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Papillary proliferation of the endometrium (PPE) is subdivided based on the complexity of the papillae and the proliferation of lesions, and the complex group is considered to have an increased risk of concurrent/subsequent endometrial neoplasia. However, the current subdivision criteria fail to prove the equivalence of the quantity of simple papillae and structural complexity. In this study, we divided PPE of 207 cases from 2014 to 2022 into 3 groups according to structural complexity and proliferation degrees: Group 1 equaled to the simple PPE with a simple papillary structure and typical localized proliferation; group 2 had the simple structure similar to group 1 but occupy over 50% of the endometrial polyp or > 2 lesions in the surface of nonpolypoid endometrium; group 3 had the truly complex branching papillae despite of its proportion. Group 3 was implicated with significantly more concurrent endometrial neoplasia (EAH and carcinoma) compared with groups 1 and 2 (P < 0.01), while no difference was found between groups 1 and 2. In 128 cases with no concurrent endometrial abnormalities in the initial biopsy or curettage specimens, 4 cases presented endometrial neoplasia (3 carcinoma and 1 atypical hyperplasia) in the subsequent specimens, all of which presented PPE of group 3 but not group 1 or 2 in the prior tissues (P < 0.01). The immunochemistry of 83 cases showed similar expressions of ER, PTEN, ARID1A, PTEN, p16, β-catenin, and p53 between PPE and the surrounding normal endometrium. Nearly 100% of PPE cases lost expressions of PR. A total of 2/83 cases showing PAX2 expression were all in the group 3 and correlated with endometrial neoplasia (2/17, 11.76%, P < 0.05). 76/83 (91.57%) of PPE lesions had KRAS mutations, and the distributions of which were similar among 3 groups. The frequency of mucinous metaplasia was significantly higher in the PPE lesions with KRAS mutations (72/74, 97.30%, P < 0.01). Group 3 showed higher frequency of single KRAS mutations compared with the combination of groups 1 and 2 (P < 0.01). Finally, the concordance of KRAS mutation profiles between PPE and endometrial neoplasia was significantly higher in group 3 than either group 1 or 2 (P < 0.01), while no difference was found between group 1 and 2. Thus, a new 2-tier subdivision system only emphasizing the complexity of papillae is recommended, which might precisely predict the risk of endometrial neoplasia and neoplasia-related molecular characteristics. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated that extranodal extension (ENE) is associated with prognosis in breast cancer. Whether this association should be described in pathological reports warrants further investigation. In this research, we evaluated the predictive value of ENE in axillary lymph nodes (ALNs) in invasive breast cancer and explored the feasibility of employing ENE to predict clinicopathological features, nodal burden, disease recurrence-free survival (DRFS) and overall survival (OS) in clinical practice. In addition, the cutoff values of perpendicular diameter ENE (PD-ENE) and circumferential diameter ENE (CD-ENE) of ENE were investigated. A total of 402 cases of primary invasive breast cancer were extracted from Fudan University Shanghai Cancer Center; these patients underwent axillary lymph node dissection (ALND) between 2010 and 2015. ENE in the ALN was defined as the tumor cells breaking through the lymph node capsule into peripheral adipose tissue and causing connective tissue reactions. Relationships between ENE and clinicopathological features, nodal burden, disease recurrence-free survival (DRFS) and overall survival (OS) were analyzed. PD-ENE was defined by measuring from the point where tumor tissue broke the node capsule to the highest point of the tumor cells in the perinodal adipose tissue.K The average PD-ENE was 1.8 mm; therefore, we divided ENE-positive patients into two groups: PD-ENE no greater than 2 mm and PD-ENE greater than 2 mm. CD-ENE was defined as measuring along the nodal capsule as the distance between peripheral edges of the ENE area. According to the average circumferential diameter (CD-ENE), we classified ENE-positive patients into two groups: CD-ENE no greater than 3 mm and CD-ENE greater than 3 mm. Correlations between ENE cutoffs and prognosis were analyzed. In this cohort of patients, 158 (39.3%) cases were positive for ENE in ALN.98 (24.4%) cases had PD-ENE no larger than 2 mm, and 60 (14.9%) cases had PD-ENE larger than 2 mm. Also, 112 (27.9%) cases had CD-ENE no larger than 3 mm, and 46 (11.4%) cases had CD-ENE larger than 3 mm. Statistical analysis indicated that histological grade, N stage, and HER2 overexpression subtype were associated with ENE. The presence of ENE had significant statistical correlations with nodal burden, including N stage, median metastatic tumor diameter and peri-lymph node vascular invasion (p < 0.001, p < 0.001, p = 0.001, respectively). Cox regression analysis demonstrated that patients with ENE exhibited significantly reduced DRFS in both univariable analysis (HR 2.126, 95% CI 1.453–3.112, p < 0.001) and multivariable analysis (HR 1.745, 95% CI 1.152–2.642, p = 0.009) compared with patients without ENE. For overall survival (OS), patients with ENE were associated with OS in univariable analysis (HR 2.505, 95% CI 1.337–4.693, p = 0.004) but not in multivariable analysis (HR 1.639, 95% CI 0.824–3.260, p = 0.159). Kaplan–Meier curves and log-rank test showed that patients with ENE in ALN had lower DRFS and OS (for DRFS: p < 0.0001; and for OS: p = 0.002, respectively). However, neither the PD-ENE group (divided by 2 mm) nor the CD-ENE group (divided by 3 mm) exhibited significant differences regarding nodal burden and prognosis. Our study indicated that ENE in the ALN was a predictor of prognosis in breast cancer. ENE was an independent prognostic factor for DRFS and was associated with OS. ENE in the ALN was associated with a higher nodal burden. The size of ENE, which was classified by a 3-mm (CD-ENE) or 2-mm (PD-ENE) cutoff value, had no significant prognostic value in this study. Based on our findings, the presence of ENE should be included in routine pathological reports of breast cancers. However, the cutoff values of ENE warrant further investigation. [ABSTRACT FROM AUTHOR]

Cloud computing enables resource-constrained clients to economically outsource their huge computation workloads to a powerful cloud server. This promising computing paradigm is able to realize client-cloud cooperative computations. It also brings in new security concerns and challenges, such as input/output privacy and efficiency. Since large matrix rank decomposition computation (RDC) is ubiquitous in the fields of science and engineering, a first step is taken forward to design a protocol that enables clients to securely and efficiently outsource RDC to a public cloud in this paper. It is analytically shown that the proposed protocol is correct and secure. Extensive theoretical analysis and experimental evaluation also show its high-efficiency and immediate practicability. It is hoped that the proposed protocol can shed light on designing other novel secure outsourcing protocols, and inspire powerful companies and working groups to finish the programming of the demanded all-inclusive scientific computations outsourcing software system. It is believed that such software system can be profitable by means of providing large-scale scientific computation services for so many potential clients. The proposed RDC outsourcing protocol is a step forward to realize such integrated software system. [ABSTRACT FROM AUTHOR]

Ricin is a toxic protein derived from castor beans and composed of a cytotoxic A chain and a galactose-binding B chain linked by a disulfide bond, which can inhibit protein synthesis and cause cell death. Owing to its high toxicity, ease of preparation, and lack of medical countermeasures, ricin has been listed as both chemical and biological warfare agents. For homeland security or public safety, the unambiguous, sensitive, and rapid methods for identification and quantification of ricin in complicated matrices are of urgent need. Mass spectrometric analysis, which provides specific and sensitive characterization of protein, can be applied to confirm and quantify ricin. Here, we report a liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method in which ricin was extracted and enriched from serum by immunocapture using anti-ricin monoclonal antibody 3D74 linked to magnetic beads, then digested by trypsin, and analyzed by LC-ESI-MS/MS. Among 19 distinct peptides observed in LC-quadrupole/time of flight-MS (LC-QTOF-MS), two specific and sensitive peptides, T (VGLPINQR) and T (DNCLTSDSNIR), were chosen, and a highly sensitive determination of ricin was established in LC-triple quadrupole-MS (LC-QqQ-MS) operating in multiple reaction monitoring mode. These specific peptides can definitely distinguish ricin from the homologous protein Ricinus communis agglutinin (RCA120), even though the amino acid sequence homology of the A-chain of ricin and RCA120 is up to ca. 93 % and that of B-chain is ca. 85 %. Furthermore, peptide T was preferred in the quantification of ricin because its sensitivity was at least one order of magnitude higher than that of the peptide T. Combined with immunocapture enrichment, this method provided a limit of detection of ca. 2.5 ng/mL and the limit of quantification was ca. 5 ng/mL of ricin in serum, respectively. Both precision and accuracy of this method were determined and the RSD was less than 15 %. This established method was then applied to measure ricin in serum samples collected from rats exposed to ricin at the dosage of 50 μg/kg in an intravenous injection manner. The results showed that ca. 10 ng/mL of the residual ricin in poisoned rats serum could be detected even at 12 h after exposure. [ABSTRACT FROM AUTHOR]

The precise stage of lymph node (LN) metastasis is a strong prognostic factor in breast cancers, and sentinel lymph node (SLN) is the first station of nodal metastasis. A number of patients have extranodal extension (ENE) in SLN, whereas the clinical values of ENE in SLN in breast cancers are still in exploration. The aim of our study was to evaluate the predictive and prognostic values of ENE in SLN in breast cancers, and to investigate the feasibility of ENE to predict non-SLN metastasis, nodal burden, disease free survival (DFS) and overall survival (OS) in clinical practice. 266 cases of primary invasive breast cancer (cT1-2N0 breast cancer) underwent SLN biopsy and axillary lymph node dissection (ALND) between 2008 and 2015 were extracted from the pathology database of Fudan University Shanghai Cancer Center. ENE in SLN was defined as extension of neoplastic cells through the lymph-nodal capsule into the peri-nodal adipose tissue, and was classified as no larger than 2 mm and larger than 2 mm group. The associations between ENE and clinicopathological features, non-SLN metastasis, nodal burden, DFS, and OS were analyzed. In the 266 patients with involved SLN, 100(37.6%) were positive for ENE in SLN. 67 (25.2%) cases had ENE no larger than 2 mm in diameter, and 33(12.4%) had ENE larger than 2 mm. Among the clinicopathological characteristics, the presence of ENE in SLN was associated with higher pT and pN stages, PR status, lympho-vascular invasion. Logistic regression analysis indicated that patients with ENE in SLN had higher rate of non-SLN metastasis (OR4.80, 95% CI 2.47–9.34, P < 0.001). Meanwhile, in patients with SLN micrometastasis or 1–2 SLNs involvement, ENE positive patients had higher rate of non-SLN metastasis, comparing with ENE negative patients (P < 0.001, P = 0.004 respectively). The presence of ENE in SLN was correlated with nodal burden, including the pattern and number of involved SLN (P < 0.001, P < 0.001 respectively), the number of involved non-SLN and total positive LNs (P < 0.001, P < 0.001 respectively). Patients with ENE had significantly higher frequency of pN2 disease (P < 0.001). For the disease recurrence and survival status, Cox regression analysis showed that patients with ENE in SLN had significantly reduced DFS (HR 3.05, 95%CI 1.13–10.48, P = 0.008) and OS (HR 3.34, 95%CI 0.74–14.52, P = 0.092) in multivariate analysis. Kaplan–Meier curves and log-rank test showed that patients with ENE in SLN had lower DFS and OS (for DFS: P < 0.001; and for OS: P < 0.001 respectively). Whereas no significant difference was found in nodal burden between ENE ≤ 2 mm and > 2 mm groups, except the number of SLN metastasis was higher in patients with ENE > 2 mm. Cox regression analysis, Kaplan–Meier curves and log-rank test indicated that the size of ENE was not an independent factor of DFS and OS. Our study indicated that ENE in SLN was a predictor for non-SLN metastasis, nodal burden and prognosis in breast cancers. Patients with ENE in SLN had a higher rate of non-SLN metastasis, higher frequency of pN2 disease, and poorer prognosis. Patients with ENE in SLN may benefit from additional ALND, even in SLN micrometastasis or 1–2 SLNs involvement patients. The presence of ENE in SLN should be evaluated in clinical practice. Size of ENE which was classified by a 2 mm cutoff value had no significant predictive and prognostic values in this study. The cutoff values of ENE in SLN need further investigation. [ABSTRACT FROM AUTHOR]