) and non-increase groups. Success was defined as either esodeviation of 8 PD or under or exodeviation of 5 PD or under at distance at postoperative 6 months. Results The increase group included 44 patients (58.7%). The mean deviation angle before PPA was 27.4 PD, and after the 4-week PPA, there was an average increase of 9.4 PD. The success rate was 90.9% in the increase group and 96.8% in the non-increase group (p = 0.316). There were no intergroup differences in preoperative clinical characteristics, esotropia types, postoperative deviation angle or postoperative near stereopsis (p > 0.05). Conclusions The results of this study indicated a beneficial effect of 4-week PPA in esotropia of various types, specifically by uncovering the hidden esodeviation in the increase group and simulating the postoperative alignment in both the increase and the non-increase groups.

Abstract Although previous studies have examined the signaling pathway involved in melanogenesis through which ultraviolet (UV) or α-melanocyte-stimulating hormones (α-MSH) stimuli act as key inducers to produce melanin at the stratum basal layer of the epidermis, the signaling pathway regulating melanogenesis is still controversial. This study reports that α-MSH, not UVA and UVB, acted as a major stimulus of melanogenesis in B16F10 melanoma cells. Signaling pathway analysis using gene knockdown technology and chemical inhibitors, the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/p90 ribosomal S6 kinase 2 (RSK2) played an important role in melanogenesis. Unexpectedly, LY294002, a PI3K inhibitor, increased melanogenesis without UV or α-MSH stimulation, suggesting that the PI3K/AKT signaling pathway may not be a major signaling pathway for melanogenesis. Chemical inhibition of the MEKs/ERKs/RSK2 signaling pathway using U0126 or BI-D1870 suppressed melanogenesis by stimulation of UVA or α-MSH stimulation, or both. In particular, the genetic depletion of RSK2 or constitutive active (CA)-RSK2 overexpression showed that RSK2 plays a key role in melanogenesis. Interestingly, forkhead box protein O4 (FOXO4) was phosphorylated by RSK2, resulting in the increase of FOXO4’s transactivation activity. Notably, the FOXO4 mutant harboring serine-to-alanine replacement at the phosphorylation sites totally abrogated the transactivation activity and reduced melanin production, indicating that RSK2-mediated FOXO4 activity plays a key role in melanogenesis. Furthermore, kaempferol, a flavonoid inhibiting the RSK2 activity, suppressed melanogenesis. In addition, FOXO4-wt overexpression showed that FOXO4 enhance melanin synthesis. Overall, the RSK2-FOXO4 signaling pathway plays a key role in modulating melanogenesis.

Abstract The neurodevelopmental outcomes of preterm infants can be stratified based on the level of prematurity. We explored brain structural networks in extremely preterm (EP;

Abstract Accumulating evidence demonstrates that the activity regulation of ELK3, a member of the E26 transformation-specific oncogene family, is critical to regulating cell proliferation, migration, and survival in human cancers. However, the molecular mechanisms of how ELK3 induces chemoresistance in prostate cancer (PCa) have not been elucidated. In this study, we found that SPOP and ELK3 are an interacting partner. The interaction between SPOP and ELK3 resulted in increased ELK3 ubiquitination and destruction, assisted by checkpoint kinase-mediated ELK3 phosphorylation. Notably, the modulation of SPOP-mediated ELK3 protein stability affected the c-Fos-induced cell proliferation and invasion of PCa cells. The clinical involvement of the SPOP-ELK3 axis in PCa development was confirmed by an immunohistochemical assay on 123 PCa tissues, with an inverse correlation between increased ELK3 and decreased SPOP being present in ~80% of the specimens. This observation was supported by immunohistochemistry analysis using a SPOP-mutant PCa specimen. Finally, docetaxel treatment induced cell death by activating checkpoint kinase- and SPOP-mediated ELK3 degradation, while SPOP-depleted or SPOP-mutated PCa cells showed cell death resistance. Notably, this observation was correlated with the protein levels of ELK3. Taken together, our study reveals the precise mechanism of SPOP-mediated degradation of ELK3 and provides evidence that SPOP mutations contribute to docetaxel resistance in PCa.

Abstract This retrospective study aimed to determine risk factors associated with post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants. Patients taking anticoagulants who were planned to undergo periodontal flap operation, tooth extraction or implant surgery were included. Patients were divided into two subgroups according to the maintenance of anticoagulants following medical consultation: (1) maintenance group and (2) discontinuation group. The analysed patient-related factors included systemic diseases, maintenance of anticoagulants and types of anticoagulant. Intra- and post-operative treatment-related factors, haemostatic methods and post-operative bleeding were collected for statistical analyses. There were 35 post-operative bleeding complications (6.5%) in the 537 included patients: 21 (8.6%) in maintenance group and 14 (4.8%) in discontinuation group. The type of anticoagulant (p = 0.037), tooth extraction combined with bone grafting (p = 0.016) and type of implant surgery (p = 0.032) were significantly related to the post-operative bleeding rate. In the maintenance group, atrial fibrillation [odds ratio (OR) = 6.051] and vitamin K inhibitors (OR = 3.679) were associated with a significantly higher bleeding risk. From this result, it can be inferred that the decision to continue anticoagulants should be made carefully based on the types of anticoagulant and the characteristics of dentoalveolar surgeries performed: extraction with bone grafting, multiple implantations and involvement of maxillary arch.

IntroductionFatty degeneration of the vertebral bodies and paravertebral muscles is associated with the presence, severity, and prognosis of spinal disease such as intervertebral disc degeneration. Therefore, the fat fraction (FF) of the vertebral bodies and paraspinal muscles has been considered a potential biomarker for assessing the pathophysiology, progression, and treatment response of spinal disease. Magnetic resonance spectroscopy (MRS) is considered the reference standard for fat quantification; however, it has limitations of a long acquisition time and is technically demanding. Chemical shift-encoding water-fat imaging, called the Dixon method, has recently been applied for rapid fat quantification with high spatial resolution. However, the Dixon method has not been validated in veterinary medicine, and we hypothesized that the Dixon method would provide a comparable assessment of the FF to MRS but would be faster and easier to implement in dogs.MethodsIn this prospective study, we assessed the FF of the lumbar vertebral bodies and paravertebral muscles from the first to sixth lumbar vertebrae using MRS, the two-point Dixon method (LAVA-FLEX), and the six-point Dixon method (IDEAL-IQ) and compared these techniques.Results and discussionThe FFs of vertebral bodies and paravertebral muscles derived from LAVA-FLEX and IDEAL-IQ showed significant correlations and agreement with those obtained with MRS. In particular, the FFs obtained with IDEAL-IQ showed higher correlations and better agreement with those obtained with MRS than those derived by LAVA-FLEX. Both Dixon methods showed excellent intra- and interobserver reproducibility for FF analysis of the vertebral bodies and paraspinal muscles. However, the test–retest repeatability of vertebral body and paraspinal muscle FF analysis was low for all three sequences, especially for the paraspinal muscles. The results of this study showed that LAVA-FLEX and IDEAL-IQ have high reproducibility and that their findings were highly correlated with the FFs of the lumber vertebral bodies and paraspinal muscles determined by MRS in dogs. The FF analysis could be performed much more easily and quickly using LAVA-FLEX and IDEAL-IQ than using MRS. In conclusion, LAVA-FLEX and IDEAL-IQ can be used as routine procedures in spinal magnetic resonance imaging in dogs for FF analysis of the vertebral bodies and paraspinal muscles.

As COVID-19 enters the endemic phase, public reluctance towards getting COVID-19 booster vaccinations presents a challenge for personal and public health. This hesitation increases the personal vulnerability to the virus and makes it more difficult to control the spread of COVID-19 across the community. Thus, this challenge underlines the need for alternate non-pharmaceutical preventive strategies. This study addresses the need by identifying and ranking the non-pharmaceutical preventive measures using the Fuzzy Analytic Hierarchy Process (FAHP) method. The FAHP approach utilises fuzzy logic to prioritise criteria and alternatives, offering a comprehensive assessment of preventative measures. We presented a case study where three experts were invited to rate three criteria and four alternatives using a nine-point scale with fuzzy numbers. The results indicate that alternative A2 (social distancing) emerges as the most effective measure, while surprisingly, alternative A3 (mask-wearing) is the least preferred. These rankings highlight the importance of effective non-pharmaceutical interventions to raise awareness and encourage people to take precautions in their daily lives during the endemic phase. Additionally, these findings provide the authorities with a valuable benchmark against future pandemics.

IntroductionChildren who have experienced the coronavirus disease 2019 (COVID-19) pandemic are at an increased risk of adverse neurologic developmental outcomes. Limited data exist on the environmental influences of during the COVID-19 pandemic on preterm infant development. This study aimed to investigate whether COVID-19 exposure affects the neurodevelopmental outcomes in preterm children up to 3 years of age.MethodsThis prospective cohort study included all very low birth weight (VLBW) infants from the Korean Neonatal Network who had undergone a neurodevelopmental assessment between January 2015, and May 2022. The neurodevelopmental outcomes along with the scores on the Bayley Scales of Infant and Toddler Development (BSID) and the Korean Developmental Screening Test for Infants and Children of pediatric patients aged 18–24 and 33–39 months who were exposed to COVID-19 were compared with those of VLBW children born and tested before the pandemic.ResultsThe cohort included 1,683 VLBW infants. The pandemic group had significantly lower language scores on the BSID-III at ages 18–24 months (p = 0.021) and 33–39 months (p = 0.023) than the pre-pandemic group after adjusting for gestational age, morbidity, and environmental factors. At 2nd follow-up period, the pandemic group showed significantly lower scores in the cognitive (p = 0.026) domains with a mean difference of 7 points and had a significantly higher percentage of ≤−1SD in the gross motor domain (p

Severe fever with thrombocytopenia syndrome virus (SFTSV) or Dabie bandavirus is an emerging pathogen responsible for SFTS. It is considered a novel threat to human health, given the high associated fatality. SFTSV is a segmented negative-strand RNA virus containing three single-stranded RNAs, with the M segment encoding the glycoproteins Gn and Gc. Gc is vital for viral entry into the host cell surface, along with the Gn protein. As the Gc is the surface-exposable antigen from virions, it is a critical diagnostic marker of infection. Although various SFTSV Gn or N protein-based sero-diagnostic methods have been developed, there are no commercially available sero-diagnostic kits. Therefore, we generated monoclonal antibodies (mAbs) against SFTSV Gc and explored their application in serum diagnostic tests to develop sensitive serodiagnostic tools covering broad-range genotypes (A to F). First, 10 SFTSV Gc antibody-binding fragments (Fabs) were isolated using a phage display system and converted into human IgGs. Enzyme-linked immunosorbent assays (ELISA) of the SFTSV and Rift Valley fever virus (RVFV: same genus as SFTSV) Gc antigens showed that all antibodies attached to the SFTSV Gc protein had high affinity. An immunofluorescence assay (IFA), to verify the cross-reactivity of seven antibodies with high affinities for various SFTSV genotypes (A, B2, B3, D, and F) and detect mAb binding with intact Gc proteins, revealed that five IgG type mAbs were bound to intact Gc proteins of various genotypes. Six high-affinity antibodies were selected using ELISA and IFA. The binding capacity of the six antibodies against the SFTSV Gc antigen was measured using surface plasmon resonance. All antibodies had high binding capacity. Consequently, these antibodies serve as valuable markers in the serological diagnosis of SFTSV.

Introduction There is a lack of evidence to support the effectiveness of prolonged β-blocker therapy after stabilisation of patients with acute myocardial infarction (AMI) without heart failure (HF) or left ventricular systolic dysfunction.Methods and analysis The SMart Angioplasty Research Team: DEcision on Medical Therapy in Patients with Coronary Artery DIsease or Structural Heart Disease Undergoing InterventiON (SMART-DECISION) trial is a multicentre, prospective, open-label, randomised, non-inferiority trial designed to determine whether discontinuing β-blocker therapy after ≥1 year of maintenance in stabilised patients after AMI is non-inferior to continuing it. Patients eligible for participation are those without HF or left ventricular systolic dysfunction (ejection fraction >40%) who have been continuing β-blocker therapy for ≥1 year after AMI. A total of 2540 patients will be randomised 1:1 to continuation of β-blocker therapy or not. Randomisation will be stratified according to the type of AMI (ie, ST-segment-elevation MI or non-ST-segment-elevation MI), type of β-blocker (carvedilol, bisoprolol, nebivolol or other) and participating centre. The primary study endpoint is a composite of all-cause death, MI and hospitalisation for HF over a median follow-up period of 3.5 years (minimum, 2.5 years; maximum, 4.5 years). Adverse effects related to β-blocker therapy, the occurrence of atrial fibrillation, medical costs and Patient-reported Outcomes Measurement Information system-29 questionnaire responses will also be collected as secondary endpoints.Ethics and dissemination Ethics approval for this study was granted by the Institutional Review Board of Samsung Medical Center (no. 2020-10-176). Informed consent is obtained from every participant before randomisation. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences.Trial registration number ClinicalTrials.gov, NCT04769362.

Abstract Halide perovskite single crystals (SCs) have attracted much attention for their application in high‐performance x‐ray detectors owing to their desirable properties, including low defect density, high mobility–lifetime product (μτ), and long carrier diffusion length. However, suppressing the inherent defects in perovskites and overcoming the ion migration primarily caused by these defects remains a challenge. This study proposes a facile process for dipping Cs0.05FA0.9MA0.05PbI3 SCs synthesized by a solution‐based inverse temperature crystallization method into a 2‐phenylethylammonium iodide (PEAI) solution to reduce the number of defects, inhibit ion migration, and increase x‐ray sensitivity. Compared to conventional spin coating, this simple dipping process forms a two‐dimensional PEA2PbI4 layer on all SC surfaces without further treatment, effectively passivating all surfaces of the inherently defective SCs and minimizing ion migration. As a result, the PEAI‐treated perovskite SC‐based x‐ray detector achieves a record x‐ray sensitivity of 1.3 × 105 μC Gyair−1 cm−2 with a bias voltage of 30 V at realistic clinical dose rates of 1–5 mGy s−1 (peak potential of 110 kVp), which is 6 times more sensitive than an untreated SC‐based detector and 3 orders of magnitude more sensitive than a commercial α‐Se‐based detector. Furthermore, the PEAI‐treated‐perovskite SC‐based x‐ray detector exhibits a low detection limit (73 nGy s−1), improved x‐ray response, and clear x‐ray images by a scanning method, highlighting the effectiveness of the PEAI dipping approach for fabricating next‐generation x‐ray detectors.

Ammonia (NH3) has been a subject of great interest due to its important roles in diverse technological applications. However, high toxicity and corrosiveness of NH3 has made it an important task to develop an efficient carrier to safely capture NH3 with high capacity. Here, we employ a machine learning (ML) model to discover high-performance metal organic frameworks (MOFs) that will work as efficient NH3 carriers. By constructing databases at two distinct conditions, adsorption and desorption, through Grand Canonical Monte Carlo (GCMC) simulations to train ML models, we identify eight novel MOFs as potentially efficient NH3 carriers through screening the large-scale MOF databases with the trained models and GCMC verification. The identified MOFs exhibit the average NH3 working capacity exceeding 1100 mg/g, and subsequent molecular dynamics simulations demonstrate mechanical stability of the predicted MOFs. Moreover, analyses of the diffusion mechanism within the proposed MOFs underscore the strong dependence of NH₃ gas diffusivity on the structural details of the materials.