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Abstract Despite the current widespread use of chromosomal microarray analysis (CMA) and exome/genome sequencing for the genetic diagnosis of unexplained intellectual disability (ID) in children, gaining improved diagnostic yields and defined guidelines remains a significant challenge. This is a cohort study of children with unexplained ID. We analyzed the diagnostic yield and its correlation to clinical phenotypes in children with ID who underwent concurrent CMA and clinical exome sequencing (CES). A total of 154 children were included (110 [71.4%] male; mean [SD] age, 51.9 [23.1] months). The overall diagnosis yield was 26.0–33.8%, with CMA contributing 12.3–14.3% and CES contributing 13.6–19.4%, showing no significant difference. The diagnostic rate was significantly higher when gross motor delay (odds ratio, 6.69; 95% CI, 3.20–14.00; P

Abstract Preterm birth prediction is essential for improving neonatal outcomes. While many machine learning techniques have been applied to predict preterm birth using health records, inflammatory markers, and vaginal microbiome data, the role of prenatal oral microbiome remains unclear. This study aimed to compare oral microbiome compositions between a preterm and a full-term birth group, identify oral microbiome associated with preterm birth, and develop a preterm birth prediction model using machine learning of oral microbiome compositions. Participants included singleton pregnant women admitted to Jeonbuk National University Hospital between 2019 and 2021. Subjects were divided into a preterm and a full-term birth group based on pregnancy outcomes. Oral microbiome samples were collected using mouthwash within 24 h before delivery and 16S ribosomal RNA sequencing was performed to analyze taxonomy. Differentially abundant taxa were identified using DESeq2. A random forest classifier was applied to predict preterm birth based on the oral microbiome. A total of 59 women participated in this study, with 30 in the preterm birth group and 29 in the full-term birth group. There was no significant difference in maternal clinical characteristics between the preterm and the full-birth group. Twenty-five differentially abundant taxa were identified, including 22 full-term birth-enriched taxa and 3 preterm birth-enriched taxa. The random forest classifier achieved high balanced accuracies (0.765 ± 0.071) using the 9 most important taxa. Our study identified 25 differentially abundant taxa that could differentiate preterm and full-term birth groups. A preterm birth prediction model was developed using machine learning of oral microbiome compositions in mouthwash samples. Findings of this study suggest the potential of using oral microbiome for predicting preterm birth. Further multi-center and larger studies are required to validate our results before clinical applications.

Polybenzoxazine (PBz) aerogels hold immense potential, but their conventional production methods raise environmental and safety concerns. This research addresses this gap by proposing an eco-friendly approach for synthesizing high-performance carbon derived from polybenzoxazine. The key innovation lies in using eugenol, ethylene diamine, and formaldehyde to create a polybenzoxazine precursor. This eliminates hazardous solvents by employing the safer dimethyl sulfoxide. An acidic catalyst plays a crucial role, not only in influencing the microstructure but also in strengthening the material’s backbone by promoting inter-chain connections. Notably, this method allows for ambient pressure drying, further enhancing its sustainability. The polybenzoxazine acts as a precursor to produce two different carbon materials. The carbon material produced from the calcination of PBz is denoted as PBZC, and the carbon material produced from the gelation and calcination of PBz is denoted as PBZGC. The structural characterization of these carbon materials was analyzed through different techniques, such as XRD, Raman, XPS, and BET analyses. BET analysis showed increased surface of 843 m2 g−1 for the carbon derived from the gelation method (PBZGC). The electrochemical studies of PBZC and PBZGC imply that a well-defined morphology, along with suitable porosity, paves the way for increased conductivity of the materials when used as electrodes for supercapacitors. This research paves the way for utilizing heteroatom-doped, polybenzoxazine aerogel-derived carbon as a sustainable and high-performing alternative to traditional carbon materials in energy storage devices.

Developmental delays (DD) and congenital anomalies (CA) are prevalent yet often remain undiagnosed despite comprehensive genetic testing. This study aims to investigate the diagnostic yield of trio whole-genome sequencing (WGS) in children presenting with DD or CA who remained undiagnosed after previous genetic testing. A prospective cohort study was conducted on children with undiagnosed DD or CA at a single tertiary hospital. All participants suspected of genetic conditions had undergone chromosome analysis, chromosome microarray analysis (CMA), and clinical exome sequencing (CES); however, a subset remained undiagnosed. The WGS test was administered to both the affected children and their parents. A total of 52 children were included, and 10 (19.2%) had undergone a genetic diagnosis through WGS. Eight of these cases were associated with autosomal dominant and de novo variants. WGS led to successful diagnosis due to several factors, including small structural variants, genes not covered in the CES panel, the discovery of newly implicated genes, issues related to coverage depth, low variant allele frequency, challenges in variant interpretation, and differences in the interpretation of variants of unknown significance among clinicians. This study highlights the clinical value of trio WGS testing in undiagnosed children with DD or CA. Notably, an additional 19.2% of affected children were diagnosed through this method.

This study developed multi-linear regression (MLR) quantitative structure-activity relationships (QSARs) to predict n-TiO2 aggregation in the presence of high concentrations of representative emerging organic contaminants (EOCs), which presented favorable conditions to interaction with n-TiO2. The largest diameter change (Δ 517 nm at 0 h and Δ 1164 nm at 12 h) of n-TiO2 was observed by estrone, while the smallest diameter change (Δ −114 nm at 0 h and – 4 nm at 12 h) was observed by lincomycin during experimental periods. In addition, the zeta potential changes of n-TiO2 were observed that the biggest changes were observed by 17β-estradiol (−1.3 mV) and alachlor (−10.02 mV) at 0 h, while 17β-estradiol (−1.31 mV) and pendimethalin (−11.4 mV) showed the biggest changes at 12 h comparing to control. These changes of n-TiO2 diameter and zeta potential may implicate the effects of unique physico-chemical properties of each EOC on the surface modification of n-TiO2. Based on the interaction results, this study investigated the QSARs between n-TiO2 aggregation and physico-chemical descriptors of EOCs with 7 representative descriptors (pKa, Cw, log Kow, M.W., P.S.A., M.V., # of HBD) for predicting n-TiO2 aggregation rate kinetics at 0 h and 12 h by applying MATLAB statistical methods (model 1 - fitlm and model 2 - stepwiselm). In a model 1, QSARs showed the good coefficients of determination (R2 = 0.92) at 0 h and (R2 = 0.87) at 12 h with 7 descriptors. In a model 2, QSARs showed the goodness of fit of a model (R2 = 0.9998) with 8 descriptors (pKa, Cw, log Kow, M.W., P.S.A., M.V., #HBD, pKa⋅#H bond donors) at 0 h, while QSARs showed the coefficients of determination (R2 = 0.68) with 2 descriptors (pKa, M.V.) at 12 h. Particularly, we observed that some descriptors of EOCs such as pKa and # of HBD having polarity have more influenced on the n-TiO2 aggregation rate kinetics. Our developed QSARs demonstrated that the 7 descriptors of EOCs were significantly effective descriptors for predicting n-TiO2 aggregation rate kinetics in favorable conditions, which may implicate the complexity interactions between heterogeneous surfaces of n-TiO2 and physico-chemical properties of EOCs.

Background: The ongoing COVID-19 pandemic has seen the emergence of numerous novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. In this study, we compared the efficacy of three different forms of immunization against the wild-type, delta, and omicron variants of the virus: two doses of the BNT or AZ vaccine (BNT/BNT or AZ/AZ) as homologous vaccination, three doses of AZ/AZ/BNT as heterologous vaccination, and naturally occurring immunization in severe COVID-19 cases. Methods: We collected serum samples from vaccine recipients (67 receiving BNT/BNT, 111 receiving AZ/AZ, and 18 receiving AZ/AZ/BNT) and 46 patients who were admitted to the hospital with severe COVID-19. Blood samples were taken one month after the last injection and the efficacy of the vaccination was determined using the surrogate virus neutralization test (sVNT), with a positive result defined as an inhibition rate of over 30%. Serum samples from COVID-19 patients were taken at various points during their hospitalization and tested for inhibition rates. Results: Our results indicated that there was no notable difference in the levels of neutralizing antibodies (nAb) in vaccine recipients and patients against the wild-type and delta variants. However, when it came to the omicron variant, the vaccine recipients had significantly lower nAb titers. Among the vaccine recipients, those who received a booster dose of BNT after their first two doses of AZ (AZ/AZ/BNT) demonstrated the highest level of protection against the omicron variant at 44.4%, followed closely by the COVID-19 patients. In analyzing the serial samples taken from hospitalized COVID-19 patients, we observed that their inhibition rates against the wild-type and delta variants improved over time, while the inhibition rate against the omicron variant decreased. Conclusion: In conclusion, our findings suggest that heterologous booster vaccination after primary vaccination produces higher nAb titers and provides a higher level of protection against the omicron variant compared to primary vaccination alone. This protective effect was similar to that observed in patients with severe COVID-19.

This study explores the influence of solution concentration, specifically that of water and ethylene glycol mixtures, on the optical and supercapacitive properties of cobalt tungstate (CoWO4) nanoparticles. CoWO4 nanoparticles were synthesized using varying ratios of water to ethylene glycol to ascertain the optimal conditions for enhanced performance. Detailed characterization was conducted using UV–Vis spectroscopy, photoluminescence (PL) spectroscopy, cyclic voltammetry (CV), and galvanostatic charge–discharge (GCD) to evaluate the optical properties and electrochemical behavior, respectively. The results revealed that the solution concentration significantly impacted the bandgap, absorbance, and emission properties of the CoWO4 nanoparticles. Effective bandgap tuning was achieved by altering the solution concentration. When using only water, the nanoparticles displayed the lowest bandgap of 2.57 eV. In contrast, a solution with equal water and ethylene glycol concentrations resulted in the highest bandgap of 2.65 eV. Additionally, the electrochemical studies demonstrated that the water/ethylene glycol ratio markedly influenced the charge storage capacity and cyclic stability of the nanoparticles. The results indicated that the solvent concentration significantly influenced the crystallinity, particle size, and surface morphology of the CoWO4 nanoparticle nanoparticles, which affected their optical properties and electrochemical performance. Notably, nanoparticles synthesized with a 1.25:0.75 proportion of water to ethylene glycol exhibited superior supercapacitive performance, with a specific capacitance of 661.82 F g−1 at a current density of 7 mA cm−2 and 106% capacitance retention after 8000 charge–discharge cycles. These findings underscore the critical role of solvent composition in tailoring the functional properties of CoWO4 nanoparticles, providing insights for their application in optoelectronic devices and energy storage systems.

This study presents a promising method for creating high-performance supercapacitor electrodes. The approach involves crafting a unique composite material—nickel-cobalt-layered double hydroxides (NiCo-LDH) grown on carbon nanoballs (CNBs). This is achieved by first creating a special carbon material rich in oxygen and nitrogen from a polybenzoxazine source. At first, eugenol, ethylene diamine and paraformaldehyde undergo Mannich condensation to form the benzoxazine monomer, which undergoes self-polymerization in the presence of heat to produce polybenzoxazine. This was then carbonized and activated to produce CNBs containing heteroatoms. Then, through a hydrothermal technique, NiCo-LDH nanocages are directly deposited onto the CNBs, eliminating the need for complicated templates. The amount of CNBs used plays a crucial role in performance. By optimizing the CNB content to 50%, a remarkable specific capacitance of 1220 F g−1 was achieved, along with excellent rate capability and impressive cycling stability, retaining 86% of its capacitance after 5000 cycles. Furthermore, this NiCo-LDH/CNB composite, when combined with active carbon in a supercapacitor configuration, delivered outstanding overall performance. The exceptional properties of this composite, combined with its simple and scalable synthesis process, position it as a strong contender for next-generation sustainable energy storage devices. The ease of fabrication also opens doors for its practical application in advancing energy storage technologies.

In recent years, polybenzoxazine aerogels have emerged as promising materials for various applications. However, their full potential has been hindered by the prevalent use of hazardous solvents during the preparation process, which poses significant environmental and safety concerns. In light of this, there is a pressing need to explore alternative methods that can mitigate these issues and propel the practical utilization of polybenzoxazine aerogels. To address this challenge, a novel approach involving the synthesis of heteroatom self-doped mesoporous carbon from polybenzoxazine has been devised. This process utilizes eugenol, stearyl amine, and formaldehyde to create the polybenzoxazine precursor, which is subsequently treated with ethanol as a safer solvent. Notably, the incorporation of boric acid in this method serves a dual purpose: it not only facilitates microstructural regulation but also reinforces the backbone strength of the material through the formation of intermolecular bridged structures between polybenzoxazine chains. Moreover, this approach allows ambient pressure drying, further enhancing its practicability and environmental friendliness. The resultant carbon materials, designated as ESC-N and ESC-G, exhibit distinct characteristics. ESC-N, derived from calcination, possesses a surface area of 289 m2 g−1, while ESC-G, derived from the aerogel, boasts a significantly higher surface area of 673 m2 g−1. Furthermore, ESC-G features a pore size distribution ranging from 5 to 25 nm, rendering it well suited for electrochemical applications such as supercapacitors. In terms of electrochemical performance, ESC-G demonstrates exceptional potential. With a specific capacitance of 151 F g−1 at a current density of 0.5 A g−1, it exhibits superior energy storage capabilities compared with ESC-N. Additionally, ESC-G displayed a more pronounced rectangular shape in its cyclic voltammogram at a low voltage scanning rate of 20 mV s−1, indicative of enhanced electrochemical reversibility. The impedance spectra of both carbon types corroborated these findings, further validating the superior performance of ESC-G. Furthermore, ESC-G exhibits excellent cycling stability, retaining its electrochemical properties even after 5000 continuous charge–discharge cycles. This robustness underscores its suitability for long-term applications in supercapacitors, reaffirming the viability of heteroatom-doped polybenzoxazine aerogels as a sustainable alternative to traditional carbon materials.

Polymer gels are cross-linked polymer networks swollen by a solvent. These cross-linked networks are interconnected to produce a three-dimensional molecular framework. It is this cross-linked network that provides solidity to the gel and helps to hold the solvent in place. The present work deals with the fabrication of polybenzoxazine carbon (PBzC)-based gels that could function as a solid electrode in flexible supercapacitors (SCs). With the advantage of molecular design flexibility, polybenzoxazine-based carbon containing different hetero-atoms was synthesized. A preliminary analysis of PBzC including XRD, Raman, XPS, and SEM confirmed the presence of hetero-atoms with varying pore structures. These PBz-carbons, upon reaction with polyvinyl alcohol (PVA) and acrylamide (AAm), produced a composite polymer hydrogel, PVA/poly (AAm)/PBzC. The performance of the synthesized hydrogel was analyzed using a three-electrode system. PVA/poly (AAm)/PBzC represented the working electrode. The inclusion of PBzC within the PVA/poly (AAm) matrix was evaluated by cyclic voltammetry and galvanostatic charge/discharge measurements. A substantial increase in the CV area and a longer charge/discharge time signified the importance of PBzC inclusion. The PVA/poly (AAm)/PBzC electrode exhibited larger specific capacitance (Cs) of 210 F g−1 at a current density of 0.5 A g−1 when compared with the PVA/poly (AAm) electrode [Cs = 92 F g−1]. These improvements suggest that the synthesized composite hydrogel can be used in flexible supercapacitors requiring light weight and wearability.

Abstract The majority of the vitamin D that is present in the blood binds to vitamin D binding protein (VDBP) and circulates in the form of a complex (VDBP-Complex). Knowing the level of vitamin D in the body is crucial for vitamin D-related treatments so that the right dosage of vitamin D can be given. In other words, it is essential to distinguish between the protein VDBP and the complex form bound to vitamin D. As a novel way for the detection of VDBP-Complex, a more effective phage display methodology was applied in this study along with the addition of two approaches. In order to screen a sequence specific to the target only, the pre-binding method and after-binding method were performed. VDBP-Complex was directly coated on the petri dishes. In order to select phages that specifically bind to the VDBP-Complex, random phages were attached, and selected by 7 times of biopanning. Individual DNA sequences were analyzed for each biopanning to find specific peptide sequences for VDBP-Complex. The affinity of binding phages was verified by ELISA assay using an anti-M13 antibody. The phage having a sequence of SFTKTSTFTWRD (called as M3) has shown the highest binding affinity to VDBP-Complex. As a result of the removal test of VDBP-Complex using magnetic beads conjugated with M3 peptide, it was confirmed that significant decrease of VDBP-Complex. The unique characteristic of the M3 sequence was confirmed through a sequence-modified peptide (SFT motif). That is, it is expected that the M3 peptide may be used to determine the vitamin D levels in the blood.

The distinct physicochemical characteristics of metal-free graphitic carbon nitride (g-C3N4) are gaining interest in various fields, including energy storage and conversion. However, the electrochemical performance of this material is constrained, owing to its minimal surface area. Incorporating a surfactant is one of the ways to resolve the issue of surface area and therefore improve the electrochemical performance of g-C3N4. This research delves into a method aimed at improving the supercapacitive capabilities of 2D g-C3N4 sheets through the implementation of a cationic surfactant, cetyltrimethylammonium bromide (CTAB). Electrochemical studies reveal that the CTAB-assisted g-C3N4 sheets exhibit remarkable improvements in specific capacitance, cyclic stability, and comparative rate capability in relation to pristine g-C3N4. The specific capacitance of g-C3N4 with CTAB exceeds about 28%, which gives 162. 8 F g−1. This value is 117.7 F g−1 for electrode material without CTAB at 0.5 mA cm−2. This improved electrochemical performance can be credited to the heightened surface area, improved electronic conductivity, and optimized charge transfer kinetics facilitated by the CTAB surfactant. We aim to emphasize the enhancement of the overall performance of g-C3N4-based supercapacitors for advanced energy storage systems.

To maximize the use of ZnS low-dimensional nanoparticles as high-performance supercapacitor electrodes, this work describes a simple one-pot synthesis method for producing a cluster of these particles. The ZnS nanoparticles fabricated in this work exhibit a cluster with unique low-dimensional (0D, 1D, and 2D) characteristics. Structural, morphological, and electrochemical investigations are all part of the thorough characterization of the produced materials. An X-ray diffraction pattern of clustered ZnS nanoparticles reflects the phase formation with highly stable cubic blende sphalerite polymorph. The confirmation of nanoparticle cluster formation featuring multiple low-dimensional nanostructures was achieved through field emission scanning electron microscopy (FE-SEM), while the internal structure was assessed using transmission electron microscopy (TEM). Systematically assessing the ZnS nanoparticles’ electrochemical performance reveals their prospective qualities as supercapacitor electrode materials. The electrode assembled with this material on Ni foam demonstrates elevated specific capacitance (areal capacitance) values, reaching 716.8 F.g⁻1 (2150.4 mF.cm−2) at a current density of 3 mA.cm⁻2. Moreover, it reflects 69.1% capacitance retention with a four times increase in current density, i.e., 495.5 F.g−1 (1486.56 mF.cm−2) capacitance was archived at 12 mA.cm−2 with 100% Coulombic efficiency. Furthermore, the electrode exhibits prolonged cycling capability with 77.7% capacitance retention, as evidenced by its charge–discharge measurements sustained over 15,000 cycles at a current density of 25 mA cm⁻2.

A novel porous carbon, derived from polybenzoxazine and subjected to hydrogen peroxide treatment, has been meticulously crafted to serve dual functions as a supercapacitor and a CO2 capture material. While supercapacitors offer a promising avenue for electrochemical energy storage, their widespread application is hampered by relatively low energy density. Addressing this limitation, our innovative approach introduces a three-dimensional holey carbon ball framework boasting a hierarchical porous structure, thereby elevating its performance as a metal-free supercapacitor electrode. The key to its superior performance lies in the intricate design, featuring a substantial ion-accessible surface area, well-established electron and ion transport pathways, and a remarkable packing density. This unique configuration endows the holey carbon ball framework electrode with an impressive capacitance of 274 F g−1. Notably, the electrode exhibits outstanding rate capability and remarkable longevity, maintaining a capacitance retention of 82% even after undergoing 5000 cycles in an aqueous electrolyte. Beyond its prowess as a supercapacitor, the hydrogen peroxide-treated porous carbon component reveals an additional facet, showcasing an exceptional CO2 adsorption capacity. At temperatures of 0 and 25 °C, the carbon material displays a CO2 adsorption capacity of 4.4 and 4.2 mmol/g, respectively, corresponding to equilibrium pressures of 1 bar. This dual functionality renders the porous carbon material a versatile and efficient candidate for addressing the energy storage and environmental challenges of our time.

Supercapacitors (SCs) are considered as emerging energy storage devices that bridge the gap between electrolytic capacitors and rechargeable batteries. However, due to their low energy density, their real-time usage is restricted. Hence, to enhance the energy density of SCs, we prepared hetero-atom-doped carbon along with bimetallic oxides at different calcination temperatures, viz., HC/NiCo@600, HC/NiCo@700, HC/NiCo@800 and HC/NiCo@900. The material produced at 800 °C (HC/NiCo@800) exhibits a hierarchical 3D flower-like morphology. The electrochemical measurement of the prepared materials was performed in a three-electrode system showing an enhanced specific capacitance for HC/NiCo@600 (Cs = 1515 F g−1) in 1 M KOH, at a current density of 1 A g−1, among others. An asymmetric SC device was also fabricated using HC/NiCo@800 as anode and HC as cathode (HC/NiCo@600//HC). The fabricated device had the ability to operate at a high voltage window (~1.6 V), exhibiting a specific capacitance of 142 F g−1 at a current density of 1 A g−1; power density of 743.11 W kg−1 and energy density of 49.93 Wh kg−1. Altogether, a simple strategy of hetero-atom doping and bimetallic inclusion into the carbon framework enhances the energy density of SCs.

While somatic gain-of-function mutations in the CTNNB1 gene cause diverse malignancies, germline loss-of-function mutations cause neurodevelopmental disorders or familial exudative vitreoretinopathy. In particular, CTNNB1-related neurodevelopmental disorders have various phenotypes, and a genotype-phenotype relationship has not been established. We report two patients with CTNNB1-related neurodevelopmental disorder whose clinical features were similar to those of cerebral palsy, hindering diagnosis.

ABSTRACT Staphylococcus aureus is a common pathogen that causes health care-related and community-associated infections. In this study, we provide a novel system that can recognize and kill S. aureus bacteria. The system is specifically based on a combination of the phage display library technique and yeast vacuoles. A phage clone displaying a peptide capable of specific binding to a whole S. aureus cell was selected from a 12-mer phage peptide library. The peptide sequence was SVPLNSWSIFPR. The selected phage’s ability to bind specifically with S. aureus was confirmed using an enzyme-linked immunosorbent assay, and the chosen peptide was then synthesized. The results showed that the synthesized peptides displayed high affinity with S. aureus but low binding ability with other strains, including Gram-negative and Gram-positive bacteria such as Salmonella sp., Shigella spp., Escherichia coli, and Corynebacterium glutamicum. In addition, yeast vacuoles were used as a drug carrier by encapsulating daptomycin, a lipopeptide antibiotic used to treat Gram-positive bacterial infections. The expression of specific peptides at the encapsulated vacuole membrane created an efficient system that can specifically recognize and kill S. aureus bacteria. IMPORTANCE The phage display method was used to select peptides with high affinity and specificity for S. aureus, and these peptides were then induced to be expressed on the surface of yeast vacuoles. These surface-modified vacuoles can act as drug carriers, with drugs such as the lipopeptide antibiotic daptomycin loaded inside. An advantage of using yeast vacuoles as a drug carrier is that they can be easily produced through yeast culture, making the approach cost-effective and suitable for large-scale production and potential implementation in clinical settings. This novel approach offers a promising way to specifically target and eliminate S. aureus that could ultimately lead to improved treatment of bacterial infections and reduced risk of antibiotic resistance.

Abstract Epigenetic dysregulation is reported in multiple cancers including Ewing sarcoma (EwS). However, the epigenetic networks underlying the maintenance of oncogenic signaling and therapeutic response remain unclear. Using a series of epigenetics‐ and complex‐focused CRISPR screens, RUVBL1, the ATPase component of NuA4 histone acetyltransferase complex, is identified to be essential for EwS tumor progression. Suppression of RUVBL1 leads to attenuated tumor growth, loss of histone H4 acetylation, and ablated MYC signaling. Mechanistically, RUVBL1 controls MYC chromatin binding and modulates the MYC‐driven EEF1A1 expression and thus protein synthesis. High‐density CRISPR gene body scan pinpoints the critical MYC interacting residue in RUVBL1. Finally, this study reveals the synergism between RUVBL1 suppression and pharmacological inhibition of MYC in EwS xenografts and patient‐derived samples. These results indicate that the dynamic interplay between chromatin remodelers, oncogenic transcription factors, and protein translation machinery can provide novel opportunities for combination cancer therapy.

Pathogenic variants of DNMT3A have been implicated in Tatton-Brown-Rahman syndrome, an overgrowth disorder with macrocephaly and intellectual disability. However, there are recent reports of variants in the same gene giving rise to an opposing clinical phenotype presenting with microcephaly, growth failure, and impaired development—named Heyn-Sproul-Jackson syndrome (HESJAS). Here, we present a case of HESJAS caused by a novel pathogenic variant of DNMT3A. A five-year-old girl presented with severe developmental delay. Perinatal and family history were non-contributory. Physical exam showed microcephaly and facial dysmorphic features, and neurodevelopmental assessments revealed profound global developmental delay. Brain magnetic resonance imaging findings were normal; however, brain 3D computed tomography revealed craniosynostosis. Next generation sequencing revealed a novel heterozygous variant in DNMT3A (NM_175629.2: c.1012_1014 + 3del). The patient's parents did not carry the variant. In this report, a novel feature associated with HESJAS (craniosynostosis) is described, along with a more detailed account of clinical manifestations than those in the original report.

Intermittent fasting (IF), an alternating pattern of dietary restriction, reduces obesity-induced insulin resistance and inflammation. However, the crosstalk between adipose tissue and the hippocampus in diabetic encephalopathy is not fully understood. Here, we investigated the protective effects of IF against neuroinflammation and cognitive impairment in high-fat diet(HFD)-fed mice. Histological analysis revealed that IF reduced crown-like structures and adipocyte apoptosis in the adipose tissue of HFD mice. In addition to circulating lipocalin-2 (LCN2) and galectin-3 (GAL3) levels, IF reduced HFD-induced increases in LCN2- and GAL3-positive macrophages in adipose tissue. IF also improved HFD-induced memory deficits by inhibiting blood–brain barrier breakdown and neuroinflammation. Furthermore, immunofluorescence showed that IF reduced HFD-induced astrocytic LCN2 and microglial GAL3 protein expression in the hippocampus of HFD mice. These findings indicate that HFD-induced adipocyte apoptosis and macrophage infiltration may play a critical role in glial activation and that IF reduces neuroinflammation and cognitive impairment by protecting against blood–brain barrier leakage.

This work demonstrates the evolution of different architectures of Cu-Co bimetallic sulfide on Ni-foam. A simple solvent-changing strategy has been adopted to develop these architectures through a solvothermal approach. When water and ethylene glycol was used as a solvent, the surface of Ni-foam seemed to be covered with a snowflake-like architecture. On the addition of glycerol instead of ethylene glycol, the growth of spongy rectangular prisms from mud-like bricks was initiated. Analyzing electrochemically, both electrodes deliver excellent capacitance. The electrode developed with water and glycerol was found to be richer in terms of capacitive performance, which gives 1459.7 F/gm (5692.8 mF/cm2) at a higher current density of 5 mA/cm2. An over-33% increment in capacitance was noted when compared with the specific capacitance (areal capacitance) of another electrode which can provide 986.6 F/gm (3157 mF/cm2) at the same current density. Both electrodes are richer in terms of providing higher rate capability above 75%, even if the current density is increased by three times. Furthermore, both electrodes deliver long-lasting storage capability, with above 80% capacitance retention over 10,000 charge–discharge cycles even at a higher current density of 60 mA/cm2. This simple solvent-changing approach can be useful for developing electrode materials with outstanding capacitive performance.

Age-related microglial activation is associated with cognitive impairment. Tonicity-responsive enhancer-binding protein (TonEBP) is a critical mediator of microglial activation in response to neuroinflammation. However, the precise role of TonEBP in the middle-aged brain is not yet known. We used TonEBP haploinsufficient mice to investigate the role of TonEBP in middle-aged or amyloid β oligomer (AβO)–injected brains and examined the effect of TonEBP knockdown on AβO-treated BV2 microglial cells. Consistent with an increase in microglial activation with aging, hippocampal TonEBP expression levels were increased in middle-aged (12-month-old) and old (24-month-old) mice compared with young (6-month-old) mice. Middle-aged TonEBP haploinsufficient mice showed reduced microglial activation and fewer memory deficits than wild-type mice. Electron microscopy revealed that synaptic pruning by microglial processes was reduced by TonEBP haploinsufficiency. TonEBP haploinsufficiency also reduced dendritic spine loss and improved memory deficits in AβO-treated mice. Furthermore, TonEBP knockdown attenuated migration and phagocytosis in AβO-treated BV2 cells. These findings suggest that TonEBP plays important roles in age-related microglial activation and memory deficits.

Background: The aim of this study was to analyze the inhibitory effects of copper, brass (78% copper, 22% tin), and stainless steel surfaces on multidrug-resistant Acinetobacter baumannii (MRAB), extended-spectrum beta-lactamase (ESBL) Escherichia coli, and carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: MRAB, ESBL E. coli, and CRKP were isolated at Uijeongbu St.Mary’s Hospital in 2020. A. baumannii ATCC BAA-747, E. coli ATCC 25922, and K. pneumoniae ATCC 700603 were used as reference strains. The initial bacterial cell count of each inoculum was adjusted to 8 log CFU/mL using phosphate buffered saline, Copper, brass, and stainless steel plates were inoculated with 9 mL of MRAB, ESBL E. coli, and CRKP inoculum solutions. The bacterial cell count was measured from the beginning to the 20th day in an incubator maintained at 35°C. Results: MRAB, ESBL E. coli, and CRKP isolates were not detected on the copper and brass plates after 4, 5.5, and 6.5 hours, respectively. MRAB, ESBL E. coli, and CRKP isolates were not detected on the stainless steel plate after 15, 20, and 20 days, respectively. The bactericidal effects of copper and brass were much stronger than those of stainless steel. Conclusion: The use of copper and copper alloys should be considered to prevent cross-infection in hospitals.

Adverse events following vaccination with the ChAdOx1 COVID-19 vaccine may be associated with the titer of neutralizing antibodies (NAbs) against SARS-CoV-2. In this cross-sectional study, a total of 82 HCWs who received the ChAdOx1 COVID-19 vaccine and did not have previous COVID-19 history were enrolled during March 2021. Blood samples were collected from HCWs 3 weeks after the first and second doses of vaccine, and NAbs were estimated using two types of commercially available kits, the cPass™ SARS-CoV-2 NAbs Kit (Genscript Biotech, Piscataway, NJ, USA) and R-FIND SARS-CoV-2 NAbs ELISA (SG Medical, Seoul, Korea). Median percent signal inhibition of NAbs was significantly higher after the second than after the first dose of vaccine, as determined using both the Genscript (median 43.1[IQR 71.2] vs. 93.6[83.1], p = 0.004) and R-FIND (53.2[82.6] vs. 76.8 [90.6], p = 0.03) kits. The percent signal inhibition of NAbs after the second dose of vaccine was higher in HCWs with than without systemic adverse events after the second dose, as determined using both the Genscript (p = 0.03) and R-FIND (p = 0.07) kits. The two doses of the ChAdOx1 vaccine induced high value of NAbs 3 weeks after vaccination. Immune responses were stronger in HCWs with than without adverse reactions after the second dose of ChAdOx1 vaccine.

Background: Plasmodium vivax is a major pathogen that causes malaria in South Korea. Several genetic polymorphisms in dihydrofolate reductase (pvdhfr ), P. vivax multidrug resistance protein 1 (pvmdr1 ), and P. vivax hydroxymethylpterin pyrophosphokinasedihydropteroate synthetase (pvdhps) genes are known to be associated with drug resistance in P. vivax. The objective of this study was to profile the known polymorphisms of P. vivax resistance genes in patients at a secondary hospital in South Korea. Methods: A total of 12 patients with confirmed P. vivax infections were enrolled for this study. Sanger sequencing was performed for the pvdhfr, pvmdr1, and pvdhps genes to detect polymorphisms of these drug resistance genes. Results: Each specimen had single or double polymorphism in pvdhfr. One specimen had a polymorphism in pvdhps. However, no specimen had any polymorphisms in pvmdr1. There was no strain with multi-polymorphisms exceeding double polymorphisms, which reported the geographic location of treatment failure. Conclusion: No specimen showed chloroquine-resistance polymorphism in pvmdr1. Treatment with first-line therapy was successful. The prevalence of F57L in pvdhfr was higher than that reported previously. This change must be confirmed by further monitoring and surveillance of the strains with multi-polymorphisms.

An intermittent fasting (IF) regimen has been shown to protect against metabolic dysfunction-associated steatohepatitis (MASH). However, the precise mechanism remains unclear. Here, we explored how IF reduced hepatic lipid accumulation, inflammation, and fibrosis in mice with MASH. The mice were fed a high-fat diet (HFD) for 30 weeks and either continued on the HFD or were subjected to IF for the final 22 weeks. IF reduced body weight, insulin resistance, and hepatic lipid accumulation in HFD-fed mice. Lipidome analysis revealed that IF modified HFD-induced hepatic lipid composition. In particular, HFD-induced impaired autophagic flux was reversed by IF. The decreased hepatic lysosome-associated membrane protein 1 level in HFD-fed mice was upregulated in HFD+IF-fed mice. However, increased hepatic lysosomal acid lipase protein levels in HFD-fed mice were reduced by IF. IF attenuated HFD-induced hepatic inflammation and galectin-3-positive Kupffer cells. In addition to the increases in hepatic hydroxyproline and lumican levels, lipocalin-2-mediated signaling was reversed in HFD-fed mice by IF. Taken together, our findings indicate that the enhancement of the autophagy–lysosomal pathway may be a critical mechanism of MASH reduction by IF.

The research community is actively exploring ways to create cost-efficient and high-performing electrocatalysts for the oxygen evolution reaction. In this investigation, an innovative technique was employed to produce heteroatom-doped carbon containing NiCo oxides, i.e., HC/NiCo oxide@800, in the form of a three-dimensional hierarchical flower. This method involved the reduction of a bimetallic (Ni, Co) metal–organic framework, followed by carefully controlled oxidative calcination. The resulting porous flower-like structure possess numerous advantages, such as expansive specific surface areas, excellent conductivity, and multiple electrocatalytic active sites for both hydrogen and oxygen evolution reactions. Moreover, the presence of oxygen vacancies within HC/NiCo oxide@800 significantly enhances the conductivity of the NiCo substance, thus expediting the kinetics of both the processes. These benefits work together synergistically to enhance the electrocatalytic performance of HC/NiCo oxide@800. Empirical findings reveal that HC/NiCo oxide@800 electrocatalysts demonstrate exceptional catalytic activity, minimal overpotential, and remarkable stability when deployed for both hydrogen evolution and oxygen evolution reactions in alkaline environments. This investigation introduces a fresh avenue for creating porous composite electrocatalysts by transforming metal–organic frameworks with controllable structures. This approach holds promise for advancing electrochemical energy conversion devices by facilitating the development of efficient and customizable electrocatalytic materials.

Abstract Background Diabetic individuals have increased circulating inflammatory mediators which are implicated as underlying causes of neuroinflammation and memory deficits. Tonicity-responsive enhancer-binding protein (TonEBP) promotes diabetic neuroinflammation. However, the precise role of TonEBP in the diabetic brain is not fully understood. Methods We employed a high-fat diet (HFD)-only fed mice or HFD/streptozotocin (STZ)-treated mice in our diabetic mouse models. Circulating TonEBP and lipocalin-2 (LCN2) levels were measured in type 2 diabetic subjects. TonEBP haploinsufficient mice were used to investigate the role of TonEBP in HFD/STZ-induced diabetic mice. In addition, RAW 264.7 macrophages were given a lipopolysaccharide (LPS)/high glucose (HG) treatment. Using a siRNA, we examined the effects of TonEBP knockdown on RAW264 cell’ medium/HG-treated mouse hippocampal HT22 cells. Results Circulating TonEBP and LCN2 levels were higher in experimental diabetic mice or type 2 diabetic patients with cognitive impairment. TonEBP haploinsufficiency ameliorated the diabetic phenotypes including adipose tissue macrophage infiltrations, neuroinflammation, blood–brain barrier leakage, and memory deficits. Systemic and hippocampal LCN2 proteins were reduced in diabetic mice by TonEBP haploinsufficiency. TonEBP (+ / −) mice had a reduction of hippocampal heme oxygenase-1 (HO-1) expression compared to diabetic wild-type mice. In particular, we found that TonEBP bound to the LCN2 promoter in the diabetic hippocampus, and this binding was abolished by TonEBP haploinsufficiency. Furthermore, TonEBP knockdown attenuated LCN2 expression in lipopolysaccharide/high glucose-treated mouse hippocampal HT22 cells. Conclusions These findings indicate that TonEBP may promote neuroinflammation and cognitive impairment via upregulation of LCN2 in diabetic mice.

Proper design of multifunctional electrocatalyst that are abundantly available on earth, cost-effective and possess excellent activity and electrochemical stability towards oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are required for effective hydrogen generation from water-splitting reaction. In this context, the work herein reports the fabrication of nitrogen-rich porous carbon (NRPC) along with the inclusion of non-noble metal-based catalyst, adopting a simple and scalable methodology. NRPC containing nitrogen and oxygen atoms were synthesized from polybenzoxazine (Pbz) source, and non-noble metal(s) are inserted into the porous carbon surface using hydrothermal process. The structure formation and electrocatalytic activity of neat NRPC and monometallic and bimetallic inclusions (NRPC/Mn, NRPC/Ni and NRPC/NiMn) were analyzed using XRD, Raman, XPS, BET, SEM, TEM and electrochemical measurements. The formation of hierarchical 3D flower-like morphology for NRPC/NiMn was observed in SEM and TEM analyses. Especially, NRPC/NiMn proves to be an efficient electrocatalyst providing an overpotential of 370 mV towards OER and an overpotential of 136 mV towards HER. Moreover, it also shows a lowest Tafel slope of 64 mV dec−1 and exhibits excellent electrochemical stability up to 20 h. The synergistic effect produced by NRPC and bimetallic compounds increases the number of active sites at the electrode/electrolyte interface and thus speeds up the OER process.

Abstract Dynamin-related protein 1 (Drp1)-mediated mitochondrial dysfunction is associated with synaptic injury in the diabetic brain. However, the dysfunctional mitochondria by Drp1 deletion in the diabetic brain are poorly understood. Here, we investigated the effects of neuron-specific Drp1 deletion on synaptic damage and mitophagy in the hippocampus of a high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice. HFD/STZ-induced diabetic mice exhibited metabolic disturbances and synaptic damages. Floxed Drp1 mice were crossed with Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα)-Cre mice, to generate neuron-specific Drp1 knockout (Drp1cKO) mice, which showed marked mitochondrial swelling and dendritic spine loss in hippocampal neurons. In particular, diabetic Drp1cKO mice exhibited an increase in dendritic spine loss and higher levels of oxidative stress and neuroinflammation compared with diabetic wild-type (WT) mice. Diabetic WT mice generally displayed increased Drp1-induced small mitochondrial morphology in hippocampal neurons, but large mitochondria were prominently observed in diabetic Drp1cKO mice. The levels of microtubule-associated protein 1 light-chain 3 and lysosomal-associated membrane protein 1 proteins were significantly increased in the hippocampus of diabetic Drp1cKO mice compared with diabetic WT mice. The inhibition of Drp1 adversely promotes synaptic injury and neurodegeneration in the diabetic brain. The findings suggest that the exploratory mechanisms behind Drp1-mediated mitochondrial dysfunction could provide a possible therapeutic target for diabetic brain complications.

Leigh syndrome is a neurodegenerative disorder that presents with fluctuation and stepwise deterioration, such as neurodevelopmental delay and regression, dysarthria, dysphagia, hypotonia, dystonia, tremor, spasticity, epilepsy, and respiratory problems. The syndrome characteristically presents symmetric necrotizing lesions in the basal ganglia, brainstem, cerebellum, thalamus, and spinal cord on cranial magnetic resonance imaging. To date, more than 85 genes are known to be associated with Leigh syndrome. Here, we present a rare case of a child who developed Leigh syndrome due to pathogenic variants of NDUFAF6, which encodes an assembly factor of complex I, a respiratory chain subunit. A targeted next-generation sequencing analysis related to mitochondrial disease revealed a missense variant (NM_152416.4:c.371T > C; p.Ile124Thr) and a frameshift variant (NM_152416.4:c.233_242del; p.Leu78GInfs*10) inherited biparentally. The proband underwent physical therapy and nutrient cocktail therapy, but his physical impairment gradually worsened.

Despite the demand for clean water, it is commonly deficient. In the past two decades, there has been renewed interest in the development of clean water generation processes from atmospheric moisture. Atmospheric water generation is a two-stage process; in the first stage, the moisture is accumulated in an absorber material, and in the second stage, the absorbed moisture is recovered to a vessel by thermal and/or mechanical processes. One of the keys to achieving high efficiency in such processes is the moisture-absorbing agent, which works passively without electricity. Several materials are currently undergoing research, such as metal–organic frameworks (MOF) and hygroscopic salts. However, most approaches would likely be challenging to scale up from technical and economic perspectives. This work aims to develop a commonly accessible, cost-effective, environmentally friendly, and highly effective moisture absorber. Calcium chloride (CaCl2) was chosen as the main salt of interest due to its deliquescence; however, it is known to suffer from agglomeration upon repeated absorption–desorption trials, which decreases efficacy. To overcome this problem, a simple infusion of the salt into the sponges significantly reduced the agglomeration problem of the salt while also improving its absorption rate and maximum water uptake by ~30% at 27 °C and 80% relative humidity (RH) compared to a sample without the cellulose sponge. To elucidate the science behind this synergistic interaction, time-dependent water uptake measurements at controlled conditions were carried out using a microbalance in an environmental chamber. Then, the data were analyzed using a double exponential equation. A physical model of the moisture absorption mechanism in the salt/sponge system was proposed. Finally, a complete atmospheric water generation device prototype was demonstrated by incorporating the salt/sponge absorber into a custom-designed Peltier-based distillation chamber.

Hexamethylenetetramine, an aldehyde-releasing agent, is used as a preservative in various food, cosmetics, and medical treatments, such as a treatment for urinary tract infections. It has been reported to be allergenic on contact with the skin, with the additional possibility of causing toxicity once absorbed systemically. Despite its potential toxicity, there are no reports on the in vivo bioavailability of hexamethylenetetramine following oral or dermal administration. In this study, we developed a new simple and sensitive LC–MS/MS method for the determination of hexamethylenetetramine in plasma and applied this method to characterize the toxicokinetics. The developed assay had a sufficient specificity and sensitivity for toxicokinetic characterization, and its accuracy and precision were verified. Following iv injection, the plasma concentration of hexamethylenetetramine showed mono exponential decay, with an elimination half-life of about 1.3 h. Following oral administration, the Tmax reached an average of 0.47 h and bioavailability was estimated as 89.93%. After percutaneous administration, it reached Cmax on average at 2.9–3.6 h. Although the absorption rate was relatively slow, its average bioavailability was calculated as 77.19–78.91%. Overall, most of the orally and percutaneously administered hexamethylenetetramine was absorbed into systemic circulation. The derived results in this study are expected to be utilized as the scientific evidence for further toxicokinetic study and risk assessment.

Magnetic anisotropy strongly influences the performance of the magnetocaloric effect. We investigated the magnetocaloric properties of the NdAlGe single crystal with I41md structure. The temperature-dependent magnetization revealed significant anisotropic properties; stable antiferromagnetic transition at TN = 6 K for H//a and meta-magnetic spin reorientation at low temperature (T ≤ 5 K) within an intermediate field (H = 2 T) for H//c. During the metamagnetic spin reorientation, the abrupt change of the magnetic entropy leads to a significant magnetocaloric effect with negative magnetic entropy change (∆SM) by −13.80 J kg−1 K−1 at TC = 5.5 K for H = 5 T along the H//c axis. In addition, the antiferromagnetic state for H//a shows the inverse magnetocaloric effect(I-MCE) by positive entropy change ∆SM = 2.64 J kg−1 K−1 at TN = 6 K for H = 5 T. This giant MCE accompanied by the metamagnetic transition resulted in a significantly large relative cooling power (158 J/kg at H = 5 T) for H//c. The giant MCE and I-MCE can be applied to the rotational magnetocaloric effect (R-MCE) depending on the crystal orientations. NdAlGe exhibits rotational entropy change ∆Sc−a = −12.85 J kg−1 K at Tpeak = 7.5 K, H = 5 T. With comparison to conventional MCE materials, NdAlGe is suggested as promising candidate of R-MCE, which is a novel type of magnetic refrigeration system.

Abstract Introduction Recent advances in genetic analysis have led to the discovery of novel genetic subtypes of precursor B‐cell acute lymphoblastic leukemia (B‐ALL) with prognostic relevance. In this study, we studied a cohort of pediatric B‐ALL patients to retrospectively determine the incidence of patients harboring novel genetic subtypes, as well as their outcome. Methods B‐ALL patients (N = 190) diagnosed in a single Korean hospital were included in the study. Patients' medical records were reviewed for data on established genetic abnormalities and outcome. CRLF2 expression was analyzed by quantitative RT‐PCR. Anchored multiplex PCR‐based enrichment was used to detect fusions and point mutations in 81 ALL‐related genes. Results Incidence of established recurrent genetic subtypes was as follows: high hyperdiploidy (21.6%), ETV6‐RUNX1 (21.6%), BCR‐ABL1 (7.9%), KMT2A rearrangement (7.4%) TCF3‐PBX1/TCF3‐HLF (7.4%), and hypodiploidy (1.1%). Incidence of new genetic subtypes was as follows: BCR‐ABL1‐like (13.2%), ETV6‐RUNX1‐like (2.1%), EWSR1‐ZNF384 (1.1%), and iAMP21 (1.1%). Median age at diagnosis of BCR‐ABL1‐like ALL was 6.8 years. According to type of genetic abnormality, BCR‐ABL1‐like ALL was divided into ABL class (12%), CRLF2 class (8%), JAK‐STAT class (12%), and RAS class (68%). The 5‐year event‐free survival (EFS) of BCR‐ABL1‐like patients was significantly inferior to non‐BCR‐ABL1‐like low‐ and standard‐risk patients (71.5 ± 9.1% vs 92.5 ± 3.2%, P = .001) and comparable to non‐BCR‐ABL1‐like high (75.2 ± 6.2%) and very high‐risk patients (56.8 ± 7.4%). All four ETV6‐RUNX1‐like patients survived event‐free. Conclusion Analogous to previous studies, incidence of BCR‐ABL1‐like ALL in our cohort was 13.2% with outcome comparable to high and very high‐risk patients. A significantly high number of RAS class mutations was a distinct feature of our BCR‐ABL1‐like ALL group.

Adzuki bean is well known as a potential functional food that improves metabolic complications from obesity and diabetes. Lipocalin-2 (LCN2) has been implicated to have an important role in obesity and diabetes. However, the protective roles of adzuki bean MY59 extract (ABE) on insulin resistance and hepatic steatosis are not fully understood. In the present study, we investigated the effects of ABE on LCN2 expression in high-fat diet (HFD)-fed mice. ABE reduced HFD-induced fat mass and improved insulin resistance. In addition to hepatic steatosis, HFD-fed mice showed many apoptotic cells and neutrophils in the epididymal fat pads. However, these findings were significantly reduced by ABE supplementation. In particular, we found that increased LCN2 proteins from serum, epididymal fat pads, and liver in HFD-fed mice are significantly reduced by ABE. Furthermore, ABE reduced increased heme oxygenase-1 and superoxide dismutase-1 expressions in adipose tissue and liver in HFD-fed mice. We found that hepatic nuclear factor-kappa B (NF-κB) p65 expression in HFD-fed mice was also reduced by ABE. Thus, these findings indicate that ABE feeding could improve insulin resistance and hepatic steatosis by decreasing LCN2-mediated inflammation and oxidative stress in HFD-fed mice.

BCR-ABL1–positive acute leukemia can be classified into three disease categories: B-lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML), and mixed-phenotype acute leukemia (MPAL). We conducted an integrative analysis of RNA sequencing (RNA-seq) data obtained from 12 BCR-ABL1–positive B-ALL, AML, and MPAL samples to evaluate its diagnostic utility. RNA-seq facilitated the identification of all p190 BCR-ABL1 with accurate splicing sites and a new gene fusion involving MAP2K2. Most of the clinically significant mutations were also identified including single-nucleotide variations, insertions, and deletions. In addition, RNA-seq yielded differential gene expression profile according to the disease category. Therefore, we selected 368 genes differentially expressed between AML and B-ALL and developed two differential diagnosis models based on the gene expression data using 1) scoring algorithm and 2) machine learning. Both models showed an excellent diagnostic accuracy not only for our 12 BCR-ABL1–positive cases but also for 427 public gene expression datasets from acute leukemias regardless of specific genetic aberration. This is the first trial to develop models of differential diagnosis using RNA-seq, especially to evaluate the potential role of machine learning in identifying the disease category of acute leukemia. The integrative analysis of gene expression data by RNA-seq facilitates the accurate differential diagnosis of acute leukemia with successful detection of significant gene fusion and/or mutations, which warrants further investigation.

CPVC fibers were prepared using a low-cost chlorinate polyvinyl chloride (CPVC) precursor using wet spinning, and various elongation rates were applied (0%, 50%, 100%, and 125%) to improve the physicochemical properties. CPVC fibers were carbonized in a nitrogen atmosphere to prepare CPVC carbon fibers, and physicochemical changes were observed by applying the same elongation rates. The CPVC fiber changed from aliphatic to aromatic carbon chemically, such as C-Cl peak intensity disappeared after carbonization and C = C bonding peak was newly discovered. After CPVC carbonization, CPVC carbon fiber, which has an elongation of 125%, has the maximum mechanical properties (tensile strength of up to 1.83GPa, modulus of 172GPa) by inducing a change in the carbon fiber structure, so it can be applied to the automotive industry in the future.

Background: Lipocalin-2 (LCN2) is an acute-phase protein that has been linked to insulin resistance, diabetes, and neuroinflammatory diseases. Triggering receptor expressed on myeloid cells-2 (TREM2) has been also implicated in microglia-mediated neuroinflammation. However, the potential role of LCN2 on TREM2 in diabetic mouse models is not fully understood. Methods: We investigated hepatic and hippocampal TREM2 expressions in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic LCN2 knockout (KO) mice. Results: In addition to increased serum LCN2 level, diabetic wild-type (WT) mice had insulin resistance and hepatic steatosis. However, LCN2 deletion attenuated these metabolic parameters in diabetic mice. We also found that LCN2 deletion reduced hepatic inflammation and microglial activation in diabetic mice. In particular, diabetic LCN2 KO mice had a reduction in hepatic and hippocampal TREM2 expressions compared with diabetic WT mice. Furthermore, we found that many TREM2-positive Kupffer cells and microglia in diabetic WT mice were reduced through LCN2 deletion. Conclusions: These findings indicate that LCN2 may promote hepatic inflammation and microglial activation via upregulation of TREM2 in diabetic mice.

BackgroundThe clinical significance of upper airway respiratory virus (RV) detection in patients with hematologic malignancies remains unclear. We aimed to investigate the association between upper airway RV detection and prognosis in critically ill patients with hematologic malignancies.MethodsThis retrospective observational study included 331 critically ill patients with hematologic malignancies who presented respiratory symptoms and their nasopharyngeal swab was tested using a multiplex PCR assay between January 2017 and December 2018. A logistic regression model was used to adjust for potential confounding factors in the association between assay positivity and in-hospital mortality.ResultsAmong the 331 analyzed patients, RVs were detected in 29.0%. The overall mortality rates in the intensive care unit and hospital were 56.8% and 65.9%, respectively. Positive upper airway RV detection was associated with relapsed hematologic malignancies, higher level of C-reactive protein, and prior use of high dose steroids and anti-cancer chemotherapeutic drugs. Furthermore, it was independently associated with in-hospital mortality (adjusted odds ratio, 2.36; 95% confidence interval, 1.23 to 4.54). Among different RVs, parainfluenza virus was more prevalent among patients who died in the hospital than among those who survived (11.5% vs. 3.5%, P = 0.027).ConclusionsRV detection in the upper respiratory tract was relatively common in our cohort and was significantly associated with a poor prognosis. Thus, it can be used as a predictor of prognosis. Moreover, RV presence in the upper respiratory tract should be examined in patients who have previously been prescribed with high dose corticosteroids and anti-cancer drugs.

Periodontitis is a widespread chronic inflammatory disease caused by interactions between periodontal bacteria and homeostasis in the host. We aimed to investigate the performance and reliability of machine learning models in predicting the severity of chronic periodontitis. Mouthwash samples from 692 subjects (144 healthy controls and 548 generalized chronic periodontitis patients) were collected, the genomic DNA was isolated, and the copy numbers of nine pathogens were measured using multiplex qPCR. The nine pathogens are as follows: Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), Campylobacter rectus (Cr), Aggregatibacter actinomycetemcomitans (Aa), Peptostreptococcus anaerobius (Pa), and Eikenella corrodens (Ec). By adding the species one by one in order of high accuracy to find the optimal combination of input features, we developed an algorithm that predicts the severity of periodontitis using four machine learning techniques. The accuracy was the highest when the models classified “healthy” and “moderate or severe” periodontitis (H vs. M-S, average accuracy of four models: 0.93, AUC = 0.96, sensitivity of 0.96, specificity of 0.81, and diagnostic odds ratio = 112.75). One or two red complex pathogens were used in three models to distinguish slight chronic periodontitis patients from healthy controls (average accuracy of 0.78, AUC = 0.82, sensitivity of 0.71, and specificity of 0.84, diagnostic odds ratio = 12.85). Although the overall accuracy was slightly reduced, the models showed reliability in predicting the severity of chronic periodontitis from 45 newly obtained samples. Our results suggest that a well-designed combination of salivary bacteria can be used as a biomarker for classifying between a periodontally healthy group and a chronic periodontitis group.

Cellulose pulp (CP), polyurethane (PU), and curcumin-based biocompatible composite films were prepared using a simple cost-effective method. Significant structural and microstructural changes were studied using FT-IR spectroscopy, XRD, and SEM. The 5% and 10% gravimetric losses of the CP/PU/curcumin composite were found to be in the range 87.2–182.3 °C and 166.7–249.8 °C, respectively. All the composites exhibited single Tg values in the range 147.4–154.2 °C. The tensile strength of CP was measured to be 93.2 MPa, which dropped to 14.1 MPa for the 1:0.5 CP/PU composite and then steadily increased to 30.5 MPa with further addition of PU. The elongation at the break of the composites decreased from 8.1 to 3.7% with the addition of PU. The addition of PU also improved the water vapor permeability (3.96 × 10−9 to 1.75 × 10−9 g m−1 s−1 Pa−1) and swelling ratio (285 to 202%) of the CP composite films. The CP/PU/curcumin composite exhibited good antioxidant activity and no cytotoxicity when tested on the HaCat cell line. The visual appearance and UV transmittance (86.2–32.9% at 600 nm) of the CP composite films were significantly altered by the incorporation of PU and curcumin. This study demonstrates that CP/PU/curcumin composites can be used for various packaging and biomedical applications.

Lipocalin-2 (LCN2) is an inflammatory protein with diverse functions in the brain. Although many studies have investigated the mechanism of LCN2 in brain injuries, the effect of LCN2 on amyloid-toxicity-related memory deficits in a mouse model of Alzheimer’s disease (AD) has been less studied. We investigated the role of LCN2 in human AD patients using a mouse model of AD. We created an AD mouse model by injecting amyloid-beta oligomer (AβO) into the hippocampus. In this model, animals exhibited impaired learning and memory. We found LCN2 upregulation in the human brain frontal lobe, as well as a positive correlation between white matter ischemic changes and serum LCN2. We also found increased astrocytic LCN2, microglia activation, iron accumulation, and blood–brain barrier disruption in AβO-treated hippocampi. These findings suggest that LCN2 is involved in a variety of amyloid toxicity mechanisms, especially neuroinflammation and oxidative stress.

Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist that protects against brain injury. However, little is known about the effect of Ex-4 on kainic acid (KA)-induced seizures and hippocampal cell death. Therefore, this study evaluated the neuroprotective effects of Ex-4 pretreatment in a mouse model of KA-induced seizures. Three days before KA treatment, mice were intraperitoneally injected with Ex-4. We found that Ex-4 pretreatment reversed KA-induced reduction of GLP-1R expression in the hippocampus and attenuated KA-induced seizure score, hippocampal neuronal death, and neuroinflammation. Ex-4 pretreatment also dramatically reduced hippocampal lipocalin-2 protein in KA-treated mice. Furthermore, immunohistochemical studies showed that Ex-4 pretreatment significantly alleviated blood–brain barrier leakage. Finally, Ex-4 pretreatment stimulated hippocampal expression of phosphorylated cyclic adenosine monophosphate (cAMP) response element-binding protein (p-CREB), a known target of GLP-1/GLP-1R signaling. These findings indicate that Ex-4 pretreatment may protect against KA-induced neuronal damage by regulating GLP-1R/CREB-mediated signaling pathways.

Recently, the American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention advised against performing the interferon-γ-release assay (IGRA) test for individuals with a low risk of TB, and also recommended retesting low-risk individuals with an initial positive IGRA result. However, to evaluate both sensitivity and specificity of available tests, we compared the performance of the Standard E TB-Feron (TBF) and QuantiFERON-TB Gold Plus (QFT-Plus) assays in healthcare workers (HCWs) and tuberculosis (TB) patients. We also retrospectively investigated diabetes mellitus (DM) comorbidity among the enrolled TB patients. We prospectively collected samples from 177 HCWs and 48 TB patients. The TBF and QFT-Plus tests were performed and analyzed according to the manufacturers’ instructions. We also defined IGRA results between 0.2 and 0.7 IU/mL as ‘borderline’. The agreement rate between TBF and QFT-Plus was 92.0% (207/225) with a Cohen’s kappa value of 0.77 (95% CI, 0.68–0.87). While the majority (26/31, 83.9%) of borderline TBF results were in HCWs, the majority (14/19, 73.7%) of borderline QFT-Plus results were in TB patients. Discordant results were found in 18 samples, with TBF-positive/QFT-Plus-negative or indeterminate results in 11 HCWs and seven TB patients. After resampling from 10 HCWs (seven borderline-positive and three positive results, all

Dental caries are one of the chronic diseases caused by organic acids made from oral microbes. However, there was a lack of knowledge about the oral microbiome of Korean children. The aim of this study was to analyze the metagenome data of the oral microbiome obtained from Korean children and to discover bacteria highly related to dental caries with machine learning models. Saliva and plaque samples from 120 Korean children aged below 12 years were collected. Bacterial composition was identified using Illumina HiSeq sequencing based on the V3–V4 hypervariable region of the 16S rRNA gene. Ten major genera accounted for approximately 70% of the samples on average, including Streptococcus, Neisseria, Corynebacterium, and Fusobacterium. Differential abundant analyses revealed that Scardovia wiggsiae and Leptotrichia wadei were enriched in the caries samples, while Neisseria oralis was abundant in the non-caries samples of children aged below 6 years. The caries and non-caries samples of children aged 6–12 years were enriched in Streptococcus mutans and Corynebacterium durum, respectively. The machine learning models based on these differentially enriched taxa showed accuracies of up to 83%. These results confirmed significant alterations in the oral microbiome according to dental caries and age, and these differences can be used as diagnostic biomarkers.

Obesity and insulin resistance accelerate aging-related sarcopenia, which is associated with iron load and oxidative stress. Lipocalin-2 (LCN2) is an iron-binding protein that has been associated with skeletal muscle regeneration, but details regarding its role in obese sarcopenia remain unclear. Here, we report that elevated LCN2 levels in skeletal muscle are linked to muscle atrophy-related inflammation and oxidative stress in leptin-deficient ob/ob mice. RNA sequencing analyses indicated the LCN2 gene expression is enhanced in skeletal muscle of ob/ob mice with sarcopenia. In addition to muscular iron accumulation in ob/ob mice, expressions of iron homeostasis-related divalent metal transporter 1, ferritin, and hepcidin proteins were increased in ob/ob mice compared to lean littermates, whereas expressions of transferrin receptor and ferroportin were reduced. Collectively, these findings demonstrate that LCN2 functions as a potent proinflammatory factor in skeletal muscle in response to obesity-related sarcopenia and is thus a therapeutic candidate target for sarcopenia treatment.