Correlation of androgen receptor with ultrasound, clinicopathological features and clinical outcomes in breast cancer.

BACKGROUND: This study aimed to explore whether there is an association between androgen receptor (AR) expression and ultrasound, clinicopathological features and prognosis of breast cancer. METHODS: A total of 141 breast cancer patients were included in this retrospective study. AR expression was analyzed by immunohistochemistry. The images of B-mode, color Doppler and strain elastography from 104 patients were collected continuously, and the corresponding ultrasound characteristics were obtained. The differences in ultrasound and clinicopathological features in different AR status were analyzed. Progression-free survival (PFS) of patients was obtained through up to 90 months of follow-up; then, the effect of AR on PFS was analyzed. Subsequently, a nomogram was constructed to predict the AR status. The predictive accuracy was calculated using C-index. RESULTS: The positive expression of AR (AR +) was associated with lower histological grade (p = 0.034) and lower Ki-67 level (p = 0.029). Triple-negative breast cancer (TNBC) had the lowest probability of AR + (p < 0.001). The AR + group mostly showed unsmooth margin (p < 0.001), posterior acoustic shadowing (p = 0.002) and higher elasticity score (p = 0.022) on ultrasound. The echo pattern of most tumors with AR + was heterogeneous (p = 0.024) in Luminal A subtype. AR + could be a sign of a better prognosis in overall breast cancer (p < 0.001), as well as in human epidermal growth factor receptor 2 (HER2) overexpression and Luminal B subtypes (p = 0.001 and 0.025). The nomogram showed relatively reliable performance with a C-index of 0.799. CONCLUSION: Our research demonstrated that AR expression was closely related to ultrasound, clinicopathological features and prognosis of breast cancer.

Radiogenomic analysis of prediction HER2 status in breast cancer by linking ultrasound radiomic feature module with biological functions.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpressed associated with poor prognosis in breast cancer and HER2 has been defined as a therapeutic target for breast cancer treatment. We aimed to explore the molecular biological information in ultrasound radiomic features (URFs) of HER2-positive breast cancer using radiogenomic analysis. Moreover, a radiomics model was developed to predict the status of HER2 in breast cancer. METHODS: This retrospective study included 489 patients who were diagnosed with breast cancer. URFs were extracted from a radiomics analysis set using PyRadiomics. The correlations between differential URFs and HER2-related genes were calculated using Pearson correlation analysis. Functional enrichment of the identified URFs-correlated HER2 positive-specific genes was performed. Lastly, the radiomics model was developed based on the URF-module mined from auxiliary differential URFs to assess the HER2 status of breast cancer. RESULTS: Eight differential URFs (p < 0.05) were identified among the 86 URFs extracted by Pyradiomics. 25 genes that were found to be the most closely associated with URFs. Then, the relevant biological functions of each differential URF were obtained through functional enrichment analysis. Among them, Zone Entropy is related to immune cell activity, which regulate the generation of calcification in breast cancer. The radiomics model based on the Logistic classifier and URF-module showed good discriminative ability (AUC = 0.80, 95% CI). CONCLUSION: We searched for the URFs of HER2-positive breast cancer, and explored the underlying genes and biological functions of these URFs. Furthermore, the radiomics model based on the Logistic classifier and URF-module relatively accurately predicted the HER2 status in breast cancer.

Genome-Wide Association Study Identifies a Rice Panicle Blast Resistance Gene Pb3 Encoding NLR Protein.

Rice blast is a worldwide fungal disease that seriously affects the yield and quality of rice. Identification of resistance genes against rice blast disease is one of the effective ways to control this disease. However, panicle blast resistance genes, which are useful in the fields, have rarely been studied due to the difficulty in phenotypic identification and the environmental influences. Here, panicle blast resistance-3 (Pb3) was identified by a genome-wide association study (GWAS) based on the panicle blast resistance phenotypes of 230 Rice Diversity Panel I (RDP-I) accessions with 700,000 single-nucleotide polymorphism (SNP) markers. A total of 16 panicle blast resistance loci (PBRLs) within three years including one repeated locus PBRL3 located in chromosome 11 were identified. In addition, 7 genes in PBRL3 were identified as candidate genes by haplotype analysis, which showed significant differences between resistant and susceptible varieties. Among them, one nucleotide-binding domain and Leucine-rich Repeat (NLR) gene Pb3 was highly conserved in multiple resistant rice cultivars, and its expression was significantly induced after rice blast inoculation. Evolutionary analysis showed that Pb3 was a typical disease resistance gene containing coiled-coil, NB-ARC, and LRR domains. T-DNA insertion mutants and CRISPR lines of Pb3 showed significantly reduced panicle blast resistance. These results indicate that Pb3 is a panicle blast resistance gene and GWAS is a rapid method for identifying panicle blast resistance in rice.

Nomograms predicting recurrence in patients with triple negative breast cancer based on ultrasound and clinicopathological features.

OBJECTIVES: The clinicopathological and ultrasound features associated with recurrence in patients with triple negative breast cancer (TNBC) were used to develop a nomogram to predict the prognosis of TNBC. METHODS: Clinicopathological data of 300 patients with TNBC treated between July 2012 and September 2014 were retrospectively reviewed. The endpoint was progression-free survival (PFS). Prognostic factors were screened by multivariate COX regression to develop nomograms. The C-index and calibration curves were used to evaluate the predictive accuracy and discriminatory ability of nomograms. RESULTS: Of 300 patients with TNBC followed-up for 5 years, 80 (26.7%) had PFS events. Five informative prognostic factors (large size, vertical orientation, posterior acoustic enhancement, lymph node involvement, and high pathological stage) were screened and used to construct a nomogram for PFS. The C-index of the PFS nomogram was 0.88 (p < 0.01, 95% confidence interval, 0.85-0.90), indicating good predictive accuracy. CONCLUSIONS: We developed and validated a nomogram for predicting PFS in TNBC. Vertical orientation and posterior acoustic enhancement in ultrasound images of TNBC were associated with worse outcomes. ADVANCES IN KNOWLEDGE: Patients with TNBC have a very poor prognosis and patients have a high risk of recurrence, and our study developed a nomogram based on ultrasound and clinicopathological features for TNBC patients to improve the accuracy of individualized prediction of recurrence and provide help for clinical treatment.

Genome-Wide Association Study Identifies a Rice Panicle Blast Resistance Gene, Pb2, Encoding NLR Protein.

Rice blast is one of the main diseases in rice and can occur in different rice growth stages. Due to the complicated procedure of panicle blast identification and instability of panicle blast infection influenced by the environment, most cloned rice resistance genes are associated with leaf blast. In this study, a rice panicle blast resistance gene, Pb2, was identified by genome-wide association mapping based on the panicle blast resistance phenotypes of 230 Rice Diversity Panel 1 (RDP1) accessions with 700,000 single-nucleotide polymorphism (SNP) markers. A genome-wide association study identified 18 panicle blast resistance loci (PBRL) within two years, including 9 reported loci and 2 repeated loci (PBRL2 and PBRL13, PBRL10 and PBRL18). Among them, the repeated locus (PBRL10 and PBRL18) was located in chromosome 11. By haplotype and expression analysis, one of the Nucleotide-binding domain and Leucine-rich Repeat (NLR) Pb2 genes was highly conserved in multiple resistant rice cultivars, and its expression was significantly upregulated after rice blast infection. Pb2 encodes a typical NBS-LRR protein with NB-ARC domain and LRR domain. Compared with wild type plants, the transgenic rice of Pb2 showed enhanced resistance to panicle and leaf blast with reduced lesion number. Subcellular localization of Pb2 showed that it is located on plasma membrane, and GUS tissue-staining observation found that Pb2 is highly expressed in grains, leaf tips and stem nodes. The Pb2 transgenic plants showed no difference in agronomic traits with wild type plants. It indicated that Pb2 could be useful for breeding of rice blast resistance.

Predicting Pathological Complete Response After Neoadjuvant Chemotherapy in Advanced Breast Cancer by Ultrasound and Clinicopathological Features Using a Nomogram.

BACKGROUND AND AIMS: Prediction of pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) for breast cancer is critical for surgical planning and evaluation of NAC efficacy. The purpose of this project was to assess the efficiency of a novel nomogram based on ultrasound and clinicopathological features for predicting pCR after NAC. METHODS: This retrospective study included 282 patients with advanced breast cancer treated with NAC from two centers. Patients received breast ultrasound before NAC and after two cycles of NAC; and the ultrasound, clinicopathological features and feature changes after two cycles of NAC were recorded. A multivariate logistic regression model was combined with bootstrapping screened for informative features associated with pCR. Then, we constructed two nomograms: an initial-baseline nomogram and a two-cycle response nomogram. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were analyzed. The C-index was used to evaluate predictive accuracy. RESULTS: Sixty (60/282, 21.28%) patients achieved pCR. Triple-negative breast cancer (TNBC) and HER2-amplified types were more likely to obtain pCR. Size shrinkage, posterior acoustic pattern, and elasticity score were identified as independent factors by multivariate logistic regression. In the validation cohort, the two-cycle response nomogram showed better discrimination than the initial-baseline nomogram, with the C-index reaching 0.79. The sensitivity, specificity, and NPV of the two-cycle response nomogram were 0.77, 0.77, and 0.92, respectively. CONCLUSION: The two-cycle response nomogram exhibited satisfactory efficiency, which means that the nomogram was a reliable method to predict pCR after NAC. Size shrinkage after two cycles of NAC was an important in dependent factor in predicting pCR.

Molecular Characteristics and Drug Resistance of Mycobacterium tuberculosis Isolate Circulating in Shaanxi Province, Northwestern China.

Objective: Shaanxi is the most highly populated province with high burdens of tuberculosis in northwestern China. The aim of this study was to investigate the molecular characteristics and drug resistance of Mycobacterium tuberculosis isolates from Shaanxi province of China in 2018. Methods: Phenotypic drug susceptibility testing and spoligotyping methods were performed on 518 M. tuberculosis isolates; drug-resistant isolates were sequenced in 11 drug loci, including katG, inhA, oxyR-ahpC, rpoB, embB, rpsL, rrs1 (nucleotides 388-1084), gyrA, gyrB, rrs2 (nucleotides 1158-1674), and eis. Results: The prevalences of isoniazid, rifampicin, ethambutol, streptomycin, ofloxacin, and kanamycin resistance were 22.0%, 19.3%, 7.9%, 23.8%, 10.4%, and 3.3%, respectively. The Beijing family (82.8%) was the predominant genotype, followed by the T (9.3%), H (0.6%), CAS (0.4%), LAM (0.4%), and U (0.4%) families. The percentage of Beijing genotype in a central area (88.1%) was higher than in the south (77.3%) and the north area (80.1%) (p < 0.05), while the sex, age, and treatment history between Beijing and non-Beijing family were not statistically different. Mutation analysis found that the most prevalent mutations were katG315, rpoB531, embB306, rpsL43, gyrA94, and rrs1401; the Beijing family exhibited a high rate of isoniazid-resistant isolates carrying katG315 mutations (p < 0.05). Furthermore, compared with the phenotypic data, the sensitivities of isoniazid, rifampicin, ethambutol, streptomycin, ofloxacin, and kanamycin resistance by sequencing base on 11 loci were 85.1%, 94.0%, 53.7%, 74.8%, 77.8%, and 64.7%, respectively. Conclusions: Shaanxi has a serious epidemic of drug-resistant tuberculosis, Beijing family is the predominant genotype, and the distribution showed geographic diversity. The prevalence of Beijing genotypes has a tendency to promote the transmission of high-level isoniazid-resistant M. tuberculosis. Besides, the hot spot regions localized in the embB, rrs2, and eis gene appear not to serve as excellent biomarkers for predicting ethambutol and kanamycin resistance in Shaanxi.

Genotypes of Mycobacterium tuberculosis isolates circulating in Shaanxi Province, China.

OBJECTIVES: The prevalence of drug-resistant TB in Shaanxi Province is higher than other areas. This study was aimed to investigate the genetic diversity and epidemiology of Mycobacterium tuberculosis clinical strains in Shaanxi Province, China. METHODS: From January to December 2016, a total of 298 Mycobacterium tuberculosis clinical isolates from smear-positive pulmonary tuberculosis patients were genotyped by Mcspoligotyping and 15-locus VNTR. RESULTS: We found that the Beijing family strains was the most prominent family(81.54%, 243/298). Other family strains included T family(9.06%, 27/298), U family(0.67%, 2/298), LAM9 family(0.34%, 1/298) and Manu family(0.34%, 1/298). The rates of multidrug-resistant (MDR) M.Tuberculosis, age, type of case and education between Beijing and non-Beijing family strains were not statistically different, while the distribution in the three different regions among these was statistically significant. VNTR results showed that strains were classified into 280 genotypes, and 33 (11.07%) strains could be grouped into 14 clusters. 11 of the 15-VNTR loci were highly or moderately discriminative according to the Hunter-Gaston discriminatory index. CONCLUSIONS: We concluded that the Beijing family genotype was the most prevalent genotype and 15-locus VNTR typing might be suitable for genotyping of M. tuberculosis in Shaanxi Province. There was less association between Beijing family genotypes and drug resistance in our study area.

Molecular characteristics and in vitro susceptibility to bedaquiline of Mycobacterium tuberculosis isolates circulating in Shaanxi, China.

OBJECTIVE: The aim of this study was to investigate the molecular characteristics and in vitro susceptibility to bedaquiline of Mycobacterium tuberculosis (MTB) isolates from Shaanxi, China. METHODS: The minimum inhibitory concentration (MIC) of bedaquiline was determined using the microplate alamarBlue assay for 518 MTB isolates from Shaanxi. Isolates with MIC values of bedaquiline ≥0.12 µg/mL were sequenced for the atpE, Rv0678, and pepQ genes. Drug susceptibility testing and spoligotyping were also conducted for all strains. RESULTS: Ten (1.93%) bedaquiline-resistant strains were isolated from 518 tuberculosis patients. The resistance rate of bedaquiline was not correlated to sex, age, treatment history, region, or genotype. Five bedaquiline-resistant isolates and one bedaquiline-susceptible isolate were found to carry Rv0678 mutations; six mutation types were identified, including G5T, A263G, C185T, G19deletion, C265T, and T323C. No mutations within the atpE and pepQ genes were observed. CONCLUSIONS: Bedaquiline showed strong in vitro antibacterial activity against MTB isolates, and the Rv0678 gene serves as the major mechanism contributing to bedaquiline resistance among MTB isolates from Shaanxi, China. Three novel mutation types (G19deletion, C265T, and T323C) of the Rv0678 gene were associated with resistance to bedaquiline. Furthermore, in addition to the current three resistance-associated genes (atpE, Rv0678, and pepQ), other mechanisms of resistance to bedaquiline may exist that need further study.

Continuously wavelength-tunable mode-locked Tm fiber laser using stretched SMF-GIMF-SMF structure as both saturable absorber and filter.

We demonstrate, for the first time, use of a stretched single mode-graded-index multimode-single mode fiber (SMF-GIMF-SMF) structure as a saturable absorber (SA) for a passively mode-locked Tm fiber laser. Such an all-fiber SA was based on the nonlinear multimode interference (NL-MMI). Stable fundamentally mode-locking operation was obtained at a pump threshold of 100mW. The output soliton pulses had a center wavelength, spectral width, pulse duration, and repetition rate of 1931 nm, 3.77 nm, 1.2ps, and 19.94 MHz, respectively. Furthermore, the SMF-GIMF-SMF structure can also be used as a filter to tune the laser. Continuously tunable mode-locking was experimentally demonstrated only by varying the stretched length of GIMF. Our results indicate that the stretched SMF-GIMF-SMF structure could serve as a SA together with a bandpass filter, which makes it advantageous for wavelength-tunable mode locking lasers.