Comparison of Two Ultrasmall Superparamagnetic Iron Oxides on Cytotoxicity and MR Imaging of Tumors

Purpose: This study was performed to compare the cytotoxicity and magnetic resonance (MR) contrast in diverse cultured cells and xenograft tumors models of two ultra-small superparamagnetic iron oxides (USPIOs), thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) and monocrystalline iron oxide nanoparticles (MION-47)

Predicting Axillary Lymph Node Metastasis in Early Breast Cancer Using Deep Learning on Primary Tumor Biopsy Slides

Objectives: To develop and validate a deep learning (DL)-based primary tumor biopsy signature for predicting axillary lymph node (ALN) metastasis preoperatively in early breast cancer (EBC) patients with clinically negative ALN. Methods: A total of 1,058 EBC patients with pathologically confirmed ALN status were enrolled from May 2010 to August 2020. A DL core-needle biopsy (DL-CNB) model was built on the attention-based multiple instance-learning (AMIL) framework to predict ALN status utilizing the DL features, which were extracted from the cancer areas of digitized whole-slide images (WSIs) of breast CNB specimens annotated by two pathologists. Accuracy, sensitivity, specificity, receiver operating characteristic (ROC) curves, and areas under the ROC curve (AUCs) were analyzed to evaluate our model. Results: The best-performing DL-CNB model with VGG16_BN as the feature extractor achieved an AUC of 0.816 (95% confidence interval (CI): 0.758, 0.865) in predicting positive ALN metastasis in the independent test cohort. Furthermore, our model incorporating the clinical data, which was called DL-CNB+C, yielded the best accuracy of 0.831 (95%CI: 0.775, 0.878), especially for patients younger than 50 years (AUC: 0.918, 95%CI: 0.825, 0.971). The interpretation of DL-CNB model showed that the top signatures most predictive of ALN metastasis were characterized by the nucleus features including density ($p$ = 0.015), circumference ($p$ = 0.009), circularity ($p$ = 0.010), and orientation ($p$ = 0.012). Conclusion: Our study provides a novel DL-based biomarker on primary tumor CNB slides to predict the metastatic status of ALN preoperatively for patients with EBC. The codes and dataset are available at https://github.com/bupt-ai-cz/BALNMPComment: Update Table 1 and corresponding description

Inventarisasi Tanaman Peneduh Jalan Penjerap Timbal di Purwokerto

Tanaman peneduh jalan adalah tanaman yang berada di tepi jalan. Tanaman peneduh jalan memiliki dua fungsi yaitu sebagai estetika dan ekologis. Salah satu fungsi ekologis tanaman peneduh jalan adalah mengakumulasi bahan pencemar. Jenis pencemaran yang memerlukan penanganan secara sistematis dan komprehensif adalah pencemaran timbal (Pb). Pb banyak dihasilkan oleh aktivitas pembakaran bahan bakar minyak kendaraan bermotor. Jenis tanaman peneduh jalan yang berpotensi mengakumulasi Pb belum tereksplorasi sehingga dilakukan riset yang dapat menghasilkan database jenis spesies yang mampu mengurangi Pb di lingkungan. Tujuan penelitian adalah menginventarisasi jenis tanaman peneduh jalan penjerap Pb. Manfaat penelitian adalah mendapatkan jenis tanaman peneduh jalan yang berpotensi penjerap Pb. Metode penelitian yang digunakan adalah survai di 8 (delapan) jalan di wilayah Purwokerto. Sampel daun tanaman peneduh jalan diambil secara acak terpilih di sepanjang jalan tersebut. Hasil penelitian menunjukkan jenis-jenis tanaman peneduh jalan yang berpotensi menjerap Pb adalah Glodogan (Polyalthea longifolia), Angsana (Pterocarpus indicus), Filicium (Filicium decipiends), Ketapang (Terminalia catappa), Beringin (Ficus benjamina), Kupu-kupu (Bauhinia tomentosa), Puspa (Schima wallichii), Kenari (Canarium ovatum) dan Genitu (Chrysophyllum cainito)

Breast Cancer Immunohistochemical Image Generation: a Benchmark Dataset and Challenge Review

For invasive breast cancer, immunohistochemical (IHC) techniques are often used to detect the expression level of human epidermal growth factor receptor-2 (HER2) in breast tissue to formulate a precise treatment plan. From the perspective of saving manpower, material and time costs, directly generating IHC-stained images from hematoxylin and eosin (H&E) stained images is a valuable research direction. Therefore, we held the breast cancer immunohistochemical image generation challenge, aiming to explore novel ideas of deep learning technology in pathological image generation and promote research in this field. The challenge provided registered H&E and IHC-stained image pairs, and participants were required to use these images to train a model that can directly generate IHC-stained images from corresponding H&E-stained images. We selected and reviewed the five highest-ranking methods based on their PSNR and SSIM metrics, while also providing overviews of the corresponding pipelines and implementations. In this paper, we further analyze the current limitations in the field of breast cancer immunohistochemical image generation and forecast the future development of this field. We hope that the released dataset and the challenge will inspire more scholars to jointly study higher-quality IHC-stained image generation.Comment: 13 pages, 11 figures, 2table

Construction of a Food-grade Expression Vector Based on pyrF Gene in Lactococcus lactis

In this study, the pyrF screening marker and the genomic DNA fragments were used to construct the expression vectors in food-grade Lactococcus lactis (L. lactis). Such expression system could potentially be used to express and produce food-grade and medicinal polypeptides. Firstly, the NZ3900 ΔpyrF auxotrophic strain was created from the homologous recombination mutant cassette. Secondly, the repA and repC genes were used as the replication elements, the pyrF gene as the screening marker, the P32 and P8 elements from L. lactis as the promoters, and the Tusp45 and TpepN from L. lactis as the terminators, all of which were constructed in the expression plasmid pLD. Finally, the reporter gene ZsGreen (a fluorescent protein) was used to verify the expression of recombinant protein in the NZ3900 ΔpyrF mutant strain and the genetic stability of pLD-ZsG plasmid. The result showed that the prototrophic ZsGreen positive transformants could grow normally in common Elliker culture medium, and the green fluorescent signal was observed under a fluorescence microscope. In addition, ZsGreen protein could be highly expressed in NZ3900 ΔpyrF and the expression plasmid could be stably transmitted through at least 30 generations, according to the results of the PCR and Western blotting, indicating that the recombinant protein was expressed in L. lactis in a stable manner. Based on the above results, the approach for creating an L. lactis expression vector (without antibiotic resistance gene) based on the pyrF auxotrophic marker is feasible and offers a basis for further investigation into the use of L. lactis to manufacture food- and pharmaceutical-grade polypeptides

Gradient differences of immunotherapy efficacy in metastatic melanoma related to sunlight exposure pattern: A population-based study

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized metastatic melanoma (MM) treatment in just a few years. Ultraviolet (UV) in sunlight is the most significant environmental cause of melanoma, which is considered to be the main reason for tumor mutation burden (TMB) increase in melanoma. High TMB usually predicts that PD-1 inhibitors are effective. The sunlight exposure pattern of MM might be a clinical feature that matches TMB. The relationship between sunlight exposure patterns and immunotherapy response in MM is unclear. This study aims to investigate the correlation between sunlight exposure patterns and immunotherapy response in MM and establish nomograms that predict 3- and 5-year overall survival (OS) rate.MethodsWe searched the Surveillance, Epidemiology, and End Results (SEER) database and enrolled MM cases from 2005-2016. According to the advent of ICIs in 2011, the era was divided into the non-ICIs era (2005-2010) and the ICIs era (2011-2016). Patients were divided into three cohorts according to the primary site sunlight exposure patterns: head and neck in the first cohort, trunk arms and legs in the second cohort, and acral sites in the third cohort. We compared survival differences for each cohort between the two eras, performed stratified analysis, established nomograms for predicting 3- and 5-year OS rate, and performed internal validation.ResultsComparing the survival difference between the ICIs and non-ICIs era, head and neck melanoma showed the greatest improvement in survival, with 3- and 5-year OS rate increasing by 10.2% and 9.1%, respectively (P=0.00011). In trunk arms and legs melanoma, the 3- and 5-year OS rate increased by 4.6% and 3.9%, respectively (P<0.0001). There is no improvement in survival in acral melanoma (AM) between the two eras (P=0.78). The receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and calibration graphs show good discrimination and accuracy of nomograms. Decision curve analysis (DCA) suggests good clinical utility of nomograms.ConclusionsBased on the classification of sunlight exposure patterns, there is a gradient difference in immunotherapy efficacy for MM. The degree of sunlight exposure is positively correlated with immunotherapy response. The nomograms are sufficiently accurate to predict 3- and 5-year OS rate for MM, allowing for individualized clinical decisions for future clinical work

RAS/BRAF Circulating Tumor DNA Mutations as a Predictor of Response to First-Line Chemotherapy in Metastatic Colorectal Cancer Patients

Background. Since circulating tumor DNA (ctDNA) offers clear advantages as a minimally invasive method for tumor monitoring compared with tumor tissue, we aimed to evaluate genotyping ctDNA using a next-generation sequencing- (NGS-) based panel to identify the prognostic value of mutation status in metastatic colorectal cancer (mCRC) patients with primary tumor resected and with subsequent lines of treatment in this study. Methods. 76 mCRC patients treated in Beijing Chao-Yang Hospital from 2011 to 2017 were enrolled. Genotyping of RAS/BRAF in tumor tissue and ctDNA was determined by ARMS PCR and with a 40-gene panel using NGS, respectively. Patient clinicopathologic features and RAS/BRAF gene mutation status were evaluated by survival analysis for disease-free survival (DFS) and progression-free survival (PFS). Results. Among 76 patients, KRAS distributions were not significantly correlated with any clinicopathologic features. The concordance between tumor tissue and ctDNA KRAS mutation was 81.25%. Mutations of RAS/BRAF had no significant impact on DFS after surgery (hazard ratio (HR), 1.205; 95% CI, 0.618 to 2.349; P=0.5837) but prognosticated poorer PFS in subsequent first-line therapy (HR, 3.351; 95% CI, 1.172 to 9.576; P=0.024). Conclusion. ctDNA was comparable with tumor tissue for mutation detection. RAS/BRAF mutations detected in ctDNA predict a worse PFS in mCRC patients with first-line chemotherapy. Our results provide support for the prognostic value of RAS/BRAF ctDNA mutation detection in mCRC patients

An HR-MAS MR Metabolomics Study on Breast Tissues Obtained with Core Needle Biopsy

BACKGROUND: Much research has been devoted to the development of new breast cancer diagnostic measures, including those involving high-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopic techniques. Previous HR-MAS MR results have been obtained from post-surgery samples, which limits their direct clinical applicability. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we performed HR-MAS MR spectroscopic studies on 31 breast tissue samples (13 cancer and 18 non-cancer) obtained by percutaneous core needle biopsy. We showed that cancer and non-cancer samples can be discriminated very well with Orthogonal Projections to Latent Structure-Discriminant Analysis (OPLS-DA) multivariate model on the MR spectra. A subsequent blind test showed 69% sensitivity and 94% specificity in the prediction of the cancer status. A spectral analysis showed that in cancer cells, taurine- and choline-containing compounds are elevated. Our approach, additionally, could predict the progesterone receptor statuses of the cancer patients. CONCLUSIONS/SIGNIFICANCE: HR-MAS MR metabolomics on intact breast tissues obtained by core needle biopsy may have a potential to be used as a complement to the current diagnostic and prognostic measures for breast cancers

Efficiency Analysis of Private Lending Market in China—Based on Hurst Index

This paper explored the efficiency of the private lending market based on the fractal market theory. We used the rescaled range analysis method and the generalized Hurst exponent analysis method respectively, and we got that the private lending market had not yet reached the weakly efficient level and was anti-persistent. Then we further used the time-varying Hurst index to describe the dynamic changes in the efficiency of the private lending market and analyzed the Chinese stock market and foreign exchange market as a comparative analysis. We found that among the three markets, the efficiency of the private lending market was the lowest, and that there was a correlation between the efficiencies of the three markets, and its effectiveness was affected by the other two markets. Finally, based on the above analysis results, we put forward relevant suggestions on the development of the private lending market and provided a decision basis for investors in the private financing market

An HR-MAS MR Metabolomics Study on Breast Tissues Obtained with Core Needle Biopsy

학위논문 (박사)-- 서울대학교 대학원 : 의과학과 의과학 전공, 2013. 2. 문우경.Introduction: Much research has been devoted to the development of new breast cancer diagnostic measures, including those involving high-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopic techniques. Previous HR-MAS MR results have been obtained from surgical specimen, which limits their direct clinical applicability. Methodology/Principal Findings: In the present study, we performed HR-MAS MR spectroscopic studies on 31 breast tissue samples (13 cancer and 18 non-cancer) obtained by percutaneous core needle biopsy. We employed Carr Purcell Meiboom Gill (CPMG) pulse sequence which can selectively suppress signals with short relaxation times, most notably, lipid signals abundant in core needle biopsy samples. Cancer and non-cancer samples were discriminated very well with Orthogonal Projections to Latent Structure-Discriminant Analysis (OPLS-DA) multivariate model on the MR spectra. A subsequent blind test showed 69% sensitivity and 94% specificity in the prediction of the cancer status. A spectral analysis showed that in cancer cells, taurine- (3.43 ppm) and choline- (3.23 ppm) containing compounds are elevated. Conclusions/Significance: HR-MAS MR metabolomics on intact breast tissues obtained by core needle biopsy may have a potential to be used as a complement to the current diagnostic measures for breast cancers.Table 1. Clinical and histological data on 31samples from 22 patients ----------22 Table 2. Tumor characteristics of the 13 patients -----------------------------------23 Chapter 2 Figure 1. Schematic illustration of HR-MAS MR spectra study ----------------- 24 Figure 2. HR-MAS MR spectra of breast tissue samples --------------------------25 Figure 3. Multivariate discrimination model-----------------------------------------26 Figure 4. Prediction result for cancer status based on OPLS-DA model -------- 27 Figure 5. Signals contributing to differentiation-------------------------------------28 Figure 6. Average spectra and Mann-Whitney U test for marker signals ------- 29 Figure 7. Discrimination based on prognostic markers ----------------------------30 Supplement Figure 1. Multivariate discrimination model--------------------------31 Supplement Figure 2. H&E staining and immunohistochemistry analysis-------32Docto