Population Pharmacokinetic Modeling and Exposure-Efficacy and Body Weight-Response Analyses for Tezepelumab in Patients With Severe, Uncontrolled Asthma.

Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. This analysis assessed the suitability of a fixed-dose regimen of tezepelumab 210 mg every 4 weeks (Q4W) in adults and adolescents with severe, uncontrolled asthma. A population pharmacokinetic model was developed using data from 1368 patients with asthma or healthy participants enrolled in 8 clinical studies (phases 1-3). Tezepelumab exposure-efficacy relationships were analyzed in the phase 3 NAVIGATOR study (NCT03347279), using asthma exacerbation rates over 52 weeks and changes in pre-bronchodilator forced expiratory volume in 1 s at week 52. Tezepelumab pharmacokinetics were well characterized by a 2-compartment linear disposition model with first-order absorption and elimination following subcutaneous and intravenous administration at 2.1-420 and 210-700 mg, respectively. There were no clinically relevant effects on tezepelumab pharmacokinetics from age (≥12 years), sex, race/ethnicity, renal or hepatic function, disease severity (inhaled corticosteroid dose level), concomitant asthma medication use, smoking history, or anti-drug antibodies. Body weight was the most influential covariate on tezepelumab exposure, but no meaningful differences in efficacy or safety were observed across body weight quartiles in patients with asthma who received tezepelumab 210 mg subcutaneously Q4W. There was no apparent relationship between tezepelumab exposure and efficacy at this dose regimen, suggesting that it is on the plateau of the exposure-response curve of tezepelumab. In conclusion, a fixed-dose regimen of tezepelumab 210 mg subcutaneously Q4W is appropriate for eligible adults and adolescents with severe, uncontrolled asthma.

CCDC58 is a potential biomarker for diagnosis, prognosis, immunity, and genomic heterogeneity in pan-cancer.

Coiled-coil domain-containing 58 (CCDC58) is a member of the CCDC protein family. Similar to other members, CCDC58 exhibits potential tumorigenic roles in a variety of malignancies. However, there is no systematic and comprehensive pan-cancer analysis to investigate the diagnosis, prognosis, immune infiltration, and other related functions of CCDC58. We used several online websites and databases, such as TCGA, GTEx, UALCAN, HPA, CancerSEA, BioGRID, GEPIA 2.0, TIMER 2.0, and TISIDB, to extract CCDC58 expression data and clinical data of patients in pan-cancer. Then, the relationship between CCDC58 expression and diagnosis, prognosis, genetic alterations, DNA methylation, genomic heterogeneity, and immune infiltration level were determined. In addition, the biological function of CCDC58 in liver hepatocellular carcinoma (LIHC) was investigated. Pan-cancer analysis results showed that CCDC58 was differentially expressed in most tumors and showed excellent performance in diagnosis and prediction of prognosis. The expression of CCDC58 was highly correlated with genetic alterations, DNA methylation, and genomic heterogeneity in some tumors. In addition, the correlation analysis of CCDC58 with the level of immune infiltration and immune checkpoint marker genes indicated that CCDC58 might affect the composition of the tumor immune microenvironment. Enrichment analysis showed that CCDC58-related genes were mainly linked to mitosis, chromosome, and cell cycle. Finally, biological function experiments demonstrated that CCDC58 plays an important role in tumor cell proliferation and migration. CCDC58 was first identified as a pan-cancer biomarker. It may be used as a potential therapeutic target to improve the prognosis of patients in the future.

Psychometric properties of the Chinese version of the Quick Delay Questionnaire (C-QDQ) and ecological characteristics of reward-delay impulsivity of adults with ADHD.

BACKGROUND: The Quick Delay Questionnaire (QDQ) is a short questionnaire designed to assess delay-related difficulties in adults. This study aimed to examine the reliability and validity of the Chinese version of the QDQ (C-QDQ) in Chinese adults, and explore the ecological characteristics of delay-related impulsivity in Chinese adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Data was collected from 302 adults, including ADHD (n = 209) and healthy controls (HCs) (n = 93). All participants completed the C-QDQ. The convergent validity, internal consistency, retest reliability and confirmatory factor analysis (CFA) of the C-QDQ were analyzed. The correlations between C-QDQ and two laboratory measures of delay-related difficulties and Barratt Impulsiveness Scale-11 (BIS-11), the comparison of C-QDQ scores between ADHD subgroups and HCs were also analyzed. RESULTS: The Cronbach's α of C-QDQ was between 0.83 and 0.89. The intraclass correlation coefficient of C-QDQ was between 0.80 and 0.83. The results of CFA of C-QDQ favoured the original two-factor model (delay aversion and delay discounting). Significant positive associations were found between C-QDQ scores and BIS-11 total score and performance on the laboratory measure of delay-related difficulties. Participants with ADHD had higher C-QDQ scores than HCs, and female ADHD reported higher scores on delay discounting subscale than male. ADHD-combined type (ADHD-C) reported higher scores on delay aversion subscale than ADHD-inattention type (ADHD-I). CONCLUSION: The C-QDQ is a valid and reliable tool to measure delay-related responses that appears to have clinical utility. It can present the delay-related impulsivity of patients with ADHD. Compared to HCs, the level of reward-delay impulsivity was higher in ADHD.

Inhibition of endoplasmic reticulum stress attenuates morphine protracted abstinence-induced anxiety-like behaviors in the male mice.

The anxiety caused by morphine protracted abstinence is considered to be an important factor contributes to drug-seeking and relapse. Endoplasmic reticulum (ER) stress plays important roles in many kinds of mental disorders including drug addiction and anxiety, but it is unclear whether ER stress is involved in anxiety-like behaviors induced by morphine withdrawal. In this study, by using behavioral test, western blot, immunofluorescence, electron transmission microscope, we found that: (1) Inhibition of endoplasmic reticulum stress by 4-Phenylbutyric acid (4-PBA) could attenuate anxiety-like behaviors induced by morphine withdrawal. (2) The endoplasmic reticulum stress-related proteins in the lateral habenula (LHb) but not in the nucleus accumbens (NAc), ventral pallidum (VP), basolateral amygdala (BLA) and CA1 of hippocampus was upregulated by morphine withdrawal, upregulation of endoplasmic reticulum stress-related proteins in the lateral habenula induced by morphine withdrawal was inhibited by 4-PBA. (3) Endoplasmic reticulum stress-related protein CHOP and eIF2α were expressed in neurons but not in microglia in the LHb. (4) Morphine withdrawal induced neuronal morphological change in the LHb, which was attenuated by 4-PBA.

MAFLD as part of systemic metabolic dysregulation.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. In recent years, a new terminology and definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. Compared to the NAFLD definition, MAFLD better emphasizes the pathogenic role of metabolic dysfunction in the development and progression of this highly prevalent condition. Metabolic disorders, including overweight/obesity, type 2 diabetes mellitus (T2DM), atherogenic dyslipidemia and hypertension, are often associated with systemic organ dysfunctions, thereby suggesting that multiple organ damage can occur in MAFLD. Substantial epidemiological evidence indicates that MAFLD is not only associated with an increased risk of liver-related complications, but also increases the risk of developing several extra-hepatic diseases, including new-onset T2DM, adverse cardiovascular and renal outcomes, and some common endocrine diseases. We have summarized the current literature on the adverse effect of MAFLD on the development of multiple extrahepatic (cardiometabolic and endocrine) complications and examined the role of different metabolic pathways and organ systems in the progression of MAFLD, thus providing new insights into the role of MAFLD as a multisystem metabolic disorder. Our narrative review aimed to provide insights into potential mechanisms underlying the known associations between MAFLD and extrahepatic diseases, as part of MAFLD as a multisystem disease, in order to help focus areas for future drug development targeting not only liver disease but also the risk of extrahepatic complications.

Stereoselective Synthesis of Polysubstituted Conjugated Dienes Enabled by Photo-driven Sequential Sigmatropic Rearrangement.

We here report a highly stereoselective method for the synthesis of polysubstituted conjugated dienes from α-aryl α-diazo alkynyl ketones and pyrazole-substituted unsymmetric aminals under mild conditions, which was driven by photo and involved 1,6-dipolar ion intermediate and quadruple sigmatropic rearrangements, was successfully developed. In this transformation, the cleavage of four bonds and the recombination of five bonds were achieved in one operational step. This protocol also provided a modular tool for constructing dienes via "one-pot" strategy from the three components of amines, pyrazol and α-alkynyl-α-diazoketones. The mechanistic investigation combining control experiments and therotical calculations indicated that the plausible reaction path underwent the 1,6-sigmatropic rearrangement of 1,6-dipolar ion intermediate instead of the 1,5-sigmatropic rearrangement of 1,5-dipolar ion intermediate.

Cerebral venous congestion alters CNS homeostatic plasticity, evoking tinnitus-like behavior.

BACKGROUND: Brain function and neuronal activity depend on a constant supply of blood from the cerebral circulation. The cerebral venous system (CVS) contains approximately 70% of the total cerebral blood volume; similar to the cerebral arterial system, the CVS plays a prominent role in the maintenance of central nervous system (CNS) homeostasis. Impaired venous autoregulation, which can appear in forms such as cerebral venous congestion, may lead to metabolic abnormalities in the brain, causing severe cerebral functional defects and even chronic tinnitus. However, the role of cerebral venous congestion in the progression of tinnitus is underrecognized, and its pathophysiology is still incompletely understood. This study elucidated the specific pathogenetic role of cerebral venous congestion in the onset and persistence of tinnitus and the possible neurophysiological mechanisms. RESULTS: We found that a rat model of cerebral venous congestion exhibited tinnitus-like behavioral manifestations at 14 days postoperatively; from that point onward, they showed signs of persistent tinnitus without significant hearing impairment. Subsequent neuroimaging and neurochemical findings showed CNS homeostatic plasticity disturbance in rats with cerebral venous congestion, reflected in increased neural metabolic activity, ultrastructural synaptic changes, upregulated synaptic efficacy, reduced inhibitory synaptic transmission (due to GABA deficiency), and elevated expression of neuroplasticity-related proteins in central auditory and extra-auditory pathways. CONCLUSION: Collectively, our data suggest that alternations in CNS homeostatic plasticity may play a vital role in tinnitus pathology caused by cerebral venous congestion. These findings provide a new perspective on tinnitus related to cerebral venous congestion and may facilitate the development of precise interventions to interrupt its pathogenesis.

CCL20 and CD8A as potential diagnostic biomarkers for HBV-induced liver fibrosis in chronic hepatitis B.

Background: The main cause of the liver fibrosis (LF) remains hepatitis B virus (HBV) infection, especially in China. Histologically, liver fibrosis still occurs progressively in chronic hepatitis B (CHB) patients, even if HBV-DNA is negative or undetectable. The diagnosis of LF is beneficial to control the development of it, also it may promote the reversal of LF. Although liver biopsy is the gold standard of diagnosis in LF at present, it isa traumatic diagnosis. There are no diagnostic biomarkers as yet for the condition. It is badly in need of biomarkers clinically, which is simple to test, minimally invasive, highly specific, and sensitive. Early detection of HBV-LF development is crucial in the prevention, treatment, and prognosis prediction of HBV-LF. Cytokines are closely associated with both immune regulation and inflammation in the progression of hepatitis B virus associated-liver fibrosis (HBV-LF). In this bioinformatic study, we not only analyzed the relationship between HBV-LF and immune infiltration, but also identified key genes to uncover new therapeutic targets. Objectives: To find potential biomarkers for liver fibrosis in the development of chronic hepatic B patients. Materials and methods: We obtained two sets of data including CHB/healthy control and CHB/HBV-LF from the Integrated Gene Expression (GEO) database to select for differential expression analysis. Protein-protein interaction (PPI) network was also generated, while key genes and important gene modules involved in the occurrence and development of HBV-LF were identified. These key genes were analyzed by functional enrichment analysis, module analysis, and survival analysis. Furthermore, the relationship between these two diseases and immune infiltration was explored. Results: Among the identified genes, 150 were individually associated with CHB and healthy control in the differential gene expression (DGE) analysis. While 14 with CHB and HBV-LF. It was also analyzed in the Robust rank aggregation (RRA) analysis, 34 differential genes were further identified by Cytohubba. Among 34 differential genes, two core genes were determined: CCL20 and CD8A. CCL20 was able to predict CHB positivity (area under the receiver operating characteristic curve [AUC-ROC] = 0.883, 95% confidence interval [CI] 0.786-0.963), while HBV-LF positivity ([AUC-ROC] = 0.687, 95% confidence interval [CI] 0.592-0.779). And CD8A was able to predict CHB positivity ([AUC-ROC] = 0.960, 95% confidence interval [CI] 0.915-0.992), while HBV-LF positivity ([AUC-ROC] = 0.773, 95% confidence interval [CI] 0.680-0.856). Relationship between CCL20 gene expression and LF grades was P < 0.05, as well as CD8A. Conclusion: CCL20 and CD8A were found to be potential biomarkers and therapeutic targets for HBV-LF. It is instructive for research on the progression of LF in HBV patients, suppression of chronic inflammation, and development of molecularly targeted-therapy for HBV-LF.

Verteporfin fluorescence in antineoplastic-treated pancreatic cancer cells found concentrated in mitochondria.

BACKGROUND: Traditional treatments for pancreatic cancer (PC) are inadequate. Photodynamic therapy (PDT) is non-invasive, and proven safe to kill cancer cells, including PC. However, the mitochondrial concentration of the photosensitizer, such as verteporfin, is key. AIM: To investigate the distribution of fluorescence of verteporfin in PC cells treated with antitumor drugs, post-PDT. METHODS: Workable survival rates of PC cells (AsPC-1, BxPC-3) were determined with chemotherapy [doxorubicin (DOX) and gemcitabine (GEM)] and non-chemotherapy [sirolimus (SRL) and cetuximab (CTX)] drugs in vitro, with or without verteporfin, as measured via MTT, flow cytometry, and laser confocal microscopy. Reduced cell proliferation was associated with GEM that was more enduring compared with DOX. Confocal laser microscopy allowed observation of GEM- and verteporfin-treated PC cells co-stained with 4',6-diamidino-2-phenylindole and MitoTracker Green to differentiate living and dead cells and subcellular localization of verteporfin, respectively. RESULTS: Cell survival significantly dropped upon exposure to either chemotherapy drug, but not to SRL or CTX. Both cell lines responded similarly to GEM. The intensity of fluorescence was associated with the concentration of verteporfin. Additional experiments using GEM showed that survival rates of the PC cells treated with 10 µmol/L verteporfin (but not less) were significantly lower relative to nil verteporfin. Living and dead stained cells treated with GEM were distinguishable. After GEM treatment, verteporfin was observed primarily in the mitochondria. CONCLUSION: Verteporfin was observed in living cells. In GEM -treated human PC cells, verteporfin was particularly prevalent in the mitochondria. This study supports further study of PDT for the treatment of PC after neoadjuvant chemotherapy.

3D bioprinting approaches for spinal cord injury repair.

Regenerative healing of spinal cord injury (SCI) poses an ongoing medical challenge by causing persistent neurological impairment and a significant socioeconomic burden. The complexity of spinal cord tissue presents hurdles to successful regeneration following injury, due to the difficulty of forming a biomimetic structure that faithfully replicates native tissue using conventional tissue engineering scaffolds. 3D bioprinting is a rapidly evolving technology with unmatched potential to create 3D biological tissues with complicated and hierarchical structure and composition. With the addition of biological additives such as cells and biomolecules, 3D bioprinting can fabricate preclinical implants, tissue or organ-like constructs, andin vitromodels through precise control over the deposition of biomaterials and other building blocks. This review highlights the characteristics and advantages of 3D bioprinting for scaffold fabrication to enable SCI repair, including bottom-up manufacturing, mechanical customization, and spatial heterogeneity. This review also critically discusses the impact of various fabrication parameters on the efficacy of spinal cord repair using 3D bioprinted scaffolds, including the choice of printing method, scaffold shape, biomaterials, and biological supplements such as cells and growth factors. High-quality preclinical studies are required to accelerate the translation of 3D bioprinting into clinical practice for spinal cord repair. Meanwhile, other technological advances will continue to improve the regenerative capability of bioprinted scaffolds, such as the incorporation of nanoscale biological particles and the development of 4D printing.

Ultrasound modification on milk fat globule membrane and soy lecithin to improve the physicochemical properties, microstructure and stability of mimicking human milk fat emulsions.

Starting from the consideration of the structure of human milk fat globule (MFG), this study aimed to investigate the effects of ultrasonic treatment on milk fat globule membrane (MFGM) and soy lecithin (SL) complexes and their role in mimicking human MFG emulsions. Ultrasonic power significantly affected the structure of the MFGM-SL complex, further promoting the unfolding of the molecular structure of the protein, and then increased solubility and surface hydrophobicity. Furthermore, the microstructure of mimicking MFG emulsions without sonication was unevenly distributed, and the average droplet diameter was large. After ultrasonic treatment, the droplets of the emulsion were more uniformly dispersed, the particle size was smaller, and the emulsification properties and stability were improved to varying degrees. Especially when the ultrasonic power was 300 W, the mimicking MFG emulsion had the highest encapsulation rate and emulsion activity index and emulsion stability index were increased by 60.88 % and 117.74 %, respectively. From the microstructure, it was observed that the spherical droplets of the mimicking MFG emulsion after appropriate ultrasonic treatment remain well separated without obvious flocculation. This study can provide a reference for the screening of milk fat globules mimicking membrane materials and the further utilization and development of ultrasound in infant formula.

The development and validation of automated machine learning models for predicting lymph node metastasis in Siewert type II T1 adenocarcinoma of the esophagogastric junction.

Background: Lymph node metastasis (LNM) is considered an essential prognosis factor for adenocarcinoma of the esophagogastric junction (AEG), which also affects the treatment strategies of AEG. We aimed to evaluate automated machine learning (AutoML) algorithms for predicting LNM in Siewert type II T1 AEG. Methods: A total of 878 patients with Siewert type II T1 AEG were selected from the Surveillance, Epidemiology, and End Results (SEER) database to develop the LNM predictive models. The patients from two hospitals in Suzhou were collected as the test set. We applied five machine learning algorithms to develop the LNM prediction models. The performance of predictive models was assessed using various metrics including accuracy, sensitivity, specificity, the area under the curve (AUC), and receiver operating characteristic (ROC) curve. Results: Patients with LNM exhibited a higher proportion of male individuals, a poor degree of differentiation, and submucosal infiltration, with statistical differences. The deep learning (DL) model demonstrated relatively good accuracy (0.713) and sensitivity (0.868) among the five models. Moreover, the DL model achieved the highest AUC (0.781) and sensitivity (1.000) in the test set. Conclusion: The DL model showed good predictive performance among five AutoML models, indicating the advantage of AutoML in modeling LNM prediction in patients with Siewert type II T1 AEG.

Quality of asynchronous webchats vs in-person consultations for postpartum depression in China: a cross-sectional, mixed methods study using standardized patients.

Background: Prompt professional care for postpartum depression (PPD) is difficult to obtain in China. Though online consultations improve accessibility and reduce stigma, the quality of services compared to in-person consultations is unclear. Methods: Five trained, undisclosed "standardized patients" (SPs) made "asynchronous webchats" visits and in-person visits with psychiatrists. Visits were made to 85 psychiatrists who were based in 69 hospitals in ten provincial capital cities. The care between online and in-person consultations with the same psychiatrist was compared, including diagnosis, guideline adherence, and patient-centeredness. False discovery rate (FDR) was used to adjust p values. Third visits using asynchronous webchats were made to psychiatrists who offered discrepant diagnoses. Thematic content analysis was used for the discrepancies. Findings: The proportion of diagnostic accuracy was lower for online than in-person visits (76.5% [65/85] vs 91.8% [78/85]; pFDR = 0.0066), as were the proportions of completing questions involving clinical history (16.6% vs 42.7%; pFDR < 0.0001), and management decisions (16.2% vs 27.5%; pFDR < 0.0001) consistent with recommended guidelines. Patient-centeredness was lower online than in-person (pFDR < 0.0001). Fifteen of 16 psychiatrists completed third visits, most of them considered lack of nonverbal information online as a key barrier. Interpretation: Online consultations using asynchronous webchats were inferior to in-person consultations, with respect to diagnostic accuracy, adherence to recommended clinical guidelines, and patient-centeredness. To fully realise the potential benefits of online consultations and to prevent safety issues, there is an urgent need for major improvement in the quality and oversight of these consultations. Funding: China Medical Board, National Natural Science Foundation of China, and Swiss Agency for Development and Cooperation Global Cooperation Department.

Nutrient deprivation induces mouse embryonic diapause mediated by Gator1 and Tsc2.

Embryonic diapause is a special reproductive phenomenon in mammals that helps embryos to survive various harsh stresses. However, the mechanisms of embryonic diapause induced by the maternal environment is still unclear. Here, we uncovered that nutrient deficiency in uterine fluid was essential for the induction of mouse embryonic diapause, shown by a decreased concentration of arginine, leucine, isoleucine, lysine, glucose and lactate in the uterine fluid of mice suffering from maternal starvation or ovariectomy. Moreover, mouse blastocysts cultured in a medium with reduced levels of these six components could mimic diapaused blastocysts. Our mechanistic study indicated that amino acid starvation-dependent Gator1 activation and carbohydrate starvation-dependent Tsc2 activation inhibited mTORC1, leading to induction of embryonic diapause. Our study elucidates the essential environmental factors in diapause induction.

Quantifying the Relationship Between Unilateral Induced Metamorphopsia and Stereopsis Impairment.

Purpose: To investigate the relationship between unilateral metamorphopsia, characterized by visual distortions in one eye, and impaired stereopsis. Methods: Utilizing both near and distance measurements through advanced testing systems, including 4K smartphones and an active shutter three-dimensional system, we simulated varying degrees of unilateral metamorphopsia in 30 healthy young adults aged between 21 and 29 years. Two types of contour-based stereotest symbols, lines and squares, were developed. Distortions were classified into six distinct patterns, each further divided into eight grades of severity. Participants were tasked with identifying visual targets, and their stereothresholds were determined under different conditions of induced distortion. Stereopsis was measured within a range of 2.9 to 1.0 log arcsec, at 0.2 log arcsec intervals. Stereopsis changes under different distortion scenarios were analyzed using the generalized estimating equations, with a sequential Bonferroni adjustment applied for pairwise comparisons. Results: A direct and quantifiable correlation was observed between the severity of metamorphopsia and reductions in stereopsis. As the degree of visual distortion increased, notably in both frequency and amplitude, there was a corresponding decline in stereopsis. This relationship held true in both near and distance measurements of stereopsis. Statistical analyses further reinforced these findings, highlighting a significant detrimental effect of distortion components on stereoacuity. Conclusions: The findings highlight the clinical significance of understanding the interplay between unilateral metamorphopsia and stereopsis. Early interventions in conditions leading to metamorphopsia might be critical to maintaining optimal stereopsis.

(±)-Involucrasin D, a pair of enantiomeric bisflavonoid from the roots of Shuteria involucrata and its anti-inflammatory activity.

An undescribed bisflavonoid, named involucrasin D (1), along with two known flavonoids, 2(S)7,3',5'-trihydroxydihydroflavone (2) and sigmone (3) were isolated from the roots of Shuteria involucrata. A further chiral separation of 1 to yielded a pair of enantiomers (+)-1 and (-)-1. The structures were elucidated based on spectroscopic analyses and electron circular dichroism (ECD) calculations. Among them, bisflavonoid 1 and its enantiomers displayed remarkable anti-inflammatory effects by inhibiting the production of TNF-α and IL-6 in a dose-dependent manner.

Association of cardiometabolic and triglyceride-glucose index with left ventricular diastolic function in asymptomatic individuals.

BACKGROUND AND AIMS: Obesity and insulin resistance are associated with left ventricular diastolic dysfunction (LVDD) and increased risk of heart failure. Cardiometabolic index (CMI) and triglyceride glucose (TyG) are new indexes to assess visceral obesity and insulin resistance, respectively. The study aimed to investigate the clinical usefulness of these indexes for identifying LVDD individuals. METHODS AND RESULTS: Overall, 1898 asymptomatic individuals were included in this cross-sectional study. Participants underwent anthropometrics, serum biochemical evaluation, and echocardiography. Multiple linear regression analysis revealed that both indexes were independent determinants of diastolic parameters among females; while for males, CMI and TyG were not associated with A velocity. In the multivariate logistic analysis, the proportion of LVDD in the third and fourth quartiles of CMI remained significantly greater than that in the lowest quartile in females (Q3 vs. Q1: odds ratio (OR) = 2.032, 95% confidence interval (CI): 1.181-3.496; Q4 vs. Q1: OR = 2.393, 95% CI: 1.347-4.249); while in males, the incidence of LVDD was significantly greater only in the fourth quartile. For TyG, the presence of LVDD in the fourth quartile was significantly greater in both genders. The discriminant values between the CMI (AUC: 0.704, 95% CI: 0.668-0.739) and TyG (AUC: 0.717, 95% CI: 0.682-0.752) were similar in females. Both indexes performed better in females than in males to identify LVDD. CONCLUSION: The CMI and TyG might both serve as effective tools to identify LVDD in routine health check-ups in primary care, mainly in females. With simpler parameters, the CMI could be utilized in medically resource-limited areas.

Ultrasound radiomics-based artificial intelligence model to assist in the differential diagnosis of ovarian endometrioma and ovarian dermoid cyst.

Background: Accurately differentiating between ovarian endometrioma and ovarian dermoid cyst is of clinical significance. However, the ultrasound appearance of these two diseases is variable, occasionally causing confusion and overlap with each other. This study aimed to develop a diagnostic classification model based on ultrasound radiomics to intelligently distinguish and diagnose the two diseases. Methods: We collected ovarian ultrasound images from participants diagnosed as patients with ovarian endometrioma or ovarian dermoid cyst. Feature extraction and selection were performed using the Mann-Whitney U-test, Spearman correlation analysis, and the least absolute shrinkage and selection operator (LASSO) regression. We then input the final features into the machine learning classifiers for model construction. A nomogram was established by combining the radiomic signature and clinical signature. Results: A total of 407 participants with 407 lesions were included and categorized into the ovarian endometriomas group (n = 200) and the dermoid cyst group (n = 207). In the test cohort, Logistic Regression (LR) achieved the highest area under curve (AUC) value (0.981, 95% CI: 0.963-1.000), the highest accuracy (94.8%), and the highest sensitivity (95.5%), while LightGBM achieved the highest specificity (97.1%). A nomogram incorporating both clinical features and radiomic features achieved the highest level of performance (AUC: 0.987, 95% CI: 0.967-1.000, accuracy: 95.1%, sensitivity: 88.0%, specificity: 100.0%, PPV: 100.0%, NPV: 88.0%, precision: 93.6%). No statistical difference in diagnostic performance was observed between the radiomic model and the nomogram (P > 0.05). The diagnostic indexes of radiomic model were comparable to that of senior radiologists and superior to that of junior radiologist. The diagnostic performance of junior radiologists significantly improved with the assistance of the model. Conclusion: This ultrasound radiomics-based model demonstrated superior diagnostic performance compared to those of junior radiologists and comparable diagnostic performance to those of senior radiologists, and it has the potential to enhance the diagnostic performance of junior radiologists.

[Corrigendum] Induction of microRNA­let­7a inhibits lung adeno-carcinoma cell growth by regulating cyclin D1.

After the publication of the article, an interested reader drew to the authors' attention that, in the western blots shown in Fig. 5C and D, a pair of data panels were inadvertently duplicated comparing between panels (C) and (D); in addition, the cell migration data shown in Fig. 7F on p. 1852 were selected incorrectly. The authors have examined their original data, and realize that these errors arose inadvertently as a consequence of their mishandling of their data. The revised versions of Figs. 5 and 7, featuring the corrected data for the caspase-8 experiment in Fig. 5C and alternative data for the cell migration assay experiments in Fig. 7F, are shown on the next two pages. The revised data shown for these Figures do not affect the overall conclusions reported in the paper. All the authors agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. Furthermore, the authors apologize to the readership for any inconvenience caused. [Oncology Reports 40: 1843-1854, 2018; DOI: 10.3892/or.2018.6593].