Publications by authors named "Weiguo Chen"

161 Publications

Optical-Gain-based Sensing Using Inorganic-Ligand-Passivated Colloidal Quantum Dots.

Nano Lett 2021 Sep 13. Epub 2021 Sep 13.

Hefei National Laboratory for Physical Sciences at the Microscale and School of Physical Sciences, University of Science and Technology of China, Hefei 230026, China.

Thanks to their extremely large surface-to-volume ratio, colloidal quantum dots are potential high-performance sensing materials. However, previous sensing works using their spontaneous emission suffer from low sensitivities. The absence of an amplification process and the presence of the steric hindrance of long-chain organic ligands are two possible causations. Herein we propose that these two issues can be circumvented by using the amplified spontaneous emission of colloidal quantum dots capped by short-chain inorganic ligands. To exemplify this concept, we performed humidity sensing and observed a ∼31 times enhancement in sensitivity. Meanwhile, we found that the amplified spontaneous emission threshold power was reduced by 34% in a high humidity environment. On the basis of our transient absorption measurements, we attribute these observations to the mitigation of ultrafast subpicosecond trapping processes, which are enabled by the absorption of water molecules.
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http://dx.doi.org/10.1021/acs.nanolett.1c02547DOI Listing
September 2021

A deep learning-machine learning fusion approach for the classification of benign, malignant, and intermediate bone tumors.

Eur Radiol 2021 Aug 25. Epub 2021 Aug 25.

Department of Radiology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Baiyun District, Guangzhou, Guangdong Province, People's Republic of China.

Objectives: To build and validate deep learning and machine learning fusion models to classify benign, malignant, and intermediate bone tumors based on patient clinical characteristics and conventional radiographs of the lesion.

Methods: In this retrospective study, data were collected with pathologically confirmed diagnoses of bone tumors between 2012 and 2019. Deep learning and machine learning fusion models were built to classify tumors as benign, malignant, or intermediate using conventional radiographs of the lesion and potentially relevant clinical data. Five radiologists compared diagnostic performance with and without the model. Diagnostic performance was evaluated using the area under the curve (AUC).

Results: A total of 643 patients' (median age, 21 years; interquartile range, 12-38 years; 244 women) 982 radiographs were included. In the test set, the binary category classification task, the radiological model of classification for benign/not benign, malignant/nonmalignant, and intermediate/not intermediate had AUCs of 0.846, 0.827, and 0.820, respectively; the fusion models had an AUC of 0.898, 0.894, and 0.865, respectively. In the three-category classification task, the radiological model achieved a macro average AUC of 0.813, and the fusion model had a macro average AUC of 0.872. In the observation test, the mean macro average AUC of all radiologists was 0.819. With the three-category classification fusion model support, the macro AUC improved by 0.026.

Conclusion: We built, validated, and tested deep learning and machine learning models that classified bone tumors at a level comparable with that of senior radiologists. Model assistance may somewhat help radiologists' differential diagnoses of bone tumors.

Key Points: • The deep learning model can be used to classify benign, malignant, and intermediate bone tumors. • The machine learning model fusing information from radiographs and clinical characteristics can improve the classification capacity for bone tumors. • The diagnostic performance of the fusion model is comparable with that of senior radiologists and is potentially useful as a complement to radiologists in a bone tumor differential diagnosis.
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http://dx.doi.org/10.1007/s00330-021-08195-zDOI Listing
August 2021

The diagnostic value of chest X-ray in coronavirus disease 2019: A comparative study of X-ray and CT.

Sci Prog 2021 Jul-Sep;104(3):368504211016204

Radiology Department, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

As the coronavirus disease 2019 (COVID-19) epidemic spreads around the world, the demand for imaging examinations increases accordingly. The value of conventional chest radiography (CCR) remains unclear. In this study, we aimed to investigate the diagnostic value of CCR in the detection of COVID-19 through a comparative analysis of CCR and CT. This study included 49 patients with 52 CT images and chest radiographs of pathogen-confirmed COVID-19 cases and COVID-19-suspected cases that were found to be negative (non-COVID-19). The performance of CCR in detecting COVID-19 was compared to CT imaging. The major signatures that allowed for differentiation between COVID-19 and non-COVID-19 cases were also evaluated. Approximately 75% (39/52) of images had positive findings on the chest x-ray examinations, while 80.7% (42/52) had positive chest CT scans. The COVID-19 group accounted for 88.4% (23/26) of positive chest X-ray examinations and 96.1% (25/26) of positive chest CT scans. The sensitivity, specificity, and accuracy of CCR for abnormal shadows were 88%, 80%, and 87%, respectively, for all patients. For the COVID-19 group, the accuracy of CCR was 92%. The primary signature on CCR was flocculent shadows in both groups. The shadows were primarily in the bi-pulmonary, which was significantly different from non-COVID-19 patients ( = 0.008). The major CT finding of COVID-19 patients was ground-glass opacities in both lungs, while in non-COVID-19 patients, consolidations combined with ground-glass opacities were more common in one lung than both lungs ( = 0.0001). CCR showed excellent performance in detecting abnormal shadows in patients with confirmed COVID-19. However, it has limited value in differentiating COVID-19 patients from non-COVID-19 patients. Through the typical epidemiological history, laboratory examinations, and clinical symptoms, combined with the distributive characteristics of shadows, CCR may be useful to identify patients with possible COVID-19. This will allow for the rapid identification and quarantine of patients.
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http://dx.doi.org/10.1177/00368504211016204DOI Listing
September 2021

Can the delayed phase of quantitative contrast-enhanced mammography improve the diagnostic performance on breast masses?

Quant Imaging Med Surg 2021 Aug;11(8):3684-3697

Department of Ultrasonic Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Contrast-enhanced mammography (CEM) is an imaging tool for breast cancer detection. Most quantitative analyses of CEM involve two phases, and it is unknown whether an added delayed phase can improve its diagnostic performance compared to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). This study aimed to evaluate whether the delayed phase improves the diagnostic performance of CEM in distinguishing malignant and benign masses.

Methods: This prospective study enrolled 111 women with 111 pathologically confirmed breast masses. CEM was performed after the injection of contrast agent between 2-3 minutes (T1, early phase), 4-5 minutes (T2, second phase), and 7-9 minutes (T3, delayed phase). The quantitative enhanced gray value of lesions (LGV) and the lesion to background grey value ratio (LBR) were measured within each phase's corresponding region of interest (ROI). Based on their changes, the kinetic enhancement pattern was assessed among the three phases, and the diagnostic performance was subsequently measured.

Results: The LGV and LBR of malignant masses were significantly greater than those of benign lesions. The diagnostic performance of LGV and LBR at the delayed phase was consistent with that of the second phase but poorer than that of the early phase. The sensitivity of LGV + LGV + LGV was less than that of LGV + LGV (86.5% 95.1%) with a similar area under the curve (AUC), specificity, positive-predictive value (PPV), negative-predictive value (NPV), and accuracy. The sensitivity of LBR + LBR + LBR increased by 19.6%, and specificity decreased by 20.7% compared with LBR + LBR. The LGV + LGV + LGV + kinetic enhancement (T1-T3) had the lowest sensitivity (67.0%), but the highest specificity (75.8%), and the sensitivity of LBR + LBR + LBR + kinetic enhancement (T1-T3) was higher than that of LBR + LBR + kinetic enhancement (T1-T2) (90.2% 63.4%, respectively).

Conclusions: The addition of a delayed CEM phase for breast cancer diagnosis yielded limited performance improvement. The quantitative analysis combined with enhancement patterns between the two consecutive phases has great potential to distinguish between malignant and benign lesions.
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http://dx.doi.org/10.21037/qims-20-1092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245946PMC
August 2021

Aqueous extracts of induce S-phase arrest and apoptosis in human melanoma A375 cells.

Oncol Lett 2021 Aug 30;22(2):628. Epub 2021 Jun 30.

Institute of Sericultural and Tea, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang 310021, P.R. China.

, also called 'Sanghuang' mushroom in Chinese, has various medicinal uses, but its effects on human melanoma cells have not been reported. The present study investigated the inhibitory ability and potential anticancer mechanism of the aqueous extracts of (SH). The results revealed that SH inhibited the proliferation of A375 human melanoma cells in a dose-dependent manner, and flow cytometry analysis suggested that SH induced A375 cell cycle arrest at S phase and apoptosis. Reverse transcription-quantitative PCR, western blotting and immunofluorescence analyses indicated that SH induced S-phase arrest by upregulating p21 expression, and p21 inhibited the expression of cyclin-cyclin-dependent kinases complexes at both the RNA and protein levels. In addition, SH induced apoptosis of A375 cells by inhibiting the expression levels of the anti-apoptosis gene . Therefore, the results suggested that SH may be a potential candidate for the treatment of human melanoma, thus providing new ideas for developing drugs that target melanoma.
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http://dx.doi.org/10.3892/ol.2021.12889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258622PMC
August 2021

Clinical characteristics and disease outcomes in ER+ breast cancer: a comparison between HER2+ patients treated with trastuzumab and HER2- patients.

BMC Cancer 2021 Jul 13;21(1):807. Epub 2021 Jul 13.

General Surgery Department, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 22nd Floor, 197 Ruijin Er Road, Shanghai, 200025, China.

Background: Trastuzumab has changed the prognosis of HER2+ breast cancer. We aimed to investigate the prognosis of ER+/HER2+ patients treated with trastuzumab, thus to guide escalation endocrine treatment in ER+ breast cancer.

Methods: ER-positive early breast cancer patients operated at Ruijin Hospital between Jan. 2009 and Dec. 2017 were retrospectively included. Eligible patients were grouped as HER2-negative (HER2-neg) or HER2-positive with trastuzumab treatment (HER2-pos-T). Kaplan-Meier analysis and Cox proportional hazards model were used to compare the disease-free survival (DFS) and overall survival (OS) between these two groups.

Results: A total of 3761 patients were enrolled: 3313 in the HER2-neg group and 448 in the HER2-pos-T group. Patients in the HER2-pos-T group were associated with pre/peri-menopause, higher histological grade, LVI, higher Ki-67 level, lower ER and PR levels (all P <  0.05). At a median follow-up of 62 months, 443 DFS events and 191 deaths were observed. The estimated 5-year DFS rate was 89.7% in the HER2-neg group and 90.2% in the HER2-pos-T group (P = 0.185), respectively. Multivariable analysis demonstrated that patients in the HER2-pos-T group had a better DFS than patients in the HER2-neg group (HR 0.52, 95% CI: 0.37-0.73, P <  0.001). The estimated 5-year OS rates were 96.0% and 96.3% in the two groups, respectively (P = 0.133). Multivariate analysis found that HER2-pos-T group was still associated with significantly better OS compared with the HER2-neg group (HR 0.38, 95% CI: 0.22-0.67, P = 0.037).

Conclusion: ER+/HER2+ breast cancer patients treated with trastuzumab were associated with superior outcome compared with ER+/HER2- patients, indicating HER2-positivity itself may not be an adverse factor for ER+ patients in the era of trastuzumab.
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http://dx.doi.org/10.1186/s12885-021-08555-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278709PMC
July 2021

Combined Estrogen Receptor and Progesterone Receptor Level Can Predict Survival Outcome in Human Epidermal Growth Factor Receptor 2-positive Early Breast Cancer.

Clin Breast Cancer 2021 Jun 16. Epub 2021 Jun 16.

Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Background: In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, emerging evidence imply that clinical behaviors differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2+ breast cancer. Our study aimed to determine the influence of different ER/PR levels on survival outcome of HER2+ early breast cancer.

Patients And Methods: Nine hundred and nineteen early HER2+ breast cancer patients treated between 2009 and 2016 were retrospectively reviewed and HR+/HER2+ patients were further divided based on ER level (Low/L: 1%-9%; Median/M: 10%-79%; High/H: 80%-100%) and PR level (Low/L: 0%-19%; High/H: 20%-100%) according to restricted cubic spline (RCS) smoothing curve. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and log rank test.

Results: Four hundred and forty two HR+/HER2+ and 477 HR-/HER2+ breast cancer patients were included in our study and 73.2% received target therapy (HR+ 69.7%, HR- 76.5%). While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 93.0% vs. 86.8%, P < .001), no significant difference was observed between DFS in ER+/PR+ and ER+/PR- subgroup (94.4% vs. 90.4%, P = .22). However, a potential correlation was found between ER/PR levels and DFS in HR+/HER2+ (P = .074) tumors. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR. In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.10 (95%CI 0.01-0.74, P = .024) in all patients and 0.14 (95%CI, 0.02-1.02, P = .053) in patients receiving anti-HER2 therapy.

Conclusion: ER/PR expression may become a predictor of survival benefit in HER2+ early breast cancer and a higher ER/PR level might be associated with better DFS.
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http://dx.doi.org/10.1016/j.clbc.2021.05.012DOI Listing
June 2021

Differential DNA Methylation and Gene Expression Between ALV-J-Positive and ALV-J-Negative Chickens.

Front Vet Sci 2021 31;8:659840. Epub 2021 May 31.

Guangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China.

Avian leukosis virus subgroup J (ALV-J) is an oncogenic virus that causes serious economic losses in the poultry industry; unfortunately, there is no effective vaccine against ALV-J. DNA methylation plays a crucial role in several biological processes, and an increasing number of diseases have been proven to be related to alterations in DNA methylation. In this study, we screened ALV-J-positive and -negative chickens. Subsequently, we generated and provided the genome-wide gene expression and DNA methylation profiles by MeDIP-seq and RNA-seq of ALV-J-positive and -negative chicken samples; 8,304 differentially methylated regions (DMRs) were identified by MeDIP-seq analysis ( ≤ 0.005) and 515 differentially expressed genes were identified by RNA-seq analysis ( ≤ 0.05). As a result of an integration analysis, we screened six candidate genes to identify ALV-J-negative chickens that possessed differential methylation in the promoter region. Furthermore, TGFB2 played an important role in tumorigenesis and cancer progression, which suggested TGFB2 may be an indicator for identifying ALV-J infections.
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http://dx.doi.org/10.3389/fvets.2021.659840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203102PMC
May 2021

Efficacy of adjuvant chemotherapy stratified by age and the 21-gene recurrence score in estrogen receptor-positive breast cancer.

BMC Cancer 2021 Jun 15;21(1):707. Epub 2021 Jun 15.

Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Background: The 21-gene recurrence score (RS) can predict chemotherapy benefit in estrogen receptor-positive, human epidermal growth factor receptor-2-negative (ER+/HER2-) early breast cancer patients. Age would influence the interaction between RS and chemotherapy effect. The current study aimed to determine RS thresholds which were predictive of chemotherapy benefit in young and old women, respectively.

Methods: Patients diagnosed with pN0-1, ER+/HER2- breast cancer between 2009 and 2016 were retrospectively reviewed. Propensity score matching was performed according to chemotherapy usage. After stratifying patients with different cutoffs of age, the RS threshold indicating chemotherapy benefit in each age strata were determined by cox proportional hazard models.

Results: A total of 1227 patients were included. The median age was 58 years and the median RS was 24. After matching, the RS thresholds suggesting chemotherapy benefit varied with age. For patients ≤55 years, chemotherapy benefit was observed in those having RS > 25 (P = 0.03), with 4-year invasive disease-free survival (IDFS) of 97.0 and 89.3% in patients receiving chemotherapy or not. While patients derived no benefit from chemotherapy if they had RS ≤25 (P = 0.66, 4-year IDFS: 95.3% vs. 94.6%). For patients > 55 years, adjuvant chemotherapy was associated with better prognosis in those with RS > 36 (P = 0.014, 4-year IDFS: 94.7% vs. 76.2%), but not in those having RS ≤36 (P = 0.13, 4-year IDFS: 92.3% vs. 95.8%).

Conclusions: Old patients need higher RS thresholds to demonstrate the chemotherapy benefit. Further efforts are warranted to investigate the association between age and predictive RS thresholds.
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http://dx.doi.org/10.1186/s12885-021-08461-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207606PMC
June 2021

Comprehensive Association Analysis of 21-Gene Recurrence Score and Obesity in Chinese Breast Cancer Patients.

Front Oncol 2021 26;11:619840. Epub 2021 Mar 26.

Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: A center-specific 21-gene recurrence score (RS) assay has been validated in Luminal-like, HER2-, pN0-1 Chinese breast cancer patients with both predictive and prognostic value. The association between RS and host factors such as obesity remains unclear. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic value of RS among non-overweight, overweight and obese patients.

Patients And Methods: Luminal-like patients between January 2009 and December 2018 were retrospectively reviewed. Association and subgroup analysis between BMI and RS were conducted. Single-gene expression in RS panel was compared according to BMI status. Disease-free survival (DFS) and overall survival (OS) were calculated according to risk category and BMI status.

Results: Among 1876 patients included, 124 (6.6%), 896 (47.8%) and 856 (45.6%) had RS < 11, RS 11-25, and RS ≥ 26, respectively. Risk category was significantly differently distributed by BMI status (=0.033). Obese patients were more likely to have RS < 11 (OR 2.45, 95% CI 1.38-4.35, =0.002) compared with non-overweight patients. The effect of BMI on RS significantly varied according to menstruation (<0.05). Compared to non-overweight patients, obese ones presented significantly higher , , , , and (all <0.05) mRNA expression, and such difference was mainly observed in postmenopausal population. After a median follow-up of 39.40 months (range 1.67-119.53), RS could significantly predict DFS in whole population (=0.001). RS was associated with DFS in non-overweight (=0.046), but not in overweight (=0.558) or obese (=0.114) population.

Conclusions: RS was differently distributed among different BMI status, which interacted with menopausal status. Estrogen receptor and proliferation group genes were more expressed in obese patients, especially in postmenopausal population.
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http://dx.doi.org/10.3389/fonc.2021.619840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032994PMC
March 2021

African Swine Fever Virus Protein E199L Promotes Cell Autophagy through the Interaction of PYCR2.

Virol Sin 2021 Apr 8;36(2):196-206. Epub 2021 Apr 8.

College of Animal Science, South China Agricultural University & Lingnan Guangdong Laboratory of Modern Agriculture & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, Guangzhou, 510642, China.

African swine fever virus (ASFV), as a member of the large DNA viruses, may regulate autophagy and apoptosis by inhibiting programmed cell death. However, the function of ASFV proteins has not been fully elucidated, especially the role of autophagy in ASFV infection. One of three Pyrroline-5-carboxylate reductases (PYCR), is primarily involved in conversion of glutamate to proline. Previous studies have shown that depletion of PYCR2 was related to the induction of autophagy. In the present study, we found for the first time that ASFV E199L protein induced a complete autophagy process in Vero and HEK-293T cells. Through co-immunoprecipitation coupled with mass spectrometry (CoIP-MS) analysis, we firstly identified that E199L interact with PYCR2 in vitro. Importantly, our work provides evidence that E199L down-regulated the expression of PYCR2, resulting in autophagy activation. Overall, our results demonstrate that ASFV E199L protein induces complete autophagy through interaction with PYCR2 and down-regulate the expression level of PYCR2, which provide a valuable reference for the role of autophagy during ASFV infection and contribute to the functional clues of PYCR2.
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http://dx.doi.org/10.1007/s12250-021-00375-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027715PMC
April 2021

Synthesis of Mammogram From Digital Breast Tomosynthesis Using Deep Convolutional Neural Network With Gradient Guided cGANs.

IEEE Trans Med Imaging 2021 08 30;40(8):2080-2091. Epub 2021 Jul 30.

Synthetic digital mammography (SDM), a 2D image generated from digital breast tomosynthesis (DBT), is used as a potential substitute for full-field digital mammography (FFDM) in clinic to reduce the radiation dose for breast cancer screening. Previous studies exploited projection geometry and fused projection data and DBT volume, with different post-processing techniques applied on re-projection data which may generate different image appearance compared to FFDM. To alleviate this issue, one possible solution to generate an SDM image is using a learning-based method to model the transformation from the DBT volume to the FFDM image using current DBT/FFDM combo images. In this study, we proposed to use a deep convolutional neural network (DCNN) to learn the transformation to generate SDM using current DBT/FFDM combo images. Gradient guided conditional generative adversarial networks (GGGAN) objective function was designed to preserve subtle MCs and the perceptual loss was exploited to improve the performance of the proposed DCNN on perceptual quality. We used various image quality criteria for evaluation, including preserving masses and MCs which are important in mammogram. Experiment results demonstrated progressive performance improvement of network using different objective functions in terms of those image quality criteria. The methodology we exploited in the SDM generation task to analyze and progressively improve image quality by designing objective functions may be helpful to other image generation tasks.
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http://dx.doi.org/10.1109/TMI.2021.3071544DOI Listing
August 2021

Using Machine Learning to Unravel the Value of Radiographic Features for the Classification of Bone Tumors.

Biomed Res Int 2021 11;2021:8811056. Epub 2021 Mar 11.

Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.

Objectives: To build and validate random forest (RF) models for the classification of bone tumors based on the conventional radiographic features of the lesion and patients' clinical characteristics, and identify the most essential features for the classification of bone tumors.

Materials And Methods: In this retrospective study, 796 patients (benign bone tumors: 412 cases, malignant bone tumors: 215 cases, intermediate bone tumors: 169 cases) with pathologically confirmed bone tumors from Nanfang Hospital of Southern Medical University, Foshan Hospital of TCM, and University of Hong Kong-Shenzhen Hospital were enrolled. RF models were built to classify tumors as benign, malignant, or intermediate based on conventional radiographic features and potentially relevant clinical characteristics extracted by three musculoskeletal radiologists with ten years of experience. SHapley Additive exPlanations (SHAP) was used to identify the most essential features for the classification of bone tumors. The diagnostic performance of the RF models was quantified using receiver operating characteristic (ROC) curves.

Results: The features extracted by the three radiologists had a satisfactory agreement and the minimum intraclass correlation coefficient (ICC) was 0.761 (CI: 0.686-0.824, < .001). The binary and tertiary models were built to classify tumors as benign, malignant, or intermediate based on the imaging and clinical features from 627 and 796 patients. The AUC of the binary (19 variables) and tertiary (22 variables) models were 0.97 and 0.94, respectively. The accuracy of binary and tertiary models were 94.71% and 82.77%, respectively. In descending order, the most important features influencing classification in the binary model were margin, cortex involvement, and the pattern of bone destruction, and the most important features in the tertiary model were margin, high-density components, and cortex involvement.

Conclusions: This study developed interpretable models to classify bone tumors with great performance. These should allow radiographers to identify imaging features that are important for the classification of bone tumors in the clinical setting.
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http://dx.doi.org/10.1155/2021/8811056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984886PMC
May 2021

Bladder muscle regeneration enhanced by sustainable delivery of heparin from bilayer scaffolds carrying stem cells in a rat bladder partial cystectomy model.

Biomed Mater 2021 04 15;16(3). Epub 2021 Apr 15.

Department of Urology and Orthopaedic Surgery, The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu 215006, People's Republic of China.

In bladder tissue engineering, regeneration of muscle is of equal importance to epithelial regeneration. However, as yet there is no effective strategy for promoting bladder muscle regeneration. In this study we aim to promote bladder muscle regeneration by sustainably delivering heparin from a bilayer scaffold carrying stem cells. The bilayer scaffold [heparin-polycaprolactone (PCL)/bladder decellularized matrix (BAM) Hep-PB/PCL] comprises an electrospun layer (Hep-PB electrospun membrane) and a three-dimensional (3D) printed layer (PCL scaffold), fabricated via coaxial-electrospinning and 3D printing, respectively. Heparin was encapsulated into the core of the Hep-PB fibers with a core-shell structure to sustain its release. The morphology of the bilayer scaffold and the microstructure of the electrospun fibers were characterized. The release behavior of heparin from various electrospun membranes was evaluated. The role of Hep-PB in promoting myogenic differentiation of the adipose-derived stem cells (ADSCs) through sustainable release of heparin was also evaluated. After 7 d culture, Hep-PB/PCL scaffolds carrying ADSCs (defined as ASHP) were used for bladder reconstruction in a rat partial cystotomy model. The result shows that the PCL printed scaffold has ordered macropores (∼370 μm), unlike the compact microstructure of electrospun films. The Hep-PB membrane exhibits a sustained release behavior for heparin. This membrane also shows better growth and proliferation of ADSCs than the other membranes. The polymerase chain reaction results show that the expression of smooth muscle cell markers in ADSCs is enhanced by the Hep-PB scaffold. The results of retrograde urethrography and histological staining indicate that the bladder volume in the ASHP group recovers better, and the regenerated bladder muscle bundles are arranged in a more orderly fashion compared with the direct suture and bladder decellularized matrix groups. Therefore, findings from this study show that bladder muscle regeneration could be enhanced by bilayer scaffolds delivering heparin and carrying stem cells, which may provide a new strategy for bladder tissue engineering.
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http://dx.doi.org/10.1088/1748-605X/abf08bDOI Listing
April 2021

An Interpretable Model-Based Prediction of Severity and Crucial Factors in Patients with COVID-19.

Biomed Res Int 2021 1;2021:8840835. Epub 2021 Mar 1.

Department of Medical Services Section, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.

This study established an interpretable machine learning model to predict the severity of coronavirus disease 2019 (COVID-19) and output the most crucial deterioration factors. Clinical information, laboratory tests, and chest computed tomography (CT) scans at admission were collected. Two experienced radiologists reviewed the scans for the patterns, distribution, and CT scores of lung abnormalities. Six machine learning models were established to predict the severity of COVID-19. After parameter tuning and performance comparison, the optimal model was explained using Shapley Additive explanations to output the crucial factors. This study enrolled and classified 198 patients into mild ( = 162; 46.93 ± 14.49 years old) and severe ( = 36; 60.97 ± 15.91 years old) groups. The severe group had a higher temperature (37.42 ± 0.99°C vs. 36.75 ± 0.66°C), CT score at admission, neutrophil count, and neutrophil-to-lymphocyte ratio than the mild group. The XGBoost model ranked first among all models, with an AUC, sensitivity, and specificity of 0.924, 90.91%, and 97.96%, respectively. The early stage of chest CT, total CT score of the percentage of lung involvement, and age were the top three contributors to the prediction of the deterioration of XGBoost. A higher total score on chest CT had a more significant impact on the prediction. In conclusion, the XGBoost model to predict the severity of COVID-19 achieved excellent performance and output the essential factors in the deterioration process, which may help with early clinical intervention, improve prognosis, and reduce mortality.
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http://dx.doi.org/10.1155/2021/8840835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930914PMC
March 2021

Molecular Subtype May Be More Associated With Prognosis and Chemotherapy Benefit Than Tumor Size in T1N0 Breast Cancer Patients: An Analysis of 2,168 Patients for Possible De-Escalation Treatment.

Front Oncol 2021 19;11:636266. Epub 2021 Feb 19.

Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Purpose: Breast cancer (BC) patients with T1N0 tumors have relatively favorable clinical outcomes. However, it remains unclear whether molecular subtypes can aide in prognostic prediction for such small, nodal-negative BC cases and guide decision-making about escalating or de-escalating treatments.

Patients And Methods: T1N0 BC patients diagnosed between 2009 and 2017 were included and classified into three subgroups according to receptor status: 1) hormonal receptor (HR)+/human epidermal growth factor receptor-2 (HER2)-; 2) HER2+; and 3) triple negative (TN) (HR-/HER2-). Patients' characteristics and relapse events were reviewed. Kaplan-Meier analysis and Cox regression were used to assess the iDFS and BCSS. The effects of risk factors and adjuvant treatment benefits were evaluated by calculating hazard ratios (HRs) for invasive disease-free survival (iDFS) and breast cancer-specific survival (BCSS) with Cox proportional hazards models.

Results: In total, 2,168 patients (1,435 HR+/HER2-, 427 HER2+, 306 TN) were enrolled. The 5-year iDFS rates were 93.6, 92.7, and 90.6% for HR+/HER2-, HER2+, and TN patients, respectively (P = 0.039). Multivariate analysis demonstrated that molecular subtype (P = 0.043), but not tumor size (P = 0.805), was independently associated with iDFS in T1N0 BC. TN patients [HRs = 1.77, 95% confidence interval (CI) = 1.11-2.84, P = 0.018] had a higher recurrence risk than HR+/HER2- patients. Adjuvant chemotherapy benefit was not demonstrated in all T1N0 patients but interacted with molecular subtype status. TN (adjusted HRs = 2.31, 95% CI = 0.68-7.54) and HER2+ (adjusted HRs = 2.26, 95% CI = 0.95-5.63) patients receiving chemotherapy had superior iDFS rates. Regarding BCSS, molecular subtype tended to be related to outcome (P = 0.053) and associated with chemotherapy benefit (P = 0.005).

Conclusion: Molecular subtype was more associated with disease outcome and chemotherapy benefit than tumor size in T1N0 BC patients, indicating that it may guide possible clinical de-escalating therapy in T1N0 BC.
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http://dx.doi.org/10.3389/fonc.2021.636266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933524PMC
February 2021

A nomogram to predict the high-risk RS in HR+/HER2-breast cancer patients older than 50 years of age.

J Transl Med 2021 02 16;19(1):75. Epub 2021 Feb 16.

Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.

Background: The 21-gene recurrence score (RS) testing can predict the prognosis for luminal breast cancer patients. Meanwhile, patients > 50 years with RS > 25 have improved survival with adjuvant chemotherapy. The current study aimed to develop a nomogram with routine parameters to predict RS.

Methods: We included patients diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative who underwent the 21-gene RS testing and aged > 50 years. The primary outcome was high-risk RS (> 25). Univariate and multivariate analyses were performed to identify significant predictors. A predictive nomogram based on logistic model was developed and evaluated with receiver operating characteristic (ROC) curves. The nomogram was internally validated for discrimination and calibration with bootstrapping method, and externally validated in another cohort. We then assessed the nomogram in different subgroups of patients and compared it with several published models.

Results: A total of 1100 patients were included. Five clinicopathological parameters were used as predictors of a high-risk RS, including tumor grade, histologic subtype, ER expression, PR expression, and Ki-67 index. The area under the curve (AUC) was 0.798 (95% CI 0.772-0.825) and optimism adjusted AUC was 0.794 (95% CI 0.781-0.822). External validation demonstrated an AUC value of 0.746 (95% CI 0.685-0.807), which had no significant difference with the training cohort (P = 0.124). Calibration plots indicated that the nomogram-predicted results were well fitted to the actual outcomes in both internal and external validation. The nomogram had better discriminate ability in patients who had tumors > 2 cm (AUC = 0.847, 95% CI 0.804-0.890). When compared with four other existing models, similar AUC was observed between our nomogram and the model constructed by discriminate Lee et al. CONCLUSIONS: We developed a user-friendly nomogram to predict the high-risk RS in luminal breast cancer patients who were older than 50 years of age, which could guide treatment decision making for those who have no access to the 21-gene RS testing.
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http://dx.doi.org/10.1186/s12967-021-02743-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885620PMC
February 2021

Metabolite profiling of the hyphal exudates of Rhizophagus clarus and Rhizophagus irregularis under phosphorus deficiency.

Mycorrhiza 2021 May 18;31(3):403-412. Epub 2021 Jan 18.

Faculty of Agriculture, Yamagata University, Tsuruoka, 997-8555, Japan.

Arbuscular mycorrhizal (AM) fungal extraradical hyphae exude their metabolites into the soil. Root exudate metabolites are affected by plant species and P status. However, the effect of P status on AM hyphal exudate metabolites has been unknown. This study aimed to examine hyphal exudate metabolite composition of two AM fungal species and their response to P deficiency through metabolite profiling. Rhizophagus clarus and R. irregularis were grown in a two-compartment in vitro culture system of Linum usitatissimum roots on solid modified Strullu-Romand medium in combination with two P levels (3 µM (P3) and 30 µM (P30)). Hyphal exudates were collected from the hyphal compartment at 118 days after inoculation (DAI). The metabolite composition of the hyphal exudates was determined by capillary electrophoresis/time-of-flight mass spectrometry, resulting in the identification of a total of 141 metabolites at 118 DAI. In the hyphal exudates of R. clarus, the concentrations of 18 metabolites, including sugars, amino acids, and organic acids, were significantly higher (p < 0.05) under P3 than under P30 conditions. In contrast, the concentrations of 10 metabolites, including sugar and amino acids, in the hyphal exudates of R. irregularis were significantly lower (p < 0.05) under P3 than under P30 conditions. These findings suggest that the extraradical hyphae of AM fungi exude diverse metabolites of which concentrations are affected by P conditions and differ between AM fungal species.
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http://dx.doi.org/10.1007/s00572-020-01016-zDOI Listing
May 2021

UCHL1, a deubiquitinating enzyme, regulates lung endothelial cell permeability in vitro and in vivo.

Am J Physiol Lung Cell Mol Physiol 2021 04 13;320(4):L497-L507. Epub 2021 Jan 13.

Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.

Increasing evidence suggests an important role for deubiquitinating enzymes (DUBs) in modulating a variety of biological functions and diseases. We previously identified the upregulation of the DUB ubiquitin carboxyl terminal hydrolase 1 (UCHL1) in murine ventilator-induced lung injury (VILI). However, the role of UCHL1 in modulating vascular permeability, a cardinal feature of acute lung injury (ALI) in general, remains unclear. We investigated the role of UCHL1 in pulmonary endothelial cell (EC) barrier function in vitro and in vivo and examined the effects of UCHL1 on VE-cadherin and claudin-5 regulation, important adherens and tight junctional components, respectively. Measurements of transendothelial electrical resistance confirmed decreased barrier enhancement induced by hepatocyte growth factor (HGF) and increased thrombin-induced permeability in both UCHL1-silenced ECs and in ECs pretreated with LDN-57444 (LDN), a pharmacological UCHL1 inhibitor. In addition, UCHL1 knockdown (siRNA) was associated with decreased expression of VE-cadherin and claudin-5, whereas silencing of the transcription factor FoxO1 restored claudin-5 levels. Finally, UCHL1 inhibition in vivo via LDN was associated with increased VILI in a murine model. These findings support a prominent functional role of UCHL1 in regulating lung vascular permeability via alterations in adherens and tight junctions and implicate UCHL1 as an important mediator of ALI.
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http://dx.doi.org/10.1152/ajplung.00492.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238159PMC
April 2021

Regulation of differentiation of annulus fibrosus-derived stem cells using heterogeneous electrospun fibrous scaffolds.

J Orthop Translat 2021 Jan 3;26:171-180. Epub 2020 Mar 3.

Departments of Orthopaedic Surgery and Urology, The First Affiliated Hospital, Orthopedic Institute, Medical College, Soochow University, Suzhou, Jiangsu, China.

Background: Tissue engineering of the annulus fibrosus (AF) shows promise as a treatment for patients with degenerative disc disease (DDD). However, it remains challenging due to the intrinsic heterogeneity of AF tissue. Fabrication of scaffolds recapitulating the specific cellular, componential, and microstructural features of AF, therefore, is critical to successful AF tissue regeneration.

Methods: Poly-L-lactic acid (PLLA) fibrous scaffolds with various fiber diameters and orientation were prepared to mimic the microstructural characteristics of AF tissue using electrospinning technique. AF-derived stem cells (AFSCs) were cultured on the PLLA fibrous scaffolds for 7 days.

Results: The morphology of AFSCs significantly varied when cultured on the scaffolds with various fiber diameters and orientation. AFSCs were nearly round on scaffolds with small fibers. However, they became spindle-shaped on scaffolds with large fibers. Meanwhile, upregulated expression of collagen-I gene happened in cells cultured on scaffolds with large fibers, while enhanced expression of collagen-II and aggrecan genes was seen on scaffolds with small fibers. The production of related proteins also showed similar trends. Further, culturing AFSCs on a heterogeneous scaffold by overlaying membranes with different fiber sizes led to the formation of a hierarchical structure approximating native AF tissue.

Conclusion: Findings from this study demonstrate that fibrous scaffolds with different fiber sizes effectively promoted the differentiation of AFSCs into specific cells similar to the types of cells at various AF zones. It also provides a valuable reference for regulation of cell differentiation and fabrication of engineered tissues with complex hierarchical structures using the physical cues of scaffolds.

The Translational Potential Of This Article: Effective AF repair is an essential need for treating degenerative disc disease. Tissue engineering is a promising approach to achieving tissue regeneration and restoring normal functions of tissues. By mimicking the key structural features of native AF tissue, including fiber size and alignment, this study deciphered the effect of scaffold materials on the cell differentiation and extracellular matrix deposition, which provides a solid basis for designing new strategies toward more effective AF repair and regeneration.
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http://dx.doi.org/10.1016/j.jot.2020.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773966PMC
January 2021

Prognostic value of the 21-gene recurrence score in ER-positive, HER2-negative, node-positive breast cancer was similar in node-negative diseases: a single-center study of 800 patients.

Front Med 2021 Aug 6;15(4):621-628. Epub 2020 Dec 6.

Comprehensive Breast Health Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer. This study aimed to evaluate the prognostic significance of the 21-gene recurrence score (RS) in Chinese patients with pN0-1, estrogen receptor-positive (ER), human epidermal growth factor receptor 2-negative (HER2) breast cancer. Among 800 patients recruited between 2009 and 2016, the median RS was 24 (0-69), with 27.4%, 46.8%, and 25.9% patients classified into low-, intermediate-, and high-risk groups. Cox regression analysis demonstrated that the high-risk category was associated with significantly higher odds of invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) events compared with the low-risk category (IDFS: HR = 2.450, 95% CI 1.017-5.902, P = 0.046; DDFS: HR = 2.829, 95% CI 1.013-7.901, P = 0.047). No significant association between RS category and overall survival (OS) was found (intermediate vs. low: HR= 1.244, 95% CI 0.292-5.297, P = 0.768; high vs. low: HR = 2.933, 95% CI 0.759-11.327, P = 0.119). RS, as a continuous variable, was a highly significant predictor for IDFS (HR= 1.028, 95% CI 1.010-1.047, P = 0.002), DDFS (HR= 1.030, 95% CI 1.010-1.051, P = 0.003), and OS (HR= 1.034, 95% CI 1.007-1.063, P = 0.014). Our findings suggested that RS may predict IDFS in Chinese patients with ER/HER2 breast cancer with N0 or N1 disease.
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http://dx.doi.org/10.1007/s11684-020-0738-0DOI Listing
August 2021

Vasonatrin peptide, a synthetic natriuretic peptide, attenuates myocardial injury and oxidative stress in isoprenaline-induced cardiomyocyte hypertrophy.

Peptides 2021 03 24;137:170474. Epub 2020 Dec 24.

Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address:

Isoprenaline-induced cardiac hypertrophy can deteriorate to heart failure, which is a leading cause of mortality. Endogenous vasonatrin peptide (VNP) has been reported to be cardioprotective against myocardial ischemia/reperfusion injury in diabetic rats. However, little is known about the effect of exogenous VNP on cardiac hypertrophy. We further explored whether VNP attenuated isoprenaline-induced cardiomyocyte hypertrophy by examining the levels and activities of cGMP and PKG. In this study, we found that VNP significantly attenuated isoprenaline-induced myocardial hypertrophy and cardiac fibroblast activation in vivo. Moreover, VNP effectively halted the activation of apoptosis and oxidative stress in the isoprenaline-treated myocardium. VNP promoted superoxide dismutase (SOD) activity. Further study revealed that the protective effects of VNP might be mediated by the activity of the cGMP-PKG signaling pathway in vivo or in vitro, while the use of agonists and antagonists confirmed these results. Therefore, we demonstrated that the antiapoptosis and antioxidative stress effects of VNP depends on elevated cGMP-PKG signaling activity both in vivo and in vitro. These results suggest that VNP may be used in the treatment of myocardial hypertrophy.
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http://dx.doi.org/10.1016/j.peptides.2020.170474DOI Listing
March 2021

QTL mapping and candidate gene analysis of seed vigor-related traits during artificial aging in wheat (Triticum aestivum).

Sci Rep 2020 12 16;10(1):22060. Epub 2020 Dec 16.

Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing, 100081, People's Republic of China.

High vigor seeds have greater yield potential than those with low vigor; however, long-term storage leads to a decline in this trait. The objective of this study was to identify quantitative trait loci (QTLs) for seed vigor-related traits under artificial aging conditions using a high-density genetic linkage map of wheat (Triticum aestivum) and mine the related candidate genes. A doubled haploid population, derived from a cross between Hanxuan 10 × Lumai 14, was used as the experimental material. Six controlled-environment treatments were set up, i.e. the seeds were aged for 0, 24, 36, 48, 60, and 72 h at a high temperature (48 °C) and under high humidity (relative humidity 100%). Eight traits including seed germination percentage, germination energy, germination index, seedling length, root length, seedling weight, vigor index, and simple vigor index were measured. With the prolongation of artificial aging treatment, these traits showed a continuous downward trend and significant correlations were observed between most of them. A total of 49 additive QTLs for seed vigor-related traits were mapped onto 12 chromosomes (1B, 2D, 3A, 3B, 3D, 4A, 4D, 5A, 5B, 5D, 6D, and 7A); and each one accounted for 6.01-17.18% of the phenotypic variations. Twenty-five pairs of epistatic QTLs were detected on all chromosomes, except for 5D, 6A, and 7D, and each epistasis accounted for 7.35-26.06% of the phenotypic variations. Three additive QTL hot spots were found on chromosomes 5A, 5B, and 5D, respectively. 13 QTLs, QGEe5B, QGIe5B, QSLc5B, QSLd5B, QSLf5B, QRLd5B, QRLe5B, QRLf5B, QVId5B, QVIe5B, QVIf5B, QSVId5B, and QSVIe5B, were located in the marker interval AX-94643729 ~ AX-110529646 on 5B and the physical interval 707,412,449-710,959,479 bp. Genes including TRAESCS5B01G564900, TRAESCS5B01G564200, TRAESCS5B01G562600, TraesCS5B02G562700, TRAESCS5B01G561300, TRAESCS5B01G561400, and TRAESCS5B01G562100, located in this marker interval, were found to be involved in regulating the processes of carbohydrate and lipid metabolism, transcription, and cell division during the germination of aging seeds, thus they were viewed as candidate genes for seed viability-related traits. These findings provide the basis for the seed-based cloning and functional identification of related candidate genes for seed vigor.
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http://dx.doi.org/10.1038/s41598-020-75778-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745025PMC
December 2020

Multi-path synergic fusion deep neural network framework for breast mass classification using digital breast tomosynthesis.

Phys Med Biol 2020 12 4;65(23):235045. Epub 2020 Dec 4.

Radiotherapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095 People's Republic of China. Contributed equally.

Objective: To develop and evaluate a multi-path synergic fusion (MSF) deep neural network model for breast mass classification using digital breast tomosynthesis (DBT).

Methods: We retrospectively collected 441 patients who had undergone DBT in which the regions of interest (ROIs) covering the malignant/benign breast mass were extracted for model training and validation. In the proposed MSF framework, three multifaceted representations of the breast mass (gross mass, overview, and mass background) are extracted from the ROIs and independently processed by a multi-scale multi-level features enforced DenseNet (MMFED). The three MMFED sub-models are finally fused at the decision level to generate the final prediction. The advantages of the MMFED over the original DenseNet, as well as different fusion strategies embedded in MSF, were comprehensively compared.

Results: The MMFED was observed to be superior to the original DenseNet, and multiple channel fusions in the MSF outperformed the single-channel MMFED and double-channel fusion with the best classification scores of area under the receiver operating characteristic (ROC) curve (87.03%), Accuracy (81.29%), Sensitivity (74.57%), and Specificity (84.53%) via the weighted fusion method embedded in MSF. The decision level fusion-based MSF was significantly better (in terms of the ROC curve) than the feature concatenation-based fusion (p< 0.05), the single MMFED using a fused three-channel image (p< 0.04), and the multiple MMFED end-to-end training (p< 0.004).

Conclusions: Integrating multifaceted representations of the breast mass tends to increase benign/malignant mass classification performance and the proposed methodology was verified to be a promising tool to assist in clinical breast cancer screening.
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http://dx.doi.org/10.1088/1361-6560/abaeb7DOI Listing
December 2020

HER2 positivity is not associated with adverse prognosis in high-risk estrogen receptor-positive early breast cancer patients treated with chemotherapy and trastuzumab.

Breast 2020 Dec 15;54:235-241. Epub 2020 Oct 15.

Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China. Electronic address:

Co-expression of human epidermal growth factor receptor-2 (HER2) and hormone receptor (HR) predicted worse prognosis in early breast cancer before trastuzumab was developed. We aimed to investigate whether HER2 positivity was still associated with worse outcome in high-risk estrogen receptor (ER) positive patients treated with trastuzumab and chemotherapy. In the present study, 227 ER+/HER2+ patients treated with trastuzumab and chemotherapy (HER2-pos-T group) and 1097 ER+/HER2-patients treated with chemotherapy alone (HER2-neg group) during 2009 and 2015 were retrospectively enrolled for the comparison of disease-free survival (DFS) and overall survival (OS). At a median follow-up of 59 months, 174 DFS events and 69 deaths were observed. The estimated 5-year DFS rate was 94.2% in the HER2-pos-T group and 87.4% in the HER2-neg group (Log-rank P = 0.014). HER2-pos-T group was associated with significantly better DFS in multivariate analysis (HR 0.38, 95% CI: 0.22-0.67, Log-rank P = 0.001). The estimated 5-year OS rates for the two groups were 97.2% and 95.7%, respectively (Log-rank P = 0.183). In multivariable analysis, patients in the HER2-pos-T group had significantly better OS compared with those in the HER2-neg group (HR 0.40, 95% CI: 0.17-0.95, Log-rank P = 0.037). We concluded that high-risk ER+/HER2+ breast cancer patients treated with chemotherapy and trastuzumab had superior prognosis compared with ER+/HER2-patients. Therefore, HER2 positivity itself may not be considered as an unfavorable factor for ER + patients in the era of trastuzumab.
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http://dx.doi.org/10.1016/j.breast.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653101PMC
December 2020

Early response and pathological complete remission in Breast Cancer with different molecular subtypes: a retrospective single center analysis.

J Cancer 2020 6;11(23):6916-6924. Epub 2020 Oct 6.

Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China.

To evaluate the association of clinical early response and pathological complete remission (pCR) in breast cancer patients with different molecular subtypes. Breast cancer patients who received neoadjuvant treatment (NAT) with clinical early response assessment from October 2008 to October 2018 were retrospectively analyzed. Clinical early response was defined as tumor size decreasing ≥30% evaluated by ultrasound after two cycles of NAT. Chi-square test was used to compare the pCR rates between the responder and non-responder groups with different molecular subtypes. Multivariate logistic regression was used to identify independent factors associated with the pCR. A total of 328 patients were included: 100 responders and 228 non-responders. The progesterone receptor (PR) expression was an independent factor associated with clinical early response (OR=2.39, 95%CI=1.41-4.05, =0.001). The pCR rate of breast was 50.0% for responders and 18.0% for non-responders (<0.001). Regarding different molecular subtypes, responders had higher pCR rates than non-responders for patients with HER2 overexpression (OR=10.66, 95%CI=2.18-52.15, =0.001), triple negative (OR=3.29, 95%CI=1.23-8.84, =0.016) and Luminal (HER2-) subtypes (OR=8.58, 95%CI=3.05-24.10, <0.001) respectively. Moreover, pCR rate can be achieved as high as 88.2% in HER2 overexpression patients with early clinical response, which was significantly higher than patients without early response (41.3%, =0.001). Multivariate analysis showed that clinical early response was an independent factor associated with the pCR rate (OR=4.87, 95%CI=2.72-8.72, <0.001). Early response was significantly associated with a higher pCR rate in breast cancer patients receiving NAT, especially for patients with HER2 overexpression subtype, which warrants further clinical evaluation.
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http://dx.doi.org/10.7150/jca.46805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591996PMC
October 2020

Cigarette Smoke and Nicotine-Containing Electronic-Cigarette Vapor Downregulate Lung WWOX Expression, Which Is Associated with Increased Severity of Murine Acute Respiratory Distress Syndrome.

Am J Respir Cell Mol Biol 2021 01;64(1):89-99

Division of Pulmonary, Critical Care, Sleep and Allergy Medicine, University of Illinois, Chicago, Illinois.

A history of chronic cigarette smoking is known to increase risk for acute respiratory distress syndrome (ARDS), but the corresponding risks associated with chronic e-cigarette use are largely unknown. The chromosomal fragile site gene, WWOX, is highly susceptible to genotoxic stress from environmental exposures and thus an interesting candidate gene for the study of exposure-related lung disease. Lungs harvested from current versus former/never-smokers exhibited a 47% decrease in WWOX mRNA levels. Exposure to nicotine-containing e-cigarette vapor resulted in an average 57% decrease in WWOX mRNA levels relative to vehicle-treated controls. In separate studies, endothelial (EC)-specific WWOX knockout (KO) versus WWOX flox control mice were examined under ARDS-producing conditions. EC WWOX KO mice exhibited significantly greater levels of vascular leak and histologic lung injury. ECs were isolated from digested lungs of untreated EC WWOX KO mice using sorting by flow cytometry for CD31 CD45cells. These were grown in culture, confirmed to be WWOX deficient by RT-PCR and Western blotting, and analyzed by electric cell impedance sensing as well as an FITC dextran transwell assay for their barrier properties during methicillin-resistant or LPS exposure. WWOX KO ECs demonstrated significantly greater declines in barrier function relative to cells from WWOX flox controls during either methicillin-resistant or LPS treatment as measured by both electric cell impedance sensing and the transwell assay. The increased risk for ARDS observed in chronic smokers may be mechanistically linked, at least in part, to lung WWOX downregulation, and this phenomenon may also manifest in the near future in chronic users of e-cigarettes.
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http://dx.doi.org/10.1165/rcmb.2020-0145OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780991PMC
January 2021

A Novel Prognostic Scoring System Integrating Gene Expressions and Clinicopathological Characteristics to Predict Very Early Relapse in Node-Negative Estrogen Receptor-Positive/HER2-Negative Breast Cancer.

Front Oncol 2020 11;10:1335. Epub 2020 Sep 11.

Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Despite low aggressiveness in tumor biology and high responsiveness to endocrine therapy, subgroups of patients with estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer relapse early in the first two years after initiation of endocrine therapy, indicating potential endocrine resistance. Accordingly, we attempted to establish a scoring system to inform the first-2-year prognosis (F2P Score). Patients with node-negative ER+/HER2- breast cancer and complete data of gene expressions in a 21-gene panel were retrospectively retrieved from Shanghai Jiao Tong University Breast Cancer Database (SJTU-BCDB). The F2P Score was established based on the clinical and genomic variables associated with the first-2-year relapse after shrinkage correction and validated using the bootstrap resampling method. Model performance was quantified by Harrell's concordance-index (C-index) and Bayesian information criteria (BIC). The F2P Score was established by integrating the clinical (age and tumor size) and genomic (, and ) variables with a C-index of 0.71 and BIC of 397.46. Bootstrap C-index was 0.72 (95% CI, 0.62-0.81) and BIC was 396.75 (95% CI, 252.37-541.13). A higher score indicated an increased likelihood of a first-2-year relapse, when used as continuous (HR, 2.94; 95% CI, 1.87-4.61) or categorical (HR, 3.68; 95% CI, 1.70-8.00) predictors in multivariate analysis. Both continuous and categorical F2P Score also remained prognostic for overall survival and other endpoints. No significant interaction was observed between the F2P Score and treatment subgroups. Additionally, the F2P Score outperformed the IHC4, clinical treatment score and 21-gene test in predicting first-2-year relapse. The F2P Score reported herein, integrating the clinicopathological and genomic variables, may inform prognosis and endocrine responsiveness. After the benefits and risks have been considered, treatment escalation may be an alternative strategy for patients with a higher score.
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http://dx.doi.org/10.3389/fonc.2020.01335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518385PMC
September 2020

Validation of the Prognostic Stage of American Joint Committee on Cancer Eighth Edition Staging Manual in Invasive Lobular Carcinoma Compared to Invasive Ductal Carcinoma and Proposal of a Novel Score System.

Front Oncol 2020 18;10:1471. Epub 2020 Aug 18.

Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The objective of this study was to evaluate the American Joint Committee on Cancer (AJCC) pathological prognostic stage among patients with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) and to propose a modified score system if necessary. Women diagnosed with IDC and ILC during 2010-2015 in the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively identified. Disease-specific survival (DSS) and overall survival (OS) were estimated by Kaplan-Meier method. Predictive performances of different staging systems were evaluated based on Harrell concordance index (C-index) and Akaike Information Criterion (AIC). Multivariate Cox models were conducted to build preferable score systems. A total of 184,541 female patients were included in the final analyses, with a median follow-up of 30.0 months. In IDC cohort, the pathological prognostic stage (C-index, 0.8281; AIC, 110274.5) was superior to the anatomic stage (C-index, 0.8125; AIC, 112537.0; < 0.001 for C-index) in risk stratification with respect to DSS. In ILC cohort, the prognostic stage (C-index, 0.8281; AIC, 7124.423) didn't outperform the anatomic stage (C-index, 0.8324; AIC, 7144.818; = 0.748 for C-index) with respect to DSS. Similar results were observed with respect to OS. The score system defined by anatomic stage plus grade plus estrogen receptor and progesterone receptor (AS+GEP) allows for better staging (C-index, 0.8085; AIC, 7178.448) for ILC patients. Compared with anatomic stage, the pathological prognostic stage provided more accurate stratification for patients with IDC, but not for patients with ILC. The AS+GEP score system may fit ILC tumors better.
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http://dx.doi.org/10.3389/fonc.2020.01471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461987PMC
August 2020

Additive value of exposure parameters for breast cancer diagnosis in digital mammography.

Eur Radiol 2021 Apr 26;31(4):2539-2547. Epub 2020 Sep 26.

Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.

Objectives: To investigate the effect of different breast lesions on exposure parameters in digital mammography and to determine whether the exposure parameters can additively improve diagnostic efficiency.

Methods: Craniocaudal view and mediolateral view full-field digital mammography images from 982 women with unilateral lesions (341 with malignant lesions, 189 with benign lesions, and 452 healthy women) obtained at Nanfang Hospital were reviewed. Differences in exposure parameters (tube voltage and load, breast thickness (BT), and average glandular dose (AGD)) between breasts were calculated. The relationships between parameter differences and lesion size were explored. A logistic regression model was used based on the AGD and BT differences, and the area under the receiver operating characteristic curve (AUC) was used to assess the performance of these parameters in differentiating malignant from benign and healthy subjects. Independently, data from 129 women (82 with malignant and 47 with benign lesions) treated at Sun Yat-sen Memorial Hospital were collected to validate the model.

Results: Differences in tube voltage and load, BT, and AGD between breasts were significantly greater in the malignant subjects than benign (p < 0.05) and healthy subjects (p < 0.05). The AUCs for the comparisons of malignant vs. healthy subjects, malignant vs. benign subjects, and benign vs. healthy subjects were 0.77 ± 0.02, 0.72 ± 0.02, and 0.57 ± 0.02, respectively. The model combining the exposure parameters with the BI-RADS category resulted in a higher AUC (0.910 ± 0.03) compared with physician diagnosis alone (0.820 ± 0.04) for differentiating between malignant and benign lesions.

Conclusions: Exposure parameters additively improved diagnostic accuracy for breast cancer and yielded more reliable results.

Key Points: • Differences in kVp, mAs, BT, and AGD between breasts were significantly greater in the malignant subjects than benign and healthy subjects. • The model combining exposure parameters with the BI-RADS category resulted in a higher AUC compared with the physician's diagnosis for differentiating between malignant and benign lesions. • Exposure parameters additively improved diagnostic accuracy for breast cancer.
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http://dx.doi.org/10.1007/s00330-020-07311-9DOI Listing
April 2021
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