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In the 2020 Democratic Presidential Primary campaigns, six women, the most in history, announced their candidacy for the presidency. Using computational topic modeling and network analysis of 84,000 newspaper articles (2.2 million paragraphs), we analyze how gender and electability was discussed during the Primaries. Results reveal that male candidates, and especially Joe Biden, were frequently compared with the incumbent, Donald Trump, while coverage of female candidates focused directly on social policy. Trump's attack on Biden during the impeachment process produced a lasting effect by promoting discourse topics traditionally dominated by men. This crowded out the topics emphasized by women, such as health care and education. Women candidates' press coverage was also more reactionary than men's. Although explicit reference to gender as a discourse topic has decreased, which suggests growing gender parity within the political process, gendered policy salience emerges transitively in comparison with the incumbent. Transitive policy salience emerges as a key explanatory variable that articulates the indirect path media coverage can lead to the marginalization of women candidates. [ABSTRACT FROM AUTHOR]

The pyrazole ring structure is extensively spotted as a pharmacophore and fortify‐cation of the modern organic synthesis toolbox, which demands synthetic tactics to generate its derivatives. Especially, pyrazolo‐pyrimidinones are crucial part to synthesize phosphodiesterase type 5 (PDE5) such as sildenafil and lodenafil. Herein, we report a simple and efficient route for Sildenafil and derivatives from easily available materials. [ABSTRACT FROM AUTHOR]

The article focuses on the mass resignation of resident physicians in South Korea in response to controversial government health care reforms, highlighting systemic issues such as low reimbursement rates, excessive workloads, and inadequate support for deferred specialties.

Photon-counting detector (PCD)-based computed tomography (CT) offers several advantages over conventional energy-integrating detector-based CT. Among them, the ability to discriminate energy exhibits significant potential for clinical applications because it provides material-specific information. That is, material decomposition (MD) can be achieved through energy discrimination. In this study, deep learning-based material decomposition was performed using live animal data. We propose MD-Unet, which is a deep learning strategy for material decomposition based on an Unet architecture trained with data from three energy bins. To mitigate the data insufficiency, we developed a pretrained model incorporating various simulation data forms and augmentation strategies. Incorporating these approaches into model training results in enhanced precision in material decomposition, thereby enabling the identification of distinct materials at individual pixel locations. The trained network was applied to the acquired animal data to evaluate material decomposition results. Compared with conventional methods, the newly generated MD-Unet demonstrated more accurate material decomposition imaging. Moreover, the network demonstrated an improved material decomposition ability and significantly reduced noise. In addition, they can potentially offer an enhancement level similar to that of a typical contrast agent. This implies that it can acquire images of the same quality with fewer contrast agents administered to patients, thereby demonstrating its significant clinical value. [ABSTRACT FROM AUTHOR]

Background: The prevalence of metastatic pheochromocytoma and paraganglioma (PPGL) is approximately 15%–20%. Although there are indicators to assess metastatic risks, none of them predict metastasis reliably. Therefore, we aimed to develop and validate a scoring system using clinical, genetic, and biochemical risk factors to preoperatively predict the metastatic risk of PPGL. Methods: In the cross‐sectional cohort (n = 180), clinical, genetic, and biochemical risk factors for metastasis were identified using multivariate logistic regression analysis, and a novel scoring system was developed. The scoring system was validated and compared with the age, size of tumor, extra‐adrenal location, and secretory type (ASES) score in the longitudinal cohort (n = 114). Results: In the cross‐sectional cohort, pseudohypoxia group‐related gene variants (SDHB, SDHD, or VHL), methoxytyramine >0.16 nmol/L, and tumor size >6.0 cm were independently associated with metastasis after multivariate logistic regression. Using them, the gene variant, methoxytyramine, and size of tumor (GMS) score were developed. In the longitudinal cohort, Harrell's concordance index of the GMS score (0.873, 95% confidence interval [CI]: 0.738–0.941) was higher than that of the ASES score (0.713, 95% CI: 0.567–0.814, p = 0.007). In the longitudinal cohort, a GMS score ≥2 was significantly associated with a higher risk of metastasis (hazard ratio = 25.07, 95% CI: 5.65–111.20). A GMS score ≥2 (p < 0.001), but not ASES score ≥2 (p = 0.090), was associated with shorter progression‐free survival. Conclusion: The GMS scoring system, which integrates gene variant, methoxytyramine level, and tumor size, provides a valuable preoperative approach to assess metastatic risk in PPGL. [ABSTRACT FROM AUTHOR]

Purpose: Fibular hemimelia has denoted a spectrum of postaxial longitudinal deficiency with fibular aplasia/hypoplasia; the term "terminal hemimelia" is reserved for patients with postaxial longitudinal deficiency having a normal fibula. We aimed to delineate the characteristics of terminal hemimelia. Methods: In total, 30 patients with postaxial longitudinal deficiency who had a normal or hypoplastic fibula and visited our institution between 1992 and 2022 were reviewed. Patients were divided into terminal hemimelia and classic fibular hemimelia groups, and their demographic characteristics and clinical and radiographic findings were compared. Results: Femoral shortening, knee valgus, and tibial spine hypoplasia were less common in terminal hemimelia (n = 13) than in classic fibular hemimelia (n = 17) (p = 0.03, p < 0.001, and p = 0.003, respectively). None of the patients in the terminal hemimelia group exhibited knee instability, whereas 12% of patients with classic fibular hemimelia did. Ball-and-socket ankle and absence of lateral rays were commonly observed in both groups. However, tarsal coalition was observed less frequently in terminal hemimelia (p = 0.004). All terminal hemimelia patients exhibited a painless plantigrade foot without ankle instability. Despite limb-length discrepancy at maturity averaging 40.4 mm for terminal hemimelia and 67.0 mm for classic fibular hemimelia (p < 0.001), patients with terminal hemimelia, except for one, exhibited > 20 mm of limb-length discrepancy. However, 46% of them underwent limb-length equalization procedures, mostly single-stage tibial lengthening, at a mean age of 11.2 years. Conclusion: Terminal hemimelia may present with a milder phenotype than classic fibular hemimelia. It mainly overlaps with the symptoms of fibular hemimelia below the ankle joint and manifests as limb-length discrepancy. However, a considerable number of patients with terminal hemimelia required limb-length equalization procedures, for example single-stage tibial lengthening. Level of evidence: level IV. [ABSTRACT FROM AUTHOR]

Prime period sequences can serve as the fundamental tool to construct arbitrary composite period sequences. This is a review study of the prime period perfect Gaussian integer sequence (PGIS). When cyclic group { 1 , 2 , ... , N − 1 } can be partitioned into k cosets, where N = k f + 1 is an odd prime number, the construction of a degree-(k + 1) PGIS can be derived from either matching the flat magnitude spectrum criterion or making the sequence with ideal periodic autocorrelation function (PACF). This is a systematic approach of prime period N = k f + 1 PGIS construction, and is applied to construct PGISs with degrees 1, 2, 3 and 5. However, for degrees larger than 3, matching either the flat magnitude spectrum or achieving the ideal PACF encounters a great challenge of solving a system of nonlinear constraint equations. To deal with this problem, the correlation and convolution operations can be applied upon PGISs of lower degrees to generate new PGISs with a degree of 4 and other higher degrees, e.g., 6, 7, 10, 11, 12, 14, 20 and 21 in this paper. In this convolution-based scheme, both degree and pattern of a PGIS vary and can be indeterminate, which is rather nonsystematic compared with the systematic approach. The combination of systematic and nonsystematic schemes contributes great efficiency for constructing abundant PGISs with various degrees and patterns for the associated applications. [ABSTRACT FROM AUTHOR]

Background: Current guidelines regarding periprocedural glycemic control to prevent complications after nonsurgical invasive procedures are insufficient. Transarterial chemoembolization (TACE) is a widely used treatment for unresectable hepatocellular carcinoma. We aimed to investigate the association between diabetes mellitus (DM) per se and the degree of hyperglycemia with postprocedural complications after TACE. Methods: A total of 22,159 TACE procedures performed at Seoul National University Hospital from 2005 to 2018 were retrospectively analyzed. The associations between DM, preprocedural glycosylated hemoglobin (HbA1c), and periprocedural average glucose with postprocedural adverse outcomes were evaluated. The primary outcome was occurrence of postprocedural bacteremia. Secondary outcomes were acute kidney injury (AKI), delayed discharge and death within 14 days. Periprocedural glucose was averaged over 3 days: the day of, before, and after the TACE procedures. Propensity score matching was applied for procedures between patients with or without DM. Results: Periprocedural average glucose was significantly associated with bacteremia (adjusted odds ratio per 50 mg/dL of glucose, 1.233; 95% confidence interval, 1.071 to 1.420; P=0.004), AKI, delayed discharge, and death within 14 days. DM per se was only associated with bacteremia and AKI. Preprocedural HbA1c was associated with delayed discharge. Average glucose levels above 202 and 181 mg/dL were associated with a significantly higher risk of bacteremia and AKI, respectively, than glucose levels of 126 mg/dL or lower. Conclusion: Periprocedural average glucose, but not HbA1c, was associated with adverse outcomes after TACE, which is a nonsurgical invasive procedure. This suggests the importance of periprocedural glycemic control to reduce postprocedural complications. [ABSTRACT FROM AUTHOR]

Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim of this study was to explore the efficacy of TCM treatments against SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. Antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis (S. baicalensis) was found to be effective against SARS-CoV-2 infection, as it mediated the interaction between the viral spike protein and the hACE2 protein. Moreover, the active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside found in S. baicalensis, respectively, exhibited strong inhibitory activities targeting the viral spike protein and the hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors from S. baicalensis that mediate the interaction between the Omicron spike protein and the hACE2 receptor. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed. [ABSTRACT FROM AUTHOR]

Background: Phytoplasmas are parasitic plant pathogens that reside intracellularly within the sieve tube cells. Phytoplasmas induce various symptoms, including floral virescence, phyllody, leaf yellowing, and witches'-broom. Currently, it is challenging to culture phytoplasma in vitro. In the laboratory, phytoplasmas are generally maintained in alternative host plants, such as Catharanthus roseus. Grafting is used to transmit phytoplasmas among the alternative hosts. During the experiment, scions from infected plants are grafted onto healthy plants using a side grafting method. However, the practice has certain limitations, including its inability to be applied to small plants and its irregular disease incidence. Results: Here, we demonstrate a new approach, penetration grafting, to overcome the limitations of side grafting. This grafting method allows phytoplasma to be efficiently and uniformly transmitted into the inoculated plants. No significant difference was observed in phytoplasma accumulation between both grafting techniques. However, penetration grafting allows rapid symptom development, saving waiting time and reducing space usage. Conclusions: This study provides a reliable and stable method for experiments that require grafting transmission. [ABSTRACT FROM AUTHOR]

This research aims to enhance MXene (Ti3C2Tx) synthesis from MAX phases (Ti3AlC2) through a hydro‐solvothermal exfoliation process, with a focus on reducing time and temperature requirements. Prior hydrothermal studies have encountered challenges due to high reaction temperatures. In comparison to previous research, this work achieves superior results at lower temperatures. Two optimized MXene preparation routes are investigated and the etchant's impact on MXene surface chemistry is analyzed. Comprehensive X‐ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Energy Dispersive X‐ray Spectroscopy (EDS), X‐ray Photoelectron Spectroscopy (XPS), Fourier transform infrared (FTIR), Raman spectroscopy, and Atomic Force Microscopy (AFM) analyses provide insights into hydrosolvothermal synthesis (H‐Ti3C2Tx) multilayers(ML), confirming/challenging recent spectroscopic assignments. Remarkably, hydro‐solvothermal treatment induces significant changes in surface composition, increasing hydroxyl (─OH) groups without oxidation and reducing fluorine (─F) groups on the H‐ Ti3C2Tx surface. These study's results hold promise for applications in energy storage and electromagnetic wave shielding. This research accomplishes three main objectives: i) secures hydrothermal synthesis of two‐ dimensional (2D) MXenes, ii) efficiently utilizes lithium fluroide‐ hydrochloric acid (LiF−HCl) etching for high‐quality MXene flakes with minimal defects, and iii) understands hydro‐solvothermal kinetics. This approach advances MXene synthesis with enhanced material quality and production efficiency (>98%), in a more eco‐friendly and safer manner. This eco‐conscious synthesis underscores MXene's versatility and eco‐friendly methods' significance, reshaping MXene exploration and sustainable material synthesis, with potential implications for future electrochemical applications. [ABSTRACT FROM AUTHOR]

Recent measurement of the parity-violating (PV) asymmetry in the elastic electron scattering on 2 7 Al target evokes the interest in the distribution of the neutron in the nucleus. In this work, we calculate the neutron skin thickness ( R n p ) of 2 7 Al with nonrelativistic nuclear structure models. We focus on the role of the effective mass, symmetry energy and pairing force. Models are selected to have effective masses in the range (0.58–1.05) M where M is the nucleon mass in free space, and stiffness of the symmetry energy is varied by choosing the slope of the symmetry energy in the range 9.4–100.5 MeV. Effect of pairing force is investigated by calculating nuclear properties with and without pairing. With constant force pairing, we obtain R n p = 0. 0 0 1 –0.013 fm. The result is independent of the effective mass and symmetry energy. However, R n p is negative when the pairing force is switched off, so the pairing force plays an essential role to make R n p positive and constrained in a narrow range. We also calculate the PV asymmetry ( A pv ) in the elastic electron- 2 7 Al scattering in the Born approximation at the kinematics of the Qweak experiment. We obtain a very narrow-ranged result A pv = (2. 0 7 − 2. 0 9) × 1 0 − 6 . The result is consistent with the experiment and insensitive to the effective mass and symmetry energy. [ABSTRACT FROM AUTHOR]

Liver transplantation (LT) is typically performed at specialized, high-volume centers. However, some smaller centers also offer liver transplantation services, but their outcomes and safety have been a subject of debate. To overcome these difficulties, we tried to build a Catholic Medical Center (CMC) network to share our experiences and overcome the lack of volume. In this study, we reviewed the overall outcome of patients undergoing LT at a small-volume procedure center, with a focus on patient and graft survival rates. Between July 2014 and September 2021, 60 adults underwent LT at Bucheon Saint Mary's Hospital. The overall outcomes were analyzed in terms of perioperative outcomes, complications, and overall survival rate. In addition, the patients were divided into a benign end-stage liver disease (ESLD) group (n = 44) and a hepatocellular carcinoma (HCC) group (n = 16). The baseline characteristics, perioperative outcomes, complications, and overall survival rate were analyzed between the 2 groups. Of a total of 60 LT, living donor liver transplantation (LDLT) was 26, and deceased donor liver transplantation was 34. LDLT was 14 (31.8%) in the ESLD group and 12 (75.0%) in the HCC group. The overall 1-year, 3-year, and 5-year survival rates were 86.7%, 79.7%, and 77.7%, respectively. The survival difference was not statistically significant (P =.214) between the 2 groups. We suggest that with appropriate patient selection and adequate resources, LT can be safely performed at smaller centers with the assistance of the CMC network, thus expanding access to this life-saving procedure. [ABSTRACT FROM AUTHOR]

Halocins, the proteinaceous antimicrobial agents produced by haloarchaea, may be used for the preservation of salted foods and the treatment of diseases. For their application and function explanation, it is necessary to produce the active recombinants. In this work, a haloarchaeal strain producing halocin was isolated from the salt-fermented shrimp and identified as Natrinema sp. RNS21 by 16S rRNA gene sequence analysis. From 1 L of RNS21 culture, about 0.32 mg of halocin with 96% purity was obtained. Based on the molecular weight, stability and amino acid sequence alignment, the antimicrobial peptide belonged to the halocin C8 (HalC8) family. HalC8 was expressed by fusion with glutathione-S-transferase (GST) in E. coli, followed by affinity purification and enterokinase (EK) cleavage. About 6.2 mg of recombinant HalC8 with 95% purity was obtained from 1 L of E. coli culture. MALDI-TOF–MS and RP-HPLC analysis indicated that the molecular weight and folding pattern of purified recombinant HalC8 were the same as those of native HalC8. Recombinant HalC8 showed obvious inhibitory activity against Haloferax volcanii. Contrast to native HalC8, the active recombinant HalC8 could be easily produced in a short time with a high yield. [ABSTRACT FROM AUTHOR]

Plant triterpenoids are secondary metabolites with high chemical diversity and interesting biological properties. Chestnuts are deciduous trees in the genus Castanea, and their nuts have been used as an important food. In this work, we identified various types of triterpenes, such as α-amyrin, β-amyrin, lupeol, and friedelin, in the leaves and/or stem bark of Korean chestnut (Castanea crenata). Triterpene biosynthesis occurs by the cyclization of 2,3-oxidosqualene to triterpenes, catalyzed by oxidosqualene cyclases (OSCs). A total of 65 putative OSC sequences were obtained from the leaf transcriptome data of C. crenata plants using PacBio sequencing. We selected 5 putative OSC unigenes, named CcOSC1-5, for functional characterization of genes involved in triterpene biosynthesis. Functional characterization of the CcOSC1-5 genes by heterologous expression in erg7 mutant yeast revealed that both CcOSC1 and CcOSC2 had a similar function, encoding multifunctional triterpene synthases producing mainly β-amyrin and a small amount of α-amyrin and lupeol. CcOSC3 encodes mixed amyrin synthase, which mainly produces β-amyrin and a small amount of α-amyrin. CcOSC4 produced mainly α-amyrin and lupeol and a small amount of β-amyrin. CcOSC5 encodes an enzyme for lupeol production as a single product. In conclusion, we identified various triterpenes and functionally characterized the triterpene synthase genes that participate in β-amyrin, α-amyrin, and lupeol biosynthesis in C. crenata. [ABSTRACT FROM AUTHOR]

Backgrounds: Determining the precise localization of diseased physes is crucial for guiding the treatment of growth disturbances. Conventional radiography, computed tomography (CT), and magnetic resonance imaging only provide information on physeal anatomy. Planar bone scintigraphy and bone single-photon emission computed tomography (SPECT) resolutions are suboptimal for clinically managing growth disturbances. Bone SPECT/CT, which provides high-resolution functional information, can be a useful tool for evaluating growth disturbances. The purposes of this study were to identify the conditions in which bone SPECT/CT outperforms planar scintigraphy or SPECT for evaluating the location and activity of diseased physes and to assess surgical outcomes using bone SPECT/CT findings in pediatric patients experiencing long bone growth disturbances. Methods: Fifty-nine patients who underwent bone SPECT/CT between January 2018 and January 2021 to evaluate physeal activity using technetium-99 m-labeled 2,3-dicarboxypropane-1,1-diphosphonate (99mTc-DPD) were included. The proportions of patients for whom certain modalities provided sufficient data for selecting treatment plans for growth disturbances were compared based on the site of the diseased physis, growth disturbance cause, and shape of deformity (i.e., SPECT/CT vs. planar scintigraphy and SPECT/CT vs. SPECT). For assessing surgical outcomes, progression of post-surgical deformity was investigated by measuring the angles reflecting the degree of deformity, iliac crest height difference, or ulnar variance on radiographs. Results: Bone SPECT/CT was sufficient for selecting a treatment plan, but planar scintigraphy or SPECT alone was insufficient in every 10 patients with diseased physes inside the femoral head (p = 0.002) and in every six with physes that were severely deformed or whose locations were unclear on conventional radiography (p = 0.03). In the proximal or distal tibia, where the tibial and fibular physes often overlapped on planar scintigraphy due to leg rotation, bone SPECT/CT was sufficient in 33/34 patients (97%), but planar scintigraphy and SPECT were sufficient in 10/34 (29%) (p < 0.001) and 24/34 (71%) patients, respectively (p = 0.004). No progression or deformity recurrence occurred. Conclusions: Bone SPECT/CT may be indicated in proximal femoral growth disturbance, when the physis is unclear on conventional radiography or severely deformed, the leg exhibits rotational deformity, or the patient is noncompliant. [ABSTRACT FROM AUTHOR]

Summary: This article proposes a virtual angle‐based adaptive control method for trajectory tracking and balancing of ball‐balancing robots without velocity measurements. The trajectory tracking and balancing control of ball‐balancing robots is challenging due to underactuation and uncertain nonlinearities. The hierarchical control strategy, which designs the control system using a linear combination of trajectory tracking and balancing errors, can be a solution. However, it has a local minimum problem where the convergence of tracking and balancing errors is not guaranteed even though the linear combination error is zero. Therefore, a virtual angle‐based control method is presented, which can solve the underactuation problem without the local minimum issue. In addition, a neural network‐based observer is developed to estimate the velocity information of ball‐balancing robots with uncertainties, and the input saturation problem is considered. It is proven that all tracking and balancing errors are bounded and can be made arbitrarily small in the Lyapunov sense. Finally, simulation results are provided to verify the effectiveness of the proposed control system. [ABSTRACT FROM AUTHOR]

Background: This study aimed to analyze the differences in the stability of fractures, stress distribution around the distal-most screw according to the length of the plate and the trajectory of the bolt in Pauwels type III femoral neck fracture using the femoral neck system (FNS). Methods: Finite element models of Pauwels type III femoral neck fractures were established with surgical variations in the trajectory of the bolt (central, inferior, valgus, and varus) and length of the lateral plate (1- and 2-hole plate). The models were subsequently subjected to normal walking and stair-climbing loads. Results: The screw-holding cortical bone in subtrochanter in the model with a 2-hole plate and the bolt in the inferior trajectory and the models with 1-hole or 2-hole plate and the bolt in valgus trajectory had shown greater maximum principal strain than the models with central or varus trajectories. The gap and sliding distance on the fracture surface were larger with inferior or varus trajectories of the bolt and smaller with the valgus trajectory of the bolt under both loads, compared to those of the central trajectory. Conclusion: For the fixation of Pauwels type III femoral neck fracture, the trajectory of the FNS bolt and the length of the plate affect the mechanical stability of the fracture and the strain of cortical bone around the distal-most screw. The surgical target should stay on the central trajectory of the bolt and the 2-hole plate's mechanical benefits did not exceed the risk. [ABSTRACT FROM AUTHOR]

Pterygium is an abnormal growth of fibrous conjunctival tissue that invades the cornea, resulting in corneal distortion, astigmatism, and increased higher-order aberrations (HOAs). However, few studies have compared eyes with pterygium to normal fellow eyes when interpreting HOAs and there is no study that revealed the effect of the thickness or grading of the pterygium on the change of HOAs. Therefore, we evaluated the effects of nasal pterygium by comparing the normal fellow eye of 59 patients. The pterygium significantly increased with-the-rule corneal astigmatism and corneal irregularity. Trefoils, horizontal coma, and quatrefoils were significantly induced by the pterygium. The grading of the pterygium was not correlated with its characteristics except for the thickness. In multiple linear regression analysis, pterygium-induced corneal astigmatic/irregularity values and horizontal trefoil/quatrefoil were associated with the area of the pterygium. The length of the pterygium was an independent inducer of oblique trefoil/quatrefoil, while horizontal coma was independently associated with both its length and width. The thickness was not correlated with any optical parameters. Together, the results demonstrate that nasal pterygium significantly induces corneal astigmatism, irregularity and some HOAs. These pterygium-associated changes in optical parameters could be predicted by the length, width and area of the pterygium. [ABSTRACT FROM AUTHOR]

Here, we propose a quantum asymmetric key cryptography scheme using Grover's quantum search algorithm. In the proposed scheme, Alice generates a pair of public and private keys, keeps the private keys safe, and only discloses public keys to the outside. Bob uses Alice's public key to send a secret message to Alice and Alice uses her private key to decrypt the secret message. Furthermore, we discuss the safety of quantum asymmetric key encryption techniques based on quantum mechanical properties. [ABSTRACT FROM AUTHOR]

Bcl-2-associated anthanogene (BAG) family proteins regulate plant defense against biotic and abiotic stresses; however, the function and precise mechanism of action of each individual BAG protein are not yet clear. In this study, we investigated the biochemical and molecular functions of the Arabidopsis thaliana BAG2 (AtBAG2) protein, and elucidated its physiological role under stress conditions using mutant plants and transgenic yeast strains. The T-DNA insertion atbag2 mutant plants were highly susceptible to heat shock, whereas transgenic yeast strains ectopically expressing AtBAG2 exhibited outstanding thermotolerance. Moreover, a biochemical analysis of GST-fused recombinant proteins produced in bacteria revealed that AtBAG2 exhibits molecular chaperone activity, which could be attributed to its BAG domain. The relevance of the molecular chaperone function of AtBAG2 to the cellular heat stress response was confirmed using yeast transformants, and the experimental results showed that overexpression of the AtBAG2 sequence encoding only the BAG domain was sufficient to impart thermotolerance. Overall, these results suggest that the BAG domain-dependent molecular chaperone activity of AtBAG2 is indispensable for the heat stress response of Arabidopsis. This is the first report demonstrating the role of AtBAG2 as a sole molecular chaperone in Arabidopsis. [ABSTRACT FROM AUTHOR]

We seek a simple but physically motivated model of strongly interacting matter applicable in atomic nuclei and the dense matter in the core of neutron stars. For densities below and somewhat above normal nuclear density, energy density functional (EDF) theory based on nucleonic degrees of freedom is the ideal candidate. We have explored that direction within the KIDS (Korea-IBS-Daegu-SKKU) framework, which we review in this contribution. The formalism for the KIDS-EoS and microscopic KIDS-EDF and optimization options for the EDF are described in a practical way to facilitate further applications. At densities higher than one nucleon per single-nucleon volume, i.e., roughly 0.4 fm − 3 , nucleonic degrees of freedom are no longer appropriate. The pseudo-conformal symmetry emergent in dense, topologically altered nuclear matter provides a simple expression for the energy per baryon in terms of the baryonic density. Besides resembling a simple EDF for dense matter, the expression has the appeal that it predicts a converged speed of sound at high densities. It can thus be implemented as a special case of the constant speed of sound (CSS) model. Here we consider a matching between representative nucleonic KIDS-EoSs and the CSS model, including the pseudo-conformal EoS, and apply the unified model to describe the mass–radius relation of neutron stars and examine the compatibility of CSS cores with heavy neutron stars. Although an abrupt transition to the pseudo-conformal regime at low densities does not favor heavy neutron stars, intermediate scenarios including a cusp in the speed of sound are not ruled out, while some appear more favorable to heavy stars than purely nucleonic matter. [ABSTRACT FROM AUTHOR]

To maintain normal glucose homeostasis after a meal, it is essential to secrete an adequate amount of insulin from pancreatic β-cells. However, if pancreatic β-cells solely depended on the blood glucose level for insulin secretion, a surge in blood glucose levels would be inevitable after the ingestion of a large amount of carbohydrates. To avoid a deluge of glucose in the bloodstream after a large carbohydrate-rich meal, enteroendocrine cells detect the amount of nutrient absorption from the gut lumen and secrete incretin hormones at scale. Since insulin secretion in response to incretin hormones occurs only in a hyperglycemic milieu, pancreatic β-cells can secrete a "Goldilocks" amount of insulin (i.e., not too much and not too little) to keep the blood glucose level in the normal range. In this regard, pancreatic β-cell sensitivity to glucose and incretin hormones is crucial for maintaining normal glucose homeostasis. In this Namgok lecture 2022, we review the effects of current anti-diabetic medications on pancreatic β-cell sensitivity to glucose and incretin hormones. [ABSTRACT FROM AUTHOR]

We report the synthesis of [6,7,5]‐tricyclic compounds containing an oxabicyclo [3.2.1] octane system from 1,6‐enyne carbonyl. We also synthesized [6,7,6]‐tricyclic compound from 1,7‐enyne carbonyl through Au‐catalyzed cyclization. The synthesis of oxacyclic compounds using iodine or oxygen is environmentally friendly cyclization methods. Oxacyclic compounds are useful for synthesizing various diterpene alkaloids. [ABSTRACT FROM AUTHOR]

'Miyagawa-wase' mandarin (Citrus. unshiu Marc. cv. Miyagawa-wase) is one of the most widely cultivated citrus varieties in Korea. Previously, we used γ-irradiation to develop new citrus varieties by mutation breeding, a useful tool for increasing genetic diversity in a short time. One of the new citrus varieties we generated, Jedae-unshiu, produces uniquely shaped fruit with vertical troughs on the flavedo. Although comparative analyses of genome-wide variation and transcriptomics have been reported for seedless or color-change citrus variants, little is known regarding genetic variants linked to morphological variation in citrus fruits. In this study, genome-wide single nucleotide polymorphisms (SNPs) and insertion/deletion (InDel) variants were identified in Jedae-unshiu by whole-genome re-sequencing and subjected to functional annotation by gene ontology (GO) analysis. The results show that InDel-containing genes are more highly represented in the GO database than SNP-containing genes. In addition, we compared Jedae-unshiu and wild-type control transcriptomes to identify candidate genetic determinants of the unique fruit phenotype of Jedae-unshiu. A total of 641 unique, differentially expressed genes (DEGs) were identified in Jedae-unshiu relative to wild-type control, including 388 up-regulated and 253 down-regulated genes. The DEGs were mapped to GO terms and subjected to Kyoto Encyclopedia of Genes and Genomes pathway analysis to identify DEGs involved in cellular processes potentially linked to the unique phenotype of Jedae-unshiu fruit. The expression of 10 DEGs (5 up- and 5 down-regulated) was quantified by reverse transcriptase-polymerase chain reaction (RT-PCR). Our findings provide insight into putative genetic determinants of fruit morphology in citrus. [ABSTRACT FROM AUTHOR]

An efficient and facile method for producing 2,3-dihydronaphtho[2,3-b]furan and 3,4-dihydro-2H-benzo[g]chromene has been developed. This methodology utilizes an inexpensive and simple PTSA catalyst for the cyclization reaction of ortho-oxalate-, ortho-keto-, and ortho-formyl arylacetylenols to produce the corresponding products in high yield. This procedure was also successfully applied to the large-scale synthesis of the naphthofuran skeleton, which can be found in various natural products and pharmaceuticals. [ABSTRACT FROM AUTHOR]

Airway epithelial cells are a major site of airway inflammation and may play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Diesel particulate matter (DPM) is associated with mucus hypersecretion and airway inflammation and has been reported to overexpress airway mucin in the NCI-H292 airway epithelial cells. Therefore, regulation of mucin hypersecretion is essential for developing novel anti-inflammatory agents. This study aimed to investigate the effects of cell-free supernatant (CFS) from Lactobacillus and Streptococcus on nitro oxide (NO) production in RAW264.7 and proteins associated with mucus production in NCI-H292 cells. We observed that NO production was reduced by CFS from Lactobacillus and Streptococcus in RAW 264.7, and MUC4, MUC5AC, and MUC5B gene expression was increased by phosphorylation of nuclear factor kappa B (NF-κB) p65 and cAMP response element-binding protein (CREB) in DPM-stimulated NCI-H292 cells. However, CFS from L. paracasei MG4272, MG4577, L. gasseri MG4247, and S. thermophilus MG5140 inhibited mRNA expression related to mucus production by downregulating the CREB/NfκB signaling pathway. These results suggest that CFS from L. paracasei MG4272, MG4577, L. gasseri MG4247, and S. thermophilus MG5140 can contribute as a strategic candidate to the prevention of airway inflammatory diseases caused by DPM. [ABSTRACT FROM AUTHOR]

This article analyzes South Korea's unification policies and makes ethical suggestions in light of Christian theological and ethical theories of war and peace. Since 1948, South and North Korea have repeatedly confronted each other with heavily armed forces. Unification would be considered the achievement of the Korean people's endeavour to deter military warfare and promote peace between the two Koreas. In this regard, it is understandable that unification policy-making should retain tension reduction and peaceful coexistence as its fundamental goals. Public discussions in unification policy-making inevitably involve such issues as prohibition or justification of the use of violence or military force and procedures and methods of promoting peace. In analyzing unification policies in Christian ethical terms, such Christian war-peace tenets as pacifism, just war, and holy war contribute to this analysis, given that their primary concerns lie in maintaining peace and justifying violence for the sake of peace. [ABSTRACT FROM AUTHOR]

While roll-to-roll nanoimprint lithography (R2R NIL) can be capitalized in highly scalable fabrication of nanopatterns, preparation of large-area flexible molds remains the main challenge. In this work, we demonstrate that tiling of small-area nanopatterns in a slightly overlapped fashion can provide a practical solution to it; sequentially performing the UV NIL processes onto self-replicable UV-curable resin drops by using a small tile mold can create large-area-tiled molds. We systematically investigated that controlling the tile NIL force and several parameters is crucial to minimize the seams between tiles. We also present that the R2R NIL system can be improved by integrating a linear UV LED module for prompt UV curing before the as-imprinted nanopattern reflows, which is critical for high-resolution, high-quality nanopatterning. By using the tiled mold containing 45 nm-half-pitch nanogratings and operating the UV LED-integrated R2R NIL system, we exemplify that sub 50 nm-resolution nanopatterns can be faithfully created. [ABSTRACT FROM AUTHOR]

We present and analyze a database of 1.13 million public Instagram posts during the Black Lives Matter protests of 2020, which erupted in response to George Floyd's public murder by police on May 25. Our aim is to understand the growing role of visual media, focusing on a) the emergent opinion leaders and b) the subsequent press concerns regarding frames of legitimacy. We perform a comprehensive view of the spatial (where) and temporal (when) dynamics, the visual and textual content (what), and the user communities (who) that drove the social movement on Instagram. Results reveal the emergence of non-institutional opinion leaders such as meme groups, independent journalists, and fashion magazines, which contrasts with the institutionally reinforcing nature of Twitter. Visual analysis of 1.69 million photos show symbols of injustice are the most viral coverage, and moreover, actual protest coverage is framed positively, in contrast with combatant frames traditionally found from legacy media. Together, these factors helped facilitate the online movement through three phases, culminating with online international solidarity in #BlackOutTuesday. Through this case study, we demonstrate the precarious nature of protest journalism, and how content creators, journalists, and everyday users co-evolved with social media to shape one of America's largest-ever human rights movements. [ABSTRACT FROM AUTHOR]

In capacitively coupled plasmas (CCPs) operated under various pressure conditions in semiconductor manufacturing processes, the transition in discharge characteristics is observed depending on local or nonlocal electron kinetics. A two‐dimensional (2D) particle‐in‐cell (PIC) simulation is required because the one‐dimensional PIC method cannot capture the effect of device structures and because fluid models cannot treat the self‐consistent change in the energy distributions. Using a 2D PIC simulation parallelized with a graphics processing unit, we investigated the transition of electron kinetics for the variation of the driving voltage, gas pressure, the gap distance between upper and lower electrodes, and the sidewall condition. Moreover, the mechanism for electron energy relaxation in a CCP is elucidated to develop a method to improve the process uniformity. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the effects of subconjunctival injection of aflibercept, a soluble protein decoy for VEGFR-1 and VEGFR-2, on corneal angiogenesis and VEGFR-expressing CD11b+ cells in a mouse model of suture-induced corneal neovascularization.Corneal neovascularization was induced in BALB/c mice by placing three sutures on the cornea. Immediately after surgery, either 200 µg aflibercept (5 µL) or an equal volume of phosphate-buffered saline (PBS) was administered into the subconjunctival space. Seven days after later, corneal new vessels were quantified through clinical examination and measurement of the CD31-stained area in corneal flat mounts. The levels of pro-angiogenic and inflammatory markers in the cornea were evaluated using RT-qPCR. The percentages of VEGFR-2+CD11b+ cells and VEGFR-3+CD11b+ cells were analyzed in the cornea, blood, and draining cervical lymph nodes (DLNs) using flow cytometry.Subconjunctival injection of aflibercept significantly reduced the growth of corneal new vessels compared to subconjunctival PBS injection. The mRNA levels of Cd31, vascular growth factors (Vegfc and Angpt1), and pro-angiogenic/inflammatory markers (Tek/Tie2, Mrc1, Mrc2, and Il6) in the cornea were downregulated by subconjunctival aflibercept. Also, the percentage of VEGFR-3+CD11b+ cells in the cornea, blood, and DLNs was decreased by aflibercept, whereas that of VEGFR-2+CD11b+ cells was unaffected.Subconjunctival aflibercept administration inhibits inflammatory angiogenesis in the cornea and reduces the numbers of cornea-infiltrating and circulating VEGFR-3+CD11b+ cells.Methods: This study aimed to investigate the effects of subconjunctival injection of aflibercept, a soluble protein decoy for VEGFR-1 and VEGFR-2, on corneal angiogenesis and VEGFR-expressing CD11b+ cells in a mouse model of suture-induced corneal neovascularization.Corneal neovascularization was induced in BALB/c mice by placing three sutures on the cornea. Immediately after surgery, either 200 µg aflibercept (5 µL) or an equal volume of phosphate-buffered saline (PBS) was administered into the subconjunctival space. Seven days after later, corneal new vessels were quantified through clinical examination and measurement of the CD31-stained area in corneal flat mounts. The levels of pro-angiogenic and inflammatory markers in the cornea were evaluated using RT-qPCR. The percentages of VEGFR-2+CD11b+ cells and VEGFR-3+CD11b+ cells were analyzed in the cornea, blood, and draining cervical lymph nodes (DLNs) using flow cytometry.Subconjunctival injection of aflibercept significantly reduced the growth of corneal new vessels compared to subconjunctival PBS injection. The mRNA levels of Cd31, vascular growth factors (Vegfc and Angpt1), and pro-angiogenic/inflammatory markers (Tek/Tie2, Mrc1, Mrc2, and Il6) in the cornea were downregulated by subconjunctival aflibercept. Also, the percentage of VEGFR-3+CD11b+ cells in the cornea, blood, and DLNs was decreased by aflibercept, whereas that of VEGFR-2+CD11b+ cells was unaffected.Subconjunctival aflibercept administration inhibits inflammatory angiogenesis in the cornea and reduces the numbers of cornea-infiltrating and circulating VEGFR-3+CD11b+ cells.Results: This study aimed to investigate the effects of subconjunctival injection of aflibercept, a soluble protein decoy for VEGFR-1 and VEGFR-2, on corneal angiogenesis and VEGFR-expressing CD11b+ cells in a mouse model of suture-induced corneal neovascularization.Corneal neovascularization was induced in BALB/c mice by placing three sutures on the cornea. Immediately after surgery, either 200 µg aflibercept (5 µL) or an equal volume of phosphate-buffered saline (PBS) was administered into the subconjunctival space. Seven days after later, corneal new vessels were quantified through clinical examination and measurement of the CD31-stained area in corneal flat mounts. The levels of pro-angiogenic and inflammatory markers in the cornea were evaluated using RT-qPCR. The percentages of VEGFR-2+CD11b+ cells and VEGFR-3+CD11b+ cells were analyzed in the cornea, blood, and draining cervical lymph nodes (DLNs) using flow cytometry.Subconjunctival injection of aflibercept significantly reduced the growth of corneal new vessels compared to subconjunctival PBS injection. The mRNA levels of Cd31, vascular growth factors (Vegfc and Angpt1), and pro-angiogenic/inflammatory markers (Tek/Tie2, Mrc1, Mrc2, and Il6) in the cornea were downregulated by subconjunctival aflibercept. Also, the percentage of VEGFR-3+CD11b+ cells in the cornea, blood, and DLNs was decreased by aflibercept, whereas that of VEGFR-2+CD11b+ cells was unaffected.Subconjunctival aflibercept administration inhibits inflammatory angiogenesis in the cornea and reduces the numbers of cornea-infiltrating and circulating VEGFR-3+CD11b+ cells.Conclusion: This study aimed to investigate the effects of subconjunctival injection of aflibercept, a soluble protein decoy for VEGFR-1 and VEGFR-2, on corneal angiogenesis and VEGFR-expressing CD11b+ cells in a mouse model of suture-induced corneal neovascularization.Corneal neovascularization was induced in BALB/c mice by placing three sutures on the cornea. Immediately after surgery, either 200 µg aflibercept (5 µL) or an equal volume of phosphate-buffered saline (PBS) was administered into the subconjunctival space. Seven days after later, corneal new vessels were quantified through clinical examination and measurement of the CD31-stained area in corneal flat mounts. The levels of pro-angiogenic and inflammatory markers in the cornea were evaluated using RT-qPCR. The percentages of VEGFR-2+CD11b+ cells and VEGFR-3+CD11b+ cells were analyzed in the cornea, blood, and draining cervical lymph nodes (DLNs) using flow cytometry.Subconjunctival injection of aflibercept significantly reduced the growth of corneal new vessels compared to subconjunctival PBS injection. The mRNA levels of Cd31, vascular growth factors (Vegfc and Angpt1), and pro-angiogenic/inflammatory markers (Tek/Tie2, Mrc1, Mrc2, and Il6) in the cornea were downregulated by subconjunctival aflibercept. Also, the percentage of VEGFR-3+CD11b+ cells in the cornea, blood, and DLNs was decreased by aflibercept, whereas that of VEGFR-2+CD11b+ cells was unaffected.Subconjunctival aflibercept administration inhibits inflammatory angiogenesis in the cornea and reduces the numbers of cornea-infiltrating and circulating VEGFR-3+CD11b+ cells. [ABSTRACT FROM AUTHOR]

Prostate specific membrane antigen (PSMA) is known to be overexpressed in prostate cancer cells, providing as a diagnostic and therapeutic target for prostate cancer. A lutetium-labeled PSMA targeted ligand, 177Lu-DOTA-PSMA-GUL is a novel radiopharmaceutical, which has been developed for the treatment of prostate cancer. While the GUL domain of 177Lu-DOTA-PSMA-GUL binds to the antigen, the beta-emitting radioisotope, 177Lu-labeled DOTA, interacts with prostate cancer cells. However, the in vivo pharmacokinetics of intact 177Lu-DOTA-PSMA-GUL has never been characterized. This study aimed to evaluate the pharmacokinetics and tissue distribution of the radiopharmaceutical in rats by using its stable isotope-labeled analog, 175Lu-DOTA-PSMA-GUL. A sensitive liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis of 175Lu-DOTA-PSMA-GUL was developed and validated. Following intravenous injection, the plasma concentration–time profiles of 175Lu-DOTA-PSMA-GUL showed a multi-exponential decline with the average elimination half-life of 0.30 to 0.33 h. Systemic exposure increased with the dose and renal excretion is the major elimination route. Tissue distribution of 175Lu-DOTA-PSMA-GUL was most substantial in kidneys, followed by the prostate. The developed LC–MS/MS assay and the in vivo pharmacokinetic data of 175Lu-DOTA-PSMA-GUL would provide helpful information for further clinical studies to be developed as a novel therapeutic agent for prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Reported bacteraemia outcomes following inactive empirical antibiotics (based on in vitro testing) are conflicting, potentially reflecting heterogeneity in causative species, MIC breakpoints defining resistance/susceptibility, and times to rescue therapy.Methods: We investigated adult inpatients with Escherichia coli bacteraemia at Oxford University Hospitals, UK, from 4 February 2014 to 30 June 2021 who were receiving empirical amoxicillin/clavulanate with/without other antibiotics. We used Cox regression to analyse 30 day all-cause mortality by in vitro amoxicillin/clavulanate susceptibility (activity) using the EUCAST resistance breakpoint (>8/2 mg/L), categorical MIC, and a higher resistance breakpoint (>32/2 mg/L), adjusting for other antibiotic activity and confounders including comorbidities, vital signs and blood tests.Results: A total of 1720 E. coli bacteraemias (1626 patients) were treated with empirical amoxicillin/clavulanate. Thirty-day mortality was 193/1400 (14%) for any active baseline therapy and 52/320 (16%) for inactive baseline therapy (P = 0.17). With EUCAST breakpoints, there was no evidence that mortality differed for inactive versus active amoxicillin/clavulanate [adjusted HR (aHR) = 1.27 (95% CI 0.83-1.93); P = 0.28], nor of an association with active aminoglycoside (P = 0.93) or other active antibiotics (P = 0.18). Considering categorical amoxicillin/clavulanate MIC, MICs > 32/2 mg/L were associated with mortality [aHR = 1.85 versus MIC = 2/2 mg/L (95% CI 0.99-3.73); P = 0.054]. A higher resistance breakpoint (>32/2 mg/L) was independently associated with higher mortality [aHR = 1.82 (95% CI 1.07-3.10); P = 0.027], as were MICs > 32/2 mg/L with active empirical aminoglycosides [aHR = 2.34 (95% CI 1.40-3.89); P = 0.001], but not MICs > 32/2 mg/L with active non-aminoglycoside antibiotic(s) [aHR = 0.87 (95% CI 0.40-1.89); P = 0.72].Conclusions: We found no evidence that EUCAST-defined amoxicillin/clavulanate resistance was associated with increased mortality, but a higher resistance breakpoint (MIC > 32/2 mg/L) was. Additional active baseline non-aminoglycoside antibiotics attenuated amoxicillin/clavulanate resistance-associated mortality, but aminoglycosides did not. Granular phenotyping and comparison with clinical outcomes may improve AMR breakpoints. [ABSTRACT FROM AUTHOR]

To investigate the effect of fucosyltransferase (FUT) 1-mediated fucosylation on meibomian glands (MG), we first confirmed that FUT1 and its fucosylated products were expressed in the eyelid, conjunctiva and skin in wild-type (WT) mice, whereas their mRNA and protein levels were downregulated in Fut1 knock-out (KO) mice. We then evaluated age-dependent changes in the total and acinar areas of MG, meibocyte differentiation, lipid synthesis, and eyelid inflammation and oxidative stress in Fut1 KO and WT mice. Results show that both the total and acinar areas of MG were smaller in Fut1 KO mice than in WT mice in all evaluated age groups. Meibocyte differentiation, lipid-producing capacities and the enzyme levels responsible for lipid synthesis were reduced in Fut1 KO mice, compared to WT controls. The levels of pro-inflammatory cytokines and oxidative-stress-related markers were elevated in the eyelids and MG of FUT1 KO mice. These findings demonstrate the physiologic function of FUT1-mediated fucosylation in MG development and function, and indicate its potential role in ocular surface homeostasis. [ABSTRACT FROM AUTHOR]

Several recent preclinical studies have reported that dynamic changes in miRNA expression contribute to hearing function. This study aims to investigate miRNA expression changes in the cochlear nuclei (CN) of rats following chronic noise exposure. Eight-week-old rats (n = 14) were exposed to noise for 4 weeks. The control rats (n = 14) were raised under identical conditions without noise. Two months after noise exposure, the auditory brainstem response (ABR) was examined, and the cochlea and CN were harvested. In the CN, the expression levels of arc, neurocan, and brevican were measured (n = 6 per group). Furthermore, the expression levels of miRNAs and their predicted target genes were measured in the CN (n = 8 per group). ABR thresholds were elevated after 4 weeks of noise exposure, which were maintained for 3 months. In CN, the protein expression of arc and brevican was higher in the noise-exposed group than in the control group (0.95 [standard deviation (SD) = 0.53] vs. 3.19 [SD = 1.00], p < 0.001 for arc and 1.02 [SD = 0.10] vs. 1.66 [SD = 0.24], p < 0.001 for brevican). The noise-exposed rats exhibited lower expression levels of miR-758-5p, miR-15b-5p, miR-212-3p, miR-199a-5p, and miR-134-3p than the control rats (all p < 0.001). The AMPK signaling pathway was predicted to be regulated by these miRNAs. The predicted target genes AKT3, SIRT1, and PRKAA1 were highly expressed in noise-exposed rats. In CN of noise-exposed rats, the miRNAs of miR-758-5p, miR-15b-5p, miR-212-3p, miR-199a-5p, and miR-134-3p were reduced and related to AMPK signaling including AKT3 and SIRT1 expression. These modulation of signaling pathways could mediate the increased expression of brevican in the CN of noise-exposed rats. [ABSTRACT FROM AUTHOR]

In this paper we propose a new concept of quasi-uniform monotonicity weaker than the uniform monotonicity which has been developed in the study of nonlinear operator equation Au = b. We prove that if A is a quasi-uniformly monotone and hemi-continuous operator, then A−1 is strictly monotone, bounded and continuous, and thus the Galerkin approximations converge. Also we show an application of a quasi-uniformly monotone and hemi-continuous operator to the proof of the well-posedness and convergence of Galerkin approximations to the solution of steady-state electromagnetic p-curl systems. [ABSTRACT FROM AUTHOR]

Objective: We investigated whether (1) imported pre-cut tissue is feasible for Descemet membrane endothelial keratoplasty (DMEK) in eyes of Asian patients, (2) the clinical outcome is comparable between the endothelium‐in and endothelium‐out methods, and (3) the corneal edema-induced anterior curvature changes may have an effect on the refractive error. Methods: The medical records of 32 DMEK patients who underwent either the endothelium-out or endothelium-in method using imported pre-cut grafts with a 3-day pre-cut-to-use time were retrospectively analyzed. Fuchs' endothelial dystrophy (37.5%) and bullous keratopathy (62.5%) cases were included. The main clinical outcome measures were graft survival, best corrected visual acuity (BCVA), endothelial cell density (ECD), corneal thickness (CT), and complications. Correlation of the anterior curvature changes with refractive error was analyzed in the DMEK with cataract surgery group. Results: The overall survival rate was 71.9%. Final graft failures were caused by rejection, glaucoma, and infection. Visual acuities improved by 89.3%. BCVA better than 20/40 and 20/20 was found in 75% and 28.6% of patients, respectively. The ECDs at 3 months and 1 year were 1400 and 1083 cells/mm2, respectively. The mean survival time, ECD, BCVA, CT, and complication rates were not different between the endothelium-in and endothelium-out methods. A hyperopic shift by +0.42 D was not related to the anterior curvature changes. Conclusion: Imported pre-cut tissues with a ≤ 3-day pre-cut-to-use time are feasible for DMEK in the treatment of corneal endothelial edema in eyes of Asian patients, and both endothelium-in and endothelium-out methods appear to be comparatively effective. Edema-induced anterior curvature change may not affect the refractive shift. [ABSTRACT FROM AUTHOR]

The effect of statins on aminoglycoside-induced ototoxicity is controversial. This study aimed to explore the role of pravastatin (PV) in kanamycin-induced hearing loss in rats. Adult rats were intraperitoneally treated with 20 mg/kg/day of kanamycin (KM) for 10 days. In the PV- and PV + KM-treated rats, 25 mg/kg/day of PV was intraperitoneally administered for 5 days. The auditory brainstem response (ABR) thresholds were measured before and after drug treatment using a smartEP system at 4, 8, 16, and 32 kHz. Cochlear changes in poly ADP-ribose (PAR) polymerase (PARP), PAR, and caspase 3 were estimated using Western blotting. PV administration did not increase the ABR thresholds. The KM-treated rats showed elevated ABR thresholds at 4, 8, 16, and 32 kHz. The PV + KM-treated rats demonstrated lower ABR thresholds than the KM-treated rats at 4, 8, and 16 kHz. The cochlear outer hair cells and spiral ganglion cells were relatively preserved in the PV + KM-treated rats when compared with that in the KM-treated rats. The cochlear expression levels of PARP, PAR, and caspase 3 were higher in the KM-treated rats. The PV + KM-treated rats showed lower levels of PARP, PAR, and caspase 3 than the KM-treated rats. PV protected cochleae from KM-induced hearing loss in rats. The regulation of autophagy and apoptosis mediated the otoprotective effects of PV. [ABSTRACT FROM AUTHOR]

Background: Optimal management of primary aldosteronism (PA) is crucial due to the increased risk of cardiovascular and cerebrovascular diseases. Adrenal venous sampling (AVS) is the gold standard method for determining subtype but is technically challenging and invasive. Some PA patients do not benefit clinically from surgery. We sought to develop an algorithm to improve decision- making before engaging in AVS and surgery in clinical practice. Methods: We conducted the ongoing Korean Primary Aldosteronism Study at two tertiary centers. Study A involved PA patients with successful catheterization and a unilateral nodule on computed tomography and aimed to predict unilateral aldosterone-producing adenoma (n=367). Study B involved similar patients who underwent adrenalectomy and aimed to predict postoperative outcome (n=330). In study A, we implemented important feature selection using the least absolute shrinkage and selection operator regression. Results: We developed a unilateral PA prediction model using logistic regression analysis: lowest serum potassium level ≤3.4 mEq/L, aldosterone-to-renin ratio ≥150, plasma aldosterone concentration ≥30 ng/mL, and body mass index <25 kg/m2 (area under the curve, 0.819; 95% confidence interval, 0.774 to 0.865; sensitivity, 97.6%; specificity, 25.5%). In study B, we identified female, hypertension duration <5 years, anti-hypertension medication <2.5 daily defined dose, and the absence of coronary artery disease as predictors of clinical success, using stepwise logistic regression models (sensitivity, 94.2%; specificity, 49.3%). We validated our algorithm in the independent validation dataset (n=53). Conclusion: We propose this new outcome-driven diagnostic algorithm, simultaneously considering unilateral aldosterone excess and clinical surgical benefits in PA patients. [ABSTRACT FROM AUTHOR]

Begomoviruses belonging to the family Geminiviridae are plant‐infecting DNA viruses. Begomoviral movement protein (MP) has been reported to be required for virus movement, host range determination, and symptom development. In the present study, the FK506‐binding protein (FKBP)‐type peptidyl‐prolyl cis‐trans isomerase (NbFKPPIase) of Nicotiana benthamiana was identified by a yeast two‐hybrid screening system using the MP of tomato leaf curl New Delhi virus (ToLCNDV) oriental melon (OM) isolate (MPOM) as bait. Transient silencing of the gene encoding NbFKPPIase increased replication of three test begomoviruses, and transient overexpression decreased viral replication, indicating that NbFKPPIase plays a role in defence against begomoviruses. However, infection of N. benthamiana by ToLCNDV‐OM or overexpression of the gene encoding MPOM drastically reduced the expression of the gene encoding NbFKPPIase. Fluorescence resonance energy transfer analysis revealed that MPOM interacted with NbFKPPIase in the periphery of cells. Expression of the gene encoding NbFKPPIase was induced by salicylic acid but not by methyl jasmonate or ethylene. Moreover, the expression of the gene encoding NbFKPPIase was down‐regulated in response to 6‐benzylaminopurine and up‐regulated in response to gibberellin or indole‐3‐acetic acid, suggesting a role of NbFKPPIase in plant development. Transcriptome analysis and comparison of N. benthamiana transient silencing and overexpression of the gene encoding MPOM led to the identification of several differentially expressed genes whose functions are probably associated with cell cycle regulation. Our results indicate that begomoviruses could suppress NbFKPPIase‐mediated defence and biological functions by transcriptional inhibition and physical interaction between MP and NbFKPPIase to facilitate infection. [ABSTRACT FROM AUTHOR]

Objective: Primary aldosteronism (PA) shows histological heterogeneity and clinical variability, including the coexistence of hypercortisolemia. Immunohistochemical analyses of steroidogenic enzymes in adrenal tissues have provided new insights into the pathogenesis of PA. However, a comprehensive analysis of the association between enzyme expression and clinical characteristics of PA has rarely been conducted. We aimed to investigate the correlation between clinical characteristics and steroidogenic enzyme expression in PA. Design: A retrospective case‐control study. Patients: Consecutive patients who underwent unilateral adrenalectomy for PA (n = 180). Patients with adrenal Cushing's syndrome (CS) (n = 29) and nonfunctioning adenoma (n = 6) as comparator groups. Measurements: A tissue microarray of adrenal adenomas was constructed and immunostained for CYP11B1, CYP11B2 and CYP17A1. The expression of the three enzymes was compared between PA and other adrenal diseases and between PA with and without mild autonomous cortisol excess (MACE). Results: Adrenal adenomas in PA showed lower CYP11B1, higher CYP11B2 and lower CYP17A1 expression than those in adrenal CS (p <.001). Nonfunctioning adenomas showed low expression of the three enzymes. PA with MACE showed higher CYP11B1 expression than PA without MACE. CYP11B1 expression was positively correlated with the severity of hypercortisolemia, and CYP11B2 was positively correlated with that of hyperaldosteronism. The expression of CYP11B1 and CYP11B2 had a negative correlation. Patients with absent clinical improvement after adrenalectomy had lower CYP11B2 expression than those with complete success. Conclusions: Variable expression of steroidogenic enzymes in adrenal adenoma underlies the clinical heterogeneity of PA and is associated with treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: To compare the efficacy and safety of two insulin self-titration algorithms, Implementing New Strategies with Insulin Glargine for Hyperglycemia Treatment (INSIGHT) and EDITION, for insulin glargine 300 units/mL (Gla-300) in Korean individuals with uncontrolled type 2 diabetes mellitus (T2DM). Methods: In a 12-week, randomized, open-label trial, individuals with uncontrolled T2DM requiring basal insulin were randomized to either the INSIGHT (adjusted by 1 unit/day) or EDITION (adjusted by 3 units/week) algorithm to achieve a fasting selfmonitoring of blood glucose (SMBG) in the range of 4.4 to 5.6 mmol/L. The primary outcome was the proportion of individuals achieving a fasting SMBG ≤5.6 mmol/L without nocturnal hypoglycemia at week 12. Results: Of 129 individuals (age, 64.1±9.5 years; 66 [51.2%] women), 65 and 64 were randomized to the INSIGHT and EDITION algorithms, respectively. The primary outcome of achievement was comparable between the two groups (24.6% vs. 23.4%, P=0.876). Compared with the EDITION group, the INSIGHT group had a greater reduction in 7-point SMBG but a similar decrease in fasting plasma glucose and glycosylated hemoglobin. The increment of total daily insulin dose was significantly higher in the INSIGHT group than in the EDITION group (between-group difference: 5.8±2.7 units/day, P=0.033). However, body weight was significantly increased only in the EDITION group (0.6±2.4 kg, P=0.038). There was no difference in the occurrence of hypoglycemia between the two groups. Patient satisfaction was significantly increased in the INSIGHT group (P=0.014). Conclusion: The self-titration of Gla-300 using the INSIGHT algorithm was effective and safe compared with that using the EDITION algorithm in Korean individuals with uncontrolled T2DM (ClinicalTrials.gov number: NCT03406663). [ABSTRACT FROM AUTHOR]

Background: The detection and identification of pathogenic microorganisms are essential for the treatment of osteoarticular infection. However, obtaining a sufficient amount of specimen from pediatric patients is often difficult. Herein, we aimed to demonstrate the effectiveness of the blood culture bottle (BCB) system in pediatric osteoarticular infections. We hypothesized that our BCB culture method is superior to the conventional swab and tissue culture methods in terms of required specimen size, incubation time, and microbial identification rate.Methods: We analyzed the prospectively collected data of pediatric patients who underwent surgical treatment for osteoarticular infections between August 2016 and October 2019. Four needles were dipped in the infected fluid or tissue during the surgical procedure as soon as the infected area was exposed and were used to inoculate 2 aerobic pediatric BCBs and 2 anaerobic general BCBs. We also collected 2 conventional swab samples and 2 tissue samples from the identical area. The microbial identification rate and the time required for identification were compared between BCB, swab, and tissue cultures.Results: Forty patients constituted the study group; 13 patients had osteomyelitis, 17 patients had septic arthritis, and 10 patients had both. Of these 40 patients, the microbial identification rate was higher with BCB cultures (27 [68%]) than with swab cultures (18 [45%]; p = 0.004) or tissue cultures (15 [38%]; p < 0.001). Nine samples (9 patients [23%]) were only positive in the BCB culture. Positive microbial growth was not detected with conventional culture methods when microorganisms did not grow on the BCB culture. Compared with swab culture (4.3 ± 1.1 days; p < 0.001) or tissue culture (4.4 ± 1.1 days; p < 0.001), the BCB culture reduced the time required for microbial identification (3.5 ± 0.9 days).Conclusions: In pediatric osteoarticular infections, the BCB culture system improved the microbial identification rate, reduced the time to identification, and permitted a smaller-volume specimen, compared with traditional culture systems.Level Of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Induction treatment with rituximab—an anti-CD20 monoclonal antibody—may increase the risk of varicella-zoster virus (VZV) reactivation in patients with antineutrophil-cytoplasmic-antibody-associated vasculitis (AAV). Our case report shows VZV reactivation following rituximab treatment in AAV patients. The recombinant zoster vaccine should be recommended before the start of induction treatment with rituximab. [ABSTRACT FROM AUTHOR]

Employing the Korea-IBS-Daegu-SKKU (KIDS) density functional for the hadron phase and the MIT bag model with vector (vBag) model for the quark phase, we obtain hadron-quark phase transition in neutron stars considering Maxwell construction. The structural properties of the resultant hybrid stars are computed for three different values of bag constant (B) in the range B1/4 = (145-160 MeV). We study the effects of symmetry energy (J) on the hybrid star properties with the different KIDS model and found that J has important influence not only on the transition properties like the transition mass, transition radius and jump in density due to phase transition, but also on the stability of the hybrid stars. The vector repulsion of the quark phase via the parameter GV has profound influence in obtaining reasonable hybrid star configurations, consistent with the recent astrophysical constraints on the structural properties of compact stars. Within the aforesaid range of B, the value of GV is constrained to be 0.3 < GV < 0.4 in order to obtain reasonable hybrid star configurations. [ABSTRACT FROM AUTHOR]

The contributions of phytoplankton and bacteria cells to alkalinity (AT) were measured in seawater samples obtained from 205 locations including the East Sea, the North Pacific Ocean, the Bering Sea, the Chukchi Sea, and the Arctic Ocean. We attributed the differences in AT values measured for unfiltered versus filtered samples to AT components contributed by phytoplankton (retained on a 0.7 μm filter) and by phytoplankton and bacteria combined (AT−BIO; retained on a 0.45 μm filter). The AT−BIO values reached 10–19 μmol kg−1 in the East Sea and the North Pacific Ocean, and progressively decreased to a level of 1 μmol kg−1 with distance toward the Arctic Ocean. The study shows that the AT−BIO values are non‐negligible in coastal and open ocean environments and need to be considered when assessing the accuracy of carbon parameters calculated using the thermodynamic models that use measured AT as an input parameter. Plain Language Summary: In seawater thermodynamic calculations involving measured alkalinity, estimates of alkalinity contributed by bicarbonate and carbonate ions only are needed, and are made by correcting measured alkalinity values for contributions from borate and hydroxide ions, and from other minor chemical species. Among those minor components, contributions from phytoplankton and bacteria cells are an uncharacterized component of measured alkalinity. The present study shows that the contribution of particulate organic matter (mostly phytoplankton and bacteria) to measured alkalinity is significant in ocean environments. The common practice of making alkalinity measurements using unfiltered seawater in field studies could lead to overestimation of carbonate alkalinity when converting total alkalinity to carbonate alkalinity, because most total alkalinity data have been assumed to have negligible biological components. This overestimation could subsequently lead to errors in the calculated parameters. Thus the biological component in the total alkalinity needs to be taken into account when predicting carbon parameters using the thermodynamic models that use measured alkalinity as an input parameter. Key Points: Phytoplankton and bacteria cells contributed to alkalinity during the titration of seawaterThe biological components in alkalinity were non‐negligible in coastal and open ocean environmentsThe biological components in alkalinity varied markedly depending on phytoplankton species in seawater [ABSTRACT FROM AUTHOR]

Background: Hemihyperplasia and hemihypoplasia result in leg length discrepancy (LLD) by causing skeletal asymmetry. Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are opposite growth-affecting disorders caused by opposite epigenetic alterations at the same chromosomal locus, 11p15, to induce hemihyperplasia and hemihypoplasia, respectively. Because of their somatic mosaicism, BWS and SRS show a wide spectrum of clinical phenotypes. We evaluated the underlying epigenetic alterations and potential epigenotype-phenotype correlations, focusing on LLD, in a group of individuals with isolated hemihyperplasia/hemihypoplasia.Results: We prospectively collected paired blood-tissue samples from 30 patients with isolated hemihyperplasia/hemihypoplasia who underwent surgery for LLD. Methylation-specific multiplex-ligation-dependent probe amplification assay (MS-MLPA) and bisulfite pyrosequencing for differentially methylated regions 1 and 2 (DMR1 and DMR2) on chromosome 11p15 were performed using the patient samples. Samples from patients showing no abnormalities in MS-MLPA or bisulfite pyrosequencing were analyzed by single nucleotide polymorphism (SNP) microarray and CDKN1C Sanger sequencing. We introduced a metric named as the methylation difference, defined as the difference in DNA methylation levels between DMR1 and DMR2. The correlation between the methylation difference and the predicted LLD at skeletal maturity, calculated using a multiplier method, was evaluated. Predicted LLD was standardized for stature. Ten patients (33%) showed epigenetic alterations in MS-MLPA and bisulfite pyrosequencing. Of these, six and four patients had epigenetic alterations related to BWS and SRS, respectively. The clinical diagnosis of hemihyperplasia/hemihypoplasia was not compatible with the epigenetic alterations in four of these ten patients. No patients showed abnormalities in SNP array or their CDKN1C sequences. The standardized predicted LLD was moderately correlated with the methylation difference using fat tissue (r = 0.53; p = 0.002) and skin tissue (r = 0.50; p = 0.005) in all patients.Conclusions: Isolated hemihyperplasia and hemihypoplasia can occur as a spectrum of BWS and SRS. Although the accurate differentiation between isolated hemihyperplasia and isolated hemihypoplasia is important in tumor surveillance planning, it is often difficult to clinically differentiate these two diseases without epigenetic tests. Epigenetic tests may play a role in the prediction of LLD, which would aid in treatment planning. [ABSTRACT FROM AUTHOR]