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Coronavirus genomes sequester their start codons within stem-loop 5 (SL5), a structured, 5' genomic RNA element. In most alpha- and betacoronaviruses, the secondary structure of SL5 is predicted to contain a four-way junction of helical stems, some of which are capped with UUYYGU hexaloops. Here, using cryogenic electron microscopy (cryo-EM) and computational modeling with biochemically determined secondary structures, we present three-dimensional structures of SL5 from six coronaviruses. The SL5 domain of betacoronavirus severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2), resolved at 4.7 Å resolution, exhibits a T-shaped structure, with its UUYYGU hexaloops at opposing ends of a coaxial stack, the T's "arms." Further analysis of SL5 domains from SARS-CoV-1 and MERS (7.1 and 6.4 to 6.9 Å resolution, respectively) indicate that the junction geometry and inter-hexaloop distances are conserved features across these human-infecting betacoronaviruses. The MERS SL5 domain displays an additional tertiary interaction, which is also observed in the non-human-infecting betacoronavirus BtCoV-HKU5 (5.9 to 8.0 Å resolution). SL5s from human-infecting alphacoronaviruses, HCoV-229E and HCoV-NL63 (6.5 and 8.4 to 9.0 Å resolution, respectively), exhibit the same coaxial stacks, including the UUYYGU-capped arms, but with a phylogenetically distinct crossing angle, an X-shape. As such, all SL5 domains studied herein fold into stable tertiary structures with cross-genus similarities and notable differences, with implications for potential protein-binding modes and therapeutic targets.
Subject(s)
Alphacoronavirus , COVID-19 , Coronavirus 229E, Human , Humans , SARS-CoV-2/genetics , RNAABSTRACT
Although CRISPR-Cas9 technology is poised to revolutionize the treatment of diseases with underlying genetic mutations, it faces some significant issues limiting clinical entry. They include low-efficiency in vivo systemic delivery and undesired off-target effects. Here, we demonstrate, by modifying Cas9 with phosphorothioate-DNA oligos (PSs), that one can efficiently deliver single and bi-specific CRISPR-Cas9/guide RNA (gRNA) dimers in vitro and in vivo with reduced off-target effects. We show that PS-Cas9/gRNA-mediated gene knockout preserves chimeric antigen receptor T cell viability and expansion in vitro and in vivo. PS-Cas9/gRNA mediates gene perturbation in patient-derived tumor organoids and mouse xenograft tumors, leading to potent tumor antitumor effects. Further, HER2 antibody-PS-Cas9/gRNA conjugate selectively perturbs targeted genes in HER2+ ovarian cancer xenografts in vivo. Moreover, we created bi-specific PS-Cas9 with two gRNAs to target two adjacent sequences of the same gene, leading to efficient targeted gene disruption ex vivo and in vivo with markedly reduced unintended gene perturbation. Thus, the cell-penetrating PS-Cas9/gRNA can achieve efficient systemic delivery and precision in gene disruption.
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Molecule-inclusive closed cage compounds present a unique platform for molecular motion in an isolated environment. This study showcases the incorporation of a tadpole-like polar molecule (1-propyl-1H-imidazole, PIm) into a supramolecular cage formed by duad semicage p-tert-butylcalix[4]arene. The ferroelectric phase transition as well as the cage-confined motion of encapsulated PIm was studied in detail. The unusual quadrastable state of the PIm in the paraelectric phase allows for the modulation of dipolar polarization over a broad temperature/frequency range. This compound represents the first example of a clathrate molecular ferroelectric featuring a molecule-inclusive supramolecular cage, and it also contributes to the understanding of cage-confined molecular dynamics.
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BACKGROUND: Both venetoclax plus a hypomethylating agent (VEN/HMA) and cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CAG) are low-intensity regimens for older patients with acute myeloid leukemia (AML) that show good efficacy and safety. It is unknown how VEN/HMA compares with the CAG regimen for the treatment of newly diagnosed AML. METHODS: The outcomes of patients with newly diagnosed AML treated with VEN/HMA were compared with those of patients treated with a CAG-based regimen. Propensity score matching between these two cohorts at a 1:1 ratio was performed according to age at diagnosis, sex, Eastern Cooperative Oncology Group performance status, state of fitness, and European LeukemiaNet (ELN) 2022 risk stratification to minimize bias. RESULTS: A total of 84 of 96 patients in the VEN/HMA cohort were matched with 84 of 147 patients in the CAG cohort. VEN/HMA resulted in a better response than the CAG-based regimens, as indicated by a higher composite complete remission (CRc) rate (82.1% vs. 60.7%; p = .002) and minimal residual disease negativity rate (88.2% vs. 68.2%; p = .009). In patients with an ELN adverse risk, VEN/HMA was associated with a higher CRc rate compared to CAG (80.5% vs. 58.3%; p = .006). VEN/HMA was associated with longer event-free survival (EFS) (median EFS, not reached vs. 4.5 months; p = .0004), whereas overall survival (OS) was comparable between the two cohorts (median OS, not reached vs. 18 months; p = .078). CONCLUSIONS: The VEN/HMA regimen may result in a better response than CAG-based treatment in older patients with newly diagnosed AML.
Subject(s)
Aclarubicin , Antineoplastic Combined Chemotherapy Protocols , Bridged Bicyclo Compounds, Heterocyclic , Cytarabine , Granulocyte Colony-Stimulating Factor , Leukemia, Myeloid, Acute , Propensity Score , Sulfonamides , Humans , Female , Male , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Aged , Cytarabine/administration & dosage , Cytarabine/therapeutic use , Aclarubicin/administration & dosage , Aclarubicin/therapeutic use , Middle Aged , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/administration & dosage , Sulfonamides/administration & dosage , Sulfonamides/therapeutic use , Granulocyte Colony-Stimulating Factor/administration & dosage , Granulocyte Colony-Stimulating Factor/therapeutic use , Aged, 80 and overABSTRACT
BACKGROUND AND AIMS: The global rise of chronic hepatitis B (CHB) superimposed on hepatic steatosis (HS) warrants noninvasive, precise tools for assessing fibrosis progression. This study leveraged machine learning (ML) to develop diagnostic models for advanced fibrosis and cirrhosis in this patient population. METHODS: Treatment-naive CHB patients with concurrent HS who underwent liver biopsy in 10 medical centers were enrolled as a training cohort and an independent external validation cohort (NCT05766449). Six ML models were implemented to predict advanced fibrosis and cirrhosis. The final models, derived from SHAP (Shapley Additive exPlanations), were compared with Fibrosis-4 Index, nonalcoholic fatty liver disease Fibrosis Score, and aspartate aminotransferase-to-platelet ratio index using the area under receiver-operating characteristic curve (AUROC) and decision curve analysis (DCA). RESULTS: Of 1,198 eligible patients, the random forest model achieved AUROCs of 0.778 (95% confidence interval [CI], 0.749-0.807) for diagnosing advanced fibrosis (random forest advanced fibrosis model) and 0.777 (95% CI, 0.748-0.806) for diagnosing cirrhosis (random forest cirrhosis model) in the training cohort, and maintained high AUROCs in the validation cohort. In the training cohort, the random forest advanced fibrosis model obtained an AUROC of 0.825 (95% CI, 0.787-0.862) in patients with hepatitis B virus DNA ≥105 IU/mL, and the random forest cirrhosis model had an AUROC of 0.828 (95% CI, 0.774-0.883) in female patients. The 2 models outperformed Fibrosis-4 Index, nonalcoholic fatty liver disease Fibrosis Score, and aspartate aminotransferase-to-platelet ratio index in the training cohort, and also performed well in the validation cohort. CONCLUSIONS: The random forest models provide reliable, noninvasive tools for identifying advanced fibrosis and cirrhosis in CHB patients with concurrent HS, offering a significant advancement in the comanagement of the 2 diseases. CLINICALTRIALS: gov, Number: NCT05766449.
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BACKGROUND: Although, immune checkpoint inhibitors (ICIs) have been widely applied in the therapy of malignant tumors, the efficacy and safety of ICIs in patients with tumors and pre-existing CAD, especially chronic coronary syndromes (CCS) or their risk factors (CRF), is not well identified. METHODS: This was a nationwide multicenter observational study that enrolled participants who diagnosed with solid tumors and received ICIs therapy. The main efficacy indicators were progression-free survival (PFS) and overall survival (OS), followed by objective response rate (ORR) and disease control rate (DCR). Safety was assessed by describing treatment-related adverse events (TRAEs) during ICIs therapy evaluated by the Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). RESULTS: In the current research, we retrospectively analyzed the data of 551 patients diagnosed with solid tumors and received ICIs therapy, and these patients were divided into CCS/CRF group and non-CCS/CRF group. Patients with CCS/CRF had more favorable PFS and OS than patients without CCS/CRF (P < 0.001) and the pre-existing CCS/CRF was a protective factor for survival. The ORR (51.8% vs. 39.1%) and DCR (95.8% vs. 89.2%) were higher in CCS/CRF group than in non-CCS/CRF group (P = 0.003, P = 0.006). In this study, there was no significant difference in treatment-related adverse events (TRAEs), including immune-related adverse events (irAEs), between the two groups. CONCLUSIONS: We concluded that ICIs appear to have better efficacy in malignant solid tumor patients with pre-existing CCS/CRF and are not accompanied by more serious irAEs.
Subject(s)
Immune Checkpoint Inhibitors , Neoplasms , Humans , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Female , Male , Neoplasms/drug therapy , Neoplasms/complications , Neoplasms/immunology , Middle Aged , Retrospective Studies , Aged , Risk Factors , Adult , Aged, 80 and over , Cohort StudiesABSTRACT
The construction of defective sites is one of the effective strategies to create high-activity Metal-Organic frameworks (MOFs) catalysts. However, traditional synthesis methods usually suffer from cumbersome synthesis steps and disordered defect structures. Herein, a cluster-cluster co-nucleation (CCCN) strategy is presented that involves the in situ introduction of size-matched functional polyoxometalates (H6P2W18O62, {P2W18}) to intervene the nucleation process of cluster-based MOFs (UiO-66), achieving one-step inducement of exposed defective sites without redundant post-processing. POM-induced UiO-66 ({P2W18}-0.1@UiO-66) exhibits a classical reo topology for well-defined cluster defects. Moreover, the defective sites and the interaction between POM and skeletal cluster nodes are directly observed by Integrated Differential Phase Contrast in Scanning Transmission Electron Microscopy (iDPC-STEM). Owing to the molecular-level proximity between defective sites and POM in the same nano-reaction space, {P2W18}-0.1@UiO-66 exhibits efficient tandem catalysis in the preparation of γ-valerolactone (γ-GVL) from laevulinic acid (LA) by the combination of Lewis and Brønsted acids with 11 times higher performance than defective UiO-66 formed by conventional coordination modulation strategy. The CCCN strategy is applicable to different POM and has the potential to be extended to other cluster-based MOFs, which will pave a new way for the construction of functional MOFs with multi-centered synergistic catalysis.
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Chronic hepatitis B virus (HBV) infection is a significant global public health concern, and the clearance of HBV is closely linked to the activity of HBV-specific T cells, which is regulated by various co-suppressor molecules. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is among these co-suppressor molecules which induces T cell exhaustion by competitively inhibiting CD28 and dampening the function of HBV-specific T cells. CTLA-4 also plays a role in the regulation of T helper (Th) cell differentiation and influences cytokine release. In addition, CTLA-4 can impact glucose metabolism in hepatocellular carcinoma through its interaction with T regulatory (Treg) cells. This review aims to provide a comprehensive overview of the existing literature related to the role of CTLA-4 in HBV patients across different subsets of T cells. Additionally, we propose a discussion on the possible mechanisms through which CTLA-4 may contribute to HBV infection, as well as the development of HBV-induced cirrhosis and hepatocellular carcinoma.
Subject(s)
CTLA-4 Antigen , Carcinoma, Hepatocellular , Hepatitis B virus , Hepatitis B, Chronic , Humans , CTLA-4 Antigen/metabolism , Hepatitis B, Chronic/immunology , Hepatitis B, Chronic/complications , Hepatitis B virus/immunology , Hepatitis B virus/physiology , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/virology , Liver Neoplasms/immunology , Liver Neoplasms/virology , T-Lymphocytes, Regulatory/immunology , Liver Cirrhosis/immunology , Liver Cirrhosis/virologyABSTRACT
Leaf development is a multifaceted and dynamic process orchestrated by a myriad of genes to shape the proper size and morphology. The dynamic genetic network underlying leaf development remains largely unknown. Utilizing a synergistic genetic approach encompassing dynamic genome-wide association study (GWAS), time-ordered gene co-expression network (TO-GCN) analyses and gene manipulation, we explored the temporal genetic architecture and regulatory network governing leaf development in Populus. We identified 42 time-specific and 18 consecutive genes that displayed different patterns of expression at various time points. We then constructed eight TO-GCNs that covered the cell proliferation, transition, and cell expansion stages of leaf development. Integrating GWAS and TO-GCN, we postulated the functions of 27 causative genes for GWAS and identified PtoGRF9 as a key player in leaf development. Genetic manipulation via overexpression and suppression of PtoGRF9 revealed its primary influence on leaf development by modulating cell proliferation. Furthermore, we elucidated that PtoGRF9 governs leaf development by activating PtoHB21 during the cell proliferation stage and attenuating PtoLD during the transition stage. Our study provides insights into the dynamic genetic underpinnings of leaf development and understanding the regulatory mechanism of PtoGRF9 in this dynamic process.
Subject(s)
Genome-Wide Association Study , Populus , Plant Leaves/anatomy & histology , Gene Regulatory Networks , Gene Expression Regulation, PlantABSTRACT
Rare variants contribute significantly to the 'missing heritability' of quantitative traits. The genome-wide characteristics of rare variants and their roles in environmental adaptation of woody plants remain unexplored. Utilizing genome-wide rare variant association study (RVAS), expression quantitative trait loci (eQTL) mapping, genetic transformation, and molecular experiments, we explored the impact of rare variants on stomatal morphology and drought adaptation in Populus. Through comparative analysis of five world-wide Populus species, we observed the influence of mutational bias and adaptive selection on the distribution of rare variants. RVAS identified 75 candidate genes correlated with stomatal size (SS)/stomatal density (SD), and a rare haplotype in the promoter of serine/arginine-rich splicing factor PtoRSZ21 emerged as the foremost association signal governing SS. As a positive regulator of drought tolerance, PtoRSZ21 can recruit the core splicing factor PtoU1-70K to regulate alternative splicing (AS) of PtoATG2b (autophagy-related 2). The rare haplotype PtoRSZ21hap2 weakens binding affinity to PtoMYB61, consequently affecting PtoRSZ21 expression and SS, ultimately resulting in differential distribution of Populus accessions in arid and humid climates. This study enhances the understanding of regulatory mechanisms that underlie AS induced by rare variants and might provide targets for drought-tolerant varieties breeding in Populus.
Subject(s)
Adaptation, Physiological , Droughts , Gene Expression Regulation, Plant , Haplotypes , Plant Proteins , Plant Stomata , Populus , Populus/genetics , Populus/physiology , Populus/anatomy & histology , Plant Stomata/physiology , Plant Stomata/genetics , Haplotypes/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Adaptation, Physiological/genetics , Quantitative Trait Loci/genetics , Serine-Arginine Splicing Factors/genetics , Serine-Arginine Splicing Factors/metabolism , Genome-Wide Association Study , Alternative Splicing/genetics , Genetic Variation , Drought ResistanceABSTRACT
Cytokines may related to intrauterine Hepatitis B virus (HBV) transmission. 205 HBsAg(+) pregnant cases and 74 HBsAg(-) women were included. Neonatal blood samples were taken within 24 h of delivery and before HBV vaccinations. Serological HBV biomarkers and cytokines were detected. 21.9 % of the newborns from HBsAg(+) women were intrauterinally transmitted, including 7.3 % with dominant transmission (DBT) and 14.6 % occult transmission (OBT). HBV DNA load (odd ratio [OR], 1.44; 95 % confidence interval [CI], 1.05-1.98), interferon-γ (IFN-γ) (OR, 1.01; 95 %CI, 1.00-1.02) and toll-like receptor 9 (TLR9) (OR, 1.27; 95 %CI, 1.06-1.52) positively correlated with DBT. Only IFN-γ (OR, 1.01; 95 %CI, 1.00-1.01) positively associated with OBT. According to the generated restricted cubic spline, TLR9 was positively correlates with rise of DBT in a log-shape. It may be possible to develop a nomogram which intercalates these factors to predict intrauterine HBV transmissions. Further research should consider immune processes involved in chorioamnionitis.
Subject(s)
Cytokines , Hepatitis B virus , Hepatitis B , Infectious Disease Transmission, Vertical , Toll-Like Receptor 9 , Humans , Female , Pregnancy , Cross-Sectional Studies , Hepatitis B/transmission , Hepatitis B/blood , Hepatitis B/immunology , China/epidemiology , Adult , Cytokines/blood , Hepatitis B virus/immunology , Infant, Newborn , Hepatitis B Surface Antigens/blood , Hepatitis B Surface Antigens/immunology , DNA, Viral/blood , Interferon-gamma/blood , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/virologyABSTRACT
The defense response of peach (Prunus persica) to insect attack involves changes in gene expression and metabolites. Piercing/sucking insects such as green peach aphid cause direct damage by obtaining phloem nutrients and indirect damage by spreading plant viruses. To investigate the response of peach trees to aphids, the leaf transcriptome and metabolome of two genotypes with different sensitivities to green peach aphid (GPA, Myzus persicae) were studied. The transcriptome analysis of infected peach leaves showed two different response patterns. The gene expression of aphid-susceptible peach plants infected by aphids was more similar to that of the control plants, while the gene expression of aphid-resistant peach plants infected by aphids showed strongly induced changes in gene expression compared with the response in the control plants. Furthermore, gene transcripts in defense-related pathways, including plant-pathogen interaction, MAPK signaling, and several metabolic pathways, were more strongly enriched upon aphid infestation. Untargeted secondary metabolite profiling confirmed that aphid treatment induced larger changes in aphid-resistant peaches than in aphid-susceptible peaches. Consistent with transcriptomic alterations, nine triterpenoids showed extremely significant GPA-induced accumulation in aphid-resistant peaches, whereas triterpenoid abundance remained predominantly unchanged or undetected in aphid- susceptible peaches. Furthermore, some types of transcription factors (including WRKYs, ERFs, NACs, etc.) were more strongly induced upon GPA infestation in aphid-resistant peaches but not in aphid-susceptible peaches. Aphid feeding-dependent transcriptome and metabolite profiles provide the foundation for understanding the molecular mechanisms underlying the response of peach to aphid infestation. These results suggested that accumulation of specialized triterpenoids and the corresponding pathway transcripts may play a key role in peach GPA resistance.
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The use of finite entanglement scaling with matrix product states (MPS) has become a crucial tool for studying one-dimensional critical lattice theories, especially those with emergent conformal symmetry. We argue that finite entanglement introduces a relevant deformation in the critical theory. As a result, the bipartite entanglement Hamiltonian defined from the MPS can be understood as a boundary conformal field theory with a physical and an entanglement boundary. We are able to exploit the symmetry properties of the MPS to engineer the physical conformal boundary condition. The entanglement boundary, on the other hand, is related to the concrete lattice model and remains invariant under this relevant perturbation. Using critical lattice models described by the Ising, Potts, and free compact boson conformal field theories, we illustrate the influence of the symmetry and the relevant deformation on the conformal boundaries in the entanglement spectrum.
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The disorder operator is often designed to reveal the conformal field theory (CFT) information in quantum many-body systems. By using large-scale quantum Monte Carlo simulation, we study the scaling behavior of disorder operators on the boundary in the two-dimensional Heisenberg model on the square-octagon lattice with gapless topological edge state. In the Affleck-Kennedy-Lieb-Tasaki phase, the disorder operator is shown to hold the perimeter scaling with a logarithmic term associated with the Luttinger liquid parameter K. This effective Luttinger liquid parameter K reflects the low-energy physics and CFT for (1+1)D boundary. At bulk critical point, the effective K is suppressed but it keeps finite value, indicating the coupling between the gapless edge state and bulk fluctuation. The logarithmic term numerically captures this coupling picture, which reveals the (1+1)D SU(2)_{1} CFT and (2+1)D O(3) CFT at boundary criticality. Our Letter paves a new way to study the exotic boundary state and boundary criticality.
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We present the results for the complete next-to-leading order electroweak corrections to ppâHH at the Large Hadron Collider, focusing on the dominant gluon-gluon fusion process. While the corrections at the total cross-section level are approximately -4%, those near the energy of HH production threshold exceed +15%, and corrections at the high-energy region are around -10%, leading to a shape distortion for the differential distributions. Our findings substantially diminish the theoretical uncertainties associated with this pivotal process, providing valuable input for understanding the shape of the Higgs boson potential upon comparison with experimental measurements.
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Proton exchange membrane fuel cells (PEMFCs) and alkaline membrane fuel cells (AEMFCs) have received great attention as energy devices of the next generation. Accelerating oxygen reduction reaction (ORR) kinetics is the key to improve PEMFC and AEMFC performance. Platinum-based catalysts are the most widely used catalysts for the ORR, but their high price and low abundance limit the commercialization of fuel cells. Non-noble metal-nitrogen-carbon (M-N-C) is considered to be the most likely material class to replace Pt-based catalysts, among which Fe-N-C and Co-N-C have been widely studied due to their excellent intrinsic ORR performance and have made great progress in the past decades. With the improvement of synthesis technology and a deeper understanding of the ORR mechanism, some reported Fe-N-C and Co-N-C catalysts have shown excellent ORR activity close to that of commercial Pt/C catalysts. Inspired by the progress, regulation strategies for Fe-N-C and Co-N-C catalysts are summarized in this Review from 5â perspectives: (1)â coordinated atoms, (2)â environmental heteroatoms and defects, (3)â dual-metal active sites, (4)â metal-based particle promoters, and (5)â curved carbon layers. We also make suggestions on some challenges facing Fe-N-C and Co-N-C research.
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BACKGROUND: Although papillary thyroid cancer (PTC) patients are known to have an excellent prognosis, up to 30% of patients experience disease recurrence after initial treatment. Accurately predicting disease prognosis remains a challenge given that the predictive value of several predictors remains controversial. Thus, we investigated whether machine learning (ML) approaches based on comprehensive predictors can predict the risk of structural recurrence for PTC patients. METHODS: A total of 2244 patients treated with thyroid surgery and radioiodine were included. Twenty-nine perioperative variables consisting of four dimensions (demographic characteristics and comorbidities, tumor-related variables, lymph node (LN)-related variables, and metabolic and inflammatory markers) were analyzed. We applied five ML algorithms-logistic regression (LR), support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), and neural network (NN)-to develop the models. The area under the receiver operating characteristic (AUC-ROC) curve, calibration curve, and variable importance were used to evaluate the models' performance. RESULTS: During a median follow-up of 45.5 months, 179 patients (8.0%) experienced structural recurrence. The non-stimulated thyroglobulin, LN dissection, number of LNs dissected, lymph node metastasis ratio, N stage, comorbidity of hypertension, comorbidity of diabetes, body mass index, and low-density lipoprotein were used to develop the models. All models showed a greater AUC (AUC = 0.738 to 0.767) than did the ATA risk stratification (AUC = 0.620, DeLong test: P < 0.01). The SVM, XGBoost, and RF model showed greater sensitivity (0.568, 0.595, 0.676), specificity (0.903, 0.857, 0.784), accuracy (0.875, 0.835, 0.775), positive predictive value (PPV) (0.344, 0.272, 0.219), negative predictive value (NPV) (0.959, 0.959, 0.964), and F1 score (0.429, 0.373, 0.331) than did the ATA risk stratification (sensitivity = 0.432, specificity = 0.770, accuracy = 0.742, PPV = 0.144, NPV = 0.938, F1 score = 0.216). The RF model had generally consistent calibration compared with the other models. The Tg and the LNR were the top 2 important variables in all the models, the N stage was the top 5 important variables in all the models. CONCLUSIONS: The RF model achieved the expected prediction performance with generally good discrimination, calibration and interpretability in this study. This study sheds light on the potential of ML approaches for improving the accuracy of risk stratification for PTC patients. TRIAL REGISTRATION: Retrospectively registered at www.chictr.org.cn (trial registration number: ChiCTR2300075574, date of registration: 2023-09-08).
Subject(s)
Iodine Radioisotopes , Thyroid Neoplasms , Humans , Thyroid Cancer, Papillary , Neoplasm Recurrence, Local/epidemiology , Machine Learning , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/surgery , Retrospective StudiesABSTRACT
BACKGROUND: The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. METHODS: Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA < 7 log10 IU/mL), moderate (7 log10 IU/mL ≤ HBV DNA < 8 log10 IU/mL), and high (HBV DNA ≥ 8 log10 IU/mL). APRI, FIB-4, transient elastography, or liver biopsy were used to assess liver fibrosis. RESULTS: The median age of patients was 33.0 years and 57.9% patients were male. 18.8%, 52.1%, and 29.1% of patients had low, moderate, and high HBV DNA levels, respectively. The APRI (0.33 vs. 0.26 vs. 0.26, P < 0.001), FIB-4 (1.03 vs. 0.71 vs. 0.68, P < 0.001), and LSM values (7.6 kPa vs. 5.6 kPa vs. 5.5 kPa, P = 0.086) were higher in low HBV DNA group than other two groups. Low HBV DNA group had higher proportions of significant fibrosis (24.8% vs. 9.9% vs. 3.3%, P < 0.001) and cirrhosis (7.7% vs. 2.5% vs. 1.1%, P = 0.004) than moderate and high HBV DNA groups. Moderate (OR 3.095, P = 0.023) and low (OR 4.968, P = 0.003) HBV DNA were independent risk factors of significant fibrosis. CONCLUSION: Lower HBV DNA level was associated with more severe liver fibrosis in HBeAg-positive CHB patients with ALT.
Subject(s)
Alanine Transaminase , DNA, Viral , Hepatitis B e Antigens , Hepatitis B virus , Hepatitis B, Chronic , Liver Cirrhosis , Humans , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/virology , Hepatitis B, Chronic/pathology , Hepatitis B, Chronic/blood , Male , Female , Adult , Liver Cirrhosis/virology , Liver Cirrhosis/blood , Liver Cirrhosis/pathology , DNA, Viral/blood , Alanine Transaminase/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Middle Aged , Viral Load , Young Adult , Liver/pathology , Liver/virology , BiopsyABSTRACT
RESEARCH QUESTION: What is the value of 2D ultrasonography in the diagnosis and assessment of intrauterine adhesions (IUA)? DESIGN: This was a prospective study conducted at a hysteroscopy centre. RESULTS: Of a total of 600 subjects recruited, 41 dropped out and 559 were finally enrolled and analysed. The observed 2D ultrasonography features, in decreasing order of frequency, were 'irregular endometrium' (37.9%), 'broken endometrial echo' (23.4%), 'thin endometrium' (13.7%), 'loss of endometrial echo' (13.1%,), 'hyperechoic focus' (12.5%) and 'fluid in the cavity' (8.8%). The sensitivity of individual ultrasound features ranged from 8.8% to 37.9%, whereas the specificity of individual ultrasound features ranged from 78.9% to 100%. When all the six ultrasound features were considered together, the sensitivity and specificity were 71.7% and 66.2% respectively. The sensitivity, specificity and accuracy of ultrasound diagnosis in the mid-proliferative phase, peri-ovulatory phase and mid-luteal phase did not appear to be significantly different statistically, although the results in the mid-proliferative phase appeared to be consistently higher than those in the mid-luteal phase. In women confirmed to have IUA, the likelihood of the adhesions being severe in nature in the presence of zero, one, two or three or more ultrasound features was 8.7%, 23.0%, 40.2% and 80.5%, respectively (P < 0.001). CONCLUSIONS: The findings in this study support the notions that ultrasonography examination in women suspected to have IUA cannot replace hysteroscopy in the diagnosis of the condition. However, it does provide useful clinical information regarding severity and could help in the planning of hysteroscopy to optimize management.
Subject(s)
Sensitivity and Specificity , Ultrasonography , Uterine Diseases , Humans , Female , Tissue Adhesions/diagnostic imaging , Prospective Studies , Ultrasonography/methods , Adult , Uterine Diseases/diagnostic imaging , Middle Aged , Hysteroscopy/methods , Endometrium/diagnostic imaging , Endometrium/pathologyABSTRACT
OBJECTIVE: This study aimed to investigate the correlation between positive psychological capital, post-traumatic growth, social support, and quality of life (QOL) in patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted at the First Affiliated Hospital of Xinjiang Medical University from October 2022 to May 2023. A sample of 330 hospitalized SLE patients was selected for this study. The collected data included demographic information, the SLE disease activity index, the Positive Mental Capital Questionnaire, the Chinese version of the Post-Traumatic Growth Scale, the Social Support Rating Scale, and the Chinese version of the Lupus Quality of Life Scale. RESULTS: The QOL score among the 330 SLE patients was measured as M(P25, P75) of 105 (83.00,124.00). Positive psychological capital, post-traumatic growth, and social support demonstrated significant positive correlations with the QOL in SLE patients (p < 0.05). Multiple linear regression analysis revealed that literacy, disease level, disease duration, occupation, marital status, psychological capital, social support, and post-traumatic growth were influential factors associated with the QOL in SLE patients. CONCLUSION: Medical professionals should be attentive to the psychological well-being of SLE patients and should consider implementing early psychological interventions. These interventions are crucial for enhancing the QOL for individuals diagnosed with SLE.