bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the Strength Parameters of Drilling Pumps during the Formation of Contact Stresses in Gears
Authors: Savinkin Vitaliy Vladimirovich , Kolisnichenko Sergey Nikolayevich , Sandu Andrei Victor , Ivanova Olga Vladimirovna , Vizureanu Petrica , Zhumekenova Zaure Zhetpysbayevna
Published: July 2021

The relevance of this research lies in the need to develop scientifically based methods for calculating and designing a transmission shaft with a hardened coating of increased strength and service life of a core drilling pump drive that can allow for a redistributing of resistance forces along the contact surfaces of the gear. This relevance is confirmed by the need to improve domestic methods for designing drive shafts of increased reliability which can ensure the development of frozen soils during deposits exploration. The purpose of the research is to increase the energy efficiency and service life of the high-loaded drive gear teeth of core drilling pump transmission shafts by justifying the critical loads and stresses in hardened gear coatings acting under intense wear of the contact surface with a broken contact symmetry. The criteria for the effective wear area with an uneven contact cross-section at the maximum bending moments of the transmission shaft of the drilling pump were justified and presented in the work. Additionally, the process of interaction of the transmission shaft gear teeth with the eccentric shaft gear at uneven axial torques was investigated. The effective power (Ng) of the gearing of the drive transmission shaft gear and the eccentric shaft gear, which characterizes the energy consumption of the drill bit depth stroke, was justified. This work also proposes a method of substantiating the technological and power parameters of the transmission shaft by using Legendre polynomials. A nomographic chart was developed for the determination of the dependence of the contact stress base cycles on the change in the load distribution factor and the contact spot deviation factor from the design axis λ.
Using Task Farming to Optimise a Street-Scale Resolution Air Quality Model of the West Midlands (UK)
Authors: Zhong Jian , Hood Christina , Johnson Kate , Stocker Jenny , Handley Jonathan , Wolstencroft Mark , Mazzeo Andrea , Cai Xiaoming , Bloss William James
Published: July 2021

High resolution air quality models combining emissions, chemical processes, dispersion and dynamical treatments are necessary to develop effective policies for clean air in urban environments, but can have high computational demand. We demonstrate the application of task farming to reduce runtime for ADMS-Urban, a quasi-Gaussian plume air dispersion model. The model represents the full range of source types (point, road and grid sources) occurring in an urban area at high resolution. Here, we implement and evaluate the option to automatically split up a large model domain into smaller sub-regions, each of which can then be executed concurrently on multiple cores of a HPC or across a PC network, a technique known as task farming. The approach has been tested for a large model domain covering the West Midlands, UK (902 km2), as part of modelling work in the WM-Air (West Midlands Air Quality Improvement Programme) project. Compared to the measurement data, overall, the model performs well. Air quality maps for annual/subset averages and percentiles are generated. For this air quality modelling application of task farming, the optimisation process has reduced weeks of model execution time to approximately 35 h for a single model configuration of annual calculations.
Analysis of Mineral Aerosol in the Surface Layer over the Caspian Lowland Desert by the Data of 12 Summer Field Campaigns in 2002–2020
Authors: Chkhetiani Otto G. , Vazaeva Natalia V. , Chernokulsky Alexander V. , Shukurov Karim A. , Gubanova Dina P. , Artamonova Maria S. , Maksimenkov Leonid O. , Kozlov Fedor A. , Kuderina Tatyana M.
Published: July 2021

In-situ knowledge on characteristics of mineral aerosols is important for weather and climate prediction models, particularly for modeling such processes as the entrainment, transport and deposition of aerosols. However, field measurements of the dust emission flux, dust size distribution and its chemical composition under realistic wind conditions remain rare. In this study, we present experimental data over annual expeditions in the arid and semi-arid zones of the Caspian Lowland Desert (Kalmykia, south of Russia); we evaluate characteristics of mineral aerosol concentration and fluxes, estimate its chemical composition and calculate its long-distance transport characteristics. The mass concentration in different years ranges from several tens to several hundred of μg m−3. The significant influence of wind velocity on the value of mass and counting concentration and on the proposed entrainment mechanisms is confirmed. An increased content of anthropogenic elements (S, Sn, Pb, Bi, Mo, Ag, Cd, Hg, etc.), which is characteristic for all observation points in the south of the European Russia, is found. The trajectory analysis show that long-range air particles transport from the Caspian Lowland Desert to the central regions of European Russia tends to increase in the recent decades.
Sarcopenia Worsening One Month after Transarterial Radioembolization Predicts Progressive Disease in Patients with Advanced Hepatocellular Carcinoma
Authors: Vallati Giulio Eugenio , Trobiani Claudio , Teodoli Leonardo , Lai Quirino , Cappelli Federico , Ungania Sara , Catalano Carlo , Lucatelli Pierleone
Published: July 2021

(1) Background: To demonstrate correlation between skeletal muscle depletion measured before and after one month of TARE treatment and its induced local response rate. (2) Material and methods: For this retrospective, single center study, we evaluated 86 patients with HCC treated with TARE. Sarcopenia status was measured using the psoas muscle index (PMI). The PMI was calculated according to the formula: PMI [mm/m2]: [(minor diameter of left psoas + major diameter of left psoas + minor diameter of right psoas + major diameter of right psoas)/4]/height in m2. Population was divided in two groups according to the delta value of PMI measured at the time of TARE and one month after TARE, a group in which the delta PMI was stable or increased (No-Sarcopenia group; n = 42) vs. a group in which the delta-PMI decreased (Sarcopenia group; n = 44). Patient response was evaluated at 1, 3 and 6 months after TARE treatment with CT/MRI. (3) Results: When the radiological response of the tumor was evaluated according to the mRECIST criteria, the two groups were similar in terms of rates of complete response (p = 0.42), partial response (p = 0.26) and stable disease (p = 0.59). Progressive disease (PD) was more commonly observed in the Sarcopenia group (38.6% vs. 11.9%; p = 0.006). (4) Conclusions: Worsening of sarcopenia status measured one month after TARE is able to predict patients who will undergo disease progression.
Modeling Cardiomyopathies in a Dish: State-of-the-Art and Novel Perspectives on hiPSC-Derived Cardiomyocytes Maturation
Authors: Lodola Francesco , De Giusti Verónica Celeste , Maniezzi Claudia , Martone Daniele , Stadiotti Ilaria , Sommariva Elena , Maione Angela Serena
Published: July 2021

The stem cell technology and the induced pluripotent stem cells (iPSCs) production represent an excellent alternative tool to study cardiomyopathies, which overcome the limitations associated with primary cardiomyocytes (CMs) access and manipulation. CMs from human iPSCs (hiPSC–CMs) are genetically identical to patient primary cells of origin, with the main electrophysiological and mechanical features of CMs. The key issue to be solved is to achieve a degree of structural and functional maturity typical of adult CMs. In this perspective, we will focus on the main differences between fetal-like hiPSC-CMs and adult CMs. A viewpoint is given on the different approaches used to improve hiPSC-CMs maturity, spanning from long-term culture to complex engineered heart tissue. Further, we outline limitations and future developments needed in cardiomyopathy disease modeling.
Expressional Profiling of TEX11, ESRα and BOLL Genes in Yak under Different Feeding Conditions
Authors: Kalwar Qudratullah , Chu Min , Ahmad Anum Ali , Xiong Lin , Zhang Yongfeng , Ding Xuezhi , Yan Ping
Published: July 2021

Previous studies have demonstrated that nutrition plays a crucial part in improving the reproductive potential of farm animals; however, there is currently no research on the transcription and expression profiling of genes in yaks under different feeding conditions. Therefore, this research was planned to compare the transcription and expression profiles of TEX11, ESRα, and BOLL in yaks under natural grazing with concentrate supplementation (NG + CS) and NG without concentrate supplementation. The transcription and expressional levels of TEX11, ESRα, and BOLL mRNA were explored from the testes of yaks using qPCR, Western blotting, immunofluorescence, and immunochemistry. The results of the qPCR illustrated that the transcription levels of TEX11, ESRα, and BOLL were upregulated in the NG + CS group compared to those in the NG group. Moreover, the results of the immunochemistry and immunofluorescence showed that the expression of TEX11, ESRα, and BOLL proteins increased after concentrate supplementation. Meanwhile, ESRα protein levels were lower in the testes and epididymides of yaks in the NG group than in those in the NG + CS group. Similarly, BOLL protein expression was higher in the testes and epididymides of the NG + CS group, but its expression was lower in the epididymides of the NG group. Furthermore, Western blotting showed that the molecular weights of ESRα and BOLL proteins were 64 kDa and 31 kDa, respectively. Finally, in the conclusion we summarize how a proper level of dietary energy supplementation can improve the reproductive potential of yaks by upregulating genes related to reproduction.
Cholinesterase Research
Authors: Korabecny Jan , Soukup Ondrej
Published: July 2021

Cholinesterases are fundamental players in the peripheral and central nervous systems [...]
Physical Frailty/Sarcopenia as a Key Predisposing Factor to Coronavirus Disease 2019 (COVID-19) and Its Complications in Older Adults
Authors: Ali Amira Mohammed , Kunugi Hiroshi
Published: July 2021

The tremendously rising numbers of aged populations are associated with a heightened risk for motor and functional declines. Sarcopenia is an active age-related process that involves progressive losses of skeletal muscle mass, muscle strength, and muscle function. Muscle failure is a major cause of frailty, disability, falls, hospitalization, dependency, institutionalization, and low quality of life in older seniors. Therefore, sarcopenia considerably heightens the annual cost of care worldwide. This narrative review elaborates on sarcopenia as a deleterious condition in old age while spotting the light on its association with the coronavirus disease 2019 (COVID-19). It discusses its pathophysiology and the most possible options for preventing and treating sarcopenia. The literature shows that the dynamic of sarcopenia is complex, involving multifaceted physiological alterations relevant to aging, unhealthy behaviors (e.g., undernutrition or inadequate dietary intake and physical inactivity/immobility or sedentary lifestyle), and multiple pathogenic conditions such as metabolic, inflammatory, and endocrinal disorders. Frail individuals express nutritional deficiencies, immune deficit, oxidative stress, metabolic alterations, gut microbial alterations, neurological insult, etc. Such physiological dysfunctions are closely linked to increased vulnerability to COVID-19 among older adults and people with non-communicable diseases such as diabetes mellitus, cardiovascular disorders, and obesity. Available studies report higher occurrence of severe COVID-19 and COVID-19-related complications (ICU admission, mechanical ventilation, and in-hospital mortality) among frail compared with non-frail and prefrail individuals. Effective pharmacological treatments of sarcopenia are not currently available. However, physical activity and nutritional interventions (e.g., fast digestive proteins, vitamin D, and natural products such as bee products) may prevent the development of sarcopenia in early stages of the disease or limit disease progress. Such interventions may also lower vulnerability to COVID-19.
Innate and Adaptive Immune Assessment at Admission to Predict Clinical Outcome in COVID-19 Patients
Authors: San Segundo David , Arnáiz de las Revillas Francisco , Lamadrid-Perojo Patricia , Comins-Boo Alejandra , González-Rico Claudia , Alonso-Peña Marta , Irure-Ventura Juan , Olmos José Manuel , Fariñas María Carmen , López-Hoyos Marcos
Published: July 2021

During the COVID-19 pandemic, many studies have been carried out to evaluate different immune system components to search for prognostic biomarkers of the disease. A broad multiparametric antibody panel of cellular and humoral components of the innate and the adaptative immune response in patients with active SARS-CoV-2 infection has been evaluated in this study. A total of 155 patients were studied at admission into our center and were categorized according to the requirement of oxygen therapy as mild or severe (the latter being those with the requirement). The patients with severe disease were older and had high ferritin, D-dimer, C-reactive protein, troponin, interleukin-6 (IL-6) levels, and neutrophilia with lymphopenia at admission. Moreover, the patients with mild symptoms had significantly increased circulating non-classical monocytes, innate lymphoid cells, and regulatory NK cells. In contrast, severe patients had a low frequency of Th1 and regulatory T cells with increased activated and exhausted CD8 phenotype (CD8+CD38+HLADR+ and CD8+CD27−CD28−, respectively). The predictive model included age, ferritin, D-dimer, lymph counts, C4, CD8+CD27−CD28−, and non-classical monocytes in the logistic regression analysis. The model predicted severity with an area under the curve of 78%. Both innate and adaptive immune parameters could be considered potential predictive biomarkers of the prognosis of COVID-19 disease.
Differential Diagnosis and Treatment of Itching in Children and Adolescents
Authors: Kang Seok-Young , Um Ji-Young , Chung Bo-Young , Kim Jin-Cheol , Park Chun-Wook , Kim Hye-One
Published: July 2021

Itching is prevalent in children with skin disorders and associated with effects on their mood, quality of life, and social functioning. Surprisingly, there are no data on childhood prevalence of pruritus in the general population. The aim of this article is to explore the epidemiology, clinical manifestation, and treatment for itch (pruritus) in the pediatric population (from infancy to adolescence), and to be helpful to primary care physicians who assess and diagnose pediatric patients with itching. In this study, we searched for specific keywords using PubMed and MEDLINE (Ovid) and, then, refined the retrieved searches for each cause and treatment. As a result of reviewing the literature, atopic dermatitis was shown to be the most common cause of itching, especially during infancy and through preschool. Not only skin disorders but also systemic diseases, drugs, and postburn states can predispose an individual to itching in childhood. There are traditional and newly developed treatment modalities for itching in pediatric patients. However, because the pharmacokinetics and pharmacodynamics of childhood are different from those of adults, the medications for itching have to be applied carefully for these age groups. There are many areas to be elucidated regarding the prevalence and objective assessment of pruritus in pediatric patients. Moreover, the safety profiles of medications in the pediatric population need to be better understood. Further studies to investigate itching in childhood are warranted.
Expression of miRNAs Targeting ATP Binding Cassette Transporter 1 (ABCA1) among Patients with Significant Carotid Artery Stenosis
Authors: Jeong Seonjeong , Jun Ji Hye , Kim Jae Yeon , Park Hee Jung , Cho Yong-Pil , Kim Gi Jin
Published: July 2021

Background: Carotid artery stenosis is a dynamic process associated with an increased risk of cardiovascular events. However, knowledge of biomarkers useful for identifying and quantifying high-risk carotid plaques associated with the increased incidence of cerebrovascular events is insufficient. Therefore, the objectives of this study were to evaluate the expression of ATP binding cassette transporter 1 (ABCA1) and validate its target microRNA (miRNA) candidates in human carotid stenosis arteries to identify its potential as a biomarker. Methods: In human carotid stenosis arterial tissues and plasma, the expression of ABCA1 and its target miRNAs (miRNA-33a-5p, 33b-5p, and 148a-3p) were evaluated by quantitative real time-polymerase chain reaction (qRT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). Results: The expression of ABCA1 was significantly decreased in the plasma of stenosis patients, but its expression was not different in arterial tissues (p < 0.05). However, significantly more target miRNAs were secreted by stenosis patients than normal patients (p < 0.05). Interestingly, lipotoxicity induced by the oleic and palmitic acid (OAPA) or lipopolysaccharide (LPS) treatment of human umbilical vein endothelial cells (HUVECs) dramatically enhanced the gene expression of adipogenic and inflammatory factors, whereas ABCA1 expression was significantly decreased. Conclusions: Therefore, miRNA-33a-5p, 33b-5p, and 148a-3p represent possible biomarkers of carotid artery stenosis by directly targeting ABCA1.
Anti-Inflammatory Properties of Diet: Role in Healthy Aging
Authors: Stromsnes Kristine , Correas Angela G. , Lehmann Jenny , Gambini Juan , Olaso-Gonzalez Gloria
Published: July 2021

Inflammation is a physiological process involved in the defenses of the body and the repair of tissues. It is acutely activated by infections, trauma, toxins, or allergic reactions. However, if it becomes chronic, inflammation can end up stimulating the development of diseases such as cardiovascular disease, autoimmune disease, neurological disease, or cancer. Additionally, during aging, inflammation becomes increasingly more chronic. Furthermore, we found that certain foods, such as saturated fats, have pro-inflammatory activity. Taking this into account, in this review we have discussed different diets with possible anti-inflammatory activity, the commonly ingested components of each diet and their active compounds. In addition, we have proposed some dietary guidelines, as well as a list of compounds present in foods with anti-inflammatory activity, outlining how to combine them to achieve optimal anti-inflammatory effects. Therefore, we can conclude that the compounds in our diet with anti-inflammatory activity could help alleviate the inflammatory processes derived from diseases and unhealthy diets, and thereby promote healthy aging.
Bradykinin, as a Reprogramming Factor, Induces Transdifferentiation of Brain Astrocytes into Neuron-like Cells
Authors: Lee Tsong-Hai , Liu Pei-Shan , Wang Su-Jane , Tsai Ming-Ming , Shanmugam Velayuthaprabhu , Hsieh Hsi-Lung
Published: July 2021

Kinins are endogenous, biologically active peptides released into the plasma and tissues via the kallikrein-kinin system in several pathophysiological events. Among kinins, bradykinin (BK) is widely distributed in the periphery and brain. Several studies on the neuro-modulatory actions of BK by the B2BK receptor (B2BKR) indicate that this neuropeptide also functions during neural fate determination. Previously, BK has been shown to induce differentiation of nerve-related stem cells into neuron cells, but the response in mature brain astrocytes is unknown. Herein, we used rat brain astrocyte (RBA) to investigate the effect of BK on cell transdifferentiation into a neuron-like cell morphology. Moreover, the signaling mechanisms were explored by zymographic, RT-PCR, Western blot, and immunofluorescence staining analyses. We first observed that BK induced RBA transdifferentiation into neuron-like cells. Subsequently, we demonstrated that BK-induced RBA transdifferentiation is mediated through B2BKR, PKC-δ, ERK1/2, and MMP-9. Finally, we found that BK downregulated the astrocytic marker glial fibrillary acidic protein (GFAP) and upregulated the neuronal marker neuron-specific enolase (NSE) via the B2BKR/PKC-δ/ERK pathway in the event. Therefore, BK may be a reprogramming factor promoting brain astrocytic transdifferentiation into a neuron-like cell, including downregulation of GFAP and upregulation of NSE and MMP-9 via the B2BKR/PKC-δ/ERK cascade. Here, we also confirmed the transdifferentiative event by observing the upregulated neuronal nuclear protein (NeuN). However, the electrophysiological properties of the cells after BK treatment should be investigated in the future to confirm their phenotype.
BTK, NUTM2A, and PRPF19 Are Novel KMT2A Partner Genes in Childhood Acute Leukemia
Authors: Zerkalenkova Elena , Lebedeva Svetlana , Borkovskaia Aleksandra , Soldatkina Olga , Plekhanova Olga , Tsaur Grigory , Maschan Michael , Maschan Aleksey , Novichkova Galina , Olshanskaya Yulia
Published: July 2021

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with acute leukemias, especially in infants. KMT2A is rearranged with a big variety of partner genes and in multiple breakpoint locations. Detection of all types of KMT2A rearrangements is an essential part of acute leukemia initial diagnostics and follow-up, as it has a strong impact on the patients’ outcome. Due to their high heterogeneity, KMT2A rearrangements are most effectively uncovered by next-generation sequencing (NGS), which, however, requires a thorough prescreening by cytogenetics. Here, we aimed to characterize uncommon KMT2A rearrangements in childhood acute leukemia by conventional karyotyping, FISH, and targeted NGS on both DNA and RNA level with subsequent validation. As a result of this comprehensive approach, three novel KMT2A rearrangements were discovered: ins(X;11)(q26;q13q25)/KMT2A-BTK, t(10;11)(q22;q23.3)/KMT2A-NUTM2A, and inv(11)(q12.2q23.3)/KMT2A-PRPF19. These novel KMT2A-chimeric genes expand our knowledge of the mechanisms of KMT2A-associated leukemogenesis and allow tracing the dynamics of minimal residual disease in the given patients.
Microglia: The Real Foe in HIV-1-Associated Neurocognitive Disorders?
Authors: Borrajo López Ana , Penedo Maria Aránzazu , Rivera-Baltanas Tania , Pérez-Rodríguez Daniel , Alonso-Crespo David , Fernández-Pereira Carlos , Olivares José Manuel , Agís-Balboa Roberto Carlos
Published: July 2021

The current use of combined antiretroviral therapy (cART) is leading to a significant decrease in deaths and comorbidities associated with human immunodeficiency virus type 1 (HIV-1) infection. Nonetheless, none of these therapies can extinguish the virus from the long-lived cellular reservoir, including microglia, thereby representing an important obstacle to curing HIV. Microglia are the foremost cells infected by HIV-1 in the central nervous system (CNS) and are believed to be involved in the development of HIV-1-associated neurocognitive disorder (HAND). At present, the pathological mechanisms contributing to HAND remain unclear, but evidence suggests that removing these infected cells from the brain, as well as obtaining a better understanding of the specific molecular mechanisms of HIV-1 latency in these cells, should help in the design of new strategies to prevent HAND and achieve a cure for these diseases. The goal of this review was to study the current state of knowledge of the neuropathology and research models of HAND containing virus susceptible target cells (microglial cells) and potential pharmacological treatment approaches under investigation.
An Analysis of Heterogeneity in German Speaking Birdwatchers Reveals Three Distinct Clusters and Gender Differences
Authors: Randler Christoph
Published: July 2021

The purpose of this study was to segment birdwatchers into clusters. Members from a wide range of bird related organizations, from highly specialized birders as well as Facebook bird group members were studied to provide a diverse dataset (n = 2766; 50.5% men). Birding specialization was measured with a battery of questionnaires. Birding specialization encompassed the three constructs of skill/competence, behavior, personal and behavioral commitment. Additionally, involvement, measured by centrality to lifestyle, attraction, social bonding, and identity, was used. The NbClust analyses showed that a three-cluster solution was the optimal solution. Then, k-means cluster analysis was applied on three groups: casual/novice, intermediate, and specialist/advanced birdwatchers. More men than women were in the specialist/advanced group and more women than men in the casual/novice group. As a conclusion, this study confirms a three-cluster solution for segmenting German birdwatchers based on a large and diverse sample and a broad conceptualization of the construct birding specialization. These data can be used to address different target audiences (novices, advanced birders) with different programs, e.g., in nature conservation.
Microglial Metamorphosis in Three Dimensions in Virus Limbic Encephalitis: An Unbiased Pictorial Representation Based on a Stereological Sampling Approach of Surveillant and Reactive Microglia
Authors: da Silva Creão Leonardo Sávio , Neto João Bento Torres , de Lima Camila Mendes , dos Reis Renata Rodrigues , de Sousa Aline Andrade , dos Santos Zaire Alves , Diniz José Antonio Picanço , Diniz Daniel Guerreiro , Diniz Cristovam Wanderley Picanço
Published: July 2021

Microglia influence pathological progression in neurological diseases, reacting to insults by expressing multiple morphofunctional phenotypes. However, the complete morphological spectrum of reactive microglia, as revealed by three-dimensional microscopic reconstruction, has not been detailed in virus limbic encephalitis. Here, using an anatomical series of brain sections, we expanded on an earlier Piry arbovirus encephalitis study to include CA1/CA2 and assessed the morphological response of homeostatic and reactive microglia at eight days post-infection. Hierarchical cluster and linear discriminant function analyses of multimodal morphometric features distinguished microglial morphology between infected animals and controls. For a broad representation of the spectrum of microglial morphology in each defined cluster, we chose representative cells of homeostatic and reactive microglia, using the sum of the distances of each cell in relation to all the others. Based on multivariate analysis, reactive microglia of infected animals showed more complex trees and thicker branches, covering a larger volume of tissue than in control animals. This approach offers a reliable representation of microglia dispersion in the Euclidean space, revealing the morphological kaleidoscope of surveillant and reactive microglia morphotypes. Because form precedes function in nature, our findings offer a starting point for research using integrative methods to understand microglia form and function.
Rhesus Monkeys Have a Counting Ability and Can Count from One to Six
Authors: Sun Weiming , Li Baoming , Ma Chaolin
Published: July 2021

Counting ability is one of the many aspects of animal cognition and has enjoyed great interest over the last couple of decades. The impetus for studying counting ability in nonhuman animals has likely come from more than a general interest in animal cognition, as the analysis of animal abilities amplifies our understanding of human cognition. In addition, a model animal with the ability to count could be used to replace human subjects in related studies. Here we designed a behavioral paradigm to train rhesus monkeys to count 1-to-6 visual patterns presented sequentially with long and irregular interpattern intervals on a touch screen. The monkeys were required to make a response to the sixth pattern exclusively, inhibiting response to any patterns appearing at other ordinal positions. All stimulus patterns were of the same size, color, location, and shape to prevent monkeys making the right choice due to non-number physical cues. In the long delay period, the monkey had to enumerate how many patterns had been presented sequentially and had to remember in which ordinal position the current pattern was located. Otherwise, it was impossible for them to know which pattern was the target one. The results show that all three monkeys learned to correctly choose the sixth pattern within 3 months. This study provides convincing behavioral evidence that rhesus monkeys may have the capacity to count.
Understanding the Emotional Impact of GIFs on Instagram through Consumer Neuroscience
Authors: Rúa-Hidalgo Idoia , Galmes-Cerezo Maria , Cristofol-Rodríguez Carmen , Aliagas Irene
Published: July 2021

The ability of GIFs to generate emotionality in social media marketing strategies is analyzed. The aim of this work is to show how neuroscience research techniques can be integrated into the analysis of emotions, improving the results and helping to guide actions in social networks. This research is structured in two phases: an experimental study using automated biometric analysis (facial coding, GSR and eye tracking) and an analysis of declared feelings in the comments of Instagram users. Explicit valence, type of emotion, length of comment and proportion of emojis are extracted. The results indicate that the explicit measure of emotional valence shows a higher and more positive emotional level than the implicit one. This difference is influenced differently by the engagement and the proportion of emojis in the comment. A further step has been taken in the measurement of user emotionality in social media campaigns, including not only content analysis, but also providing new insights thanks to neuromarketing.
Involvement of HIF-1α in the Detection, Signaling, and Repair of DNA Double-Strand Breaks after Photon and Carbon-Ion Irradiation
Authors: Wozny Anne-Sophie , Gauthier Arnaud , Alphonse Gersende , Malésys Céline , Varoclier Virginie , Beuve Michael , Brichart-Vernos Delphine , Magné Nicolas , Vial Nicolas , Ardail Dominique , Nakajima Tetsuo , Rodriguez-Lafrasse Claire
Published: July 2021

Hypoxia-Inducible Factor 1α (HIF-1α), which promotes cancer cell survival, is the main regulator of oxygen homeostasis. Hypoxia combined with photon and carbon ion irradiation (C-ions) stabilizes HIF-1α. Silencing HIF-1α under hypoxia leads to substantial radiosensitization of Head-and-Neck Squamous Cell Carcinoma (HNSCC) cells after both photons and C-ions. Thus, this study aimed to clarify a potential involvement of HIF-1α in the detection, signaling, and repair of DNA Double-Strand-Breaks (DSBs) in response to both irradiations, in two HNSCC cell lines and their subpopulations of Cancer-Stem Cells (CSCs). After confirming the nucleoshuttling of HIF-1α in response to both exposure under hypoxia, we showed that silencing HIF-1α in non-CSCs and CSCs decreased the initiation of the DSB detection (P-ATM), and increased the residual phosphorylated H2AX (γH2AX) foci. While HIF-1α silencing did not modulate 53BP1 expression, P-DNA-PKcs (NHEJ-c) and RAD51 (HR) signals decreased. Altogether, our experiments demonstrate the involvement of HIF-1α in the detection and signaling of DSBs, but also in the main repair pathways (NHEJ-c and HR), without favoring one of them. Combining HIF-1α silencing with both types of radiation could therefore present a potential therapeutic benefit of targeting CSCs mostly present in tumor hypoxic niches.
De-Palmitoylation of Tissue Factor Regulates Its Activity, Phosphorylation and Cellular Functions
Authors: Ettelaie Camille , Featherby Sophie , Rondon Araci M. R. , Greenman John , Versteeg Henri H. , Maraveyas Anthony
Published: July 2021

In this study, the role of de-palmitoylation of tissue factor (TF) in the decryption of its activity was explored. TF-tGFP constructs were prepared by mutagenesis-substitution at Cys245 to prevent or mimic palmitolyation. Additionally, to reduce TF de-palmitoylation, the expression of palmitoyl-protein thioesterases (PPT) was suppressed. Other TF mutants were prepared with altered flexibility, hydrophobicity or length of the transmembrane domain. The outcome of these alterations on fXa-generation, fVIIa binding, Ser253 phosphorylation and TF-microvesicle release were assessed in endothelial cells, and the influence on endothelial and MCF-7 cell proliferation and apoptosis was analysed. Preventing TF palmitoylation (TFSer245-tGFP), increasing the hydrophobicity (TFPhe241-tGFP) or lengthening (TFLongTM-tGFP) of the transmembrane domain enhanced fXa-generation in resting cells compared to cells expressing TFWt-tGFP, but fXa-generation was not further increased following PAR2 activation. Extending the available length of the transmembrane domain enhanced the TF-tGFP release within microvesicles and Ser253 phosphorylation and increased cell proliferation. Moreover, prevention of PKCα-mediated Ser253 phosphorylation with Gö6976 did not preclude fXa-generation. Conversely, reducing the hydrophobicity (TFSer242-tGFP), shortening (TFShortTM-tGFP) or reducing the flexibility (TFVal225-tGFP) of the transmembrane domain suppressed fXa-generation, fVIIa-HRP binding and Ser253 phosphorylation following PAR2 activation. PPT knock-down or mimicking palmitoylation (TFPhe245-tGFP) reduced fXa-generation without affecting fVIIa binding. This study has for the first time shown that TF procoagulant activity is regulated through de-palmitoylation, which alters the orientation of its transmembrane domain and is independent of TF phosphorylation. However, Ser253 phosphorylation is facilitated by changes in the orientation of the transmembrane domain and can induce TF-cellular signalling that influences cellular proliferation/apoptosis.
Targeted Mass Spectrometry Enables Quantification of Novel Pharmacodynamic Biomarkers of ATM Kinase Inhibition
Authors: Whiteaker Jeffrey R. , Wang Tao , Zhao Lei , Schoenherr Regine M. , Kennedy Jacob J. , Voytovich Ulianna , Ivey Richard G. , Huang Dongqing , Lin Chenwei , Colantonio Simona , Caceres Tessa W. , Roberts Rhonda R. , Knotts Joseph G. , Kaczmarczyk Jan A. , Blonder Josip , Reading Joshua J. , Richardson Christopher W. , Hewitt Stephen M. , Garcia-Buntley Sandra S. , Bocik William , Hiltke Tara , Rodriguez Henry , Harrington Elizabeth A. , Barrett J. Carl , Lombardi Benedetta , Marco-Casanova Paola , Pierce Andrew J. , Paulovich Amanda G.
Published: July 2021

The ATM serine/threonine kinase (HGNC: ATM) is involved in initiation of repair of DNA double-stranded breaks, and ATM inhibitors are currently being tested as anti-cancer agents in clinical trials, where pharmacodynamic (PD) assays are crucial to help guide dose and scheduling and support mechanism of action studies. To identify and quantify PD biomarkers of ATM inhibition, we developed and analytically validated a 51-plex assay (DDR-2) quantifying protein expression and DNA damage-responsive phosphorylation. The median lower limit of quantification was 1.28 fmol, the linear range was over 3 orders of magnitude, the median inter-assay variability was 11% CV, and 86% of peptides were stable for storage prior to analysis. Use of the assay was demonstrated to quantify signaling following ionizing radiation-induced DNA damage in both immortalized lymphoblast cell lines and primary human peripheral blood mononuclear cells, identifying PD biomarkers for ATM inhibition to support preclinical and clinical studies.
Family History and Gastric Cancer Risk: A Pooled Investigation in the Stomach Cancer Pooling (STOP) Project Consortium
Authors: Vitelli-Storelli Facundo , Rubín-García María , Pelucchi Claudio , Benavente Yolanda , Bonzi Rossella , Rota Matteo , Palli Domenico , Ferraroni Monica , Lunet Nuno , Morais Samantha , Ye Weimin , Plymoth Amelie , Malekzadeh Reza , Tsugane Shoichiro , Hidaka Akihisa , Aragonés Nuria , Castaño-Vinyals Gemma , Zaridze David Georgievich , Maximovich Dmitry , Vioque Jesus , García-de-la-Hera Manuela , Zhang Zuo-Feng , Shigueaki Hamada Gerson , Pakseresht Mohammadreza , Pourfarzi Farhad , Mu Lina , Boccia Stefania , Pastorino Roberta , Yu Guo-Pei , Lagiou Areti , Lagiou Pagona , Negri Eva , La Vecchia Carlo , Martín Vicente
Published: July 2021

Although there is a clear relationship between family history (FH) and the risk of gastric cancer (GC), quantification is still needed in relation to different histological types and anatomical sites, and in strata of covariates. The objective was to analyze the risk of GC according to first-degree FH in a uniquely large epidemiological consortium of GC. This investigation includes 5946 cases and 12,776 controls from 17 studies of the Stomach Cancer Pooling (StoP) Project consortium. Summary odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were calculated by pooling study-specific ORs using fixed-effect model meta-analysis techniques. Stratified analyses were carried out by sex, age, tumor location and histological type, smoking habit, socioeconomic status, alcohol intake and fruit consumption. The pooled OR for GC was 1.84 (95% CI: 1.64–2.04; I2 = 6.1%, P heterogeneity = 0.383) in subjects with vs. those without first-degree relatives with GC. No significant differences were observed among subgroups of sex, age, geographic area or study period. Associations tended to be stronger for non-cardia (OR = 1.82; 95% CI: 1.59–2.05 for subjects with FH) than for cardia GC (OR = 1.38; 95% CI: 0.98–1.77), and for the intestinal (OR = 1.92; 95% CI: 1.62–2.23) than for the diffuse histotype (OR = 1.62; 95% CI: 1.28–1.96). This analysis confirms the effect of FH on the risk of GC, reporting an approximately doubled risk, and provides further quantification of the risk of GC according to the subsite and histotype. Considering these findings, accounting for the presence of FH to carry out correct prevention and diagnosis measures is of the utmost importance.
Ethanol-Induced Cell Damage Can Result in the Development of Oral Tumors
Authors: Hoes Lore , Dok Rüveyda , Verstrepen Kevin J. , Nuyts Sandra
Published: July 2021

Alcohol consumption is an underestimated risk factor for the development of precancerous lesions in the oral cavity. Although alcohol is a well-accepted recreational drug, 26.4% of all lip and oral cavity cancers worldwide are related to heavy drinking. Molecular mechanisms underlying this carcinogenic effect of ethanol are still under investigation. An important damaging effect comes from the first metabolite of ethanol, being acetaldehyde. Concentrations of acetaldehyde detected in the oral cavity are relatively high due to the metabolization of ethanol by oral microbes. Acetaldehyde can directly damage the DNA by the formation of mutagenic DNA adducts and interstrand crosslinks. Additionally, ethanol is known to affect epigenetic methylation and acetylation patterns, which are important regulators of gene expression. Ethanol-induced hypomethylation can activate the expression of oncogenes which subsequently can result in malignant transformation. The recent identification of ethanol-related mutational signatures emphasizes the role of acetaldehyde in alcohol-associated carcinogenesis. However, not all signatures associated with alcohol intake also relate to acetaldehyde. This finding highlights that there might be other effects of ethanol yet to be discovered.
Identification of Cancer Hub Gene Signatures Associated with Immune-Suppressive Tumor Microenvironment and Ovatodiolide as a Potential Cancer Immunotherapeutic Agent
Authors: Chen Jia-Hong , Wu Alexander T. H. , Lawal Bashir , Tzeng David T. W. , Lee Jih-Chin , Ho Ching-Liang , Chao Tsu-Yi
Published: July 2021

Despite the significant advancement in therapeutic strategies, breast, colorectal, gastric, lung, liver, and prostate cancers remain the most prevalent cancers in terms of incidence and mortality worldwide. The major causes ascribed to these burdens are lack of early diagnosis, high metastatic tendency, and drug resistance. Therefore, exploring reliable early diagnostic and prognostic biomarkers universal to most cancer types is a clinical emergency. Consequently, in the present study, the differentially expressed genes (DEGs) from the publicly available microarray datasets of six cancer types (liver, lung colorectal, gastric, prostate, and breast cancers), termed hub cancers, were analyzed to identify the universal DEGs, termed hub genes. Gene set enrichment analysis (GSEA) and KEGG mapping of the hub genes suggested their crucial involvement in the tumorigenic properties, including distant metastases, treatment failure, and survival prognosis. Notably, our results suggested high frequencies of genetic and epigenetic alterations of the DEGs in association with tumor staging, immune evasion, poor prognosis, and therapy resistance. Translationally, we intended to identify a drug candidate with the potential for targeting the hub genes. Using a molecular docking platform, we estimated that ovatodiolide, a bioactive anti-cancer phytochemical, has high binding affinities to the binding pockets of the hub genes. Collectively, our results suggested that the hub genes were associated with establishing an immune-suppressive tumor microenvironment favorable for disease progression and promising biomarkers for the early diagnosis and prognosis in multiple cancer types and could serve as potential druggable targets for ovatodiolide.
Acid Microenvironment in Bone Sarcomas
Authors: Di Pompo Gemma , Cortini Margherita , Baldini Nicola , Avnet Sofia
Published: July 2021

In bone sarcomas, extracellular proton accumulation is an intrinsic driver of malignancy. Extracellular acidosis increases stemness, invasion, angiogenesis, metastasis, and resistance to therapy of cancer cells. It reprograms tumour-associated stroma into a protumour phenotype through the release of inflammatory cytokines. It affects bone homeostasis, as extracellular proton accumulation is perceived by acid-sensing ion channels located at the cell membrane of normal bone cells. In bone, acidosis results from the altered glycolytic metabolism of bone cancer cells and the resorption activity of tumour-induced osteoclasts that share the same ecosystem. Proton extrusion activity is mediated by extruders and transporters located at the cell membrane of normal and transformed cells, including vacuolar ATPase and carbonic anhydrase IX, or by the release of highly acidic lysosomes by exocytosis. To date, a number of investigations have focused on the effects of acidosis and its inhibition in bone sarcomas, including studies evaluating the use of photodynamic therapy. In this review, we will discuss the current status of all findings on extracellular acidosis in bone sarcomas, with a specific focus on the characteristics of the bone microenvironment and the acid-targeting therapeutic approaches that are currently being evaluated.
Sonodynamic Treatment Induces Selective Killing of Cancer Cells in an In Vitro Co-Culture Model
Authors: Foglietta Federica , Pinnelli Vanessa , Giuntini Francesca , Barbero Nadia , Panzanelli Patrizia , Durando Gianni , Terreno Enzo , Serpe Loredana , Canaparo Roberto
Published: July 2021

Sonodynamic Therapy (SDT) is a new anticancer strategy based on ultrasound (US) technique and is derived from photodynamic therapy (PDT); SDT is still, however, far from clinical application. In order to move this therapy forward from bench to bedside, investigations have been focused on treatment selectivity between cancer cells and normal cells. As a result, the effects of the porphyrin activation by SDT on cancer (HT-29) and normal (HDF 106-05) cells were studied in a co-culture evaluating cell cytotoxicity, reactive oxygen species (ROS) production, mitochondrial function and plasma membrane fluidity according to the bilayer sonophore (BLS) theory. While PDT induced similar effects on both HT-29 and HDF 106-05 cells in co-culture, SDT elicited significant cytotoxicity, ROS production and mitochondrial impairment on HT-29 cells only, whereas HDF 106-05 cells were unaffected. Notably, HT-29 and HDF 106-05 showed different cell membrane fluidity during US exposure. In conclusion, our data demonstrate a marked difference between cancer cells and normal cells in co-culture in term of responsiveness to SDT, suggesting that this different behavior can be ascribed to diversity in plasma membrane properties, such as membrane fluidity, according to the BLS theory.
Interaction of Adenosine, Modified Using Carborane Clusters, with Ovarian Cancer Cells: A New Anticancer Approach against Chemoresistance
Authors: Bednarska-Szczepaniak Katarzyna , Przelazły Ewelina , Kania Katarzyna Dominika , Szwed Marzena , Litecká Miroslava , Grűner Bohumír , Leśnikowski Zbigniew J.
Published: July 2021

Platinum compounds remain the first-line drugs for the treatment of most lethal gynecological malignancies and ovarian cancers. Acquired platinum resistance remains a major challenge in gynecological oncology. Considering the unique physicochemical properties of the metallacarboranes modifier and the significant role of nucleoside derivatives as anticancer antimetabolites, we designed and synthesized a set of adenosine conjugates with metallacarboranes containing iron, cobalt, or chromium as semi-abiotic compounds that influence the cisplatin sensitivity of ovarian cancer cells. Adherent cultures of ovarian carcinoma cell lines and multicellular spheroids, ranging from sensitive to highly resistant including experimental cell lines “not responding” to platinum drugs were used. Iron-containing metallacarborane conjugates showed the best anticancer activity, especially against resistant cells. Compound modified at the C2′ nucleoside position showed the best activity in resistant cancer cells and highly resistant cancer spheroids exposed to cisplatin, increasing cell cycle arrest, apoptosis or necrosis, and reactive oxygen species production. Moreover, it showed high cellular accumulation and did not induce cross-resistance to cisplatin, carboplatin, doxorubicin, paclitaxel, or gemcitabine in long-term cultures. The reference nido-carborane derivative (no metal ions) and unmodified nucleosides were not as effective. These findings indicate that metallacarborane modification of adenosine may sensitize ovarian cancer cells to cisplatin in combination treatment.
Naturally Occurring Oxazole Structural Units as Ligands of Vanadium Catalysts for Ethylene-Norbornene (Co)polymerization
Authors: Ochędzan-Siodłak Wioletta , Siodłak Dawid , Banaś Karolina , Halikowska Katarzyna , Wierzba Sławomir , Doležal Karel
Published: July 2021

1,3-Oxazole and 4,5-dihydro-1,3-oxazole are common structural motifs in naturally occurring peptides. A series of vanadium complexes were synthesized using VCl3(THF)3 and methyl substituted (4,5-dihydro-1,3-oxazol-2-yl)-1,3-oxazoles as ligands and analyzed using NMR and MS methods. The complexes were found to be active catalysts both in ethylene polymerization and ethylene-norbornene copolymerization. The position of methyl substituent in the ligand has considerable impact on the performance of (co)polymerization reaction, as well as on the microstructure, and thus physical properties of the obtained copolymers.