bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospects for the Development of High Energy Density Dielectric Capacitors
Authors: Burke Andrew
Published: August 2021

In this paper, the design of high energy density dielectric capacitors for energy storage in vehicle, industrial, and electric utility applications have been considered in detail. The performance of these devices depends primarily on the dielectric constant and breakdown strength characteristics of the dielectric material used. A review of the literature on composite polymer materials to assess their present dielectric constants and the various approaches being pursued to increase energy density found that there are many papers in which materials having dielectric constants of 20–50 were reported, but only a few showing materials with very high dielectric constants of 500 and greater. The very high dielectric constants were usually achieved with nanoscale metallic or carbon particles embedded in a host polymer and the maximum dielectric constant occurred near the percolation threshold particle loading. In this study, an analytical method to calculate the dielectric constant of composite dielectric polymers with various types of nanoparticles embedded is presented. The method was applied using an Excel spreadsheet to calculate the characteristics of spiral wound battery cells using various composite polymers with embedded particles. The calculated energy densities were strong functions of the size of the particles and thickness of the dielectric layer in the cell. For a 1000 V cell, an energy density of 100–200 Wh/kg was calculated for 3–5 nm particles and 3–5 µ thick dielectric layers. The results of this study indicate that dielectric materials with an effective dielectric constant of 500–1000 are needed to develop dielectric capacitor cells with battery-like energy density. The breakdown strength would be 300–400 V/µ in a reverse sandwich multilayer dielectric arrangement. The leakage current of the cell would be determined from appropriate DC testing. These high energy density dielectric capacitors are very different from electrochemical capacitors that utilize conducting polymers and liquid electrolytes and are constructed much like batteries. The dielectric capacitors have a very high cell voltage and are constructed like conventional ceramic capacitors.
A Secure Random Number Generator with Immunity and Propagation Characteristics for Cryptography Functions
Authors: Saha Rahul , Geetha Ganesan , Kumar Gulshan , Buchanan William J. , Kim Tai-hoon
Published: August 2021

Cryptographic algorithms and functions should possess some of the important functional requirements such as: non-linearity, resiliency, propagation and immunity. Several previous studies were executed to analyze these characteristics of the cryptographic functions specifically for Boolean and symmetric functions. Randomness is a requirement in present cryptographic algorithms and therefore, Symmetric Random Function Generator (SRFG) has been developed. In this paper, we have analysed SRFG based on propagation feature and immunity. Moreover, NIST recommended statistical suite has been tested on SRFG outputs. The test values show that SRFG possess some of the useful randomness properties for cryptographic applications such as individual frequency in a sequence and block-based frequency, long run of sequences, oscillations from 0 to 1 or vice-versa, patterns of bits, gap bits between two patterns, and overlapping block bits. We also analyze the comparison of SRFG and some existing random number generators. We observe that SRFG is efficient for cryptographic operations in terms of propagation and immunity features.
A Network Parameter Database False Data Injection Correction Physics-Based Model: A Machine Learning Synthetic Measurement-Based Approach
Authors: Zou Tierui , Aljohani Nader , Nagaraj Keerthiraj , Zou Sheng , Ruben Cody , Bretas Arturo , Zare Alina , McNair Janise
Published: August 2021

Concerning power systems, real-time monitoring of cyber–physical security, false data injection attacks on wide-area measurements are of major concern. However, the database of the network parameters is just as crucial to the state estimation process. Maintaining the accuracy of the system model is the other part of the equation, since almost all applications in power systems heavily depend on the state estimator outputs. While much effort has been given to measurements of false data injection attacks, seldom reported work is found on the broad theme of false data injection on the database of network parameters. State-of-the-art physics-based model solutions correct false data injection on network parameter database considering only available wide-area measurements. In addition, deterministic models are used for correction. In this paper, an overdetermined physics-based parameter false data injection correction model is presented. The overdetermined model uses a parameter database correction Jacobian matrix and a Taylor series expansion approximation. The method further applies the concept of synthetic measurements, which refers to measurements that do not exist in the real-life system. A machine learning linear regression-based model for measurement prediction is integrated in the framework through deriving weights for synthetic measurements creation. Validation of the presented model is performed on the IEEE 118-bus system. Numerical results show that the approximation error is lower than the state-of-the-art, while providing robustness to the correction process. Easy-to-implement model on the classical weighted-least-squares solution, highlights real-life implementation potential aspects.
Risk Factors of Avulsion Fracture after Iliac Crestal Flap for Jaw Reconstruction
Authors: Jo Ye-Joon , Choi Jun-Seok , Bang Jin-Ah , Kim Jin , Moon Seong-Yong
Published: August 2021

The iliac crestal flap is often used in maxillofacial reconstruction surgery because it has a similar bone contour to jaw bone. However, complications occur frequently in this flap, and the avulsion fracture of the anterior superior iliac spine (ASIS) occurs only in rare cases. The purpose of this study is to evaluate the risk factors affecting fractures that may occur after iliac crestal flap harvesting. In this study, we performed preoperative and postoperative CT scans of the iliac bones of 22 patients who underwent iliac crestal flaps between February 2013 and July 2019. Three of these patients had fractures within 1 month after surgery. After converting DICOM files to a three-dimensional model using Mimics software, some reference points were defined for analysis. The patients were classified into fracture and non-fracture groups. The patients’ age and sex, harvested bone, residual bone and absolute bed rest (ABR) periods were investigated. The patients’ age and sex were not associated with fracture occurrence. There was a statistically significant difference in the width of the anterior–superior part of residual bone. The fracture group showed statistically significantly shorter ABR periods. In the case of the iliac crestal flap, it was found that the factors that can affect the occurrence of fractures are the width of the residual bone and the ABR period. Iliac avulsion fracture can be prevented when the remaining bone is sufficient and the ABR period is prolonged sufficiently.
Virtual Reality Visualization of CFD Simulated Blood Flow in Cerebral Aneurysms Treated with Flow Diverter Stents
Authors: Baheri Islami Sima , Wesolowski Mike , Revell William , Chen Xiongbiao
Published: August 2021

Virtual reality (VR) has the potential to be a powerful tool for the visualization of simulated blood flow in cerebral aneurysms. This paper presents our study aimed at developing the VR visualization of computational fluid dynamics (CFD) simulations of cerebral aneurysms treated with flow-diverting (FD) stents. First, a spherical sidewall aneurysm located at a simplified internal carotid artery was considered for investigating the impact of stent deployment and positioning on the corresponding spatially time-varying blood flow behavior. The three-dimensional unsteady blood flow over a cardiac cycle was simulated numerically using the finite volume method, and the distributions of hemodynamic parameters inside the aneurysm sac, and on its wall, were presented with and without stent cases. Two stent positions, with and without a gap between the artery wall and stent, were considered to show the influence of correct stent position on aneurysm treatment. Second, a straightforward workflow was developed to import, process, and visualize the CFD analysis data in a VR environment by using open-source software with a high resolution. The Unity3D engine was used for displaying the processed animations in a VR environment operated on a head-mounted display (HMD). The refining process of each frame of time-varying CFD data was automated. The animated flow elements rendered in the VR environment were velocity vectors, velocity contours, streamlines, particle traces, and point clouds. CFD results showed that proper stenting facilitates thrombosis and occlusion of the aneurysm by modification of the flow patterns, which leads to lower inflow jet velocities into the aneurysm, longer turnover time, lower aneurysm-averaged kinetic energy, and lower wall shear stress. Additionally, the results indicated that a gap between the stent and the parent artery may lead to undesirable hemodynamic alterations. The VR visualization illustrated that the recognition of the potential in danger regions of aneurysms and the evaluation of the performance of FD stents in aneurysm treatment can be conducted without the need for several slices through the parent artery and aneurysm, as is required for traditional postprocessing methods. Through VR visualization, the details of the simulation results become readily available by navigating in the 3D animated flow elements using a high-degree-of-freedom headset.
Numerical Validation of the Radiative Model for the Solar Cadaster Developed for Greater Geneva
Authors: Govehovitch Benjamin , Thebault Martin , Bouty Karine , Giroux-Julien Stéphanie , Peyrol Éric , Guillot Victor , Ménézo Christophe , Desthieux Gilles
Published: August 2021

The achievement of the targets for reducing greenhouse gas emissions set by the Paris Agreements and the Swiss federal law on the reduction of greenhouse gas emissions (CO2 law) requires massive use of renewable energies, which cannot be achieved without their adoption by the general public. The solar cadaster developed as part of the INTERREG G2 Solar project is intended to assess the solar potential of buildings at the scale of Greater Geneva—for both industrial buildings and for individual residential buildings—at a resolution of 1 m. The new version of the solar cadaster is intended to assess the solar potential of roofs, as well as that of vertical facades. The study presented here aims to validate this new version through a comparison with results obtained with two other simulation tools that are widely used and validated by the scientific community. The good accordance with the results obtained with ENVI-met and DIVA-for-Rhino demonstrates the capability of the radiative model developed for the solar cadaster of Greater Geneva to accurately predict the radiation levels of building facades in configurations with randomly distributed buildings (horizontally or vertically).
Bioclimatic Conditions of June 2019 in Poland on a Multi-Year Background (1966–2019)
Authors: Tomczyk Arkadiusz Marek
Published: August 2021

The study objective was to characterise human-biometeorological conditions in the summer season in the period 1966–2019 in Poland, with particular consideration of June 2019. The study was conducted based on data from the Institute of Meteorology and Water Management—National Research Institute (IMGW–PIB) for the years 1966–2019. The data provided the basis for the calculation of the Universal Thermal Climate Index (UTCI). The study revealed high spatial variability of human-biometeorological conditions in Poland, with strenuous character intensifying from the north to the south of the country. An increase in UTCI in the summer season was recorded in the studied multi-annual period. It was the most intensive in the north-eastern Poland. The consequence of the observed changes was an increase in the frequency of days with heat stress categories (days with UTCI > 26.0 °C), and a decrease in the frequency of days with cold stress categories (days with UTCI < 9.0 °C). Season 2019 stood out at the scale of the entire country in the context of the multi-annual period. This particularly concerns June, when mean monthly UTCI values were the highest in the analysed multi-annual period.
Mapping Nighttime and All-Day Radiative Cooling Potential in Europe and the Influence of Solar Reflectivity
Authors: Vilà Roger , Medrano Marc , Castell Albert
Published: August 2021

Radiative cooling is a natural process to cool down surfaces through the rejection of thermal radiation using the outer space as a cold sink, taking advantage of the transparency of the atmospheric windows (8–14 μm), which partially matches the infrared radiation band. With the development of new materials that have a high reflectivity of solar radiation, daytime radiative cooling can be achieved. This phenomenon depends on the optical properties of the surface and the local weather conditions. In this research, climatological data from 1791 weather stations were used to present detailed nighttime and all-day radiative cooling maps for the potential implementation of radiative cooling-based technologies. The paper offers a parametric study of the variation of the potential as a result of decreasing the solar reflectivity. The results show that southern Europe is the region with the highest potential while northern Europe holds more hours of available radiative cooling. After varying the solar reflectivity from 1 to 0.5 the average power reduces from 60.18 to 45.32 W/m2, and energy from 527.10 to 264.87 kWh/m2·year. For solar reflectivity lower than 0.5, all-day radiative coolers behave as nighttime radiative coolers, but power and energy values improve significantly for high values of solar reflectivity. Small variations of solar reflectivity have greater impacts on the potential at higher reflectivity values than at lower ones.
θ*-Weak Contractions and Discontinuity at the Fixed Point with Applications to Matrix and Integral Equations
Authors: Perveen Atiya , Alfaqih Waleed M. , Sessa Salvatore , Imdad Mohammad
Published: August 2021

In this paper, the notion of θ*-weak contraction is introduced, which is utilized to prove some fixed point results. These results are helpful to give a positive response to certain open question raised by Kannan and Rhoades on the existence of contractive definition which does not force the mapping to be continuous at the fixed point. Some illustrative examples are also given to support our results. As applications of our result, we investigate the existence and uniqueness of a solution of non-linear matrix equations and integral equations of Volterra type as well.
Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics
Authors: Škubník Jan , Pavlíčková Vladimíra Svobodová , Ruml Tomáš , Rimpelová Silvie
Published: August 2021

Treatment of blood malignancies and other cancer diseases has been mostly unfeasible, so far. Therefore, novel treatment regimens should be developed and the currently used ones should be further elaborated. A stable component in various cancer treatment regimens consists of vincristine, an antimitotic compound of natural origin. Despite its strong anticancer activity, mostly, it cannot be administered as monotherapy due to its unspecific action and severe side effects. However, vincristine is suitable for combination therapy. Multidrug treatment regimens including vincristine are standardly applied in the therapy of non-Hodgkin lymphoma and other malignancies, in which it is combined with drugs of different mechanisms of action, mainly with DNA-interacting compounds (for example cyclophosphamide), or drugs interfering with DNA synthesis (for example methotrexate). Besides, co-administration of vincristine with monoclonal antibodies has also emerged, the typical example of which is the anti-CD20 antibody rituximab. Although in some combination anticancer therapies, vincristine has been replaced with other drugs exhibiting lesser side effects, though, in most cases, it is still irreplaceable. This is strongly evidenced by the number of active clinical trials evaluating vincristine in combination cancer therapy. Therefore, in this article, we have reviewed the most common cancer treatment regimens employing vincristine and bring an overview of current trends in the clinical development of this compound.
Subtype Differences in the Interaction of HIV-1 Matrix with Calmodulin: Implications for Biological Functions
Authors: Dick Alexej , Cocklin Simon
Published: August 2021

The HIV-1 Gag polyprotein plays essential roles during the late stage of the HIV-1 replication cycle, and has recently been identified as a promising therapeutic target. The N-terminal portion of the HIV-1 Gag polyprotein encodes the myristoylated matrix (MA) protein, which functions in the trafficking of the structural proteins to the plasma membrane (PM) and facilitation of envelope incorporation into budding virus. Numerous host cell proteins interact with the MA portion of the Gag polyprotein during this process. One such factor is the ubiquitous calcium-binding protein calmodulin (CaM), which interacts preferentially with myristoylated proteins, thereby regulating cell physiology. The exact role of this interaction is poorly understood to date. Atomic resolution structures revealed the nature of the CaM-MA interaction for clade B isolates. In this study, we expanded our knowledge and characterized biophysically and computationally the CaM interaction with MA from other HIV-1 clades and discovered differences in the CaM recognition as compared to the prototypical clade B MA, with significant alterations in the interaction with the MA protein from clade C. Structural investigation and in silico mutational analysis revealed that HIV-1 MA protein from clade C, which is responsible for the majority of global HIV-1 infections, interacts with lower affinity and altered kinetics as compared to the canonical clade B. This finding may have implications for additional altered interaction networks as compared to the well-studied clade B. Our analysis highlights the importance of expanding investigations of virus-host cell factor interaction networks to other HIV-1 clades.
Adropin Serum Levels in Patients with Primary Sjögren’s Syndrome
Authors: Danolić Marijana Janković , Perković Dijana , Petrić Marin , Barišić Igor , Gugo Katarina , Božić Joško
Published: August 2021

Primary Sjögren’s syndrome (pSS) patients have higher prevalence of endothelial dysfunction and premature atherosclerosis. Recent studies investigated adropin, a secretory protein that can regulate lipid metabolism and insulin resistance and protect endothelial cells’ function and that has an anti-inflammatory effect. The aim of this study was to determine adropin levels in pSS patients compared to healthy controls. Additional goals were exploring the correlation between adropin and several metabolic and immunological parameters in pSS, including disease specific antibodies, EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), and Sjögren’s Syndrome Disease Damage Index (SSDDI). This research included 52 pSS patients and 52 healthy controls. pSS patients have significantly higher adropin levels compared to the control group (3.76 ± 0.68 vs. 3.14 ± 0.69 ng/mL, p < 0.001). Correlation analysis showed that adropin levels in pSS patients have positive correlation with high-density lipoprotein (HDL) (r = 0.290, p = 0.036) and anti SSA/Ro52 antibodies (r = 0.307, p = 0.026) and negative correlation with SSDDI (r = −0.401, p = 0.003). Multivariant linear regression showed that adropin levels are independently associated with HDL (β ± SE, 0.903 ± 0.283, p = 0.002) and SSDDI (β ± SE, −0.202 ± 0.073, p = 0.008). Our findings imply that adropin could be involved in the pathophysiology of pSS, yet it remains to be elucidated in future studies whether adropin has a protective or detrimental role in this setting.
Spns2 Transporter Contributes to the Accumulation of S1P in Cystic Fibrosis Human Bronchial Epithelial Cells
Authors: Zulueta Aida , Dei Cas Michele , Luciano Francesco , Mingione Alessandra , Pivari Francesca , Righi Ilaria , Morlacchi Letizia , Rosso Lorenzo , Signorelli Paola , Ghidoni Riccardo , Paroni Rita , Caretti Anna
Published: August 2021

The role of S1P in Cystic Fibrosis (CF) has been investigated since 2001, when it was first described that the CFTR channel regulates the inward transport of S1P. From then on, various studies have associated F508del CFTR, the most frequent mutation in CF patients, with altered S1P expression in tissue and plasma. We found that human bronchial epithelial immortalized and primary cells from CF patients express more S1P than the control cells, as evidenced by mass spectrometry analysis. S1P accumulation relies on two- to four-fold transcriptional up-regulation of SphK1 and simultaneous halving of SGPL1 in CF vs. control cells. The reduction of SGPL1 transcription protects S1P from irreversible degradation, but the excessive accumulation is partially prevented by the action of the two phosphatases that are up-regulated compared to control cells. For the first time in CF, we describe that Spns2, a non-ATP dependent transporter that normally extrudes S1P out of the cells, shows deficient transcriptional and protein expression, thus impairing S1P accrual dissipation. The in vitro data on CF human bronchial epithelia correlates with the impaired expression of Spns2 observed in CF human lung biopsies compared to healthy control.
Modified Vaccinia Virus Ankara as a Viral Vector for Vaccine Candidates against Chikungunya Virus
Authors: García-Arriaza Juan , Esteban Mariano , López Daniel
Published: August 2021

There is a need to develop a highly effective vaccine against the emerging chikungunya virus (CHIKV), a mosquito-borne Alphavirus that causes severe disease in humans consisting of acute febrile illness, followed by chronic debilitating polyarthralgia and polyarthritis. In this review, we provide a brief history of the development of the first poxvirus vaccines that led to smallpox eradication and its implications for further vaccine development. As an example, we summarize the development of vaccine candidates based on the modified vaccinia virus Ankara (MVA) vector expressing different CHIKV structural proteins, paying special attention to MVA-CHIKV expressing all of the CHIKV structural proteins: C, E3, E2, 6K and E1. We review the characterization of innate and adaptive immune responses induced in mice and nonhuman primates by the MVA-CHIKV vaccine candidate and examine its efficacy in animal models, with promising preclinical findings needed prior to the approval of human clinical trials.
Pathophysiological Implication of Pattern Recognition Receptors in Fetal Membranes Rupture: RAGE and NLRP Inflammasome
Authors: Choltus Helena , Lavergne Marilyne , De Sousa Do Outeiro Coraline , Coste Karen , Belville Corinne , Blanchon Loïc , Sapin Vincent
Published: August 2021

Preterm prelabor ruptures of fetal membranes (pPROM) are a pregnancy complication responsible for 30% of all preterm births. This pathology currently appears more as a consequence of early and uncontrolled process runaway activation, which is usually implicated in the physiologic rupture at term: inflammation. This phenomenon can be septic but also sterile. In this latter case, the inflammation depends on some specific molecules called “alarmins” or “damage-associated molecular patterns” (DAMPs) that are recognized by pattern recognition receptors (PRRs), leading to a microbial-free inflammatory response. Recent data clarify how this activation works and which receptor translates this inflammatory signaling into fetal membranes (FM) to manage a successful rupture after 37 weeks of gestation. In this context, this review focused on two PRRs: the receptor for advanced glycation end-products (RAGE) and the NLRP7 inflammasome.
Association between Self-Reported Pain, Cognition, and Neuropathology in Older Adults Admitted to an Outpatient Memory Clinic—A Cross-Sectional Study
Authors: Madariaga Víctor I. , Overdorp Eduard , Claassen Jurgen A. H. R. , Brazil Inti A. , Oosterman Joukje M.
Published: August 2021

Cognitive impairment has been linked to reduced self-reporting of pain. However, it is unclear whether the various cognitive functions are similarly and/or independently associated with such pain report measures. In the present study, we explored how executive functioning (EF), memory, and global cognition relate to self-reported pain and investigated whether underlying neuropathology partially accounts for these results. We used Lasso categorical regression to analyze data from 179 individuals visiting a memory clinic. The data included the self-reported pain occurrence, intensity, severity and frequency, clinical diagnoses, neuropsychological scores, white matter hyperintensities, medial temporal lobe atrophy, depressive symptoms, and demographics. Our results showed that worse memory and EF performance predicted a lower pain occurrence. In those individuals who did report pain, worse memory predicted lower pain intensity, severity, and frequency levels, but for EF reversed effects were found, with worse EF predicting higher pain scores. These relationships were only partially explained by reductions in white matter and medial temporal lobe integrity. Similar effects were found for depressive symptoms. Our findings highlight the distinct associations of EF and memory with self-reported pain. A similar pattern of relationships found for both self-reported pain and depressive symptoms may reflect shared latent affective components.
Problem Talk in Adolescence: Temperament and Attachment as Predictors of Co-Rumination Trajectories in Boys and Girls
Authors: Bastin Margot , Mezulis Amy H. , Aldrich Jaclyn T. , Bosmans Guy , Nelis Sabine , Raes Filip , Bijttebier Patricia
Published: August 2021

Co-rumination has consistently been shown to be maladaptive in the context of emotional well-being. However, not much is known about factors that predict one’s tendency to co-ruminate. The current study investigated temperament, attachment, and gender as predictors of co-rumination trajectories in a sample of 1549 early and middle adolescents from fifth to ninth grade (53.4% girls; Mage = 12.93). Analyses were performed on four waves of data with one-year intervals using multi-level modeling. First, girls were found to be more likely to co-ruminate. Second, high positive affectivity in boys and girls and high effortful control in boys was related to higher co-rumination. Third, high attachment anxiety and high general trust in the availability and support of a mother were predictive of higher co-rumination levels. High attachment avoidance was negatively related to co-rumination in boys. High positive affectivity in boys and girls and high trust in boys predicted decreases in reported co-rumination levels over time. Results highlight differences between boys and girls in factors that predict the tendency to co-ruminate. The current study adds to the literature by helping to identify factors associated with the development of co-rumination, which is a well-established risk factor of internalizing symptoms. Monitoring youth affected with these vulnerabilities may be recommended for prevention efforts.
The Impact of Economic Recessions on Depression, Anxiety, and Trauma-Related Disorders and Illness Outcomes—A Scoping Review
Authors: Guerra Olivia , Eboreime Ejemai
Published: August 2021

In the wake of a global economic recession secondary to the COVID-19 pandemic, this scoping review seeks to summarize the current quantitative research on the impact of economic recessions on depression, anxiety, traumatic disorders, self-harm, and suicide. Seven research databases (PsycINFO, MEDLINE, Embase, Web of Science: Core Collection, National Library of Medicine PubMed, PubMed Central, and Google Scholar) were searched for keywords returning 3412 preliminary results published since 2008 in Organisation for Economic Coordination and Development (OECD)nations. These were screened by both authors for inclusion/exclusion criteria resulting in 127 included articles. Articles included were quantitative studies in OECD countries assessing select mental disorders (depression, anxiety, and trauma-/stress-related disorders) and illness outcomes (self-harm and suicide) during periods of economic recession. Articles were limited to publication from 2008 to 2020, available online in English, and utilizing outcome measures specific to the disorders and outcomes specified above. A significant relationship was found between periods of economic recession and increased depressive symptoms, self-harming behaviour, and suicide during and following periods of recession. Results suggest that existing models for mental health support and strategies for suicide prevention may be less effective than they are in non-recession times. It may be prudent to focus public education and medical treatments on raising awareness and access to supports for populations at higher risk, including those vulnerable to the impacts of job or income loss due to low socioeconomic status preceding the recession or high levels of financial strain, those supporting others financially, approaching retirement, and those in countries with limited social safety nets. Policy makers should be aware of the potential protective nature of unemployment safeguards and labour program investment in mitigating these negative impacts. Limited or inconclusive data were found on the relationship with traumatic disorders and symptoms of anxiety. In addition, research has focused primarily on the working-age adult population with limited data available on children, adolescents, and older adults, leaving room for further research in these areas.
The Effects of High-Intensity Interval Training vs. Moderate-Intensity Continuous Training on Inflammatory Markers, Body Composition, and Physical Fitness in Overweight/Obese Survivors of Breast Cancer: A Randomized Controlled Clinical Trial
Authors: Hooshmand Moghadam Babak , Golestani Fateme , Bagheri Reza , Cheraghloo Neda , Eskandari Mozhgan , Wong Alexei , Nordvall Michael , Suzuki Katsuhiko , Pournemati Parisa
Published: August 2021

Background: Chronic inflammation associated with breast cancer (BC) poses a major challenge in care management and may be ameliorated by physical activity. This randomized controlled trial assessed the effects of a 12-week high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on inflammatory markers, body composition, and physical fitness in BC survivors (BCS). Methods: Forty BCS (age = 57 ± 1 years; body mass [BM] = 74.8 ± 1.5 kg; VO2peak = 20.8 ± 2.1 mL·kg−1·min−1) were randomly assigned to three groups: HIIT (n = 15), MICT (n = 15), or control (CON; n = 15). The intervention groups (HIIT and MICT) performed their respective exercise protocols on a cycle ergometer 3 days/week for 12 weeks while the CON group maintained their current lifestyle. Baseline and post-intervention assessments included body composition (BM, fat mass (FM), lean mass (LM)), physical fitness (VO2peak, lower body strength (LBS), upper body strength (UBS)), and serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), leptin, and adiponectin. Results: Both intervention groups significantly (p < 0.05) decreased BM (HIIT = −1.8 kg, MICT = −0.91 kg), FM (HIIT = −0.81 kg, MICT = −0.18 kg), TNF-α (HIIT = −1.84 pg/mL, MICT = −0.99 pg/mL), IL-6 (HIIT = −0.71 pg/mL, MICT = −0.36 pg/mL), leptin (HIIT = −0.35 pg/mL, MICT = −0.16 pg/mL) and increased VO2peak (HIIT = 0.95 mL·kg−1·min−1, MICT = 0.67 mL·kg−1·min−1), LBS (HIIT = 2.84 kg, MICT = 1.53 kg), UBS (HIIT = 0.53 kg, MICT = 0.53 kg), IL-10 (HIIT = 0.63 pg/mL, MICT = 0.38 pg/mL), and adiponectin (HIIT = 0.23 ng/mL, MICT = 0.1 ng/mL) compared to baseline. The changes in BM, FM, TNF-α, leptin, and LBS were significantly greater in HIIT compared to all other groups. Conclusions: Our findings indicate that compared to the often-recommended MICT, HIIT may be a more beneficial exercise therapy for the improvement of inflammation, body composition and LBS in BCS; and consequently, merits long-term study
Pancreatic Lineage Specifier PDX1 Increases Adhesion and Decreases Motility of Cancer Cells
Authors: Kondratyeva Liya , Chernov Igor , Kopantzev Eugene , Didych Dmitry , Kuzmich Alexey , Alekseenko Irina , Kostrov Sergey , Sverdlov Eugene
Published: August 2021

Intercellular interactions involving adhesion factors are key operators in cancer progression. In particular, these factors are responsible for facilitating cell migration and metastasis. Strengthening of adhesion between tumor cells and surrounding cells or extracellular matrix (ECM), may provide a way to inhibit tumor cell migration. Recently, we demonstrated that PDX1 ectopic expression results in the reduction of pancreatic cancer line PANC-1 cell motility in vitro and in vivo, and we now provide experimental data confirming the hypothesis that suppression of migration may be related to the effect of PDX1 on cell adhesion. Cell migration analyses demonstrated decreased motility of pancreatic Colo357 and PANC-1 cell lines expressing PDX1. We observed decreased expression levels of genes associated with promoting cell migration and increased expression of genes negatively affecting cell motility. Expression of the EMT regulator genes was only mildly induced in cells expressing PDX1 during the simulation of the epithelial-mesenchymal transition (EMT) by the addition of TGFβ1 to the medium. PDX1-expressing cancer cell lines showed increased cell adhesion to collagen type I, fibronectin, and poly-lysine. We conclude that ectopic expression of PDX1 reduces the migration potential of cancer cells, by increasing the adhesive properties of cells and reducing the sensitivity to TGFβ1-induced EMT.
Effective Oncoleaking Treatment of Pancreatic Cancer by Claudin-Targeted Suicide Gene Therapy with Clostridium perfringens Enterotoxin (CPE)
Authors: Pahle Jessica , Kobelt Dennis , Aumann Jutta , Behrens Diana , Daberkow Ole , Mokritzkij Margarita , Piontek Jörg , Stein Ulrike , Walther Wolfgang
Published: August 2021

Pancreatic cancer (PC) is one of the most lethal cancers worldwide, associated with poor prognosis and restricted therapeutic options. Clostridium perfringens enterotoxin (CPE), is a pore-forming (oncoleaking) toxin, which binds to claudin-3 and -4 (Cldn3/4) causing selective cytotoxicity. Cldn3/4 are highly upregulated in PC and represent an effective target for oncoleaking therapy. We utilized a translation-optimized CPE vector (optCPE) for new suicide approach of PC in vitro and in cell lines (CDX) and patient-derived pancreatic cancer xenografts (PDX) in vivo. The study demonstrates selective toxicity in Cldn3/4 overexpressing PC cells by optCPE gene transfer, mediated by pore formation, activation of apoptotic/necrotic signaling in vitro, induction of necrosis and of bystander tumor cell killing in vivo. The optCPE non-viral intratumoral in vivo jet-injection gene therapy shows targeted antitumoral efficacy in different CDX and PDX PC models, leading to reduced tumor viability and induction of tumor necrosis, which is further enhanced if combined with chemotherapy. This selective oncoleaking suicide gene therapy improves therapeutic efficacy in pancreas carcinoma and will be of value for better local control, particularly of unresectable or therapy refractory PC.
Kallikrein 5 Inhibition by the Lympho-Epithelial Kazal-Type Related Inhibitor Hinders Matriptase-Dependent Carcinogenesis
Authors: da Silva Elaine Zayas Marcelino , Fraga-Silva Thais Fernanda de Campos , Yuan Yao , Alves Márcia Gaião , Publio Gabriel Azevedo , da Fonseca Carol Kobori , Kodama Márcio Hideki , Vieira Gabriel Viliod , Candido Marina Ferreira , Innocentini Lara Maria Alencar Ramos , Miranda Mateus Gonçalves , da Silva Alfredo Ribeiro , Alves-Filho Jose Carlos , Bonato Vania Luiza Deperon , Iglesias-Bartolome Ramiro , Sales Katiuchia Uzzun
Published: August 2021

Head and neck squamous cell carcinoma remains challenging to treat with no improvement in survival rates over the past 50 years. Thus, there is an urgent need to discover more reliable therapeutic targets and biomarkers for HNSCC. Matriptase, a type-II transmembrane serine protease, induces malignant transformation in epithelial stem cells through proteolytic activation of pro-HGF and PAR-2, triggering PI3K-AKT-mTOR and NFKB signaling. The serine protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI) inhibits the matriptase-driven proteolytic pathway, directly blocking kallikreins in epithelial differentiation. Hence, we hypothesized LEKTI could inhibit matriptase-dependent squamous cell carcinogenesis, thus implicating kallikreins in this process. Double-transgenic mice with simultaneous expression of matriptase and LEKTI under the keratin-5 promoter showed a prominent rescue of K5-Matriptase+/0 premalignant phenotype. Notably, in DMBA-induced SCC, heterotopic co-expression of LEKTI and matriptase delayed matriptase-driven tumor incidence and progression. Co-expression of LEKTI reverted altered Kallikrein-5 expression observed in the skin of K5-Matriptase+/0 mice, indicating that matriptase-dependent proteolytic pathway inhibition by LEKTI occurs through kallikreins. Moreover, we showed that Kallikrein-5 is necessary for PAR-2-mediated IL-8 release, YAP1-TAZ/TEAD activation, and matriptase-mediated oral squamous cell carcinoma migration. Collectively, our data identify a third signaling pathway for matriptase-dependent carcinogenesis in vivo. These findings are critical for the identification of more reliable biomarkers and effective therapeutic targets in Head and Neck cancer.
Single-Cell Cloning of Breast Cancer Cells Secreting Specific Subsets of Extracellular Vesicles
Authors: Fathi Mohsen , Joseph Robiya , Adolacion Jay R T. , Martinez-Paniagua Melisa , An Xingyue , Gabrusiewicz Konrad , Mani Sendurai A. , Varadarajan Navin
Published: August 2021

Extracellular vesicles (EVs) mediate communication in health and disease. Conventional assays are limited in profiling EVs secreted from large populations of cells and cannot map EV secretion onto individual cells and their functional profiles. We developed a high-throughput single-cell technique that enabled the mapping of dynamics of EV secretion. By utilizing breast cancer cell lines, we established that EV secretion is heterogeneous at the single-cell level and that non-metastatic cancer cells can secrete specific subsets of EVs. Single-cell RNA sequencing confirmed that pathways related to EV secretion were enriched in the non-metastatic cells compared with metastatic cells. We established isogenic clonal cell lines from non-metastatic cells with differing propensities for CD81+CD63+EV secretion and showed for the first time that specificity in EV secretion is an inheritable property preserved during cell division. Combined in vitro and animal studies with these cell lines suggested that CD81+CD63+EV secretion can impede tumor formation. In human non-metastatic breast tumors, tumors enriched in signatures of CD81+CD63+EV have a better prognosis, higher immune cytolytic activity, and enrichment of pro-inflammatory macrophages compared with tumors with low CD81+CD63+EVs signatures. Our single-cell methodology enables the direct integration of EV secretion with multiple cellular functions and enables new insights into cell/disease biology.
Anti-Viral Pattern Recognition Receptors as Therapeutic Targets
Authors: Hennessy Conor , McKernan Declan P.
Published: August 2021

Pattern recognition receptors (PRRs) play a central role in the inflammation that ensues following microbial infection by their recognition of molecular patterns present in invading microorganisms but also following tissue damage by recognising molecules released during disease states. Such receptors are expressed in a variety of cells and in various compartments of these cells. PRR binding of molecular patterns results in an intracellular signalling cascade and the eventual activation of transcription factors and the release of cytokines, chemokines, and vasoactive molecules. PRRs and their accessory molecules are subject to tight regulation in these cells so as to not overreact or react in unnecessary circumstances. They are also key to reacting to infection and in stimulating the immune system when needed. Therefore, targeting PRRs offers a potential therapeutic approach for chronic inflammatory disease, infections and as vaccine adjuvants. In this review, the current knowledge on anti-viral PRRs and their signalling pathways is reviewed. Finally, compounds that target PRRs and that have been tested in clinical trials for chronic infections and as adjuvants in vaccine trials are discussed.
DYRK1A Kinase Inhibitors Promote β-Cell Survival and Insulin Homeostasis
Authors: Barzowska Agata , Pucelik Barbara , Pustelny Katarzyna , Matsuda Alex , Martyniak Alicja , Stępniewski Jacek , Maksymiuk Anna , Dawidowski Maciej , Rothweiler Ulli , Dulak Józef , Dubin Grzegorz , Czarna Anna
Published: August 2021

The rising prevalence of diabetes is threatening global health. It is known not only for the occurrence of severe complications but also for the SARS-Cov-2 pandemic, which shows that it exacerbates susceptibility to infections. Current therapies focus on artificially maintaining insulin homeostasis, and a durable cure has not yet been achieved. We demonstrate that our set of small molecule inhibitors of DYRK1A kinase potently promotes β-cell proliferation, enhances long-term insulin secretion, and balances glucagon level in the organoid model of the human islets. Comparable activity is seen in INS-1E and MIN6 cells, in isolated mice islets, and human iPSC-derived β-cells. Our compounds exert a significantly more pronounced effect compared to harmine, the best-documented molecule enhancing β-cell proliferation. Using a body-like environment of the organoid, we provide a proof-of-concept that small–molecule–induced human β-cell proliferation via DYRK1A inhibition is achievable, which lends a considerable promise for regenerative medicine in T1DM and T2DM treatment.
Single-Cell Omics in Dissecting Immune Microenvironment of Malignant Gliomas—Challenges and Perspectives
Authors: Kaminska Bozena , Ochocka Natalia , Segit Pawel
Published: August 2021

Single-cell technologies allow precise identification of tumor composition at the single-cell level, providing high-resolution insights into the intratumoral heterogeneity and transcriptional activity of cells in the tumor microenvironment (TME) that previous approaches failed to capture. Malignant gliomas, the most common primary brain tumors in adults, are genetically heterogeneous and their TME consists of various stromal and immune cells playing an important role in tumor progression and responses to therapies. Previous gene expression or immunocytochemical studies of immune cells infiltrating TME of malignant gliomas failed to dissect their functional phenotypes. Single-cell RNA sequencing (scRNA-seq) and cytometry by time-of-flight (CyTOF) are powerful techniques allowing quantification of whole transcriptomes or >30 protein targets in individual cells. Both methods provide unprecedented resolution of TME. We summarize the findings from these studies and the current state of knowledge of a functional diversity of immune infiltrates in malignant gliomas with different genetic alterations. A precise definition of functional phenotypes of myeloid and lymphoid cells might be essential for designing effective immunotherapies. Single-cell omics studies have identified crucial cell subpopulations and signaling pathways that promote tumor progression, influence patient survival or make tumors vulnerable to immunotherapy. We anticipate that the widespread usage of single-cell omics would allow rational design of oncoimmunotherapeutics.
Development of Core Contents of Point-of-Care Ultrasound Curriculum for Pediatric Emergency Medicine Physician Training: A Modified Delphi Survey
Authors: Kwon Jae-Hyun , Lee Jin-Hee , Ha Young-Rock , Park June-Dong ,   on behalf of the Division of Pediatric Emergency Ultrasound, Korean Society of Pediatric Emergency Medicine and Society of Emergency & Critical Care Imaging
Published: August 2021

Background: As the frequency of ultrasound use in pediatric emergency departments increases, it is necessary to train pediatric emergency medicine (PEM) physicians on pediatric point-of-care ultrasonography (POCUS). We discussed the core content of POCUS applications and proposed a POCUS training curriculum for PEM physicians in South Korea. Methods: Twenty-three experts were included if had performed over 1500 POCUS scans, had at least three years of experience teaching POCUS to physicians, were POCUS instructors or had completed a certified pediatric POCUS program. Experts rated 61 possible POCUS applications in terms of the importance of their inclusion in a PEM POCUS curriculum using the modified Delphi technique. Results: In round one, twelve (52.2%) out of 23 experts responded to the email. Eleven experts satisfied the inclusion criteria. Eleven experts participated in round one of a survey and agreed on 27 (44.3%) out of a total of 61 items. In round two, all 11 experts participated in the survey; they agreed on two (5.9%) of the remaining 34 items, and no items were excluded. Conclusion: Using the Delphi method, 61 applications were discussed, and a consensus was reached on 29 core applications.
Effectiveness of Oral Sensory-Motor Stimulation in Premature Infants in the Neonatal Intensive Care Unit (NICU) Systematic Review
Authors: Rodriguez Gonzalez Paula , Perez-Cabezas Veronica , Chamorro-Moriana Gema , Ruiz Molinero Carmen , Vazquez-Casares Ana María , Gonzalez-Medina Gloria
Published: August 2021

The aim of this study was to identify and to assess the best evidence currently available on the effectiveness of oral sensory-motor stimulation in preterm infants in the neonatal intensive care unit. We performed a systematic review following the Preferred Reporting Items for Systematic Reviews (PRISMA) statements. The search was conducted using the Pubmed, Web of Science (WOS), PEDro and Scopus databases. Clinical trials were reviewed and PEDro rating scale was used to assess the methodological quality of these studies. Results: 1267 studies were found and 11 were relevant and included in this review. Improvements were obtained in achieving independent feeding, maturation of the sucking pattern, transition to full feeding, motor function and length of hospital stay in most studies. Conclusions: there is evidence to support the benefits of the use of oral sensorimotor stimulation to achieve independent oral feeding in preterm infants, thereby reducing their stay in the Neonatal Intensive Care Unit.
UV Durable LCOS for Laser Processing
Authors: Sakurai Yasuki , Nishitateno Masashi , Ito Masahiro , Takatoh Kohki
Published: August 2021

Liquid-Crystal-On-Silicon (LCOS) Spatial Light Modulator (SLM) is widely used as a programmable adaptive optical element in many laser processing applications with various wavelength light sources. We report UV durable liquid-crystal-on-silicon spatial light modulators for one-shot laser material processing. Newly developed LCOS consists of UV transparent materials and shows a lifetime 480 times longer than the conventional one in 9.7 W/cm2 illumination at 355 nm. We investigated the durability of polymerization inhibitor mixed liquid crystal in order to extend its lifetime.