Publications by authors named "Jiani Hu"

190 Publications

Immune modulating activity of the CHK1 inhibitor prexasertib and anti-PD-L1 antibody LY3300054 in patients with high-grade serous ovarian cancer and other solid tumors.

Cancer Immunol Immunother 2021 Mar 20. Epub 2021 Mar 20.

Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, USA.

Background: Checkpoint kinase 1 (CHK1) has dual roles in both the DNA damage response and in the innate immune response to genotoxic stress. The combination of CHK1 inhibition and immune checkpoint blockade has the potential to enhance anti-tumoral T-cell activation.

Methods: This was an open-label phase 1 study evaluating the CHK1 inhibitor prexasertib and the anti-PD-L1 antibody LY3300054. After a lead-in of LY3300054 (Arm A), prexasertib (Arm B) or the combination (Arm C), both agents were administered intravenously at their respective recommended phase 2 doses (RP2Ds) on days 1 and 15 of a 28-day cycle. Flow cytometry of peripheral blood was performed before and during treatment to analyze effects on immune cell populations, with a focus on T cell subsets and activation. Plasma cytokines and chemokines were analyzed using the Luminex platform.

Results: Among seventeen patients enrolled, the combination was tolerable at the monotherapy RP2Ds, 105 mg/m prexasertib and 700 mg LY3300054. Dose-limiting toxicities included one episode each of febrile neutropenia (Arm C) and grade 4 neutropenia lasting > 5 days (Arm B). One patient had immune-related AST/ALT elevation after 12 cycles. Three patients with CCNE1-amplified, high-grade serous ovarian cancer (HGSOC) achieved partial response (PR), 2 lasting > 12 months; a fourth such patient maintained stable disease > 12 months. Analysis of peripheral blood demonstrated evidence of CD8 + T-cell activation in response to treatment.

Conclusions: Prexasertib in combination with PD-L1 blockade was tolerable and demonstrated preliminary activity in CCNE1-amplified HGSOC with evidence of cytotoxic T-cell activation in patient blood samples.

Trial Registration: ClinicalTrials.gov identifier: NCT03495323. Registered April 12, 2018.
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http://dx.doi.org/10.1007/s00262-021-02910-xDOI Listing
March 2021

Early cardiac involvement in patients with acute COVID-19 infection identified by multiparametric cardiovascular magnetic resonance imaging.

Eur Heart J Cardiovasc Imaging 2021 Mar 4. Epub 2021 Mar 4.

Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Aims: In order to determine acute cardiac involvement in patients with COVID-19, we quantitatively evaluated tissue characteristics and mechanics by non-invasive cardiac magnetic resonance (CMR) in a cohort of patients within the first 10 days of the onset of COVID symptoms.

Methods And Results: Twenty-five patients with reverse transcription polymerase chain reaction confirmed COVID-19 and at least one marker of cardiac involvement [cardiac symptoms, abnormal electrocardiograph (ECG), or abnormal cardiac biomarkers] and 25 healthy age- and gender-matched control subjects were recruited to the study. Patients were divided into those with elevated (n = 8) or normal TnI (n = 17). There were significant differences in global longitudinal strain among patients who were positive and negative for hs-TnI, and controls [-12.3 (-13.3, -11.5)%, -13.1 (-14.2, -9.8)%, and -15.7 (-18.3, -12.7)%, P = 0.004]. Native myocardial T1 relaxation times in patients with positive and negative hs-TnI manifestation (1169.8 ± 12.9 and 1113.2 ± 31.2 ms) were significantly higher than the normal (1065 ± 57 ms) subjects, respectively (P < 0.001). The extracellular volume (ECV) of patients who were positive and negative for hs-TnI was higher than that of the normal controls [32 (31, 33)%, 29 (27, 30)%, and 26 (24, 27.5)%, P < 0.001]. In our study, quantitative T2 mapping in patients who were positive and negative for hs-TnI [51 (47.9, 52.8) and 48 (47, 49.4) ms] was significantly higher than the normal [42 (41, 45.2) ms] subjects (P < 0.001).

Conclusion: In patients with early-stage COVID-19, myocardial oedema, and functional abnormalities are a frequent finding, while irreversible regional injury such as necrosis may be infrequent.
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http://dx.doi.org/10.1093/ehjci/jeab042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989521PMC
March 2021

Fangchinoline exerts anticancer effects on colorectal cancer by inducing autophagy via regulation AMPK/mTOR/ULK1 pathway.

Biochem Pharmacol 2021 Feb 18;186:114475. Epub 2021 Feb 18.

Institute of Tissue Engineering and Stem Cells, Cancer Biotherapy Key Laboratory of Nanchong Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong 637000, China. Electronic address:

Autophagy has become a promising target for cancer therapy. Fangchinoline (Fan) has been shown to exert anticancer effects in some types of cancers. However, the anticancer effects on colorectal cancer (CRC) and the underlying mechanisms have never been elucidated. More specifically, regulation of autophagy in CRC by Fan has never been reported before. In the present study, Fan was found to induce apoptosis and autophagic flux in the CRC cell lines HT29 and HCT116, which was reflected by the enhanced levels of LC3-II protein and p62 degradation, and the increased formation of autophagosomes and puncta formation by LC3-II. Meanwhile, combination with the early-stage autophagy inhibitor 3-methyladenine (3-MA) but not the late-stage autophagy inhibitor chloroquine (CQ) further increased Fan-induced cell death, which suggested the cytoprotective function of autophagy induced by Fan in both HT29 and HCT116 cells. Moreover, Fan treatment demonstrated a dose- and time-dependently increase in the phosphorylation of AMPK and decrease in the phosphorylation of mammalian target of rapamycin (mTOR) and ULK1, leading to the activation of the AMPK/mTOR/ULK1 signaling pathway. Furthermore, in the HT29 xenograft model, Fan inhibited tumor growth in vivo. These results indicate that Fan inhibited CRC cell growth both in vitro and in vivo and revealed a new molecular mechanism involved in the anticancer effect of Fan on CRC, suggesting that Fan is a potent autophagy inducer and might be a promising anticancer agent.
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http://dx.doi.org/10.1016/j.bcp.2021.114475DOI Listing
February 2021

Texture Analysis of Native T1 Images as a Novel Method for Noninvasive Assessment of Uremic Cardiomyopathy.

J Magn Reson Imaging 2021 Feb 18. Epub 2021 Feb 18.

Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Noncontrast cardiac T times are increased in dialysis patients which might indicate fibrotic alterations in uremic cardiomyopathy.

Purpose: To explore the application of the texture analysis (TA) of T images in the assessment of myocardial alterations in dialysis patients.

Study Type: Case-control study.

Population: A total of 117 subjects, including 22 on hemodialysis, 44 on peritoneal dialysis, and 51 healthy controls.

Field Strength: A 3 T, steady-state free precession (SSFP) sequence, modified Look-Locker imaging (MOLLI).

Assessment: Two independent, blinded researchers manually delineated endocardial and epicardial borders of the left ventricle (LV) on midventricular T maps for TA.

Statistical Tests: Texture feature selection was performed, incorporating reproducibility verification, machine learning, and collinearity analysis. Multivariate linear regressions were performed to examine the independent associations between the selected texture features and left ventricular function in dialysis patients. Texture features' performance in discrimination was evaluated by sensitivity and specificity. Reproducibility was estimated by the intraclass correlation coefficient (ICC).

Results: Dialysis patients had greater T values than normal (P < 0.05). Five texture features were filtered out through feature selection, and four showed a statistically significant difference between dialysis patients and healthy controls. Among the four features, vertical run-length nonuniformity (VRLN) had the most remarkable difference among the control and dialysis groups (144 ± 40 vs. 257 ± 74, P < 0.05), which overlap was much smaller than Global T times (1268 ± 38 vs. 1308 ± 46 msec, P < 0.05). The VRLN values were notably elevated (cutoff = 170) in dialysis patients, with a specificity of 97% and a sensitivity of 88%, compared with T times (specificity = 76%, sensitivity = 60%). In dialysis patients, VRLN was significantly and independently associated with left ventricular ejection fraction (P < 0.05), global longitudinal strain (P < 0.05), radial strain (P < 0.05), and circumferential strain (P < 0.05); however, T was not.

Data Conclusion: The texture features obtained by TA of T images and VRLN may be a better parameter for assessing myocardial alterations than T times.

Level Of Evidence: 4 TECHNICAL EFFICACY: Stage 3.
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http://dx.doi.org/10.1002/jmri.27529DOI Listing
February 2021

SFace: Sigmoid-Constrained Hypersphere Loss for Robust Face Recognition.

IEEE Trans Image Process 2021 5;30:2587-2598. Epub 2021 Feb 5.

Deep face recognition has achieved great success due to large-scale training databases and rapidly developing loss functions. The existing algorithms devote to realizing an ideal idea: minimizing the intra-class distance and maximizing the inter-class distance. However, they may neglect that there are also low quality training images which should not be optimized in this strict way. Considering the imperfection of training databases, we propose that intra-class and inter-class objectives can be optimized in a moderate way to mitigate overfitting problem, and further propose a novel loss function, named sigmoid-constrained hypersphere loss (SFace). Specifically, SFace imposes intra-class and inter-class constraints on a hypersphere manifold, which are controlled by two sigmoid gradient re-scale functions respectively. The sigmoid curves precisely re-scale the intra-class and inter-class gradients so that training samples can be optimized to some degree. Therefore, SFace can make a better balance between decreasing the intra-class distances for clean examples and preventing overfitting to the label noise, and contributes more robust deep face recognition models. Extensive experiments of models trained on CASIA-WebFace, VGGFace2, and MS-Celeb-1M databases, and evaluated on several face recognition benchmarks, such as LFW, MegaFace and IJB-C databases, have demonstrated the superiority of SFace.
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http://dx.doi.org/10.1109/TIP.2020.3048632DOI Listing
February 2021

Perceptions of patients with early stage breast cancer toward research biopsies.

Cancer 2020 Dec 15. Epub 2020 Dec 15.

Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Background: The objective of this study was to describe the perspective of patients with early breast cancer toward research biopsies. The authors hypothesized that more patients at academic sites than at community-based sites would be willing to consider these procedures.

Methods: In total, 198 patients with early stage breast cancer were recruited from 3 academic centers (n = 102) and from 1 community oncology practice (n = 96). The primary objective was to compare the proportion of patients willing to consider donating excess tissue biospecimens from surgery, from a clinically indicated breast biopsy, or from a research purposes-only biopsy (RPOB) between practice types.

Results: Most patients (93% at academic sites, 94% at the community oncology site) said they would consider donating excess tissue from surgery for research. One-half of patients from academic or community sites would consider donating tissue from a clinically indicated breast biopsy. On univariate analysis, significantly fewer patients from academic sites would consider an RPOB (22% at academic sites, 42% at the community site; P = .003); however, this difference was no longer significant on multivariate analysis (P = .96). Longer transportation times and unfavorable prior experiences were associated with less willingness to consider an RPOB on multivariate analysis. Significantly fewer patients from academic sites (14%) than from the community site (35%) would consider a research biopsy in a clinical trial (P = .04). Contributing to scientific knowledge, return of results, and a personal request by their physician were the strongest factors influencing patients' willingness to undergo research biopsies.

Conclusions: The current results rejected the hypothesis that more patients with early breast cancer at academic sites would be willing to donate tissue biospecimens for research compared with those at community oncology sites. These findings identify modifiable factors to consider in biobanking studies and clinical trials.
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http://dx.doi.org/10.1002/cncr.33371DOI Listing
December 2020

Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases.

Breast Cancer Res 2020 11 30;22(1):131. Epub 2020 Nov 30.

Dana-Farber Cancer Institute, Dana-Farber/Brigham & Women's Cancer Center, 450 Brookline Avenue, Boston, MA, 02215, USA.

Background: We aimed to examine the safety and efficacy of bevacizumab and carboplatin in patients with breast cancer brain metastases.

Methods: We enrolled patients with breast cancer and > 1 measurable new or progressive brain metastasis. Patients received bevacizumab 15 mg/kg intravenously (IV) on cycle 1 day 1 and carboplatin IV AUC = 5 on cycle 1 day 8. Patients with HER2-positive disease also received trastuzumab. In subsequent cycles, all drugs were administered on day 1 of each cycle. Contrast-enhanced brain MRI was performed at baseline, 24-96 h after the first bevacizumab dose (day + 1), and every 2 cycles. The primary endpoint was objective response rate in the central nervous system (CNS ORR) by composite criteria. Associations between germline VEGF single nucleotide polymorphisms (rs699947, rs2019063, rs1570360, rs833061) and progression-free survival (PFS) and overall survival (OS) were explored, as were associations between early (day + 1) MRI changes and outcomes.

Results: Thirty-eight patients were enrolled (29 HER2-positive, 9 HER2-negative); all were evaluable for response. The CNS ORR was 63% (95% CI, 46-78). Median PFS was 5.62 months and median OS was 14.10 months. As compared with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, patients with ECOG PS 1-2 had significantly worse PFS and OS (all P < 0.01). No significant associations between VEGF genotypes or early MRI changes and clinical outcomes were observed.

Conclusions: The combination of bevacizumab and carboplatin results in a high rate of durable objective response in patients with brain metastases from breast cancer. This regimen warrants further investigation.

Trial Registration: NCT01004172 . Registered 28 October 2009.
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http://dx.doi.org/10.1186/s13058-020-01372-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706261PMC
November 2020

Methods for separating microplastics from complex solid matrices: Comparative analysis.

J Hazard Mater 2021 May 20;409:124640. Epub 2020 Nov 20.

School of Ecological and Environmental Sciences, Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, East China Normal University, Shanghai 200241, China.

Microplastics (MPs) are widely found in complex solid matrices such as soil, sediments and sludge. The separation procedure is crucial for effective analysis of MPs, but existing methods varied among studies. Here, we systematically summarize and compare separation methods including density, oil, electrostatic, magnetic, and solvent extraction separation. Density separation is the most commonly used approach, but time-consuming and discharging hazardous materials dependent on extraction solutions. In contrast, oil, electrostatic, magnetic separation and solvent extraction separation are emerging approaches with advantages of low-cost, quick, or environmentally-friendly, but with high request of instruments. Despite variation among these approaches, the separation efficiency is closely related to characteristics of MPs including polymer types, sizes and shapes. The treatment of digestion and fluorescence staining can facilitate the detection of MPs. This analysis suggests that further optimization and improvement of existing approaches can facilitate the development of new separation technology for assaying MPs in complex environmental matrices.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124640DOI Listing
May 2021

A mathematical model for predicting intracranial pressure based on noninvasively acquired PC-MRI parameters in communicating hydrocephalus.

J Clin Monit Comput 2020 Oct 1. Epub 2020 Oct 1.

Cardiovascular Research Centre, Royal Brompton Hospital, London, SW3 6NP, UK.

To develop and validate a mathematical model for predicting intracranial pressure (ICP) noninvasively using phase-contrast cine MRI (PC-MRI). We performed a retrospective analysis of PC-MRI from patients with communicating hydrocephalus (n = 138). The patients were recruited from Shenzhen Second People's Hospital between November 2017 and April 2020, and randomly allocated into training (n = 97) and independent validation (n = 41) groups. All participants underwent lumbar puncture and PC-MRI in order to evaluate ICP and cerebrospinal fluid (CSF) parameters (i.e., aqueduct diameter and flow velocity), respectively. A novel ICP-predicting model was then developed based on the nonlinear relationships between the CSF parameters, using the Levenberg-Marquardt and general global optimisation methods. There was no significant difference in baseline demographic characteristics between the training and independent validation groups. The accuracy of the model for predicting ICP was 0.899 in the training cohort (n = 97) and 0.861 in the independent validation cohort (n = 41). We obtained an ICP-predicting model that showed excellent performance in the noninvasive diagnosis of clinically significant communicating hydrocephalus.
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http://dx.doi.org/10.1007/s10877-020-00598-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528454PMC
October 2020

Noninvasive evaluation of early diabetic nephropathy using diffusion kurtosis imaging: an experimental study.

Eur Radiol 2021 Apr 30;31(4):2281-2288. Epub 2020 Sep 30.

Department of Pathology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.

Objectives: To evaluate the value of renal diffusion kurtosis imaging (DKI) in the diagnosis of early diabetic nephropathy (DN) in a rat model.

Materials And Methods: Forty male Zucker diabetic fatty rats that spontaneously developed type 2 diabetes mellitus (DM) and 20 age-matched nondiabetic lean Zucker rats were included. Renal DKI scans and histological examinations were performed on the rats in batches at the end of the 4th, 8th, 12th, 16th, and 20th week after DM model was built. Based on renal histopathological appearance, included animals were divided into three groups: a nondiabetic control group, a DM group without DN, and an early DN group. Mean kurtosis (MK) and mean diffusivity (MD) values of renal cortex and medulla were analyzed statistically.

Results: MK values of renal cortex and medulla tended to increase from the control group to the early DN group, respectively, while MD values tended to decrease. The cutoff MD and MK values of renal cortex and medulla showed different values in discriminating early DN from controls. Among them, cutoff MK value of medulla of 0.62 was the best parameter (sensitivity, 93.9%; specificity, 96.4%; and area under the curve, 0.95). For discriminate early DN from DM without DN and DM without DN from controls, cutoff MK value of renal cortex or medulla achieved an area under the curve of 0.76-0.85.

Conclusions: MR DKI may be valuable for the noninvasive detection of early DN, and MK value might serve as a more sensitive biomarker of early DN than MD value.

Key Points: • In this article, diffusion kurtosis imaging (DKI) was used to detect the changes in the kidneys due to early diabetic nephropathy (DN). • MR DKI may be valuable for the noninvasive detection of early DN. • The mean kurtosis values of renal cortex and medulla might serve as a more sensitive biomarker of early DN than the mean diffusivity values.
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http://dx.doi.org/10.1007/s00330-020-07322-6DOI Listing
April 2021

Diagnostic Utility of the Simplified Perfusion Fraction for Identifying Myocardial Injury in Patients With Reperfused ST-segment Elevation Myocardial Infarction.

J Magn Reson Imaging 2021 02 25;53(2):516-526. Epub 2020 Aug 25.

Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Acute myocardial infarction (AMI) is a disease with high morbidity and mortality worldwide and the evaluation of myocardial injury and perfusion status following myocardial ischemia and reperfusion is of clinical value.

Purpose: To assess the diagnostic utility of simplified perfusion fraction (SPF) in differentiating salvage and infarcted myocardium and its predictive value for left ventricular remodeling in patients with reperfusion ST-segment elevation myocardial infarction (STEMI).

Study Type: Prospective.

Population: Forty-one reperfused STEMI patients and 20 healthy volunteers.

Field Strength/sequence: 3.0T MRI. The MR examination included cine, T -short tau inversion recovery (T -STIR), first pass perfusiong (FPP),phase sensitive inversion recovery (PSIR), and diffusion-weighted imaging (DWI).

Assessment: SPF values among different myocardium regions (infarcted, salvaged, remote, and MVO) and stages of reperfused STEMI patients as well as normal controls were measured. The diagnostic utility of SPF values in differentiating salvaged and infarcted myocardium was assessed.

Statistical Analysis: Independent t-test and the Mann-Whitney U-test. Logistic regression.

Results: SPF values in healthy controls were not significantly different than SPF values in the remote myocardium of patients (40.09 ± 1.47% vs. 40.28 ± 1.93%, P = 0.698). In reperfusion STEMI patients, SPF values were lower in infarcted myocardium compared to remote and salvaged myocardium (32.15 ± 2.36% vs. 40.28 ± 1.93%, P < 0.001; 32.15 ± 2.36% vs. 36.68 ± 2.71%, P < 0.001). SPF values of infarcted myocardium showed a rebound increase from acute to convalescent stages (32.15 ± 2.36% vs. 34.69 ± 3.69%, P < 0.001). When differentiating infarcted and salvaged myocardium, SPF values demonstrated an area under the curve (AUC) of 0.89 (sensitivity 85.4%, specificity 80.5%, cutoff 34.42%). Lower SPF values were associated with lower odds ratio (OR = 0.304) of left ventricular remodeling after adjusting for potential confounders with a confidence interval (CI) of 0.129-0.717, P = 0.007.

Data Conclusion: SPF might be able to differentiate salvaged and infarcted myocardium and is a strong predictor of left ventricular remodeling in reperfused STEMI patients. Level of Evidence 2 Technical Efficacy Stage 2.
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http://dx.doi.org/10.1002/jmri.27310DOI Listing
February 2021

Myocardial extracellular volume fraction radiomics analysis for differentiation of reversible versus irreversible myocardial damage and prediction of left ventricular adverse remodeling after ST-elevation myocardial infarction.

Eur Radiol 2021 Jan 12;31(1):504-514. Epub 2020 Aug 12.

Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 PuJian Road, Shanghai, 200127, People's Republic of China.

Objectives: Our study sought to explore the prognostic value of radiomic TA (texture analysis) on quantitative ECV (extracellular volume) fraction mapping to differentiate between reversible and irreversible myocardial damage and to predict left ventricular adverse remodeling in patients with reperfused STEMI (ST-elevation myocardial infarction).

Methods: This observational prospective cohort study identified 70 patients (62 ± 9 years, 62 men [85.70%]) with STEMI for TA who consecutively performed native and contrast T1 mapping. Texture features were extracted from each stack of ECV mapping based on ROI (region of interest) analysis.

Results: After texture feature selection and dimension reduction, five selected texture features were found to be statistically significant for differentiating the extent of myocardial injury. ROC (receiver operating characteristic) curve analysis for the differentiation of unsalvageable infarction and salvageable myocardium demonstrated a significantly higher AUC (area under the curve) (0.91 [95% CI, 0.86-0.96], p < 0.0001) for horizontal fraction than other texture features (p < 0.05). LVAR (left ventricular adverse remodeling) was predicted by those selected features. The differences in qualitative and quantitative baseline parameters and horizontal fractions were significant between the patients with and without LVAR. LGE (late gadolinium enhancement) and horizontal fraction features of infarcted myocardium in acute STEMI were the only two parameters selected in forming the optimal overall multivariable model for LVAR at 6 months.

Conclusions: Radiomic analysis of ECV could discriminate reversible from irreversible myocardial injury after STEMI. LGE as well as radiomics TA (texture analysis) of ECV may provide an alternative to predict LVAR and functional recovery.

Key Points: • ECV quantification was able to differentiate between infarcted myocardium and non-infarcted myocardium. • Radiomics analysis of ECV could discriminate reversible from irreversible myocardial injury. • Radiomics TA analysis shows a promising similarity with LGE findings which could aid the prognosis of myocardial infarction patients.
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http://dx.doi.org/10.1007/s00330-020-07117-9DOI Listing
January 2021

Biodegradation and disintegration of expanded polystyrene by land snails Achatina fulica.

Sci Total Environ 2020 Dec 28;746:141289. Epub 2020 Jul 28.

School of Ecological and Environmental Sciences, Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, East China Normal University, Shanghai 200241, China; Shanghai Engineering Research Center of Biotransformation of Organic Solid Waste, East China Normal University, Shanghai 200241, China; Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, East China Normal University, Shanghai 200241, China. Electronic address:

Despite increasing evidence of widespread plastic pollution in soil, it remains largely unknown about the fate of plastic influenced by soil animals. In this study, ingestion and biodegradation capability of expanded polystyrene (PS) foam was investigated in a globally distributed soil invertebrate, Achatina fulica. After 4-week exposure, 18.5 ± 2.9 mg polystyrene was ingested per snail, and egested microplastics (1.343 ± 0.625 mm) in feces with significant mass loss of mean 30.7%. Gel permeation chromatography analysis indicated a significant increase in weight-average molecular weight (M) and number-average molecular weight (M) of feces-residual PS, indicating limited extent depolymerization. Fourier transform infrared spectroscopy and proton nuclear magnetic resonance confirmed the formation of functional groups of oxidized intermediates. Suppression of gut microbes with oxytetracycline did not affect the depolymerization, indicating the independence of gut microbes. High-throughput sequencing analysis revealed significant shifts in the gut microbiome after ingestion of PS, with an increase of family Enterobacteriaceae, Sphingobacteriaceae, and Aeromonadaceae, suggesting that gut microorganisms were associated with PS biodegradation. These findings suggest that plastic litter can be disintegrated into microplastics and partially biodegraded by A. fulica, which highlights the significance of soil animals for the fate of plastic and its biodegradation in soil environments.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141289DOI Listing
December 2020

A radiomics model of liver CT to predict risk of hepatic encephalopathy secondary to hepatitis B related cirrhosis.

Eur J Radiol 2020 Sep 26;130:109201. Epub 2020 Jul 26.

Department of Radiology, Wayne State University, Detroit, MI, USA.

Purpose: To build a radiomics model of liver contrast-enhanced computed tomography (CT) to predict hepatic encephalopathy secondary to Hepatitis B related cirrhosis.

Materials And Methods: This study consisted of 304 consecutive patients with first-diagnosed hepatitis B related cirrhosis. 212 and 92 patients were randomly computer-generated into training and testing cohorts, among which 38 and 21 patients endured HE, respectively. 356 radiomics features of liver were extracted from portal venous-phase CT data, and 3 clinical features were collected from medical record. After data were standardized by Z-score, we used least absolute shrinkage and selection operator to choose useful radiomics features. Ultimately, three predictive models including a radiomics model, a clinical model and an integrated model of radiomics and clinical features were built by analysis of R-software. Predictive performance was tested by multivariable logistic regression, and evaluated by area under receiver-operating characteristic curve (AUC), and accuracy.

Results: 19 radiomics features of liver CT were selected. The selected radiomics features and 3 relevant clinical features were applied to develop a radiomics model, a clinical model, and an integrated model of both radiomics and clinical features. The integrated model showed better performance than the radiomics model or clinical model to predict HE (AUC = 0.94 vs. 0.91 or 0.76, and 0.87 vs. 0.86 or 0.73; accuracy = 0.93 vs. 0.89 or 0.83, and 0.83 vs. 0.84 or 0.77) in the training and testing cohorts, respectively.

Conclusion: The integrated model of radiomics and clinical features could well predict HE secondary to hepatitis B related cirrhosis.
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http://dx.doi.org/10.1016/j.ejrad.2020.109201DOI Listing
September 2020

Subvoxel vascular imaging of the midbrain using USPIO-Enhanced MRI.

Neuroimage 2020 10 29;220:117106. Epub 2020 Jun 29.

Department of Radiology, Wayne State University, Detroit, MI, USA; Magnetic Resonance Innovations, Inc., Bingham Farms, MI, USA. Electronic address:

There is an urgent need for better detection and understanding of vascular abnormalities at the micro-level, where critical vascular nourishment and cellular metabolic changes occur. This is especially the case for structures such as the midbrain where both the feeding and draining vessels are quite small. Being able to monitor and diagnose vascular changes earlier will aid in better understanding the etiology of the disease and in the development of therapeutics. In this work, thirteen healthy volunteers were scanned with a dual echo susceptibility weighted imaging (SWI) sequence, with a resolution of 0.22 ​× ​0.44 ​× ​1 ​mm at 3T. Ultra-small superparamagnetic iron oxides (USPIO) were used to induce an increase in susceptibility in both arteries and veins. Although the increased vascular susceptibility enhances the visibility of small subvoxel vessels, the accompanying strong signal loss of the large vessels deteriorates the local tissue contrast. To overcome this problem, the SWI data were acquired at different time points during a gradual administration (final concentration ​= ​4 ​mg/kg) of the USPIO agent, Ferumoxytol, and the data was processed to combine the SWI data dynamically, in order to see through these blooming artifacts. The major vessels and their tributaries (such as the collicular artery, peduncular artery, peduncular vein and the lateral mesencephalic vein) were identified on the combined SWI data using arterio-venous maps. Dynamically combined SWI data was then compared with previous histological work to validate that this protocol was able to detect small vessels on the order of 50 ​μm-100 ​μm. A complex division-based phase unwrapping was also employed to improve the quality of quantitative susceptibility maps by reducing the artifacts due to aliased voxels at the vessel boundaries. The smallest detectable vessel size was then evaluated by revisiting numerical simulations, using estimated true susceptibilities for the basal vein and the posterior cerebral artery in the presence of Ferumoxytol. These simulations suggest that vessels as small as 50 ​μm should be visible with the maximum dose of 4 ​mg/kg.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117106DOI Listing
October 2020

Barriers to Clinical Trial Accrual: Perspectives of Community-Based Providers.

Clin Breast Cancer 2020 10 7;20(5):395-401.e3. Epub 2020 May 7.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. Electronic address:

Background: Only a small proportion of patients with cancer enroll onto clinical trials. Previous studies have explored patient-related barriers to trial participation; however, few studies have focused on the provider perspective. We aimed to describe referral practices and barriers to referrals of patients with breast cancer for clinical trials, including the utilization of web-based trial-matching tools.

Materials And Methods: In 2016, we distributed 120 surveys to attendees of a breast oncology continuing medical education course. The survey addressed referral patterns, trial knowledge, and perceptions of web-based trial-matching tools. After survey completion, participants were provided a link to the Dana-Farber Cancer Institute trial-matching tool. Three months later, a follow-up survey was sent to assess their use of this tool. Descriptive statistics were used to summarize survey data.

Results: Ninety-six (80%) participants completed the first survey; 5 respondents did not actively treat patients with breast cancer and were excluded. Respondents included medical (30%) and surgical (22%) oncologists, nurse practitioners/physician assistants (26%), and other (22%). Neoadjuvant and metastatic trials were deemed the highest priority. The primary reported barriers included perceived lack of patient interest, lack of trial awareness, and logistical barriers. Emailing trial investigators directly was the preferred method of trial referral. Although 80% indicated that web-based tools would increase trial referrals, our follow-up survey revealed that only 18% of respondents used our web-based tool.

Conclusion: Our respondents valued trial participation for their patients but found it difficult to manage. Further research is needed regarding how to increase the likelihood that patients are presented with appropriate trial options.
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http://dx.doi.org/10.1016/j.clbc.2020.05.001DOI Listing
October 2020

Size-dependent cellular internalization and effects of polystyrene microplastics in microalgae P. helgolandica var. tsingtaoensis and S. quadricauda.

J Hazard Mater 2020 11 4;399:123092. Epub 2020 Jun 4.

School of Ecological and Environmental Sciences, East China Normal University, Shanghai, 200241, China; Shanghai Engineering Research Center of Biotransformation of Organic Solid Waste, East China Normal University, Shanghai, 200241, China; Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, East China Normal University, Shanghai, 200241, China. Electronic address:

Microplastics (MPs) are persistent contaminants in aquatic environments. Microalgae, as the main phytoplankton and primary producers, usually co-exist with MPs. Despite previous studies that have proved the interaction of MPs and microalgae, it is largely unknown whether MPs can be uptake into cells of microalgae. In this study, both marine P. helgolandica var. tsingtaoensis and freshwater microalgae S. quadricauda were respectively exposed to 10 mg/L polystyrene microbeads with five diameter sizes: 1.0, 2.0, 3.0, 4.0, and 5.0 μm. Confocal laser scanning and 3D image analysis showed that mean 24.0 % or 11.3 % cells of P. helgolandica var. tsingtaoensis contained 1.0 μm or 2.0 μm MPs after 72 h exposure. While mean 43.3 % or 15.3 % of S. quadricauda individuals engulfed 1.0 μm or 2.0 μm MPs within cells. But, none of 3.0-5.0 μm MPs were observed within algal cells. These results demonstrate the size-dependent cellular internalization of MPs in microalgae. Exposure to 1.0-2.0 μm PS MPs caused a significant reduction in the density of microalgae and influenced photosynthesis, which suggests cellular internalization of MPs can influence algal fertility and growth. This discovery first confirms cellular internalization of MPs in phytoplankton, of significance for the fate and eco-toxicity of MPs in the aquatic ecosystem.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123092DOI Listing
November 2020

Magnetic Resonance Imaging and Modeling of the Glymphatic System.

Diagnostics (Basel) 2020 May 27;10(6). Epub 2020 May 27.

Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.

The glymphatic system is a newly discovered waste drainage pathway in the brain; it plays an important role in many neurological diseases. Ongoing research utilizing various cerebrospinal fluid tracer infusions, either directly or indirectly into the brain parenchyma, is investigating clearance pathways by using distinct imaging techniques. In the present review, we discuss the role of the glymphatic system in various neurological diseases and efflux pathways of brain waste clearance based on current evidence and controversies. We mainly focus on new magnetic resonance imaging (MRI) modeling techniques, along with traditional computational modeling, for a better understanding of the glymphatic system function. Future sophisticated modeling techniques hold the potential to generate quantitative maps for glymphatic system parameters that could contribute to the diagnosis, monitoring, and prognosis of neurological diseases. The non-invasive nature of MRI may provide a safe and effective way to translate glymphatic system measurements from bench-to-bedside.
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http://dx.doi.org/10.3390/diagnostics10060344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344900PMC
May 2020

A single-center, retrospective study of COVID-19 features in children: a descriptive investigation.

BMC Med 2020 05 6;18(1):123. Epub 2020 May 6.

Imaging Center, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, No.100 Hongkong Road, Wuhan, 430016, China.

Background: Compared to adults, there are relatively few studies on COVID-19 infection in children, and even less focusing on the unique features of COVID-19 in children in terms of laboratory findings, locations of computerized tomography (CT) lesions, and the role of CT in evaluating clinical recovery. The objective of this study is to report the results from patients at Wuhan Children's Hospital, located within the initial center of the outbreak.

Methods: Clinical, imaging, and laboratory data of 76 children were collected retrospectively and analyzed with the Fisher exact test and Cox regression statistical methods.

Results: Among 50 children with a positive COVID-19 real-time reverse-transcriptase polymerase chain reaction (PCR), five had negative PCR results initially but showed positive results in subsequent tests. Eight (16%) patients had lymphopenia, seven (14%) with thrombocytopenia, four (8%) with lymphocytosis, two (4%) with thrombocytosis, ten (20%) with elevated C-reactive protein, four (8%) with hemoglobin above, and six (12%) with below standard reference values. Seven (14%) of the 50 had no radiologic evidence of disease on chest CT. For the 43 patients who had abnormal CT findings, in addition to previously reported patterns of ground-glass opacity (67%), local patchy shadowing (37%), local bilateral patchy shadowing (21%), and lesion location of lower lobes (65%), other CT features include that an overwhelming number of pediatric patients had lesions in the subpleural area (95%) and 22 of the 28 lower lobe lesions were in the posterior segment (78%). Lesions in most of the 15 patients (67%) who received chest CT at discharge were not completely absorbed, and 26% of these pediatric patients had CT lesions that were either unchanged or worse.

Conclusions: There were a few differences between COVID-19 children and COVID-19 adults in terms of laboratory findings and CT characteristics. CT is a powerful tool to detect and characterize COVID-19 pneumonia but has little utility in evaluating clinical recovery for children. These results oppose current COVID-19 hospital discharge criteria in China, as one requirement is that pulmonary imaging must show significant lesion absorption prior to discharge. These differences between pediatric and adult cases of COVID-19 may necessitate pediatric-specific discharge criteria.
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http://dx.doi.org/10.1186/s12916-020-01596-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200209PMC
May 2020

Avoiding Peg-Filgrastim Prophylaxis During the Paclitaxel Portion of the Dose-Dense Doxorubicin-Cyclophosphamide and Paclitaxel Regimen: A Prospective Study.

J Clin Oncol 2020 07 24;38(21):2390-2397. Epub 2020 Apr 24.

Dana-Farber Cancer Institute, Boston, MA.

Purpose: The use of growth factors adds considerable expense and some toxicity to adjuvant breast cancer chemotherapy. We tested the feasibility and safety of omitting routine peg-filgrastim use during the paclitaxel portion of the dose-dense doxorubicin-cyclophosphamide-paclitaxel regimen.

Patients And Methods: This was a prospective, single-arm study in which patients 18 to 65 years of age who completed 4 cycles of dose-dense doxorubicin-cyclophosphamide for stage I-III breast cancer received paclitaxel 175 mg/m every 2 weeks. Peg-filgrastim was administered after paclitaxel only if patients had had febrile neutropenia in a prior cycle or at investigator discretion if patients had infections or treatment delays of > 1 week. Once a patient received peg-filgrastim, it was administered in all future cycles. The primary end point was the rate of paclitaxel completion within 7 weeks from cycle 1 day 1 to cycle 4 day 1. If ≥ 100 out of 125 patients completed 4 cycles of paclitaxel without dose delay, the regimen would be considered feasible.

Results: The enrollment goal of 125 patients was met. Median age was 46 years (range, 21-65 years), and 112 patients (90% [95% CI, 83% to 94%]) completed dose-dense paclitaxel within 7 weeks. Omission of peg-filgrastim was not causally related to noncompletion of paclitaxel in any patients. The most common reasons for dose reduction or delays were nonhematologic. One patient experienced febrile neutropenia but was able to complete paclitaxel on time. Eight patients (6.4%) received peg-filgrastim during the trial. Overall, peg-filgrastim was administered in only 4.3% of paclitaxel cycles.

Conclusion: Omission of routine peg-filgrastim during dose-dense paclitaxel according to a prespecified algorithm seems to be safe and feasible and was associated with a 95.7% reduction in the use of peg-filgrastim relative to the current standard of care.
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http://dx.doi.org/10.1200/JCO.19.02484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367545PMC
July 2020

Discrepancy between FDG-PET/CT and contrast-enhanced CT in the staging of patients with inflammatory breast cancer: implications for treatment planning.

Breast Cancer Res Treat 2020 Jun 21;181(2):383-390. Epub 2020 Apr 21.

Inflammatory Breast Cancer Program, Medical Oncology, Susan F. Smith Center for Women's Cancers, Dana-Farber Cancer Institute, Boston, USA.

Purpose: Optimizing treatment strategies for patients with inflammatory breast cancer (IBC) relies on accurate initial staging. This study compared contrast-enhanced computed tomography (ce-CT) and FDG-PET/CT for initial staging of IBC to determine the frequency of discordance between the two imaging modalities and potential impact on management.

Methods: 81 patients with IBC underwent FDG-PET/CT and ce-CT prior to starting treatment. FDG-PET/CT and ce-CT scans were independently reviewed for locoregional and distant metastases and findings recorded by anatomic site as negative, equivocal, or positive for breast cancer involvement. Each paired ce-CT and FDG-PET/CT case was classified as concordant or discordant for findings. Discordant findings were subclassified as (a) related to the presence or absence of distant metastases; (b) affecting the locoregional radiation therapy plan; or (c) due to incidental findings not related to IBC.

Results: There were 47 discordant findings between ce-CT and FDG-PET/CT in 41 of 81 patients (50.6%). Thirty (63.8%) were related to the presence or absence of distant metastases; most commonly disease detection on FDG-PET/CT but not ce-CT (n = 12). FDG-PET/CT suggested alterations of the locoregional radiation therapy plan designed by CT alone in 15 patients. FDG-PET/CT correctly characterized 5 of 7 findings equivocal for metastatic IBC on ce-CT.

Conclusions: This study demonstrates differences between ce-CT and FDG-PET/CT for initial staging of IBC and how these differences potentially affect patient management. Preliminary data suggest that FDG-PET/CT may be the imaging modality of choice for initial staging of IBC. Prospective trials testing initial staging with FDG-PET/CT versus important clinical end-points in IBC are warranted.
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http://dx.doi.org/10.1007/s10549-020-05631-4DOI Listing
June 2020

The feasibility of differentiating colorectal cancer from normal and inflammatory thickening colon wall using CT texture analysis.

Sci Rep 2020 04 14;10(1):6346. Epub 2020 Apr 14.

Department of Radiology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.

To investigate the diagnostic value of texture analysis (TA) for differentiating between colorectal cancer (CRC), colonic lesions caused by inflammatory bowel disease (IBD), and normal thickened colon wall (NTC) on computed tomography (CT) and assess which scanning phase has the highest differential diagnostic value. In all, 107 patients with CRC, 113 IBD patients with colonic lesions, and 96 participants with NTC were retrospectively enrolled. All subjects underwent multiphase CT examination, including pre-contrast phase (PCP), arterial phase (AP), and portal venous phase (PVP) scans. Based on these images, classification by TA and visual classification by radiologists were performed to discriminate among the three tissue types. The performance of TA and visual classification was compared. Precise TA classification results (error, 2.03-12.48%) were acquired by nonlinear discriminant analysis for CRC, IBD and NTC, regardless of phase or feature selection. PVP images showed a better ability to discriminate the three tissues by comprising the three scanning phases. TA showed significantly better performance in discriminating CRC, IBD and NTC than visual classification for residents, but there was no significant difference in classification between TA and experienced radiologists. TA could provide useful quantitative information for the differentiation of CRC, IBD and NTC on CT, particularly in PVP images.
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http://dx.doi.org/10.1038/s41598-020-62973-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156692PMC
April 2020

The capability of detecting small vessels beyond the conventional MRI sensitivity using iron-based contrast agent enhanced susceptibility weighted imaging.

NMR Biomed 2020 05 11;33(5):e4256. Epub 2020 Feb 11.

Department of Radiology, Wayne State University, Detroit, Michigan.

Imaging brain microvasculature is important in cerebrovascular diseases. However, there is still a lack of non-invasive, non-radiation, and whole-body imaging techniques to investigate them. The aim of this study is to develop an ultra-small superparamagnetic iron oxide (USPIO) enhanced susceptibility weighted imaging (SWI) method for imaging micro-vasculature in both animal (~10 μm in rat) and human brain. We hypothesized that the USPIO-SWI technique could improve the detection sensitivity of the diameter of small subpixel vessels 10-fold compared with conventional MRI methods. Computer simulations were first performed with a double-cylinder digital model to investigate the theoretical basis for this hypothesis. The theoretical results were verified using in vitro phantom studies and in vivo rat MRI studies (n = 6) with corresponding ex vivo histological examinations. Additionally, in vivo human studies (n = 3) were carried out to demonstrate the translational power of the USPIO-SWI method. By directly comparing the small vessel diameters of an in vivo rat using USPIO-SWI with the small vessel diameters of the corresponding histological slide using laser scanning confocal microscopy, 13.3-fold and 19.9-fold increases in SWI apparent diameter were obtained with 5.6 mg Fe/kg and 16.8 mg Fe/kg ferumoxytol, respectively. The USPIO-SWI method exhibited its excellent ability to detect small vessels down to about 10 μm diameter in rat brain. The in vivo human study unveiled hidden arterioles and venules and demonstrated its potential in clinical practice. Theoretical modeling simulations and in vitro phantom studies also confirmed a more than 10-fold increase in the USPIO-SWI apparent diameter compared with the actual small vessel diameter size. It is feasible to use SWI blooming effects induced by USPIO to detect small vessels (down to 10 μm in diameter for rat brain), well beyond the spatial resolution limit of conventional MRI methods. The USPIO-SWI method demonstrates higher potential in cerebrovascular disease investigations.
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http://dx.doi.org/10.1002/nbm.4256DOI Listing
May 2020

A new index for assessing cerebral ventricular volume in idiopathic normal-pressure hydrocephalus: a comparison with Evans' index.

Neuroradiology 2020 Jun 1;62(6):661-667. Epub 2020 Feb 1.

Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center; Shenzhen Second People's Hospital, 3002 SunGang Road West, Shenzhen, 518035, China.

Purpose: To recommend a new simple and explicit index termed the anteroposterior diameter of the lateral ventricle index (ALVI) for assessing brain ventricular size in neuroimaging and to compare Evans index (EI) between idiopathic normal pressure hydrocephalus (iNPH) patients and age-matched healthy elderly subjects.

Methods: Retrospective measurements of ventricular volume (VV), relative VV (RVV), the EI, and the ALVI were taken from thin-section CT scans for 23 pre-shunt-insertion iNPH patients and 62 age-matched healthy elderly volunteers. The area under the receiver operating characteristic (ROC) curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to assess the effectiveness of ALVI scores for predicting VV.

Results: The correlations between VV or RVV and ALVI scores (VV, r = 0.957; RVV, r = 0.983) were significantly stronger than the corresponding correlations with EI scores (VV, r = 0.843; RVV, r = 0.840). The AUC for ALVI scores was significantly greater than the AUC for EI scores. Furthermore, with the inclusion of the ALVI, the NRI value was 0.14 and the IDI value was 0.14; these improvements were also statistically significant.

Conclusion: The ALVI is a more accurate and more explicitly defined marker of VV than the EI and assesses ventricular enlargement effectively. We suggest that ventricular enlargement of the healthy elderly be defined by ALVI > 0.50.
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http://dx.doi.org/10.1007/s00234-020-02361-8DOI Listing
June 2020

Detecting sub-voxel microvasculature with USPIO-enhanced susceptibility-weighted MRI at 7 T.

Magn Reson Imaging 2020 04 3;67:90-100. Epub 2020 Jan 3.

Department of Radiology, Wayne State University, Detroit, MI, United States; The MRI Institute for Biomedical Research, Waterloo, ON, Canada. Electronic address:

Background: Susceptibility weighted imaging (SWI) combines phase with magnitude information to better image sub-voxel veins. Recently, it has been extended to image very small sub-voxel arteries and veins by injecting intravenously the ultra-small superparamagnetic iron oxide, Ferumoxytol.

Objective: To determine practical experimental imaging parameters for sub-voxel cerebral vessels at 7 T.

Methods: Six Wistar-Kyoto rats aged 7-13 weeks were imaged. For a given spatial resolution, SWI was acquired pre- and post- Ferumoxytol with doses of 2, 4, 6 and 8 mg/kg and echo times (TEs) of 5, 10 and 15 ms at each dose. The spatial resolutions of 62.5 × 125 × 250 μm (acquisition time of 7.5 min) and 62.5 × 62.5 × 125 μm (30 min) were used. Both SWI and quantitative susceptibility mapping (QSM) data were analyzed. Contrast-to-noise ratio (CNR) was measured and used to determine the optimal practical imaging parameters for detection of small cortical penetrating arteries.

Results: For a given spatial resolution with an aspect ratio (frequency: phase: slice) of 2:4:8 relative to the vessel size, we found the TE-dose index (TE x dose) must be at least 40 ms·mg/kg for both SWI and QSM to reveal the most vessels. The higher the TE-dose index, the better the image quality for both SWI and QSM up to 60 ms·mg/kg.

Conclusions: There is an optimal TE-dose index for improved visualization of sub-voxel vessels. Choosing the smallest TE and the largest allowed dose made it possible to run the sequence efficiently. In practice, the aspect ratio of 2:4:8 and the TE-dose index ranging from 40 to 60 ms·mg/kg provided the optimal and most practical solution.
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http://dx.doi.org/10.1016/j.mri.2019.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480016PMC
April 2020

Prevalence of microplastics in animal-based traditional medicinal materials: Widespread pollution in terrestrial environments.

Sci Total Environ 2020 Mar 18;709:136214. Epub 2019 Dec 18.

School of Ecological and Environmental Sciences, Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, East China Normal University, Shanghai 200241, China. Electronic address:

Microplastics (MPs) pollution is an emerging environmental and health concern. MPs have been extensively observed in the aquatic environment, yet rarely investigated in the terrestrial ecosystem, especially in relation to health risks. To evaluate potential MPs pollution in land-dwelling animal medicine materials, we collected 20 types of small animal-based medicinal materials and 10 types of available fresh terrestrial animals from eight different regions in China. MPs were found in all medicinal materials with an average incidence rate of 94.67%. The abundance of MPs was in the range of 1.80 ± 0.38 to 7.80 ± 0.83 items/individual or 1.59 ± 0.33 to 43.56 ± 9.22 items/g (dry weight), with polymer distribution by polyethylene terephthalate (40.45%), rayon (30.64%), polyethylene (10.11%), nylon (7.35%), polypropylene (5.93%), and polyvinyl chloride (5.52%). The majority of MPs were microfibers (84.68%), with 15.32% of fragments. Moreover, MPs were directly observed in the intestine, detected in all ten types of fresh medicinal animals with the abundance of 0.83 ± 0.35 to 3.42 ± 0.46 items/individual. Furthermore, significant positive correlations (R: 0.32-0.99, p < 0.05) of MPs characteristics were found between medicinal materials and fresh animals, including shape, size, color, and polymer distribution of MPs. The results support that MPs in the medicinal materials were likely derived from living animals. This study demonstrates the prevalence of MPs in animal-based, traditional medicinal materials, and also suggests widespread MPs pollution in terrestrial environments and latent health risks.
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http://dx.doi.org/10.1016/j.scitotenv.2019.136214DOI Listing
March 2020

EGFL9 promotes breast cancer metastasis by inducing cMET activation and metabolic reprogramming.

Nat Commun 2019 11 6;10(1):5033. Epub 2019 Nov 6.

Barbara Ann Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, 4100 John R, Detroit, MI, 48201, USA.

The molecular mechanisms driving metastatic progression in triple-negative breast cancer (TNBC) patients are poorly understood. In this study, we demonstrate that epidermal growth factor-like 9 (EGFL9) is significantly upregulated in basal-like breast cancer cells and associated with metastatic progression in breast tumor samples. Functionally, EGFL9 is both necessary and sufficient to enhance cancer cell migration and invasion, as well as distant metastasis. Mechanistically, we demonstrate that EGFL9 binds cMET, activating cMET-mediated downstream signaling. EGFL9 and cMET co-localize at both the cell membrane and within the mitochondria. We further identify an interaction between EGFL9 and the cytochrome c oxidase (COX) assembly factor COA3. Consequently, EGFL9 regulates COX activity and modulates cell metabolism, promoting a Warburg-like metabolic phenotype. Finally, we show that combined pharmacological inhibition of cMET and glycolysis reverses EGFL9-driven stemness. Our results identify EGFL9 as a therapeutic target for combating metastatic progression in TNBC.
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http://dx.doi.org/10.1038/s41467-019-13034-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834558PMC
November 2019

CT radiomic features for predicting resectability of oesophageal squamous cell carcinoma as given by feature analysis: a case control study.

Cancer Imaging 2019 Oct 16;19(1):66. Epub 2019 Oct 16.

Department of Radiology, Wayne State University, Detroit, MI, USA.

Background: Computed tomography (CT) is commonly used in all stages of oesophageal squamous cell carcinoma (SCC) management. Compared to basic CT features, CT radiomic features can objectively obtain more information about intratumour heterogeneity. Although CT radiomics has been proved useful for predicting treatment response to chemoradiotherapy in oesophageal cancer, the best way to use CT radiomic biomarkers as predictive markers for determining resectability of oesophageal SCC remains to be developed. This study aimed to develop CT radiomic features related to resectability of oesophageal SCC with five predictive models and to determine the most predictive model.

Methods: Five hundred ninety-one patients with oesophageal SCC undergoing contrast-enhanced CT were enrolled in this study, and were composed by 270 resectable cases and 321 unresectable cases. Of the 270 resectable oesophageal SCCs, 91 cases were primary resectable tumours; and the remained 179 cases received neoadjuvant therapy after CT, shrank on therapy, and changed to resectable tumours. Four hundred thirteen oesophageal SCCs including 189 resectable cancers and 224 unresectable cancers were randomly allocated to the training cohort; and 178 oesophageal SCCs including 81 resectable tumours and 97 unresectable tumours were allocated to the validation group. Four hundred ninety-five radiomic features were extracted from CT data for identifying resectability of oesophageal SCC. Useful radiomic features were generated by dimension reduction using least absolute shrinkage and selection operator. The optimal radiomic features were chosen using multivariable logistic regression, random forest, support vector machine, X-Gradient boost and decision tree classifiers. Discriminating performance was assessed with area under receiver operating characteristic curve (AUC), accuracy and F-1score.

Results: Eight radiomic features were selected to create radiomic models related to resectability of oesophageal SCC (P-values < 0.01 for both cohorts). Multivariable logistic regression model showed the best performance (AUC = 0.92 ± 0.04 and 0.87 ± 0.02, accuracy = 0.87 and 0.86, and F-1score = 0.93 and 0.86 in training and validation cohorts, respectively) in comparison with any other model (P-value < 0.001). Good calibration was observed for multivariable logistic regression model.

Conclusion: CT radiomic models could help predict resectability of oesophageal SCC, and multivariable logistic regression model is the most predictive model.
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http://dx.doi.org/10.1186/s40644-019-0254-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796480PMC
October 2019

A phase II study of cabozantinib alone or in combination with trastuzumab in breast cancer patients with brain metastases.

Breast Cancer Res Treat 2020 Jan 20;179(1):113-123. Epub 2019 Sep 20.

Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.

Purpose: To analyze the efficacy and tolerability of cabozantinib-a small molecule inhibitor of MET and VEGFR2-alone or with trastuzumab in patients with breast cancer brain metastases (BCBM).

Methods: This single-arm phase II study enrolled patients with new or progressive measurable BCBM into 3 cohorts: Cohort 1 (HER2-positive), Cohort 2 (hormone receptor-positive/HER2-negative), and Cohort 3 (triple-negative). Patients received cabozantinib 60-mg daily on a 21-day cycle. Cohort 1 added trastuzumab every 3 weeks and had a primary objective of central nervous system (CNS) objective response rate (ORR) by RECIST 1.1. Secondary objectives for all cohorts were progression-free survival, overall survival, toxicity, and changes in vascular parameters and circulating biomarkers. Cohorts 2 and 3 also had CNS ORR as a secondary objective.

Results: Thirty-six BCBM patients enrolled (cohort 1, n = 21; cohort 2, n = 7; cohort 3, n = 8), with a median age of 50. Patients had a median of 3 prior lines for metastatic disease (range 1-9). Treatments prior to enrollment included craniotomy (n = 4), whole brain radiation (n = 24) and stereotactic radiosurgery (n = 11). CNS ORR was 5% in cohort 1, 14% in cohort 2, and 0% in cohort 3. Most common grade 3/4 adverse events included elevations in lipase (11%), AST (8%), ALT (6%), hyponatremia (8%), and hypertension (6%). Cabozantinib increased plasma concentrations of CA-IX, soluble (s)MET, PlGF, sTIE-2, VEGF, and VEGF-D, and decreased sVEGFR2 and TNF-α and total tumor blood volume.

Conclusions: Cabozantinib had insufficient activity in heavily pretreated BCBM patients. Biomarker analysis showed that cabozantinib had antiangiogenic activity and increased tissue hypoxia.

Trial Registration: Clinicaltrial.gov registration: NCT02260531.
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http://dx.doi.org/10.1007/s10549-019-05445-zDOI Listing
January 2020