The Relationship between Types of Os Trigonum and Findings of Conventional Ankle Magnetic Resonance Imaging: A Study Based on Three-Dimensional Magnetic Resonance Imaging.

This study aimed to investigate the dimensions and types of the os trigonum and evaluate their relationship with various pathologic conditions on the posterior ankle using ankle MRI images. A total of 124 non-contrast-enhanced ankle and foot MR images of 123 consecutive patients were included in this retrospective study. The images were presented randomly, and they contained no patient information. The MR images were retrospectively and independently reviewed by two reviewers with a fellowship-trained musculoskeletal radiologist. The images were classified as type I and II based on the ossicle's medial border overlying the talus's posterior process and the groove for the flexor hallucis longus tendon (FHL). The study revealed that patients with type II os trigonum had a longer transverse diameter of the ossicle than type I, and there were statistically significant differences. Detachment status tended to be less in type I than in type II os trigonum, and the differences between the groups were statistically significant. There were no significant differences between type I and II os trigonum regarding posterior talofibular ligament (PTFL) abnormality, bone marrow edema, FHL tenosynovitis, and posterior synovitis. The study concluded that the os trigonum is a common cause of posterior ankle impingement, and type II os trigonum has a longer transverse diameter of the ossicle than type I.

ChatGPT's Accuracy on Magnetic Resonance Imaging Basics: Characteristics and Limitations Depending on the Question Type.

Our study aimed to assess the accuracy and limitations of ChatGPT in the domain of MRI, focused on evaluating ChatGPT's performance in answering simple knowledge questions and specialized multiple-choice questions related to MRI. A two-step approach was used to evaluate ChatGPT. In the first step, 50 simple MRI-related questions were asked, and ChatGPT's answers were categorized as correct, partially correct, or incorrect by independent researchers. In the second step, 75 multiple-choice questions covering various MRI topics were posed, and the answers were similarly categorized. The study utilized Cohen's kappa coefficient for assessing interobserver agreement. ChatGPT demonstrated high accuracy in answering straightforward MRI questions, with over 85% classified as correct. However, its performance varied significantly across multiple-choice questions, with accuracy rates ranging from 40% to 66.7%, depending on the topic. This indicated a notable gap in its ability to handle more complex, specialized questions requiring deeper understanding and context. In conclusion, this study critically evaluates the accuracy of ChatGPT in addressing questions related to Magnetic Resonance Imaging (MRI), highlighting its potential and limitations in the healthcare sector, particularly in radiology. Our findings demonstrate that ChatGPT, while proficient in responding to straightforward MRI-related questions, exhibits variability in its ability to accurately answer complex multiple-choice questions that require more profound, specialized knowledge of MRI. This discrepancy underscores the nuanced role AI can play in medical education and healthcare decision-making, necessitating a balanced approach to its application.

The Development and Validation of an AI Diagnostic Model for Sacroiliitis: A Deep-Learning Approach.

PURPOSE: Sacroiliitis refers to the inflammatory condition of the sacroiliac joints, frequently causing lower back pain. It is often associated with systemic conditions. However, its signs on radiographic images can be subtle, which may result in it being overlooked or underdiagnosed. This study aims to utilize artificial intelligence (AI) to create a diagnostic tool for more accurate sacroiliitis detection in radiological images, with the goal of optimizing treatment plans and improving patient outcomes. MATERIALS AND METHOD: The study included 492 patients who visited our hospital. Right sacroiliac joint films were independently evaluated by two musculoskeletal radiologists using the Modified New York criteria (Normal, Grades 1-4). A consensus reading resolved disagreements. The images were preprocessed with Z-score standardization and histogram equalization. The DenseNet121 algorithm, a convolutional neural network with 201 layers, was used for learning and classification. All steps were performed on the DEEP:PHI platform. RESULT: The AI model exhibited high accuracy across different grades: 94.53% (Grade 1), 95.83% (Grade 2), 98.44% (Grade 3), 96.88% (Grade 4), and 96.09% (Normal cases). Sensitivity peaked at Grade 3 and Normal cases (100%), while Grade 4 achieved perfect specificity (100%). PPVs ranged from 82.61% (Grade 1) to 100% (Grade 4), and NPVs peaked at 100% for Grade 3 and Normal cases. The F1 scores ranged from 64.41% (Grade 1) to 95.38% (Grade 3). CONCLUSIONS: The AI diagnostic model showcased a robust performance in detecting and grading sacroiliitis, reflecting its potential to enhance diagnostic accuracy in clinical settings. By facilitating earlier and more accurate diagnoses, this model could substantially impact treatment strategies and patient outcomes.

Identification of Essential Genes for the Establishment of Spray-Induced Gene Silencing-Based Disease Control in Fusarium graminearum.

As resistance to chemical fungicides continues to increase inFusarium graminearum, there is a growing need to develop novel disease control strategies. To discover essential genes that could serve as new disease control targets, we selected essential gene candidates that had failed to be deleted in previous studies. Thirteen genes were confirmed to be essential, either by constructing conditional promoter replacement mutants or by employing a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated editing strategy. We synthesized double-stranded RNAs (dsRNAs) targeting these essential genes and analyzed their protective effects in plants using a spray-induced gene silencing (SIGS) method. When dsRNAs targeting Fg10360, Fg13150, and Fg06123 were applied to detached barley leaves prior to fungal inoculation, disease lesions were greatly reduced. Our findings provide evidence of the potential of essential genes identified by a SIGS method to be effective targets for the control of fungal diseases.

Past and Future Epidemiological Perspectives and Integrated Management of Rice Bakanae in Korea.

In the past, rice bakanae was considered an endemic disease that did not cause significant losses in Korea; however, the disease has recently become a serious threat due to climate change, changes in farming practices, and the emergence of fungicide-resistant strains. Since the bakanae outbreak in 2006, its incidence has gradually decreased due to the application of effective control measures such as hot water immersion methods and seed disinfectants. However, in 2013, a marked increase in bakanae incidence was observed, causing problems for rice farmers. Therefore, in this review, we present the potential risks from climate change based on an epidemiological understanding of the pathogen, host plant, and environment, which are the key elements influencing the incidence of bakanae. In addition, disease management options to reduce the disease pressure of bakanae below the economic threshold level are investigated, with a specific focus on resistant varieties, as well as chemical, biological, cultural, and physical control methods. Lastly, as more effective countermeasures to bakanae, we propose an integrated disease management option that combines different control methods, including advanced imaging technologies such as remote sensing. In this review, we revisit and examine bakanae, a traditional seed-borne fungal disease that has not gained considerable attention in the agricultural history of Korea. Based on the understanding of the present significance and anticipated risks of the disease, the findings of this study are expected to provide useful information for the establishment of an effective response strategy to bakanae in the era of climate change.

Occurrence of human leukocyte antigen B51-related ankylosing spondylitis in a family: Two case reports.

BACKGROUND: Ankylosing spondylitis (AS) is strongly associated with the human leukocyte antigen (HLA) B27 haplotype. In regions where conventional polymerase chain reaction for HLA typing is available for antigens such as HLA B27 or HLA B51, it is common to perform the HLA B27 test for evaluation of AS. While HLA B27-associated clustered occurrences of AS have been reported in families, we report the first case series of HLA B51-related occurrences of AS in a family. CASE SUMMARY: A father and his daughters were diagnosed with AS and did not have the HLA B27 haplotype. Although they were positive for HLA B51, they exhibited no signs of Behçet's disease (BD). Of the five daughters, one had AS, and three, including the daughter with AS, were positive for HLA B51. The two daughters with the HLA B51 haplotype (excluding the daughter with AS) exhibited bilateral grade 1 sacroiliitis, whereas the daughters without the HLA B51 haplotype did not have sacroiliitis. Thus, this Korean family exhibited a strong association with the HLA B51 haplotype and clinical sacroiliitis, irrespective of the symptoms of BD. CONCLUSION: It is advisable to check for HLA B51 positivity in patients with AS/spondyloarthropathy who test negative for HLA B27.

TNP and its analogs: Modulation of IP6K and CYP3A4 inhibition.

Inositol hexakisphosphate kinase (IP6K) is an important mammalian enzyme involved in various biological processes such as insulin signalling and blood clotting. Recent analyses on drug metabolism and pharmacokinetic properties on TNP (N2-(m-trifluorobenzyl), N6-(p-nitrobenzyl)purine), a pan-IP6K inhibitor, have suggested that it may inhibit cytochrome P450 (CYP450) enzymes and induce unwanted drug-drug interactions in the liver. In this study, we confirmed that TNP inhibits CYP3A4 in type I binding mode more selectively than the other CYP450 isoforms. In an effort to find novel purine-based IP6K inhibitors with minimal CYP3A4 inhibition, we designed and synthesised 15 TNP analogs. Structure-activity relationship and biochemical studies, including ADP-Glo kinase assay and quantification of cell-based IP7 production, showed that compound 9 dramatically reduced CYP3A4 inhibition while retaining IP6K-inhibitory activity. Compound 9 can be a tool molecule for structural optimisation of purine-based IP6K inhibitors.

Structure-Functional Analysis of Human Cytochrome P450 2C8 Using Directed Evolution.

The human genome includes four cytochrome P450 2C subfamily enzymes, and CYP2C8 has generated research interest because it is subject to drug-drug interactions and various polymorphic outcomes. To address the structure-functional complexity of CYP2C8, its catalytic activity was studied using a directed evolution analysis. Consecutive rounds of random mutagenesis and screening using 6-methoxy-luciferin produced two mutants, which displayed highly increased luciferase activity. Wild-type and selected mutants were expressed on a large scale and purified. The expression levels of the D349Y and D349Y/V237A mutants were ~310 and 460 nmol per liter of culture, respectively. The steady-state kinetic analysis of paclitaxel 6α-hydroxylation showed that the mutants exhibited a 5-7-fold increase in kcat values and a 3-5-fold increase in catalytic efficiencies (kcat/KM). In arachidonic acid epoxidation, two mutants exhibited a 30-150-fold increase in kcat values and a 40-110-fold increase in catalytic efficiencies. The binding titration analyses of paclitaxel and arachidonic acid showed that the V237A mutation had a lower Kd value, indicating a tighter substrate-binding affinity. The structural analysis of CYP2C8 indicated that the D349Y mutation was close enough to the putative binding domain of the redox partner; the increase in catalytic activity could be partially attributed to the enhancement of the P450 coupling efficiency or electron transfer.

Structural insights into CYP107G1 from rapamycin-producing Streptomyces rapamycinicus.

Rapamycin is a clinically important macrolide agent with immunosuppressant and antiproliferative properties, produced by the actinobacterium, Streptomyces rapamycinicus. Two cytochrome P450 enzymes are involved in the biosynthesis of rapamycin. CYP107G1 and CYP122A2 catalyze the oxidation reactions of C27 and C9 of pre-rapamycin, respectively. To understand the structural and biochemical features of P450 enzymes in rapamycin biosynthesis, the CYP107G1 and CYP122A2 genes were cloned, their recombinant proteins were expressed in Escherichia coli, and the purified enzymes were characterized. Both enzymes displayed low spin states in the absolute spectra of ferric forms, and the titrations with rapamycin induced type I spectral changes with Kd values of 4.4 ± 0.4 and 3.0 ± 0.3 µM for CYP107G1 and CYP122A2, respectively. The X-ray crystal structures of CYP107G1 and its co-crystal complex with everolimus, a clinical rapamycin derivative, were determined at resolutions of 2.9 and 3.0 Å, respectively. The overall structure of CYP107G1 adopts the canonical scaffold of cytochrome P450 and possesses large substrate pocket. The distal face of the heme group is exposed to solvents to accommodate macrolide access. When the structure of the everolimus-bound CYP107G1 complex (CYP107G1-Eve) was compared to that of the ligand-free CYP107G1 form, no significant conformational change was observed. Hence, CYP107G1 has a relatively rigid structure with versatile loops to accommodate a bulky substrate. The everolimus molecule is bound to the substrate-binding pocket in the shape of a squeezed donut, and its elongated structure is bound perpendicular to a planar heme plane and I-helix.

Inhibition of cytochrome P450 2B6 by Astragalus extract mixture HT042.

Astragalus extract mixture (AEM) HT042 is a functional food approved by the MFDS (Korean FDA) for increasing height. It comprises a mixture of three standardized extracts from Astragalus membranaceus root, Eleutherococcus senticosus stem, and Phlomis umbrosa root. In this study, drug-functional food interaction was analyzed using six major human cytochrome P450 enzymes. The inhibitory effect of AEM HT042 on P450 activities was studied using a P450-NADPH P450 reductase reconstitution system. Among the six P450 enzymes (1A2, 2A6, 2B6, 2D6, 2C9, and 3A4), only P450 2B6 activity was markedly decreased by AEM HT042 addition. The bupropion hydroxylation activity of P450 2B6 was analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A calculated IC50 value of 10.62 µg/ml was obtained. To identify the inhibitory compounds in the mixture, four active compounds in AEM HT042 were analyzed. Shanzhiside methylester exhibited inhibitory effects on P450 2B6, whereas formononetin, eleutheroside E, and sesamoside did not affect P450 2B6 activity at all. Our results suggest that shanzhiside methylester in AEM HT042 is responsible for the inhibitory effect on P450 2B6 metabolism. Characterization of the inhibitory effect on P450 can help determine the safe administration of functional foods along with many clinical drugs that are metabolized by P450.

Functional Characterization of Pharmcogenetic Variants of Human Cytochrome P450 2C9 in Korean Populations.

Human cytochrome P450 2C9 is a highly polymorphic enzyme that is required for drug and xenobiotic metabolism. Here, we studied eleven P450 2C9 genetic variants-including three novel variants F69S, L310V, and Q324X-that were clinically identified in Korean patients. P450 2C9 variant enzymes were expressed in Escherichia coli and their bicistronic membrane fractions were prepared The CO-binding spectra were obtained for nine enzyme variants, indicating P450 holoenzymes, but not for the M02 (L90P) variant. The M11 (Q324X) variant could not be expressed due to an early nonsense mutation. LC-MS/MS analysis was performed to measure the catalytic activities of the P450 2C9 variants, using diclofenac as a substrate. Steady-state kinetic analysis revealed that the catalytic efficiency of all nine P450 2C9 variants was lower than that of the wild type P450 2C9 enzyme. The M05 (R150L) and M06 (P279T) variants showed high kcat values; however, their Km values were also high. As the M01 (F69S), M03 (R124Q), M04 (R125H), M08 (I359L), M09 (I359T), and M10 (A477T) variants exhibited higher Km and lower kcat values than that of the wild type enzyme, their catalytic efficiency decreased by approximately 50-fold compared to the wild type enzyme. Furthermore, the novel variant M07 (L310V) showed lower kcat and Km values than the wild type enzyme, which resulted in its decreased (80%) catalytic efficiency. The X-ray crystal structure of P450 2C9 revealed the presence of mutations in the residues surrounding the substrate-binding cavity. Functional characterization of these genetic variants can help understand the pharmacogenetic outcomes.

CYP52A23 from Candida albicans and its Substrate Preference for Fatty Acid Hydroxylation.

The pathogenic fungus Candida albicans contains genes encoding five fatty acid hydroxylases belonging to the CYP52 family in its genome. Our previous study reported that CYP52A21 demonstrated typical omega-hydroxylation of lauric acid (Kim D, Cryle MJ, De Voss JJ, Ortiz de Montellano PR (2007) Arch Biochem Biophys 464, 213-220). Functional characterization of CYP52 fatty acid hydroxylases was studied, and their selectivity for hydroxylation was analyzed. Genes for four other CYP52 members (CYP52A22, CYP52A23, CYP52A24, and CYP52C3) from C. albicans were cloned, and their recombinant enzymes were expressed in Escherichia coli. CO-binding spectral analyses showed that the functional P450 holoenzyme was obtained only in CYP52A23, while no holoenzyme peak was observed in the other three CYP52 enzymes. Spectral change of the type II binding was observed in purified CYP52A23 when titrated with fatty acids but none was observed with alkanes. The gas chromatography-mass spectrometry (GC-MS) analysis revealed that CYP52A23 predominantly exhibited omega-hydroxylation activity during the oxidation reaction of fatty acids. Interestingly, it was found that CYP52A23 preferred longer-chain fatty acids (stearic acid and arachidic acid) for its catalytic activities while CYP52A21 preferred mid-chain fatty acids (lauric acid and mystic acid). To analyze the selectivity of fatty acids, hybrid mutagenesis of genes encoding CYP52A21 and CYP52A23 by overlap extension polymerase chain reaction was conducted. Two hybrid mutants containing the N-terminal fragments of CYP52A21 and C-terminal fragments of CYP52A23 displayed higher catalytic activity in palmitic acid and arachidic acid. These results suggested that the C-terminal part of CYP52A23 may be responsible for its preference to longer-chain fatty acids.