bluuebunny/crossref_metadata_2025 huggingface dataset:
Origin and Residence Time of Groundwater in the Shallow Coastal Aquifer of Eastern Dahomey Basin, Southwestern Nigeria, Using δ18O and δD Isotopes
Authors: Aladejana Jamiu A. , Kalin Robert M. , Hassan Ibrahim , Sentenac Philippe , Tijani Moshood N.
Published: November 2020

This study employed stable isotopes of δ18O and δ2H in conjunction with other hydrological parameters to understand the origin, inferred residence time, and seasonal effect of groundwater in the shallow aquifers of the eastern Dahomey Basin. A total of 230 groundwater samples (97 in the wet season and 133 in the dry season) were collected from the borehole and shallow aquifer between May 2017 and April 2018. Groundwater analysis included major ions and δ18O and δ2H, isotopes data in precipitation from three selected Global Network of Isotope in Precipitation (GNIP) stations across West Africa, Douala in Cameroon, Cotonou in Republic of Benin, and Kano in Nigeria were used in comparative analysis. Results of the hydrochemical model revealed Ca-HCO3 and Na-Cl as dominant water types with other mixing water types such as Ca–SO4, Ca–Cl, Na–SO4, and K–Mg–HCO3, which characterised early stage of groundwater transformation as it infiltrates through vadose zone into the aquifer. δ18O and δ2H precipitation data from the three stations plotted along with the groundwater samples indicate recent meteoric water origin, with little effect of evaporation during the dry season. The plot of Total Dissolved Solids (TDS) against δ18O showed clustering of the water samples between the recharge and the evaporation zone with dry season samples trending towards increased TDS, which is an indication of the subtle effect of evaporation during this period. Tracing groundwater types along the flow paths within the basin is problematic and attributed to the heterogeneity of the aquifer with anthropogenic influences. Moreover, a comparison of the δ18O and δ2H isotopic compositions of groundwater and precipitation in the three selected stations, with their respective deuterium excess (D-excess) values established low evapotranspiration induced isotope enrichment, which could be due to higher precipitation and humidity in the region resulting in low isotope fractionation; hence, little effect of seasonal variations. The study, therefore, suggested groundwater recharge in the shallow aquifer in the eastern Dahomey Basin is of meteoric origin with a short residence time of water flows from soils through the vadose zone to the aquifers.
An Empirical Evaluation of Nuclei Segmentation from H&E Images in a Real Application Scenario
Authors: Putzu Lorenzo , Fumera Giorgio
Published: November 2020

Cell nuclei segmentation is a challenging task, especially in real applications, when the target images significantly differ between them. This task is also challenging for methods based on convolutional neural networks (CNNs), which have recently boosted the performance of cell nuclei segmentation systems. However, when training data are scarce or not representative of deployment scenarios, they may suffer from overfitting to a different extent, and may hardly generalise to images that differ from the ones used for training. In this work, we focus on real-world, challenging application scenarios when no annotated images from a given dataset are available, or when few images (even unlabelled) of the same domain are available to perform domain adaptation. To simulate this scenario, we performed extensive cross-dataset experiments on several CNN-based state-of-the-art cell nuclei segmentation methods. Our results show that some of the existing CNN-based approaches are capable of generalising to target images which resemble the ones used for training. In contrast, their effectiveness considerably degrades when target and source significantly differ in colours and scale.
A Complete VADER-Based Sentiment Analysis of Bitcoin (BTC) Tweets during the Era of COVID-19
Authors: Pano Toni , Kashef Rasha
Published: November 2020

During the COVID-19 pandemic, many research studies have been conducted to examine the impact of the outbreak on the financial sector, especially on cryptocurrencies. Social media, such as Twitter, plays a significant role as a meaningful indicator in forecasting the Bitcoin (BTC) prices. However, there is a research gap in determining the optimal preprocessing strategy in BTC tweets to develop an accurate machine learning prediction model for bitcoin prices. This paper develops different text preprocessing strategies for correlating the sentiment scores of Twitter text with Bitcoin prices during the COVID-19 pandemic. We explore the effect of different preprocessing functions, features, and time lengths of data on the correlation results. Out of 13 strategies, we discover that splitting sentences, removing Twitter-specific tags, or their combination generally improve the correlation of sentiment scores and volume polarity scores with Bitcoin prices. The prices only correlate well with sentiment scores over shorter timespans. Selecting the optimum preprocessing strategy would prompt machine learning prediction models to achieve better accuracy as compared to the actual prices.
Comparison of Three Glycoproteomic Methods for the Analysis of the Secretome of CHO Cells Treated with 1,3,4-O-Bu3ManNAc
Authors: Mertz Joseph L. , Sun Shisheng , Yin Bojiao , Hu Yingwei , Bhattacharya Rahul , Bettenbaugh Michael J. , Yarema Kevin J. , Zhang Hui
Published: November 2020

Comprehensive analysis of the glycoproteome is critical due to the importance of glycosylation to many aspects of protein function. The tremendous complexity of this post-translational modification, however, makes it difficult to adequately characterize the glycoproteome using any single method. To overcome this pitfall, in this report we compared three glycoproteomic analysis methods; first the recently developed N-linked glycans and glycosite-containing peptides (NGAG) chemoenzymatic method, second, solid-phase extraction of N-linked glycoproteins (SPEG), and third, hydrophilic interaction liquid chromatography (HILIC) by characterizing N-linked glycosites in the secretome of Chinese hamster ovary (CHO) cells. Interestingly, the glycosites identified by SPEG and HILIC overlapped considerably whereas NGAG identified many glycosites not observed in the other two methods. Further, utilizing enhanced intact glycopeptide identification afforded by the NGAG workflow, we found that the sugar analog 1,3,4-O-Bu3ManNAc, a “high flux” metabolic precursor for sialic acid biosynthesis, increased sialylation of secreted proteins including recombinant human erythropoietin (rhEPO).
Prognostic Implication of SOX2 Expression Associated with p16 in Oropharyngeal Cancer: A Study of Consecutive Tissue Microarrays and TCGA
Authors: Seok Jungirl , Ryu Chang Hwan , Ryu Junsun , Kim Ji-Hyun , Lee Sang-Jin , Park Weon Seo , Jung Yuh-Seog
Published: November 2020

For oropharyngeal squamous cell carcinoma (OPSCC), there are not enough additional robust biomarkers for subgrouping after the distinct classification using p16. As SOX2 is an emerging biomarker for cancer treatment, its clinical implication in OPSCC was evaluated using a consecutive tissue microarray (TMA) cohort consisting of 111 patients who underwent surgery as an initial treatment from May 2002 to December 2016 and 79 patients in The Cancer Genome Atlas (TCGA) dataset. In both datasets, p16+/SOX2High (HPV+/SOX2High in TCGA) showed the best prognosis among the four groups classified by SOX2 and p16 for 5-year overall survival (OS) and recurrence (all p < 0.05), but SOX2 did not make a significant difference in the prognosis of the p16− group. In the TMA cohort, SOX2High was significantly correlated with response to radiotherapy and lower pathologic T classification in the p16+ group (p = 0.001). In TCGA, correlations between SOX2 and tumor stage classification or radiotherapy were not observed; however, HPV+/SOX2High had a significantly low tumor mutation burden among the four groups (all p < 0.05). In summary, SOX2 was proven to be a potential marker to predict overall survival and recurrence in p16+ OPSCC. However, the role of SOX2 has not yet been confirmed in p16− OPSCC patients.
Global Picture of Genetic Relatedness and the Evolution of Humankind
Authors: Khvorykh Gennady V. , Mulyar Oleh A. , Fedorova Larisa , Khrunin Andrey V. , Limborska Svetlana A. , Fedorov Alexei
Published: November 2020

We performed an exhaustive pairwise comparison of whole-genome sequences of 3120 individuals, representing 232 populations from all continents and seven prehistoric people including archaic and modern humans. In order to reveal an intricate picture of worldwide human genetic relatedness, 65 million very rare single nucleotide polymorphic (SNP) alleles have been bioinformatically processed. The number and size of shared identical-by-descent (IBD) genomic fragments for every pair of 3127 individuals have been revealed. Over 17 million shared IBD fragments have been described. Our approach allowed detection of very short IBD fragments (<20 kb) that trace common ancestors who lived up to 200,000 years ago. We detected nine distinct geographical regions within which individuals had strong genetic relatedness, but with negligible relatedness between the populations of these regions. The regions, comprising nine unique genetic components for mankind, are the following: East and West Africa, Northern Europe, Arctica, East Asia, Oceania, South Asia, Middle East, and South America. The level of admixture in every studied population has been apportioned among these nine genetic components. Genetically, long-term neighboring populations are strikingly similar to each other in spite of any political, religious, and cultural differences. The topmost admixture has been observed at the center of Eurasia. These admixed populations (including Uyghurs, Azerbaijanis, Uzbeks, and Iranians) have roughly equal genetic contributions from the Middle East, Europe, China, and India, with additional significant traces from Africa and Arctic. The entire picture of relatedness of all the studied populations unfolds and presents itself in the form of shared number/size of IBDs.
ATM Inhibitor Suppresses Gemcitabine-Resistant BTC Growth in a Polymerase θ Deficiency-Dependent Manner
Authors: Pan Yi-Ru , Wu Chiao-En , Yeh Chun-Nan
Published: November 2020

Patients with advanced biliary tract cancer (BTC) inevitably experience progression after first-line, gemcitabine-based chemotherapy, due to chemo-resistance. The genetic alterations of DNA damage repair (DDR) genes are usually determined in BTC tumors. In this study, we found that the POLQ mRNA levels are downregulated and the ataxia-telangiectasia mutated (ATM) inhibitor AZD0156 was more sensitive in gemcitabine-resistant BTC sublines than in the parental cell lines. The knockdown of DNA polymerase θ does not affect cell proliferation, but its combination with the ATM inhibitor facilitated cell death in gemcitabine-resistant and gemcitabine-intensive BTC cells. Moreover, in the DNA damage caused by photon, hydrogen peroxide, or chemotherapy drugs, synthetic lethal interactions were found in combination with ATM inhibition by AZD0156 and DNA polymerase θ depletion, resulting in increased DNA damage accumulation and micronucleus formation, as well as reduced cell survival and colony formation. Collectively, our results reveal that ATM acts as a potential target in gemcitabine-resistant and DNA polymerase θ-deficient BTC.
Magnoflorine—Isolation and the Anticancer Potential against NCI-H1299 Lung, MDA-MB-468 Breast, T98G Glioma, and TE671 Rhabdomyosarcoma Cancer Cells
Authors: Okon Estera , Kukula-Koch Wirginia , Halasa Marta , Jarzab Agata , Baran Marzena , Dmoszynska-Graniczka Magdalena , Angelis Apostolis , Kalpoutzakis Eleftherios , Guz Malgorzata , Stepulak Andrzej , Wawruszak Anna
Published: November 2020

Magnoflorine (MGN) is a quaternary aporphine alkaloid that exhibits numerous therapeutic properties, including neuropsychopharmacological, anti-anxiety, immunomodulatory, anti-inflammatory, antioxidant, or antifungal activities. The aim of the present study was an investigation of the influence of MGN on viability, proliferation, induction of apoptosis, and cell cycle arrest in NCI-H1299 lung, MDA-MB-468 breast, T98G glioma, and TE671 rhabdomyosarcoma cancer cells. MGN was isolated from the roots of Berberis cretica L. by counter-current partition chromatography (CPC). Cell viability and proliferation assessments were performed by means of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and 5-bromo-2ʹ-deoxyuridine (BrDU) assays, respectively. The induction of apoptosis and cell cycle progression was measured using fluorescence-activated cell sorting analysis. MGN in high doses inhibits proliferation, induces apoptosis, and inhibits cell cycle in S/G2 phases in a dose-dependent manner. MGN seems to be a promising anti-cancer compound in therapy of some types of lung, breast, glioma, and rhabdomyosarcoma cancers, for which current standard therapies are limited or have severe strong side effects.
Curcumin against Prostate Cancer: Current Evidence
Authors: Termini Deborah , Den Hartogh Danja J. , Jaglanian Alina , Tsiani Evangelia
Published: November 2020

Cancer is a condition characterized by remarkably enhanced rates of cell proliferation paired with evasion of cell death. These deregulated cellular processes take place following genetic mutations leading to the activation of oncogenes, the loss of tumor suppressor genes, and the disruption of key signaling pathways that control and promote homeostasis. Plant extracts and plant-derived compounds have historically been utilized as medicinal remedies in different cultures due to their anti-inflammatory, antioxidant, and antimicrobial properties. Many chemotherapeutic agents used in the treatment of cancer are derived from plants, and the scientific interest in discovering plant-derived chemicals with anticancer potential continues today. Curcumin, a turmeric-derived polyphenol, has been reported to possess antiproliferative and proapoptotic properties. In the present review, we summarize all the in vitro and in vivo studies examining the effects of curcumin in prostate cancer.
Vasculogenesis from Human Dental Pulp Stem Cells Grown in Matrigel with Fully Defined Serum-Free Culture Media
Authors: Luzuriaga Jon , Irurzun Jon , Irastorza Igor , Unda Fernando , Ibarretxe Gaskon , Pineda Jose R.
Published: November 2020

The generation of vasculature is one of the most important challenges in tissue engineering and regeneration. Human dental pulp stem cells (hDPSCs) are some of the most promising stem cell types to induce vasculogenesis and angiogenesis as they not only secrete vascular endothelial growth factor (VEGF) but can also differentiate in vitro into both endotheliocytes and pericytes in serum-free culture media. Moreover, hDPSCs can generate complete blood vessels containing both endothelial and mural layers in vivo, upon transplantation into the adult brain. However, many of the serum free media employed for the growth of hDPSCs contain supplements of an undisclosed composition. This generates uncertainty as to which of its precise components are necessary and which are dispensable for the vascular differentiation of hDPSCs, and also hinders the transfer of basic research findings to clinical cell therapy. In this work, we designed and tested new endothelial differentiation media with a fully defined composition using standard basal culture media supplemented with a mixture of B27, heparin and growth factors, including VEGF-A165 at different concentrations. We also optimized an in vitro Matrigel assay to characterize both the ability of hDPSCs to differentiate to vascular cells and their capacity to generate vascular tubules in 3D cultures. The description of a fully defined serum-free culture medium for the induction of vasculogenesis using human adult stem cells highlights its potential as a relevant innovation for tissue engineering applications. In conclusion, we achieved efficient vasculogenesis starting from hDPSCs using serum-free culture media with a fully defined composition, which is applicable for human cell therapy purposes.
Bone Marrow-Sparing IMRT in Anal Cancer Patients Undergoing Concurrent Chemo-Radiation: Results of the First Phase of a Prospective Phase II Trial
Authors: Arcadipane Francesca , Silvetti Patrick , Olivero Francesco , Gastino Alessio , De Luca Viola , Mistrangelo Massimiliano , Cassoni Paola , Racca Patrizia , Gallio Elena , Lesca Adriana , Fiandra Christian , Ricardi Umberto , Franco Pierfrancesco
Published: November 2020

Purpose: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with 18FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. Methods: a one-armed two-stage Simon’s design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0–G2 (vs. G3–G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the β = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0–G2 acute HT to further proceed with the trial. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. Results: from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0–G2 events, way above the threshold set by the trial design. Conclusion: 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial.
Recurrence Risk after Radical Colorectal Cancer Surgery—Less Than before, But How High Is It?
Authors: Osterman Erik , Hammarström Klara , Imam Israa , Osterlund Emerik , Sjöblom Tobias , Glimelius Bengt
Published: November 2020

Adjuvant chemotherapy aims at eradicating tumour cells sometimes present after radical surgery for a colorectal cancer (CRC) and thereby diminish the recurrence rate and prolong time to recurrence (TTR). Remaining tumour cells will lead to recurrent disease that is usually fatal. Adjuvant therapy is administered based upon the estimated recurrence risk, which in turn defines the need for this treatment. This systematic overview aims at describing whether the need has decreased since trials showing that adjuvant chemotherapy provides benefits in colon cancer were performed decades ago. Thanks to other improvements than the administration of adjuvant chemotherapy, such as better staging, improved surgery, the use of radiotherapy and more careful pathology, recurrence risks have decreased. Methodological difficulties including intertrial comparisons decades apart and the present selective use of adjuvant therapy prevent an accurate estimate of the magnitude of the decreased need. Furthermore, most trials do not report recurrence rates or TTR, only disease-free and overall survival (DFS/OS). Fewer colon cancer patients, particularly in stage II but also in stage III, today display a sufficient need for adjuvant treatment considering the burden of treatment, especially when oxaliplatin is added. In rectal cancer, neo-adjuvant treatment will be increasingly used, diminishing the need for adjuvant treatment.
Unsupervised Hierarchical Clustering of Pancreatic Adenocarcinoma Dataset from TCGA Defines a Mucin Expression Profile that Impacts Overall Survival
Authors: Jonckheere Nicolas , Auwercx Julie , Hadj Bachir Elsa , Coppin Lucie , Boukrout Nihad , Vincent Audrey , Neve Bernadette , Gautier Mathieu , Treviño Victor , Van Seuningen Isabelle
Published: November 2020

Mucins are commonly associated with pancreatic ductal adenocarcinoma (PDAC) that is a deadly disease because of the lack of early diagnosis and efficient therapies. There are 22 mucin genes encoding large O-glycoproteins divided into two major subgroups: membrane-bound and secreted mucins. We investigated mucin expression and their impact on patient survival in the PDAC dataset from The Cancer Genome Atlas (PAAD-TCGA). We observed a statistically significant increased messenger RNA (mRNA) relative level of most of the membrane-bound mucins (MUC1/3A/4/12/13/16/17/20), secreted mucins (MUC5AC/5B), and atypical mucins (MUC14/18) compared to normal pancreas. We show that MUC1/4/5B/14/17/20/21 mRNA levels are associated with poorer survival in the high-expression group compared to the low-expression group. Using unsupervised clustering analysis of mucin gene expression patterns, we identified two major clusters of patients. Cluster #1 harbors a higher expression of MUC15 and atypical MUC14/MUC18, whereas cluster #2 is characterized by a global overexpression of membrane-bound mucins (MUC1/4/16/17/20/21). Cluster #2 is associated with shorter overall survival. The patient stratification appears to be independent of usual clinical features (tumor stage, differentiation grade, lymph node invasion) suggesting that the pattern of membrane-bound mucin expression could be a new prognostic marker for PDAC patients.
Early Changes of the Standardized Uptake Values (SUVmax) Predict the Efficacy of Everolimus-Exemestane in Patients with Hormone Receptor-Positive Metastatic Breast Cancer
Authors: Sirico Marianna , Bernocchi Ottavia , Sobhani Navid , Giudici Fabiola , Corona Silvia P. , Vernieri Claudio , Nichetti Federico , Cappelletti Maria Rosa , Milani Manuela , Strina Carla , Cervoni Valeria , Barbieri Giuseppina , Ziglioli Nicoletta , Dester Martina , Bianchi Giulia Valeria , De Braud Filippo , Generali Daniele
Published: November 2020

Background: The mTORC1 inhibitor everolimus has been approved in combination with the aromatase inhibitor exemestane for the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (HR+ mBC) progressing on prior therapy with a non-steroidal aromatase inhibitor. To date, no predictive biomarkers of tumor sensitivity/resistance for everolimus-based treatments have been identified. We hypothesized that precocious changes in the Standardized Uptake Volume (∆SUV%), as assessed by 18F-Fluorodeoxyglucosepositron-emission tomography (18F-FDG PET/CT), may be a marker of everolimus efficacy. Methods: This was a retrospective study including 31 HR+ HER2- patients treated with everolimus and exemestane in two Italian centers between 2013 and 2018. The objective of the study was to investigate ∆SUV% as a predictive marker of everolimus antitumor efficacy. 18F-FDG PET/CT scans were performed at baseline and after three months of treatment. Patients were defined as long responders (LRs) if disease progression occurred at least 10 months after treatment initiation and long survivors (LSs) if death occurred later than 36 months after starting therapy. ROC analysis was used to determine the optimal cut-off values of ∆SUV% to distinguish LRs from non-LRs and LSs from non-LSs. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method. Results: The SUVmax values decreased significantly from baseline to 3 months after therapy (p = 0.003). Dynamic changes of SUVmax (Delta SUV) had a higher accuracy in discriminating long-responders from non-long-responders (AUC = 0.67, Delta SUV cut-off = 28.8%) respects to its ability to identify long survivors from no-long survivors (AUC = 0.60, Delta SUV cut-off = 53.8%). Patients were divided into groups according to the Delta SUV cut-offs and survival outcomes were evaluated: patients with a decrease of ∆SUV% ≥ 28.8% had significantly better PFS (10 months-PFS: 63.2%, 95% CI: 37.9–80.4% and 16.7%, 95% CI: 2.7–41.3% respectively, p = 0.005). As regard as OS, patients with ∆SUV% ≥ 53.8% had longer OS when compared to patients with ∆SUV% < 53.8% (36 month-OS: 82.5% vs. 45.9% vs. p = 0.048). Conclusion: We found two precocious ∆SUV% thresholds capable of identifying HR+ HER2-mBC patients, which would achieve long-term benefit or long-term survival during everolimus-exemestane therapy. These results warrant further validation in prospective studies and should be integrated with molecular biomarkers related to tumor metabolism and mTORC1 signaling.
Animal Models: A Useful Tool to Unveil Metabolic Changes in Hepatocellular Carcinoma
Authors: Serra Marina , Columbano Amedeo , Perra Andrea , Kowalik Marta Anna
Published: November 2020

Hepatocellular carcinoma (HCC) is one the most frequent and lethal human cancers. At present, no effective treatment for advanced HCC exist; therefore, the overall prognosis for HCC patients remains dismal. In recent years, a better knowledge of the signaling pathways involved in the regulation of HCC development and progression, has led to the identification of novel potential targets for therapeutic strategies. However, the obtained benefits from current therapeutic options are disappointing. Altered cancer metabolism has become a topic of renewed interest in the last decades, and it has been included among the core hallmarks of cancer. In the light of growing evidence for metabolic reprogramming in cancer, a wide number of experimental animal models have been exploited to study metabolic changes characterizing HCC development and progression and to further expand our knowledge of this tumor. In the present review, we discuss several rodent models of hepatocarcinogenesis, that contributed to elucidate the metabolic profile of HCC and the implications of these changes in modulating the aggressiveness of neoplastic cells. We also highlight the apparently contrasting results stemming from different animal models. Finally, we analyze whether these observations could be exploited to improve current therapeutic strategies for HCC.
Epithelial Transfer of the Tyrosine Kinase Inhibitors Erlotinib, Gefitinib, Afatinib, Crizotinib, Sorafenib, Sunitinib, and Dasatinib: Implications for Clinical Resistance
Authors: Honeywell Richard J. , Kathmann Ietje , Giovannetti Elisa , Tibaldi Carmelo , Smit Egbert F. , Rovithi Maria N. , Verheul Henk M.W. , Peters Godefridus J.
Published: November 2020

Background: tyrosine kinase inhibitors (TKIs) inhibit phosphorylation of signaling proteins. TKIs often show large variations in the clinic due to poor pharmacology, possibly leading to resistance. We compared gut absorption of inhibitors of epidermal growth factor receptor (erlotinib, gefitinib, and afatinib), ALK-cMET (crizotinib), PDGFR/BCR-Abl (dasatinib), and multikinase inhibitors (sunitinib and sorafenib). In clinical samples, we measured the disposition of each compound within various blood compartments. Methods: we used an optimized CaCo2 gut epithelial model to characterize 20 µM TKI absorption. The apical/basolateral transfer is considered to represent the gut/blood transfer. Drugs were measured using LC-MS/MS. Results: sorafenib and sunitinib showed the highest apical/basolateral transfer (Papp 14.1 and 7.7 × 10−6 cm/s, respectively), followed by dasatinib (3.4), afatinib (1.5), gefitinib (0.38), erlotinib (0.13), and crizotinib (n.d.). However, the net absorptions for dasatinib, afatinib, crizotinib, and erlotinib were highly negative (efflux ratios >5) or neutral/negative, sorafenib (0.86), gefitinib (1.0), and sunitinib (1.6). A high negative absorption may result in resistance because of a poor exposure of tissues to the drug. Accumulation of the TKIs at the end of the transfer period (A->B) was not detectable for erlotinib, very low for afatinib 0.45 pmol/μg protein), followed by gefitinib (0.79), dasatinib (1.1), sorafenib (1.65), and crizotinib (2.11), being highest for sunitinib (11.9). A similar pattern was found for accumulation of these drugs in other colon cell lines, WiDr and HT29. In clinical samples, drugs accumulated consistently in red blood cells; blood to plasma ratios were all >3 (sorafenib) or over 30 for erlotinib. Conclusions: TKIs are consistently poorly absorbed, but accumulation in red blood cells seems to compensate for this.
Mechanisms of Taxane Resistance
Authors: Maloney Sara M. , Hoover Camden A. , Morejon-Lasso Lorena V. , Prosperi Jenifer R.
Published: November 2020

The taxane family of chemotherapy drugs has been used to treat a variety of mostly epithelial-derived tumors and remain the first-line treatment for some cancers. Despite the improved survival time and reduction of tumor size observed in some patients, many have no response to the drugs or develop resistance over time. Taxane resistance is multi-faceted and involves multiple pathways in proliferation, apoptosis, metabolism, and the transport of foreign substances. In this review, we dive deeper into hypothesized resistance mechanisms from research during the last decade, with a focus on the cancer types that use taxanes as first-line treatment but frequently develop resistance to them. Furthermore, we will discuss current clinical inhibitors and those yet to be approved that target key pathways or proteins and aim to reverse resistance in combination with taxanes or individually. Lastly, we will highlight taxane response biomarkers, specific genes with monitored expression and correlated with response to taxanes, mentioning those currently being used and those that should be adopted. The future directions of taxanes involve more personalized approaches to treatment by tailoring drug–inhibitor combinations or alternatives depending on levels of resistance biomarkers. We hope that this review will identify gaps in knowledge surrounding taxane resistance that future research or clinical trials can overcome.
Metal-Organic Frameworks as a Platform for CO2 Capture and Chemical Processes: Adsorption, Membrane Separation, Catalytic-Conversion, and Electrochemical Reduction of CO2
Authors: Elhenawy Salma Ehab Mohamed , Khraisheh Majeda , AlMomani Fares , Walker Gavin
Published: November 2020

The continuous rise in the atmospheric concentration of carbon dioxide gas (CO2) is of significant global concern. Several methodologies and technologies are proposed and applied by the industries to mitigate the emissions of CO2 into the atmosphere. This review article offers a large number of studies that aim to capture, convert, or reduce CO2 by using a superb porous class of materials (metal-organic frameworks, MOFs), aiming to tackle this worldwide issue. MOFs possess several remarkable features ranging from high surface area and porosity to functionality and morphology. As a result of these unique features, MOFs were selected as the main class of porous material in this review article. MOFs act as an ideal candidate for the CO2 capture process. The main approaches for capturing CO2 are pre-combustion capture, post-combustion capture, and oxy-fuel combustion capture. The applications of MOFs in the carbon capture processes were extensively overviewed. In addition, the applications of MOFs in the adsorption, membrane separation, catalytic conversion, and electrochemical reduction processes of CO2 were also studied in order to provide new practical and efficient techniques for CO2 mitigation.
Enhanced Photocatalytic Activity of BiVO4/Bi2S3/SnS2 Heterojunction under Visible Light
Authors: Meng Sopheak , Ogawa Takaya , Okumura Hideyuki , Ishihara Keiichi N.
Published: November 2020

Heterojunction photocatalysts have attracted a significant amount of attention due to their advantages over a single photocatalyst and, particularly, their superior spatial charge separation. Herein, the BiVO4/Bi2S3/SnS2 heterojunction was synthesized via solvothermal synthesis with different ratios of BiVO4 to SnS2. The photodegradation rate of the 0.03 BiVO4/SnS2 sample for rhodamine B removal is 2.3 times or 2.9 times greater than that of a single SnS2 or BiVO4, respectively. The chemical bond between photocatalysts is confirmed by X-ray photoelectron spectroscopy (XPS), and the synchronized shift observed in binding energies strongly indicates the electron screening effect at the heterojunction. A Z-scheme model is proposed to explain charge transfer pathway in the system, in which the formation of Bi2S3 plays a crucial role in the enhanced photocatalytic performance of the heterojunction.
A Tumor-Targeted Replicating Oncolytic Adenovirus Ad-TD-nsIL12 as a Promising Therapeutic Agent for Human Esophageal Squamous Cell Carcinoma
Authors: Zhang Zifang , Zhang Chunyang , Miao Jinxin , Wang Zhizhong , Wang Zhimin , Cheng Zhenguo , Wang Pengju , Dunmall Louisa S. Chard , Lemoine Nicholas R. , Wang Yaohe
Published: November 2020

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in China and existing therapies have been unable to significantly improve prognosis. Oncolytic adenoviruses (OAds) are novel promising anti-tumor drugs and have been evaluated in several cancers including ESCC. However, the antitumour efficacy of the first generation OAds (H101) as single agent is limited. Therefore, more effective OAds are needed. Our previous studies demonstrated that the novel oncolytic adenovirus Ad-TD-nsIL12 (human adenovirus type 5 with E1ACR2, E1B19K, E3gp19K-triple deletions)harboring human non-secretory IL-12 had significant anti-tumor effect, with no toxicity, in a Syrian hamster pancreatic cancer model. In this study, we evaluated the anti-tumor effect of Ad-TD-nsIL12 in human ESCC. The cytotoxicity of Ad-TD-nsIL12, H101 and cisplatin were investigated in two newly established patient-derived tumor cells (PDCs) and a panel of ESCC cell lines in vitro. A novel adenovirus-permissive, immune-deficient Syrian hamster model of PDCs subcutaneous xenograft was established for in vivo analysis of efficacy. The results showed that Ad-TD-nsIL12 was more cytotixic to and replicated more effectively in human ESCC cell lines than H101. Compared with cisplatin and H101, Ad-TD-nsIL12 could significantly inhibit tumor growth and tumor angiogenesis as well as enhance survival rate of animals with no side effects. These findings suggest that Ad-TD-nsIL12 has superior anti-tumor potency against human ESCC with a good safety profile.
Changes in Striatal Medium Spiny Neuron Morphology Resulting from Dopamine Depletion Are Reversible
Authors: Witzig Victoria Sofie , Komnig Daniel , Falkenburger Björn H.
Published: November 2020

The classical motor symptoms of Parkinson’s disease (PD) are caused by degeneration of dopaminergic neurons in the substantia nigra, which is followed by secondary dendritic pruning and spine loss at striatal medium spiny neurons (MSN). We hypothesize that these morphological changes at MSN underlie at least in part long-term motor complications in PD patients. In order to define the potential benefits and limitations of dopamine substitution, we tested in a mouse model whether dendritic pruning and spine loss can be reversible when dopaminergic axon terminals regenerate. In order to induce degeneration of nigrostriatal dopaminergic neurons we used the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57BL/6J mice; 30 mg/kg MPTP was applied i.p. on five consecutive days. In order to assess the consequences of dopamine depletion, mice were analyzed 21 days after the last injection. In order to test reversibility of MSN changes we exploited the property of this model that striatal axon terminals regenerate by sprouting within 90 days and analyzed a second cohort 90 days after MPTP. Degeneration of dopaminergic neurons was confirmed by counting TH-positive neurons in the substantia nigra and by analyzing striatal catecholamines. Striatal catecholamine recovered 90 days after MPTP. MSN morphology was visualized by Golgi staining and quantified as total dendritic length, number of dendritic branch points, and density of dendritic spines. All morphological parameters of striatal MSN were reduced 21 days after MPTP. Statistical analysis indicated that dendritic pruning and the reduction of spine density represent two distinct responses to dopamine depletion. Ninety days after MPTP, all morphological changes recovered. Our findings demonstrate that morphological changes in striatal MSN resulting from dopamine depletion are reversible. They suggest that under optimal conditions, symptomatic dopaminergic therapy might be able to prevent maladaptive plasticity and long-term motor complications in PD patients.
PXR and 4β-Hydroxycholesterol Axis and the Components of Metabolic Syndrome
Authors: Hukkanen Janne , Hakkola Jukka
Published: November 2020

Pregnane X receptor (PXR) activation has been found to regulate glucose and lipid metabolism and affect obesity in response to high-fat diets. PXR also modulates vascular tone. In fact, PXR appears to regulate multiple components of metabolic syndrome. In most cases, the effect of PXR action is harmful to metabolic health, and PXR can be hypothesized to play an important role in metabolic disruption elicited by exposure to endocrine-disrupting chemicals. The majority of the data on the effects of PXR activation on metabolic health come from animal and cell culture experiments. However, randomized, placebo-controlled, human trials indicate that the treatment with PXR ligands impairs glucose tolerance and increases 24-h blood pressure and heart rate. In addition, plasma 4β-hydroxycholesterol (4βHC), formed under the control of PXR in the liver, is associated with lower blood pressure in healthy volunteers. Furthermore, 4βHC regulates cholesterol transporters in peripheral tissues and may activate the beneficial reverse HDL cholesterol transport. In this review, we discuss the current knowledge on the role of PXR and the PXR–4βHC axis in the regulation of components of metabolic syndrome.
The Remaining Mysteries about Brown Adipose Tissues
Authors: Nishio Miwako , Saeki Kumiko
Published: November 2020

Brown adipose tissue (BAT), which is a thermogenic fat tissue originally discovered in small hibernating mammals, is believed to exert anti-obesity effects in humans. Although evidence has been accumulating to show the importance of BAT in metabolism regulation, there are a number of unanswered questions. In this review, we show the remaining mysteries about BATs. The distribution of BAT can be visualized by nuclear medicine examinations; however, the precise localization of human BAT is not yet completely understood. For example, studies of 18F-fluorodeoxyglucose PET/CT scans have shown that interscapular BAT (iBAT), the largest BAT in mice, exists only in the neonatal period or in early infancy in humans. However, an old anatomical study illustrated the presence of iBAT in adult humans, suggesting that there is a discrepancy between anatomical findings and imaging data. It is also known that BAT secretes various metabolism-improving factors, which are collectively called as BATokines. With small exceptions, however, their main producers are not BAT per se, raising the possibility that there are still more BATokines to be discovered. Although BAT is conceived as a favorable tissue from the standpoint of obesity prevention, it is also involved in the development of unhealthy conditions such as cancer cachexia. In addition, a correlation between browning of mammary gland and progression of breast cancers was shown in a xenotransplantation model. Therefore, the optimal condition should be carefully determined when BAT is considered as a measure the prevention of obesity and improvement of metabolism. Solving BAT mysteries will open a new door for health promotion via advanced understanding of metabolism regulation system.
Development of a Pressure Stable Inline Droplet Generator with Live Droplet Size Measurement
Authors: Preiss Felix Johannes , Dagenbach Teresa , Fischer Markus , Karbstein Heike Petra
Published: November 2020

For the research on droplet deformation and breakup in scaled high-pressure homogenizing units, a pressure stable inline droplet generator was developed. It consists of an optically accessible flow channel with a combination of stainless steel and glass capillaries and a 3D printed orifice. The droplet size is determined online by live image analysis. The influence of the orifice diameter, the mass flow of the continuous phase and the mass flow of the disperse phase on the droplet diameter were investigated. Furthermore, the droplet detachment mechanisms were identified. Droplet diameters with a small diameter fluctuation between 175 µm and 500 µm could be realized, which allows a precise adjustment of the capillary (Ca) and Weber (We) Number in the subsequent scaled high pressure homogenizer disruption unit. The determined influence of geometry and process parameters on the resulting droplet size and droplet detachment mechanism agreed well with the literature on microfluidics. Furthermore, droplet trajectories in an exemplary scaled high-pressure homogenizer disruption unit are presented which show that the droplets can be reinjected on a trajectory close to the center axis or close to the wall, which should result in different stresses on the droplets.
Combustion Characteristics of Waste Cooking Oil–Butanol/Diesel/Gasoline Blends for Cleaner Emission
Authors: Hossain Abul K.
Published: November 2020

Sustainable green biofuels could replace a significant amount of fossil fuels responsible for environmental pollution. In this study, waste cooking oil (WCO) was tested in a diesel engine either neat or blended separately with diesel, butanol and gasoline, with an additive concentration between 10% and 30% by volume. The heating values of the WCO were slightly decreased when blended with butanol, whereas they increased when blended with either gasoline or diesel. The flash point temperatures decreased. All fuel samples were non-corrosive and non-acidic. At full load, the brake specific fuel consumption of the WCO–additive fuels was approximately 1–3% higher than diesel. The thermal efficiency of the neat WCO, neat diesel and WCO–10% diesel were very close to each other, whereas, in the case of 20% butanol blend, the efficiency decreased by about 2% when compared to the neat diesel value. The WCO–butanol fuel gave the lowest NOx emission and a 0.6% lower CO2 emission than diesel. Combustion characteristics results showed stable engine operation for all blends. The combustion duration was maximal with WCO–butanol blends. The study concluded that the WCO with 10–20% butanol or fossil diesel exhibited similar performance and emission characteristics observed for neat fossil diesel.
A Multi-Position Drum-Type Assembly for Simultaneous Film Deposition at Different Temperatures in a Single Sputter Cycle–Application to ITO Thin Films
Authors: Akhmedov Akhmed K. , Asvarov Abil S. , Muslimov Arsen E. , Kanevsky Vladimir M.
Published: November 2020

The design of a multi-position drum-type assembly (MPDTA) for heating and positioning substrates with the possibility of individually setting and controlling the temperature of each substrate, which is applicable for laboratory-type sputtering setups, is described. The above design provides the possibility of the simultaneous deposition of thin films under identical conditions on several substrates at different temperatures, making it possible to explore the temperature dependences of the films’ morphology, structure, and functional characteristics in one single vacuum deposition cycle. As a case study, the possibility of investigating such dependencies for the magnetron deposition of transparent conducting indium–tin oxide (ITO) thin films was demonstrated using the MPDTA. The investigation results revealed that the functional performances of deposited ITO thin films (resistivity and average transmittance in the visible range) improved with increasing the substrate temperature, reaching values of 1.5 × 10−4 Ω·cm and over 80%, respectively, at 300 °C.
Application of the Robust Fixed Point Iteration Method in Control of the Level of Twin Tanks Liquid
Authors: Khan Hamza , Issa Hazem , Tar József K.
Published: November 2020

Precise control of the flow rate of fluids stored in multiple tank systems is an important task in process industries. On this reason coupled tanks are considered popular paradigms in studies because they form strongly nonlinear systems that challenges the controller designers to develop various approaches. In this paper the application of a novel, Fixed Point Iteration (FPI)-based technique is reported to control the fluid level in a “lower tank” that is fed by the egress of an “upper” one. The control signal is the ingress rate at the upper tank. Numerical simulation results obtained by the use of simple sequential Julia code with Euler integration are presented to illustrate the efficiency of this approach.
Bond Behavior of Cleaned Corroded Lap Spliced Beams Repaired with Carbon Fiber Reinforced Polymer Sheets and Partial Depth Repairs
Authors: Alabduljabbar Hisham , Alyousef Rayed , Mohammadhosseini Hossein , Topper Tim
Published: November 2020

The present research investigated the bond behavior of a cleaned corroded reinforcing bar repaired with a partial depth concrete repair and a partial depth concrete repair followed by the application of fiber-reinforced polymer (FRP) sheets. Twelve lap splice beams were cast and tested under static loading. The test variables considered were a partial depth repair with prepackaged self-consolidating concrete (SCC) for six lap splice beams and additional confinement with carbon fiber reinforced polymer (CFRP) sheets for another six beams. The test results for the repaired lap splice beams were compared with those for a monolithic lap splice beam. This research found that the average bond strength increased as the bar mass loss increased for all bonded lengths. The lap splice beams repaired with partial depth were able to repair concrete with similar properties to those of the monolithic concrete. However, they had higher concrete strength than the monolithic beams which showed a higher average bond strength than the monolithic lap splice beams. The beams confined with FRP sheets showed a rise in the bond strength and the equivalent slip by 34–49%, and 56–260% as compared to the unconfined beams, respectively.
Structure and Properties of Organic Dyes in Solid State
Authors: Graiff Claudia
Published: November 2020

Color is one of the most fascinating aspects of Nature; it is part of the beauty of the environment that surrounds us, playing a key role in the acceptability of most products used in our society [...]
Microstructural Influence on Stretch Flangeability of Ferrite–Martensite Dual-Phase Steels
Authors: Kim Jae Hyung , Lee Taekyung , Lee Chong Soo
Published: November 2020

This work investigated the microstructural effect on stretch flangeability of ferrite–martensite dual-phase (DP) steels. Three types of DP steels with various martensitic structures were prepared for the research: fibrous martensite in water-quenched (WQ) sample, chained martensite in air-quenched (AQ) sample, and coarse martensite in step-quenched (SQ) sample. The WQ specimen exhibited the highest mechanical strength and hole expansion ratio compared to the AQ and SQ samples despite their similar fraction of martensite. Such a result was explained in view of uniform distribution of fine martensite and high density of geometrically necessary dislocations in the WQ specimen. Meanwhile, most cracks initiated at either rolling or transverse direction during the stretch flangeability test regardless of the martensitic morphology. It was attributed to the highest average normal anisotropy in the direction of 45° to rolling direction.