bluuebunny/crossref_metadata_2025 huggingface dataset:
Reveal of Internal, Early-Load Interfacial Debonding on Cement Textile-Reinforced Sandwich Insulated Panels
Authors: Tsangouri Eleni , Ismail Hasan , De Munck Matthias , Aggelis Dimitrios G. , Tysmans Tine
Published: January 2021

Internal interfacial debonding (IID) phenomena on sandwich façade insulated panels are detected and tracked by acoustic emission (AE). The panels are made of a thin and lightweight cementitious composite skin. In the lab, the panels are tested under incremental bending simulating service loads (i.e., wind). Local (up to 150 mm wide) skin-core detachments are reported in the early loading stage (at 5% of ultimate load) and are extensively investigated in this study, since IID can detrimentally affect the long-term durability of the structural element. A sudden rise in the AE hits rate and a shift in the wave features (i.e., absolute energy, amplitude, rise time) trends indicate the debonding onset. AE source localization, validated by digital image correlation (DIC) principal strains and out-of-plane full-field displacement mapping, proves that early debonding occurs instantly and leads to the onset of cracks in the cementitious skin. At higher load levels, cracking is accompanied by local debonding phenomena, as proven by RA value increases and average frequency drops, a result that extends the state-of-the-art in the fracture assessment of concrete structures (Rilem Technical Committee 212-ACD). Point (LVDT) and full-field (AE/DIC) measurements highlight the need for a continuous and full-field monitoring methodology in order to pinpoint the debonded zones, with the DIC technique accurately reporting surface phenomena while AE offers in-volume damage tracking.
Energy Management Optimization of a Dual Motor Lithium Ion Capacitors-Based Hybrid Super Sport Car
Authors: Franceschi Alessandro , Cavina Nicolò , Parenti Riccardo , Reggiani Maurizio , Corti Enrico
Published: January 2021

Nowadays, hybrid electric vehicles represent one of the main solutions for the reduction of greenhouse gases in the automotive sector. Alongside the reduction of CO2, hybrid electric vehicles serve as a strong alternative on drivability and performance to conventional internal combustion engine-based vehicles. Vehicles exist with various missions; super sport cars usually aim to reach peak performance and to guarantee a great driving experience to the driver, but great attention must also be paid to fuel consumption. According to the vehicle mission, hybrid electric vehicles can differ in the powertrain configuration and the choice of the energy storage system. Manufacturers have recently started to work on Lithium-Ion Capacitors (LiC) -based hybrid vehicles. This paper discusses the usage of a control-oriented vehicle and powertrain model to analyze the performance of a dual motor LiC-based hybrid V12 vehicle by Automobili Lamborghini. P3–P4 and P2–P4 parallel hybrid configurations have been selected and compared since they allow to fully exploit the potential of the LiC storage system characterized by high power. The validated model has been used to develop control strategies aimed at fuel economy and CO2 reduction, and in particular, both Rule Based Strategies (RBS) and Equivalent Consumption Minimization Strategies (ECMS) are presented in the paper. A critical comparison between the various powertrain configurations is carried out, keeping into account the peculiarities of the LiC technology and evaluating the performance of the different control approaches.
Effect of Dry–Wet Cycle Periods on Properties of Concrete under Sulfate Attack
Authors: Guo Jin-Jun , Liu Peng-Qiang , Wu Cun-Liang , Wang Kun
Published: January 2021

Dry–wet cycle conditions have significant effects on the corrosion of concrete under sulfate attack. However, previous studies have only applied them as a method for accelerating sulfate attack and not systematically studied them as an object. In order to explore the impact of sulfate attack with different dry–wet cycle periods on concrete, in this study, four dry–wet cycle periods (3, 7, 14, and 21 days) were selected. The flexure strength, relative dynamic modulus, and mass were tested, and the microstructures of the eroded specimens were also analyzed. The intensity and depth of sulfate erosion were influenced by the wet–dry cycle period. The results show that the deterioration of concrete first increased and then decreased with an extension of the dry–wet cycle period. Microstructural analysis indicated that, with an increase in the dry–wet cycle period, the corrosion depth of sulfate attack increased. Moreover, the erosion products such as ettringite and gypsum were greatly increased, in agreement with the macroscopic variations. However, excessively prolonging the dry–wet periods does not significantly further the deterioration of concrete’s performance. Therefore, considering the strength and depth of corrosion caused by sulfate attack, it would be appropriate to employ dry–wet cycle periods of 7–14 days under natural dry conditions in studies on concrete.
Study of HgOH to Assess Its Suitability for Electron Electric Dipole Moment Searches
Authors: Mitra Ramanuj , Prasannaa V. Srinivasa , Sahoo Bijaya K. , Hutzler Nicholas R. , Abe Minori , Das Bhanu Pratap
Published: January 2021

In search of suitable molecular candidates for probing the electric dipole moment (EDM) of the electron (de), a property that arises due to parity and time-reversal violating (P,T-odd) interactions, we consider the triatomic mercury hydroxide (HgOH) molecule. The impetus for this proposal is based on previous works on two systems: the recently proposed ytterbium hydroxide (YbOH) experiment that demonstrates the advantages of polyatomics for such EDM searches, and the finding that mercury halides provide the highest enhancement due to de compared to other diatomic molecules. We identify the ground state of HgOH as being in a bent geometry, and show that its intrinsic EDM sensitivity is comparable to the corresponding value for YbOH. Along with the theoretical results, we discuss plausible experimental schemes for an EDM measurement in HgOH. Furthermore, we provide pilot calculations of the EDM sensitivity for de for HgCH3 and HgCF3, that are natural extensions of HgOH.
Role of Tristetraprolin in the Resolution of Inflammation
Authors: Rappl Peter , Brüne Bernhard , Schmid Tobias
Published: January 2021

Inflammation is a crucial part of immune responses towards invading pathogens or tissue damage. While inflammatory reactions are aimed at removing the triggering stimulus, it is important that these processes are terminated in a coordinate manner to prevent excessive tissue damage due to the highly reactive inflammatory environment. Initiation of inflammatory responses was proposed to be regulated predominantly at a transcriptional level, whereas post-transcriptional modes of regulation appear to be crucial for resolution of inflammation. The RNA-binding protein tristetraprolin (TTP) interacts with AU-rich elements in the 3′ untranslated region of mRNAs, recruits deadenylase complexes and thereby facilitates degradation of its targets. As TTP regulates the mRNA stability of numerous inflammatory mediators, it was put forward as a crucial post-transcriptional regulator of inflammation. Here, we summarize the current understanding of the function of TTP with a specific focus on its role in adding to resolution of inflammation.
Antibacterial Properties of Fucoidans from the Brown Algae Fucus vesiculosus L. of the Barents Sea
Authors: Ayrapetyan Olga N. , Obluchinskaya Ekaterina D. , Zhurishkina Elena V. , Skorik Yury A. , Lebedev Dmitry V. , Kulminskaya Anna A. , Lapina Irina M.
Published: January 2021

Fucoidans, sulfated polysaccharides found in cell walls of brown algae, are considered as a promising antimicrobial component for various applications in medicine and the food industry. In this study, we compare the antibacterial properties of two fractions of fucoidan from the brown algae Fucus vesiculosus gathered in the littoral of the Barents Sea and sampled at different stages of purification. The crude fraction of fucoidan was isolated from algae by extraction with aqueous ethanol and sonication. The purified fraction was obtained by additional treatment of the crude fraction with a solution of calcium chloride. The structural features of both fractions were characterized in detail and their antibacterial effects against several Gram-positive and Gram-negative bacteria were compared by photometry, acridine orange staining assay, and atomic force microscopy. Fucoidan inhibited growth in all of the above microorganisms, showing a bacteriostatic effect with minimum inhibitory concentrations (MIC) in the range between 4 and 6 mg/mL, with E. coli being the most sensitive to both fractions. Changes in the chemical composition after treatment of the crude fraction with a solution of calcium chloride led to a decrease in the content of sulfates and uronic acids and diminished antibacterial activity.
Molecular Basis of NDT-Mediated Activation of Nucleoside-Based Prodrugs and Application in Suicide Gene Therapy
Authors: Acosta Javier , Pérez Elena , Sánchez-Murcia Pedro A. , Fillat Cristina , Fernández-Lucas Jesús
Published: January 2021

Herein we report the first proof for the application of type II 2′-deoxyribosyltransferase from Lactobacillus delbrueckii (LdNDT) in suicide gene therapy for cancer treatment. To this end, we first confirm the hydrolytic ability of LdNDT over the nucleoside-based prodrugs 2′-deoxy-5-fluorouridine (dFUrd), 2′-deoxy-2-fluoroadenosine (dFAdo), and 2′-deoxy-6-methylpurine riboside (d6MetPRib). Such activity was significantly increased (up to 30-fold) in the presence of an acceptor nucleobase. To shed light on the strong nucleobase dependence for enzymatic activity, different molecular dynamics simulations were carried out. Finally, as a proof of concept, we tested the LdNDT/dFAdo system in human cervical cancer (HeLa) cells. Interestingly, LdNDT/dFAdo showed a pronounced reduction in cellular viability with inhibitory concentrations in the low micromolar range. These results open up future opportunities for the clinical implementation of nucleoside 2′-deoxyribosyltransferases (NDTs) in cancer treatment.
DNA Damage Response
Authors: Oksenych Valentyn , Kainov Denis E.
Published: January 2021

DNA in our cells is constantly modified by internal and external factors [...]
Development of Three-Dimensional Human Intestinal Organoids as a Physiologically Relevant Model for Characterizing the Viral Replication Kinetics and Antiviral Susceptibility of Enteroviruses
Authors: Tsang Jessica Oi-Ling , Zhou Jie , Zhao Xiaoyu , Li Cun , Zou Zijiao , Yin Feifei , Yuan Shuofeng , Yeung Man-Lung , Chu Hin , Chan Jasper Fuk-Woo
Published: January 2021

Enteroviruses are important causes of hand, foot, and mouth disease, respiratory infections, and neurological infections in human. A major hurdle for the development of anti-enterovirus agents is the lack of physiologically relevant evaluation platforms that closely correlate with the in vivo state. We established the human small intestinal organoids as a novel platform for characterizing the viral replication kinetics and evaluating candidate antivirals for enteroviruses. The organoids supported productive replication of enterovirus (EV)-A71, coxsackievirus B2, and poliovirus type 3, as evidenced by increasing viral loads, infectious virus titers, and the presence of cytopathic effects. In contrast, EV-D68, which mainly causes respiratory tract infection in humans, did not replicate significantly in the organoids. The differential expression profiles of the receptors for these enteroviruses correlated with their replication kinetics. Using itraconazole as control, we showed that the results of various antiviral assays, including viral load reduction, plaque reduction, and cytopathic effect inhibition assays, were highly reproducible in the organoids. Moreover, itraconazole attenuated virus-induced inflammatory response in the organoids, which helped to explain its antiviral effects and mechanism. Collectively, these data showed that the human small intestinal organoids may serve as a robust platform for investigating the pathogenesis and evaluating antivirals for enteroviruses.
The Biology of Vasopressin
Authors: Sparapani Samantha , Millet-Boureima Cassandra , Oliver Joshua , Mu Kathy , Hadavi Pegah , Kalostian Tamar , Ali Nazifa , Avelar Carla Maria , Bardies Marion , Barrow Brenton , Benedikt Minky , Biancardi Giuliana , Bindra Raminder , Bui Lisa , Chihab Zakaria , Cossitt Ashley , Costa Jeffrey , Daigneault Tina , Dault Jocelyn , Davidson Isa , Dias Jonathan , Dufour Emie , El-Khoury Sabine , Farhangdoost Nargess , Forget Anika , Fox Alexa , Gebrael Myriam , Gentile Maria Concetta , Geraci Olivia , Gnanapragasam Ansley , Gomah Elias , Haber Elie , Hamel Claudia , Iyanker Thivya , Kalantzis Christina , Kamali Sara , Kassardjian Elsa , Kontos Hryssi Krissy , Le Thi Bich Uyen , LoScerbo Daniella , Low Yan Fang , Mac Rae Danielle , Maurer Flore , Mazhar Sana , Nguyen Alice , Nguyen-Duong Kathy , Osborne-Laroche Chelsea , Park Hwi Wun , Parolin Emilie , Paul-Cole Kahlila , Peer Leah Sarah , Philippon Margaux , Plaisir Charles-Alexandre , Porras Marroquin Jessica , Prasad Simran , Ramsarun Rewaparsad , Razzaq Saad , Rhainds Samantha , Robin Damien , Scartozzi Ryan , Singh Davindra , Fard Sajad Soleimani , Soroko Maxim , Soroori Motlagh Nastaran , Stern Kiri , Toro Laila , Toure M. Wyatt , Tran-Huynh Stephanie , Trépanier-Chicoine Sarah , Waddingham Claudia , Weekes Aaliyah Jasmine , Wisniewski Allison , Gamberi Chiara
Published: January 2021

Vasopressins are evolutionarily conserved peptide hormones. Mammalian vasopressin functions systemically as an antidiuretic and regulator of blood and cardiac flow essential for adapting to terrestrial environments. Moreover, vasopressin acts centrally as a neurohormone involved in social and parental behavior and stress response. Vasopressin synthesis in several cell types, storage in intracellular vesicles, and release in response to physiological stimuli are highly regulated and mediated by three distinct G protein coupled receptors. Other receptors may bind or cross-bind vasopressin. Vasopressin is regulated spatially and temporally through transcriptional and post-transcriptional mechanisms, sex, tissue, and cell-specific receptor expression. Anomalies of vasopressin signaling have been observed in polycystic kidney disease, chronic heart failure, and neuropsychiatric conditions. Growing knowledge of the central biological roles of vasopressin has enabled pharmacological advances to treat these conditions by targeting defective systemic or central pathways utilizing specific agonists and antagonists.
Extracellular Vesicles as Drivers of Non-Alcoholic Fatty Liver Disease: Small Particles with Big Impact
Authors: Ipsen David Højland , Tveden-Nyborg Pernille
Published: January 2021

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading chronic liver disease, negatively affecting the lives of millions of patients worldwide. The complex pathogenesis involves crosstalk between multiple cellular networks, but how the intricate communication between these cells drives disease progression remains to be further elucidated. Furthermore, the disease is not limited to the liver and includes the reprogramming of distant cell populations in different organs. Extracellular vesicles (EVs) have gained increased attention as mediators of cellular communication. EVs carry specific cargos that can act as disease-specific signals both locally and systemically. Focusing on NAFLD advancing to steatohepatitis (NASH), this review provides an update on current experimental and clinical findings of the potential role of EVs in hepatic inflammation and fibrosis, the main contributors to progressive NASH. Particular attention is placed on the characteristics of EV cargos and potential specificity to disease stages, with putative value as disease markers and treatment targets for future investigations.
Brain Metastases in Elderly Patients—The Role of Surgery in the Context of Systemic Treatment
Authors: Proescholdt Martin , Jünger Stephanie , Schödel Petra , Schebesch Karl-Michael , Doenitz Christian , Pukrop Tobias , Höhne Julius , Schmidt Nils-Ole , Kocher Martin , Schulz Holger , Ruge Maximilian , König Kevin , Goldbrunner Roland , Grau Stefan
Published: January 2021

In patients with brain metastases (BM), advanced age is considered a negative prognostic factor. To address the potential reasons for that, we assessed 807 patients who had undergone BM resection; 315 patients aged at least 65 years (group A) were compared with 492 younger patients (group B). We analyzed the impact of the pre- and postoperative Karnofsky performance status (KPS), postoperative treatment structure and post-treatment survival. BM resection significantly improved KPS scores in both groups (p = 0.0001). Median survival after BM resection differed significantly between the groups (A: 5.81 vs. B: 8.12 months; p = 0.0015). In both groups, patients who received postoperative systemic treatment showed significantly longer overall survival (p = 0.00001). However, elderly patients less frequently received systemic treatment (p = 0.0001) and the subgroup of elderly patients receiving such therapies had a significantly higher postsurgical KPS score (p = 0.0007). In all patients receiving systemic treatment, age was no longer a negative prognostic factor. Resection of BM improves the functional status of elderly patients, thus enhancing the likeliness to receive systemic treatment, which, in turn, leads to longer overall survival. In the context of such a treatment structure, age alone is no longer a prognostic factor for survival.
Clinical Efficacy and Safety of Silicone Elastomer Sheet during Decompressive Craniectomy: Anti-Adhesive Role in Cranioplasty
Authors: Kim Young Ha , Lee Chi Hyung , Kim Chang Hyeun , Son Dong Wuk , Lee Sang Weon , Song Geun Sung , Sung Soon Ki
Published: January 2021

(1) Background: Cranioplasty is a surgery to repair a skull bone defect after decompressive craniectomy (DC). If the process of dissection of the epidural adhesion tissue is not performed properly, it can cause many complications. We reviewed the effect of a silicone elastomer sheet designed to prevent adhesion. (2) Methods: We retrospectively reviewed 81 consecutive patients who underwent DC and subsequent cranioplasty at our institution between January 2015 and December 2019. We then divided the patients into two groups, one not using the silicone elastomer sheet (n = 50) and the other using the silicone elastomer sheet (n = 31), and compared the surgical outcomes. (3) Results: We found that the use of the sheet shortened the operation time by 24% and reduced the estimated blood loss (EBL) by 43% compared to the control group. Moreover, the complication rate of epidural fluid collection (EFC) in the group using the sheet was 16.7%, which was lower than that in the control group (41.7%, p < 0.023). Multivariate logistic regression analysis showed the sheet (OR 0.294, 95% CI 0.093–0.934, p = 0.039) to be significantly related to EFC. (4) Conclusions: The technique using the silicone elastomer sheet allows surgeons to easily dissect the surgical plane during cranioplasty, which shortens the operation time, reduces EBL, and minimizes complications of EFC.
Reputation Incongruence and the Preference of Stakeholder: Case of MBA Rankings
Authors: Park Jin Suk , Rhee Mooweon
Published: January 2021

In this paper, we examine the effect of an organization’s multi-dimensional reputation on the external stakeholders’ preference for an organization in the notions of reputation incongruence. We propose that an organization’s incongruent reputation, or large variations among the reputations of each dimension, can be an unfavorable signal to its stakeholders based on theoretical ideas that claim reputation incongruence induces the ambiguity and risk of an organization perceived by stakeholders. We also investigate the moderating effect of reputation incongruence by positing that this incongruence may nullify the influences of reputation dimensions on the preferences of stakeholders. These propositions about reputation incongruence are empirically examined in the context of MBA programs of the global business schools which have three dimensions of reputation—career development, globalization, and research performance.
Emotional Regulation and Overeating Behaviors in Children and Adolescents: A Systematic Review
Authors: Favieri Francesca , Marini Andrea , Casagrande Maria
Published: January 2021

The worldwide prevalence of obesity has dramatically increased, mostly in children and adolescents. The Emotional Eating theoretical model has proposed that the failure in emotional regulation could represent a risk factor for establishing maladaptive overeating behavior that represents an inadequate response to negative emotions and allows increasing body-weight. This systematic review investigates the relationship between overeating and both emotional regulation and emotional intelligence in childhood and adolescence, considering both cross-sectional and longitudinal studies. Moreover, another goal of the review is evaluating whether emotional regulation and emotional intelligence can cause overeating behaviors. The systematic search was conducted according to the PRISMA-statement in the databases Medline, PsychArtcles, PsychInfo, PubMed, Scopus, and Web of Sciences, and allows 484 records to be extracted. Twenty-six studies were selected according to inclusion (e.g., studies focused on children and adolescents without clinical conditions; groups of participants overweight or with obesity) and exclusion (e.g., studies that adopted qualitative assessment or cognitive-affective tasks to measure emotional variables; reviews, commentary, or brief reports) criteria detailed in the methods. Cross-sectional studies showed a negative association between emotional regulation and overeating behavior that was confirmed by longitudinal studies. These findings highlighted the role of maladaptive emotion regulation on overeating and being overweight. The relationship between these constructs in children and adolescents was consistent. The results indicated the complexity of this association, which would be influenced by many physiological, psychological, and social factors. These findings underline the need for further studies focused on emotion regulation in the development of overeating. They should analyze the mediation role of other variables (e.g., attachment style, peer pressure) and identify interventions to prevent and reduce worldwide overweight prevalence.
Tiny miRNAs Play a Big Role in the Treatment of Breast Cancer Metastasis
Authors: Teo Andrea York Tiang , Xiang Xiaoqiang , Le Minh TN , Wong Andrea Li-Ann , Zeng Qi , Wang Lingzhi , Goh Boon-Cher
Published: January 2021

Distant organ metastases accounts for the majority of breast cancer deaths. Given the prevalence of breast cancer in women, it is imperative to understand the underlying mechanisms of its metastatic progression and identify potential targets for therapy. Since their discovery in 1993, microRNAs (miRNAs) have emerged as important regulators of tumour progression and metastasis in various cancers, playing either oncogenic or tumour suppressor roles. In the following review, we discuss the roles of miRNAs that potentiate four key areas of breast cancer metastasis—angiogenesis, epithelial-mesenchymal transition, the Warburg effect and the tumour microenvironment. We then evaluate the recent developments in miRNA-based therapies in breast cancer, which have shown substantial promise in controlling tumour progression and metastasis. Yet, certain challenges must be overcome before these strategies can be implemented in clinical trials.
T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes
Authors: Oon Ming Liang , Lim Jing Quan , Lee Bernett , Leong Sai Mun , Soon Gwyneth Shook-Ting , Wong Zi Wei , Lim Evelyn Huizi , Li Zhenhua , Yeoh Allen Eng Juh , Chen Shangying , Ban Kenneth Hon Kim , Chung Tae-Hoon , Tan Soo-Yong , Chuang Shih-Sung , Kato Seiichi , Nakamura Shigeo , Takahashi Emiko , Ho Yong-Howe , Khoury Joseph D. , Au-Yeung Rex K. H. , Cheng Chee-Leong , Lim Soon-Thye , Chng Wee-Joo , Tripodo Claudio , Rotzschke Olaf , Ong Choon Kiat , Ng Siok-Bian
Published: January 2021

T-cell lymphomas arise from a single neoplastic clone and exhibit identical patterns of deletions in T-cell receptor (TCR) genes. Whole genome sequencing (WGS) data represent a treasure trove of information for the development of novel clinical applications. However, the use of WGS to identify clonal T-cell proliferations has not been systematically studied. In this study, based on WGS data, we identified monoclonal rearrangements (MRs) of T-cell receptors (TCR) genes using a novel segmentation algorithm and copy number computation. We evaluated the feasibility of this technique as a marker of T-cell clonality using T-cell lymphomas (TCL, n = 44) and extranodal NK/T-cell lymphomas (ENKTLs, n = 20), and identified 98% of TCLs with one or more TCR gene MRs, against 91% detected using PCR. TCR MRs were absent in all ENKTLs and NK cell lines. Sensitivity-wise, this platform is sufficiently competent, with MRs detected in the majority of samples with tumor content under 25% and it can also distinguish monoallelic from biallelic MRs. Understanding the copy number landscape of TCR using WGS data may engender new diagnostic applications in hematolymphoid pathology, which can be readily adapted to the analysis of B-cell receptor loci for B-cell clonality determination.
The Giant HECT E3 Ubiquitin Ligase HERC1 Is Aberrantly Expressed in Myeloid Related Disorders and It Is a Novel BCR-ABL1 Binding Partner
Authors: Ali Muhammad Shahzad , Panuzzo Cristina , Calabrese Chiara , Maglione Alessandro , Piazza Rocco , Cilloni Daniela , Saglio Giuseppe , Pergolizzi Barbara , Bracco Enrico
Published: January 2021

HERC E3 subfamily members are parts of the E3 ubiquitin ligases and key players for a wide range of cellular functions. Though the involvement of the Ubiquitin Proteasome System in blood disorders has been broadly studied, so far the role of large HERCs in this context remains unexplored. In the present study we examined the expression of the large HECT E3 Ubiquitin Ligase, HERC1, in blood disorders. Our findings revealed that HERC1 gene expression was severely downregulated both in acute and in chronic myelogenous leukemia at diagnosis, while it is restored after complete remission achievement. Instead, in Philadelphia the negative myeloproliferative neoplasm HERC1 level was peculiarly controlled, being very low in Primary Myelofibrosis and significantly upregulated in those Essential Thrombocytemia specimens harboring the mutation in the calreticulin gene. Remarkably, in CML cells HERC1 mRNA level was associated with the BCR-ABL1 kinase activity and the HERC1 protein physically interacted with BCR-ABL1. Furthermore, we found that HERC1 was directly tyrosine phosphorylated by the ABL kinase. Overall and for the first time, we provide original evidence on the potential tumor-suppressing or -promoting properties, depending on the context, of HERC1 in myeloid related blood disorders.
Parvovirus-Based Combinatorial Immunotherapy: A Reinforced Therapeutic Strategy against Poor-Prognosis Solid Cancers
Authors: Angelova Assia , Ferreira Tiago , Bretscher Clemens , Rommelaere Jean , Marchini Antonio
Published: January 2021

Resistance to anticancer treatments poses continuing challenges to oncology researchers and clinicians. The underlying mechanisms are complex and multifactorial. However, the immunologically “cold” tumor microenvironment (TME) has recently emerged as one of the critical players in cancer progression and therapeutic resistance. Therefore, TME modulation through induction of an immunological switch towards inflammation (“warming up”) is among the leading approaches in modern oncology. Oncolytic viruses (OVs) are seen today not merely as tumor cell-killing (oncolytic) agents, but also as cancer therapeutics with multimodal antitumor action. Due to their intrinsic or engineered capacity for overcoming immune escape mechanisms, warming up the TME and promoting antitumor immune responses, OVs hold the potential for creating a proinflammatory background, which may in turn facilitate the action of other (immunomodulating) drugs. The latter provides the basis for the development of OV-based immunostimulatory anticancer combinations. This review deals with the smallest among all OVs, the H-1 parvovirus (H-1PV), and focuses on H-1PV-based combinatorial approaches, whose efficiency has been proven in preclinical and/or clinical settings. Special focus is given to cancer types with the most devastating impact on life expectancy that urgently call for novel therapies.
Discovery of Functional Alternatively Spliced PKM Transcripts in Human Cancers
Authors: Li Xiangyu , Kim Woonghee , Arif Muhammad , Gao Chunxia , Hober Andreas , Kotol David , Strandberg Linnéa , Forsström Björn , Sivertsson Åsa , Oksvold Per , Turkez Hasan , Grøtli Morten , Sato Yusuke , Kume Haruki , Ogawa Seishi , Boren Jan , Nielsen Jens , Uhlen Mathias , Zhang Cheng , Mardinoglu Adil
Published: January 2021

Pyruvate kinase muscle type (PKM) is a key enzyme in glycolysis and plays an important oncological role in cancer. However, the association of PKM expression and the survival outcome of patients with different cancers is controversial. We employed systems biology methods to reveal prognostic value and potential biological functions of PKM transcripts in different human cancers. Protein products of transcripts were shown and detected by western blot and mass spectrometry analysis. We focused on different transcripts of PKM and investigated the associations between their mRNA expression and the clinical survival of the patients in 25 different cancers. We find that the transcripts encoding PKM2 and three previously unstudied transcripts, namely ENST00000389093, ENST00000568883, and ENST00000561609, exhibited opposite prognostic indications in different cancers. Moreover, we validated the prognostic effect of these transcripts in an independent kidney cancer cohort. Finally, we revealed that ENST00000389093 and ENST00000568883 possess pyruvate kinase enzymatic activity and may have functional roles in metabolism, cell invasion, and hypoxia response in cancer cells. Our study provided a potential explanation to the controversial prognostic indication of PKM, and could invoke future studies focusing on revealing the biological and oncological roles of these alternative spliced variants of PKM.
Predicting of Sentinel Lymph Node Status in Breast Cancer Patients with Clinically Negative Nodes: A Validation Study
Authors: Fanizzi Annarita , Pomarico Domenico , Paradiso Angelo , Bove Samantha , Diotaiuti Sergio , Didonna Vittorio , Giotta Francesco , La Forgia Daniele , Latorre Agnese , Pastena Maria Irene , Tamborra Pasquale , Zito Alfredo , Lorusso Vito , Massafra Raffaella
Published: January 2021

In the absence of lymph node abnormalities detectable on clinical examination or imaging, the guidelines provide for the dissection of the first axillary draining lymph nodes during surgery. It is not always possible to arrive at surgery without diagnostic doubts, and machine learning algorithms can support clinical decisions. The web calculator CancerMath (CM) allows you to estimate the probability of having positive lymph nodes valued on the basis of tumor size, age, histologic type, grading, expression of estrogen receptor, and progesterone receptor. We collected 993 patients referred to our institute with clinically negative results characterized by sentinel lymph node status, prognostic factors defined by CM, and also human epidermal growth factor receptor 2 (HER2) and Ki-67. Area Under the Curve (AUC) values obtained by the online CM application were comparable with those obtained after training its algorithm on our database. Nevertheless, by training the CM model on our dataset and using the same feature, we reached a sensitivity median value of 72%, whereas the online one was equal to 46%, despite a specificity reduction. We found that the addition of the prognostic factors Her2 and Ki67 could help improve performances on the classification of particular types of patients with the aim of reducing as much as possible the false positives that lead to axillary dissection. As showed by our experimental results, it is not particularly suitable for use as a support instrument for the prediction of metastatic lymph nodes on clinically negative patients.
Cascade Biocatalysis Designed for the Allylic Oxidation of α-Pinene
Authors: Gheorghita Giulia R. , Sora Cristina , Ion Sabina , Parvulescu Vasile I. , Tudorache Madalina
Published: January 2021

A biocatalytic cascade system using a cocktail of oxidoreductase enzymes (2-1B peroxidase and M120 laccase) was designed for the allylic oxidation of (+)-α-pinene into value-added products (e.g., verbenol and verbenone). The oxidative transformation involved a two-step process as follows: (+)-α-pinene was (i) oxidized on the allylic position with H2O2 mainly assisted by 2-1B peroxidase leading to verbenol as the principal reaction product, and (ii) directed to verbenone in the presence of M120 laccase responsible for further oxidation of verbenol to verbenone. The reaction environment was ensured by the acetate buffer (0.1 M, pH = 5). Optimum values for the experimental parameters (e.g., concentration of 2-1B peroxidase, M120 laccase, and H2O2) were set up. The biocatalytic cascade process was monitored for 24 h in order to evaluate the process pathway. Maximum performance under optimum conditions was reached after 5 h incubation time (e.g., 80% (+)-α-pinene conversion and 70% yield in verbenol). Therefore, the developed biocatalytic cascade system offered promising perspectives for (+)-α-pinene valorization.
Flower-Shaped C-Dots/Co3O4{111} Constructed with Dual-Reaction Centers for Enhancement of Fenton-Like Reaction Activity and Peroxymonosulfate Conversion to Sulfate Radical
Authors: Wen Zhibin , Zhu Qianqian , Zhou Jiali , Zhao Shudi , Wang Jinnan , Li Aimin , Chen Lifang , Bian Weilin
Published: January 2021

Novel flower-shaped C-dots/Co3O4{111} with dual-reaction centers were constructed to improve the Fenton-like reaction activity and peroxymonosulfate (PMS) conversion to sulfate radicals. Due to the exposure of a high surface area and Co3O4{111} facets, flower-shaped C-dots/Co3O4{111} could provide more Co(II) for PMS activation than traditional spherical Co3O4{110}. Meanwhile, PMS was preferred for adsorption on Co3O4{111} facets because of a high adsorption energy and thereby facilitated the electron transfer from Co(II) to PMS. More importantly, the Co–O–C linkage between C-dots and Co3O4{111} induced the formation of the dual-reaction center, which promoted the production of reactive organic radicals (R•). PMS could be directly reduced to SO4−• by R• over C-dots. On the other hand, electron transferred from R• to Co via Co–O–C linkage could accelerate the redox of Co(II)/(III), avoiding the invalid decomposition of PMS. Thus, C-dots doped on Co3O4{111} improved the PMS conversion rate to SO4−• over the single active site, resulting in high turnover numbers (TONs). In addition, TPR analysis indicated that the optimal content of C-dots doped on Co3O4{111} is 2.5%. More than 99% of antibiotics and dyes were degraded over C-dots/Co3O4{111} within 10 min. Even after six cycles, C-dots/Co3O4{111} still remained a high catalytic activity.
Improving Product Yield in the Direct Carboxylation of Glycerol with CO2 through the Tailored Selection of Dehydrating Agents
Authors: Razali Nurul , McGregor James
Published: January 2021

Improved yields of, and selectivities to, value-added products synthesised from glycerol are shown to be achieved through the judicious selection of dehydrating agents and through the development of improved catalysts. The direct carboxylation of glycerol with CO2 over lanthanum-based catalysts can yield glycerol carbonate in the presence of basic species, or acetins in the presence of acidic molecules. The formation of glycerol carbonate is thermodynamically limited; removal of produced water shifts the chemical equilibrium to the product side. Acetonitrile, benzonitrile and adiponitrile have been investigated as basic dehydrating agents to promote glycerol carbonate synthesis. In parallel, acetic anhydride has been studied as an acidic dehydrating agent to promote acetin formation. Alongside this, the influence of the catalyst synthesis method has been investigated allowing links between the physicochemical properties of the catalyst and catalytic performance to be determined. The use of acetonitrile and La catalysts allows the results for the novel dehydrating agents to be benchmarked against literature data. Notably, adiponitrile exhibits significantly enhanced performance over other dehydrating agents, e.g., achieving a 5-fold increase in glycerol carbonate yield with respect to acetonitrile. This is in part ascribed to the fact that each molecule of adiponitrile has two nitrile functionalities to promote the reactive removal of water. In addition, mechanistic insights show that adiponitrile results in reduced by-product formation. Considering by-product formation, 4-hydroxymethyl(oxazolidin)-2-one (4-HMO) has, for the first time, been observed in all reaction systems using cyanated species. Studies investigating the influence of the catalyst synthesis route show a complex relationship between surface basicity, surface area, crystallite phase and reactivity. These results suggest alternative strategies to maximise the yield of desirable products from glycerol through tailoring the reaction chemistry and by-product formation via an appropriate choice of dehydrating agents and co-reagents.
Abatement of 1,2,4-Trichlorobencene by Wet Peroxide Oxidation Catalysed by Goethite and Enhanced by Visible LED Light at Neutral pH
Authors: Lorenzo David , Santos Aurora , Sánchez-Yepes Andrés , Conte Leandro Óscar , Domínguez Carmen María
Published: January 2021

There is significant environmental concern about chlorinated organic compounds (COCs) in wastewater, surface water, and groundwater due to their low biodegradability and high persistence. In this work, 1,2,4-trichlorobenzene (124-TCB) was selected as a model compound to study its abatement using wet peroxide oxidation at neutral pH with goethite as a heterogeneous catalyst, which was enhanced with visible monochromatic light-emitting diode (LED) light (470 nm). A systematic study of the main operating variables (oxidant and catalyst concentration and irradiance) was accomplished to investigate their influence in the abatement of 124-TCB in water. The reaction was carried out in a well-mixed reactor of glass irradiated by a visible LED light. The hydrogen peroxide concentration was tested from 0 to 18 mM, the goethite concentration within the range 0.1–1.0 g·L−1 and the irradiance from 0.10 to 0.24 W·cm−2 at neutral pH. It was found that this oxidation method is a very efficient technique to abate 124-TCB, reaching a pollutant conversion of 0.9 when using 0.1 g·L−1 of goethite, 18 mM of H2O2, and 0.24 of W·cm−2. Moreover, the system performance was evaluated using the photonic efficiency (ratio of the moles of 124-TCB abated and the moles of photons arriving at the reactor window). The maximum photonic efficiencies were obtained using the lowest lamp powers and moderate to high catalyst loads.
C-,N- and S-Doped TiO2 Photocatalysts: A Review
Authors: Piątkowska Aleksandra , Janus Magdalena , Szymański Kacper , Mozia Sylwia
Published: January 2021

This article presents an overview of the reports on the doping of TiO2 with carbon, nitrogen, and sulfur, including single, co-, and tri-doping. A comparison of the properties of the photocatalysts synthesized from various precursors of TiO2 and C, N, or S dopants is summarized. Selected methods of synthesis of the non-metal doped TiO2 are also described. Furthermore, the influence of the preparation conditions on the doping mode (interstitial or substitutional) with reference to various types of the modified TiO2 is summarized. The mechanisms of photocatalysis for the different modes of the non-metal doping are also discussed. Moreover, selected applications of the non-metal doped TiO2 photocatalysts are shown, including the removal of organic compounds from water/wastewater, air purification, production of hydrogen, lithium storage, inactivation of bacteria, or carbon dioxide reduction.
Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists
Authors: Depommier Clara , Vitale Rosa Maria , Iannotti Fabio Arturo , Silvestri Cristoforo , Flamand Nicolas , Druart Céline , Everard Amandine , Pelicaen Rudy , Maiter Dominique , Thissen Jean-Paul , Loumaye Audrey , Hermans Michel P. , Delzenne Nathalie M. , de Vos Willem M. , Di Marzo Vincenzo , Cani Patrice D.
Published: January 2021

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.
Adenine-Based Purines and Related Metabolizing Enzymes: Evidence for Their Impact on Tumor Extracellular Vesicle Activities
Authors: Di Iorio Patrizia , Ciccarelli Renata
Published: January 2021

Extracellular vesicles (EVs), mainly classified as small and large EVs according to their size/origin, contribute as multi-signal messengers to intercellular communications in normal/pathological conditions. EVs are now recognized as critical players in cancer processes by promoting transformation, growth, invasion, and drug-resistance of tumor cells thanks to the release of molecules contained inside them (i.e., nucleic acids, lipids and proteins) into the tumor microenvironment (TME). Interestingly, secretion from donor cells and/or uptake of EVs/their content by recipient cells are regulated by extracellular signals present in TME. Among those able to modulate the EV-tumor crosstalk, purines, mainly the adenine-based ones, could be included. Indeed, TME is characterized by high levels of ATP/adenosine and by the presence of enzymes deputed to their turnover. Moreover, ATP/adenosine, interacting with their own receptors, can affect both host and tumor responses. However, studies on whether/how the purinergic system behaves as a modulator of EV biogenesis, release and functions in cancer are still poor. Thus, this review is aimed at collecting data so far obtained to stimulate further research in this regard. Hopefully, new findings on the impact of adenine purines/related enzymes on EV functions may be exploited in tumor management uncovering novel tumor biomarkers and/or druggable targets.
Advances in Plant Autophagy
Authors: Sirko Agnieszka , Masclaux-Daubresse Céline
Published: January 2021

Ubiquitin–proteasome and lysosome–autophagy are the two main cellular degradation systems controlling cellular homeostasis in eukaryotes [...]
Acknowledgment to Reviewers of Chemosensors in 2020
Authors:   Chemosensors Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Chemosensors maintains its standards for the high quality of its published papers [...]
Does Additional Physical Education Improve Exam Performance at the End of Compulsory Education? A Secondary Analysis from a Natural Experiment: The CHAMPS-Study DK
Authors: Tarp Jakob , Gejl Anne Kær , Hillman Charles H. , Wedderkopp Niels , Bugge Anna
Published: January 2021

It remains unclear whether the provision of additional physical activity in school improves academic outcomes. We conducted a secondary analysis of the Childhood Health, Activity, and Motor Performance School Study Denmark (CHAMPS-study DK), a natural experiment based on a trebling of curricular physical education, to investigate whether children receiving additional physical education performed better on their academic exams at the conclusion of compulsory education (i.e., 9th grade). Children from six intervention schools received 3–7 years of exposure to 270 weekly minutes of physical education (sports schools), while children from four control schools received the 90-min national standard (normal schools). Academic performance was based on the standard Danish 7-point scale (ranging from −03 to 12) and retrieved from national registries. The primary outcome was calculated as the average exam grade. Comparisons of participants at sports and normal schools were adjusted for individual socioeconomic factors and school-level academic environment. There were no differences in the pooled exam performance among 691 sports- and 510 normal-school participants (0.20 (95% confidence interval: −0.12 to 0.52)). Results for subject-specific exams indicated similar results. This analysis from a non-randomized natural experiment did not provide evidence that simply adding additional physical education is sufficient to affect academic performance relative to the national standard.
Cytotoxicity and Genotoxicity of Metal Oxide Nanoparticles in Human Pluripotent Stem Cell-Derived Fibroblasts
Authors: Handral Harish , Ashajyothi C. , Sriram Gopu , Kelmani Chandrakanth , Dubey Nileshkumar , Cao Tong
Published: January 2021

Advances in the use of nanoparticles (NPs) has created promising progress in biotechnology and consumer-care based industry. This has created an increasing need for testing their safety and toxicity profiles. Hence, efforts to understand the cellular responses towards nanomaterials are needed. However, current methods using animal and cancer-derived cell lines raise questions on physiological relevance. In this aspect, in the current study, we investigated the use of pluripotent human embryonic stem cell- (hESCs) derived fibroblasts (hESC-Fib) as a closer representative of the in vivo response as well as to encourage the 3Rs (replacement, reduction and refinement) concept for evaluating the cytotoxic and genotoxic effects of zinc oxide (ZnO), titanium dioxide (TiO2) and silicon-dioxide (SiO2) NPs. Cytotoxicity assays demonstrated that the adverse effects of respective NPs were observed in hESC-Fib beyond concentrations of 200 µg/mL (SiO2 NPs), 30 µg/mL (TiO2 NPs) and 20 µg/mL (ZnO NPs). Flow cytometry results correlated with increased apoptosis upon increase in NP concentration. Subsequently, scratch wound assays showed ZnO (10 µg/mL) and TiO2 (20 µg/mL) NPs inhibit the rate of wound coverage. DNA damage assays confirmed TiO2 and ZnO NPs are genotoxic. In summary, hESC-Fib could be used as an alternative platform to understand toxicity profiles of metal oxide NPs.