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1.
Heliyon ; 10(11): e30960, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38832258

ABSTRACT

Distance education supports lifelong learning and empowers individuals in rapidly changing societal conditions, yet it encounters high dropout rates due to a range of individual and societal obstacles. This study addresses the challenge of creating a practical prediction model by analyzing extensive real-world time-point data from a well-established online university in Seoul. Covering 144,540 instances from 2018 to 2022, the study integrates diverse datasets to compare the accuracy of models based on longitudinal, semester-wise, and gender-specific datasets. The demographic, academic, and online metrics identified significant dropout indicators, including age (particularly when binned), residential area, specific occupations, GPA, and LMS log metrics, using a stepwise backward elimination process. The study revealed that, despite societal changes, recent data from the last four semesters can be effectively used for stable prediction training. Gender-based analysis showed different factors influencing dropout risk for males and females. The Light Gradient Boosting Machine (LGBM) algorithm excelled in prediction accuracy, with the ROC-AUC metric affirming its superiority. However, logistic regression also showed its competitive performance and offered in-depth interpretation. In South Korea's distinct educational setting, merging advanced algorithms like LGBM with the interpretive strength of logistic regression is key for effective student support strategies.

2.
Nat Commun ; 15(1): 4883, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849395

ABSTRACT

The human methyltransferase and transcriptional coactivator MLL4 and its paralog MLL3 are frequently mutated in cancer. MLL4 and MLL3 monomethylate histone H3K4 and contain a set of uncharacterized PHD fingers. Here, we report a novel function of the PHD2 and PHD3 (PHD2/3) fingers of MLL4 and MLL3 that bind to ASXL2, a component of the Polycomb repressive H2AK119 deubiquitinase (PR-DUB) complex. The structure of MLL4 PHD2/3 in complex with the MLL-binding helix (MBH) of ASXL2 and mutational analyses reveal the molecular mechanism which is conserved in homologous ASXL1 and ASXL3. The native interaction of the Trithorax MLL3/4 complexes with the PR-DUB complex in vivo depends solely on MBH of ASXL1/2, coupling the two histone modifying activities. ChIP-seq analysis in embryonic stem cells demonstrates that MBH of ASXL1/2 is required for the deubiquitinase BAP1 recruitment to MLL4-bound active enhancers. Our findings suggest an ASXL1/2-dependent functional link between the MLL3/4 and PR-DUB complexes.


Subject(s)
DNA-Binding Proteins , Histone-Lysine N-Methyltransferase , Protein Binding , Repressor Proteins , Tumor Suppressor Proteins , Ubiquitin Thiolesterase , Tumor Suppressor Proteins/metabolism , Tumor Suppressor Proteins/genetics , Humans , Histone-Lysine N-Methyltransferase/metabolism , Histone-Lysine N-Methyltransferase/genetics , Ubiquitin Thiolesterase/metabolism , Ubiquitin Thiolesterase/genetics , Repressor Proteins/metabolism , Repressor Proteins/genetics , Animals , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Mice , Enhancer Elements, Genetic , HEK293 Cells , PHD Zinc Fingers , Histones/metabolism
3.
Sci Rep ; 14(1): 11278, 2024 05 17.
Article in English | MEDLINE | ID: mdl-38760384

ABSTRACT

In our previous study, we developed a triple-negative breast cancer (TNBC) subtype classification that correlated with the TNBC molecular subclassification. In this study, we aimed to evaluate the predictor variables of this subtype classification on the whole slide and to validate the model's performance by using an external test set. We explored the characteristics of this subtype classification and investigated genomic alterations, including genomic scar signature scores. First, TNBC was classified into the luminal androgen receptor (LAR) and non-luminal androgen receptor (non-LAR) subtypes based on the AR Allred score (≥ 6 and < 6, respectively). Then, the non-LAR subtype was further classified into the lymphocyte-predominant (LP), lymphocyte-intermediate (LI), and lymphocyte-depleted (LD) groups based on stromal tumor-infiltrating lymphocytes (TILs) (< 20%, > 20% but < 60%, and ≥ 60%, respectively). This classification showed fair agreement with the molecular classification in the test set. The LAR subtype was characterized by a high rate of PIK3CA mutation, CD274 (encodes PD-L1) and PDCD1LG2 (encodes PD-L2) deletion, and a low homologous recombination deficiency (HRD) score. The non-LAR LD TIL group was characterized by a high frequency of NOTCH2 and MYC amplification and a high HRD score.


Subject(s)
Lymphocytes, Tumor-Infiltrating , Receptors, Androgen , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/classification , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/immunology , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Female , Middle Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Mutation , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , Class I Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases/metabolism
4.
Front Endocrinol (Lausanne) ; 15: 1352552, 2024.
Article in English | MEDLINE | ID: mdl-38699383

ABSTRACT

Congenital adrenal hyperplasia (CAH) and Williams Syndrome (WS; MIM # 194050) are distinct genetic conditions characterized by unique clinical features. 21-Hydroxylase deficiency (21-OHD; MIM #201910), the most common form of CAH, arises from mutations in the CYP21A2 gene, resulting in virilization of the external genitalia in affected females, early puberty in males, and short stature. Williams syndrome, caused by a microdeletion of 7q11.23, presents with distinctive facial features, intellectual disability, unique personality traits, early puberty, and short stature. This case report describe the clinical features of a 4-year-old girl referred due to progressive virilization and developmental delay. Genetic analysis confirmed concurrent CAH and WS, identifying a novel mutation in the CYP21A2 gene (c.1442T>C). Following corticosteroid therapy initiation, the patient developed central precocious puberty. This case report delves into the pubertal change patterns in a patient affected by overlapping genetic conditions, providing valuable insights in to the intricate clinical manifestation and management of these rare complex disorders.


Subject(s)
Adrenal Hyperplasia, Congenital , Puberty, Precocious , Virilism , Williams Syndrome , Humans , Female , Adrenal Hyperplasia, Congenital/complications , Adrenal Hyperplasia, Congenital/diagnosis , Adrenal Hyperplasia, Congenital/genetics , Puberty, Precocious/diagnosis , Puberty, Precocious/genetics , Puberty, Precocious/etiology , Williams Syndrome/complications , Williams Syndrome/genetics , Williams Syndrome/diagnosis , Child, Preschool , Virilism/genetics , Virilism/diagnosis , Steroid 21-Hydroxylase/genetics , Mutation
5.
Nat Commun ; 15(1): 4306, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773114

ABSTRACT

Heliorhodopsins (HeRs) have been hypothesized to have widespread functions. Recently, the functions for few HeRs have been revealed; however, the hypothetical functions remain largely unknown. Herein, we investigate light-modulation of heterodimeric multidrug resistance ATP-binding cassette transporters (OmrDE) mediated by Omithinimicrobium cerasi HeR. In this study, we classifiy genes flanking the HeR-encoding genes and identify highly conservative residues for protein-protein interactions. Our results reveal that the interaction between OcHeR and OmrDE shows positive cooperatively sequential binding through thermodynamic parameters. Moreover, light-induced OcHeR upregulates OmrDE drug transportation. Hence, the binding may be crucial to drug resistance in O. cerasi as it survives in a drug-containing habitat. Overall, we unveil a function of HeR as regulatory rhodopsin for multidrug resistance. Our findings suggest potential applications in optogenetic technology.


Subject(s)
ATP-Binding Cassette Transporters , Light , ATP-Binding Cassette Transporters/metabolism , ATP-Binding Cassette Transporters/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Protein Binding , Rhodopsins, Microbial/metabolism , Rhodopsins, Microbial/genetics , Rhodopsins, Microbial/chemistry , Optogenetics/methods
6.
Sci Rep ; 14(1): 12336, 2024 05 29.
Article in English | MEDLINE | ID: mdl-38811622

ABSTRACT

Hard ticks are known vectors of various pathogens, including the severe fever with thrombocytopenia syndrome virus, Rickettsia spp., Coxiella burnetii, Borrelia spp., Anaplasma phagocytophilum, and Ehrlichia spp. This study aims to investigate the distribution and prevalence of tick-borne pathogens in southwestern Korea from 2019 to 2022. A total of 13,280 ticks were collected during the study period, with H. longicornis accounting for 86.1% of the collected ticks. H. flava, I. nipponensis and A. testudinarium comprised 9.4%, 3.6%, and 0.8% of the ticks, respectively. Among 983 pools tested, Rickettsia spp. (216 pools, 1.6% MIR) were the most prevalent pathogens across all tick species, with R. japonica and R. monacensis frequently detected in I. nipponensis and Haemaphysalis spp., respectively. Borrelia spp. (28 pools, 0.2% MIR) were predominantly detected in I. nipponensis (27 pools, 13.8% MIR, P < 0.001). Co-infections, mainly involving Rickettsia monacensis and Borrelia afzelii, were detected in I. nipponensis. Notably, this study identified R. monacensis for the first time in A. testudinarium in South Korea. These findings offer valuable insights into the tick population and associated pathogens in the region, underscoring the importance of tick-borne disease surveillance and prevention measures.


Subject(s)
Rickettsia , Animals , Republic of Korea/epidemiology , Rickettsia/isolation & purification , Rickettsia/genetics , Ticks/microbiology , Ticks/virology , Tick-Borne Diseases/epidemiology , Tick-Borne Diseases/microbiology , Tick-Borne Diseases/virology , Prevalence , Borrelia/isolation & purification , Borrelia/genetics , Anaplasma phagocytophilum/isolation & purification , Ehrlichia/isolation & purification , Ehrlichia/genetics , Coxiella burnetii/isolation & purification , Coxiella burnetii/genetics , Phlebovirus/isolation & purification , Phlebovirus/genetics
7.
Curr Issues Mol Biol ; 46(5): 4580-4594, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38785546

ABSTRACT

The proto-oncogene MYC is frequently dysregulated in patients with diffuse large B-cell lymphoma (DLBCL) and plays a critical role in disease progression. To improve the clinical outcomes of patients with DLBCL, the development of strategies to target MYC is crucial. The use of medicinal plants for developing anticancer drugs has garnered considerable attention owing to their diverse mechanisms of action. In this study, 100 plant extracts of flora from the Republic of Korea were screened to search for novel agents with anti-DLBCL effects. Among them, Ajania pacifica (Nakai) K. Bremer and Humphries extract (APKH) efficiently suppressed the survival of DLBCL cells, while showing minimal toxicity toward normal murine bone marrow cells. APKH suppressed the expression of anti-apoptotic BCL2 family members, causing an imbalance between the pro-apoptotic and anti-apoptotic BCL2 members. This disrupted mitochondrial membrane potential, cytochrome c release, and pro-caspase-3 activation and eventually led to DLBCL cell death. Importantly, MYC expression was markedly downregulated by APKH and ectopic expression of MYC in DLBCL cells abolished the pro-apoptotic effects of APKH. These results demonstrate that APKH exerts anti-DLBCL effects by inhibiting MYC expression. Moreover, when combined with doxorubicin, an essential component of the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone), APKH synergistically enhanced the therapeutic effect of doxorubicin. This indicates that APKH may overcome drug resistance, which is common in patients with refractory/relapsed DLBCL. To identify compounds with anti-DLBCL activities in APKH, the chemical profile analysis of APKH was performed using UPLC-QTOF/MSe analysis and assessed for its anticancer activity. Based on the UPLC-QTOF/MSe chemical profiling, it is conceivable that APKH may serve as a novel agent targeting MYC and sensitizing drug-resistant DLBCL cells to CHOP chemotherapy. Further studies to elucidate how the compounds in APKH exert tumor-suppressive role in DLBCL are warranted.

8.
PLoS One ; 19(5): e0303355, 2024.
Article in English | MEDLINE | ID: mdl-38787813

ABSTRACT

In this study, we propose a generative data augmentation technique to overcome the challenges of severely limited data when designing a deep learning-based automated strabismus diagnosis system. We implement a generative model based on the StyleGAN2-ADA model for system design and assess strabismus classification performance using two classifiers. We evaluate the capability of our proposed method against traditional data augmentation techniques and confirm a substantial enhancement in performance. Furthermore, we conduct experiments to explore the relationship between the diagnosis agreement among ophthalmologists and the generation performance of the generative model. Beyond FID, we validate the generative samples on the classifier to establish their practicality. Through these experiments, we demonstrate that the generative model-based data augmentation improves overall quantitative performance in scenarios of extreme data scarcity and effectively mitigates overfitting issues during deep learning model training.


Subject(s)
Deep Learning , Strabismus , Humans , Strabismus/diagnosis , Strabismus/classification , Algorithms
9.
Int J Pharm ; 657: 124177, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38697582

ABSTRACT

We present a promising method for producing amorphous drug particles using a nozzle-free ultrasonic nebulizer with polymers, specifically polyvinylpyrrolidone (PVP), poly(acrylic acid) (PAA), and Eudragit® S 100 (EUD). Model crystalline phase drugs-Empagliflozin, Furosemide, and Ilaprazole-are selected. This technique efficiently produces spherical polymer-drug composite particles and demonstrates enhanced stability against humidity and thermal conditions, compared to the drug-only amorphous particles. The composite particles exhibit improved water dissolution compared to the original crystalline drugs, indicating potential bioavailability enhancements. While there are challenges, including the need for continuous water supply for ultrasonic component cooling, dependency on the solubility of polymers and drugs in volatile organic solvents, and mildly elevated temperatures for solvent evaporation, our method offers significant advantages over traditional approaches. It provides a straightforward, flexible process adaptable to various drug-polymer combinations and consistently yields spherical amorphous solid dispersion (ASD) particles with a narrow size distribution. These attributes make our method a valuable advancement in pharmaceutical drug formulation and delivery.


Subject(s)
Nebulizers and Vaporizers , Particle Size , Polymers , Polymers/chemistry , Drug Stability , Solubility , Drug Compounding/methods , Acrylic Resins/chemistry , Povidone/chemistry , Ultrasonics , Polymethacrylic Acids/chemistry , Furosemide/chemistry , Chemistry, Pharmaceutical/methods
10.
Biochem Biophys Res Commun ; 720: 150072, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-38749187

ABSTRACT

The Eph receptor, a prototypically large receptor protein tyrosine kinase, interacts with ephrin ligands, forming a bidirectional signaling system that impacts diverse brain functions. Eph receptors and ephrins mediate forward and reverse signaling, affecting neurogenesis, axon guidance, and synaptic signaling. While mammalian studies have emphasized their roles in neurogenesis and synaptic plasticity, the Drosophila counterparts are less studied, especially in glial cells, despite structural similarities. Using RNAi to modulate Eph/ephrin expression in Drosophila neurons and glia, we studied their roles in brain development and sleep and circadian behavior. Knockdown of neuronal ephrin disrupted mushroom body development, while glial knockdown had minimal impact. Surprisingly, disrupting ephrin in neurons or glial cells altered sleep and circadian rhythms, indicating a direct involvement in these behaviors independent from developmental effects. Further analysis revealed distinct sleep phenotypes between neuronal and glial knockdowns, underscoring the intricate interplay within the neural circuits that govern behavior. Glia-specific knockdowns showed altered sleep patterns and reduced circadian rhythmicity, suggesting an intricate role of glia in sleep regulation. Our findings challenge simplistic models of Eph/ephrin signaling limited to neuron-glia communication and emphasize the complexity of the regulatory networks modulating behavior. Future investigations targeting specific glial subtypes will enhance our understanding of Eph/ephrin signaling's role in sleep regulation across species.


Subject(s)
Circadian Rhythm , Ephrins , Mushroom Bodies , Neuroglia , Neurons , Signal Transduction , Sleep , Animals , Neuroglia/metabolism , Sleep/physiology , Sleep/genetics , Circadian Rhythm/physiology , Neurons/metabolism , Ephrins/metabolism , Ephrins/genetics , Mushroom Bodies/metabolism , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Receptors, Eph Family/metabolism , Receptors, Eph Family/genetics , Drosophila melanogaster/metabolism , Drosophila melanogaster/physiology , Drosophila melanogaster/genetics , Drosophila/metabolism
11.
Nat Commun ; 15(1): 3971, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38729931

ABSTRACT

The Berry curvature dipole (BCD) serves as a one of the fundamental contributors to emergence of the nonlinear Hall effect (NLHE). Despite intense interest due to its potential for new technologies reaching beyond the quantum efficiency limit, the interplay between BCD and NLHE has been barely understood yet in the absence of a systematic study on the electronic band structure. Here, we report NLHE realized in NbIrTe4 that persists above room temperature coupled with a sign change in the Hall conductivity at 150 K. First-principles calculations combined with angle-resolved photoemission spectroscopy (ARPES) measurements show that BCD tuned by the partial occupancy of spin-orbit split bands via temperature is responsible for the temperature-dependent NLHE. Our findings highlight the correlation between BCD and the electronic band structure, providing a viable route to create and engineer the non-trivial Hall effect by tuning the geometric properties of quasiparticles in transition-metal chalcogen compounds.

12.
Tob Induc Dis ; 222024.
Article in English | MEDLINE | ID: mdl-38779295

ABSTRACT

INTRODUCTION: Despite electronic cigarettes (e-cigarettes) being marketed as a safer alternative to combustible cigarettes, the effects of chronic e-cigarette use on vascular health remain uncertain. Our meta-analysis aimed to assess the health implications of chronic exclusive e-cigarette use on endothelial dysfunction, as measured by flow-mediated vasodilation (FMD). METHODS: PubMed, Embase and Scopus were searched for studies from 1 January 2004 to 31 March 2024. Four cross-sectional studies (n=769) were pooled using a random-effects model. The mean differences (MD) of FMD were reported by comparing exclusive e-cigarette use versus non-use; exclusive e-cigarette use versus combustible cigarette use; and combustible cigarette use versus non-use. RESULTS: A non-significant reduction in FMD in exclusive e-cigarette use compared to non-use was reported (MD of FMD: -1.47%; 95% CI: -3.96 - 1.02; I2= 84%). Similar MD of FMD in exclusive e-cigarette use and exclusive combustible cigarette use (vs non-use) suggested that both of these products might have comparable adverse influences on endothelial health. CONCLUSIONS: The limited availability of studies assessing the chronic impact of e-cigarette use restricted our ability to provide definitive findings. We emphasize the importance of additional research that explores the long-term impact of e-cigarette use on endothelial dysfunction, and identify key areas and give suggestions for further study.

13.
PLoS One ; 19(4): e0301635, 2024.
Article in English | MEDLINE | ID: mdl-38630743

ABSTRACT

Remimazolam's rapid onset and offset make it an innovative sedative for use during regional anesthesia. However, its respiratory safety profile is not well understood. We compared the continuous infusion of remimazolam with commonly used sedatives, propofol and dexmedetomidine, after regional anesthesia. In this retrospective study, the incidence of apnea (>10 seconds) was assessed in patients who underwent orthopedic surgery under regional anesthesia and received moderate to deep sedation using continuous infusion of remimazolam (group R: 0.1 mg/kg in 2 minutes followed by 0.5 mg/kg/hr). The incidence was compared with that of propofol (group P: 2-3 µg/mL target-controlled infusion) and dexmedetomidine (group D: 1 µg/kg in 10 minutes followed by 0.4-1 µg/kg/hr). Propensity score weighted multivariable logistic regression model was utilized to determine the effects of the sedative agents on the incidence of apnea. A total of 634 (191, 278, and 165 in group R, P, and D) cases were included in the final analysis. The incidence of apnea was 63.9%, 67.3%, and 48.5% in group R, P, and D, respectively. The adjusted odds ratios for apnea were 2.33 (95% CI, 1.50 to 3.61) and 2.50 (95% CI, 1.63 to 3.85) in group R and P, compared to group D. The incidence of apnea in patients receiving moderate to deep sedation using continuous infusion of remimazolam with dosage suggested in the current study was over 60%. Therefore, careful titration and respiratory monitoring is warranted.


Subject(s)
Benzodiazepines , Deep Sedation , Dexmedetomidine , Propofol , Humans , Retrospective Studies , Apnea , Hypnotics and Sedatives
14.
Article in English | MEDLINE | ID: mdl-38656187

ABSTRACT

To address the plasticization phenomenon and MOF-polymer interfacial defects, we report the synthesis of ionic cross-linked MOF MMMs from a dual brominated polymer and MOF components by using N,N'-dimethylpiperazine as the cross-linker. We synthesized brominated MIL-101(Cr) nanoparticles by using mixed linkers and prepared brominated polyimide (6FDA-DAM-Br) to form ionic cross-linked MMMs. The gas permeation properties of the polyimide, ionic cross-linked MOF-polymer MMMs, and non-cross-linked MOF-polymer MMMs with various MOF weight loadings were investigated systematically to effectively understand the effects of MOF weight loading and ionic cross-linking. The ionic cross-linked 40 wt % MOF-polymer MMM exhibited significantly enhanced gas permeability with an H2 permeability of 1640 Barrer and CO2 permeability of 1981 Barrer and slightly decreased H2/CH4, H2/N2, CO2/CH4 and CO2/N2 selectivities of 16.9, 15.4, 20.5, and 18.6, respectively. The H2 and CO2 permeabilities are approximately 2-3 fold higher than those of the pure polyimide (6FDA-DAM) membrane. Moreover, the ionic cross-linked 40 wt % MOF-polymer MMM exhibited significantly increased resistance to plasticization. This is because the brominated MOF incorporation boosted molecular transport and polymer chain rigidity, and ionic cross-linking further reduced the number of interfacial defects and polymer chain mobility.

15.
Nano Converg ; 11(1): 14, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622355

ABSTRACT

Tunability of interfacial effects between two-dimensional (2D) crystals is crucial not only for understanding the intrinsic properties of each system, but also for designing electronic devices based on ultra-thin heterostructures. A prerequisite of such heterostructure engineering is the availability of 2D crystals with different degrees of interfacial interactions. In this work, we report a controlled epitaxial growth of monolayer TaSe2 with different structural phases, 1H and 1 T, on a bilayer graphene (BLG) substrate using molecular beam epitaxy, and its impact on the electronic properties of the heterostructures using angle-resolved photoemission spectroscopy. 1H-TaSe2 exhibits significant charge transfer and band hybridization at the interface, whereas 1 T-TaSe2 shows weak interactions with the substrate. The distinct interfacial interactions are attributed to the dual effects from the differences of the work functions as well as the relative interlayer distance between TaSe2 films and BLG substrate. The method demonstrated here provides a viable route towards interface engineering in a variety of transition-metal dichalcogenides that can be applied to future nano-devices with designed electronic properties.

16.
Sci Rep ; 14(1): 8747, 2024 04 16.
Article in English | MEDLINE | ID: mdl-38627483

ABSTRACT

This study aimed to evaluate the incidence and likelihood of antibiotic-associated encephalopathy (AAE), comparing rates among the classes of antibiotics in monotherapy or in combination therapy. We also investigated the associations between the incidence of AAE and the glomerular filtration rate (GFR) and electroencephalogram features. Consecutive admissions that used any kind of antibiotics to treat infectious diseases were identified from six hospitals. We classified antibiotics according to three distinct pathophysiologic mechanisms and clinical subtypes. We searched for the incidence of AAE as the primary outcome. A total of 97,433 admission cases among 56,038 patients was identified. Cases that received type 1 antibiotics had significantly more frequent AAE compared to those that received type 2 antibiotics (adjusted odds ratio [OR], 2.62; 95% confidence interval [CI] 1.15-5.95; P = 0.021). Combined use of type 1 + 2 antibiotics was associated with a significantly higher incidence of AAE compared to the use of type 2 antibiotics alone (adjusted OR, 3.44; 95% CI 1.49-7.93; P = 0.004). Groups with GFR < 60 mL/min/1.73 m2 had significantly higher incidence rates of AAE compared to those with GFRs ≥ 90 mL/min/1.73 m2 among cases that received type 1 + 2 antibiotics. Detection of spike-and-wave or sharp-and-wave patterns on electroencephalogram was significantly more common in the combination therapy group. Combination use of antibiotics was associated with a higher incidence of AAE compared to monotherapy. The incidence of AAE significantly increased as renal function decreased, and epileptiform discharges were more likely to be detected in cases receiving combined antibiotics.


Subject(s)
Anti-Bacterial Agents , Brain Diseases , Humans , Anti-Bacterial Agents/adverse effects , Incidence , Glomerular Filtration Rate , Brain Diseases/chemically induced , Brain Diseases/epidemiology , Brain Diseases/drug therapy , Hospitals
17.
PLoS One ; 19(4): e0298870, 2024.
Article in English | MEDLINE | ID: mdl-38564629

ABSTRACT

Physical fitness (PF) includes various factors that significantly impacts athletic performance. Analyzing PF is critical in developing customized training methods for athletes based on the sports in which they compete. Previous approaches to analyzing PF have relied on statistical or machine learning algorithms that focus on predicting athlete injury or performance. In this study, six machine learning algorithms were used to analyze the PF of 1,489 male adolescent athletes across five sports, including track & field, football, baseball, swimming, and badminton. Furthermore, the machine learning models were utilized to analyze the essential elements of PF using feature importance of XGBoost, and SHAP values. As a result, XGBoost represents the highest performance, with an average accuracy of 90.14, an area under the curve of 0.86, and F1-score of 0.87, demonstrating the similarity between the sports. Feature importance of XGBoost, and SHAP value provided a quantitative assessment of the relative importance of PF in sports by comparing two sports within each of the five sports. This analysis is expected to be useful in analyzing the essential PF elements of athletes in various sports and recommending personalized exercise methods accordingly.


Subject(s)
Athletic Injuries , Football , Humans , Male , Adolescent , Athletes , Football/injuries , Swimming , Physical Fitness
18.
Hematology ; 29(1): 2343163, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38655690

ABSTRACT

BACKGROUND: Congenital dyserythropoietic anemia Ⅱ (CDA Ⅱ) is a rare inherited disorder of defective erythropoiesis caused by SEC23B gene mutation. CDA Ⅱ is often misdiagnosed as a more common type of clinically related anemia, or it remains undiagnosed due to phenotypic variability caused by the coexistence of inherited liver diseases, including Gilbert's syndrome (GS) and hereditary hemochromatosis. METHODS: We describe the case of a boy with genetically undetermined severe hemolytic anemia, hepatosplenomegaly, and gallstones whose diagnosis was achieved by targeted next generation sequencing. RESULTS: Molecular analysis revealed a maternally inherited novel intronic variant and a paternally inherited missense variant, c.[994-3C > T];[1831C > T] in the SEC23B gene, confirming diagnosis of CDA Ⅱ. cDNA analysis verified that the splice acceptor site variant results in two mutant transcripts, one with an exon 9 skip and one in which exons 9 and 10 are deleted. SEC23B mRNA levels in the patient were lower than those in healthy controls. The patient was also homozygous for the UGT1A1*6 allele, consistent with GS. CONCLUSION: Identification of the novel splice variant in this study further expands the spectrum of known SEC23B gene mutations. Molecular genetic approaches can lead to accurate diagnosis and management of CDA Ⅱ patients, particularly for those with GS coexisting.


Subject(s)
Anemia, Dyserythropoietic, Congenital , Gilbert Disease , Vesicular Transport Proteins , Humans , Anemia, Dyserythropoietic, Congenital/genetics , Anemia, Dyserythropoietic, Congenital/diagnosis , Male , Vesicular Transport Proteins/genetics , Gilbert Disease/genetics , Gilbert Disease/complications , Gilbert Disease/diagnosis , RNA Splicing , Mutation
19.
Structure ; 32(6): 706-714.e3, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38579707

ABSTRACT

Human mixed lineage leukemia 4 (MLL4), also known as KMT2D, regulates cell type specific transcriptional programs through enhancer activation. Along with the catalytic methyltransferase domain, MLL4 contains seven less characterized plant homeodomain (PHD) fingers. Here, we report that the sixth PHD finger of MLL4 (MLL4PHD6) binds to the hydrophobic motif of ten-eleven translocation 3 (TET3), a dioxygenase that converts methylated cytosine into oxidized derivatives. The solution NMR structure of the TET3-MLL4PHD6 complex and binding assays show that, like histone H4 tail, TET3 occupies the hydrophobic site of MLL4PHD6, and that this interaction is conserved in the seventh PHD finger of homologous MLL3 (MLL3PHD7). Analysis of genomic localization of endogenous MLL4 and ectopically expressed TET3 in mouse embryonic stem cells reveals a high degree overlap on active enhancers and suggests a potential functional relationship of MLL4 and TET3.


Subject(s)
DNA-Binding Proteins , Dioxygenases , Histone-Lysine N-Methyltransferase , Protein Binding , Humans , Dioxygenases/metabolism , Dioxygenases/chemistry , Dioxygenases/genetics , Animals , Mice , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , Histone-Lysine N-Methyltransferase/metabolism , Histone-Lysine N-Methyltransferase/chemistry , Histone-Lysine N-Methyltransferase/genetics , Binding Sites , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/chemistry , Proto-Oncogene Proteins/genetics , Models, Molecular , Myeloid-Lymphoid Leukemia Protein/metabolism , Myeloid-Lymphoid Leukemia Protein/chemistry , Myeloid-Lymphoid Leukemia Protein/genetics
20.
Chem Soc Rev ; 53(10): 5264-5290, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38619389

ABSTRACT

The energy storage and vehicle industries are heavily investing in advancing all-solid-state batteries to overcome critical limitations in existing liquid electrolyte-based lithium-ion batteries, specifically focusing on mitigating fire hazards and improving energy density. All-solid-state lithium-sulfur batteries (ASSLSBs), featuring earth-abundant sulfur cathodes, high-capacity metallic lithium anodes, and non-flammable solid electrolytes, hold significant promise. Despite these appealing advantages, persistent challenges like sluggish sulfur redox kinetics, lithium metal failure, solid electrolyte degradation, and manufacturing complexities hinder their practical use. To facilitate the transition of these technologies to an industrial scale, bridging the gap between fundamental scientific research and applied R&D activities is crucial. Our review will address the inherent challenges in cell chemistries within ASSLSBs, explore advanced characterization techniques, and delve into innovative cell structure designs. Furthermore, we will provide an overview of the recent trends in R&D and investment activities from both academia and industry. Building on the fundamental understandings and significant progress that has been made thus far, our objective is to motivate the battery community to advance ASSLSBs in a practical direction and propel the industrialized process.

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