bluuebunny/crossref_metadata_2025 huggingface dataset:
A Deformation of a Mercury Droplet under Acceleration in an Annular Groove
Authors: Xu HanYang , Zhao Yulong , Zhang Kai , Wang Zixi , Jiang Kyle
Published: June 2020

Microelectromechanical system (MEMS) liquid sensors may be used under large acceleration conditions. It is important to understand the deformation of the liquid droplets under acceleration for the design and applications of MEMS liquid sensors, as this will affect the performance of the sensors. This paper presents an investigation into the deformation of a mercury droplet in a liquid MEMS sensor under accelerations and reports the relationship between the deformation and the accelerations. The Laminar level set method was used in the numerical process. The geometric model consisted of a mercury droplet of 2 mm in diameter and an annular groove of 2.5 mm in width and 2.5 mm in height. The direction of the acceleration causing the droplet to deform is perpendicular to the direction of gravity. Fabrication and acceleration experiments were conducted. The deformation of the liquid was recorded using a high-speed camera. Both the simulation and experimental results show that the characteristic height of the droplets decreases as the acceleration increases. At an acceleration of 10 m/s2, the height of the droplet is reduced from 2 to 1.658 mm, and at 600 m/s2 the height is further reduced to 0.246 mm. The study finds that the droplet can deform into a flat shape but does not break even at 600 m/s2. Besides, the properties of the material in the domain surrounding the droplet and the contact angle also affect the deformation of the droplet. This work demonstrates the deformation of the liquid metal droplets under acceleration and provides the basis for the design of MEMS droplet acceleration sensors.
Study of the Dielectric Properties of Artificial Sweat Mixtures at Microwave Frequencies
Authors: Eldamak Angie R. , Thorson Sarah , Fear Elise C.
Published: June 2020

Analysis of sweat is of interest for a variety of diagnosis and monitoring applications in healthcare. In this work, detailed measurements of the dielectric properties of solutions representing the major components of sweat are presented. The measurements include aqueous solutions of sodium chloride (NaCl), potassium chloride (KCl), urea, and lactic acid, as well as their mixtures. Moreover, mixtures of NaCl, KCl, urea, and lactic acid, mimicking artificial sweat at different hydration states, are characterized, and the data are fitted to a Cole–Cole model. The complex dielectric permittivity for all prepared solutions and mixtures is studied in the range of 1–20 GHz, at temperature of 23 °C, with ionic concentrations in the range of 0.01–1.7 mol/L.
Adaptive Skills in FXS: A Review of the Literature and Evaluation of the PEDI-Computer Adaptive Test (PEDI-CAT) to Measure Adaptive Skills
Authors: Cordeiro Lisa , Villagomez Adrienne , Swain Deanna , Deklotz Sophia , Tartaglia Nicole
Published: June 2020

As adaptive skills (AS) are dynamic and may indicate the success of an intervention, they are a common domain measured in clinical trials. Typical interview tools for measuring AS are time-consuming, and questionnaire measures often lead to inconsistent information. The present study was designed to evaluate the feasibility, validity and test-retest performance of the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) in Fragile X syndrome (FXS). The PEDI-CAT is administered via tablet and uses the item response theory to efficiently determine the items administered. The PEDI-CAT was administered to 42 individuals with FXS (27 males; 15 females) aged 1.6–50.9 years (M = 14.9; SD = 11.2), followed by the Vineland-3 (VABS-3) interview for comparison. Administration was efficient (M = 21.7 min; SD = 9.5; range 8–45 min; mode = 19). Males and females did not significantly differ on the PEDI-CAT domains, except for daily activities (t(40) = −2.22, p = 0.037). Floor effects were significant for both measures, although the PEDI-CAT showed more floor effects in the mobility (35.7%) and social-cognitive (50%) domains. PEDI-CAT daily activities, mobility, social-cognitive and responsibility domains were all significantly correlated with most of the VABS-3 domains (all rho > 0.5; p < 0.01). Test-rest of the PEDI-CAT was comparable to the VABS-3. Results suggest that the PEDI-CAT is efficient, and minimal training is needed to administer it; however, it lacks specificity and shares a high rate of floor effects with the VABS-3.
Brain Network Underlying Executive Functions in Gambling and Alcohol Use Disorders: An Activation Likelihood Estimation Meta-Analysis of fMRI Studies
Authors: Quaglieri Alessandro , Mari Emanuela , Boccia Maddalena , Piccardi Laura , Guariglia Cecilia , Giannini Anna Maria
Published: June 2020

Background: Neuroimaging and neuropsychological studies have suggested that common features characterize both Gambling Disorder (GD) and Alcohol Use Disorder (AUD), but these conditions have rarely been compared. Methods: We provide evidence for the similarities and differences between GD and AUD in neural correlates of executive functions by performing an activation likelihood estimation meta-analysis of 34 functional magnetic resonance imaging studies involving executive function processes in individuals diagnosed with GD and AUD and healthy controls (HC). Results: GD showed greater bilateral clusters of activation compared with HC, mainly located in the head and body of the caudate, right middle frontal gyrus, right putamen, and hypothalamus. Differently, AUD showed enhanced activation compared with HC in the right lentiform nucleus, right middle frontal gyrus, and the precuneus; it also showed clusters of deactivation in the bilateral middle frontal gyrus, left middle cingulate cortex, and inferior portion of the left putamen. Conclusions: Going beyond the limitations of a single study approach, these findings provide evidence, for the first time, that both disorders are associated with specific neural alterations in the neural network for executive functions.
Cerebrospinal Fluid Findings of 36 Adult Patients with Autism Spectrum Disorder
Authors: Runge Kimon , Tebartz van Elst Ludger , Maier Simon , Nickel Kathrin , Denzel Dominik , Matysik Miriam , Kuzior Hanna , Robinson Tilman , Blank Thomas , Dersch Rick , Domschke Katharina , Endres Dominique
Published: June 2020

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by difficulties with social interaction, repetitive behavior, and additional features, such as special interests. Its precise etiology is unclear. Recently, immunological mechanisms, such as maternal autoantibodies/infections, have increasingly been the subject of discussion. Cerebrospinal fluid (CSF) investigations play a decisive role in the detection of immunological processes in the brain. This study therefore retrospectively analyzed the CSF findings of adult patients with ASD. CSF basic measures (white blood cell count, total protein, albumin quotient, immunoglobulin G (IgG) index, and oligoclonal bands) and various antineuronal antibody findings of 36 adult patients with ASD, who had received lumbar puncture, were compared with an earlier described mentally healthy control group of 39 patients with idiopathic intracranial hypertension. CSF protein concentrations and albumin quotients of patients with ASD were significantly higher as compared to controls (age corrected: p = 0.003 and p = 0.004, respectively); 17% of the patients with ASD showed increased albumin quotients. After correction for age and gender, the group effect for total protein remained significant (p = 0.041) and showed a tendency for albumin quotient (p = 0.079). In the CSF of two ASD patients, an intrathecal synthesis of anti-glutamate decarboxylase 65 (GAD65) antibodies was found. In total, more of the ASD patients (44%) presented abnormal findings in CSF basic diagnostics compared to controls (18%; p = 0.013). A subgroup of the patients with adult ASD showed indication of a blood–brain barrier dysfunction, and two patients displayed an intrathecal synthesis of anti-GAD65 antibodies; thus, the role of these antibodies in patients with ASD should be further investigated. The results of the study are limited by its retrospective and open design. The group differences in blood–brain barrier markers could be influenced by a different gender distribution between ASD patients and controls.
Migraine Frequency Decrease Following Prolonged Medical Cannabis Treatment: A Cross-Sectional Study
Authors: Aviram Joshua , Vysotski Yelena , Berman Paula , Lewitus Gil M. , Eisenberg Elon , Meiri David
Published: June 2020

Background: Medical cannabis (MC) treatment for migraine is practically emerging, although sufficient clinical data are not available for this indication. This cross-sectional questionnaire-based study aimed to investigate the associations between phytocannabinoid treatment and migraine frequency. Methods: Participants were migraine patients licensed for MC treatment. Data included self-reported questionnaires and MC treatment features. Patients were retrospectively classified as responders vs. non-responders (≥50% vs. <50% decrease in monthly migraine attacks frequency following MC treatment initiation, respectively). Comparative statistics evaluated differences between these two subgroups. Results: A total of 145 patients (97 females, 67%) with a median MC treatment duration of three years were analyzed. Compared to non-responders, responders (n = 89, 61%) reported lower current migraine disability and lower negative impact, and lower rates of opioid and triptan consumption. Subgroup analysis demonstrated that responders consumed higher doses of the phytocannabinoid ms_373_15c and lower doses of the phytocannabinoid ms_331_18d (3.40 95% CI (1.10 to 12.00); p < 0.01 and 0.22 95% CI (0.05–0.72); p < 0.05, respectively). Conclusions: These findings indicate that MC results in long-term reduction of migraine frequency in >60% of treated patients and is associated with less disability and lower antimigraine medication intake. They also point to the MC composition, which may be potentially efficacious in migraine patients.
Six-Steps Process of Structural Assessment of Heritage Timber Structures: Definition Based on the State of the Art
Authors: Perria Elena , Sieder Mike
Published: June 2020

Each construction material deals with specific mechanical properties, their distribution, damage mechanisms, and degradation processes. Therefore, each material requires a particular assessment approach in order to derive a reliable description of the residual performance of the structure, correctly remove the cause of damage, and proceed with the correct design of interventions. The aims of this paper are, first, the definition of a process of assessment and retrofitting of existing timber structures, both for engineered and heritage/traditional timber structures, and second, a comparison between the defined assessment process and its contents, and the content of existing guidelines, codes, and standards. In order to gain a definition of the process of assessment and retrofitting of existing timber structures, the content of scientific papers and articles was analyzed, and on this basis, an assessment process with six main steps and three milestones was developed. The content of the guidelines, codes and standards was afterwards analyzed basing on this six-steps assessment process. From a comparison among the current literature, guidelines, codes, and standards, interesting results emerged that gave us a picture of the European knowledge and interests on the assessment of existing timber structures. Not only agreement, but also discrepancies, variances, and incongruities were identified as possible topics for future research.
EGFR and αvβ6 as Promising Targets for Molecular Imaging of Cutaneous and Mucosal Squamous Cell Carcinoma of the Head and Neck Region
Authors: Baart Victor M. , van Duijn Chayenne , van Egmond Sylvia L. , Dijckmeester Willem A. , Jansen Jeroen C. , Vahrmeijer Alexander L. , Sier Cornelis F. M. , Cohen Danielle
Published: June 2020

R0 resection is paramount in cutaneous squamous cell carcinoma (CSCC) and head and neck squamous cell carcinoma (HNSCC). However, in the setting of recurrence, immunocompromised patients, or non-keratinizing squamous cell carcinoma (SCC) with a spindle growth pattern, tumor borders are difficult, if not impossible, to determine. Fluorescence-guided surgery (FGS) aids in this differentiation. Potential targets for FGS of CSCC and HNSCC were evaluated. Most sections stained intensely for αvβ6 and epidermal growth factor receptor (EGFR) on tumor cells. Normal epithelium stained less for αvβ6 than for EGFR. In addition, soft tissue and stroma stained negative for both, allowing for clear discrimination of the soft tissue margin. Tumor cells weakly expressed urokinase plasminogen activator receptor (uPAR) while expression on stromal cells was moderate. Normal epithelium rarely expressed uPAR, resulting in clear discrimination of superficial margins. Tumors did not consistently express integrin β3, carcinoembryonic antigen, epithelial cell adhesion molecule, or vascular endothelial growth factor A. In conclusion, αvβ6 and EGFR allowed for precise discrimination of SSC at the surgically problematic soft tissue margins. Superficial margins are ideally distinguished with uPAR. In the future, FGS in the surgically challenging setting of cutaneous and mucosal SCC could benefit from a tailor-made approach, with EGFR and αvβ6 as targets.
Insights into the Role of Estrogen Receptor β in Triple-Negative Breast Cancer
Authors: Sellitto Assunta , D’Agostino Ylenia , Alexandrova Elena , Lamberti Jessica , Pecoraro Giovanni , Memoli Domenico , Rocco Domenico , Coviello Elena , Giurato Giorgio , Nassa Giovanni , Tarallo Roberta , Weisz Alessandro , Rizzo Francesca
Published: June 2020

Estrogen receptors (ERα and ERβ) are ligand-activated transcription factors that play different roles in gene regulation and show both overlapping and specific tissue distribution patterns. ERβ, contrary to the oncogenic ERα, has been shown to act as an oncosuppressor in several instances. However, while the tumor-promoting actions of ERα are well-known, the exact role of ERβ in carcinogenesis and tumor progression is not yet fully understood. Indeed, to date, highly variable and even opposite effects have been ascribed to ERβ in cancer, including for example both proliferative and growth-inhibitory actions. Recently ERβ has been proposed as a potential target for cancer therapy, since it is expressed in a variety of breast cancers (BCs), including triple-negative ones (TNBCs). Because of the dependence of TNBCs on active cellular signaling, numerous studies have attempted to unravel the mechanism(s) behind ERβ-regulated gene expression programs but the scenario has not been fully revealed. We comprehensively reviewed the current state of knowledge concerning ERβ role in TNBC biology, focusing on the different signaling pathways and cellular processes regulated by this transcription factor, as they could be useful in identifying new diagnostic and therapeutic approaches for TNBC.
Oncogenic Properties of the EBV ZEBRA Protein
Authors: Germini Diego , Sall Fatimata Bintou , Shmakova Anna , Wiels Joëlle , Dokudovskaya Svetlana , Drouet Emmanuel , Vassetzky Yegor
Published: June 2020

Epstein Barr Virus (EBV) is one of the most common human herpesviruses. After primary infection, it can persist in the host throughout their lifetime in a latent form, from which it can reactivate following specific stimuli. EBV reactivation is triggered by transcriptional transactivator proteins ZEBRA (also known as Z, EB-1, Zta or BZLF1) and RTA (also known as BRLF1). Here we discuss the structural and functional features of ZEBRA, its role in oncogenesis and its possible implication as a prognostic or diagnostic marker. Modulation of host gene expression by ZEBRA can deregulate the immune surveillance, allow the immune escape, and favor tumor progression. It also interacts with host proteins, thereby modifying their functions. ZEBRA is released into the bloodstream by infected cells and can potentially penetrate any cell through its cell-penetrating domain; therefore, it can also change the fate of non-infected cells. The features of ZEBRA described in this review outline its importance in EBV-related malignancies.
A Multidisciplinary Review of the Roles of Cripto in the Scientific Literature Through a Bibliometric Analysis of its Biological Roles
Authors: Rodrigues Sousa Elisa , Zoni Eugenio , Karkampouna Sofia , La Manna Federico , Gray Peter C. , De Menna Marta , Kruithof-de Julio Marianna
Published: June 2020

Cripto is a small glycosylphosphatidylinisitol (GPI)-anchored and secreted oncofetal protein that plays important roles in regulating normal physiological processes, including stem cell differentiation, embryonal development, and tissue growth and remodeling, as well as pathological processes such as tumor initiation and progression. Cripto functions as a co-receptor for TGF-β ligands such as Nodal, GDF1, and GDF3. Soluble and secreted forms of Cripto also exhibit growth factor-like activity and activate SRC/MAPK/PI3K/AKT pathways. Glucose-Regulated Protein 78 kDa (GRP78) binds Cripto at the cell surface and has been shown to be required for Cripto signaling via both TGF-β and SRC/MAPK/PI3K/AKT pathways. To provide a comprehensive overview of the scientific literature related to Cripto, we performed, for the first time, a bibliometric analysis of the biological roles of Cripto as reported in the scientific literature covering the last 10 years. We present different fields of knowledge in comprehensive areas of research on Cripto, ranging from basic to translational research, using a keyword-driven approach. Our ultimate aim is to aid the scientific community in conducting targeted research by identifying areas where research has been conducted so far and, perhaps more importantly, where critical knowledge is still missing.
Shallow Whole-Genome Sequencing from Plasma Identifies FGFR1 Amplified Breast Cancers and Predicts Overall Survival
Authors: Bourrier Chantal , Pierga Jean-Yves , Xuereb Laura , Salaun Hélène , Proudhon Charlotte , Speicher Michael R. , Belic Jelena , Heitzer Ellen , Lockhart Brian Paul , Guigal-Stephan Nolwen
Published: June 2020

Background: Focal amplification of fibroblast growth factor receptor 1 (FGFR1) defines a subgroup of breast cancers with poor prognosis and high risk of recurrence. We sought to demonstrate the potential of circulating cell-free DNA (cfDNA) analysis to evaluate FGFR1 copy numbers from a cohort of 100 metastatic breast cancer (mBC) patients. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples were screened for FGFR1 amplification by FISH, and positive cases were confirmed with a microarray platform (OncoscanTM). Subsequently, cfDNA was evaluated by two approaches, i.e., mFAST-SeqS and shallow whole-genome sequencing (sWGS), to estimate the circulating tumor DNA (ctDNA) allele fraction (AF) and to evaluate the FGFR1 status. Results: Tissue-based analyses identified FGFR1 amplifications in 20/100 tumors. All cases with a ctDNA AF above 3% (n = 12) showed concordance for FGFR1 status between tissue and cfDNA. In one case, we were able to detect a high-level FGFR1 amplification, although the ctDNA AF was below 1%. Furthermore, high levels of ctDNA indicated an association with unfavorable prognosis based on overall survival. Conclusions: Screening for FGFR1 amplification in ctDNA might represent a viable strategy to identify patients eligible for treatment by FGFR inhibition, and mBC ctDNA levels might be used for the evaluation of prognosis in clinical drug trials.
Targeting DNA Double-Strand Break Repair Enhances Radiosensitivity of HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma to Photons and Protons
Authors: Vitti Eirini Terpsi , Kacperek Andrzej , Parsons Jason L.
Published: June 2020

The response of head and neck squamous cell carcinoma (HNSCC) to radiotherapy depends on human papillomavirus type 16 (HPV) status, and where improved outcome and survival is observed in HPV-positive disease. However, strategies to further radiosensitise the tumours, particularly relatively radioresistant HPV-negative HNSCC, are actively being sought. The impact of targeting the major protein kinases involved in the signaling of DNA double-strand break (DSB) repair, namely ataxia telangiectasia-mutated (ATM), ataxia telangiectasia and Rad3-related (ATR), and the catalytic subunit of DNA-dependent protein kinase (DNA-Pkcs), on the radiosensitisation of HNSCC cells was examined. The response to both conventional photon radiotherapy, but also proton beam therapy, was analysed by clonogenic assays and 3D spheroid growth. We observed that inhibition of ATM, ATR, and particularly DNA-Pkcs, caused a significant reduction in HNSCC cell survival post-irradiation with both photons and protons, with less of an impact on the most radiosensitive HPV-positive cell line. The inhibition of DNA-Pkcs and, to a lesser extent ATM, in combination with radiation was also more effective at inhibiting the growth of 3D spheroids derived from relatively radioresistant HPV-negative HNSCC. Similar effects of the inhibitors were observed comparing photon and proton irradiation, demonstrating the potential for targeting DSB repair as an effective combination treatment for HNSCC.
Development of a VLP-Based Vaccine Displaying an xCT Extracellular Domain for the Treatment of Metastatic Breast Cancer
Authors: Rolih Valeria , Caldeira Jerri , Bolli Elisabetta , Salameh Ahmad , Conti Laura , Barutello Giuseppina , Riccardo Federica , Magri Jolanda , Lamolinara Alessia , Parra Karla , Valenzuela Paloma , Francia Giulio , Iezzi Manuela , Pericle Federica , Cavallo Federica
Published: June 2020

Metastatic breast cancer (MBC) is the leading cause of cancer death in women due to recurrence and resistance to conventional therapies. Thus, MBC represents an important unmet clinical need for new treatments. In this paper we generated a virus-like particle (VLP)-based vaccine (AX09) to inhibit de novo metastasis formation and ultimately prolong the survival of patients with MBC. To this aim, we engineered the bacteriophage MS2 VLP to display an extracellular loop of xCT, a promising therapeutic target involved in tumor progression and metastasis formation. Elevated levels of this protein are observed in a high percentage of invasive mammary ductal tumors including triple negative breast cancer (TNBC) and correlate with poor overall survival. Moreover, xCT expression is restricted to only a few normal cell types. Here, we tested AX09 in several MBC mouse models and showed that it was well-tolerated and elicited a strong antibody response against xCT. This antibody-based response resulted in the inhibition of xCT’s function in vitro and reduced metastasis formation in vivo. Thus, AX09 represents a promising novel approach for MBC, and it is currently advancing to clinical development.
What Is the Role of Imaging in Cancers?
Authors: Evangelista Laura , Fanti Stefano
Published: June 2020

In the issue entitled “Role of Medical Imaging in Cancers”, 33 papers have been collected (23 original articles, 8 reviews, 1 brief report and 1 perspective) [...]
Improved Outcome Prediction for Appendiceal Pseudomyxoma Peritonei by Integration of Cancer Cell and Stromal Transcriptional Profiles
Authors: Isella Claudio , Vaira Marco , Robella Manuela , Bellomo Sara Erika , Picco Gabriele , Borsano Alice , Mignone Andrea , Petti Consalvo , Porporato Roberta , Ulla Alexandra Ambra , Pisacane Alberto , Sapino Anna , De Simone Michele , Medico Enzo
Published: June 2020

In recent years, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have substantially improved the clinical outcome of pseudomyxoma peritonei (PMP) originating from mucinous appendiceal cancer. However, current histopathological grading of appendiceal PMP frequently fails in predicting disease outcome. We recently observed that the integration of cancer cell transcriptional traits with those of cancer-associated fibroblasts (CAFs) improves prognostic prediction for tumors of the large intestine. We therefore generated global expression profiles on a consecutive series of 24 PMP patients treated with CRS plus HIPEC. Multiple lesions were profiled for nine patients. We then used expression data to stratify the samples by a previously published “high-risk appendiceal cancer” (HRAC) signature and by a CAF signature that we previously developed for colorectal cancer, or by a combination of both. The prognostic value of the HRAC signature was confirmed in our cohort and further improved by integration of the CAF signature. Classification of cases profiled for multiple lesions revealed the existence of outlier samples and highlighted the need of profiling multiple PMP lesions to select representative samples for optimal performances. The integrated predictor was subsequently validated in an independent PMP cohort. These results provide new insights into PMP biology, revealing a previously unrecognized prognostic role of the stromal component and supporting integration of standard pathological grade with the HRAC and CAF transcriptional signatures to better predict disease outcome.
Flavonoids in Cancer Metastasis
Authors: Liskova Alena , Koklesova Lenka , Samec Marek , Smejkal Karel , Samuel Samson Mathews , Varghese Elizabeth , Abotaleb Mariam , Biringer Kamil , Kudela Erik , Danko Jan , Shakibaei Mehdi , Kwon Taeg Kyu , Büsselberg Dietrich , Kubatka Peter
Published: June 2020

Metastasis represents a serious complication in the treatment of cancer. Flavonoids are plant secondary metabolites exerting various health beneficiary effects. The effects of flavonoids against cancer are associated not only with early stages of the cancer process, but also with cancer progression and spread into distant sites. Flavonoids showed potent anti-cancer effects against various cancer models in vitro and in vivo, mediated via regulation of key signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of epithelial-mesenchymal transition or regulatory molecules such as MMPs, uPA/uPAR, TGF-β and other contributors of the complex process of metastatic spread. Moreover, flavonoids modulated also the expression of genes associated with the progression of cancer and improved inflammatory status, a part of the complex process involved in the development of metastasis. Flavonoids also documented clear potential to improve the anti-cancer effectiveness of conventional chemotherapeutic agents. Most importantly, flavonoids represent environmentally-friendly and cost-effective substances; moreover, a wide spectrum of different flavonoids demonstrated safety and minimal side effects during long-termed administration. In addition, the bioavailability of flavonoids can be improved by their conjugation with metal ions or structural modifications by radiation. In conclusion, anti-cancer effects of flavonoids, targeting all phases of carcinogenesis including metastatic progression, should be implemented into clinical cancer research in order to strengthen their potential use in the future targeted prevention and therapy of cancer in high-risk individuals or patients with aggressive cancer disease with metastatic potential.
Detection of Circulating Tumor Plasma Cells in Monoclonal Gammopathies: Methods, Pathogenic Role, and Clinical Implications
Authors: Sanoja-Flores Luzalba , Flores-Montero Juan , Pérez-Andrés Martín , Puig Noemí , Orfao Alberto
Published: June 2020

Cancer dissemination and distant metastasis most frequently require the release of tumor cells into the blood circulation, both in solid tumors and most hematological malignancies, including plasma cell neoplasms. However, detection of blood circulating tumor cells in solid tumors and some hematological malignancies, such as the majority of mature/peripheral B-cell lymphomas and monoclonal gammopathies, has long been a challenge due to their very low frequency. In recent years, the availability of highly-sensitive and standardized methods for the detection of circulating tumor plasma cells (CTPC) in monoclonal gammopathies, e.g., next-generation flow cytometry (NGF), demonstrated the systematic presence of CTPC in blood in virtually every smoldering (SMM) and symptomatic multiple myeloma (MM) patient studied at diagnosis, and in the majority of patients with newly-diagnosed monoclonal gammopathies of undetermined significance (MGUS). These methods set the basis for further detailed characterization of CTPC vs. their bone marrow counterpart in monoclonal gammopathies, to investigate their role in the biology of the disease, and to confirm their strong impact on patient outcome when measured both at diagnosis and after initiating therapy. Here, we review the currently available techniques for the detection of CTPC, and determine their biological features, physiopathological role and clinical significance in patients diagnosed with distinct diagnostic categories of plasma cell neoplasms.
Glutathione S-Transferase pi-1 Knockdown Reduces Pancreatic Ductal Adenocarcinoma Growth by Activating Oxidative Stress Response Pathways
Authors: Singh Rahul R. , Mohammad Jiyan , Orr Megan , Reindl Katie M.
Published: June 2020

Glutathione S-transferase pi-1 (GSTP1) plays an important role in regulating oxidative stress by conjugating glutathione to electrophiles. GSTP1 is overexpressed in breast, colon, lung, and prostate tumors, where it contributes to tumor progression and drug resistance; however, the role of GSTP1 in pancreatic ductal adenocarcinoma (PDAC) is not well understood. Using shRNA, we knocked down GSTP1 expression in three different PDAC cell lines and determined the effect on cell proliferation, cell cycle progression, and reactive oxygen species (ROS) levels. Our results show GSTP1 knockdown reduces PDAC cell growth, prolongs the G0/G1 phase, and elevates ROS in PDAC cells. Furthermore, GSTP1 knockdown results in the increased phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun and the decreased phosphorylation of extracellular signal-regulated kinase (ERK), p65, the reduced expression of specificity protein 1 (Sp1), and the increased expression of apoptosis-promoting genes. The addition of the antioxidant glutathione restored cell viability and returned protein expression levels to those found in control cells. Collectively, these data support the working hypothesis that the loss of GSTP1 elevates oxidative stress, which alters mitogen-activated protein (MAP) kinases and NF-κB signaling, and induces apoptosis. In support of these in vitro data, nude mice bearing orthotopically implanted GSTP1-knockdown PDAC cells showed an impressive reduction in the size and weight of tumors compared to the controls. Additionally, we observed reduced levels of Ki-67 and increased expression of cleaved caspase-3 in GSTP1-knockdown tumors, suggesting GSTP1 knockdown impedes proliferation and upregulates apoptosis in PDAC cells. Together, these results indicate that GSTP1 plays a significant role in PDAC cell growth and provides support for the pursuit of GSTP1 inhibitors as therapeutic agents for PDAC.
Capture-Based Next-Generation Sequencing Improves the Identification of Immunoglobulin/T-Cell Receptor Clonal Markers and Gene Mutations in Adult Acute Lymphoblastic Leukemia Patients Lacking Molecular Probes
Authors: Cavagna Roberta , Guinea Montalvo Marie L. , Tosi Manuela , Paris Michela , Pavoni Chiara , Intermesoli Tamara , Bassan Renato , Mosca Andrea , Rambaldi Alessandro , Spinelli Orietta
Published: June 2020

The monitoring of minimal residual disease (MRD) in Philadelphia-negative acute lymphoblastic leukemia (ALL) requires the identification at diagnosis of immunoglobulin/T-cell receptor (Ig/TCR) rearrangements as clonality markers. Aiming to simplify and possibly improve the patients’ initial screening, we designed a capture-based next-generation sequencing (NGS) panel combining the Ig/TCR rearrangement detection with the profiling of relevant leukemia-related genes. The validation of the assay on well-characterized samples allowed us to identify all the known Ig/TCR rearrangements as well as additional clonalities, including rare rearrangements characterized by uncommon combinations of variable, diversity, and joining (V-D-J) gene segments, oligoclonal rearrangements, and low represented clones. Upon validation, the capture NGS approach allowed us to identify Ig/TCR clonal markers in 87% of a retrospective cohort (MRD-unknown within the Northern Italy Leukemia Group (NILG)-ALL 09/00 clinical trial) and in 83% of newly-diagnosed ALL cases in which conventional method failed, thus proving its prospective applicability. Finally, we identified gene variants in 94.7% of patients analyzed for mutational status with the same implemented capture assay. The prospective application of this technology could simplify clonality assessment and improve standard assay development for leukemia monitoring, as well as provide information about the mutational status of selected leukemia-related genes, potentially representing new prognostic elements, MRD markers, and targets for specific therapies.
Synthesis and Characterization of Bio-Active GFP-P4VP Core–Shell Nanoparticles
Authors: Sarnello Erik , Liu Yuzi , Palen Bethany , Sun Elaine , Zuo Xiaobing , Xu Tao , Li Tao
Published: June 2020

Bioactive core–shell nanoparticles (CSNPs) offer the unique ability for protein/enzyme functionality in non-native environments. For many decades, researchers have sought to develop synthetic materials which mimic the efficiency and catalytic power of bioactive macromolecules such as enzymes and proteins. This research studies a self-assembly method in which functionalized, polymer-core/protein-shell nanoparticles are prepared in mild conditions. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques were utilized to analyze the size and distribution of the CSNPs. The methods outlined in this research demonstrate a mild, green chemistry synthesis route for CSNPs which are highly tunable and allow for enzyme/protein functionality in non-native conditions.
Highly Active and Carbon-Resistant Nickel Single-Atom Catalysts for Methane Dry Reforming
Authors: Akri Mohcin , El Kasmi Achraf , Batiot-Dupeyrat Catherine , Qiao Botao
Published: June 2020

The conversion of CH4 and CO2 to syngas using low-cost nickel catalysts has attracted considerable interest in the clean energy and environment field. Nickel nanoparticles catalysts suffer from serious deactivation due mainly to carbon deposition. Here, we report a facile synthesis of Ni single-atom and nanoparticle catalysts dispersed on hydroxyapatite (HAP) support using the strong electrostatic adsorption (SEA) method. Ni single-atom catalysts exhibit excellent resistance to carbon deposition and high atom efficiency with the highest reaction rate of 1186.2 and 816.5 mol.gNi−1.h−1 for CO2 and CH4, respectively. Although Ni single-atom catalysts aggregate quickly to large particles, the polyvinylpyrrolidone (PVP)-assisted synthesis exhibited a significant improvement of Ni single-atom stability. Characterizations of spent catalysts revealed that carbon deposition is more favorable over nickel nanoparticles. Interestingly, it was found that, separately, CH4 decomposition on nickel nanoparticle catalysts and subsequent gasification of deposit carbon with CO2 resulted in CO generation, which indicates that carbon is reacting as an intermediate species during reaction. Accordingly, the approach used in this work for the design and control of Ni single-atom and nanoparticles-based catalysts, for dry reforming of methane (DRM), paves the way towards the development of stable noble metals-free catalysts.
Recent Advances in Homogeneous Catalysis via Metal–Ligand Cooperation Involving Aromatization and Dearomatization
Authors: Shimbayashi Takuya , Fujita Ken-ichi
Published: June 2020

Recently, an increasing number of metal complex catalysts have been developed to achieve the activation or transformation of substrates based on cooperation between the metal atom and its ligands. In such “cooperative catalysis,” the ligand not only is bound to the metal, where it exerts steric and electronic effects, but also functionally varies its structure during the elementary processes of the catalytic reaction. In this review article, we focus on metal–ligand cooperation involving aromatization and dearomatization of the ligand, thus introducing the newest developments and examples of homogeneous catalytic reactions.
Preparation of 5-HMF in a DES/Ethyl N-Butyrate Two-Phase System
Authors: Lang Jinyan , Lu Junliang , Lan Ping , Wang Na , Yang Hongyan , Zhang Heng
Published: June 2020

In this paper, a two-phase system, formed by oxalic acid/choline chloride-based deep eutectic solvent (DES) and chosen extractants, was used as a dissolution–reaction–separation system, and metal chloride was used as a catalyst to study the degradation of cellulose to produce 5-hydroxymethylfurfural (5-HMF) and glucose. The effects of the amount of organic solvent and the reaction temperature on product yield, the repeated recycling of DES, the comparison between a two-phase system and a homogeneous system, and the mechanism of cellulose degradation to 5-HMF were investigated. The results show that ethyl n-butyrate has the best extraction effect on 5-HMF. Compared with the homogeneous system, the yield of 5-HMF and glucose in the two-phase system is significantly improved. At a temperature of 140 °C and a reaction time of 120 min, the yields of glucose and 5-HMF reached the maximum, which were 23.5% and 29.8%, respectively. After DES was reused three times, the yields of glucose and 5-HMF decreased greatly, indicating that the recycling rate of DES was low.
Strategy for Modifying Layered Perovskites toward Efficient Solar Light-Driven Photocatalysts for Removal of Chlorinated Pollutants
Authors: Raciulete Monica , Papa Florica , Negrila Catalin , Bratan Veronica , Munteanu Cornel , Pandele-Cusu Jeanina , Culita Daniela C. , Atkinson Irina , Balint Ioan
Published: June 2020

We have explored an efficient strategy to enhance the overall photocatalytic performances of layered perovskites by increasing the density of hydroxyl group by protonation. The experimental procedure consisted of the slow replacement of interlayer Rb+ cation of RbLaTa2O7 Dion-Jacobson (DJ) perovskite by H+ via acid treatment. Two layered perovskites synthesized by mild (1200 °C for 18 h) and harsh (950 and 1200 °C, for 36 h) annealing treatment routes were used as starting materials. The successful intercalation of proton into D-J interlayer galleries was confirmed by FTIR spectroscopy, thermal analyses, ion chromatography and XPS results. In addition, the ion-exchange route was effective to enlarge the specific surface area, thus enhancing the supply of photocharges able to participate in redox processes involved in the degradation of organic pollutants. HLaTa_01 protonated layered perovskite is reported as a efficient photocatalyst for photomineralization of trichloroethylene (TCE) to Cl− and CO2 under simulated solar light. The enhanced activity is attributed to combined beneficial roles played by the increased specific surface area and high density of hydroxyl groups, leading to an efficiency of TCE mineralization of 68% moles after 5 h of irradiation.
Study the Effect of Various Sulfonation Methods on Catalytic Activity of Carbohydrate-Derived Catalysts for Ester Production
Authors: Deris Nur Hidayah , Rashid Umer , Soltani Soroush , Choong Thomas Shean Yaw , Nehdi Imededdine Arbi
Published: June 2020

In the present study, four types of sulfonation method, including thermal treatment with concentrated sulfuric acid (H2SO4), thermal decomposition of ammonium sulphate (NHSO4), thermal treatment with chlorosulfonic in chloroform (HSO3Cl), and in situ polymerization of poly(sodium4-styrenesulfonate) (PSS), were employed to convert incomplete carbonized glucose (ICG) to sulfonated heterogeneous catalysts for the fatty acid methyl ester (FAME) production. The characteristics of synthesized catalysts were further examined using Raman spectroscopy, Fourier transformation infrared (FT-IR), ammonia temperature programmed desorption (NH3-TPD), Brunauer–Emmett–Teller (BET), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and energy dispersive X-ray (EDX). According to experiments, the sulfonic acid density was varied in a range from 4.408 to 14.643 mmol g−1 over various sulfonation methods. The catalytic activity of synthesized catalysts over different sulfonation methods was determined by performing the conversion of palm fatty acid distillate (PFAD) to ester synthesis in a batch-system reactor. The findings reveal that using PSS-ICG resulted in the highest FAME yield of 96.3% followed by HSO3Cl-ICG of 94.8%, NHSO4-ICG of 84.2%; and H2SO4-ICG of 77.2%. According to results, the ICG sulfonated by PSS method with the highest acid density (14.643 mmol g−1) gave the highest catalytic activity over PFAD conversion to biodiesel. According to experiment results, acid density played a crucial role over FAME yield percentage. Besides acid density, it is also worth mentioning that various sulfonation methods including different mechanisms, chemicals and sulfonating agents played crucial roles in the FAME yield percentage.
Synthesis of Ce1−xPdxO2−δ Solid Solution in Molten Nitrate
Authors: Sasaki Hideaki , Sakamoto Keisuke , Mori Masami , Sakamoto Tatsuaki
Published: June 2020

CeO2-based solid solutions in which Pd partially substitutes for Ce attract considerable attention, owing to their high catalytic performances. In this study, the solid solution (Ce1−xPdxO2−δ) with a high Pd content (x ~ 0.2) was synthesized through co-precipitation under oxidative conditions using molten nitrate, and its structure and thermal decomposition were examined. The characteristics of the solid solution, such as the change in a lattice constant, inhibition of sintering, and ionic states, were examined using X-ray diffraction (XRD), scanning electron microscopy–energy-dispersive X-ray spectroscopy (SEM−EDS), transmission electron microscopy (TEM)−EDS, and X-ray photoelectron spectroscopy (XPS). The synthesis method proposed in this study appears suitable for the easy preparation of CeO2 solid solutions with a high Pd content.
The Effect of Electrolytes on the Photodegradation Kinetics of Caffeine
Authors: Rendel Pedro M. , Rytwo Giora
Published: June 2020

Unsuccessfully treated by the existing wastewater-treatment processes, caffeine concentrations in wastewater effluents and natural reservoirs are constantly rising. Photodegradation treatment processes are drawing much attention due to their potential to oxidize and remove such, and similar contaminating compounds from treated waters. In continuation to our previous work on the photodegradation kinetics of caffeine in water by UV/H2O2 and UV/TiO2, this work evaluates the influence of various electrolytes, including NaCl, KCl, MgCl2, NaBr, and KBr, on the kinetics of the UV/H2O2 photodegradation of caffeine, aiming at estimating the efficiency of the method in more complex water systems. Results show that the efficiency of the UV/H2O2 photodegradation reactions is strongly affected by ionic strength and the presence of electrolytes in the solution. While chloride electrolytes were shown to optimize or reduce the process efficiency pending on their concentration. The sole presence of NaBr and KBr shows an immediate reduction in the efficiency of the photodegradation. Empirical apparent-rate-coefficients and curves describing the effect of the different electrolytes on the photodegradation kinetics of caffeine are presented.
Flow Biocatalysis
Authors: Paradisi Francesca
Published: June 2020

The rapid evolution of enzyme technology has enabled new reactions and processes with a level of efficiency which was unimaginable only a few years ago [...]
Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy
Authors: Couto Marcos , Alamón Catalina , García María , Kovacs Mariángeles , Trias Emiliano , Nievas Susana , Pozzi Emiliano , Curotto Paula , Thorp Silvia , Dagrosa María , Teixidor Francesc , Viñas Clara , Cerecetto Hugo
Published: June 2020

One of the driving forces of carcinogenesis in humans is the aberrant activation of receptors; consequently, one of the most promising mechanisms for cancer treatment is receptor inhibition by chemotherapy. Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. Anti-tumor agents overcoming resistance and acting through two or more ways offer greater therapeutic benefits over single-mechanism entities. In this study, we report on a new family of bifunctional compounds that, offering the possibility of dual action (drug + radiotherapy combinations), may result in significant clinical benefits. This new family of compounds combines two fragments: the drug fragment is a lapatinib group, which inhibits the tyrosine kinase receptor activity, and an icosahedral boron cluster used as agents for neutron capture therapy (BNCT). The developed compounds were evaluated in vitro against different tyrosine kinase receptors (TKRs)-expressing tumoral cells, and in vitro–BNCT experiments were performed for two of the most promising hybrids, 19 and 22. We identified hybrid 19 with excellent selectivity to inhibit cell proliferation and ability to induce necrosis/apoptosis of glioblastoma U87 MG cell line. Furthermore, derivative 22, bearing a water-solubility-enhancing moiety, showed moderate inhibition of cell proliferation in both U87 MG and colorectal HT-29 cell lines. Additionally, the HT-29 cells accumulated adequate levels of boron after hybrids 19 and 22 incubations rendering, and after neutron irradiation, higher BNCT-effects than BPA. The attractive profile of developed hybrids makes them interesting agents for combined therapy.
microRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells
Authors: Jeon Jin Seok , Kim Eunbit , Bae Yun-Ui , Yang Won Mi , Lee Haekyung , Kim Hyoungnae , Noh Hyunjin , Han Dong Cheol , Ryu Seongho , Kwon Soon Hyo
Published: June 2020

Tubular injury and fibrosis are associated with progressive kidney dysfunction in advanced glomerular disease. Glomerulotubular crosstalk is thought to contribute to tubular injury. microRNAs (miRNAs) in extracellular vesicles (EVs) can modulate distant cells. We hypothesized that miRNAs in EVs derived from injured podocytes lead to tubular epithelial cell damage. As proof of this concept, tubular epithelial (HK2) cells were cultured with exosomes from puromycin-treated or healthy human podocytes, and damage was assessed. Sequencing analysis revealed the miRNA repertoire of podocyte EVs. RNA sequencing identified 63 upregulated miRNAs in EVs from puromycin-treated podocytes. Among them, five miRNAs (miR-149, -424, -542, -582, and -874) were selected as candidates for inducing tubular apoptosis according to a literature-based search. To validate the effect of the miRNAs, HK2 cells were treated with miRNA mimics. EVs from injured podocytes induced apoptosis and p38 phosphorylation of HK2 cells. The miRNA-424 and 149 mimics led to apoptosis of HK2 cells. These results show that miRNAs in EVs from injured podocytes lead to damage to tubular epithelial cells, which may contribute to the development of tubular injury in glomerular disease.