Renal anemia: from relative insufficiency of EPO to imbalance of erythropoiesis and eryptosis.

Chronic kidney disease has emerged as a major health issue both in China and worldwide. Renal anemia frequently occurs in patients with chronic kidney disease, and its severity and incidence rate increase as the disease progresses. Over the last 30 years, the administration of exogenous EPO and EPO stimulants has been employed to alleviate renal anemia, suggesting that a relative deficiency in EPO may be a primary cause. However, this approach has overshadowed other contributing factors, particularly eryptosis, which results from the reduced lifespan of red blood cells. Numerous studies reveal that there are nephrogenic and extrarenal EPO secretion indicating that an absolute deficiency of EPO is not always present in patients. Therefore, this paper speculates that renal anemia may arise when EPO-driven erythropoiesis fails to adequately compensate for aggravating eryptosis. Other factors including iron metabolism disorder, uremic toxin accumulation, inflammatory state, oxidative stress, and secondary hyperparathyroidism affect EPO reactivity bone marrow hematopoiesis and eryptosis, leading to an imbalance between red blood cell production and destruction, and cause anemia ultimately. More further studies on the pathogenesis and treatment of renal anemia would be expected to provide evidence to support our opinion.

Multi-Domain Based Dynamic Graph Representation Learning for EEG Emotion Recognition.

Graph neural networks (GNNs) have demonstrated efficient processing of graph-structured data, making them a promising method for electroencephalogram (EEG) emotion recognition. However, due to dynamic functional connectivity and nonlinear relationships between brain regions, representing EEG as graph data remains a great challenge. To solve this problem, we proposed a multi-domain based graph representation learning (MD 2 GRL) framework to model EEG signals as graph data. Specifically, MD 2 GRL leverages gated recurrent units (GRU) and power spectral density (PSD) to construct node features of two subgraphs. Subsequently, the self-attention mechanism is adopted to learn the similarity matrix between nodes and fuse it with the intrinsic spatial matrix of EEG to compute the corresponding adjacency matrix. In addition, we introduced a learnable soft thresholding operator to sparsify the adjacency matrix to reduce noise in the graph structure. In the downstream task, we designed a dual-branch GNN and incorporated spatial asymmetry for graph coarsening. We conducted experiments using the publicly available datasets SEED and DEAP, separately for subject-dependent and subject-independent, to evaluate the performance of our model in emotion classification. Experimental results demonstrated that our method achieved state-of-the-art (SOTA) classification performance in both subject-dependent and subject-independent experiments. Furthermore, the visualization analysis of the learned graph structure reveals EEG channel connections that are significantly related to emotion and suppress irrelevant noise. These findings are consistent with established neuroscience research and demonstrate the potential of our approach in comprehending the neural underpinnings of emotion.

Sex differences orchestrated by androgens at single-cell resolution.

Sex differences in mammalian complex traits are prevalent and are intimately associated with androgens1-7. However, a molecular and cellular profile of sex differences and their modulation by androgens is still lacking. Here we constructed a high-dimensional single-cell transcriptomic atlas comprising over 2.3 million cells from 17 tissues in Mus musculus and explored the effects of sex and androgens on the molecular programs and cellular populations. In particular, we found that sex-biased immune gene expression and immune cell populations, such as group 2 innate lymphoid cells, were modulated by androgens. Integration with the UK Biobank dataset revealed potential cellular targets and risk gene enrichment in antigen presentation for sex-biased diseases. This study lays the groundwork for understanding the sex differences orchestrated by androgens and provides important evidence for targeting the androgen pathway as a broad therapeutic strategy for sex-biased diseases.

Prediction of lymph node metastasis in advanced gastric adenocarcinoma based on dual-energy CT radiomics: focus on the features of lymph nodes with a short axis diameter ≥6 mm.

Objective: To explore the value of the features of lymph nodes (LNs) with a short-axis diameter ≥6 mm in predicting lymph node metastasis (LNM) in advanced gastric adenocarcinoma (GAC) based on dual-energy CT (DECT) radiomics. Materials and methods: Data of patients with GAC who underwent radical gastrectomy and LN dissection were retrospectively analyzed. To ensure the correspondence between imaging and pathology, metastatic LNs were only selected from patients with pN3, nonmetastatic LNs were selected from patients with pN0, and the short-axis diameters of the enrolled LNs were all ≥6 mm. The traditional features of LNs were recorded, including short-axis diameter, long-axis diameter, long-to-short-axis ratio, position, shape, density, edge, and the degree of enhancement; univariate and multivariate logistic regression analyses were used to establish a clinical model. Radiomics features at the maximum level of LNs were extracted in venous phase equivalent 120 kV linear fusion images and iodine maps. Intraclass correlation coefficients and the Boruta algorithm were used to screen significant features, and random forest was used to build a radiomics model. To construct a combined model, we included the traditional features with statistical significance in univariate analysis and radiomics scores (Rad-score) in multivariate logistic regression analysis. Receiver operating curve (ROC) curves and the DeLong test were used to evaluate and compare the diagnostic performance of the models. Decision curve analysis (DCA) was used to evaluate the clinical benefits of the models. Results: This study included 114 metastatic LNs from 36 pN3 cases and 65 nonmetastatic LNs from 28 pN0 cases. The samples were divided into a training set (n=125) and a validation set (n=54) at a ratio of 7:3. Long-axis diameter and LN shape were independent predictors of LNM and were used to establish the clinical model; 27 screened radiomics features were used to build the radiomics model. LN shape and Rad-score were independent predictors of LNM and were used to construct the combined model. Both the radiomics model (area under the curve [AUC] of 0.986 and 0.984) and the combined model (AUC of 0.970 and 0.977) outperformed the clinical model (AUC of 0.772 and 0.820) in predicting LNM in both the training and validation sets. DCA showed superior clinical benefits from radiomics and combined models. Conclusion: The models based on DECT LN radiomics features or combined traditional features have high diagnostic performance in determining the nature of each LN with a short-axis diameter of ≥6 mm in advanced GAC.

Protective Mechanisms of Juncus effusus and Carbonized Juncus effusus against D-Galactosamine-Induced Acute Liver Injury in Mice.

This study investigated the hepatoprotective effects of Juncus effusus (J. effusus) and Carbonized J. effusus against liver injury caused by D-galactosamine (D-GalN) in mice. J. effusus and Carbonized J. effusus were administered by gavage once daily starting seven days before the D-GalN treatment. The results of the study indicated that J. effusus and Carbonized J. effusus suppressed the D-GalN-induced generation of serum alanine transaminase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) was observed. The values of superoxide dismutase (SOD) exhibited an increase. In addition, J. effusus and Carbonized J. effusus promoted the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NADPH quinone oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1) as well as the mRNA expression of Nrf2, HO-1, NQO-1 and Glutamate cysteine ligase catalytic subunit (GCLC). The compressed Carbonized J. effusus demonstrated the optimum impact. These results suggest that J. effusus and Carbonized J. effusus protect against D-GalN-induced acute liver injury through the activation of the Nrf2 pathway.

Brazilin-7-acetate, a novel potential drug of Parkinson's disease, hinders the formation of α-synuclein fibril, mitigates cytotoxicity, and decreases oxidative stress.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the accumulation of α-synuclein (α-Syn) aggregates. However, there are currently no effective therapies for PD. Brazilin, an inhibitor of α-Syn aggregation, is unstable and toxic. Therefore, we have developed and synthesized derivatives of brazilin. One of these derivatives, called brazilin-7-acetate (B-7-A), has shown reduced toxicity and a stronger effect on inhibiting α-Syn aggregation. It showed that B-7-A prevented the formation of α-Syn fibers and disrupted existing fibers in a dosage-dependent manner. Additionally, B-7-A significantly reduced the cytotoxicity of α-Syn aggregates and alleviated oxidative stress in PC12 cells. The beneficial effects of B-7-A were also confirmed using the Caenorhabditis elegans model. These effects included preventing the accumulation of α-Syn clumps, improving behavior disorder, increasing lifespan, reducing oxidative stress, and protecting against lipid oxidation and loss. Finally, B-7-A showed good ADMET properties in silico. Based on these findings, B-7-A exhibits potential as a prospective treatment for PD.

MBL-1 and EEL-1 affect the splicing and protein levels of MEC-3 to control dendrite complexity.

Transcription factors (TFs) play critical roles in specifying many aspects of neuronal cell fate including dendritic morphology. How TFs are accurately regulated during neuronal morphogenesis is not fully understood. Here, we show that LIM homeodomain protein MEC-3, the key TF for C. elegans PVD dendrite morphogenesis, is regulated by both alternative splicing and an E3 ubiquitin ligase. The mec-3 gene generates several transcripts by alternative splicing. We find that mbl-1, the orthologue of the muscular dystrophy disease gene muscleblind-like (MBNL), is required for PVD dendrite arbor formation. Our data suggest mbl-1 regulates the alternative splicing of mec-3 to produce its long isoform. Deleting the long isoform of mec-3(deExon2) causes reduction of dendrite complexity. Through a genetic modifier screen, we find that mutation in the E3 ubiquitin ligase EEL-1 suppresses mbl-1 phenotype. eel-1 mutants also suppress mec-3(deExon2) mutant but not the mec-3 null phenotype. Loss of EEL-1 alone leads to excessive dendrite branches. Together, these results indicate that MEC-3 is fine-tuned by alternative splicing and the ubiquitin system to produce the optimal level of dendrite branches.

Clinical and radiological characteristics of pediatric COVID-19 before and after the Omicron outbreak: a multi-center study.

Introduction: The emergence of the Omicron variant has seen changes in the clinical and radiological presentations of COVID-19 in pediatric patients. We sought to compare these features between patients infected in the early phase of the pandemic and those during the Omicron outbreak. Methods: A retrospective study was conducted on 68 pediatric COVID-19 patients, of which 31 were infected with the original SARS-CoV-2 strain (original group) and 37 with the Omicron variant (Omicron group). Clinical symptoms and chest CT scans were examined to assess clinical characteristics, and the extent and severity of lung involvement. Results: Pediatric COVID-19 patients predominantly had normal or mild chest CT findings. The Omicron group demonstrated a significantly reduced CT severity score than the original group. Ground-glass opacities were the prevalent radiological findings in both sets. The Omicron group presented with fewer symptoms, had milder clinical manifestations, and recovered faster than the original group. Discussion: The clinical and radiological characteristics of pediatric COVID-19 patients have evolved with the advent of the Omicron variant. For children displaying severe symptoms warranting CT examinations, it is crucial to weigh the implications of ionizing radiation and employ customized scanning protocols and protective measures. This research offers insights into the shifting disease spectrum, aiding in the effective diagnosis and treatment of pediatric COVID-19 patients.

A comparison of the use of contrast media with different iodine concentrations for enhanced computed tomography.

Objective: In this study, we compared the enhancement of blood vessels and liver parenchyma on enhanced computed tomography (CT) of the upper abdomen with two concentrations of contrast media (400 and 300 mg I/mL) based on similar iodine delivery rate (IDR) of 0.88 and 0.9 g I/s and iodine load of 450 mg I/kg. Methods: We randomly assigned 160 patients into two groups: iomeprol 400 mg I/mL (A group) and iohexol 300 mg I/mL (B group). The CT attenuation values of the main anatomical structures in the two groups with different scanning phases were measured and the image quality of the two groups was analyzed and compared. The peak pressure and local discomfort (including fever and pain) during contrast medium injection were recorded. Results: The mean attenuation value of the abdominal aorta was 313.6 ± 29.6 in the A group and 322.4 ± 30.1 in the B group during the late arterial phase (p = 0.8). Meanwhile, the mean enhancement values of the portal vein were 176.2 ± 19.3 and 165.9 ± 24.5 in the A and B groups, respectively, during the portal venous phase (p = 0.6). The mean CT values of liver parenchyma were 117.1 ± 15.3 and 108.8 ± 18.7 in the A and B groups, respectively, during the portal venous phase (p = 0.9). There was no statistical difference in image quality, peak injection pressure (psi), and local discomfort between the two groups (p > 0.05). Conclusion: When a similar IDR and the same iodine load are used, CT images with different concentrations of contrast media have the same subjective and objective quality, and can meet the diagnostic needs.

A comprehensive investigation regarding the clinical significance of ITGB4 in oral squamous cell carcinoma combining immunohistochemistry, RNA-seq, and microarray data.

OBJECTIVE: Integrin subunit beta 4 (ITGB4), a receptor for laminins, was an oncoprotein in several malignancies. However, its clinical role in oral squamous cell carcinoma (OSCC) remains unclear. MATERIALS AND METHODS: Firstly, 99 OSCC and 13 normal oral epithelium samples were employed for immunohistochemistry (IHC) for detecting the expression level of ITGB4 protein in OSCC. Subsequently, 971 OSCC and 281 non-cancerous specimens from RNA-seq and 18 microarrays were applied for investigating the expression of ITGB4 mRNA. Furthermore, to explore the potential mechanism of ITGB4 in OSCC, the co-expressed genes of ITGB4 were initially screened using all available datasets, and were further utilized for the gene enrichment analysis. RESULTS: First, IHC showed a distinctively higher expression level of the ITGB4 protein in the OSCC group than that in the normal controls. Second, expression profile from RNA-seq and microarrays reflected that ITGB4 mRNA was dramatically overexpressed in OSCC tissues compared with non-tumor tissues. Third, standardized mean difference (SMD) with the area under the summary receiver operating characteristic (sROC) curve combining all incorporated data revealed that ITGB4 was consistently significantly upregulated in OSCC tissues, with the SMD value being 1.31 and the area under the sROC curve being 0.82. Lastly, 184 upregulated and 179 downregulated co-expressed genes of ITGB4 were utilized for enrichment analysis, which demonstrated that ITGB4 might influence the pathogenesis of OSCC through cell cycle, ECM-receptor interaction and focal adhesion pathways. CONCLUSIONS: ITGB4 might play a pivotal role in the tumorigenesis and progression of OSCC, making it a promising biomarker of OSCC.

Boosting the Phosphorescence Efficiency in Doped Organic Crystals: Critical Role of Hydrogen Bonding.

Host-guest doping systems with phthalimides (BI) and N-methylphthalimide (NMeBI) as the host and 1,8-naphthalimide (NI) and 4-bromo-1,8-naphthalimide (4BrNI) as the guest have been developed. The 0.2% NI/BI (molar ratio) with a strong C=O···H-N hydrogen bond exhibited a phosphorescence quantum efficiency (29.2%) higher than that of NI/NMeBI with a weak C=O···H-C hydrogen bond (10.1%). A similar trend was observed in the 4BrNI guest system. A remarkable phosphorescent efficiency of 42.1% was achieved in a 0.5% 4BrNI/BI composite, which represents the highest value in NI-based phosphors. This research indicates stronger hydrogen bonding may have a greater contribution in boosting the phosphorescence efficiency.

TDO2+ myofibroblasts mediate immune suppression in malignant transformation of squamous cell carcinoma.

Characterization of the dynamic change in the immunological landscape during malignant transformation from precancerous lesions to cancerous lesions in squamous cell carcinoma (SCC) is critical for the application of immunotherapy. Here, we performed single-cell RNA-Seq (scRNA-Seq) of 131,702 cells from 13 cancerous tissues of oral squamous cell carcinoma (OSCC), 3 samples of precancerous oral leukoplakia, and 8 adjacent normal samples. We found that tumor-infiltrating CD4+ and CD8+ T cells were functionally inhibited by immunosuppressive ligands expressed on various types of myeloid cells or neutrophils in the process of oral carcinogenesis. Notably, we identified a subset of myofibroblasts that exclusively expressed tryptophan 2,3-dioxygenase (TDO2). These TDO2+ myofibroblasts were located distally from tumor nests, and both CD4+ and CD8+ T cells were enriched around them. Functional experiments revealed that TDO2+ myofibroblasts were more likely to possess the ability for chemotaxis toward T cells but induced the transformation of CD4+ T cells into Tregs and caused CD8+ T cell dysfunction. We further showed that use of the TDO2 inhibitor LM10 attenuated the inhibitory states of T cells, restored the T cell antitumor response, and prevented the progression of OSCC malignant transformation in murine models. Our study reveals a multistep transcriptomic landscape of OSCC and demonstrates that TDO2+ myofibroblasts are potential targets for immunotherapy.

Shear Wave Elastography in the Diagnosis of Peripheral Neuropathy in Patients With Chronic Kidney Disease Stage 5.

Objective: To observe the feasibility of shear wave elastography (SWE) in the diagnosis of peripheral neuropathy in patients undergoing hemodialysis [chronic kidney disease stage 5 dialysis (CKD5D)]. Methods: Forty patients with CKD5D were divided into a uremic peripheral neuropathy (UPN) group (n = 25) and a non-UPN group (n = 15) according to the results of a neuro-electrophysiological examination. Sixteen healthy control subjects were also enrolled in this study. Two-dimensional ultrasound examination was conducted, and SWE was then performed to measure Young's modulus of the tibial nerve. The left and right diameters (D1), anterior and posterior diameters (D2), perimeter (C), cross-sectional area (CSA), and Young's modulus (E) were measured three times at the same non-entrapment site. The average values were recorded and calculated. The following evaluation indices were also analyzed: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Results: D1, D2, C, and CSA were not significantly different among the three groups (P > 0.05). However, the difference in the E value among the three groups was statistically significant (P < 0.05). The AUC was 0.889 based on the E value. Using a tibial nerve E value of 48.35 kPa as the cutoff value, the sensitivity, specificity, PPV, and NPV were 86.0%, 84.0%, 81.1%, and 88.1%, respectively. Conclusions: SWE is useful for the diagnosis of peripheral neuropathy in patients with CKD5D. Young's modulus of 48.35 kPa for the tibial nerve is the optimal cutoff value and has the best diagnostic efficiency for peripheral neuropathy in CKD5D patients.

Fire Behavior and Failure Model of Multilayered Wood Flour/HDPE/Polycarbonate Composites with a Sandwich Structure.

The flame retardancy of wood-polymer composites significantly affects their potential applications. Thus, multilayered wood flour/high-density polyethylene (HDPE)/polycarbonate (PC) composites were prepared via thermocompression to improve the fire retardancy of wood-polymer composites in this paper. Thermal degradation behavior, flame retardancy, and flexural strengths of the resulting composites were investigated using a thermogravimetric analysis, cone calorimetry, and mechanical testing machine, respectively. Results revealed that the boric acid treatment reduced the heat release rate and total heat release of the wood flour/HDPE composites and increased their mass of residues. However, boric acid reduced the flexural strength of the resulting composites. The combustion test indicated that PC cap layers suppressed the combustion of the resulting composites via the formation of carbon layers. Adding PC layers reduced heat release and increased the flexural strength of the resulting composites. Finally, the failure mode of the multilayered wood flour/HDPE/PC composites in the three-point flexural test was simulated by finite element analysis.

Comparison of the Application Value for Diagnosis of Chronic Kidney Disease between Color Doppler Flow Quantification Technique and Computed Tomography.

Objective: The aim of this study is to compare the application value for diagnosis of chronic kidney disease (CKD) between the color Doppler flow quantification (CDFQ) technique and computed tomography (CT). Methods: The clinical data of 88 hospitalized patients treated in the Renal Medicine of our hospital and diagnosed with CKD after pathological examination from June 2020 to June 2021 were selected for the retrospective analysis, and 32 individuals with normal physical examination results in the same period were selected as the control group. All study subjects received CDFQ and 640-slice volume CT examination, and by plotting the ROC curves, the clinical value of different diagnostic modalities was analyzed. Results: The 3D renal volumes between the stage 1 group and control group were significantly different (P < 0.05); the 3D renal volumes between the stage 2 group and control group and between the stage 2 group and stage 1 group were significantly different (P < 0.05); in the comparison between the stage 3 group versus control group/stage 2 group, the RI values, 3D renal volumes, and cortical thicknesses were significantly different (P < 0.05); in the comparison between the stage 4 group versus control group/stage 1 group, the RI values, 3D renal volumes, and cortical thicknesses were significantly different, and between the stage 4 group and stage 2 group, the RI values and cortical thicknesses were significantly different (P < 0.05); in the comparison between the stage 5 group versus control group/stage 1 group/stage 2 group/stage 3 group, the RI values, 3D renal volumes, and cortical thicknesses were significantly different, and between the stage 5 group and stage 4 group, the RI values and 3D renal volumes were significantly different (P < 0.05); among various groups, the measurement indicators of 640-slice volume CT scan were significantly different (P < 0.05); and in terms of disease classification, the AUC value, positive predictive value, negative predictive value, sensitivity, and specificity of 640-slice volume CT were higher than those of CDFQ diagnosis. Conclusion: 640-slice volume CT has a higher efficacy in diagnosing CKD and can provide a reliable basis for the selection of treatment schemes for CKD patients.

Emotional Intelligence and Knowledge Hiding Behaviors: The Mediating Role of Job Stress.

Emotion is fundamental to human experiences influencing our daily activities including cognition, communication, learning, and decision-making, but the effect of emotion on knowledge management in firms receives a little attention, especially in the field of knowledge hiding behaviors. Drawing on the cognitive appraisal theory of stress and coping as a unique theoretical lens to explicate how knowledge hiding behaviors happen, this study investigates the mediating effect of job stress in the relationship between emotional intelligence (EI) and knowledge hiding behaviors. We conducted a field study with 193 full-time employees in smart healthcare firms to test our hypotheses. Results supported the mediating effects of job stress in accounting for the relationship between EI and knowledge hiding behaviors. Our study is among the first to examine how emotional intelligence predicts knowledge hiding behaviors. This study contributes to the literature on knowledge management and emotional intelligence.

Can lymphovascular invasion be predicted by contrast-enhanced CT imaging features in patients with esophageal squamous cell carcinoma? A preliminary retrospective study.

BACKGROUND: To investigate the value of contrast-enhanced CT (CECT)-derived imaging features in predicting lymphovascular invasion (LVI) status in esophageal squamous cell carcinoma (ESCC) patients. METHODS: One hundred and ninety-seven patients with postoperative pathologically confirmed esophageal squamous cell carcinoma treated in our hospital between January 2017 and January 2019 were enrolled in our study, including fifty-nine patients with LVI and one hundred and thirty-eight patients without LVI. The CECT-derived imaging features of all patients were analyzed. The CECT-derived imaging features were divided into quantitative features and qualitative features. The quantitative features consisted of the CT attenuation value of the tumor (CTVTumor), the CT attenuation value of the normal esophageal wall (CTVNormal), the CT attenuation value ratio of the tumor-to-normal esophageal wall (TNR), the CT attenuation value difference between the tumor and normal esophageal wall (ΔTN), the maximum thickness of the tumor measured by CECT (Thickness), the maximum length of the tumor measured by CECT (Length), and the gross tumor volume measured by CECT (GTV). The qualitative features consisted of an enhancement pattern, tumor margin, enlarged blood supply or drainage vessels to the tumor (EVFDT), and tumor necrosis. For the clinicopathological characteristics and CECT-derived imaging feature analysis, the chi-squared test was used for categorical variables, the Mann-Whitney U test was used for continuous variables with a nonnormal distribution, and the independent sample t-test was used for the continuous variables with a normal distribution. The trend test was used for ordinal variables. The association between LVI status and CECT-derived imaging features was analyzed by univariable logistic analysis, followed by multivariable logistic regression and receiver operating characteristic (ROC) curve analysis. RESULTS: The CTVTumor, TNR, ΔTN, Thickness, Length, and GTV in the group with LVI were higher than those in the group without LVI (P < 0.05). A higher proportion of patients with heterogeneous enhancement pattern, irregular tumor margin, EVFDT, and tumor necrosis were present in the group with LVI (P < 0.05). As revealed by the univariable logistic analysis, the CECT-derived imaging features, including CTVTumor, TNR, ΔTN and enhancement pattern, Thickness, Length, GTV, tumor margin, EVFDT, and tumor necrosis were associated with LVI status (P < 0.05). Only the TNR (OR 8.655; 95% CI 2.125-37.776), Thickness (OR 6.531; 95% CI 2.410-20.608), and tumor margin (OR 4.384; 95% CI 2.004-9.717) were independent risk factors for LVI in the multivariable logistic regression analysis. The ROC curve analysis incorporating the above three CECT-derived imaging features showed that the area under the curve obtained by the multivariable logistic regression model was 0.820 (95% CI 0.754-0.885). CONCLUSION: The CECT-derived imaging features, including TNR, Thickness, tumor margin, and their combination, can be used as predictors of LVI status for patients with ESCC.

Diagnosis of Serosal Invasion in Gastric Adenocarcinoma by Dual-Energy CT Radiomics: Focusing on Localized Gastric Wall and Peritumoral Radiomics Features.

Objectives: To build a radiomics model and combined model based on dual-energy CT (DECT) for diagnosing serosal invasion in gastric adenocarcinoma. Materials and methods: 231 gastric adenocarcinoma patients were enrolled and randomly divided into a training (n = 132), testing (n = 58), and independent validation (n = 41) cohort. Radiomics features were extracted from the rectangular ROI of the 120-kV equivalent mixed images and iodine map (IM) images in the venous phase of DECT, which was manually delineated perpendicularly to the gastric wall in the deepest location of tumor infiltration, including the peritumoral adipose tissue within 5 mm outside the serosa. The random forest algorithm was used for radiomics model construction. Traditional features were collected by two radiologists. Univariate and multivariate logistic regression was used to construct the clinical model and combined model. The diagnostic efficacy of the models was evaluated using ROC curve analysis and compared using the Delong's test. The calibration curves were used to evaluate the calibration performance of the combined model. Results: Both the radiomics model and combined model showed high efficacy in diagnosing serosal invasion in the training, testing and independent validation cohort, with AUC of 0.90, 0.90, and 0.85 for radiomics model; 0.93, 0.93, and 0.89 for combined model. The combined model outperformed the clinical model (AUC: 0.76, 0.76 and 0.81). Conclusion: The radiomics model and combined model constructed based on tumoral and peritumoral radiomics features derived from DECT showed high diagnostic efficacy for serosal invasion in gastric adenocarcinoma.

Global transcriptomic characterization of T cells in individuals with chronic HIV-1 infection.

To obtain a comprehensive scenario of T cell profiles and synergistic immune responses, we performed single-cell RNA sequencing (scRNA-seq) on the peripheral T cells of 14 individuals with chronic human immunodeficiency virus 1 (HIV-1) infection, including nine treatment-naive (TP) and eight antiretroviral therapy (ART) participants (of whom three were paired with TP cases), and compared the results with four healthy donors (HD). Through analyzing the transcriptional profiles of CD4+ and CD8+ T cells, coupled with assembled T cell receptor sequences, we observed the significant loss of naive T cells, prolonged inflammation, and increased response to interferon-α in TP individuals, which could be partially restored by ART. Interestingly, we revealed that CD4+ and CD8+ Effector-GNLY clusters were expanded in TP cases, and persistently increased in ART individuals where they were typically correlated with poor immune restoration. This transcriptional dataset enables a deeper understanding of the pathogenesis of HIV-1 infection and is also a rich resource for developing novel immune targeted therapeutic strategies.