bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review on the Service Virtualisation and Its Structural Pillars
Authors: Farahmandpour Zeinab , Seyedmahmoudian Mehdi , Stojcevski Alex
Published: March 2021

Continuous delivery is an industry software development approach that aims to reduce the delivery time of software and increase the quality assurance within a short development cycle. The fast delivery and improved quality require continuous testing of the developed software service. Testing services are complicated and costly and postponed to the end of development due to unavailability of the requisite services. Therefore, an empirical approach that has been utilised to overcome these challenges is to automate software testing by virtualising the requisite services’ behaviour for the system being tested. Service virtualisation involves analysing the behaviour of software services to uncover their external behaviour in order to generate a light-weight executable model of the requisite services. There are different research areas which can be used to create such a virtual model of services from network interactions or service execution logs, including message format extraction, inferring control model, data model and multi-service dependencies. This paper reviews the state-of-the-art of how these areas have been used in automating the service virtualisation to make available the required environment for testing software. This paper provides a review of the relevant research within these four fields by carrying out a structured study on about 80 research works. These studies were then categorised according to their functional context as, extracting the message format, control model, data model and multi-service dependencies that can be employed to automate the service virtualisation activity. Based on our knowledge, this is the first structural review paper in service virtualisation fields.
Recent Advances in Plasma-Based Cancer Treatments: Approaching Clinical Translation through an Intracellular View
Authors: Alizadeh Elahe , Ptasińska Sylwia
Published: March 2021

Plasma medicine is a multidisciplinary field of research which is combining plasma physics and chemistry with biology and clinical medicine to launch a new cancer treatment modality. It mainly relies on utilizing low temperature plasmas in atmospheric pressure to generate and instill a cocktail of reactive species to selectively target malignant cells for inhibition the cell proliferation and tumor progression. Following a summarized review of primary in vitro and in vivo studies on the antitumor effects of low temperature plasmas, this article briefly outlines the plasma sources which have been developed for cancer therapeutic purposes. Intracellular mechanisms of action and significant pathways behind the anticancer effects of plasma and selectivity toward cancer cells are comprehensively discussed. A thorough understanding of involved mechanisms helps investigators to explicate many disputes including optimal plasma parameters to control the reactive species combination and concentration, transferring plasma to the tumors located in deep, and determining the optimal dose of plasma for specific outcomes in clinical translation. As a novel strategy for cancer therapy in clinical trials, designing low temperature plasma sources which meet the technical requirements of medical devices still needs to improve in efficacy and safety.
Nongaussian Intravoxel Incoherent Motion Diffusion Weighted and Fast Exchange Regime Dynamic Contrast-Enhanced-MRI of Nasopharyngeal Carcinoma: Preliminary Study for Predicting Locoregional Failure
Authors: Paudyal Ramesh , Chen Linda , Oh Jung Hun , Zakeri Kaveh , Hatzoglou Vaios , Tsai C. Jillian , Lee Nancy , Shukla-Dave Amita
Published: March 2021

The aim of the present study was to identify whether the quantitative metrics from pre-treatment (TX) non-Gaussian intravoxel incoherent motion (NGIVIM) diffusion weighted (DW-) and fast exchange regime (FXR) dynamic contrast enhanced (DCE)-MRI can predict patients with locoregional failure (LRF) in nasopharyngeal carcinoma (NPC). Twenty-nine NPC patients underwent pre-TX DW- and DCE-MRI on a 3T MR scanner. DW imaging data from primary tumors were fitted to monoexponential (ADC) and NGIVIM (D, D*, f, and K) models. The metrics Ktrans, ve, and τi were estimated using the FXR model. Cumulative incidence (CI) analysis and Fine-Gray (FG) modeling were performed considering death as a competing risk. Mean ve values were significantly different between patients with and without LRF (p = 0.03). Mean f values showed a trend towards the difference between the groups (p = 0.08). Histograms exhibited inter primary tumor heterogeneity. The CI curves showed significant differences for the dichotomized cutoff value of ADC ≤ 0.68 × 10−3 (mm2/s), D ≤ 0.74 × 10−3 (mm2/s), and f ≤ 0.18 (p < 0.05). τi ≤ 0.89 (s) cutoff value showed borderline significance (p = 0.098). FG’s modeling showed a significant difference for the K cutoff value of ≤0.86 (p = 0.034). Results suggest that the role of pre-TX NGIVIM DW- and FXR DCE-MRI-derived metrics for predicting LRF in NPC than alone.
Tumor Microenvironment in Metastatic Colorectal Cancer: The Arbitrator in Patients’ Outcome
Authors: Galindo-Pumariño Cristina , Collado Manuel , Herrera Mercedes , Peña Cristina
Published: March 2021

Colorectal cancer (CRC) is one of the most common cancers in western countries. Its mortality rate varies greatly, depending on the stage of the disease. The main cause of CRC mortality is metastasis, which most commonly affects the liver. The role of tumor microenvironment in tumor initiation, progression and metastasis development has been widely studied. In this review we summarize the role of the tumor microenvironment in the liver pre-metastatic niche formation, paying attention to the distant cellular crosstalk mediated by exosomes. Moreover, and based on the prognostic and predictive capacity of alterations in the stromal compartment of tumors, we describe the role of tumor microenvironment cells and related liquid biopsy biomarkers in the delivery of precise medication for metastatic CRC. Finally, we evaluate the different clinical strategies to prevent and treat liver metastatic disease, based on the targeting of the tumor microenvironment. Specifically, targeting angiogenesis pathways and regulating immune response are two important research pipelines that are being widely developed and promise great benefits.
Distinct Signatures of Genomic Copy Number Variants Define Subgroups of Merkel Cell Carcinoma Tumors
Authors: Hill Natasha T. , Kim David , Busam Klaus J. , Chu Emily Y. , Green Clayton , Brownell Isaac
Published: March 2021

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer. Most MCC tumors contain integrated Merkel cell polyomavirus DNA (virus-positive MCC, VP-MCC) and carry a low somatic mutation burden whereas virus-negative MCC (VN-MCC) possess numerous ultraviolet-signature mutations. In contrast to viral oncogenes and sequence mutations, little is known about genomic structural variants in MCC. To identify copy number variants in commonly altered genes, we analyzed genomic DNA from 31 tumor samples using the Nanostring nCounter copy number cancer panel. Unsupervised clustering revealed three tumor groups with distinct genomic structural variant signatures. The first cluster was characterized by multiple recurrent deletions in genes such as RB1 and WT1. The second cluster contained eight VP-MCC and displayed very few structural variations. The final cluster contained one VP-MCC and four VN-MCC with predominantly genomic amplifications in genes like MDM4, SKP2, and KIT and deletions in TP53. Overall, VN-MCC contained more structure variation than VP-MCC but did not cluster separately from VP-MCC. The observation that most MCC tumors demonstrate a deletion-dominated structural group signature, independent of virus status, suggests a shared pathophysiology among most VP-MCC and VN-MCC tumors.
MicroRNA as Epigenetic Modifiers in Endometrial Cancer: A Systematic Review
Authors: Favier Amélia , Rocher Grégoire , Larsen Annette K. , Delangle Romain , Uzan Catherine , Sabbah Michèle , Castela Mathieu , Duval Alex , Mehats Céline , Canlorbe Geoffroy
Published: March 2021

The objective of this systematic review is to summarize our current knowledge on the influence of miRNAs in the epigenetic deregulation of tumor-related genes in endometrial cancer (EC). We conducted a literature search on the role of miRNAs in the epigenetic regulation of EC applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following terms were used: microRNA, miRNA, miR, endometrial cancer, endometrium, epigenetic, epimutation, hypermethylation, lynch, deacetylase, DICER, novel biomarker, histone, chromatin. The miRNAs were classified and are presented according to their function (tumor suppressor or onco-miRNA), their targets (when known), their expression levels in EC tissue vs the normal surrounding tissue, and the degree of DNA methylation in miRNA loci and CpG sites. Data were collected from 201 articles, including 190 original articles, published between November 1, 2008 and September 30, 2020 identifying 313 different miRNAs implicated in epigenetic regulation of EC. Overall, we identified a total of 148 miRNAs with decreased expression in EC, 140 miRNAs with increased expression in EC, and 22 miRNAs with discordant expression levels. The literature implicated different epigenetic phenomena including altered miRNA expression levels (miR-182, -230), changes in the methylation of miRNA loci (miR-34b, -129-2, -130a/b, -152, -200b, -625) and increased/decreased methylation of target genes (miR-30d,-191). This work provides an overview of all miRNAs reported to be involved in epigenetic regulation in EC including DNA methylation and RNA-associated silencing. These findings may contribute to novel strategies in diagnosis, risk assessment, and treatments aimed at miRNAs, their target genes or DNA methylation.
Preclinical Verification of the Efficacy and Safety of Aqueous Plasma for Ovarian Cancer Therapy
Authors: Nakamura Kae , Yoshikawa Nobuhisa , Mizuno Yuko , Ito Miwa , Tanaka Hiromasa , Mizuno Masaaki , Toyokuni Shinya , Hori Masaru , Kikkawa Fumitaka , Kajiyama Hiroaki
Published: March 2021

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The major cause of EOC’s lethality is that intraperitoneal recurrence occurs with high frequency due to occult metastasis. We had demonstrated that plasma-activated medium (PAM) exerts a metastasis-inhibitory effect on ovarian cancer in vitro and in vivo. Here we investigated how PAM inhibits intraperitoneal metastasis. We studied PAM’s inhibition of micro-dissemination onto the omentum by performing in vivo imaging in combination with a sequential histological analysis. The results revealed that PAM induced macrophage infiltration into the disseminated lesion. The iNOS-positive signal was co-localized at the macrophages in the existing lesion, indicating that PAM might induce M1-type macrophages. This may be another mechanism of the antitumor effect through a PAM-evoked immune response. Intraperitoneal lavage with plasma-activated lactate Ringer’s solution (PAL) significantly improved the overall survival rate in an ovarian cancer mouse model. Our results demonstrated the efficiency and practicality of aqueous plasma for clinical applications.
Solitary Fibrous Tumor/Hemangiopericytoma Metastasizes Extracranially, Associated with Altered Expression of WNT5A and MMP9
Authors: Hong Jong-Hwan , Noh Myung-Giun , Akanda Md Rashedunnabi , Kim Yeong Jin , Kim Se Hoon , Jung Tae-Young , Jung Shin , Lee Jae-Hyuk , Rhee Joon Haeng , Kim Kyung-Keun , Kim Sung Sun , Lee Kyung-Hwa , Moon Kyung-Sub
Published: March 2021

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a mesenchymal tumor originating from various soft tissues and meninges, which carries the NAB2-STAT6 fusion gene. Meningeal/intracranial SFT/HPCs (icSFT/HPC) have a poor clinical outcome with metastatic behavior compared to soft tissue/extracranial SFT/HPCs (exSFT/HPC), but the underlying genetic factors are unclear. Differentially expressed genes (DEGs) were analyzed by NanoString nCounter assay using RNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue samples. Additionally, immunohistochemistry (IHC) was performed on 32 cases of exSFT/HPC, 18 cases of icSFT/HPC, and additional recurrent or metastatic cases to verify the findings. Pathway analysis revealed that the WNT signaling pathway was enriched in exSFT/HPC. Analysis of DEGs showed that expression of WNT5A was lower and that of MMP9 was higher in icSFT/HPC than in exSFT/HPC (p = 0.008 and p = 0.035, respectively). IHC showed that WNT5A and CD34 expression was high in exSFT/HPC (p < 0.001, both), while that of MMP9 was high in icSFT/HPC (p = 0.001). Expression of CLDN5 in tumoral vessels was locally decreased in icSFT/HPC (p < 0.001). The results suggested that decreased WNT5A expression, together with increased MMP9 expression, in icSFT/HPC, may affect vascular tightness and prompt tumor cells to metastasize extracranially.
Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression
Authors: Stålhammar Gustav , Grossniklaus Hans E.
Published: March 2021

Malignant tumors are rarely homogenous on the morphological, genome, transcriptome or proteome level. In this study, we investigate the intratumor heterogeneity of BAP-1 expression in uveal melanoma with digital image analysis of 40 tumors. The proportion of BAP-1 positive cells was measured in full tumor sections, hot spots, cold spots and in scleral margins. The mean difference between hot spots and cold spots was 41 percentage points (pp, SD 29). Tumors with gene expression class 1 (associated with low metastatic risk) and 2 (high metastatic risk) had similar intratumor heterogeneity. Similarly, the level of intratumor heterogeneity was comparable in tumors from patients that later developed metastases as in patients that did not. BAP-1 measured in any tumor region added significant prognostic information to both American Joint Committee on Cancer (AJCC) tumor size category (p ≤ 0.001) and gene expression class (p ≤ 0.04). We conclude that there is substantial intratumor heterogeneity in uveal melanoma BAP-1 expression. However, it is of limited prognostic importance. Regardless of region, analysis of BAP-1 expression adds significant prognostic information beyond tumor size and gene expression class.
Risk of Second Primary Malignancies among Patients with Early Gastric Cancer Exposed to Recurrent Computed Tomography Scans
Authors: Kim Tae Jun , Lee Yeong Chan , Min Yang Won , Lee Hyuk , Min Byung-Hoon , Lee Jun Haeng , Won Hong-Hee , Song Kyoung Doo , Jeong Woo Kyoung , Kim Jae J.
Published: March 2021

Although computed tomography (CT) scans are very useful for identification or surveillance of malignancy, they are also associated with the risk of cancer caused by ionizing radiation. We investigated the risk of second primary malignancies (SPMs) after frequent abdominopelvic CT scans in a cohort of Korean patients with early gastric cancer (EGC). We performed a cohort study of 11,072 patients who underwent resection for EGC at Samsung Medical Center and validated the results using data from 7908 patients in a Korean National Health Insurance Service cohort. Cox proportional hazards regression model was used to estimate hazard ratios (HRs) for intra-abdominal SPM. During 43,766.5 person-years of the follow-up at our center, 322 patients developed intra-abdominal SPMs. Patients who underwent receiving >8 abdominopelvic CT scans had a significantly greater risk of developing SPM (HR, 2.73; 95% CI, 1.66–4.50; p < 0.001) than those who had with ≤8 scans. For each additional abdominopelvic CT scan, the adjusted HR for SPM was 1.09 (95% confidence interval (CI), 1.03–1.14). Similar results were observed in the Korean National Health Insurance Service cohort (adjusted HR, 1.14; 95% CI, 1.07–1.22). Significantly elevated risk of SPM was still observed when considering a 2-year latency period (adjusted HR, 2.43; 95% CI, 1.37–4.48) and a 3-year latency period (adjusted HR, 2.17; 95% CI, 1.06–4.47). Frequent abdominopelvic CT scans are associated with an elevated risk of SPMs after the treatment of EGC. Thus, physicians need to weigh carefully the clinical benefits of CT examinations against the potential risks of radiation exposure.
Multi-Lens Arrays (MLA)-Assisted Photothermal Effects for Enhanced Fractional Cancer Treatment: Computational and Experimental Validations
Authors: Kim Hyejin , Pyo Hanjae , Kim Hyeonsoo , Kang Hyun Wook
Published: March 2021

Conventional photothermal therapy (PTT) for cancer typically employs an end-firing flat fiber (Flat) to deliver laser energy, leading to the incomplete treatment of target cells due to a Gaussian-shaped non-uniform beam profile. The purpose of the current study is to evaluate the feasibility of multi-lens arrays (MLA) for enhanced PTT by delivering laser light in a fractional micro-beam pattern. Computational and experimental evaluations compare the photothermal responses of gelatin phantoms and aqueous dye solutions to irradiations with Flat and MLA. In vivo colon cancer models have been developed to validate the therapeutic capacity of MLA-assisted irradiation. MLA yields 1.6-fold wider and 1.9-fold deeper temperature development in the gelatin phantom than Flat, and temperature monitoring identified the optimal treatment condition at an irradiance of 2 W/cm2 for 180 s. In vivo tests showed that the MLA group was accompanied by complete tumor eradication, whereas the Flat group yielded incomplete removal and significant tumor regrowth 14 days after PTT. The proposed MLA-assisted PTT spatially augments photothermal effects with the fractional micro-beams on the tumor and helps achieve complete tumor removal without recurrence. Further investigations are expected to optimize treatment conditions with various wavelengths and photosensitizers to warrant treatment efficacy and safety for clinical translation.
TERT Promoter Alterations in Glioblastoma: A Systematic Review
Authors: Olympios Nathalie , Gilard Vianney , Marguet Florent , Clatot Florian , Di Fiore Frédéric , Fontanilles Maxime
Published: March 2021

Glioblastoma, the most frequent and aggressive primary malignant tumor, often presents with alterations in the telomerase reverse transcriptase promoter. Telomerase is responsible for the maintenance of telomere length to avoid cell death. Telomere lengthening is required for cancer cell survival and has led to the investigation of telomerase activity as a potential mechanism that enables cancer growth. The aim of this systematic review is to provide an overview of the available data concerning TERT alterations and glioblastoma in terms of incidence, physiopathological understanding, and potential therapeutic implications.
Cutaneous Squamous Cell Carcinoma in the Age of Immunotherapy
Authors: Ishitsuka Yosuke , Hanaoka Yuma , Tanemura Atsushi , Fujimoto Manabu
Published: March 2021

Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent skin cancer globally. Because most cSCC cases are manageable by local excision/radiotherapy and hardly become life-threatening, they are often excluded from cancer registries in most countries. Compared with cutaneous melanoma that originates from the melanin-producing, neural crest-derived epidermal resident, keratinocyte (KC)-derived cancers are influenced by the immune system with regards to their pathogenetic behaviour. Congenital or acquired immunosurveillance impairments compromise tumoricidal activity and raises cSCC incidence rates. Intriguingly, expanded applications of programmed death-1 (PD-1) blockade therapies have revealed cSCC to be one of the most amenable targets, particularly when compared with the mucosal counterparts arisen in the esophagus or the cervix. The clinical observation reminds us that cutaneous tissue has a peculiarly high immunogenicity that can evoke tumoricidal recall responses topically. Here we attempt to redefine cSCC biology and review current knowledge about cSCC from multiple viewpoints that involve epidemiology, clinicopathology, molecular genetics, molecular immunology, and developmental biology. This synthesis not only underscores the primal importance of the immune system, rather than just a mere accumulation of ultraviolet-induced mutations but also reinforces the following hypothesis: PD-1 blockade effectively restores the immunity specially allowed to exist within the fully cornified squamous epithelium, that is, the epidermis.
Novel Cytotoxic Chemotherapies in Small Cell Lung Carcinoma
Authors: Cortinovis Diego , Bidoli Paolo , Canova Stefania , Colonese Francesca , Gemelli Maria , Lavitrano Maria Luisa , Banna Giuseppe Luigi , Liu Stephen V. , Morabito Alessandro
Published: March 2021

Small cell lung cancer (SCLC) is one of the deadliest thoracic neoplasms, in part due to its fast doubling time and early metastatic spread. Historically, cytotoxic chemotherapy consisting of platinum–etoposide or anthracycline-based regimens has demonstrated a high response rate, but early chemoresistance leads to a poor prognosis in advanced SCLC. Only a fraction of patients with limited-disease can be cured by chemo-radiotherapy. Given the disappointing survival rates in advanced SCLC, new cytotoxic agents are eagerly awaited. Unfortunately, few novel chemotherapy drugs have been developed in the latest decades. This review describes the results and potential application in the clinical practice of novel chemotherapy agents for SCLC.
A Principal Component of Quality of Life Measures Is Associated with Survival for Head and Neck Cancer Patients Treated with Radiation Therapy
Authors: Farrugia Mark , Yu Han , Ma Sung Jun , Iovoli Austin J. , Attwood Kristopher , Wooten Kimberly E. , Arshad Hassan , Gupta Vishal , McSpadden Ryan P. , Kuriakose Moni A. , Markiewicz Michael R. , Chan Jon M. , Hicks Wesley L. , Platek Mary E. , Ray Andrew D. , Repasky Elizabeth A. , Singh Anurag K.
Published: March 2021

Background: Health-related quality of life (HRQOL) metrics can be associated with survival in head and neck cancer (HNC); however, the impact of HRQOL recovery and the relevant HRQOL domains regarding outcome are unclear. Methods: Using a single-institution database, we retrospectively reviewed HNC patients treated with definitive or postoperative radiation therapy between 2013 and 2018. The recovery of individual HRQOL domains were determined by the ratio of the post-treatment to baseline scores. Univariate and Multivariate Cox regression were used to analyze survival outcomes. Principal component analysis was used to adjust for multicollinearity of HRQOL domains. Results: In 218 HNC patients who received radiation therapy, median follow-up was 24.8 months (interquartile range (IQR) 14.5–32.0). Principal component analysis evaluating the recovery of HRQOL domains revealed two independent principal components (PC), PC1 and PC2. PC1, which received contributions from the functional domains; physical (PF), role (RF), emotional (EF), cognitive (CF), and global health status (GQOL) was significantly associated with disease-free (HR = 0.77, 95% CI 0.61–0.98, p = 0.034) and overall survival (HR = 0.76, 95% CI 0.65–0.91, p = 0.004) on multivariate analysis and PC2, had no correlation with outcome and was mainly represented by social functioning. Unplanned hospitalization was significantly associated with lower PC1 scores (β = −0.997, Std. Error = 0.244, p < 0.001). Conclusion: Our study provides evidence that post-treatment recovery of HRQOL domains were associated with overall survival (OS) in HNC. PC1 is an attractive clinical tool to assess the recovery across multiple different HRQOL and the relationship with survival. Future prospective studies may identify patients who could benefit from additional rehabilitation based on PC1 score.
Expedition into Exosome Biology: A Perspective of Progress from Discovery to Therapeutic Development
Authors: Jan Arif Tasleem , Rahman Safikur , Badierah Raied , Lee Eun Ju , Mattar Ehab H. , Redwan Elrashdy M. , Choi Inho
Published: March 2021

Exosomes are membrane-enclosed distinct cellular entities of endocytic origin that shuttle proteins and RNA molecules intercellularly for communication purposes. Their surface is embossed by a huge variety of proteins, some of which are used as diagnostic markers. Exosomes are being explored for potential drug delivery, although their therapeutic utilities are impeded by gaps in knowledge regarding their formation and function under physiological condition and by lack of methods capable of shedding light on intraluminal vesicle release at the target site. Nonetheless, exosomes offer a promising means of developing systems that enable the specific delivery of therapeutics in diseases like cancer. This review summarizes information on donor cell types, cargoes, cargo loading, routes of administration, and the engineering of exosomal surfaces for specific peptides that increase target specificity and as such, therapeutic delivery.
Downregulation of Snail by DUSP1 Impairs Cell Migration and Invasion through the Inactivation of JNK and ERK and Is Useful as a Predictive Factor in the Prognosis of Prostate Cancer
Authors: Martínez-Martínez Desirée , Toledo Lobo María-Val , Baquero Pablo , Ropero Santiago , Angulo Javier C. , Chiloeches Antonio , Lasa Marina
Published: March 2021

Dual specificity phosphatase 1 (DUSP1) is crucial in prostate cancer (PC), since its expression is downregulated in advanced carcinomas. Here, we investigated DUSP1 effects on the expression of mesenchymal marker Snail, cell migration and invasion, analyzing the underlying mechanisms mediated by mitogen-activated protein kinases (MAPKs) inhibition. To this purpose, we used different PC cells overexpressing or lacking DUSP1 or incubated with MAPKs inhibitors. Moreover, we addressed the correlation of DUSP1 expression with Snail and activated MAPKs levels in samples from patients diagnosed with benign hyperplasia or prostate carcinoma, studying its implication in tumor prognosis and survival. We found that DUSP1 downregulates Snail expression and impairs migration and invasion in PC cells. Similar results were obtained following the inhibition of c-Jun N-terminal kinase (JNK) and extracellular-signal-regulated kinase (ERK). In clinical samples, we evidenced an inverse correlation between DUSP1 expression and Snail levels, which are further associated with JNK and ERK activation. Consequently, the pattern DUSP1high/activated JNKlow/activated ERKlow/Snaillow is associated with an overall extended survival of PC patients. In summary, the ratio between DUSP1 and Snail expression, with additional JNK and ERK activity measurement, may serve as a potential biomarker to predict the clinical outcome of PC patients. Furthermore, DUSP1 induction or inhibition of JNK and ERK pathways could be useful to treat PC.
Tumor Suppressor miR-584-5p Inhibits Migration and Invasion in Smoking Related Non-Small Cell Lung Cancer Cells by Targeting YKT6
Authors: Lee Saet Byeol , Park Young Soo , Sung Jae Sook , Lee Jong Won , Kim Boyeon , Kim Yeul Hong
Published: March 2021

Cigarette smoke (CS) affects the expression of microRNAs (miRNAs), which are important regulators of gene expression by inducing DNA methylation. However, the effects of smoking on miRNA expression have not been fully elucidated in smoking-related lung carcinogenesis. Therefore, in this study, to investigate the change of miRNA expression pattern and to identify tumor suppressor miRNAs by smoking in lung carcinogenesis, we used lung carcinogenesis model cell lines that, derived from a murine xenograft model with human bronchial epithelial cells (BEAS-2B), exposed CS or not. The microarray analysis revealed that miR-584-5p expression was downregulated with cancer progression in lung carcinogenesis model cell lines. We confirmed by pyrosequencing that the methylation level of the miR-584-5p promoter increased with cancer progression. In vitro and in vivo experiments showed that miR-584-5p suppressed migration and invasion in non-small cell lung cancer (NSCLC) cells by targeting YKT6. Furthermore, we showed that high level of YKT6 was associated with a poor survival rate in NSCLC patients with a history of smoking. These results suggest that miR-584-5p acts as a tumor suppressor and is a potential molecular biomarker for smoking-related NSCLC.
The Emerging Role of Extracellular Vesicles in Endocrine Resistant Breast Cancer
Authors: La Camera Giusi , Gelsomino Luca , Caruso Amanda , Panza Salvatore , Barone Ines , Bonofiglio Daniela , Andò Sebastiano , Giordano Cinzia , Catalano Stefania
Published: March 2021

Breast cancer is the most common solid malignancy diagnosed in females worldwide, and approximately 70% of these tumors express estrogen receptor α (ERα), the main biomarker of endocrine therapy. Unfortunately, despite the use of long-term anti-hormone adjuvant treatment, which has significantly reduced patient mortality, resistance to the endocrine treatments often develops, leading to disease recurrence and limiting clinical benefits. Emerging evidence indicates that extracellular vesicles (EVs), nanosized particles that are released by all cell types and responsible for local and systemic intercellular communications, might represent a newly identified mechanism underlying endocrine resistance. Unraveling the role of EVs, released by transformed cells during the tumor evolution under endocrine therapy, is still an open question in the cancer research area and the molecular mechanisms involved should be better defined to discover alternative therapeutic approaches to overcome resistance. In this review, we will provide an overview of recent findings on the involvement of EVs in sustaining hormonal resistance in breast cancer and discuss opportunities for their potential use as biomarkers to monitor the therapeutic response and disease progression.
Patterns of Sequelae in Women with a History of Localized Breast Cancer: Results from the French VICAN Survey
Authors: Delrieu Lidia , Bouaoun Liacine , Fatouhi Douae El , Dumas Elise , Bouhnik Anne-Deborah , Noelle Hugo , Jacquet Emmanuelle , Hamy Anne-Sophie , Coussy Florence , Reyal Fabien , Heudel Pierre-Etienne , Bendiane Marc-Karim , Fournier Baptiste , Michallet Mauricette , Fervers Béatrice , Fagherazzi Guy , Pérol Olivia
Published: March 2021

Breast cancer (BC) remains complex for women both physically and psychologically. The objectives of this study were to (1) assess the evolution of the main sequelae and treatment two and five years after diagnosis in women with early-stage breast cancer, (2) explore patterns of sequelae associated with given sociodemographic, clinical, and lifestyle factors. The current analysis was based on 654 localized BC patients enrolled in the French nationwide longitudinal survey “vie après cancer” VICAN (January–June 2010). Information about study participants was collected at enrollment, two and five years after diagnosis. Changes over time of the main sequelae were analyzed and latent class analysis was performed to identify patterns of sequelae related to BC five years after diagnosis. The mean age (±SD) of study participants at inclusion was 49.7 (±10.5) years old. Six main classes of sequelae were identified two years and five years post-diagnosis (functional, pain, esthetic, fatigue, psychological, and gynecological). A significant decrease was observed for fatigue (p = 0.03) and an increase in cognitive sequelae was reported (p = 0.03). Two latent classes were identified—functional and esthetic patterns. Substantial sequelae remain up to five years after BC diagnosis. Changes in patient care pathways are needed to identify BC patients at a high risk.
Immune-Related Mutational Landscape and Gene Signatures: Prognostic Value and Therapeutic Impact for Head and Neck Cancer
Authors: Feng Bohai , Hess Jochen
Published: March 2021

Immunotherapy by immune checkpoint inhibition has become a main pillar in the armamentarium to treat head and neck cancer and is based on the premise that the host immune system can be reactivated to successfully eliminate cancer cells. However, the response rate remains low and only a small subset of head and neck cancer patients achieves a durable clinical benefit. The availability of multi-omics data and emerging computational technologies facilitate not only a deeper understanding of the cellular composition in the tumor immune microenvironment but also enables the study of molecular principles in the complex regulation of immune surveillance versus tolerance. These knowledges will pave the way to apply immunotherapy more precisely and effectively. This review aims to provide a holistic view on how the immune landscape dictates the tumor fate and vice versa, and how integrative analysis of multi-omics data contribute to our current knowledge on the accuracy of predictive biomarkers and on a broad range of factors influencing the response to immunotherapy in head and neck cancer.
Acute Hepatitis in a Yemeni Immigrant Associated with Khat: A “Biological Amphetamine” Carried in Cultures
Authors: Patel Harish , Kumar Kishore , Essrani Rajesh Kumar , Niazi Masooma , Makker Jasbir , Nayudu Suresh Kumar
Published: March 2021

Viral infections, alcohol, hepatic steatosis, autoimmunity medications and herbal supplements are common etiologies of hepatitis. Khat (Catha Edulis) is a commonly used recreational substance in East African and Middle Eastern countries. Khat has been reported in the literature to be associated with hepatotoxicity, which can present in several forms, including chronic liver disease. The possible pathogenesis of liver injury could be secondary to biochemical components of Khat itself or additives such as pesticides or preservatives. An autoimmune mechanism of liver injury has also been postulated, supported by sparse evidence. We present a case of a Yemeni immigrant with acute hepatitis whose fear about social norms and breaching confidentiality made it challenging to identify Khat as being the underlying cause. A 34-year-old man from Yemen presented with right upper quadrant pain of one day duration. He had predominantly elevated transaminases with mild elevation in bilirubin. His investigations were negative for the viral, metabolic or biliary etiology. A persistent focus on clinical history and the well-established physician–patient relationship revealed a history of Khat use. The liver biopsy finding of lobular hepatitis was compatible with drug-induced liver injury and established the finding of Khat hepatotoxicity. Subsequently, the patient improved with conservative management.
Management of the Elderly Patients with High-Grade Serous Ovarian Cancer in the REAL-WORLD Setting
Authors: Liontos Michalis , Papatheodoridi Alkistis , Andrikopoulou Angeliki , Thomakos Nikolaos , Haidopoulos Dimitrios , Rodolakis Alexandros , Zagouri Flora , Bamias Aristotelis , Dimopoulos Meletios-Athanasios
Published: March 2021

Treatment of elderly patients with neoplasia is challenging. Age is a known prognostic factor in ovarian cancer but the optimal treatment of elderly patients has not been determined. We undertook a retrospective analysis to determine clinical practice in advanced-stage ovarian cancer patients older than 70 years of age. Methods: Medical records of women with high-grade serous ovarian cancer, stage III and IV were retrospectively analyzed. Results: A total of 735 patients were identified with a median age of 61.5 years. 22.4% among them were older than 70 years of age at diagnosis. First-line Progression-Free Survival (PFS) and Overall Survival (OS) were significantly worse in elderly patients in comparison to the younger ones [mPFS 11.3 months vs. 14.8 months, (p < 0.001) and mOS 30.2 months vs. 45.6 months (p < 0.001)]. However, elderly patients were characterized by worse ECOG-Performance Status and they were more frequently treated with Neoadjuvant Chemotherapy followed by Interval Debulking Surgery, while often they were more frequently denied debulking surgery compared to patients under 70 years of age. Moreover, elderly patients received more frequently monotherapy with platinum as frontline treatment. In contrast, there was no significant difference in the outcome of the debulking surgery in comparison to the younger patients or the frequency that gBRCA test was performed. Age over 70 years did not retain its significance for either Progression-Free Survival or Overall Survival when adjusted for all other reported prognostic factors. Conclusions: Elderly ovarian cancer patients have a worse prognosis. Comprehensive geriatric assessment should be performed for the optimal treatment of these patients.
Effect of Protection of Mountainous Vegetation against Over-Grazing and Over-Cutting in South Sinai, Egypt
Authors: Shaltout Kamal H. , Eid Ebrahem M. , Al-Sodany Yassin M. , Heneidy Selim Z. , Shaltout Salma K. , El-Masry Safaa A.
Published: March 2021

In this study, we evaluated the species diversity, density, cover, and size index of plant species within and outside 37 enclosures in the South Sinai mountainous region (Egypt), which had been protected for six years (March 2012–March 2018) against over-grazing and over-cutting for medicinal and fuel purposes. Within and outside the enclosures, the plant species were recorded, and their density (individuals per 100 m2) and cover (cm per 100 cm) were estimated using the line-intercept method. The biovolume of each individual of each species was calculated as the average of its height and diameter. The species richness was calculated as the average number of species per enclosure, and the species turnover was calculated as the ratio between the total number of species and the species richness. The relative evenness was calculated using the Shannon–Weaver index, whereas the relative concentration of dominance was calculated using the Simpson index. Detrended correspondence analysis (DCA) was applied to ordinate the vegetation inside and outside the enclosures depending on the species cover. The unpaired t-test was applied to assess the statistically significant differences in the species density, cover, and biovolume inside and outside the enclosures. By the end of the six-year period, the vegetation pattern inside the enclosures became more or less stable, presumably because of the stopping of grazing and cutting, which also led to an increase in the plant diversity, density, and cover. In general, the protection of vegetation in South Sinai improved its diversity, density, and cover. In addition, the topographic and physiographic heterogeneity in this region results in microclimatic variations, which play a major role in governing its natural vegetation.
Trees Increase Ant Species Richness and Change Community Composition in Iberian Oak Savannahs
Authors: Gaytán Álvaro , Bautista José L. , Bonal Raúl , Moreno Gerardo , González-Bornay Guillermo
Published: March 2021

Iberian man-made oak savannahs (so called dehesas) are traditional silvopastoral systems with a high natural value. Scattered trees provide shelter and additional food to livestock (cattle in our study sites), which also makes possible for animals depending on trees in a grass-dominated landscape to be present. We compared dehesas with nearby treeless grasslands to assess the effects of oaks on ant communities. Formica subrufa, a species associated with decayed wood, was by far the most abundant species, especially in savannahs. Taxa specialized in warm habitats were the most common both in dehesas and grasslands, as expected in areas with a Mediterranean climate. Within dehesas, the number of species was higher below oak canopies than outside tree cover. Compared to treeless grasslands, the presence of oaks resulted in a higher species richness of aphid-herding and predator ants, probably because trees offer shelter and resources to predators. The presence of oaks changed also the species composition, which differed between grasslands and dehesas. In self-standing scattered oaks, ant communities did not differ between the trunks and soil below canopies. These results stress the conservation value of trees in dehesas; within grasslands, they offer an additional microhabitat for species that would otherwise be scarce or absent.
Onset of the Mach Reflection of Zel’dovich–von Neumann–Döring Detonations
Authors: Jing Tianyu , Ren Huilan , Li Jian
Published: March 2021

The present study investigates the similarity problem associated with the onset of the Mach reflection of Zel’dovich–von Neumann–Döring (ZND) detonations in the near field. The results reveal that the self-similarity in the frozen-limit regime is strictly valid only within a small scale, i.e., of the order of the induction length. The Mach reflection becomes non-self-similar during the transition of the Mach stem from “frozen” to “reactive” by coupling with the reaction zone. The triple-point trajectory first rises from the self-similar result due to compressive waves generated by the “hot spot”, and then decays after establishment of the reactive Mach stem. It is also found, by removing the restriction, that the frozen limit can be extended to a much larger distance than expected. The obtained results elucidate the physical origin of the onset of Mach reflection with chemical reactions, which has previously been observed in both experiments and numerical simulations.
Sizing and Coordination Strategies of Battery Energy Storage System Co-Located with Wind Farm: The UK Perspective
Authors: Fan Fulin , Zorzi Giorgio , Campos-Gaona David , Burt Graeme , Anaya-Lara Olimpo , Nwobu John , Madariaga Ander
Published: March 2021

The rapid development and growth of battery storage have heightened an interest in the co-location of battery energy storage systems (BESS) with renewable energy projects which enables the stacking of multiple revenue streams while reducing connection charges of BESS. To help wind energy industries better understand the coordinated operation of BESS and wind farms and its associated profits, this paper develops a simulation model to implement a number of coordination strategies where the BESS supplies enhanced frequency response (EFR) service and enables the time shift of wind generation based on the UK perspective. The proposed model also simulates the degradation of Lithium-Ion battery and incorporates a state of charge (SOC) dependent limit on the charge rate derived from a constant current-constant voltage charging profile. In addition, a particle swarm optimisation-based battery sizing algorithm is developed here on the basis of the simulation model to determine the optimal size of the co-located BESS along with SOC-related strategy variables that maximise the net present value of the wind + BESS system at the end of the EFR contract.
Predicting Capacity Fade in Silicon Anode-Based Li-Ion Batteries
Authors: Dasari Harika , Eisenbraun Eric
Published: March 2021

While silicon anodes hold promise for use in lithium-ion batteries owing to their very high theoretical storage capacity and relatively low discharge potential, they possess a major problem related to their large volume expansion that occurs with battery aging. The resulting stress and strain can lead to mechanical separation of the anode from the current collector and an unstable solid electrolyte interphase (SEI), resulting in capacity fade. Since capacity loss is in part dependent on the cell materials, two different electrodes, Lithium Nickel Oxide or LiNi0.8Co0.15Al0.05O2 (NCA) and LiNi1/3Mn1/3Co1/3O2 (NMC 111), were used in combination with silicon to study capacity fade effects using simulations in COMSOL version 5.5. The results of these studies provide insight into the effects of anode particle size and electrolyte volume fraction on the behavior of silicon anode-based batteries with different positive electrodes. It was observed that the performance of a porous matrix of solid active particles of silicon anode could be improved when the active particles were 150 nm or smaller. The range of optimized values of volume fraction of the electrolyte in the silicon anode were determined to be between 0.55 and 0.40. The silicon anode behaved differently in terms of cell time with NCA and NMC. However, NMC111 gave a high relative capacity in comparison to NCA and proved to be a better working electrode for the proposed silicon anode structure.
Optimization of Thermal Backfill Configurations for Desired High-Voltage Power Cables Ampacity
Authors: Czapp Stanislaw , Ratkowski Filip
Published: March 2021

The ampacity of high-voltage power cables depends, among others, on their core cross-sectional area as well as thermal resistivity of the thermal backfill surrounding the cables. The cross-sectional area of the power cables’ core is selected according to the expected power to be transferred via the cable system. Usually, the higher the power transfer required, the higher the cross-sectional area of the core. However, the cost of high-voltage power cables is relatively high and strictly depends on the dimensions of the core. Therefore, from the economic point of view, it is interesting to focus on the improvement of the thermal condition around the cables, by changing the dimension of the thermal backfill, instead of increasing the power cables’ core cross-sectional area. In practice, it is important to find the optimal dimensions of both cable core and thermal backfill to achieve the economically attractive solution of the power cable transfer system. This paper presents a mathematical approach to the power-cable system design, which enables selecting the cost-optimal cross-section of a power cable core depending on the dimensions of the thermal backfill. The proposal herein allows us to indicate the condition in which it is advantageous to increase the core cross-sectional area or to expand the dimension of the backfill. In this approach, the optimal backfill geometry can also be evaluated. The investment costs of the 110 kV power cable system with the core cross-sectional areas consecutively equal to 630, 800 and 1000 mm2 have been compared.
Analysis and Simulations of the Primary Frequency Control during a System Split in Continental Europe Power System
Authors: Ippolito Mariano G. , Musca Rossano , Zizzo Gaetano
Published: March 2021

The occurrence of system separations in the power system of Continental Europe has been observed in recent decades as a critical event which might cause power imbalances higher than the reference incident specified per system design, representing an actual challenge for the stability and safe operation of the system. This work presents an analysis and simulations of the primary frequency control in the Continental Europe synchronous area in conditions of system separation. The adopted approach is based on fundamental aspects of the frequency-containment reserve process. The analysis takes an actual event into consideration, which determined the separation of the system in January 2021. The main purpose of the work is the development of specific models and simulations able to reproduce the actual split event. Due to specific arrangements discussed in detail, it is possible to obtain a substantial match between the simulations and the frequencies registered after the system split. The work also provides insight into the importance of the temporal sequence of power imbalances and defensive actions in the primary frequency control process. The models developed in the work are finally used to investigate the separation event under different operating conditions, such as missing defensive actions and low inertia scenarios.