Data from small cell neuroendocrine carcinoma of the cervix: FIGO 2018 staging is more accurate than FIGO 2009

Objective To compare the prognostic value of International Federation of Gynecology and Obstetrics (FIGO) 2009 and 2018 staging systems in surgical patients with small cell neuroendocrine carcinoma of the cervix (SCNEC). Methods We re-staged 64 surgical IB–IIA (FIGO 2009) SCNEC patients according to the FIGO 2018 system and refined stage IIIC of FIGO 2018 based on tumor local invasion. The prognostic factors were analyzed, and the advantages of FIGO 2018 were compared with 2009. Results The 5-year overall survival rate (OS) was 78.5% for stage I and 22.2% for stage II (FIGO 2009). In FIGO 2018, there was no difference between stage I and II, and the 5-year OS was 74.1%, 60.2%, and 0% for stage I/II, IIIC1, and IIIC2. After combining stage IIIC with the local invasion stage (T1 was limited to the cervix and vagina; T2 involved the parametrium; T3 involved the pelvic or abdominal cavity), the 5-year OS for stage IIICT1, IIICT2, and IIICT3 was 83.3%, 30.0%, and 0%, respectively. Conclusions For stage II SCNEC patients, FIGO 2009 underestimated the prognosis, while FIGO 2018 was more accurate. For stage IIIC, FIGO 2018 might be more individualized and accurate after combining stage IIIC with tumor local invasion.

Darwin’s naturalization conundrum disentangled: the role of phylogenetic relatedness depends on the invasion stages

Darwin’s naturalization hypothesis predicts successful invaders to be distantly related to native species, whereas his pre-adaptation hypothesis predicts the opposite. It has been suggested that depending on the invasion stage (i.e. introduction, naturalization, and invasiveness), both hypotheses, now known as Darwin’s naturalization conundrum, could hold true. We tested this by analysing whether the likelihood of introduction for cultivation as well as subsequent stages of naturalization and invasion of species alien to Southern Africa are correlated with their phylogenetic distance to the native flora of this region. While species were more likely to be introduced for cultivation if they are distantly related to the native flora, the probability of subsequent naturalization was higher for species closely related to the native flora. Furthermore, the probability of becoming invasive was higher for naturalized species distantly related to the native flora. These results were consistent across three different metrics of phylogenetic distance. Our study reveals that the relationship between phylogenetic distance to the native flora and success of an alien species depends on the invasion stage.

Toward Identifying APT Malware through API System Calls

Self-developed malware was usually used by advanced persistent threat (APT) attackers to launch APT attacks. Therefore, we can enhance the understanding and cognition of APT attacks by comprehending the behavior of APT malware. Unfortunately, the current research cannot effectively explain the relationship between the recognition, detection, and defense of APT. The model of similar studies also lacks an explanation about it. To defend against APT attacks and inquire about the similarity of different APT attacks, this study proposes an APT malware classification method based on a combination of multiple deep learning algorithms and transfer learning by collecting malware used in several famous APT groups in public. By extracting the application programming interface (API) system calls, with the vector representation of features by combining dynamic LSTM and attention algorithm, we can obtain API at different APT families classification contributions trained dynamic. Thus, we used transfer learning to perform multiple classifications of the APT family. This study aims to reduce the burden of network security staff from reviewing a large number of suspicious files when defending against APT attacks. Additionally, it can effectively intercept them in the initial invasion stage of APT to perform targeted defense against specific APT attacks by combining threat intelligence in public. The experimental result shows that the proposed method can achieve 99.2% in distinguishing common malware from APT malware and assign APT malware to different APT families with an accuracy of 95.5%.

Comparative transcriptomic profiling of susceptible and resistant cultivars of pigeonpea demonstrates early molecular responses during Fusarium udum infection

Vascular wilt caused by Fusarium udum Butler is the most important disease of pigeonpea throughout the world. F. udum isolate MTCC 2204 (M1) inoculated pigeonpea plants of susceptible (ICP 2376) and resistant (ICP 8863) cultivars were taken at invasion stage of pathogenesis process for transcriptomic profiling to understand defense signaling reactions that interplay at early stage of this plant–pathogen encounter. Differential transcriptomic profiles were generated through cDNA-AFLP from M1 inoculated resistant and susceptible pigeonpea root tissues. Twenty five percent of transcript derived fragments (TDFs) were found to be pathogen induced. Among them 73 TDFs were re-amplified and sequenced. Homology search of the TDFs in available databases and thorough study of scientific literature identified several pathways, which could play crucial role in defense responses of the F. udum inoculated resistant plants. Some of the defense responsive pathways identified to be active during this interaction are, jasmonic acid and salicylic acid mediated defense responses, cell wall remodeling, vascular development and pattering, abscisic acid mediated responses, effector triggered immunity, and reactive oxygen species mediated signaling. This study identified important wilt responsive regulatory pathways in pigeonpea which will be helpful for further exploration of these resistant components for pigeonpea improvement.

The Antiviral Effect of Novel Steroidal Derivatives on Flaviviruses

Flaviviruses are the major emerging arthropod-borne pathogens globally. However, there is still no practical anti-flavivirus approach. Therefore, existing and emerging flaviviruses desperately need active broad-spectrum drugs. In the present study, the antiviral effect of steroidal dehydroepiandrosterone (DHEA) and 23 synthetic derivatives against flaviviruses such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), and Dengue virus (DENV) were appraised by examining the characteristics of virus infection both in vitro and in vivo. Our results revealed that AV1003, AV1004 and AV1017 were the most potent inhibitors of flavivirus propagation in cells. They mainly suppress the viral infection in the post-invasion stage in a dose-dependent manner. Furthermore, orally administered compound AV1004 protected mice from lethal JEV infection by increasing the survival rate and reducing the viral load in the brain of infected mice. These results indicate that the compound AV1004 might be a potential therapeutic drug against JEV infection. These DHEA derivatives may provide lead scaffolds for further design and synthesis of potential anti-flavivirus potential drugs.

The Prognostic Significance of MACC1 Expression in Breast Cancer and Its Relationship to Immune Cells in the Tumor Microenvironment and Patient Survival

Breast cancer (BC) is one of the most prevalent malignancies among females worldwide. Globally, distant metastases were reported to be responsible for a large proportion of breast cancer-related deaths. The metastasis-associated colon cancer-1 (MACC1) gene was reported as a reliable biomarker for early detection of metastasis and prediction of prognosis of breast cancer. This study investigated the prognostic significance of MACC1 in breast cancer in relation to the clinicopathologic characteristics and patients’ survival. Furthermore, the possible correlation between MACC1 expression and the different immune cells in the tumor microenvironment was explored. MACC1 mRNA was identified using quantitative reverse transcription polymerase chain reaction in 120 breast cancer specimens and adjacent non-cancerous tissues. MACC1 mRNA expression was significantly higher in the cancerous relative to the non-cancerous tissues (p < 0.001). High MACC1 expression was significantly associated with poor prognostic parameters, such as larger tumor size, grade III tumors, positive nodal metastasis, lymphovascular invasion, stage III tumors, and elevated Ki-67 expression. Higher MACC1 mRNA levels were positively correlated with CD163+ tumor-associated macrophages (r = 0.614, p < 0.001), and were negatively correlated with CD56+ natural killer cells (r = −0.398, p < 0.001) and CD8+ cytotoxic T lymphocytes (r = −0.323, p < 0.001). MACC1 expression was associated with poor patient overall survival (OS) and progression-free survival (PFS) (p < 0.001). Multivariate analysis suggested that MACC1 expression and the presence of lymphovascular invasion could be independent prognostic indicators for breast cancer (p = 0.015 and 0.042, respectively). In conclusion, MACC1 is highly expressed in cancerous tissues and is significantly related to poor prognostic factors, overall survival, and progression-free survival. MACC1 may influence infiltration of the immune cells in the tumor microenvironment, enhance immune escape of tumor cells, and may serve as a reliable independent prognostic factor for breast cancer.

Correlation of Serum HER-2/neu Levels with Clinico-Pathological Variables and Tissue Immunohistochemistry in Breast Carcinoma

Introduction: Serum levels of HER-2/neu protein is raised in primary as well as metastatic breast cancer and decreased serum HER-2/neu concentration in patients treated with HER- 2/neu inhibitors like trastuzumab is a good prognostic indicator in metastatic cases. Aims: To evaluate the concordance of serum HER-2/neu concentration with tissue HER-2/neu immunohistochemistry and determine its relationship with various prognostic indicators like age, size of tumour, lymph node status, grade, and stage of tumour. Materials and methods: The preoperative serum samples of 56 clinically and cytologically diagnosed cases of breast carcinoma were taken and postoperative mastectomy specimens were examined for the histologic type, lympho-vascular invasion, stage, and grade of the tumour. Immunohistochemical study of HER-2/neu xpression and HER-2/neu serum biochemistry was studied. Results: Age of the patients ranged from 25-75 years. Twenty-three cases (41.1%) were premenopausal while 33 cases (58.9%) postmenopausal. Forty-seven cases (83.9%) were of the infiltrating ductal carcinoma (NOS) type. Serum positivity for HER-2/neu was noted in 29 (51.8%) cases. Serum HER-2/neu levels showed a positive correlation with increase in tumour size, grade, stage of tumour and lymph node involvement. Serum HER-2/neu positivity was seen in 20 (68.9%) IHC positive patients and 9 (33.3%) IHC negative patients, with a statistically significant correlation (p=0.005). Conclusions: Serum HER-2/neu levels directly correlate with prognostic factors like tumour size, grade, stage of the tumour and lymph node metastasis and can be used as a complimentary tool to tissue HER-2/neu immunohistochemistry.

Evidence for multiple introductions of an invasive wild bee species currently under rapid range expansion in Europe

Background Invasive species are increasingly driving biodiversity decline, and knowledge of colonization dynamics, including both drivers and dispersal modes, are important to prevent future invasions. The bee species Megachile sculpturalis (Hymenoptera: Megachilidae), native to East-Asia, was first recognized in Southeast-France in 2008, and has since spread throughout much of Europe. The spread is very fast, and colonization may result from multiple fronts. Result To track the history of this invasion, codominant markers were genotyped using Illumina sequencing and the invasion history and degree of connectivity between populations across the European invasion axis were investigated. Distinctive genetic clusters were detected with east–west differentiations in Middle-Europe. Conclusion We hypothesize that the observed cluster formation resulted from multiple, independent introductions of the species to the European continent. This study draws a first picture of an early invasion stage of this wild bee and forms a foundation for further investigations, including studies of the species in their native Asian range and in the invaded range in North America.

Surgical Treatment of Advanced Thyroid Cancer with Tracheal Invasion

Introduction. Tracheal invasion in thyroid cancer occurs in one-third of locally advanced cases and is the third most common site of infiltration following strap muscles and recurrent laryngeal nerves. Surgical resection plays an important role in the management strategy followed by either radioactive iodine or external beam radiotherapy. Nonetheless, there has been still controversy about the optimal extension of the surgery. Case Presentation. Total thyroidectomy, airway resection and bilateral neck dissection were performed in two cases diagnosed as advanced thyroid cancer with tracheal invasion (stage IV according to McCaffrey). The first case underwent partial tracheal resection and direct anastomosis by the V-shape technique, while the latter one required tracheal resection and permanent tracheotomy. After one-year follow-up, no evidence of tumor recurrence or any postoperative complications were found. Conclusion. Surgical resection still remains the mainstay of management for advanced thyroid cancer in general and for tracheal invasion cases in particular. The decision of surgical resection and tracheal reconstruction methods mostly depends on the extent of tracheal invasion.