bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dark Web Marketplaces and COVID-19: before the vaccine
Authors: Bracci Alberto , Nadini Matthieu , Aliapoulios Maxwell , McCoy Damon , Gray Ian , Teytelboym Alexander , Gallo Angela , Baronchelli Andrea 
Published: January 2021

AbstractThe COVID-19 pandemic has reshaped the demand for goods and services worldwide. The combination of a public health emergency, economic distress, and misinformation-driven panic have pushed customers and vendors towards the shadow economy. In particular, dark web marketplaces (DWMs), commercial websites accessible via free software, have gained significant popularity. Here, we analyse 851,199 listings extracted from 30 DWMs between January 1, 2020 and November 16, 2020. We identify 788 listings directly related to COVID-19 products and monitor the temporal evolution of product categories including Personal Protective Equipment (PPE), medicines (e.g., hydroxyclorochine), and medical frauds. Finally, we compare trends in their temporal evolution with variations in public attention, as measured by Twitter posts and Wikipedia page visits. We reveal how the online shadow economy has evolved during the COVID-19 pandemic and highlight the importance of a continuous monitoring of DWMs, especially now that real vaccines are available and in short supply. We anticipate our analysis will be of interest both to researchers and public agencies focused on the protection of public health.
A Practical Tutorial for Decision Tree Induction
Authors: Hernández Víctor Adrián Sosa , Monroy Raúl , Medina-Pérez Miguel Angel , Loyola-González Octavio , Herrera Francisco 
Published: January 2021

Experts from different domains have resorted to machine learning techniques to produce explainable models that support decision-making. Among existing techniques, decision trees have been useful in many application domains for classification. Decision trees can make decisions in a language that is closer to that of the experts. Many researchers have attempted to create better decision tree models by improving the components of the induction algorithm. One of the main components that have been studied and improved is the evaluation measure for candidate splits.In this article, we introduce a tutorial that explains decision tree induction. Then, we present an experimental framework to assess the performance of 21 evaluation measures that produce different C4.5 variants considering 110 databases, two performance measures, and 10× 10-fold cross-validation. Furthermore, we compare and rank the evaluation measures by using a Bayesian statistical analysis. From our experimental results, we present the first two performance rankings in the literature of C4.5 variants. Moreover, we organize the evaluation measures into two groups according to their performance. Finally, we introduce meta-models that automatically determine the group of evaluation measures to produce a C4.5 variant for a new database and some further opportunities for decision tree models.
Ligands of the Mitochondrial 18 kDa Translocator Protein Attenuate Apoptosis of Human Glioblastoma Cells Exposed to Erucylphosphohomocholine
Authors: Kugler Wilfried , Veenman Leo , Shandalov Yulia , Leschiner Svetlana , Spanier Ilana , Lakomek Max , Gavish Moshe 
Published: January 2021

Background: We have previously shown that the anti-neoplastic agent erucylphosphohomocholine (ErPC3) requires the mitochondrial 18 kDa Translocator protein (TSPO), formerly known as the peripheral-type benzodiazepine receptor (PBR), to induce cell death via the mitochondrial apoptosis pathway.Methods: With the aid of the dye JC-1 and cyclosporin A, applied to glioblastoma cells, we now investigated the significance of opening of the mitochondrial permeability transition pore (MPTP) for ErPC3-induced apoptosis in interaction with the TSPO ligands, PK 11195 and Ro5 4864. Furthermore, we measured cytochrome c release, and caspase-9 and -3 activation in this paradigm.Results: The human glioblastoma cell lines, U87MG, A172 and U118MG express the MPTP-associated TSPO, voltage-dependent anion channel and adenine nucleotide transporter. Indeed, ErPC3-induced apoptosis was inhibited by the MPTP blocker cyclosporin A and by PK 11195 and Ro5 4864 in a concentration-dependent manner. Furthermore, PK 11195 and Ro5 4864 inhibited collapse of the mitochondrial membrane potential, cytochrome c release, and caspase-9 and -3 activation caused by ErPC3 treatment.Conclusions: This study shows that PK 11195 and Ro5 4864 inhibit the pro-apoptotic function of ErPC3 by blocking its capacity to cause a collapse of the mitochondrial membrane potential. Thus, the TSPO may serve to open the MPTP in response to anti-cancer drugs such as ErPC3.
Alterations in AP‐1 and AP‐1 Regulatory Genes during HPV‐Induced Carcinogenesis
Authors: de Wilde Jillian , De-Castro Arce Johanna , Snijders Peter J. F. , Meijer Chris J. L. M. , Rösl Frank , Steenbergen Renske D. M. 
Published: January 2021

Background: Previous studies demonstrated a functional involvement of the AP‐1 transcription factor in HPV‐induced cervical carcinogenesis. Here, we aimed to obtain further insight in expression alterations of AP‐1 family members during HPV‐mediated transformation and their relationship to potential regulatory (Notch1, Net) and target (CADM1) genes.Methods: mRNA expression levels of c‐Jun, JunB, junD, c‐Fos, FosB, Fra‐1, Fra‐2, Notch1, Net and CADM1 were determined by quantitative RT‐PCR in primary keratinocytes (n=5), early (n=4) and late (n=4) passages of non‐tumorigenic HPV‐immortalized keratinocytes and in tumorigenic cervical cancer cell lines (n=7). In a subset of cell lines protein expression and AP‐1 complex composition was determined.Results: Starting in immortal stages c‐Fos, Fra‐2 and JunB expression became up regulated towards tumorigenicity, whereas Fra‐1, c‐Jun, Notch1, Net and CADM1 became down regulated. The onset of deregulated expression varied amongst the AP‐1 members and was not directly related to altered Notch1, Net or CADM1 expression. Nevertheless, a shift in AP‐1 complex composition from Fra‐1/c‐Jun to c‐Fos/c‐Jun heterodimers was only observed in tumorigenic cells.Conclusion: HPV‐mediated transformation is associated with altered AP‐1, Notch1, Net and CADM1 transcription. Whereas the onset of deregulated expression of various AP‐1 family members became already manifest during the immortal state, a shift in AP‐1 complex composition appeared a rather late event associated with tumorigenicity.
Presence of a High Amount of Stroma and Downregulation of SMAD4 Predict for Worse Survival for Stage I–II Colon Cancer Patients
Authors: Mesker Wilma E. , Liefers Gerrit-Jan , Junggeburt Jan M. C. , van Pelt Gabi W. , Alberici Paola , Kuppen Peter J. K. , Miranda Noel F. , van Leeuwen Karin A. M. , Morreau Hans , Szuhai Karoly , Tollenaar Rob A. E. M. , Tanke Hans J. 
Published: January 2021

Background: For stage I–II colon cancer a significant number (5–25%) of patients has recurrent disease within 5 years. There is need to identify these high-risk patients as they might benefit from additional treatment.Stroma-tissue surrounding the cancer cells plays an important role in the tumor behavior. The proportion of intra-tumor stroma was evaluated for the identification of high-risk patients. In addition, protein expression of markers involved in pathways related to stroma production and epithelial-to-mesenchymal transition (EMT) was analyzed: β-catenin, TGF-β-R2 and SMAD4.Methods: In a retrospective study of 135 patients with stage I–II colon cancer, the amount of stroma was estimated on routine haematoxylin–eosin stained histological sections. Sections were also immunohistochemically stained for β-catenin, TGF-β-R2 and SMAD4.Results: Of 135 analyzed patients 34 (25.2%) showed a high proportion of stroma (stroma-high) and 101 (74.8%) a low proportion (stroma-low). Significant differences in overall-survival and disease-free-survival were observed between the two groups, with stroma-high patients showing poor survival (OS p < 0.001, HZ 2.73, CI 1.73–4.30; DFS p < 0.001, HZ 2.43, CI 1.55–3.82). A high-risk group was identified with stroma-high and SMAD4 loss (OS p = 0.008, HZ 7.98, CI 4.12–15.44, DFS p = 0.005, HZ 6.57, CI 3.43–12.56); 12 of 14 (85.7%) patients died within 3 years. In a logistic-regression analysis a high proportion of stroma and SMAD4 loss were strongly related (HZ 5.42, CI 2.13–13.82, p < 0.001).Conclusion: Conventional haematoxylin–eosin stained tumor slides contain more prognostic information than previously fathomed. This can be unleashed by assessing the tumor–stroma ratio. The combination of analyzing the tumor–stroma ratio and staining for SMAD4 results in an independent parameter for confident prediction of clinical outcome.
Large Scale Genomic Instability as an Additive Prognostic Marker in Early Prostate Cancer
Authors: Pretorius Maria E. , Wæhre Håkon , Abeler Vera M. , Davidson Ben , Vlatkovic Ljiljana , Lothe Ragnhild A. , Giercksky Karl-Erik , Danielsen Håvard E. 
Published: January 2021

Background: The clinical outcome for the individual prostate cancer patient is often difficult to predict, due to lack of reliable independent prognostic biomarkers. We tested DNA ploidy as a prognostic factor for clinical outcome in 186 patients treated with radical prostatectomy.Methods: DNA ploidy was measured using an automatic image cytometry system and correlated with preoperative PSA, age at surgery, Mostofi grade, surgical margins and Gleason score.Results: The mean follow up time after operation was 73.3 months (range 2–176 months). Of the 186 prostatectomies, 96 were identified as diploid, 61 as tetraploid and 29 as aneuploid. Twenty-three per cent, 36% and 62% of the diploid, tetraploid and aneuploid cases respectively, suffered from relapse during the observation time. DNA ploidy, Gleason score, Mostofi grading, surgical margins and preoperative PSA were all significant predictors of relapse in a univariate analysis. On multivariate analysis, only Gleason score and DNA ploidy proved to be independently predictors of disease recurrence. Furthermore, among the 68 cases identified with Gleason score 7, DNA ploidy was the only significant predictor of disease recurrence.Conclusion: Our data suggest that DNA ploidy should be included as an important additive prognostic factor for prostate cancer, especially for patients identified with Gleason score 7 tumours.
Genomic Profiling by Array Comparative Genomic Hybridization Reveals Novel DNA Copy Number Changes in Breast Phyllodes Tumours
Authors: Kuijper Arno , Snijders Antoine M. , Berns Els M. J. J. , Kuenen-Boumeester Vibeke , van der Wall Elsken , Albertson Donna G. , van Diest Paul J. 
Published: January 2021

Breast phyllodes tumour (PT) is a rare fibroepithelial tumour. The genetic alterations contributing to its tumorigenesis are largely unknown. To identify genomic regions involved in pathogenesis and progression of PTs we obtained genome-wide copy number profiles by array comparative genomic hybridization (CGH).DNA was isolated from fresh-frozen tissue samples. 11 PTs and 3 fibroadenomas, a frequently occurring fibroepithelial breast tumour, were analyzed. Arrays composed of 2464 genomic clones were used, providing a resolution of ~1.4 Mb across the genome. Each clone contains at least one STS for linkage to the human genome sequence.No copy number changes were detected in fibroadenomas. On the other hand, 10 of 11 PT (91%) showed DNA copy number alterations. The mean number of chromosomal events in PT was 5.5 (range 0–16) per case. A mean of 2.0 gains (range 0–10) and 3.0 losses (range 0–9) was seen per case of PT. Three cases showed amplifications. DNA copy number change was not related to PT grade. We observed recurrent loss on chromosome 1q, 4p, 10, 13q, 15q, 16, 17p, 19 and X. Recurrent copy number gain was seen on 1q, 2p, 3q, 7p, 8q, 16q, 20.In this study we used array CGH for genomic profiling of fibroepithelial breast tumours. Whereas most PT showed chromosomal instability, fibroadenomas lacked copy number changes. Some copy number aberrations had not previously been associated with PT. Several well-known cancer related genes, such as TP53 and members of the Cadherin, reside within the recurrent regions of copy number alteration. Since copy number change was found in all benign PT, genomic instability may be an early event in PT genesis.
Protein Oxidation in Breast Microenvironment: Nipple Aspirate Fluid Collected from Breast Cancer Women Contains Increased Protein Carbonyl Concentration
Authors: Mannello Ferdinando , Tonti Gaetana A. , Medda Virginia 
Published: January 2021

Background: Protein carbonyl levels are the most frequently used biomarker of protein oxidation in several human diseases, including cancer. Breast cancer, a worldwide disease with increasing incidence, develops from ductal/lobular epithelium from which nipple aspirate fluid can be collected and analysed to assess tissue metabolic activity. Our aims were to perform an exploratory investigation on the protein carbonyl accumulation in breast secretions from healthy and cancer patients and its correlation with lipid peroxidation markers.Methods: Protein carbonyls were determined by ELISA in 288 Nipple Aspirate Fluids (NAF) from Control, Pre-malignant and Cancer patients.Results: Significantly higher protein carbonyl concentration was found in NAF from breast cancer (BC) patients compared to Control subjects. Cancer patients accumulated in NAF significantly higher levels of carbonyls in post-menopausal condition. A significant inverse relationship between carbonyls and 8-F2α-isoprostanes in NAF was found in Cancer patients. NAF levels of protein carbonyls are significantly higher in women with pre-malignant conditions than in healthy subjects.Conclusions: Our results support the hypothesis that oxidative stress in breast microenvironment plays a role in breast cancer; measurement of protein and lipid oxidative products in NAF may improve the identification of women at increased breast cancer risk.
Molecular Detection of Minimal Residual Cancer in Surgical Margins of Head and Neck Cancer Patients
Authors: Graveland A. Peggy , Maaker Michiel de , Braakhuis Boudewijn J. M. , de Bree Remco , Eerenstein Simone E. J. , Bloemena Elisabeth , Leemans C. René , Brakenhoff Ruud H. 
Published: January 2021

A great disappointment in head and neck cancer surgery is that 10–30% of head and neck squamous cell carcinoma (HNSCC) patients develop local recurrences despite histopathologically tumor-free surgical margins. These recurrences result from either minimal residual cancer (MRC) or preneoplastic lesions that remain behind after tumor resection. Distinguishing MRC from preneoplasic lesions is important to tailor postoperative radiotherapy more adequately. Here we investigated the suitability of quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) using human Ly-6D (hLy-6D) transcripts as molecular marker to detect MRC in surgical margins.Submucosal samples of deep surgical margins were collected from 18 non-cancer control patients and 67 HNSCC patients of whom eight had tumor-positive surgical margins. The samples were analyzed with hLy-6D qRT-PCR, and the data were analyzed in relation to the clinicohistological parameters.A significant difference was shown between the group of patients with histopathological tumor-positive surgical margins and the non-cancer control group (p < 0.001), and the group of patients with histopathological tumor-free surgical margins (p = 0.001).This study shows a novel approach for molecular analysis of deep surgical margins in head and neck cancer surgery. The preliminary data of this approach for detection of MRC in deep margins of HNSCC patients are promising.
Different Angiogenic Potential in Low and High Grade Sporadic Clear Cell Renal Cell Carcinoma Is Not Related to Alterations in the von Hippel–Lindau Gene
Authors: Baldewijns Marcella M. , van Vlodrop Iris J. H. , Smits Kim M. , Vermeulen Peter B. , Van den Eynden Gert G. , Schot Fiona , Roskams Tania , van Poppel Hein , van Engeland Manon , de Bruïne Adriaan P. 
Published: January 2021

Background: von Hippel–Lindau (VHL) inactivation is common in sporadic clear cell renal cell carcinomas (ccRCC). pVHL is part of the ubiquitin ligase complex that targets the alpha subunits of hypoxia-inducible transcription factor (HIF) for degradation under well-oxygenated conditions. In the absence of wild-type pVHL, as observed in VHL patients and most sporadic ccRCCs, constitutive upregulation of HIF results in transcriptional activation of angiogenesis-related genes, such as VEGF. Differences in angiogenic activity within the group of ccRCCs were reported and strong genotype-phenotype correlations were found in patients with VHL disease, raising a question about the importance of VHL inactivation status in angiogenic behaviour and tumour progression.Methods: To address this question, we investigated the influence of VHL mutation (direct sequencing)/hypermethylation (methylation-specific PCR) on angiogenesis/tumour parameters (immunohistochemistry) in 150 patients with sporadic ccRCC.Results: We found no significant association between VHL mutation or methylation and angiogenesis/tumour parameters.Conclusions: These data indicate that tumour progression and angiogenesis are not directly influenced by VHL alterations and that additional genetic/epigenetic events should be considered to explain the diverse angiogenic and proliferative behaviour during tumour progression.
Quantitative Fluorescence Determination of Long-Fragment DNA in Stool as a Marker for the Early Detection of Colorectal Cancer
Authors: Calistri Daniele , Rengucci Claudia , Molinari Chiara , Ricci Enrico , Cavargini Elena , Scarpi Emanuela , Milandri Gian Luigi , Fabbri Carla , Ravaioli Alberto , Russo Antonio , Amadori Dino , Silvestrini Rosella 
Published: January 2021

Background: A variety of molecular markers have been evaluated for the development of a non-invasive approach to the diagnosis of colorectal cancer. We aimed to validate the diagnostic accuracy, using the same threshold as in the previous pilot study, of fluorescent long DNA test as a relatively simple and inexpensive tool for colorectal cancer detection.Methods: A case-control study was conducted on 100 healthy subjects and 100 patients at first diagnosis of colorectal cancer. Human long-fragment DNA in stool was quantified by fluorescence primers and a standard curve and expressed in DNA nanograms.Results: We validated the 25-ng value, which emerged as the most accurate cut-off in the pilot study, obtaining 79% (95% CI, 71–87%) sensitivity and 89% (95% CI, 83–95%) specificity. Specificity was very high for all cut-off values (15–40 ng) analyzed, ranging from 78 to 96%. Sensitivity was only slightly lower, reaching 84% at the lowest cut-off and maintaining a good level at the higher values. Diagnostic potential was independent of gender, age and tumor site.Conclusion: Fecal DNA analysis is a non-invasive and fairly simple test showing high diagnostic potential. These characteristics, together with the small amount of stool required, make it potentially suitable to be used alongside or as an alternative to current non-invasive screening approaches. Our next step will be to validate these results in a large-scale cohort study of a screening population, which is needed prior to implementation into clinical practice.
BRCA2 Heterozygosity Delays Cytokinesis in Primary Human Fibroblasts
Authors: Jonsdottir Asta Björk , Vreeswijk Maaike P. G. , Wolterbeek Ron , Devilee Peter , Tanke Hans J. , Eyfjörd Jorunn E. , Szuhai Karoly 
Published: January 2021

Background: Inherited mutations in the tumour suppressor gene BRCA2 greatly increase the risk of developing breast, ovarian and other types of cancers. So far, most studies have focused on the role of BRCA-pathways in the maintenance of genomic stability.In this study we investigated the potential role of the BRCA2 protein in cytokinesis in unmodified primary human fibroblast carrying a heterozygous mutation in the BRCA2 gene.Methods: Cell divisions were monitored with time lapse live-cell imaging. BRCA2 mRNA expression levels in BRCA2+/− and BRCA2+/+ cells were quantified with quantitative real-time polymerase chain reaction (qRT-PCR). To investigate the localization of the BRCA2 protein during cytokinesis, immunofluorescence staining using antibody directed against BRCA2 was carried out. Immunofluorescence staining was performed directly after live-cell imaging and cells with delayed cytokinesis, of which the co-ordinates were saved, were automatically repositioned and visualized.Results: We demonstrate that unmodified primary human fibroblasts derived from heterozygous BRCA2 mutation carriers show significantly prolonged cytokinesis.A Subset of the BRCA2+/− cells had delayed cytokinesis (40 min or longer) making the mean cell division time 6 min longer compared with BRCA2+/+ cells, 33 min versus 27 min, respectively. Lower BRCA2 mRNA expression levels were observed in the BRCA2 heterozygous samples compared with the BRCA2 wild type samples.The BRCA2 protein localizes and accumulates to the midbody during cytokinesis, and no difference was detected in distribution and localization of the protein between BRCA2+/− and BRCA2+/+ samples or cells with delayed cytokinesis and normal division time.Conclusion: The delayed cytokinesis phenotype of the BRCA2 heterozygous cells and localization of the BRCA2 protein to the midbody confirms that BRCA2 plays a role in cytokinesis. Our observations indicate that in a subset of cells the presence of only one wild type BRCA2 allele is insufficient for efficient cytokinesis.
The TFIIH Subunit p89 (XPB) Localizes to the Centrosome during Mitosis
Authors: Weber Achim , Chung Hye-Jung , Springer Erik , Heitzmann Dirk , Warth Richard 
Published: January 2021

Background: The general transcription factor II H (TFIIH), comprised of a core complex and an associated CAK-complex, functions in transcription, DNA repair and cell cycle control. Mutations of the two largest subunits, p89 (XPB) and p80 (XPD), cause the hereditary cancer-prone syndrome xeroderma pigmentosum.Methods: The TFIIH subunit p89 was monitored during interphase and cell division by immunofluorescence staining, GFP-fusion constructs including deletions, live cell imaging and immuno-precipitations.Results: Here we demonstrate that during cell division, from prophase until telophase, the TFIIH core subunit p89, but not other subunits of TFIIH, associates with the centrosomes and the adjacent parts of the mitotic spindle. With overall constant levels throughout mitosis, p89 re-localizes to the newly formed nuclei by the end of mitosis. Furthermore, p89 interacts with the centrosomal protein γ-tubulin. Truncations of p89 result in an abnormal subcellular distribution during interphase and abolished centrosomal association during mitosis.Conclusions: Our observations suggest a so far unappreciated role for p89 in cell cycle regulation, and may be the structural basis for a long known, but hitherto unexplained interaction between p89 and tubulin.