Disease-specific health-related quality of life trajectories up to 15 years after curative treatment for esophageal cancer-a prospective cohort study.

BACKGROUND: The presence of distinct long-term disease-specific HRQL trajectories after curative treatment for esophageal cancer and factors associated with such trajectories are unclear. MATERIALS AND METHODS: This population-based and longitudinal cohort study included 425 esophageal cancer patients who underwent curative treatment, including esophagectomy, in Sweden in 2001-2005 and were followed up until 2020, that is, 15-year follow-up. The outcomes were 10 disease-specific HRQL symptoms, measured by the well-validated EORTC QLQ-OES18 questionnaire at 6 months (n = 402 patients), and 3 (n = 178), 5 (n = 141), 10 (n = 92), and 15 years (n = 52) after treatment. HRQL symptoms were examined for distinct trajectories by growth mixture models. Weighted logistic regression models provided odds ratios (OR) with 95% confidence intervals (95% CI) for nine factors in relation to HRQL trajectories: age, sex, education, proxy baseline HRQL, comorbidity, tumor histology, chemo(radio)therapy, pathological tumor stage, and postoperative complications. RESULTS: Distinct HRQL trajectories were identified for each of the 10 disease-specific symptoms. HRQL trajectories with more symptoms tended to persist or alleviate over time, while trajectories with fewer symptoms were more stable. Eating difficulty had three trajectories: persistently less, persistently moderate, and persistently more symptoms. The OR of having a persistently more eating difficulty trajectory was decreased for adenocarcinoma histology (OR = 0.44, 95% CI 0.21-0.95), and increased for pathological tumor stage III-IV (OR = 2.19, 95% CI 0.99-4.82) and 30-day postoperative complications (OR = 2.54, 95% CI 1.26-5.12). CONCLUSION: Distinct trajectories with long-term persistent or deteriorating disease-specific HRQL symptoms were identified after esophageal cancer treatment. Tumor histology, tumor stage, and postoperative complications may facilitate detection of high-risk patients for unwanted trajectories.

The genomic trajectory of ovarian high-grade serous carcinoma can be observed in STIC lesions.

Ovarian high-grade serous carcinoma (HGSC) originates in the fallopian tube, with secretory cells carrying a TP53 mutation, known as p53 signatures, identified as potential precursors. p53 signatures evolve into serous tubal intraepithelial carcinoma (STIC) lesions, which in turn progress into invasive HGSC, which readily spreads to the ovary and disseminates around the peritoneal cavity. We recently investigated the genomic landscape of early- and late-stage HGSC and found higher ploidy in late-stage (median 3.1) than early-stage (median 2.0) samples. Here, to explore whether the high ploidy and possible whole-genome duplication (WGD) observed in late-stage disease were determined early in the evolution of HGSC, we analysed archival formalin-fixed paraffin-embedded (FFPE) samples from five HGSC patients. p53 signatures and STIC lesions were laser-capture microdissected and sequenced using shallow whole-genome sequencing (sWGS), while invasive ovarian/fallopian tube and metastatic carcinoma samples underwent macrodissection and were profiled using both sWGS and targeted next-generation sequencing. Results showed highly similar patterns of global copy number change between STIC lesions and invasive carcinoma samples within each patient. Ploidy changes were evident in STIC lesions, but not p53 signatures, and there was a strong correlation between ploidy in STIC lesions and invasive ovarian/fallopian tube and metastatic samples in each patient. The reconstruction of sample phylogeny for each patient from relative copy number indicated that high ploidy, when present, occurred early in the evolution of HGSC, which was further validated by copy number signatures in ovarian and metastatic tumours. These findings suggest that aberrant ploidy, suggestive of WGD, arises early in HGSC and is detected in STIC lesions, implying that the trajectory of HGSC may be determined at the earliest stages of tumour development. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Chronic stress dysregulates the Hippo/YAP/14-3-3η pathway and induces mitochondrial damage in basolateral amygdala in a mouse model of depression.

Rationale: Recent evidence highlights the pivotal role of mitochondrial dysfunction in mood disorders, but the mechanism involved remains unclear. We studied whether the Hippo/YAP/14-3-3η signaling pathway mediates mitochondrial abnormalities that result in the onset of major depressive disorder (MDD) in a mouse model. Methods: The ROC algorithm was used to identify a subpopulation of mice that were exposed to chronic unpredictable mild stress (CUMS) and exhibited the most prominent depressive phenotype (Dep). Electron microscopy, biochemical assays, quantitative PCR, and immunoblotting were used to evaluate synaptic and mitochondrial changes in the basolateral amygdala (BLA). RNA sequencing was used to explore changes in the Hippo pathway and downstream target genes. In vitro pharmacological inhibition and immunoprecipitation was used to confirm YAP/14-3-3η interaction and its role in neuronal mitochondrial dysfunction. We used virus-mediated gene overexpression and knockout in YAP transgenic mice to verify the regulatory effect of the Hippo/YAP/14-3-3η pathway on depressive-like behavior. Results: Transcriptomic data identified a large number of genes and signaling pathways that were specifically altered from the BLA of Dep mice. Dep mice showed notable synaptic impairment in BLA neurons, as well as mitochondrial damage characterized by abnormal mitochondrial morphology, compromised function, impaired biogenesis, and alterations in mitochondrial marker proteins. The Hippo signaling pathway was activated in Dep mice during CUMS, and the transcriptional regulatory activity of YAP was suppressed by phosphorylation of its Ser127 site. 14-3-3η was identified as an important co-regulatory factor of the Hippo/YAP pathway, as it can respond to chronic stress and regulate cytoplasmic retention of YAP. Importantly, the integrated Hippo/YAP/14-3-3η pathway mediated neuronal mitochondrial dysfunction and depressive behavior in Dep mice. Conclusion: The integrated Hippo/YAP/14-3-3η pathway in the BLA neuron is critical in mediating depressive-like behaviors in mice, suggesting a causal role for this pathway in susceptibility to chronic stress-induced depression. This pathway therefore may present a therapeutic target against mitochondrial dysfunction and synaptic impairment in MDD.

Colossal anisotropic absorption of spin currents induced by chirality.

The chiral induced spin selectivity (CISS) effect, in which the structural chirality of a material determines the preference for the transmission of electrons with one spin orientation over that of the other, is emerging as a design principle for creating next-generation spintronic devices. CISS implies that the spin preference of chiral structures persists upon injection of pure spin currents and can act as a spin analyzer without the need for a ferromagnet. Here, we report an anomalous spin current absorption in chiral metal oxides that manifests a colossal anisotropic nonlocal Gilbert damping with a maximum-to-minimum ratio of up to 1000%. A twofold symmetry of the damping is shown to result from differential spin transmission and backscattering that arise from chirality-induced spin splitting along the chiral axis. These studies reveal the rich interplay of chirality and spin dynamics and identify how chiral materials can be implemented to direct the transport of spin current.

Impacts of pilot carbon emission trading policies on urban environmental pollution: Evidence from China.

The trading of carbon emissions is a crucial regulatory method to address environmental pollution issues. This study takes China's carbon emission trading pilot policy established in 2013 as a quasi-natural experiment and uses the DID model to empirically test the urban panel data from 2006 to 2019. The results show that the carbon emission trading pilot policy can effectively reduce urban environmental pollution, and this effect is more noticeable in mid-western cities, northern cities, cities with fewer resources, and large-scale cities. In addition, to address the urban environmental pollution problem through this policy, the government is encouraged to raise its environmental protection awareness and put more effort into the innovation of technology. In general, this study uses carbon emission trading policies from China to confirm that market-based incentive environmental regulation tools can effectively reduce environmental pollution in urban areas. These findings can provide more theoretical support and empirical evidence for the government to use mechanisms of the market to effectively solve pollution problems, improve ecological environment quality, and accelerate the realization of green economy.

Enhancing multiple myeloma staging: a novel cell death risk model approach.

The prognostication of survival trajectories in multiple myeloma (MM) patients presents a substantial clinical challenge. Leveraging transcriptomic and clinical profiles from an expansive cohort of 2,088 MM patients, sourced from the Gene Expression Omnibus and The Cancer Genome Atlas repositories, we applied a sophisticated nested lasso regression technique to construct a prognostic model predicated on 28 gene pairings intrinsic to cell death pathways, thereby deriving a quantifiable risk stratification metric. Employing a threshold of 0.15, we dichotomized the MM samples into discrete high-risk and low-risk categories. Notably, the delineated high-risk cohort exhibited a statistically significant diminution in survival duration, a finding which consistently replicated across both training and external validation datasets. The prognostic acumen of our cell death signature was further corroborated by TIME ROC analyses, with the model demonstrating robust performance, evidenced by AUC metrics consistently surpassing the 0.6 benchmark across the evaluated arrays. Further analytical rigor was applied through multivariate COX regression analyses, which ratified the cell death risk model as an independent prognostic determinant. In an innovative stratagem, we amalgamated this risk stratification with the established International Staging System (ISS), culminating in the genesis of a novel, refined ISS categorization. This tripartite classification system was subjected to comparative analysis against extant prognostic models, whereupon it manifested superior predictive precision, as reflected by an elevated C-index. In summation, our endeavors have yielded a clinically viable gene pairing model predicated on cellular mortality, which, when synthesized with the ISS, engenders an augmented prognostic tool that exhibits pronounced predictive prowess in the context of multiple myeloma.

The miR-641-STIM1 and SATB1 axes play important roles in the regulation of the Th17/Treg balance in ITP.

Immune thrombocytopenia (ITP) is an autoimmune disease caused by T-cell dysfunction. Recently, several studies have shown that a disturbed Th17/Treg balance contributes to the development of ITP. MicroRNAs (miRNAs) are small noncoding RNA moleculesthat posttranscriptionally regulate gene expression. Emerging evidences have demonstrated that miRNAs play an important role in regulating the Th17/Treg balance. In the present study, we found that miR-641 was upregulated in ITP patients. In primary T cells, overexpression of miR-641 could cause downregulation of its target genes STIM1 and SATB1, thus inducing a Th17 (upregulated)/Treg (downregulated) imbalance. Inhibition of miR-641 by a miR-641 sponge in primary T cells of ITP patients or by antagomiR-641 in an ITP murine model could cause upregulation of STIM1 and SATB1, thus restoring Th17/Treg homeostasis. These results suggested that the miR-641-STIM/SATB1 axis plays an important role in regulating the Th17/Treg balance in ITP.

PFASs in Cerebrospinal Fluids and Blood-CSF Barrier Permeability in Patients with Cognitive Impairment.

Attention has been drawn to the associations between PFASs and human cognitive decline. However, knowledge on the occurrence and permeability of PFASs in the brains of patients with cognitive impairment has not been reported. Here, we determined 30 PFASs in paired sera and cerebrospinal fluids (CSFs) from patients with cognitive impairment (n = 41) and controls without cognitive decline (n = 18). We revealed similar serum PFAS levels but different CSF PFAS levels, with lower CSF PFOA (median: 0.125 vs 0.303 ng/mL, p < 0.05), yet higher CSF PFOS (0.100 vs 0.052 ng/mL, p < 0.05) in patients than in controls. Blood-brain transfer rates also showed lower RCSF/Serum values for PFOA and higher RCSF/Serum values for PFOS in patients, implying potential heterogeneous associations with cognitive function. The RCSF/Serum values for C4-C14 perfluoroalkyl carboxylates exhibited a U-shape trend with increasing chain length. Logistic regression analyses demonstrated that CSF PFOS levels were linked to the heightened risk of cognitive impairment [odds ratio: 3.22 (1.18-11.8)] but not for serum PFOS. Toxicity inference results based on the Comparative Toxicogenomics Database suggested that PFOS in CSF may have a greater potential to impair human cognition than other PFASs. Our results contribute to a better understanding of brain PFAS exposure and its potential impact on cognitive function.

Digital finance and green innovation efficiency: empirical data from Chinese listed manufacturing companies.

Amid the flourishing digital economy, digital finance overcomes the constraints of the conventional financial model and largely improves the supply efficiency and use of funds. This provides new opportunities for manufacturing corporations to improve their green innovation efficiency. Employing Chinese Shenzhen and Shanghai A-share listed manufacturing corporations between 2011 and 2021, this paper conducts an empirical analysis to study the effect of digital finance on corporate green innovation efficiency. Discoveries suggest that digital finance significantly improves manufacturing corporations' green innovation efficiency. After a few robustness tests, the results are still accurate. According to a mechanism analysis, digital finance increases the effectiveness of green innovation in manufacturing corporations by removing financing constraints. According to the heterogeneity analysis, the impact of digital finance on manufacturing corporations exhibits distinctive financial and geographical regional heterogeneity, particularly accentuated in Zhejiang Province and the central and western regions. This paper can provide a valuable reference for digital finance in supporting manufacturing corporations in green innovation ventures and improving the level of green innovation in the context of digitalization.

Cancer-related fatigue trajectories up to 5 years after curative treatment for oesophageal cancer.

BACKGROUND: Whether cancer-related fatigue develops differently after curative-intended oesophageal cancer treatment and the related modifiable factors are unclear. METHODS: This population-based and longitudinal cohort included 409 oesophageal cancer patients who underwent curative oesophagectomy in 2013-2020 in Sweden. The main outcome was cancer-related fatigue trajectories with measurements at 1, 1.5, 2, 2.5, 3, 4 and 5 years postoperatively by validated EORTC QLQ-FA12 questionnaire, and analysed using growth mixture models. Weighted logistic regressions provided odds ratios (OR) with 95% confidence intervals (95% CI) for underlying sociodemographic, clinical, and patient-reported outcome factors in relation to the identified trajectories. RESULTS: Two distinct overall cancer-related fatigue trajectories were identified: low level of persistent fatigue and high level of increasing fatigue, with 64% and 36% of patients, respectively. The odds of having high level of fatigue trajectory were increased by Charlson comorbidity index (≥ 2 versus 0: OR = 2.52, 95% CI 1.07-5.94), pathological tumour Stage (III-IV versus 0-I: OR = 2.52, 95% CI 1.33-4.77), anxiety (OR = 7.58, 95% CI 2.20-26.17), depression (OR = 15.90, 95% CI 4.44-56.93) and pain (continuous score: OR = 1.02, 95% CI 1.01-1.04). CONCLUSIONS: Long-term trajectories with high level of increasing cancer-related fatigue and the associated modifiable factors were identified after oesophageal cancer treatment. The results may facilitate early identification and targeted intervention for such high-risk patients.

Health-related quality of life trajectories up to 15 years after curative treatment for esophageal cancer: a prospective cohort study.

BACKGROUND: The differentiation of specific, long-term health-related quality of life (HRQL) trajectories among esophageal cancer survivors remains unclear. The authors aimed to identify potentially distinctly different HRQL-trajectories and uncover the underlying factors of such trajectories in patients having undergone surgery (esophagectomy) for esophageal cancer. MATERIALS AND METHODS: This nationwide, prospective, and longitudinal cohort study included 420 patients who underwent curative treatment for esophageal cancer, including esophageal cancer surgery, in Sweden from 2001to 2005. The main outcome was HRQL summary score trajectories, measured by the well-validated EORTC QLQ-C30 questionnaire at 6 months, 3, 5, 10, and 15 years after esophagectomy, and analyzed using growth mixture models. Potentially underlying factors for these trajectories (age, sex, education, proxy baseline HRQL, comorbidity, tumor histology, chemo(radio)therapy, pathological tumor stage, and postoperative complications) were analyzed using weighted logistic regression providing odds ratios (OR) with 95% CI. RESULTS: Four distinct HRQL summary score trajectories were identified: Persistently good, improving, deteriorating, and persistently poor. The odds of belonging to a persistently poor trajectory were decreased by longer education (>12 years versus <9 years: OR 0.18, 95% CI: 0.05-0.66) and adenocarcinoma histology (adenocarcinoma versus squamous cell carcinoma: OR 0.37, 95% CI: 0.16-0.85), and increased by more advanced pathological tumor stage (III-IV versus 0-I: OR 2.82, 95% CI: 1.08-7.41) and postoperative complications (OR 2.94, 95% CI: 1.36-6.36). CONCLUSION: Distinct trajectories with persistently poor or deteriorating HRQL were identified after curative treatment for esophageal cancer. Education, tumor histology, pathological tumor stage, and postoperative complications might influence HRQL trajectories. The results may contribute to a more tailored follow-up with timely and targeted interventions. Future research remains to confirm these findings.

Identification and validation of 5-methylcytosine-associated genes in diffuse large B-cell lymphoma.

5-methylcytosine modifications play a significant role in carcinogenesis; however, studies exploring 5-methylcytosine-related genes in diffuse large B-cell lymphoma patients are lacking. In this study, we aimed to understand the potential role and clinical prognostic impact of 5-methylcytosine regulators in diffuse large B-cell lymphoma and identify a prognostic biomarker based on 5-methylcytosine-associated genes. Gene expression profiles and corresponding clinical information of diffuse large B-cell lymphoma patients and normal controls were obtained from The Cancer Genome Atlas, Gene Expression Omnibus, and Genotype-Tissue Expression databases. Diffuse large B-cell lymphoma was divided into three clusters according to the 5-methylcytosine regulators, and differentially expressed genes were screened among the three clusters. Univariate Cox and Lasso-Cox regression analyses were used to screen prognostic genes and construct a prognostic risk model. Kaplan-Meier curve analysis, univariate and multivariate Cox regression analyses, and time-dependent receiver operator characteristic curve analysis were used to evaluate prognostic factors. GSVA was used to enrich potential pathways associated with 5-methylcytosine modification patterns. SsGSEA and CIBERSORT were used to assess immune cell infiltration. Six 5-methylcytosine-related genes (TUBB4A, CD3E, ZNF681, HAP1, IL22RA2, and POSTN) were used to construct a prognostic risk model, which was proved to have a good predictive effect. In addition, univariate and multivariate Cox regression risk scores were independent prognostic factors for diffuse large B-cell lymphoma. Further analysis showed that the 5-methylcytosine risk score was significantly correlated with immune cell infiltration and immune checkpoint of diffuse large B-cell lymphoma. Our study reveals for the first time a potential role for 5-methylcytosine modifications in diffuse large B-cell lymphoma, provides novel insights for future studies on diffuse large B-cell lymphoma, and offers potential prognostic biomarkers and therapeutic targets for patients with diffuse large B-cell lymphoma.

Immune modulation of gut microbiota and its metabolites in chronic hepatitis B.

The gut microbiota is a diverse ecosystem consisting of 100 trillion microbiomes. The interaction between the host's gut and distal organs profoundly impacts various functions such as metabolism, immunity, neurology, and nutrition within the human body. The liver, as the primary immune organ, plays a crucial role in maintaining immune homeostasis by receiving a significant influx of gut-derived components and toxins. Perturbations in gut microbiota homeostasis have been linked to a range of liver diseases. The advancements in sequencing technologies, such as 16S rRNA and metagenomics, have opened up new avenues for comprehending the intricate physiological interplay between the liver and the intestine. Metabolites produced by the gut microbiota function as signaling molecules and substrates, influencing both pathological and physiological processes. Establishing a comprehensive host-bacterium-metabolism axis holds tremendous potential for investigating the mechanisms underlying liver diseases. In this review, we have provided a summary of the detrimental effects of the gut-liver axis in chronic liver diseases, primarily focusing on hepatitis B virus-related chronic liver diseases. Moreover, we have explored the potential mechanisms through which the gut microbiota and its derivatives interact with liver immunity, with implications for future clinical therapies.

The Aurora kinase inhibitor AT9283 inhibits Burkitt lymphoma growth by regulating Warburg effect.

Objective: To investigate the effect of the kinase inhibitor AT9283 on Burkitt lymphoma (BL) cells and elucidate the underlying mechanisms. Methods: The effect of AT9283 on the proliferation of BL cell lines was tested using the MTT assay. Apoptosis and cell cycle were measured by flow cytometry. The proteins associated with the cell cycle, apoptosis, and the Warburg effect were detected using Western blotting. Alterations in glycolytic metabolism in terms of glucose intake and lactate concentrations were determined by glucose and lactate assays. Results: The current study utilized the GEPIA, the Human Protein Atlas (HAP) database and immunohistochemistry to conduct analyses, which revealed a high expression of Aurora kinases and Warburg effect-related proteins in malignant B-cell lymphoma tissues. AT9283 significantly inhibited the cell proliferation of BL cells and induced G2/M arrest. Additionally, AT9283 induced apoptosis in BL cells and reversed the Warburg effect by increasing glucose uptake and reducing lactate production. Moreover, the protein expression of hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A was significantly suppressed by AT9283, possibly through the inhibition of c-Myc and HIF-1α protein expression. Conclusion: The reversal of the Warburg effect in BL cells and the subsequent inhibition of cell proliferation and induction of apoptosis were observed by targeting Aurora A and Aurora B with AT9283. This finding may present new therapeutic options and targets for BL.

Anisotropic Nonlocal Damping in Ferromagnet/α-GeTe Bilayers Enabled by Splitting Energy Bands.

The understanding and manipulation of anisotropic Gilbert damping is crucial for both fundamental research and versatile engineering and optimization. Although several works on anisotropic damping have been reported, no direct relationship between the band structure and anisotropic damping was established. Here, we observed an anisotropic damping in Fe/GeTe manipulated by the symmetric band structures of GeTe via angle-resolved photoemission spectroscopy. Moreover, the anisotropic damping can be modified by the symmetry of band structures. Our Letter provides insightful understandings of the anisotropic Gilbert damping in ferromagnets interfaced with Rashba semiconductors and suggests the possibility of manipulating the Gilbert damping by band engineering.

Dynamic Simulation of Nitrifying Microbial Communities for Establishing Acidic Partial Nitritation in Suspended Activated Sludge.

Acidic partial nitritation (PN) is a promising technology to achieve low-cost and energy-efficient shortcut nitrogen removal from wastewater. However, a comprehensive understanding of the acidic PN under dynamic changes of pH in a sequencing batch reactor (SBR) is still lacking. In this study, we successfully established acidic PN (NO2- accumulation ratio >80%) under dynamic pH variation from 7.0 to 4.5 in a lab-scale SBR. By accumulating in situ free nitrous acid (FNA) generation based on the dynamic pH change, acidic PN maintained stability even at a low NH4+ concentration of 100 mg N L-1. The microbial community analysis revealed that two ammonium-oxidizing bacteria (AOB) genera, Nitrosospira and Nitrosomonas, successfully coexisted and cooperated during acidic PN. None of the species of nitrite-oxidizing bacteria (NOB) showed adaptation to intermittent inhibition of in situ FNA even under high DO conditions (>4.0 mg O2 L-1). Furthermore, we innovatively incorporated the classic nitrification model with the growth and decay of different nitrifying bacterial species and their inhibition by pH, FNA, and free ammonia (FA) to predict the nitrifying microbial communities shifting for establishing acidic PN. The extended model was calibrated by using short-term batch experiments and was validated by using long-term dynamic data of the nitrifying microbial community during SBR operation. The validated model was further used to identify feasible influent conditions for the SBR PN process, including influent HCO3- concentration, NH4+ concentration and molar ratio (HCO3/NH4+). Outcomes from this study support the optimal design of acidic PN-based short-cut nitrogen removal processes for future application.

Diagnostic role of transient elastography in patients with autoimmune liver diseases: A systematic review and meta-analysis.

BACKGROUND: Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy. However, previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease. The diagnostic value of transient elastography for autoimmune liver diseases (AILDs) is worth studying. AIM: To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD. METHODS: The PubMed, Cochrane Library and EMBASE databases were searched. Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs [autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)] were included. The summary area under the receiver operating characteristic curve (AUROC), diagnostic odds ratio, sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis. RESULTS: A total of 60 articles were included in this study, and the number of patients with AIH, PBC and PSC was 1594, 3126 and 501, respectively. The summary AUROC of transient elastography in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis in patients with AIH were 0.84, 0.88 and 0.90, respectively, while those in patients with PBC were 0.93, 0.93 and 0.91, respectively. The AUROC of cirrhosis for patients with PSC was 0.95. However, other noninvasive indices (aspartate aminotransferase to platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, fibrosis-4 index) had corresponding AUROCs less than 0.80. CONCLUSION: Transient elastography exerts better diagnostic accuracy in AILD patients, especially in PBC patients. The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.

Immune infiltration and drug specificity analysis of different subtypes based on functional status in angioimmunoblastic T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma (PTCL) strongly correlated with worse clinical outcomes. However, the role of characteristic pathway-related genes in patients with AITL (e.g., subtype typing and pathogenesis) remains unknown. In this study, we intended to understand the potential role and prognostic value of characteristic pathways in AITL and identified a model for subtype identification based on pathway-related functional status. Transcriptomic (RNA-seq) data were obtained from the Gene Expression Omnibus database for three sets of tumor tissues from AITL patients. AITL was divided into three clusters based on the pathway profile of patients and the best clustering k = 3, and differentially expressed genes (DEGs) in the three clusters were analyzed. The top 45 important variables associated with characteristic pathways, such as Huntington's disease, VEGF signaling pathway, nucleotide excision repair, ubiquitin-mediated proteolysis, purine metabolism, olfactory transduction, etc., were used to construct a subtype identification model. The model was experimentally validated and proved to possess good predictive efficacy. In addition, pathway-related subtype typing was significantly associated with different immune cell infiltration in AITL. Further analysis revealed that the drug IC50 values predicted also differed markedly among the different subtypes, thus further identifying some subtype-specific drugs. Our study indicates a potential role of characteristic pathways in AITL staging for the first time, provides novel insights for future research targeting AITL, and points to potential therapeutic options for patients with different subtypes of AITL.