Diagnostic performance of Node Reporting and Data System (Node-RADS) for assessing mesorectal lymph node in rectal cancer by CT.

BACKGROUND: To compare the diagnostic performance of the Node-RADS scoring system and lymph node (LN) size in preoperative LN assessment for rectal cancer (RC), and to investigate whether the selection of size as the primary criterion whereas morphology as the secondary criterion for LNs can be considered the preferred method for clinical assessment. METHODS: Preoperative CT data of 146 RC patients treated with radical resection surgery were retrospectively analyzed. The Node-RADS score and short-axis diameter of size-prioritized LNs and the morphology-prioritized LNs were obtained. The correlations of Node-RADS score to the pN stage, LNM number and lymph node ratio (LNR) were investigated. The performances on assessing pathological lymph node metastasis were compared between Node-RADS score and short-axis diameter. A nomogram combined the Node-RADS score and clinical features was also evaluated. RESULTS: Node-RADS score showed significant correlation with pN stage, LNM number and LNR (Node-RADS of size-prioritized LN: r = 0.600, 0.592, and 0.606; Node-RADS of morphology-prioritized LN: r = 0.547, 0.538, and 0.527; Node-RADSmax: r = 0.612, 0.604, and 0.610; all p < 0.001). For size-prioritized LN, Node-RADS achieved an AUC of 0.826, significantly superior to short-axis diameter (0.826 vs. 0.743, p = 0.009). For morphology-prioritized LN, Node-RADS exhibited an AUC of 0.758, slightly better than short-axis diameter (0.758 vs. 0.718, p = 0.098). The Node-RADS score of size-prioritized LN was significantly better than that of morphology-prioritized LN (0.826 vs. 0.758, p = 0.038). The nomogram achieved the best diagnostic performance (AUC = 0.861) than all the other assessment methods (p < 0.05). CONCLUSIONS: The Node-RADS scoring system outperforms the short-axis diameter in predicting lymph node metastasis in RC. Size-prioritized LN demonstrates superior predictive efficacy compared to morphology-prioritized LN. The nomogram combined the Node-RADS score of size-prioritized LN with clinical features exhibits the best diagnostic performance. Moreover, a clear relationship was demonstrated between the Node-RADS score and the quantity-dependent pathological characteristics of LNM.

Correlation between vertebral bone mineral density and multi-level virtual non-calcium imaging parameters from dual-layer spectral detector computed tomography.

Background: Virtual non-calcium (VNCa) imaging based on dual-energy computed tomography (CT) plays an increasingly important role in diagnosing spinal diseases. However, the utility of VNCa technology in the measurement of vertebral bone mineral density (BMD) is limited, especially the VNCa CT value at multiple calcium suppression levels and the slope of VNCa curve. This retrospective cross-sectional study aimed to explore the correlation between vertebral BMD and new VNCa parameters from dual-layer spectral detector CT. Methods: The dual-layer spectral detector CT and quantitative CT (QCT) data of 4 hydroxyapatite (HAP) inserts and 667 vertebrae of 234 patients (132 male and 102 female) who visited a university teaching hospital between April and May 2023 were retrospectively analyzed. The BMD values of 3 vertebrae (T12, L1, and L2) and inserts were measured using QCT, defined as QCT-BMD. The VNCa CT values and the slope λ of the VNCa attenuation curve of vertebrae and inserts were recorded. The correlations between VNCa parameters (VNCa CT value, slope λ) and QCT-BMD were analyzed. Results: For the vertebrae, the correlation coefficient ranged from -0.904 to 0.712 (all P<0.05). As the calcium suppression index (CaSI) increased, the correlation degree exhibited a decrease first and then increased, with the best correlation (r=-0.904, P<0.001) observed at the index of 25%. In contrast, the correlation coefficient for the inserts remained relatively stable (r=-0.899 to -1, all P<0.05). For the vertebrae, the values of 3 slopes λ (λ1, λ2, and λ3) derived from the VNCa attenuation curve were 6.50±1.99, 3.75±1.15, and 2.04±0.62, respectively. Regarding the inserts, the λ1, λ2, and λ3 values were 11.56 [interquartile range (IQR): 2.40-22.62], 6.68 (IQR: 1.39-13.49), and 3.63 (IQR: 0.75-7.8), respectively. For the vertebrae, all 3 correlation coefficients between 3 slopes λ and QCT-BMD were 0.956 (all P<0.05). For the inserts, the 3 correlation coefficients were 0.996, 0.998, and 1 (all P<0.05), respectively. Conclusions: A promising correlation was detected between VNCa CT parameters and QCT-BMD in vertebrae, warranting further investigation to explore the possibility of VNCa imaging to assess BMD.

Mechanistic insights into cardiovascular effects of ultrafine particle exposure: A longitudinal panel study.

BACKGROUND: Ultrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated. OBJECTIVES: This study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved. METHODS: A longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses. RESULTS: Short-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0-3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7-12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism. DISCUSSION: This study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.

Acute kidney injury in hospitalized patients with nonmalignant pleural effusions: a retrospective cohort study.

BACKGROUND: Nonmalignant pleural effusion (NMPE) is common and remains a definite health care problem. Pleural effusion was supposed to be a risk factor for acute kidney injury (AKI). Incidence of AKI in NMPE patients and whether there is correlation between the size of effusions and AKI is unknown. OBJECTIVE: To assess the incidence of AKI in NMPE inpatients and its association with effusion size. STUDY DESIGN AND METHOD: We conducted a retrospective cohort study of inpatients admitted to the Chinese PLA General Hospital with pleural effusion from 2018-2021. All patients with pleural effusions confirmed by chest radiography (CT or X-ray) were included, excluding patients with diagnosis of malignancy, chronic dialysis, end-stage renal disease (ESRD), community-acquired AKI, hospital-acquired AKI before chest radiography, and fewer than two serum creatinine tests during hospitalization. Multivariate logistic regression and LASSO logistic regression models were used to identify risk factors associated with AKI. Subgroup analyses and interaction tests for effusion volume were performed adjusted for the variables selected by LASSO. Causal mediation analysis was used to estimate the mediating effect of heart failure, pneumonia, and eGFR < 60 ml/min/1.73m2 on AKI through effusion volume. RESULTS: NMPE was present in 7.8% of internal medicine inpatients. Of the 3047 patients included, 360 (11.8%) developed AKI during hospitalization. After adjustment by covariates selected by LASSO, moderate and large effusions increased the risk of AKI compared with small effusions (moderate: OR 1.47, 95%CI 1.11-1.94 p = 0.006; large: OR 1.86, 95%CI 1.05-3.20 p = 0.028). No significant modification effect was observed among age, gender, diabetes, bilateral effusions, and eGFR. Volume of effusions mediated 6.8% (p = 0.005), 4.0% (p = 0.046) and 4.6% (p < 0.001) of the effect of heart failure, pneumonia and low eGFR on the development of AKI respectively. CONCLUSION: The incidence of AKI is high among NMPE patients. Moderate and large effusion volume is independently associated with AKI compared to small size. The effusion size acts as a mediator in heart failure, pneumonia, and eGFR.

Causal effects of inflammatory bowel disease on risk of type 2 diabetes: a two-sample multivariable Mendelian randomization study.

AIM: This study aimed to explore the causal association between inflammatory bowel disease (IBD) and the risk of type 2 diabetes (T2D) based on a two-sample Mendelian randomization (MR) study. METHODS: Summary single nucleotide polymorphism (SNP)-phenotype association data were obtained from published two genome-wide association studies (GWAS) including SNPs related to IBD, UC, or CD in European participants (n = 71,997) and East Asian participants (n = 16,805). Two GWAS including SNPs associated with T2D included 655,666 Europeans and 433,540 East Asians. A series of screening processes were performed to select qualified instrumental SNPs strongly related to exposure. We applied the inverse variance weighted (IVW), the MR-Egger regression, and the weighted median to estimate the causal effects of IBD, ulcerative colitis (UC) or Crohn' disease (CD) on T2D. Cochran's Q test was conducted to evaluate the statistical heterogeneity between SNPs in the IVW method. The leave-one-out analysis was employed to assess whether the results were caused by any single SNP associated with IBD, UC, or CD. Odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: The IVW results demonstrated that IBD could increase the risk of T2D in the European population (OR = 1.0230, 95%CI: 1.0073-1.0390). UC was positively associated with the risk of T2D according to the weighted median (OR = 1.0274, 95%CI: 1.0009-1.0546) and IVW (OR = 1.0244, 95%CI: 1.0071-1.0421) results in the European population. The IVW results indicated that the CD was positively associated with the risk of T2D in the European population (OR = 1.0187, 95%CI: 1.0045-1.0330). In the East Asian population, there are no associations between the IBD, UC, or CD and the risk of T2D (all P > 0.05). MVMR results revealed that the causal effect UC on T2D was still statistically significant after including body mass index (BMI) or low-density lipoprotein (LDL). CONCLUSION: IBD, UC, or CD had causal effects on the risk of T2D in the European population, which might provide evidence for the prevention of T2D in patients with IBD, UC, or CD.

CT-based radiomics for differentiating peripherally located pulmonary sclerosing pneumocytoma from carcinoid.

BACKGROUND: Pulmonary sclerosing pneumocytoma (PSP) and pulmonary carcinoid (PC) are difficult to distinguish based on conventional imaging examinations. In recent years, radiomics has been used to discriminate benign from malignant pulmonary lesions. However, the value of radiomics based on computed tomography (CT) images to differentiate PSP from PC has not been well explored. PURPOSE: We aimed to investigate the feasibility of radiomics in the differentiation between PSP and PC. METHODS: Fifty-three PSP and fifty-five PC were retrospectively enrolled and then were randomly divided into the training and test sets. Univariate and multivariable logistic analyses were carried to select clinical predictor related to differential diagnosis of PSP and PC. A total of 1316 radiomics features were extracted from the unenhanced CT (UECT) and contrast-enhanced CT (CECT) images, respectively. The minimum redundancy maximum relevance and the least absolute shrinkage and selection operator were used to select the most significant radiomics features to construct radiomics models. The clinical predictor and radiomics features were integrated to develop combined models. Two senior radiologists independently categorized each patient into PSP or PC group based on traditional CT method. The performances of clinical, radiomics, and combined models in differentiating PSP from PC were investigated by the receiver operating characteristic (ROC) curve. The diagnostic performance was also compared between the combined models and radiologists. RESULTS: In regard to differentiating PSP from PC, the area under the curves (AUCs) of the clinical, radiomics, and combined models were 0.87, 0.96, and 0.99 in the training set UECT, and were 0.87, 0.97, and 0.98 in the training set CECT, respectively. The AUCs of the clinical, radiomics, and combined models were 0.84, 0.92, and 0.97 in the test set UECT, and were 0.84, 0.93, and 0.98 in the test set CECT, respectively. In regard to the differentiation between PSP and PC, the combined model was comparable to the radiomics model, but outperformed the clinical model and the two radiologists, whether in the test set UECT or CECT. CONCLUSIONS: Radiomics approaches show promise in distinguishing between PSP and PC. Moreover, the integration of clinical predictor (gender) has the potential to enhance the diagnostic performance even further.

Enhanced TRPC3 transcription through AT1R/PKA/CREB signaling contributes to mitochondrial dysfunction in renal tubular epithelial cells in D-galactose-induced accelerated aging mice.

Aging-associated renal dysfunction promotes the pathogenesis of chronic kidney disease. Mitochondrial dysfunction in renal tubular epithelial cells is a hallmark of senescence and leads to accelerated progression of renal disorders. Dysregulated calcium profiles in mitochondria contribute to aging-associated disorders, but the detailed mechanism of this process is not clear. In this study, modulation of the sirtuin 1/angiotensin II type 1 receptor (Sirt1/AT1R) pathway partially attenuated renal glomerular sclerosis, tubular atrophy, and interstitial fibrosis in D-galactose (D-gal)-induced accelerated aging mice. Moreover, modulation of the Sirt1/AT1R pathway improved mitochondrial dysfunction induced by D-gal treatment. Transient receptor potential channel, subtype C, member 3 (TRPC3) upregulation mediated dysregulated cellular and mitochondrial calcium homeostasis during aging. Furthermore, knockdown or knockout (KO) of Trpc3 in mice ameliorated D-gal-induced mitochondrial reactive oxygen species production, membrane potential deterioration, and energy metabolism disorder. Mechanistically, activation of the AT1R/PKA pathway promoted CREB phosphorylation and nucleation of CRE2 binding to the Trpc3 promoter (-1659 to -1648 bp) to enhance transcription. Trpc3 KO significantly improved the renal disorder and cell senescence in D-gal-induced mice. Taken together, these results indicate that TRPC3 upregulation mediates age-related renal disorder and is associated with mitochondrial calcium overload and dysfunction. TRPC3 is a promising therapeutic target for aging-associated renal disorders.

Epigenome-wide association study on short-, intermediate- and long-term ozone exposure in Han Chinese, the NSPT study.

Epidemiological and epigenetic studies have acknowledged ambient ozone exposure associated with inflammatory and cardiovascular disease. However, the molecular mechanisms still remained unclear, and epigenome-wide analysis in cohort were lacking, especially in Chinese. We included blood-derived DNA methylation for 3365 Chinese participants from the NSPT cohort and estimated individual ozone exposure level of short-, intermediate- and long-term, based on a validated prediction model. We performed epigenome-wide association studies which identified 59 CpGs and 30 DMRs at a strict genome-wide significance (P < 5 ×10-8). We also conducted comparison on the DNA methylation alteration corresponding to different time windows, and observed an enhanced differentiated methylation trend for intermediate- and long-term exposure, while the short-term exposure associated methylation changes did not retain. The targeted genes of methylation alteration were involved in mechanism related to aging, inflammation disease, metabolic syndrome, neurodevelopmental disorders, and oncogenesis. Underlying pathways were enriched in biological activities including telomere maintenance process, DNA damage response and megakaryocyte differentiation. In conclusion, our study is the first EWAS on ozone exposure conducted in large-scale Han Chinese cohort and identified associated DNA methylation change on CpGs and regions, as well as related gene functions and pathways.

Comparison of preoperative CT- and MRI-based multiparametric radiomics in the prediction of lymph node metastasis in rectal cancer.

Objective: To compare computed tomography (CT)- and magnetic resonance imaging (MRI)-based multiparametric radiomics models and validate a multi-modality, multiparametric clinical-radiomics nomogram for individual preoperative prediction of lymph node metastasis (LNM) in rectal cancer (RC) patients. Methods: 234 rectal adenocarcinoma patients from our retrospective study cohort were randomly selected as the training (n = 164) and testing (n = 70) cohorts. The radiomics features of the primary tumor were extracted from the non-contrast enhanced computed tomography (NCE-CT), the enhanced computed tomography (CE-CT), the T2-weighted imaging (T2WI) and the gadolinium contrast-enhanced T1-weighted imaging (CE-TIWI) of each patient. Three kinds of models were constructed based on training cohort, including the Clinical model (based on the clinical features), the radiomics models (based on NCE-CT, CE-CT, T2WI, CE-T1WI, CT, MRI, CT combing with MRI) and the clinical-radiomics models (based on CT or MRI radiomics model combing with clinical data) and Clinical-IMG model (based on CT and MRI radiomics model combing with clinical data). The performances of the 11 models were evaluated via the area under the receiver operator characteristic curve (AUC), accuracy, sensitivity, and specificity in the training and validation cohort. Differences in the AUCs among the 11 models were compared using DeLong's test. Finally, the optimal model (Clinical-IMG model) was selected to create a radiomics nomogram. The performance of the nomogram to evaluate clinical efficacy was verified by ROC curves and decision curve analysis (DCA). Results: The MRI radiomics model in the validation cohort significantly outperformed than CT radiomics model (AUC, 0.785 vs. 0.721, p<0.05). The Clinical-IMG nomogram had the highest prediction efficiency than all other predictive models (p<0.05), of which the AUC was 0.947, the sensitivity was 0.870 and the specificity was 0.884. Conclusion: MRI radiomics model performed better than both CT radiomics model and Clinical model in predicting LNM of RC. The clinical-radiomics nomogram that combines the radiomics features obtained from both CT and MRI along with preoperative clinical characteristics exhibits the best diagnostic performance.

Oral micronized progesterone versus vaginal progesterone for luteal phase support in fresh embryo transfer cycles: a multicenter, randomized, non-inferiority trial.

STUDY QUESTION: Does oral micronized progesterone result in a non-inferior ongoing pregnancy rate compared to vaginal progesterone gel as luteal phase support (LPS) in fresh embryo transfer cycles? SUMMARY ANSWER: The ongoing pregnancy rate in the group administered oral micronized progesterone 400 mg per day was non-inferior to that in the group administered vaginal progesterone gel 90 mg per day. WHAT IS KNOWN ALREADY: LPS is an integrated component of fresh IVF, for which an optimal treatment regimen is still lacking. The high cost and administration route of the commonly used vaginal progesterone make it less acceptable than oral micronized progesterone; however, the efficacy of oral micronized progesterone is unclear owing to concerns regarding its low bioavailability after the hepatic first pass. STUDY DESIGN, SIZE, DURATION: This non-inferiority randomized trial was conducted in eight academic fertility centers in China from November 2018 to November 2019. The follow-up was completed in April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1310 infertile women who underwent their first or second IVF cycles were enrolled. On the day of hCG administration, the patients were randomly assigned to one of three groups for LPS: oral micronized progesterone 400 mg/day (n = 430), oral micronized progesterone 600 mg/day (n = 440) or vaginal progesterone 90 mg/day (n = 440). LPS was started on the day of oocyte retrieval and continued till 11-12 weeks of gestation. The primary outcome was the rate of ongoing pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: In the intention-to-treat analysis, the rate of ongoing pregnancy in the oral micronized progesterone 400 mg/day group was non-inferior to that of the vaginal progesterone gel group [35.3% versus 38.0%, absolute difference (AD): -2.6%; 95% CI: -9.0% to 3.8%, P-value for non-inferiority test: 0.010]. There was insufficient evidence to support the non-inferiority in the rate of ongoing pregnancy between the oral micronized progesterone 600 mg/day group and the vaginal progesterone gel group (31.6% versus 38.0%, AD: -6.4%; 95% CI: -12.6% to -0.1%, P-value for non-inferiority test: 0.130). In addition, we did not observe a statistically significant difference in the rate of live births between the groups. LIMITATIONS, REASONS FOR CAUTION: The primary outcome of our trial was the ongoing pregnancy rate; however, the live birth rate may be of greater clinical interest. Although the results did not show a difference in the rate of live births, they should be confirmed by further trials with larger sample sizes. In addition, in this study, final oocyte maturation was triggered by hCG, and the findings may not be extrapolatable to cycles with gonadotropin-releasing hormone agonist triggers. WIDER IMPLICATIONS OF THE FINDINGS: Oral micronized progesterone 400 mg/day may be an alternative to vaginal progesterone gel in patients reluctant to accept the vaginal route of administration. However, whether a higher dose of oral micronized progesterone is associated with a poorer pregnancy rate or a higher rate of preterm delivery warrants further investigation. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a grant from the National Natural Science Foundation of China (82071718). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the number ChiCTR1800015958. TRIAL REGISTRATION DATE: May 2018. DATE OF FIRST PATIENT'S ENROLMENT: November 2018.

Identification of novel first-trimester serum biomarkers for early prediction of preeclampsia.

BACKGROUND: Preeclampsia (PE) is a leading cause of maternal and perinatal mortality and morbidity worldwide, but effective early prediction remains a challenge due to the lack of reliable biomarkers. METHODS: Based on the extensive human biobank of our large-scale assisted reproductive cohort platform, the first-trimester serum levels of 48 cytokines, total immunoglobulins (Igs), anti-phosphatidylserine (aPS) antibodies, and several previously reported PE biomarkers [including placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and activin A] were measured in 34 women diagnosed with PE and 34 matched normotensive controls. RESULTS: The PE group has significantly higher first-trimester serum levels of interleukin (IL)-2Rα, IL-9, tumor necrosis factor-ß (TNF-ß), RANTES, hepatocyte growth factor (HGF), total IgM, and total IgG, and aPS IgG optical density (OD) value, as well as lower first-trimester serum levels of PlGF and total IgA and aPS-IgG immune complexes (IC) OD value than the control group. Combining top five first-trimester serum biomarkers (total IgM, total IgG, PlGF, aPS IgG, and total IgA) achieved superior predictive value [area under the curve (AUC) and 95% confidence interval (CI) 0.983 (0.952-1.000), with a sensitivity of 100% and a specificity of 94.1%] for PE development compared to PlGF and PlGF/sFlt-1 independently [AUC and 95% CI 0.825 (0.726-0.924) and 0.670 (0.539-0.800), respectively]. CONCLUSION: We identified novel first-trimester serum biomarkers and developed an effective first-trimester prediction model using immune-related factors and PlGF for PE, which could facilitate the development of early diagnostic strategies and provide immunological insight into the further mechanistic exploration of PE.

Circ_0001715 accelerated lung adenocarcinoma process by the miR-1322/CANT1 axis.

Lung adenocarcinoma (LUAD) is a type of lung cancer, which belongs to non-small cell lung cancer and has seriously endangered the physical and mental health of people. The study of circRNAs (circRNAs) has been increasingly hot in recent years, in which circRNAs also play an important regulatory role in cancer. The aim of this study was to investigate the biological molecular mechanisms of circ_0001715 in the progression of LUAD. The expression of circ_0001715, miR-1322 and calcium-activated nucleotidase 1 (CANT1) in LUAD tissues and cell lines was assessed by quantitative reverse transcription PCR (RT-qPCR) and western bot assay. Clone formation assay, 5-Ethynyl-2'-Deoxyuridine (EDU) assay and wound healing assay were used to verify the proliferation ability of cells. Dual-luciferase reporter assay and RNA pull-down assay were performed to characterize the interactions between the three factors. Finally, a mouse tumor model was constructed to assess the tumorigenicity of circ_0001715. RT-qPCR assay results showed that circ_0001715 expression was significantly increased in LUAD tissues and cell lines. Finally, knockdown of circ_0001715 could inhibit tumor growth in vivo. Circ_0001715 regulated the progression of LUAD through the miR-1322/CANT1 axis. The results of this study provided ideas for understanding the molecular mechanisms of circ_0001715 in LUAD.

Patching sulfur vacancies: A versatile approach for achieving ultrasensitive gas sensors based on transition metal dichalcogenides.

Transition metal dichalcogenides (TMDCs) garner significant attention for their potential to create high-performance gas sensors. Despite their favorable properties such as tunable bandgap, high carrier mobility, and large surface-to-volume ratio, the performance of TMDCs devices is compromised by sulfur vacancies, which reduce carrier mobility. To mitigate this issue, we propose a simple and universal approach for patching sulfur vacancies, wherein thiol groups are inserted to repair sulfur vacancies. The sulfur vacancy patching (SVP) approach is applied to fabricate a MoS2-based gas sensor using mechanical exfoliation and all-dry transfer methods, and the resulting 4-nitrothiophenol (4NTP) repaired molybdenum disulfide (4NTP-MoS2) is prepared via a sample solution process. Our results show that 4NTP-MoS2 exhibits higher response (increased by 200 %) to ppb-level NO2 with shorter response/recovery times (61/82 s) and better selectivity at 25 °C compared to pristine MoS2. Notably, the limit of detection (LOD) toward NO2 of 4NTP-MoS2 is 10 ppb. Kelvin probe force microscopy (KPFM) and density functional theory (DFT) reveal that the improved gas sensing performance is mainly attributed to the 4NTP-induced n-doping effect on MoS2 and the corresponding increment of surface absorption energy to NO2. Additionally, our 4NTP-induced SVP approach is universal for enhancing gas sensing properties of other TMDCs, such as MoSe2, WS2, and WSe2.

Respiratory Effects of Traffic-Related Air Pollution: A Randomized, Crossover Analysis of Lung Function, Airway Metabolome, and Biomarkers of Airway Injury.

BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been associated with increased risks of respiratory diseases, but the biological mechanisms are not yet fully elucidated. OBJECTIVES: Our aim was to evaluate the respiratory responses and explore potential biological mechanisms of TRAP exposure in a randomized crossover trial. METHODS: We conducted a randomized crossover trial in 56 healthy adults. Each participant was exposed to high- and low-TRAP exposure sessions by walking in a park and down a road with high traffic volume for 4 h in random order. Respiratory symptoms and lung function, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), the ratio of FEV1 to FVC, and maximal mid-expiratory flow (MMEF), were measured before and after each exposure session. Markers of 8-isoprostane, tumor necrosis factor-α (TNF-α), and ezrin in exhaled breath condensate (EBC), and surfactant proteins D (SP-D) in serum were also measured. We used linear mixed-effects models to estimate the associations, adjusted for age, sex, body mass index, meteorological condition, and batch (only for biomarkers). Liquid chromatography-mass spectrometry was used to profile the EBC metabolome. Untargeted metabolome-wide association study (MWAS) analysis and pathway enrichment analysis using mummichog were performed to identify critical metabolomic features and pathways associated with TRAP exposure. RESULTS: Participants had two to three times higher exposure to traffic-related air pollutants except for fine particulate matter while walking along the road compared with in the park. Compared with the low-TRAP exposure at the park, high-TRAP exposure at the road was associated with a higher score of respiratory symptoms [2.615 (95% CI: 0.605, 4.626), p=1.2×10-2] and relatively lower lung function indicators [-0.075L (95% CI: -0.138, -0.012), p=2.1×10-2] for FEV1 and -0.190L/s (95% CI: -0.351, -0.029; p=2.4×10-2) for MMEF]. Exposure to TRAP was significantly associated with changes in some, but not all, biomarkers, particularly with a 0.494-ng/mL (95% CI: 0.297, 0.691; p=9.5×10-6) increase for serum SP-D and a 0.123-ng/mL (95% CI: -0.208, -0.037; p=7.2×10-3) decrease for EBC ezrin. Untargeted MWAS analysis revealed that elevated TRAP exposure was significantly associated with perturbations in 23 and 32 metabolic pathways under positive- and negative-ion modes, respectively. These pathways were most related to inflammatory response, oxidative stress, and energy use metabolism. CONCLUSIONS: This study suggests that TRAP exposure might lead to lung function impairment and respiratory symptoms. Possible underlying mechanisms include lung epithelial injury, inflammation, oxidative stress, and energy metabolism disorders. https://doi.org/10.1289/EHP11139.

Automated Prediction of Early Recurrence in Advanced Sinonasal Squamous Cell Carcinoma With Deep Learning and Multi-parametric MRI-based Radiomics Nomogram.

RATIONALE AND OBJECTIVES: Preoperative prediction of the recurrence risk in patients with advanced sinonasal squamous cell carcinoma (SNSCC) is critical for individualized treatment. To evaluate the predictive ability of radiomics signature (RS) based on deep learning and multiparametric MRI for the risk of 2-year recurrence in advanced SNSCC. MATERIALS AND METHODS: Preoperative MRI datasets were retrospectively collected from 265 SNSCC patients (145 recurrences) who underwent preoperative MRI, including T2-weighted (T2W), contrast-enhanced T1-weighted (T1c) sequences and diffusion-weighted (DW). All patients were divided into 165 training cohort and 70 test cohort. A deep learning segmentation model based on VB-Net was used to segment regions of interest (ROIs) for preoperative MRI and radiomics features were extracted from automatically segmented ROIs. Least absolute shrinkage and selection operator (LASSO) and logistic regression (LR) were applied for feature selection and radiomics score construction. Combined with meaningful clinicopathological predictors, a nomogram was developed and its performance was evaluated. In addition, X-title software was used to divide patients into high-risk or low-risk early relapse (ER) subgroups. Recurrence-free survival probability (RFS) was assessed for each subgroup. RESULTS: The radiomics score, T stage, histological grade and Ki-67 predictors were independent predictors. The segmentation models of T2WI, T1c, and apparent diffusion coefficient (ADC) sequences achieved Dice coefficients of 0.720, 0.727, and 0.756, respectively, in the test cohort. RS-T2, RS-T1c and RS-ADC were derived from single-parameter MRI. RS-Combined (combined with T2WI, T1c, and ADC features) was derived from multiparametric MRI and reached area under curve (AUC) and accuracy of 0.854 (0.749-0.927) and 74.3% (0.624-0.840), respectively, in the test cohort. The calibration curve and decision curve analysis (DCA) illustrate its value in clinical practice. Kaplan-Meier analysis showed that the 2-year RFS rate for low-risk patients was significantly greater than that for high-risk patients in both the training and testing cohorts (p < 0.001). CONCLUSION: Automated nomograms based on multi-sequence MRI help to predict ER in SNSCC patients preoperatively.

Impact of Antibiotic Exposure Before Immune Checkpoint Inhibitor Treatment on Overall Survival in Older Adults With Cancer: A Population-Based Study.

PURPOSE: Antibiotic exposure before immune checkpoint inhibitor (ICI) treatment can negatively affect outcomes through alteration in the gut microbiome, but large-scale evaluations are lacking. We performed a population-level retrospective cohort study to evaluate the impact of antibiotic exposure before starting ICI on overall survival (OS). PATIENT AND METHODS: Patients with cancer, age 65 years or older, who initiated treatment with ICIs between June 2012 and October 2018 in Ontario, Canada, were identified using systemic therapy administration data. The cohort was deterministically linked to other health care databases to obtain covariates and antibiotic prescription claim data at both 1 year and 60 days before ICI therapy. Multivariable Cox models evaluated the association between exposure and OS. RESULTS: Among the 2,737 patients with cancer who received ICIs, 59% and 19% of patients received antibiotics 1 year and 60 days before ICI therapy, respectively. Median OS was 306 days. Any antibiotic exposure within 1 year before ICI was associated with worse OS (adjusted hazard ratio [aHR], 1.12; 95% CI, 1.12 to 1.23; P = .03). In antibiotic class analysis, exposure to fluoroquinolones within 1 year (aHR, 1.26; 95% CI, 1.13 to 1.40; P < .001) or 60 days before ICI (aHR, 1.20; 95% CI, 0.99 to 1.45; P = .06) was associated with worse OS, with a dose effect seen on the basis of total weeks of exposure over 1 year (aHR, 1.07 per week; 95% CI, 1.03 to 1.11; P < .001) and 60 days (aHR, 1.12 per week; 95% CI, 1.03 to 1.23; P = .01). CONCLUSION: In this population-level study, exposure to antibiotics and specifically fluoroquinolones before ICI therapy was observed to be associated with worse OS among older adults with cancer. Interventions aimed at altering the gut microbiome to boost immunogenicity may help improve outcomes for patients receiving ICIs with prior antibiotic exposure.

ANGPTL4 inhibits granulosa cell proliferation in polycystic ovary syndrome by EGFR/JAK1/STAT3-mediated induction of p21.

Polycystic ovary syndrome (PCOS) is one of the most common, heterogenous endocrine disorders and is the leading cause of ovulatory obstacle associated with abnormal folliculogenesis. Dysfunction of ovarian granulosa cells (GCs) is recognized as a major factor that underlies abnormal follicle maturation. Angiopoietin-like 4 (ANGPTL4) expression in GCs differs between patients with and without PCOS. However, the role and mechanism of ANGPTL4 in impaired follicular development are still poorly understood. Here, the case-control study was designed to investigate the predictive value of ANGPTL4 in PCOS while cell experiments in vitro were set for mechanism research. Results found that ANGPTL4 levels in serum and in follicular fluid, and its expression in GCs, were upregulated in patients with PCOS. In KGN and SVOG cells, upregulation of ANGPTL4 inhibited the proliferation of GCs by blocking G1/S cell cycle progression, as well as the molecular activation of the EGFR/JAK1/STAT3 cascade. Moreover, the STAT3-dependent CDKN1A(p21) promoter increased CDKN1A transcription, resulting in remarkable suppression effect on GCs. Together, our results demonstrated that overexpression of ANGPTL4 inhibited the proliferation of GCs through EGFR/JAK1/STAT3-mediated induction of p21, thus providing a novel epigenetic mechanism for the pathogenesis of PCOS.

Risk factors for clinical pregnancy loss after IVF in women with PCOS.

RESEARCH QUESTION: Which factors are associated with the risk of clinical pregnancy loss in women with polycystic ovary syndrome (PCOS) undergoing IVF? DESIGN: Case-control study nested in a multicentre randomized trial comparing live birth rates between fresh and frozen embryo transfer in women with PCOS. Women with the outcome of clinical pregnancy loss were selected as the case group, those with live birth as the control group. Parameters before IVF treatment and variables during ovarian stimulation and embryo transfer were compared. RESULTS: Women with clinical pregnancy loss had higher maternal body mass index (BMI, P = 0.010), anti-Müllerian hormone (AMH, P = 0.032), 2-h glucose concentration after 75 g oral glucose tolerance test (OGTT, P = 0.025), and a higher proportion of fresh embryo transfers (P = 0.001). There were significant interactions between the types of transfer and antral follicle count (AFC, P = 0.013), 2-h glucose concentration after OGTT (P = 0.024) on clinical pregnancy loss in PCOS, indicating that these factors may have different effects on pregnancy loss after fresh versus frozen embryo transfer. When the multivariable logistic regression analysis was stratified by the fresh or frozen embryo transfer, AFC (adjusted odds ratio [aOR] 1.03, 95% confidence interval [CI] 1.01-1.05) was a risk factor for clinical pregnancy loss after fresh embryo transfer, while 2-hour glucose concentration after OGTT (aOR 1.13, 95% CI 1.01-1.25) was associated with clinical pregnancy loss in frozen embryo transfer (FET) cycles. CONCLUSIONS: In women with PCOS, fresh embryo transfer, higher BMI, AFC and 2-h glucose concentration after OGTT were risk factors for clinical pregnancy loss. FET may be a better choice to decrease the risk of clinical pregnancy loss, especially for those with higher AFC. During FET, 2-h glucose after OGTT appears to be associated with clinical pregnancy loss and warrants close monitoring.