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GNNs (Graph Neural Networks) have attracted increasing attention for their strong power on dealing with the graph structures. However, it remains a challenge to design an ideal GNN suitable for various downstream tasks. By revisiting the framework of MPNN (Message Passing Neural Network), we argue that an ideal GNN should satisfy following two conditions. First, the node embedding can absorb the knowledge from a wide range of neighbors while maintaining locality. Second, the first-order information aggregation can adapt to unknown graphs. In this paper, we first extend S 2 GC to GMGC (Generalized Markov Graph Convolution), which can maintain the node locality regardless the type of the embedded diffusion kernel. Next, we embed the improved self-gating mechanism into the GMGC framework and propose a novel model named AMGC (Attention-enabled Adaptive Markov Graph Convolution), which well satisfies the above conditions. Moreover, the advantages of AMGC can be explained in the frequency domain. First, the frequency of the first-order diffusion kernel is adaptive and no longer limited to low-pass as S 2 GC . Second, the multi-order diffusion kernel can retain more components around the core frequency compared with FAGCN. To verify the ability of AMGC, extensive experiments are conducted, including graph regression, graph classification and semi-supervised node classification. The results show that AMGC can achieve comparable performance in all graph tasks. [ABSTRACT FROM AUTHOR]

Purpose: For estrogen receptor (ER)-positive breast cancer, neoadjuvant endocrine therapy (NET) has been shown to be as effective as neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of Preoperative Endocrine Prognostic Index (PEPI). Methods: We conducted a prospective, multi-center, non-randomized, controlled trial that enrolled postmenopausal early-stage strongly ER-positive (≥ 50%) and HER2-negative breast cancer patients. All patients were given 4-month NET before surgery. The primary objective was to investigate the 5-year recurrence-free survival (RFS) in patients who had PEPI 0–1 or pathological complete response (pCR) without chemotherapy. Patients who had PEPI 0–1 or pCR were recommended to receive adjuvant endocrine therapy only and patients had PEPI ≥ 2 may receive adjuvant chemotherapy at the discretion of the treating physician. Results: A total of 410 patients were included and 352 patients constituted the per-protocol population. Overall, 9 patients (2.5%) had pCR (ypT0/is ypN0), 128 patients (36.4%) had PEPI = 0, and 56 patients (15.9%) had PEPI = 1. After a median follow-up of 60 months (4–104 months), patients who had PEPI 0–1 or pCR showed an improved 5-year RFS [99.5% (95% CI 98.5–99.9%) for PEPI 0–1 or pCR group vs. 93.7% (95% CI 89.6–97.8%) for PEPI ≥ 2 group, P = 0.028]. No survival difference was detected between patients received adjuvant chemotherapy vs. no chemotherapy among PEPI ≥ 2 cases. Conclusion: PEPI 0–1 or pCR may be used to define a group of ER-positive and HER2-negative postmenopausal early breast cancer patients with low relapse risk for whom adjuvant chemotherapy can be safely withheld. Studies on the identification and alternative treatment options for endocrine-resistant tumors are warranted. Clinical trial registration: NCT01613560. [ABSTRACT FROM AUTHOR]

The rockburst dynamic disasters in the process of deep coal mining become more and more serious. Taking the rockburst occurred in the 23130 working face of Yuejin Coal Mine as the engineering background, we study the characteristics of mining stress field around roadway, the plastic failure morphological characteristics of surrounding rock and the accumulation/release law of elastic energy before and after burst. An analysis model quantitatively describing the physical process of rockburst in the mining roadway is established, and the calculation method of dynamic release of elastic energy in the physical process of rockburst is educed. The mechanism of rockburst in mining roadway is revealed. The results show that an "L-shaped" stress concentration zone is formed within 100 m of the 23130 working face, and the principal stress ratio of the surrounding rock of the transportation roadway is 2.59–4.26. The change of the direction of the maximum principal stress has a significant effect on the burst appearance characteristics. The failure strength of different sections of the mining roadway is characterized by the elastic energy release value. With the increase of the working face distance, the elastic energy released by burst failure and the expansion variation of failure boundary radius show a nonlinear variation law that tends to decrease steadily after sharp fluctuation. The closer to the working face, the higher the burst risk. At a distance of 10 m from the working surface, the maximum principal stress reaches its maximum value. The butterfly-shaped failure system generated by the surrounding rock of the roadway has energy self-sustainability, and the elastic energy released by the sudden expansion of the butterfly leaf is enough to cause a burst damage of 1.9 magnitude. This work could provide theoretical support for the prediction and prevention of rockburst. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is a complex neurological autoimmune disease with a pathogenetic mechanism that has yet to be elucidated. Emerging evidence has revealed that genes, non-coding RNAs and genetic variants play significant roles in the pathogenesis of MG. However, the molecular mechanisms of single nucleotide polymorphisms (SNPs) located on lncRNAs could disturb lncRNA-mediated ceRNA regulatory functions still unclear in MG. In this study, we collated 276 experimentally confirmed MG risk genes and 192 MG risk miRNAs. We then constructed a lncRNA-mediated ceRNA network for MG based on multi-step computational strategies. Next, we systematically integrated risk pathways and identified candidate SNPs in lncRNAs for MG based on data acquired from public databases. In addition, we constructed a pathway-based lncRNA-SNP mediated network (LSPN) that contained 128 lncRNAs targeting 8 MG risk pathways. By analyzing network, we propose a latent mechanism for how the "lncRNA-SNP-mRNA-pathway" axis affects the pathogenesis of MG. Moreover, 25 lncRNAs and 51 SNPs on lncRNAs were extracted from the "lncRNA-SNP-mRNA-pathway" axis. Finally, functional analyses demonstrated lncRNA-SNPs mediated ceRNA regulation pairs associated with MG participated in the MAPK signaling pathway. In summary, we constructed MG-specific lncRNA-SNPs mediated ceRNA regulatory networks based on pathway in the present study, which was helpful to elucidate the roles of lncRNA-SNPs in the pathogenesis of MG and provide novel insights into mechanism of lncRNA-SNPs as potential genetic risk biomarkers of MG. [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS) is a common and serious neurological disease. Extensive evidence indicates that activation of the immune system contributes significantly to the development of IS pathology. In recent years, some long non-coding RNAs (lncRNAs), acting as competing endogenous RNAs (ceRNAs), have been reported to affect IS process, especially the immunological response after stroke. However, the roles of lncRNA-mediated ceRNAs in immune pathogenesis of IS are not systemically investigated. In the present study, we generated a global immune-related ceRNA network containing immune-related genes (IRGs), miRNAs, and lncRNAs based on experimentally verified interactions. Further, we excavated an IS immune-related ceRNA (ISIRC) network through mapping significantly differentially expressed IRGs, miRNAs, and lncRNAs of patients with IS into the global network. We analyzed the topological properties of the two networks, respectively, and found that lncRNA NEAT1 and lncRNA KCNQ1OT1 played core roles in aforementioned two immune-related networks. Moreover, the results of functional enrichment analyses revealed that lncRNAs in the ISIRC network were mainly involved in several immune-related biological processes and pathways. Finally, we identified 17 lncRNAs which were highly related to the immune mechanism of IS through performing random walk with restart for the ISIRC network. Importantly, it has been confirmed that NEAT1, KCNQ1OT1, GAS5, and RMRP could regulate immuno-inflammatory response after stroke, such as production of inflammatory factors and activation of the immune cells. Our results suggested that lncRNAs exerted an important role in the immune pathogenesis of IS and provided a new strategy to do research on IS. [ABSTRACT FROM AUTHOR]

Characterizing the pathogenicity of BRCA1 variants of uncertain significance (VUSs) is a major bottleneck in clinical management of BRCA1-associated breast cancer. Saturation genome editing (SGE) was recently reported as an innovative laboratory-based approach to assess the pathogenicity of BRCA1 variants. We combined clinical phenotypes and SGE score to identify the pathogenicity of BRCA1 VUSs detected in a cohort of 8,085 breast cancer patients. According to SGE function score, 33 out of 144 BRCA1 VUSs detected were classified into "loss of function" (n = 13), "intermediate" (n = 2), and "functional" (n = 18) groups. Compared with non-carriers, "loss of function" VUS carriers (n = 19) presented significantly worse clinicopathological characteristics. These included younger age at breast cancer diagnosis (44.4 years vs. 51.2 years, P = 0.01), stronger family history of any cancer (57.9% vs. 32.3%, P = 0.017) especially breast or ovarian cancer (47.4% vs. 9.3%, P < 0.001), more bilateral breast cancer (31.6% vs. 3.4%, P < 0.001), and triple-negative breast cancer (47.4% vs. 12.8%, P < 0.001), which were comparable to those of pathogenic variant carriers. In contrast, the clinical phenotypes of "functional" VUS carriers were similar to those of non-carriers. These results indicated that SGE was a reliable method in BRCA1 variant classification. Combining SGE function score and the available evidence, twelve out of 33 BRCA1 VUSs were reclassified as pathogenic or likely pathogenic variants and one was benign. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the effect of BCT versus mastectomy on the recurrence and survival of different-aged patients, and to investigate whether effects of BCT versus mastectomy on survival of young patients were consistent with those of old patients. Methods: Data on women with primary invasive breast cancer between 2007 and 2011 were extracted from the institutional database of Breast Center. Disparities in hormone receptor, tumor size, lymph node status, and Her-2 status between BCT and mastectomy groups were adjusted using the propensity score (PS) adjustment method. Patients were divided by age into two groups (≤ 40 years and > 40 years). We assessed proportions of local recurrence (LR), distant disease-free survival (DDFS), disease-free survival (DFS), and breast cancer-specific survival (BCSS) in different-aged groups; this assessment was further stratified by surgical treatment. Results: A total of 2964 patients were included; 565 (19%) were aged ≤ 40 years. In the entire cohort, hazard ratios (HR) of BCT versus mastectomy for DDFS and DFS were 0.56 (P = 0.029) and 0.55 (P = 0.008), respectively. After PS adjustment, there was no significant difference between BCT and mastectomy in LR, DDFS, DFS and BCSS in the young age group. In the old age group, women who underwent BCT exhibited improved DDFS (HR 0.57, 95% CI 0.39–0.84, P = 0.004). Conclusions: BCT did not significantly affect survival outcomes of young patients with breast cancer. Superior survival of BCT compared to mastectomy was observed only in old patients. [ABSTRACT FROM AUTHOR]

Anti-fungal blue light (ABL) therapies have been widely studied to treat various microbial infections in the literature. The blue light with wavelengths ranging from 400 to 470 nm has been reported to be effective to inhibit various kinds of bacteria and fungi. The existing studies usually report the viability rates of the pathogens under the irradiation of the blue light with different dosage parameters. However, to the best of our knowledge, there is still no work especially focusing on studying the effect of ABL therapies on treating candida vaginitis, where it is important to study the viability of both the Candida albicans (C. albicans) and the human vaginal epithelial cells. It is the purpose of this work to conduct ABL experiments on both of these two cells, analyze the effects, and determine the best ABL wavelength out of three candidates, i.e., 405-nm, 415-nm, and 450-nm wavelength. The viability rates of the C. albicans and the human vaginal epithelial cells irradiated by the three blue LED light sources were measured, whose irradiance (power density) were all set to 50 mW/cm2. The dynamic viability models of the C. albicans and the epithelial cells were built based on the experimental data. Moreover, in this work, we also built a functional relationship between the viability of these two types of cells, by which we further compared the effects of the blue light irradiation on both the C. albicans and vaginal epithelial cells. The experimental data showed that when an approximately 80% inhibiting rate of the C. albicans was achieved, the survival rates of the epithelial cells were 0.6700, 0.7748, and 0.6027, respectively for the treatment by the 405-nm, 415-nm, and 450-nm wavelength light. On the other hand, by simulating the functional relationship between the viability of the two types of cells, the survival rates of the epithelial cells became 0.5783, 0.6898, and 0.1918 respectively using the 405-nm, 415-nm and 450-nm wavelength light, when the C. albicans was completely inhibited. Therefore, both the experimental data and the model simulation results have demonstrated that the 415-nm light has a more effective anti-fungal result with less damage to the epithelial cells than the 405-nm and 450-nm light. [ABSTRACT FROM AUTHOR]

Purpose: Mobility of representative heavy metals during the anaerobic digestion of sludge under mesophilic and thermophilic conditions was compared. Methods: The exchangeable, carbonates (F1), Fe and Mn oxides (F2), organic matter, sulfides (F3) and residual (F4) fractions of heavy metals in sludge were fractionated by the modified BCR procedure. Inductively coupled plasma-optical emission spectrometry (ICP-OES) was used to determine the Cu, Ni and Zn concentrations of the different fractions. Results: The mobile fraction (F1, F2 and F3) of Cu, Ni and Zn increased with the progression of the anaerobic digestion process. The mobile fraction of Cu, Ni and Zn under thermophilic conditions was greater than under mesophilic conditions. The mobile fraction of Cu, Ni and Zn also increased with the increase of the ammonia concentration, especially under mesophilic conditions. The acid-soluble fraction levels of the studied metals were ranked as follows Ni > Zn > Cu. Conclusions: The mobility of the representative heavy metals (Cu, Ni and Zn) during the anaerobic digested of sludge under thermophilic conditions was greater than under mesophilic conditions. These results show that more attention to the negative impacts of heavy metals present in anaerobically digested sludge under thermophilic conditions before land applying. [ABSTRACT FROM AUTHOR]

The application of char from biomass gasification as a filling material in landfill simulation reactors was investigated to evaluate the effect of char on carbon retention and nitrogen leaching, nitrogen denitrification, and waste stabilization. Landfill simulation columns filled with fine fraction of aged refuse (AR) and solid fraction of digestate (SFD) were used, with two char application methods: embedding a char layer between AR and SFD layers and mixing char with the SFD. The experimental results show that char application increased the biodegradable organic matter content as the respiration index (RI4) of the mixture char-SFD increased up to 37.7%, which could enhance the heterotrophic denitrification. Moreover, 12.3% of ammonia leaching was avoid by applying the SFD mixed with char. These results indicate that char from biomass gasification poses a significant enhancement on nitrogen and carbon retention which might increase the denitrification capacity of the SFD in the long run. Although high nitrogen removal rates were achieved (up to 23.1 mg N/kg-TS day), the addition of char from biomass gasification has little effect on the nitrate removal. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence and clinical relevance of PALB2 germline mutations in BRCA1/2-negative breast cancer patients. Methods: The exons and intron–exon boundaries of the PALB2 gene were sequenced by multigene panel testing in a cohort of 7657 Chinese BRCA1/2-negative breast cancer patients. Results: Of the 7657 patients, 54 (0.71%) carried pathogenic PALB2 germline mutations, all of which were nonsense or frameshift mutations leading to a truncated protein. The 54 patients carried 42 distinct pathogenic mutations, of which 17 (40.5%) were novel and 8 were recurrent mutations. Compared with non-carriers, PALB2 pathogenic mutation carriers developed breast cancer at a younger age (47.52 years vs. 51.35 years, p = 0.016) and were more likely to have triple-negative (24.1% vs. 13.4%, p = 0.022) or HER2 negative (87.0% vs. 74.2%, p = 0.031) breast cancer and large breast tumors (> 2 cm) at diagnosis (72.2% vs. 57.0%, p = 0.024). PALB2 mutation carriers were also more likely to have family histories of breast and/or ovarian cancer (27.8% vs. 8.4%, p < 0.001) and any types of cancer (57.4% vs. 31.6%, p < 0.001) when compared with non-carriers. Conclusions: PALB2 germline mutations are present at 0.71% in Chinese BRCA1/2-negative breast cancer patients and are more frequent in patients with triple-negative breast cancer and family histories of breast and/or ovarian cancer. [ABSTRACT FROM AUTHOR]

Purpose: The role of long-acting hematopoietic growth factor in supporting dose-dense chemotherapy and minimizing hematologic toxicity has not been established. We investigated the efficacy and safety of once-per-cycle pegfilgrastim in breast cancer patients receiving neoadjuvant dose-dense epirubicin and cyclophosphamide (ddEC).Methods: Newly diagnosed stage I to III breast cancer patients received four cycles of ddEC (E, 100 mg/m2 and C, 600 mg/m2 every 2 weeks) and 6 mg of subcutaneous pegfilgrastim on day 2 of each cycle. The primary endpoint was to evaluate the incidence of chemotherapy delay. Secondary endpoints include the incidences of febrile neutropenia (FN) and grade 3/4 neutropenia during the four ddEC cycles.Results: A total of 240 patients were enrolled and 913 ddEC cycles were administered in the study. Chemotherapy delay occurred in 15 patients (6.3% of patients, 95% CI 3.2-9.4%) for 17 cycles (1.9% of cycles, 95% CI 1.0-2.8%). The most frequent cause of chemotherapy delay was transaminase elevation (10 patients, 12 cycles). A total of 12 patients (5.0%, 95% CI 2.2-7.8%) developed 13 episodes of FN. Of the 221 patients that completed four ddEC cycles with pegfilgrastim support, 209 patients (94.6%, 95% CI 91.6-97.6%) had a 100% relative dose intensity (RDI). A RDI ≥ 85% was achieved in 217 of 221 patients (98.2%, 95% CI 96.5-99.9%). Bone pain of any grade was recorded in 85 of 220 evaluable patients (38.6%, 95% CI 32.2-45.0%).Conclusions: Pegfilgrastim is effective and safe in facilitating four cycles of neoadjuvant ddEC, with low incidences of chemotherapy delay and febrile neutropenia. [ABSTRACT FROM AUTHOR]

Purpose: BRCA1/2 germline mutations are associated with a high risk of breast cancer, which may preclude mutation carriers from breast-conserving surgery (BCS). This study retrospectively examined whether mutation status influenced the rate of ipsilateral breast tumor recurrence (IBTR) after BCS in Chinese women. Methods: Patients who underwent BCS were enrolled in carriers group and non-carriers group according to their BRCA1/2 mutation status in the study. The correlations were analyzed between IBTR incidence and BRCA1/2 mutation. The IBTR cases were further separated into new primary tumor (NP) and true local recurrences (TR). The risk factors of NP were studied in multivariate analysis. Results: 1947 consecutive Chinese women with primary invasive breast cancer were selected. 103 patients were identified as BRCA1/2 mutation carriers and 1844 were non-carriers. BRCA1/2 mutation carriers were younger (P < 0.001) with more often negative HER-2 expression (P = 0.01) and tumor size over 2 cm (P = 0.04) than non-carriers. The median follow-up for all patients was 80 months. The rate of IBTR was 3.9% in mutated carriers and 2.0% in non-carriers, respectively (P = 0.16). In IBTR cases, NP incidence was 3.9% in carrier group and 0.6% in non-carrier group, respectively (P < 0.01). After adjustment of all clinical-pathological factors, BRCA1/2 mutation was the only statistical risk factor of NP incidence (HR = 6.29, P = 0.002), while positive lymph node was nearly statistically significant (HR = 2.70, P = 0.06). Conclusions: BCS may be a rational option for Chinese BRCA1/2 mutation carriers. High NP incidence in mutation carriers should be paid close attention in the future. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence and clinical relevance of TP53 and PIK3CA mutations in pretreatment breast cancer have been previously reported. However, little is known regarding these mutations in residual tumor tissues after neoadjuvant chemotherapy. Here, we investigated the association between TP53 and PIK3CA mutations in residual disease and survival of breast cancers. Methods: TP53 and PIK3CA somatic mutations were examined in 353 post-neoadjuvant chemotherapy residual tumor tissues by Sanger sequencing. Survival curves of patients with TP53 and PIK3CA mutations were compared using the Kaplan–Meier method. Results: Fifty-six (15.9%) of the 353 patients carried a TP53 somatic mutation and 79 patients (22.4%) carried a PIK3CA somatic mutation. A total of 18 patients carried co-mutation of TP53 and PIK3CA. Patients with somatic co-mutation were more likely to have high-grade tumors (35.3% vs. 10.6%, P = 0.010), estrogen receptor-negative tumors (55.6% vs. 26.7%, P = 0.009), progesterone receptor-negative tumors (61.1% vs. 30.5%, P = 0.008) and triple-negative tumors (35.3% vs. 13.3%, P = 0.025) compared with non-carriers. More importantly, co-mutation of TP53 and PIK3CA carriers had a significantly worse disease-free survival (DFS) and distant disease-free survival (DDFS) than non-carriers (5-year DFS: 58.0% vs. 83.2%, P < 0.001; 5-year DDFS: 70.3% vs. 86.4%, P = 0.024). Furthermore, in multivariate regression analysis, TP53 and PIK3CA co-mutation carriers showed a significantly worse DFS (adjusted hazard ratio = 3.70; 95% confidence interval, 1.79–7.63; P < 0.001). Conclusions: Patients with somatic co-mutation of TP53 and PIK3CA were associated with unfavorable survival compared with non-carriers. Co-mutation of TP53 and PIK3CA could be used as a potential prognosis marker in post-neoadjuvant chemotherapy breast cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: The ataxia telangiectasia-mutated (ATM) gene is a moderate susceptibility gene for breast cancer. However, little is known about the breast cancer phenotypes associated with ATM mutation. We therefore investigated the spectrum and clinical characteristics of ATM germline mutations in Chinese breast cancer patients. Methods: A multi-gene panel was performed to screen for ATM germline mutations in 7657 BRCA1/2-negative breast cancer patients. All deleterious mutations were validated by independent polymerase chain reaction (PCR)-Sanger sequencing. Results: A total of 31 pathogenic mutations in the ATM gene across 30 carriers were identified, and the ATM mutation rate was 0.4% (30/7,657) in this cohort. The majority of the mutations (90.3%, 28/31) were nonsense or frameshift mutations. Of the total ATM mutations, 61.3% (19/31) were novel mutations and 13 recurrent mutations were found. ATM mutations carriers were significantly more likely to have a family history of breast and/or ovarian cancer (26.7% in carriers vs. 8.6% in non-carriers, p < 0.001), as well as a family history of any cancer (60.0% in carriers vs. 31.5% in non-carriers, p = 0.001). In addition, ATM mutations carriers were significantly more likely to have oestrogen receptor (ER)-positive (p = 0.011), progesterone receptor (PR)-positive (p = 0.040), and lymph node-positive breast cancer (p = 0.034). Conclusions: The prevalence of the ATM mutation is approximately 0.4% in Chinese BRCA1/2-negative breast cancer. ATM mutation carriers are significantly more likely to have a family history of cancer and to develop ER- and/or PR-positive breast cancer or lymph node-positive breast cancer. [ABSTRACT FROM AUTHOR]

The role of nitrilotriacetic acid (NTA) with the addition of four trace elements on mesophilic anaerobic co-digestion of food waste and sludge was investigated in batch reactor. Five different NTA concentrations (0, 8, 80, 800 and 8000 μM) were evaluated. The greatest coenzyme F420 content of five digester were 1.210 ± 0.210, 1.286 ± 0.179, 1.547 ± 0.187, 1.400 ± 0.222 and 0.955 ± 0.146 μmol L−1 during whole digestion process. The ultimate biogas yield of five digester were 198.1, 200.7, 239.7, 219.5 and 174.8 mL g−1-VSadded, respectively. The results indicated that the addition of NTA increased the biogas yield of anaerobic digester at an adequate concentration (around 80 μM). [ABSTRACT FROM AUTHOR]

Purpose: Cell-cycle-checkpoint kinase 2 (CHEK2) is an important moderate-penetrance breast cancer predisposition gene; however, recurrent CHEK2 mutations found in Caucasian women are very rare in Chinese population. We investigated the mutation spectrum and clinical relevance of CHEK2 germline mutations in Chinese breast cancer patients.Methods: The entire coding regions and splicing sites of CHEK2 were screened in 7657 Chinese BRCA1/2-negative breast cancer patients, using 62-gene panel-based sequencing.Results: Out of 7657 BRCA1/2-negative breast cancer patients, 26 (0.34%) carried CHEK2 pathogenic germline mutations. Most of these mutations (92.3%, 24/26) were nonsense or frameshift mutations; 84.6% (22/26) of them were in forkhead-associated (FHA) or kinase domains. Of the 18 types of CHEK2 mutations we found, 61.1% (11/18) of were novel mutations and two recurrent mutations (Y139X and R137X) were found in this cohort. Patients with CHEK2 mutations were significantly more likely to have family histories of breast and/or ovarian cancer (23.1% vs. 8.6%, p = 0.022) and family histories of any cancer (50.0% vs. 31.6%, p = 0.044); and were significantly more likely to have lymph node-positive (53.8% vs. 27.3%, p = 0.002) and progesterone receptor (PR)-positive (88.5% vs. 64.5%, p = 0.011) breast cancers.Conclusions: Among Chinese breast cancer patients, the CHEK2 germline mutation rate is approximately 0.34% and two specific mutations (Y139X and R137X) are recurrent. Patients with CHEK2 mutations are significantly more likely to have family histories of cancer, and to develop lymph node-positive and/or PR-positive breast cancers. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the long-term prognosis of breast cancer patients with 99mTc-rituximab for sentinel lymph node biopsy (SLNB).Methods: A total of 2947 patients with negative sentinel lymph nodes (SLNs) omitting axillary lymph node dissection (ALND), treated between June 2005 and December 2013, were retrospectively analyzed. SLNB was performed prior to adjuvant therapy.Results: After a median follow-up of 62 months, 22 cases of axillary recurrence (AR) were observed. The 5-year AR rate (ARR) was 0.7% [95% confidence interval (CI) 0.3-1.1%] and the 5-year relapse-free survival (RFS) was 95.2% (95% CI 94.4-96.0%). Multivariate analysis showed that abnormal axillary ultrasound with negative fine-needle aspiration (FNA) [hazard ratio (HR) 3.79, 95% CI 1.55-9.28; P = 0.004], not receiving radiotherapy (HR 4.38, 95% CI 1.47-13.05; P = 0.008), and age ≤ 40 years (HR 2.93, 95% CI 1.19-7.20; P = 0.020) were independent risk factors for AR.Conclusions: ARR of SLNB-negative patients with 99mTc-rituximab is low. Abnormal axillary ultrasound with negative FNA, not receiving radiotherapy, and age ≤ 40 years were prognostic factors for higher ARRs. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy and frequently evolving drug resistance. Although there is growing consensus that noncoding ribonucleic acids (ncRNAs) are modulators of TLE, the knowledge about the deoxyribonucleic acid (DNA) methylation patterns of ncRNAs in TLE remains limited. In the current study, we constructed DNA methylation profiles from 30 TLE patients and 30 healthy controls for ncRNAs, primarily focusing on long ncRNAs (lncRNAs) and microRNAs (miRNAs), by reannotating data of DNA methylation BeadChip. Statistics analyses have revealed a global hypermethylation pattern in miRNA and lncRNA gene in TLE patients. Bioinformatic analyses have found aberrantly methylated miRNAs and lncRNAs are related to ion channel activity, drug metabolism, mitogen-activated protein kinase (MAPK) signaling pathway, and neurotrophin signaling pathway. Aberrantly methylated ncRNA and pathway target might be involved in TLE development and progression. The methylated and demethylated ncRNAs identified in this study provide novel insights for developing TLE biomarkers and potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Dewaterability of anaerobic digestate influences the further disposal ways. The role of mixing ratio on anaerobic co-digestion of food waste (F) and sludge (S) was investigated under mesophilic condition. Five different mixing ratios (F; F/S = 3:1; F/S = 1:1; F/S = 1:3; S) were evaluated with two replicates. The specific biogas production (SBP) of five mixing ratios were 95.5, 105.6, 95.6, 435.5 and 344.0 mL g-VS respectively. Under S condition, normalized capillary suction time (NCST) was significant correlation with protein and polysaccharide of Slime. Under F condition, NCST was significant correlated with polysaccharide of Slime. Under other conditions, the NCST was no significant correlation with protein and polysaccharide of any layers of extracellular polymeric substances (EPS). NCST increased with the increasing of sludge ratio. On day 37, NCST were 3.4 ± 0.9, 72.1 ± 15.6, 164.2 ± 37.6, 179.2 ± 30.6 and 278.1 ± 56.1 s g-TS respectively. Adequate mixing ratio (around F/S = 1:3) of food waste and sludge under mesophilic anaerobic condition could result in high SBP. The dewaterability of anaerobic digestate deteriorated with the increasing of sludge ratio in mixture of sludge and food waste. [ABSTRACT FROM AUTHOR]

We determined the prevalence and characteristics of BRCA1/2 germline mutations in a large cohort of Chinese women with breast cancer. A total of 5931 unselected Chinese women with breast cancer were enrolled in this study and underwent testing for BRCA1/2 mutations. Of these, 543 patients were familial breast cancer, 1033 were early-onset disease (≤40 years) without family history of breast cancer, and 4355 were sporadic breast cancer. In total, 232 patients (3.9 %) carried a BRCA1 or BRCA2 mutation (110 in BRCA1and 122 in BRCA2) in this cohort of 5931 patients. BRCA1/2 mutation rate was 16.9 % (92/543) in familial breast cancers, 5.2 % (54/1033) in early-onset breast cancers (≤40 years), and 2.0 % in sporadic breast cancers (>40 years), respectively. The BRCA1/2 mutation rate was 27.0 % in 111 familial breast cancers diagnosed at and before the age of 40. 41.4 % of mutations in this cohort were specific for Chinese population. Recurrent mutations accounted for 44.8 % of the entire mutations in 2382 cases that BRCA1 and BRCA2 genes were fully sequenced in this study. Both BRCA1 and BRCA2 mutation carriers were significantly more likely to be early-onset and bilateral breast cancers, high-grade cancer, and to have a family history of breast cancer compared with non-carriers. BRCA1 mutation carriers were more likely to be triple-negative cancer than BRCA2 mutation carriers and non-carriers. Our data provide guidelines for Chinese women with breast cancer who should undergo BRCA1/2 genetic testing; additionally, recurrent mutations account for nearly half of the mutations and some of them are specific for Chinese women. [ABSTRACT FROM AUTHOR]

This study aimed to compare the efficacy and safety aspects of three anthracycline-based regimens as neoadjuvant chemotherapy in primary breast cancer. Five-hundred and one patients with clinical stage I-III invasive breast cancer were randomly assigned to receive four cycles of neoadjuvant chemotherapy with either CEFci arm (5-Fu 200 mg/m daily by 24-h continuous infusion and epirubicin 100 mg/m and cyclophosphamide 600 mg/m intravenous bolus on day 1), CEF arm (cyclophosphamide 600 mg/m, epirubicin 100 mg/m, and 5-Fu 600 mg/m i.v. on day 1), or EC arm (epirubicin 100 mg/m and cyclophosphamide 600 mg/m i.v. on day 1). The pathologic responses to chemotherapy were assessed according to the Miller and Payne grading system (MP). A total of 485 patients were included in the intent-to-treat population. Breast pathologic complete response (pCR) rate was 18.9 % (31/164) in CEFci arm, 15.0 % (24/160) in CEF arm, and 12.4 % (20/161) in EC arm ( P = 0.266). MP grading system 4/5 response rate was significantly higher in CEFci arm than that in CEF arm and EC arm (44.5, 31.3 and 27.3 %, respectively, P = 0.003). There was no significant difference on grade III/IV neutropenia among three arms ( P = 0.538), but thrombocytopenia, decreased hemoglobin, and elevated aminotransferase appeared to be observed more in CEFci arm ( P = 0.040, 0.059, and 0.073, respectively). CEFci did not reach a higher pCR rate compared with CEF or EC in patients with primary breast cancer. The potential advantage of CEFci in improving pathologic response still requires further research. The accompanied hematologic and biochemical toxicities, and the catheter-related complications should also be noted. [ABSTRACT FROM AUTHOR]

BRCA1/2 mutations represent approximately 5 % of unselected Chinese women with breast cancer. However, the breast cancer risk of Chinese women with BRCA1/2 mutations is unknown. Therefore, the aim of this study was to estimate the age-specific cumulative risk of breast cancer in Chinese women who carry a BRCA1 or BRCA2 mutation. Our study included 1816 unselected Chinese women with breast cancer and 5549 female first-degree relatives of these probands. All probands were screened for BRCA1/2 mutation. The age-specific cumulative risks of BRCA1/2 carriers were estimated using the kin-cohort study by comparing the history of breast cancer in first-degree female relatives of BRCA1/2 carriers and non-carriers. Among the 1816 probands, 125 BRCA1/2 pathogenic mutations were identified (70 in the BRCA1 gene and 55 in the BRCA2 gene). The incidence of breast cancer in the first-degree female relatives of BRCA1/2 mutation carriers was significantly higher (3.7-fold and 4.4-fold for BRCA1 and BRCA2 mutation carriers, respectively) than in non-carriers. The estimated cumulative risks of breast cancer by age 70 years were 37.9 % [95 % confidence interval (CI) 24.1-54.4 %] for BRCA1 mutation carriers and 36.5 % (95 % CI 26.7-51.8 %) for BRCA2 mutation carriers, respectively. Our study suggests that the breast cancer risk of Chinese women with BRCA1/2 mutations appears to be relatively high by the age of 70. Therefore, genetic counseling, enhanced surveillance, and individual preventive strategies should be provided for Chinese women who carry a BRCA1/2 mutation. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the efficacy of physical examination (PE), ultrasound (US), and US combined with fine-needle cytology (US-FNAC) in evaluation of node status before sentinel lymph node biopsy (SLNB) for breast cancer patients. We performed a retrospective study of 3,781 breast cancer patients and calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for PE, US, and US-FNAC, respectively. A total of 3,175 cases were documented as cN and 606 as cN. Abnormal axillary nodes under US were detected in 1,152 cases, among which 821 were proven to have positive nodes by FNAC. The positive FNAC results enabled 11.7 % of cN patients (373/3,175) to avoid unnecessary SLNB. All 331 cases with abnormal US but negative FNAC results, and the 2,629 cases with normal US underwent SLNB procedure for nodal staging, and metastatic nodes were identified in 745 patients. The sensitivity of PE was 32.2 %, with a specificity of 95.5 %, a PPV of 83.5 %, a NPV of 65 %, and an accuracy of 69.3 %. The sensitivity, specificity, PPV, NPV, and accuracy of axillary US alone were 58.6, 89.4, 79.6, 75.3, and 76.7 %, respectively. Combining axillary US with FNAC resulted in sensitivity, specificity, PPV, NPV, and accuracy of 52.4, 100, 100, 74.8, and 80.3 %, respectively. Our study demonstrated that US-FNAC is a feasible and effective triage during axillary staging for newly diagnosed breast cancer patients. [ABSTRACT FROM AUTHOR]

The sludge digestate stabilized by mesophilic anaerobic digestion was further degraded through thermophilic anaerobic digestion using 0-10 % (v/v) of thermophilic, proteolytic Coprothermobacter proteolyticus, and/or methanogenic granular sludge. The results demonstrated that the temperature shift to thermophilic condition promoted abiotic solubilization of proteins and reactivated the fermentative bacteria and methanogens indigenous in the sludge digestate, resulting in a final methane yield of 6.25 mmol-CH/g-volatile suspended solid (VSS) digestate. The addition of C. proteolyticus accelerated the hydrolysis and fermentation of proteins and polysaccharides in the digestate during the early stage of thermophilic anaerobic digestion and stimulated methane production by syntrophic cooperation with methanogenic granular sludge. In the treatment with granular sludge and inoculated with 10 % (v/v) of C. proteolyticus, a final methane yield of 7 mmol-CH/g-VSS digestate was obtained, and 48.4 % proteins and 27.0 % polysaccharides were degraded. The dissolved proteins were contributed by abiotic factor, C. proteolyticus, and indigenous digestate bacteria, respectively, by around 16, 28, and 56 %. [ABSTRACT FROM AUTHOR]

It has been demonstrated that single nucleotide polymorphisms (SNPs) of SIPA1 (signal-induced proliferation associated gene 1) are associated with metastatic efficiency in both human and rodents. The purpose of this study was to determine whether SIPA1 545 C > T polymorphism was associated with overall survival in patients with metastatic breast cancer. In this study, SIPA1 545 C > T polymorphism was detected in 185 metastatic breast cancer patients using polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Survival curves for patients with SIPA1 545 C > T polymorphism was compared using the Kaplan-Meier method with log-rank tests. We found that SIPA1 545 C > T polymorphism was significantly associated with survival in 185 patients with metastatic breast cancer. Patients with SIPA1 545 T/T genotype had a significantly worse overall survival (OS) than did patients with C/T or C/C genotype (50.0% vs. 62.9%, P = 0.042). Moreover, in multivariate analysis, as compared with the C/C or C/T genotype, the T/T genotype remained an independent unfavorable prognostic marker of OS in this cohort (hazard ratio [HR] = 2.16; 95% CI = 1.12-4.15; P = 0.022). Our findings indicate that metastatic breast cancer patients with SIPA1 545 T/T genotype have a poorer survival compared to patients with C/C or C/T genotype. [ABSTRACT FROM AUTHOR]

Although there are some studies to investigate germline mutations in BRCA1/2 genes in Chinese women with familial breast cancer, many of them suffer relatively small sample size. In this study, we screened germline mutations in BRCA1/2 genes in a cohort of 409 Chinese women with familial breast cancer from north China by using a PCR-sequencing assay. A total of 43 deleterious mutations in BRCA1/2 genes were identified in this cohort, including 17 novel mutations and 6 recurrent mutations. The frequencies of BRCA1 and BRCA2 mutations were 3.9% (16/409) and 6.6% (27/409), respectively; the mutation rate of BRCA2 was 1.7-fold higher than that of BRCA1. The entire mutation rate of BRCA1/2 was 10.5% in this cohort; however, the mutation rate of BRCA1/2 genes was 23.0% in 78 familial breast cancer patients whose tumors were diagnosed at or before the age of 40. The mean age at diagnosis of breast cancer in BRCA1 carriers (42.8 years) and BRCA2 carriers (45.1 years) was younger than non-carriers (51.0 years) in this cohort ( P = 0.005; P = 0.01, respectively). In addition, both BRCA1 carriers and BRCA2 carriers were more likely to exhibit triple-negative breast cancer (ER-, PgR-, and HER2-) than non-carriers ( BRCA1 carriers vs. non-carriers, 69.2 vs. 23.0%, P = 0.001; BRCA2 carriers vs. non-carriers, 45.8 vs. 23.0%, P = 0.01). Our study suggested that the spectrum and characteristics of BRCA1/2 mutations in Chinese familial breast cancer exhibit some unique features, and Chinese women with familial breast cancer whose tumors are diagnosed at or before the age of 40 are good candidates for BRCA1/2 testing. [ABSTRACT FROM AUTHOR]

Recent studies suggested that breast cancer patients who carry a BRCA1 germline mutation benefit from poly (ADP-ribose) polymerase (PARP) inhibitors; therefore, it would be of great interest to detect BRCA1 somatic mutations in sporadic breast cancers. In this study, we detected BRCA1 somatic mutations in tumor cDNA from 144 Chinese women with sporadic breast cancer by using polymerase chain reaction (PCR)-direct sequencing assay. In total, eight BRCA1 alterations (three nonsense mutations and five missense mutations) were identified in this cohort of 144 sporadic breast cancers. We further confirmed that 5 out of 144(3.5%) sporadic breast cancer cases carried a BRCA1 somatic mutation, including two novel nonsense mutations (c.191_212del22 and c.2963C>G) resulting in a truncated protein and three missense mutations (c.114G>T, c.925A>C, and c.824G>A). The two cases with BRCA1 somatic truncating mutations also contained a TP53 somatic mutation in the tumors. Our study suggested that a small subset of sporadic breast cancers do harbor BRCA1 somatic mutations; these patients who carry a BRCA1 somatic mutation may be potential candidates for treatment with PARP inhibitors. [ABSTRACT FROM AUTHOR]

The data related to BRCA1 germline mutation in Chinese women with familial breast cancer is increasing. However, little is known the frequency of BRCA1 mutations in Chinese women with familial or early-onset breast cancer from Northern China, and few studies are available to investigate the clinicopathological characteristics of BRCA1 tumors in Chinese women. In this study, we detected germline mutations in BRCA1 in a cohort of 139 breast cancer patients who either have a family history of breast cancer ( n = 68) or whose tumors are diagnosed at or before the age of 35 ( n = 71) from Northern China. A total of 6 deleterious BRCA1 mutations were identified in this cohort, 4 of which (5587-1 del8, 3887 del AG, IVS21 + 1delG, and 2129 ins TG) are novel and one mutation (3478del5) detected in this study was only reported in Chinese population. The frequency of BRCA1 mutations in women with familial or early-onset breast cancer was 5.9% (4/68) or 2.8% (2/71) in this cohort, respectively; but the mutations were detected in 4 of 16(25.0%) familial breast cancer patients whose tumors were diagnosed before the age of 40. Moreover, BRCA1 mutation tumors tended to be high histological grade, and to be negative for ER, PgR, and Her-2 compared with tumors without BRCA1 mutations. Our study suggests that Chinese women with a family history of breast cancer whose tumors are diagnosed before age of 40 would be a suitable candidate for BRCA1 testing; and BRCA1 tumors in Chinese women exhibit an aggressive phenotype. [ABSTRACT FROM AUTHOR]

Spalling and mechanical properties of FRHPC subjected to fire were tested on notched beams. The results confirm that the internal vapor pressure is the leading reason for spalling of high-performance concrete (HPC). At the same time, the temperature-increasing velocity and constrained conditions of concrete element also play significant roles in spalling. Steel fibers cannot reduce the risk of spalling, although they have obvious beneficial effects on the mechanical properties of concrete before and after exposure to fire. Polypropylene (PP) fibers are very useful in preventing HPC from spalling, however, they have negative effects on the strengths. By using hybrid fibers (steel fibers+PP fibers), both good anti-spalling performance and improved mechanical properties come true, which may provide necessary safe guarantee for the rescue work and structure repair after fire disaster. [ABSTRACT FROM AUTHOR]

This study investigated the biogas production and dewaterability of sewage sludge with alkaline pretreatment at mesophilic and thermophilic temperatures. The total suspended solids (TSS) and volatile suspended solids (VSS) of raw sludges were 21.1 ± 2.3 and 16.2 ± 1.5 g L−1, respectively. Raw sludges were pretreated at uncontrolled, pH 8, pH 10, and pH 12 under mesophilic (Mu, M8, M10, and M12) and thermophilic (Tu, T8, T10, and T12) conditions, respectively. All the pretreatments last 6 days. The pH of pretreated sludges was adjusted to the pH 7.0 prior to inoculating with mesophilic anaerobic digested sludge and undergoing 60 days of anaerobic digestion. The ultimate biogas yield of Mu, M8, M10, M12, Tu, T8, T10, and T12 was 296.8, 384.8, 339.9, 323.1, 376.6, 322.4, 271.5, and 258.1 mL g−1-VSadded, respectively. Both the pH of alkali treatment and temperature of thermal treatment affect the performance of anaerobic digestion. High hydrolysis pH (pH 10 and pH 12) resulted in high Na+ concentration (over 4000 mg L−1), and Na+ inhibitory effect reduced the ultimate biogas yield. The normalized capillary suction time (NCST) found in the treatments of M8 and Tu were 11.8 ± 1.1 to 23.4 ± 1.7 and 27.9 ± 5.4 to 111.8 ± 1.7 s g−1-TSS, respectively. The results suggest that both the pH of alkali treatment and temperatures of mild thermal treatment affect the performance of anaerobic digestion and sludge pretreated at pH 8.0 under mesophilic conditions could achieve high biogas yield and adequate dewaterability of digested sludge. [ABSTRACT FROM AUTHOR]