bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Integrin-Linked Kinase: A Multi-functional Regulator Modulating Extracellular Pressure-Stimulated Cancer Cell Adhesion through Focal Adhesion Kinase and AKT
Authors: Wang Shouye , Basson Marc D.
Published: January 2021

Cell adhesion is important in cancer metastasis. Malignant cells in cancer patients may be exposed to physical forces such as extracellular pressure and shear, that stimulate their adhesion to matrix proteins, endothelium and surgical wounds. Pressure induces phosphorylation of AKT and focal adhesion kinase (FAK), which are required for pressure-stimulated cancer cell adhesion, but what mediates this effect is unknown. ILK may influence cell adhesion and FAK and AKT phosphorylation in other settings. We therefore hypothesized that ILK might also regulate pressure-stimulated cancer cell adhesion through AKT and FAK phosphorylation. Silencing ILK by siRNA reduced basal cancer cell adhesion and prevented the stimulation of adhesion by pressure. ILK mediated pressure-stimulated adhesion through specifically regulating phosphorylation of AKT at Ser473 and FAK at Tyr397 and 576 as well as ILK association with FAK and AKT. The siRNA-mediated loss of function of ILK in regulating increase in adhesion by pressure was not rescued by overexpression of α-parvin, an important ILK binding partner, although pressure promoted ILK–α-parvin association and translocated both ILK and α-parvin from cytosol to membrane/cytoskeleton. ILK may be a key mediator of mechanotransduced signals in cancer cells and an important therapeutic target to inhibit metastatic cancer cell adhesion.
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.
A Peptide Antagonist of the ErbB1 Receptor Inhibits Receptor Activation, Tumor Cell Growth and Migration In Vitro and Xenograft Tumor Growth In Vivo
Authors: Xu Ruodan , Povlsen Gro Klitgaard , Soroka Vladislav , Bock Elisabeth , Berezin Vladimir
Published: January 2021

The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in tumorigenesis and cancer disease progression, and therefore has become an attractive target for structure-based drug design. ErbB receptors are activated by ligand-induced homo- and heterodimerization. Structural studies have revealed that ErbB receptor dimers are stabilized by receptor–receptor interactions, primarily mediated by a region in the second extracellular domain, termed the “dimerization arm”. The present study is the first biological characterization of a peptide, termed Inherbin3, which constitutes part of the dimerization arm of ErbB3. Inherbin3 binds to the extracellular domains of all four ErbB receptors, with the lowest peptide binding affinity for ErbB4. Inherbin3 functions as an antagonist of epidermal growth factor (EGF)-ErbB1 signaling. We show that Inherbin3 inhibits EGF-induced ErbB1 phosphorylation, cell growth, and migration in two human tumor cell lines, A549 and HN5, expressing moderate and high ErbB1 levels, respectively. Furthermore, we show that Inherbin3 inhibits tumor growth in vivo and induces apoptosis in a tumor xenograft model employing the human non-small cell lung cancer cell line A549. The Inherbin3 peptide may be a useful tool for investigating the mechanisms of ErbB receptor homo- and heterodimerization. Moreover, the here described biological effects of Inherbin3 suggest that peptide-based targeting of ErbB receptor dimerization is a promising anti-cancer therapeutic strategy.
HER2 Expression in Gastric Cancer: Rare, Heterogeneous and of No Prognostic Value – Conclusions from 924 Cases of Two Independent Series
Authors: Grabsch Heike , Sivakumar Shivan , Gray Sally , Gabbert Helmut E. , Müller Wolfram
Published: January 2021

Background: Patients with gastric cancer (GC) have a poor survival and biologicals such as Trastuzumab have not been used routinely in these patients. Existing data on HER2 expression and its clinical relevance in GC are still limited and controversial.

Methods: HER2 expression was investigated by immunohistochemistry in 418 GC from Germany and 506 GC from England. Results were compared to clinicopathological parameters and patient survival.

Results: Less than 10% of all GC showed HER2 expression in more than 5% of tumour cells and 91% of these were intestinal type GC. In both series, no relationship was found between HER2 expression, patient survival or TNM stage. Marked intratumoural heterogeneity was noted.

Conclusions: This is the largest study to date demonstrating in two independent series that HER2 expression is not related to gastric cancer patient prognosis and that only a very small subgroup of intestinal type GC may potentially respond to HER2 targeting therapy. Due to prominent intratumoural heterogeneity of HER2 expression in GC, HER2 testing in endoscopic biopsies before treatment will be prone to false negative results.
Oral Cancer Genesis and Progression: DNA Near-Diploid Aneuploidization and Endoreduplication by High Resolution Flow Cytometry
Authors: Donadini Alessandra , Maffei Massimo , Cavallero Antonio , Pentenero Monica , Malacarne Davide , Nallo Emanuela Di , Truini Mauro , Navone Roberto , Mereu Paola , Scala Marco , Santelli Alida , Gandolfo Sergio , Giaretti Walter
Published: January 2021

Oral potentially malignant lesions (OPMLs) with dysplasia and aneuploidy are thought to have a high risk of progression into oral squamous cell carcinomas (OSCCs). Non-dysplastic “oral distant fields” (ODFs), characterized by clinically normal appearing mucosa sited at a distance from co-existing OPMLs, and non-dysplastic OPMLs may also represent an early pre-cancerous state. ODFs, OPMLs without and with dysplasia and OSCCs were investigated by high resolution DNA content flow cytometry (FCM). ODFs and OPMLs without dysplasia were DNA aneuploid respectively in 7/82 (8.5%) and 25/109 (23%) cases. “True normal oral mucosa” and human lymphocytes from healthy donors were DNA diploid in all cases and were used as sex specific DNA diploid controls. Dysplastic OPMLs and OSCCs were DNA aneuploid in 12/26 (46%) and 12/13 (92%) cases. The DNA aneuploid sublines were characterized by the DNA Index (DI ≠ 1). Aneuploid sublines in ODFs and in non-dysplastic and dysplastic OPMLs were near-diploid (DI < 1.4) respectively in all, 2/3 and 1/3 of the cases. DNA aneuploid OSCCs, instead, were characterized prevalently by multiple aneuploid sublines (67%), which were commonly (57%) high-aneuploid (DI ≥ 1.4). DNA near-diploid aneuploid sublines in ODFs and OPMLs appear as early events of the oral carcinogenesis in agreement with the concept of field effect. Near-diploid aneuploidization is likely to reflect mechanisms of loss of symmetry in the chromosome mitotic division. High DNA aneuploid and multiple sublines in OPMLs with dysplasia and OSCCs suggest, instead, mechanisms of “endoreduplication” of diploid and near-diploid aneuploid cells and chromosomal loss. High resolution DNA FCM seems to enable the separation of subsequent progression steps of the oral carcinogenesis.
PIDDosome Expression and the Role of Caspase-2 Activation for Chemotherapy-Induced Apoptosis in RCCs
Authors: Heikaus Sebastian , Pejin Igor , Gabbert Helmut Erich , Ramp Uwe , Mahotka Csaba
Published: January 2021

Background: The importance of caspase-2 activation for mediating apoptosis in cancer is not clear and seems to differ between different tumour types. Furthermore, only few data have been obtained concerning the expression of caspase-2, which can be alternatively spliced into caspase-2L and caspase-2S, and the other PIDDosome members PIDD and RAIDD in human tumours in vivo. We, therefore, investigated their expression in renal cell carcinomas (RCCs) of the clear cell type in vivo and analysed the role of caspase-2 in chemotherapy-induced apoptosis in RCCs in vitro.

Methods: The analyses were performed by semiquantitative real-time PCR, Western Blot and Caspase-2 Assay.

Results: Our in vivo results showed an overall decrease in proapoptotic caspase-2L expression during tumour progression due to an increase in the relative share of caspase-2S mRNA in total caspase-2 mRNA expression. Furthermore, an increase in the expression of PIDD and RAIDD could be observed. In contrast, antiapoptotic BCL-2 expression increased only during early tumour stages, whereas expression decreased in pT3 RCCs. In vitro, caspase-2 activation in RCC cell lines coincidenced with sensitivity of tumour cells towards Topotecan-induced apoptosis. However, inhibition of caspase-2 could not prevent Topotecan-induced apoptosis. Interestingly, Topotecan-resistance could be overcome by the apoptosis-sensitizing drug HA14-1.

Conclusions: Our study confirms the concept of a shift towards a more antiapoptotic transcriptional context during tumour progression in RCCs. Furthermore, it shows that caspase-2 participates in chemotherapy-induced apoptosis in RCCs although it is not mandatory for it. Additionally, inhibition of antiapoptotic BCL-2 family members might provide a possible way to overcome chemotherapy resistance of RCCs.
Emergency Food Product Packaging by Pectin-Based Antimicrobial Coatings Functionalized by Pomegranate Peel Extracts
Authors: Ghorbani Ehsan , Dabbagh Moghaddam Arasb , Sharifan Anousheh , Kiani Hossein
Published: January 2021

Emergency food products (EFPs) or energy bars are used in critical situations, such as natural disasters, to promote crisis management. EFPs require sophisticated packaging strategies. Edible coatings incorporated with natural antimicrobial agents could be considered as active packaging materials for increasing EFP safety. In this study, pectin-based coatings incorporated with pomegranate peel extracts were used to protect energy bars. Initially, total phenolic contents and antimicrobial and antioxidant properties of aqueous and ethanolic pomegranate peel extracts (PPEs) were determined. Also, PPEs were analyzed by HPLC. In the next step, the extracts were incorporated into the matrix of edible coatings as active substances. The sensory properties and microbial contamination of coated energy bars were investigated during 30 days of storage. Sixteen phenolic substances were detected in the extracts with gallic acid, ellagic acid, caffeic acid, coumaric acid, and quercetin as major ingredients. The ethanolic extract exhibited higher concentrations for all phenolic compounds. The results indicated that the ethanolic extract showed inhibitory effects on S. aureus and E. coli at concentrations of 30 and 50 mg/ml, and the aqueous extract's inhibitory effects were observed at concentrations of 50 and 80 mg/ml, respectively. The antioxidant and antibacterial effects could be attributed to high phenolic content and a combination of different substances. Microbial and sensory tests performed on coated energy bars showed that the active coatings were able to control and reduce the population of microorganisms during storage without adversely affecting sensory properties.
New Construction of Family of MLCS Algorithms
Authors: Shi Haihe , Wang Jun
Published: January 2021

The multiple longest common subsequence (MLCS) problem involves finding all the longest common subsequences of multiple character sequences. This problem is encountered in a variety of areas, including data mining, text processing, and bioinformatics, and is particularly important for biological sequence analysis. By taking the MLCS problem and algorithms for its solution as research domain, this study analyzes the domain of multiple longest common subsequence algorithms, extracts features that algorithms in the domain do and do not have in common, and creates a domain feature model for the MLCS problem by using generic programming, domain engineering, abstraction, and related technologies. A component library for the domain is designed based on the feature model for the MLCS problem, and the partition and recur (PAR) platform is used to ensure that highly reliable MLCS algorithms can be quickly assembled through component assembly. This study provides a valuable reference for obtaining rapid solutions to problems of biological sequence analysis and improves the reliability and assembly flexibility of assembling algorithms.
Nondestructive Detection of Authenticity of Thai Jasmine Rice Using Multispectral Imaging
Authors: Liu Wei , Xu Xue , Liu Changhong , Zheng Lei
Published: January 2021

The detection of authenticity is essential to the development and management of Thai jasmine rice industry. In this study, the multispectral imaging system (405–970 nm) was used for the detection of adulteration in Thai jasmine rice combined with chemometric methods including principal component analysis (PCA), partial least squares (PLS), least squares-support vector machines (LS-SVM), and backpropagation neural network (BPNN). Three varieties of rice that were similar to Thai jasmine rice in appearance were selected to perform the classification and quantitative prediction experiments by multispectral images. For the classification experiment, four varieties of rice samples could be easily classified with accuracy achieved to 92% by the BPNN model. For the quantitative prediction of adulteration proportion experiments, the results showed that, among the different chemometric methods, LS-SVM achieved the best prediction performance comparing the results of coefficient of determination, root-mean-square error (RMSEP), bias, and residual predictive deviation (RPD). It can be concluded that multispectral imaging technology with chemometric methods can be applied in the rapid and nondestructive detection of authenticity of Thai jasmine rice.
Flexible Investment Strategies for Cloud‐Native Architecture of Public Health Information Systems
Authors: Jiang Ming , Nakamoto Ichiro , Zhuang Weiqing , Zhang Weiguo , Guo Yin , Ma Liting
Published: January 2021

The randomness of public health events requires that the cloud‐native architecture, as the mainstream architecture of the new generation of the public health information system, has the appropriate flexibility to meet the needs of environmental change. The flexible acquisition of cloud‐native architecture requires organizations to invest additional resources. How to plan and formulate resource input is a topic of common concern for public health management and information systems. According to the commercial characteristics of the public health system based on cloud‐native architecture, this paper systematically analyzes the external major impact factors and auxiliary factors that affect the flexible cost investment strategy of cloud providers and combines flexible investment strategies to build a cloud‐native cost investment model. Finally, case data in practice is applied into the model, and cost planning is discussed according to different situations. The findings indicate that (1) the more cloud providers adopt the changed flexible strategy, the more conducive it is to reduce costs; (2) the larger the application load, the more cloud providers need to use flexible strategies to lower costs; (3) the less the impact of changing the flexible strategy on costs, the more conducive cloud providers use the flexible strategy to decrease costs; (4) the more uneven the distribution of diversity, the higher proportion of investment increases than the proportion of investment, and the more cloud providers consider the investment using flexible strategy. The results of the discussion provide a reference for public health organizations to use flexible strategies and change flexible strategies in a timely manner and expand the research scope of information system cost investment.
Individual and Obstetric Risk Factors of Preeclampsia among Singleton Pregnancy in Hospitals of Southern Ethiopia
Authors: Tessema Kassahun Fikadu , Gebremeskel Feleke , Getahun Firdawek , Chufamo Nega , Misker Direslgne
Published: January 2021

Background. Preeclampsia is the second most common problem that causes maternal morbidity and complication in low-income countries. In contrast to death due to other direct causes, preeclampsia-related death is appeared to be connected with multiple factors; yet, factors have paucity and are limited. Considering the clinical significance, this study aimed to identify that individual and obstetric factors of preeclampsia can be an input for disease identification involving clinicians in southern Ethiopia. Methods. A case-control study was conducted among mothers with a singleton pregnancy who attended perinatal care in all six public hospitals in the provinces around the Omo stream. A sample size of 487 women with a singleton pregnancy (163 cases and 326 controls) was involved in the study. All cases were enrolled, while controls were selected consecutively using a random sampling technique. Data were gathered using a structured questionnaire and data extraction sheet. Descriptive data were presented using percentages and numbers. Multivariable logistic regression analysis was carried out to identify factors at apvalue of less than 0.05. Results. There was a statistically significant association between the family history of hypertension (AOR = 2.42, 95% CI: 1.16–5.05), no pregnancy interval (AOR = 1.62; 95% CI: 1.03–2.55), and normal body mass index (AOR = 0.42, 95% CI: 0.21–0.87) and the occurrence of preeclampsia. Conclusion. Primary relatives with a history of chronic hypertension and no pregnancy interval were identified as risk factors of preeclampsia, while having a normal body mass index was found to be a protective factor of preeclampsia occurrence. To improve early detection and timely management of preeclampsia, the clinician should give attention to women who have no previous childbirth and whose close relatives had a history of chronic hypertension, as well as working on the protective factor is recommended.
Risk Factors for Clinically Relevant Postoperative Pancreatic Fistula (CR-POPF) after Distal Pancreatectomy: A Single Center Retrospective Study
Authors: Wang Gao Qing , Yadav Dipesh Kumar , Jiang Wei , Hua Yong Fei , Lu Cai De
Published: January 2021

Objectives. Clinically relevant postoperative pancreatic fistula (CR-POPF) is the considerable contributor to major complications after pancreatectomy. The purpose of this study was to evaluate the potential risk factor contributing to CR-POPF following distal pancreatectomy (DP) and discuss the risk factors of pancreatic fistula in order to interpret the clinical importance. Methods. In this retrospective study, 263 patients who underwent DP at Ningbo Medical Center Li Huili Hospital between January 2011 and January 2020 were reviewed in accordance with relevant guidelines and regulations. Patients’ demographics and clinical parameters were evaluated using univariate and multivariate analyses to identify the risk factors contributing to CR-POPF.

P
<
0.05

was considered statistically significant. Results. In all of the 263 patients with DP, pancreatic fistula was the most common surgical complication (19.0%). The univariate analysis of 18 factors showed that the patients with a malignant tumor, soft pancreas, and patient without ligation of the main pancreatic duct were more likely to develop pancreatic fistula. However, on multivariate analysis, the soft texture of the pancreas (OR = 2.381, 95% CI = 1.271–4.460,

P
=
0.001

) and the ligation of the main pancreatic duct (OR = 0.388, 95% CI = 0.207–0.726,

P
=
0.002

) were only an independent influencing factor for CR-POPF. Conclusions. As a conclusion, pancreatic fistula was the most common surgical complication after DP. The soft texture of the pancreas and the absence of ligation of the main pancreatic duct can increase the risk of CR-POPF.
Quantitative Analysis of a Weak Correlation between Complicated Data on the Basis of Principal Component Analysis
Authors: Pang Tao , Zhang Haitao , Wen Liliang , Tang Jun , Zhou Bing , Yang Qianxu , Li Yong , Wang Jiajun , Chen Aiming , Zeng Zhongda
Published: January 2021

The mining of weak correlation information between two data matrices with high complexity is a very challenging task. A new method named principal component analysis-based multiconfidence ellipse analysis (PCA/MCEA) was proposed in this study, which first applied a confidence ellipse to describe the difference and correlation of such information among different categories of objects/samples on the basis of PCA operation of a single targeted data. This helps to find the number of objects contained in the overlapping and nonoverlapping areas of ellipses obtained from PCA runs. Then, a quantitative evaluation index of correlation between data matrices was defined by comparing the PCA results of more than one data matrix. The similarity and difference between data matrices was further quantified through comprehensively analyzing the outcomes. Complicated data of tobacco agriculture were used as an example to illustrate the strategy of the proposed method, which includes rich features of climate, altitude, and chemical compositions of tobacco leaves. The number of objects of these data reached 171,516 with 14, 4, and 5 descriptors of climate, altitude, and chemicals, respectively. On the basis of the new method, the complex but weak relationship between these independent and dependent variables were interestingly studied. Three widely used but conventional methods were applied for comparison in this work. The results showed the power of the new method to discover the weak correlation between complicated data.
Theory of Frequency Captured of Eccentric Rotor by Vibration Environment with Same Direction
Authors: Ming Su , Rong Li , Zhiping Xie , Jiming Zheng
Published: January 2021

Aiming at the frequency synchronization phenomena of oscillating or rotating bodies, this paper proposes a novel solution to address the self‐synchronization problem of vibration systems. An integral mean method with small parameters and periodic coefficient (IMM‐SPPC) is proposed, which converts the relative motion of the electrically driven eccentric rotor and the vibration environment into a second‐order periodic coefficient differential equation. Through the calculation of the equilibrium point of the second‐order periodic coefficient differential equation and the study of its stability, the synchronization criterion and the stability criterion of the eccentric rotor and the vibration environment are deduced. The simulation results show the validity of the deduced synchronization criterion and stability criterion. The proposed IMM‐SPPC provides a new way for studying vibration synchronization.
Attenuation of SRC Kinase Activity Augments PARP Inhibitor–mediated Synthetic Lethality in BRCA2-altered Prostate Tumors
Authors: Chakraborty Goutam , Patail Nabeela Khan , Hirani Rahim , Nandakumar Subhiksha , Mazzu Ying Z. , Yoshikawa Yuki , Atiq Mohammad , Jehane Lina E. , Stopsack Konrad H. , Lee Gwo-Shu Mary , Abida Wassim , Morris Michael J. , Mucci Lorelei A. , Danila Daniel , Kantoff Philip W.
Published: January 2021

Purpose:

Alterations in DNA damage repair (DDR) pathway genes occur in 20%–25% of men with metastatic castration-resistant prostate cancer (mCRPC). Although PARP inhibitors (PARPis) have been shown to benefit men with mCRPC harboring DDR defects due to mutations in BRCA1/2 and ATM, additional treatments are necessary because the effects are not durable.

Experimental Design:

We performed transcriptomic analysis of publicly available mCRPC cases, comparing BRCA2 null with BRCA2 wild-type. We generated BRCA2-null prostate cancer cells using CRISPR/Cas9 and treated these cells with PARPis and SRC inhibitors. We also assessed the antiproliferative effects of combination treatment in 3D prostate cancer organoids.

Results:

We observed significant enrichment of the SRC signaling pathway in BRCA2-altered mCRPC. BRCA2-null prostate cancer cell lines had increased SRC phosphorylation and higher sensitivity to SRC inhibitors (e.g., dasatinib, bosutinib, and saracatinib) relative to wild-type cells. Combination treatment with PARPis and SRC inhibitors was antiproliferative and had a synergistic effect in BRCA2-null prostate cancer cells, mCRPC organoids, and Trp53/Rb1-null prostate cancer cells. Inhibition of SRC signaling by dasatinib augmented DNA damage in BRCA2-null prostate cancer cells. Moreover, SRC knockdown increased PARPi sensitivity in BRCA2-null prostate cancer cells.

Conclusions:

This work suggests that SRC activation may be a potential mechanism of PARPi resistance and that treatment with SRC inhibitors may overcome this resistance. Our preclinical study demonstrates that combining PARPis and SRC inhibitors may be a promising therapeutic strategy for patients with BRCA2-null mCRPC.
Downregulation of miR-96-5p Inhibits mTOR/NF-κb Signaling Pathway via DEPTOR in Allergic Rhinitis
Authors: Zhan Jia-Bin , Zheng Jing , Zeng Lian-Ya , Fu Zhi , Huang Qiu-Ju , Wei Xin , Zeng Min
Published: January 2021

Background: This study aims to investigate the regulatory effect of microRNA-96-5p (miR-96-5p) in the pathophysiological process of allergic rhinitis (AR). Methods: Nasal mucosal tissue samples were collected from AR patients and healthy controls. An in vitro AR model was established by stimulating human nasal epithelial cells (HNECs) with interleukin (IL)-13. The expressions of target genes and proteins were measured by qPCR, Western blot, or ELISA. Dual-luciferase reporter assay and pull-down assay were performed to confirm the interaction between miR-96-5p and DEP domain-containing mammalian target of rapamycin-interacting protein (DEPTOR). Results: The level of miR-96-5p was increased while the expression of DEPTOR was decreased in AR patients. The expressions of proinflammatory cytokines were markedly increased and the mammalian target of rapamycin (mTOR)/NF-κB pathway was activated in HNECs following IL-13 stimulation. miR-96-5p downregulation alleviated the stimulated function by IL-13. DEPTOR was the target of miR-96-5p. Knockdown of DEPTOR reversed the function of miR-96-5p inhibitor on IL-13-stimulated HNECs. Conclusions: The current study showed that miR-96-5p and DEPTOR were aberrantly expressed in AR nasal mucosa. miR-96-5p knockdown inhibited the production of inflammatory cytokines and the activation of mTOR/NF-κB pathway via targeting DEPTOR. These findings suggested that miR-96-5p might be used as a diagnostic marker and therapeutic target for the treatment of AR.
Crowned Dens Syndrome Occurring after Endoscopic Submucosal Dissection for Early Gastric Cancer
Authors: Okamoto Takeshi , Ikeya Takashi , Fukuda Katsuyuki
Published: January 2021

Crowned dens syndrome (CDS) is a rare form of pseudogout which causes acute neck pain due to calcium pyrophosphate dehydrate deposition surrounding the odontoid process, commonly causing neck pain with rigidity. While invasive procedures such as surgery are known to present a risk of acute pseudogout, reports of occurrence after endoscopic procedures are scarce. We report the case of a 75-year-old man who presented with sudden neck pain after endoscopic submucosal dissection (ESD) for gastric cancer. He could nod but could not rotate his head. Computed tomography showed calcifications surrounding the odontoid process consistent with CDS. Prolonged dietary restrictions and proton pump inhibitor use following the ESD procedure may have caused hypomagnesemia, a precipitating factor for CDS. We prescribed colchicine 1 mg/day and symptoms resolved completely in 3 days. This is the first report of CDS after ESD. CDS should be included in the differential diagnosis of neck pain after endoscopic procedures.
A Case of Cyclodialysis after Microhook Trabeculotomy Treated with Vitreous Surgery
Authors: Kudo Takashi , Suzuki Yukihiko , Yamauchi Kodai , Tando Toshio , Adachi Kobu , Nakazawa Mitsuru
Published: January 2021

We report a case of cyclodialysis with decreased visual acuity after microhook trabeculotomy (mTLO) successfully treated by vitreous surgery. A 41-year-old man had been medically treated for primary open-angle glaucoma in both eyes. He was scheduled to undergo mTLO due to progression of visual field impairment and unstable intraocular pressure in his right eye. His preoperative best-corrected visual acuity (BCVA) was 0.4 OD, and the intraocular pressure was unstable, ranging from 12 to 27 mm Hg. On the day after the operation, a shallow anterior chamber developed, and a low intraocular pressure occurred. His visual acuity continued to decrease, and cyclodialysis was confirmed by ultrasonic biomicroscopy. No improvement was obtained with medical treatment, and his BCVA dropped to 0.08 OD, while his intraocular pressure remained at 2–3 mm Hg. Three months later, a second surgery was performed by combining cataract surgery with intraocular lens implantation, vitrectomy, cryopexy for the pars plana of the ciliary body, and 20% SF6 gas tamponade. Two weeks after the reoperation, the intraocular pressure had been normalized to 12 mm Hg, and the BCVA had returned to 0.3. We successfully treated cyclodialysis as a complication after mTLO by vitreous surgery that led to the recovery of the visual acuity and intraocular pressure.
Sunitinib-Induced Acute Liver Failure
Authors: Aqsa Anum , Droubi Sami , Amarnath Shivantha , Al-Moussawi Hassan , Abergel Jeffrey
Published: January 2021

Drug-induced liver injury is an uncommon but life-threatening entity. Sunitinib is a tyrosine kinase inhibitor used for advanced and imatinib-refractory gastrointestinal stromal tumors. It causes transient elevation in liver enzymes. The incidence of fatal acute liver failure is rare. Five cases of sunitinib-induced acute liver injury have been reported in the literature thus far. We present a case of fatal acute liver failure and cardiomyopathy within 2 weeks of sunitinib therapy initiation for advanced pancreatic neuroendocrine carcinoma. We believe our case is unique due to the rarity of its presentation. It highlights hepatotoxicity as a potentially fatal side effect of sunitinib therapy.