bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct costs of inflammatory bowel diseases in a Finnish tertiary-level clinic
Authors: Rankala Rasmus , Kosonen Juuso , Mattila Kalle , Tuominen Risto , Voutilainen Markku , Mustonen Anssi
Published: June 2020

Background

Inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are chronic diseases associated with a high and continuous economic burden. The introduction of biologics has changed the distribution of costs over the past two decades, and there are no recent studies on direct costs in Finland. This study aimed to estimate the direct healthcare costs of these diseases in a tertiary-level clinic.

Methods

The data were collected during a 1-year period of patients with IBD visiting Turku University Hospital. Patients were included if they lived in the hospital district area and were over 18 years old. This comprised an IBD group of 2208 patients, including 794 cases of CD and 1414 cases of UC. A sex-matched and age-matched control group was collected for comparison. Direct costs were collected during a 1-year study period from the hospital records.

Results

Total direct costs per patient with IBD in a tertiary-level clinic were €4223 annually. IBD-generated direct costs were estimated to total €3981 per patient annually. Patients with IBD who were given infliximab had €9157 higher direct healthcare costs per patient annually than patients with IBD with no infliximab medication. Direct healthcare costs generated in a tertiary-level gastroenterological clinic averaged €1652 per patient with IBD annually. On average, patients with CD had €1111 higher direct healthcare costs annually than patients with UC.

Conclusions

The direct healthcare costs of IBD were significant, almost 17-fold higher compared with a control group. Patients with IBD administered with biologics had significantly higher costs. Patients with CD had higher annual infliximab costs than patients with UC.
Loss of hepatic Mboat7 leads to liver fibrosis
Authors: Thangapandi Veera Raghavan , Knittelfelder Oskar , Brosch Mario , Patsenker Eleonora , Vvedenskaya Olga , Buch Stephan , Hinz Sebastian , Hendricks Alexander , Nati Marina , Herrmann Alexander , Rekhade Devavrat Ravindra , Berg Thomas , Matz-Soja Madlen , Huse Klaus , Klipp Edda , Pauling Josch K , Wodke Judith AH , Miranda Ackerman Jacobo , Bonin Malte von , Aigner Elmar , Datz Christian , von Schönfels Witigo , Nehring Sophie , Zeissig Sebastian , Röcken Christoph , Dahl Andreas , Chavakis Triantafyllos , Stickel Felix , Shevchenko Andrej , Schafmayer Clemens , Hampe Jochen , Subramanian Pallavi
Published: June 2020

Objective

The rs641738C>T variant located near the membrane-bound O-acyltransferase domain containing 7 (MBOAT7) locus is associated with fibrosis in liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease, hepatitis B and C. We aim to understand the mechanism by which the rs641738C>T variant contributes to pathogenesis of NAFLD.

Design

Mice with hepatocyte-specific deletion of MBOAT7 (Mboat7Δhep) were generated and livers were characterised by histology, flow cytometry, qPCR, RNA sequencing and lipidomics. We analysed the association of rs641738C>T genotype with liver inflammation and fibrosis in 846 NAFLD patients and obtained genotype-specific liver lipidomes from 280 human biopsies.

Results

Allelic imbalance analysis of heterozygous human liver samples pointed to lower expression of the MBOAT7 transcript on the rs641738C>T haplotype. Mboat7Δhepmice showed spontaneous steatosis characterised by increased hepatic cholesterol ester content after 10 weeks. After 6 weeks on a high fat, methionine-low, choline-deficient diet, mice developed increased hepatic fibrosis as measured by picrosirius staining (p<0.05), hydroxyproline content (p<0.05) and transcriptomics, while the inflammatory cell populations and inflammatory mediators were minimally affected. In a human biopsied NAFLD cohort, MBOAT7 rs641738C>T was associated with fibrosis (p=0.004) independent of the presence of histological inflammation. Liver lipidomes of Mboat7Δhepmice and human rs641738TT carriers with fibrosis showed increased total lysophosphatidylinositol levels. The altered lysophosphatidylinositol and phosphatidylinositol subspecies in MBOAT7Δheplivers and human rs641738TT carriers were similar.

Conclusion

Mboat7 deficiency in mice and human points to an inflammation-independent pathway of liver fibrosis that may be mediated by lipid signalling and a potentially targetable treatment option in NAFLD.
SOD3 induces a HIF-2α-dependent program in endothelial cells that provides a selective signal for tumor infiltration by T cells
Authors: Carmona-Rodríguez Lorena , Martínez-Rey Diego , Fernández-Aceñero Maria Jesús , González-Martín Alicia , Paz-Cabezas Mateo , Rodríguez-Rodríguez Noe , Pérez-Villamil Beatriz , Sáez Maria Eugenia , Díaz-Rubio Eduardo , Mira Emilia , Mañes Santos
Published: June 2020

Background

Tumor-infiltrating lymphocytes (TILs), mainly CD8+cytotoxic T lymphocytes (CTL), are linked to immune-mediated control of human cancers and response to immunotherapy. Tumors have nonetheless developed specific mechanisms that selectively restrict T cell entry into the tumor microenvironment. The extracellular superoxide dismutase (SOD3) is an anti-oxidant enzyme usually downregulated in tumors. We hypothesize that upregulation of SOD3 in the tumor microenvironment might be a mechanism to boost T cell infiltration by normalizing the tumor-associated endothelium.

Results

Here we show that SOD3 overexpression in endothelial cells increased in vitro transmigration of naïve and activated CD4+and CD8+T cells, but not of myeloid cells. Perivascular expression of SOD3 also specifically increased CD4+and CD8+effector T cell infiltration into tumors and improved the effectiveness of adoptively transferred tumor-specific CD8+T cells. SOD3-induced enhanced transmigration in vitro and tumor infiltration in vivo were not associated to upregulation of T cell chemokines such as CXCL9 or CXCL10, nor to changes in the levels of endothelial adhesion receptors such as intercellular adhesion molecule-1 (ICAM-1) or vascular cell adhesion molecule-1 (VCAM-1). Instead, SOD3 enhanced T cell infiltration via HIF-2α-dependent induction of specific WNT ligands in endothelial cells; this led to WNT signaling pathway activation in the endothelium, FOXM1 stabilization, and transcriptional induction of laminin-α4 (LAMA4), an endothelial basement membrane component permissive for T cell infiltration. In patients with stage II colorectal cancer, SOD3 was associated with increased CD8+TIL density and disease-free survival. SOD3 expression was also linked to a T cell–inflamed gene signature using the COAD cohort from The Cancer Genome Atlas program.

Conclusion

Our findings suggest that SOD3-induced upregulation of LAMA4 in endothelial cells boosts selective tumor infiltration by T lymphocytes, thus transforming immunologically “cold” into “hot” tumors. High SOD3 levels are associated with human colon cancer infiltration by CD8+T cells, with potential consequences for the clinical outcome of these patients. Our results also uncover a cell type–specific, distinct activity of the WNT pathway for the regulation of T cell infiltration into tumors.
Immunomodulatory effects of renin–angiotensin system inhibitors on T lymphocytes in mice with colorectal liver metastases
Authors: Vallejo Ardila Dora Lucia , Walsh Katrina A , Fifis Theodora , Paolini Rita , Kastrappis Georgios , Christophi Christopher , Perini Marcos Vinicius
Published: June 2020

Background

It is now recognized that many anticancer treatments positively modulate the antitumor immune response. Clinical and experimental studies have shown that inhibitors of the classical renin–angiotensin system (RAS) reduce tumor progression and are associated with better outcomes in patients with colorectal cancer. RAS components are expressed by most immune cells and adult hematopoietic cells, thus are potential targets for modulating tumor-infiltrating immune cells and can provide a mechanism of tumor control by the renin–angiotensin system inhibitors (RASi).

Aim

To investigate the effects of the RASi captopril on tumor T lymphocyte distribution in a mouse model of colorectal liver metastases.

Methods

Liver metastases were established in a mouse model using an autologous colorectal cancer cell line. RASi (captopril 750 mg/kg) or carrier (saline) was administered to the mice daily via intraperitoneal injection, from day 1 post-tumor induction to endpoint (day 15 or 21 post-tumor induction). At the endpoint, tumor growth was determined, and lymphocyte infiltration and composition in the tumor and liver tissues were analyzed by flow cytometry and immunohistochemistry (IHC).

Results

Captopril significantly decreased tumor viability and impaired metastatic growth. Analysis of infiltrating T cells into liver parenchyma and tumor tissues by IHC and flow cytometry showed that captopril significantly increased the infiltration of CD3+T cells into both tissues at day 15 following tumor induction. Phenotypical analysis of CD45+CD3+T cells indicated that the major contributing phenotype to this influx is a CD4 and CD8 double-negative T cell (DNT) subtype, while CD4+T cells decreased and CD8+T cells remained unchanged. Captopril treatment also increased the expression of checkpoint receptor PD-1 on CD8+and DNT subsets .

Conclusion

Captopril treatment modulates the immune response by increasing the infiltration and altering the phenotypical composition of T lymphocytes and may be a contributing mechanism for tumor control.
Renal kinetics in acute heart failure
Authors: Nhat M Giang , Hai H Nguyen , Ngoc-Hoa Chau
Published: June 2020

Aims

Worsening renal function (WRF) in acute heart failure (AHF) has multifactorial pathophysiological mechanisms and heterogeneous prognostic impacts. The aim of this study was to determine the characteristics and renal kinetics of this phenomenon.

Methods and results

We prospectively enrolled a cohort of 196 patients admitted for AHF to the Cardiology Department at Nhan Dan Gia Dinh Hospital, from July 2016 to March 2017. AHF was defined using the 2012 European Society of Cardiology criteria. The definition and severity of WRF were based on the 2012 Kidney Disease Improving Outcome criteria for acute kidney injury. Renal recovery was classified using the 2017 Acute Disease Quality Initiative 16 Workgroup Consensus. Among the 196 patients studied, WRF developed in 43.4%. In 80.0% of patients, WRF occurred within 48 hours of admission. In the WRF group, 89.4% were at stage 1, consistent with a relative increase in median serum creatinine of 49.5%. A total of 76.5% of the patients with WRF recovered at discharge, while rapid recovery occurred in 20.0% of patients.

Conclusions

Most cases of WRF were mild, and WRF was correlated with a high rate of recovery during hospitalisation. However, rapid renal recovery was not common.
Comparison between generalised peritonitis and parietal fibrinous peritonitis in cows after caesarean section
Authors: Djebala Salem , Evrard Julien , Moula Nassim , Gille Linde , Bayrou Calixte , Eppe Justine , Casalta Hélène , Sartelet Arnaud , Bossaert Philippe
Published: June 2020

Background

Parietal fibrinous peritonitis (PFP) and generalised peritonitis (GP) are two postoperative complications in cows, characterised by fluid and fibrin accumulation throughout the peritoneum (GP) or in an encapsulated cavity (PFP). Unlike GP, PFP is scarcely documented.

Methods

Twenty‐one GP cases and 12 PFP cases were confirmed by ultrasound in cows referred to the Veterinary Clinic (Liège University) for complications after caesarean section. All cows underwent a standardised examination protocol. Blood samples were analysed for metabolic and inflammatory markers. Bacteriology was performed on peritoneal fluid samples. Treatment consisted of surgical drainage of the abdominal cavity (GP) or the encapsulated cavity (PFP). Variables concerning anamnesis, clinical findings and treatment outcomes were compared.

Results

Perioperative complications had occurred in 9/21 GP cows but 0/12 PFP cows (P<0.05). Biochemical analysis indicated pronounced inflammation and did not differ between groups. Peritoneal fluid samples of both groups were contaminated and contained similar bacteria (Trueperella pyogenes and Escherichia coli). While 11/12 PFP cows were discharged, all patients with GP died or were euthanased (P<0.05).

Conclusions

We hypothesise that PFP and GP are two different manifestations of perioperative peritoneal contamination. The severity and spread of the contamination determine the clinical presentation and the prognosis.
Investigating the production of leptoquarks by means of zeros of amplitude at photon electron collider
Authors: Bandyopadhyay Priyotosh , Dutta Saunak , Karan Anirban
Published: June 2020

Leptoquarks belong to the possible candidates for explaining various anomalies in flavor physics. Nonetheless, their existence is yet to be confirmed on the experimental side. In this paper we show how zeros of the single-photon tree-level amplitude can be used to extract information as regards leptoquarks in the case of e–$$\gamma $$γ colliders. A small number of standard model backgrounds keep the signal clean in this kind of colliders. Unlike other colliders, the zeros of the single-photon amplitude here depend on $$\sqrt{s}$$s and on the mass of leptoquark along with its electric charge. We perform a PYTHIA based simulation for reconstructing the leptoquark from its decay products of the first generation and estimating the background with luminosity of $$100\ \hbox {fb}^{-1}$$100fb-1. Our analysis is done for all the leptoquarks that can be seen at an e–$$\gamma $$γ collider with three different masses (70 GeV, 650 GeV and 1 TeV) and three different center of momentum energies (200 GeV, 2 TeV and 3 TeV). The effects of non-monochromatic photons on the zeros of the amplitude under laser backscattering and the equivalent photon approximation have also been addressed.
Photodetachment in cold ion traps
Authors: Mant Barry P. , Nötzold Markus , González-Sánchez Lola , Wester Roland , Gianturco Franco A.
Published: June 2020

We present a computational investigation of the photodetachment (PD) dynamics of C2H− in its ground, electronic 1Σ state, cooled in an ion trap with He as a buffer gas. Our analysis employs a range of PD rates from quantum dynamics, selective choices of the anion’s initial rotational state populations as the laser is switched on, and different operational trap conditions. Our results show that a variety of outcomes for the initial state-dependent PD process is possible by selecting different initial conditions in the cold trap, the latter generating a dynamical interplay between the anion’s populations of rotational states, induced by the buffer gas, and the chosen laser frequency and laser power. Specific parameter selections during the PD process will be shown to cause different abundances of the rotational states of the anion in the trap.

Graphical abstract
Study of the Functional Brain Connectivity and Lower-Limb Motor Imagery Performance After Transcranial Direct Current Stimulation
Authors: Ortiz Mario , Iáñez Eduardo , Gaxiola-Tirado Jorge A. , Gutiérrez David , Azorín José M.
Published: June 2020

The use of transcranial direct current stimulation (tDCS) has been related to the improvement of motor and learning tasks. The current research studies the effects of an asymmetric tDCS setup over brain connectivity, when the subject is performing a motor imagery (MI) task during five consecutive days. A brain–computer interface (BCI) based on electroencephalography is simulated in offline analysis to study the effect that tDCS has over different electrode configurations for the BCI. This way, the BCI performance is used as a validation index of the effect of the tDCS setup by the analysis of the classifier accuracy of the experimental sessions. In addition, the relationship between the brain connectivity and the BCI accuracy performance is analyzed. Results indicate that tDCS group, in comparison to the placebo sham group, shows a higher significant number of connectivity interactions in the motor electrodes during MI tasks and an increasing BCI accuracy over the days. However, the asymmetric tDCS setup does not improve the BCI performance of the electrodes in the intended hemisphere.
Cascading failure of interdependent networks with dependence groups obeying different distributions
Authors: Zhang Min , Wang Xiaojuan , Jin Lei , Song Mei
Published: June 2020

Recent work on the cascading failure of networks with dependence groups assumes that the number of nodes in each dependence group is equal. In this paper, we construct a model on interdependent networks with dependence groups against cascading failure. The size of dependence group is supposed to obey the Poisson Distribution and the Truncated Normal Distribution, respectively. By applying the tools of mean-field approximation and the generating function techniques, the cascading model is theoretically analyzed and the theoretical solutions are nearly consistent with the simulation values. Besides, we define three kinds of coupling preferences based on node degree, i.e. assortative coupling, disassortative coupling and random coupling. The connection between layers is no longer one-to-one correspondence of nodes, but fully connection of some groups. In addition, some factors affecting the network robustness are discussed and extensive simulations are realized on two-layer BA networks. The simulation results show that the coupling preference has influence on the network robustness and the network with dependence groups obeying the Truncated Normal Distribution performs better than the Poisson Distribution.
Weighted trapping time of weighted directed treelike network
Authors: Dai Meifeng , Hou Yongbo , Ju Tingting , Dai Changxi , Sun Yu , Su Weiyi
Published: June 2020

With the deepening of research on complex networks, many properties of complex networks are gradually studied, for example, the mean first-passage times, the average receive times and the trapping times. In this paper, we further study the average trapping time of the weighted directed treelike network constructed by an iterative way. Firstly, we introduce our model inspired by trade network, each edge [Formula: see text] in undirected network is replaced by two directed edges with weights [Formula: see text] and [Formula: see text]. Then, the trap located at central node, we calculate the weighted directed trapping time (WDTT) and the average weighted directed trapping time (AWDTT). Remarkably, the WDTT has different formulas for even generations and odd generations. Finally, we analyze different cases for weight factors of weighted directed treelike network.
The influence of the scalar unparticle on the W-pair production at ILC in the Randall–Sundrum model
Authors: Soa Dang Van , Giang Bui Thi Ha
Published: June 2020

An attempt is made to present the contribution of the scalar unparticle on some scattering processes in the Randall–Sundrum (RS) model. We have evaluated the contribution of the scalar unparticle on the W-pair production cross-sections at International Linear Colliders (ILC). The results indicate that at the low values of the scaling dimension and the bounds on scale [Formula: see text] are around few TeV, the cross-sections are much enhanced, which is quite comparable with the W-production in the Standard Model and hence it is worthwhile to explore in future colliders.
Are models of local hidden variables for the singlet polarization state necessarily constrained by the Bell inequality?
Authors: Oaknin David H.
Published: June 2020

The Bell inequality is thought to be a common constraint shared by all models of local hidden variables that aim to describe the entangled states of two qubits. Since the inequality is violated by the quantum mechanical description of these states, it purportedly allows distinguishing in an experimentally testable way the predictions of quantum mechanics from those of models of local hidden variables and, ultimately, ruling the latter out. In this paper, we show, however, that the models of local hidden variables constrained by the Bell inequality all share a subtle, though crucial, feature that is not required by fundamental physical principles and, hence, it might not be fulfilled in the actual experimental setup that tests the inequality. Indeed, the disputed feature neither can be properly implemented within the standard framework of quantum mechanics and it is even at odds with the fundamental principle of relativity. Namely, the proof of the inequality requires the existence of a preferred absolute frame of reference (supposedly provided by the lab) with respect to which the hidden properties of the entangled particles and the orientations of each one of the measurement devices that test them can be independently defined through a long sequence of realizations of the experiment. We notice, however, that while the relative orientation between the two measurement devices is a properly defined physical magnitude in every single realization of the experiment, their global rigid orientation with respect to a lab frame is a spurious gauge degree of freedom. Following this observation, we were able to explicitly build a model of local hidden variables that does not share the disputed feature and, hence, it is able to reproduce the predictions of quantum mechanics for the entangled states of two qubits.
Quantum gravity effects on thermodynamics of de Sitter black holes in massive gravity
Authors: Khan Yawar H. , Ganai Prince A.
Published: June 2020

Taking de Sitter space–time as a thermodynamic system, we study the effects of quantum gravity on thermodynamic quantities of de Sitter black holes in massive gravity. We enumerate the leading order corrections arising in quantum gravity regime on various thermodynamic quantities like Helmholtz free energy, Gibbs free energy, specific heat and pressure. Our results show that quantum corrections have tendency to induce stability. Moreover we observe that the parameters from the massive gravity have deeper effect on the evolution of de Sitter space–time in quantum gravity regime. Such an analysis could be helpful in understanding inflation and evolution of universe at early times.
Condensates beyond the horizons
Authors: Alfaro Jorge , Espriu Domènec , Gabbanelli Luciano
Published: June 2020

In this work we continue our previous studies concerning the possibility of the existence of a Bose–Einstein condensate in the interior of a static black hole, a possibility first advocated by Dvali and Gómez. We find that the phenomenon seems to be rather generic and it is associated to the presence of a horizon, acting as a confining potential. We extend the previous considerations to a Reissner–Nordström black hole and to the de Sitter cosmological horizon. In the latter case the use of static coordinates is essential to understand the physical picture. In order to see whether a BEC is preferred, we use the Brown–York quasilocal energy, finding that a condensate is energetically favorable in all cases in the classically forbidden region. The Brown–York quasilocal energy also allows us to derive a quasilocal potential, whose consequences we explore. Assuming the validity of this quasilocal potential allows us to suggest a possible mechanism to generate a graviton condensate in black holes. However, this mechanism appears not to be feasible in order to generate a quantum condensate behind the cosmological de Sitter horizon.
The effects of the Tsallis entropy in the proton internal pressure
Authors: Campos S. D. , Amarante A. M.
Published: June 2020

In this paper, one discusses the effects of Tsallis entropy on the radial pressure distribution in the proton. Using a damped confinement potential the pressure distribution is obtained from the Tsallis entropy approach, being the entropic-index [Formula: see text] connected with the proton temperature concerning some transition temperature. Then, the approach allows the study of the proton thermal evolution up to the Quark–Gluon Plasma regime. The von Laue stability condition, arising from the pressure distribution results in positive and negative energy regions. An analogy between the results for the radial pressure distribution and the proton–proton and the antiproton–proton total cross-section is performed. The negative energy region is identified with the odderon exchange while the positive represents the pomeron exchange dominance above some transition energy [Formula: see text]. The hollowness effect is also discussed in terms of the results obtained and the proposed analogy.
Quantum superposition of massive bodies
Authors: Wald Robert M.
Published: June 2020

I describe the work done in collaboration with A. Belenchia, F. Giacomini, E. Castro-Ruiz, C. Bruckner and M. Aspelmeyer that analyzes a gedanken experiment involving a massive body that is put into a quantum superposition. Remarkably, even for a nonrelativistic body, both vacuum fluctuations of the gravitational field and the quantization of gravitational radiation are essential in order to avoid inconsistencies. In addition, it is essential that the quantum body be viewed as entangled with its own Newtonian-like gravitational field in order to understand how the body may become entangled with other massive bodies via gravitational interactions.
Decoding of the Relationship between Brain and Facial Muscle Activities in Response to Dynamic Visual Stimuli
Authors: Soundirarajan Mirra , Babini Mohammad Hossein , Sim Sue , Nathan Visvamba , Namazi Hamidreza
Published: June 2020

In this research, for the first time, we analyze the relationship between facial muscles and brain activities when human receives different dynamic visual stimuli. We present different moving visual stimuli to the subjects and accordingly analyze the complex structure of electromyography (EMG) signal versus the complex structure of electroencephalography (EEG) signal using fractal theory. Based on the obtained results from analysis, presenting the stimulus with greater complexity causes greater change in the complexity of EMG and EEG signals. Statistical analysis also supported the results of analysis and showed that visual stimulus with greater complexity has greater effect on the complexity of EEG and EMG signals. Therefore, we showed the relationship between facial muscles and brain activities in this paper. The method of analysis in this research can be further employed to investigate the relationship between other human organs’ activities and brain activity.
The Value of Discretion in Africa: Evidence from Acquired Intangible Assets Under IFRS 3
Authors: Tunyi Abongeh A. , Ehalaiye Dimu , Gyapong Ernest , Ntim Collins G.
Published: June 2020

This paper examines the value of managerial discretion in financial reporting by exploring the value relevance of intangible assets acquired in business combinations (AIA) before and after the 2008 International Financial Reporting Standard (IFRS) 3 amendment. The 2008 IFRS 3 amendment gave managers the discretion to recognize previously unrecognized intangibles in the target firm, hence, we posit that if managerial discretion improves the quality of financial reporting, we should observe an increase in the value relevance of AIA after the amendment. Our empirical analysis is based on a dataset of 603 mergers announced between 2004 and 2016, across seven African countries. Consistent with our main hypothesis, we find that the value relevance of AIA, predominantly acquired goodwill (AGW), increased after the amendment, suggesting that managerial discretion improves the quality of financial information. Our results further show that the value of discretion is moderated by the underlying institutional quality, with the value relevance of AIA being greater in high-quality institutional contexts. Our findings are robust to alternative measures of AIA, alternative models for testing value relevance, and various controls for endogeneity. Overall, our findings have important implications for accounting standard-setters, governments, investors, and practitioners.
Computing the Galois group of a polynomial over a p-adic field
Authors: Doris Christopher
Published: June 2020

We present a family of algorithms for computing the Galois group of a polynomial defined over a p-adic field. Apart from the “naive” algorithm, these are the first general algorithms for this task. As an application, we compute the Galois groups of all totally ramified extensions of [Formula: see text] of degrees 18, 20 and 22, tables of which are available online.
Quadratic residues and quartic residues modulo primes
Authors: Sun Zhi-Wei
Published: June 2020

In this paper, we study some products related to quadratic residues and quartic residues modulo primes. Let [Formula: see text] be an odd prime and let [Formula: see text] be any integer. We determine completely the product [Formula: see text] modulo [Formula: see text]; for example, if [Formula: see text] then [Formula: see text] where [Formula: see text] denotes the Legendre symbol. We also determine [Formula: see text] modulo [Formula: see text].
Overdischarge and Aging Analytics of Li-Ion Cells
Authors: Juarez-Robles Daniel , Vyas Anjul Arun , Fear Conner , Jeevarajan Judith A. , Mukherjee Partha P.
Published: June 2020

Overdischarge is a potential problem in large battery packs since cells in a series string are discharged under the same load, despite having different capacities. Although a single overdischarge does not necessarily cause a safety hazard, it forces electrodes outside their safe potential range and adversely affects the integrity of cell components. This work aims to fill the knowledge gap about the combined effect of aging-induced and overdischarge–induced degradation mechanisms. Graphite/LCO pouch cells are cycled at a moderate rate using four lower cutoff voltages: 2.7 V, 1.5 V, 0.0 V, and −0.5 V. The cells aged above the onset of reverse potential have an extended cycle life with aging-induced solid electrolyte interphase (SEI) growth and electrolyte decomposition as the main degradation mechanisms. In contrast, the cells aged under reversal condition (Elower≤ 0.0 V) exhibit fast degradation, dictated by the interplay among lithium plating, cathode particle cracking, and dissolution of Cu current collector. The analysis is complemented with a comparative study of various state of health (SoH) indicators, including an internal resistance based dimensionless SoH descriptor. The results prove that overdischarge-induced abuse although benign, may turn into a malignant condition when alternated with continuous charging.
App Corner - Summer 2020
Authors: Suroviec Alice
Published: June 2020

A collection of applications that can assist the end user in their daily routine.
Recent Developments in Electrocatalysis
Authors: Suroviec Alice
Published: June 2020

Electrocatalysis is the catalytic process involving oxidation and reduction reactions through the direct transfer of electrons between species at the electrochemical interface. An electrocatalyst specifically reduces the overpotential needed to allow the thermodynamically possible reaction to occur faster. These catalysts can be homogeneous, heterogeneous, or microbial in nature. Electrocatalysts are used in a wide range of fields, including corrosion, wastewater treatment, and energy storage. These promising applications will all be critical to a more sustainable energy future. The articles in the current issue of Interface look at this question of designing and using novel electrocatalysts from several different angles.
Strategies for Electrocatalytic Reduction and Photoelectrochemical Conversion of Carbon Dioxide to Fuels and Utility Chemicals
Authors: Kulesza Pawel J. , Rutkowska Iwona A.
Published: June 2020

There has been growing recent interest in the development of approaches to effectively sequester, capture or convert carbon dioxide to carbon-based simple organic fuels or utility chemicals. In principle, the low-temperature electrocatalytic and visible-light-induced photoelectrochemical approaches to reduction of CO2 show promise owing to their environmental compatibility and feasibility to combine with renewable energy sources. Electrochemical reductions of CO2 are multi-electron and multi-proton processes with considerable kinetic barriers requiring development of carefully designed electrode materials. Furthermore, when the CO2-reduction is performed in aqueous solutions, the competitive hydrogen evolution reaction is a complicating side-reaction. An additional problem is the appearance of the poisoning or passivating CO-type intermediates. Among important issues are the development of robust specific electrocatalytic systems and stable functionalized semiconducting photocatalytic materials, as well as the understanding of structure - activity relationships. In practical electrolysis cells, the CO2-reduction (at cathode) is accompanied by water oxidation (at anode or photoanode).
Autophagic Network Analysis of the Dual Effect of Sevoflurane on Neurons Associated with GABARAPL1 and 2
Authors: Lu Guolin , Rao Dongdong , Zhou Min , Liangpu Xu  , Zhang Longxin , Zhang Sujing , Wang Yuping
Published: June 2020

Background. Sevoflurane is commonly used as a general anesthetic in neonates to aged patients. Preconditioning or postconditioning with sevoflurane protects neurons from excitotoxic injury. Conversely, sevoflurane exposure induces neurotoxicity during early or late life. However, little is known about the underlying mechanism of the dual effect of sevoflurane on neurons. Autophagy is believed to control neuronal homeostasis. We hypothesized that autophagy determined the dual effect of sevoflurane on neurons. Methods. DTome was used to identify the direct protein target (DPT) of sevoflurane. The STRING database was employed to investigate the proteins associated with the DPTs. Protein‐protein interaction was assessed using Cytoscape. WebGestalt was used to analyze gene set enrichment. The linkage between candidate genes and autophagy was identified using GeneCards. Results. This study found that 23 essential DPTs of sevoflurane interacted with 77 proteins from the STRING database. GABARAPL1 and 2, both of which are DPT‐ and autophagy‐associated proteins, were significantly expressed in the brain and enriched in GABAergic synapses. Conclusions. Taken together, our findings showed that the network of sevoflurane‐DPT‐GABARAPL1 and 2 is related to the dual effect of sevoflurane on neurons.
A Novel Linguistic Z-Number QUALIFLEX Method and Its Application to Large Group Emergency Decision Making
Authors: Ding Xue-Feng , Zhu Li-Xia , Lu Mei-Shun , Wang Qi , Feng Yi-Qi
Published: June 2020

After an unconventional emergency event occurs, a reasonable and effective emergency decision should be made within a short time period. In the emergency decision making process, decision makers’ opinions are often uncertain and imprecise, and determining the optimal solution to respond to an emergency event is a complex group decision making problem. In this study, a novel large group emergency decision making method, called the linguistic Z-QUALIFLEX method, is developed by extending the QUALIFLEX method using linguistic Z-numbers. The evaluations of decision makers on the alternative solutions are first expressed as linguistic Z-numbers, and the group decision matrix is then constructed by aggregating the evaluations of all subgroups. The QUALIFLEX method is used to rank the alternative solutions for the unconventional emergency event. Besides, a real-life example of emergency decision making is presented, and a comparison with existing methods is performed to validate the effectiveness and practicability of the proposed method. The results show that the proposed linguistic Z-QUALIFLEX can accurately express the evaluations of the decision makers and obtain a more reasonable ranking result of solutions for emergency decision making.
Impact of Hepatic Steatosis on the Antiviral Effects of PEG-IFNα-2a in Patients with Chronic Hepatitis B and the Associated Mechanism
Authors: Liang Huiqing , Liu Yaoyu , Jiang Xiaoqian , Zheng Xiaoting , Tang Jinmo , Yang Jiaen , Zhuang Hongli , Lai Penghua , Peng Li , Guo Zhenying , Cai Shanshan , Luo Dan , Xu Lingxia , Mao Qianguo , Chen Shaodong
Published: June 2020

Objective. To investigate the risk factors for hepatic steatosis in chronic hepatitis B (CHB), to determine its correlation with liver necroinflammation and fibrosis and response to peginterferon alpha-2a (PEG-IFNα-2a) antiviral therapy, and to explore the mechanisms underlying the poor antiviral effect of PEG-IFNα-2a in CHB patients with hepatic steatosis. Methods. We analysed the impact of hepatic steatosis on the antiviral effect of PEG-IFNα-2a on CHB patients in a cohort of 226 patients who underwent pretherapeutic liver biopsy. To assess the complete response (CR), virological response (VR), and biochemical response (BR), the 226 patients were treated with PEG-IFNα-2a for 48 weeks and were followed-up for 24 weeks. The expressions of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in the liver tissue were detected in all patients to explore the possible mechanism of hepatic steatosis with regard to antiviral effects. Results. The patients were divided into four groups based on the severity of hepatic steatosis: 119 with no steatosis, 76 with mild steatosis, 22 with moderate steatosis, and 9 with severe steatosis. In the hepatic steatosis groups, the proportions of male patients, patients aged >40 years, patients with hyperuricaemia, patients with a BMI>23 kg/m2, and total cholesterol (TC), triglyceride (TG), glucose (GLU), and uric acid (UA) levels were significantly higher than those in the group without steatosis, whereas the alanine aminotransferase (ALT) and aspartate transaminase (AST) levels were significantly lower than those in the group without steatosis. The multivariate analysis results indicated that a BMI>23 kg/m2 was independently associated with CHB patients with hepatic steatosis; the levels of baseline AST and UA were independently associated with CHB patients with significant hepatic steatosis, and the baseline AST level was independently associated with significant liver fibrosis. After 48 weeks of treatment and 24 weeks of follow-up, the rates of CR, VR, and BR had gradually decreased, whereas the severity of hepatic steatosis had increased. Conclusion. Hepatic steatosis can reduce the efficacy of PEG-IFNα-2a in the treatment of CHB patients, and its mechanism may be related to the different HBcAg expression patterns in liver tissue.
Cell‐to‐Cell Spread of Dengue Viral RNA in Mosquito Cells
Authors: Cheng Chih-Chieh , Yang Chao-Fu , Lo Yin-Ping , Chiang Yi-Hsuan , Sofiyatun Eny , Wang Lian-Chen , Chen Wei-June
Published: June 2020

Dengue virus (DENV) is an important mosquito‐borne arbovirus that is particularly prevalent in tropical and subtropical areas of the world. The virus is generally ingested with a blood meal, replicates in host tissues, and disseminates into salivary glands for transmission to the next host. Membrane‐bound vacuoles carrying DENV particles have been documented in mosquito cells and play a role in the cell‐to‐cell transmission of DENV2. C189 is one member of the tetraspanin family and generally increases its expression as one component of the vacuoles (C189‐VCs) within C6/36 cells infected with DENV2. In the present study, we have further demonstrated via sucrose gradient centrifugation as well as magnetic immune isolation (MI) that the RNA of DENV2 was eventually carried by C189‐VCs. In addition, viral RNA was shown to spread from donor to recipient cells in a coculture assay even when 20 mM NH4Cl was added to inhibit virus replication in the culture. In an alternate assay using the transwell system, viral RNA was only detected in recipient cells in the absence of 40 mM NH4Cl, suggesting that cell‐cell contact is required for the intercellular spread of DENV2. In turn, the formation of viral synapse (VS) derived from aggregates of viral particles was frequently observed at sites of cell contact. Taken together, the formation of C189‐VCs in C6/36 cells is induced by DENV2 infection, which may serve as a vehicle for transferring virions and also viral RNA to neighboring cells by cell‐to‐cell transmission after cell‐cell contact. This finding provides insight into the understanding of viral spread between mosquito cells. It may also elucidate the benign persistent infection in mosquito cells and efficient dissemination of DENV infection within a mosquito vector.
Hexachloronaphthalene Induces Mitochondrial-Dependent Neurotoxicity via a Mechanism of Enhanced Production of Reactive Oxygen Species
Authors: Lisek Malwina , Stragierowicz Joanna , Guo Feng , Prosseda Philipp P. , Wiktorska Magdalena , Ferenc Bozena , Kilanowicz Anna , Zylinska Ludmila , Boczek Tomasz
Published: June 2020

Hexachloronaphthalene (PCN67) is one of the most toxic among polychlorinated naphthalenes. Despite the known high bioaccumulation and persistence of PCN67 in the environment, it is still unclear to what extent exposure to these substances may interfere with normal neuronal physiology and lead to neurotoxicity. Therefore, the primary goal of this study was to assess the effect of PCN67 in neuronal in vitro models. Neuronal death was assessed upon PCN67 treatment using differentiated PC12 cells and primary hippocampal neurons. At 72 h postexposure, cell viability assays showed an IC50 value of 0.35 μg/ml and dose-dependent damage of neurites and concomitant downregulation of neurofilaments L and M. Moreover, we found that younger primary neurons (DIV4) were much more sensitive to PCN67 toxicity than mature cultures (DIV14). Our comprehensive analysis indicated that the application of PCN67 at the IC50 concentration caused necrosis, which was reflected by an increase in LDH release, HMGB1 protein export to the cytosol, nuclear swelling, and loss of homeostatic control of energy balance. The blockage of mitochondrial calcium uniporter partially rescued the cell viability, loss of mitochondrial membrane potential (ΔΨm), and the overproduction of reactive oxygen species, suggesting that the underlying mechanism of neurotoxicity involved mitochondrial calcium accumulation. Increased lipid peroxidation as a consequence of oxidative stress was additionally seen for 0.1 μg/ml of PCN67, while this concentration did not affect ΔΨm and plasma membrane permeability. Our results show for the first time that neuronal mitochondria act as a target for PCN67 and indicate that exposure to this drug may result in neuron loss via mitochondrial-dependent mechanisms.
The Prevalence of Asthma and Asthma‐Like Symptoms among Seasonal Agricultural Workers
Authors: Saglan Yasemin , Bilge Ugur , Oztas Dilek , Saglan Ramazan , Sarı Yunus Emre , Balcıoglu Huseyin , Unluoglu Ilhami
Published: June 2020

Aim. The aim of the study was to determine the prevalence and risk factors of asthma and asthma‐like symptoms in seasonal agricultural workers living in fields with toxic chemical exposure. Methods. European Community Respiratory Health Survey (ECRHS) questionnaire was used to assess the prevalence of asthma and asthma‐like symptoms in the study. Results. Of the study group, 51.1% (267) were male and the age of the study group ranged from 18 to 88 years and the mean (SD) was 45.68 (13.39) years. The prevalence of asthma attacks in seasonal agricultural workers in the last one year (current prevalence) was 11.2%; the prevalence of asthma (cumulative prevalence) was 15.1%. In the study, smoking was found to be an important risk factor for current asthma. The prevalence of cumulative asthma was higher in seasonal agricultural workers with allergic rhinitis (p < 0.05 for each). Conclusions. Seasonal agricultural workers are exposed to the worst conditions of working groups. These difficult conditions also cause many health problems. Asthma has also been identified as an important health problem among seasonal agricultural workers.
The Quantitative Relationship among the Number of the Pacing Cells Required, the Dimension, and the Diffusion Coefficient
Authors: Zhang Yue , Yin Guisheng , Wang Kuanquan
Published: June 2020

The purpose of the paper is to derive a formula to describe the quantitative relationship among the number of the pacing cells required (NPR), the dimension i, and the diffusion coefficient D (electrical coupling or gap junction G). The relationship between NPR and G has been investigated in different dimensions, respectively. That is, for each fixed i, there is a formula to describe the relationship between NPR and G; and three formulas are required for the three dimensions. However, there is not a universal expression to describe the relationship among NPR, G, and i together. In the manuscript, surveying and investigating the basic law among the existed data, we speculate the preliminary formula of the relationship among the NPR, i, and G; and then, employing the cftool in MATLAB, the explicit formulas are derived for different cases. In addition, the goodness of fit (R2) is computed to evaluate the fitting of the formulas. Moreover, the 1D and 2D ventricular tissue models containing biological pacemakers are developed to derive more data to validate the formula. The results suggest that the relationship among the NPR, i, and the G (D) could be described by a universal formula, where the NPR scales with the i (the dimension) power of the product of the square root of G (D) and a constant b which is dependent on the strength of the pacing cells and so on.
A Phase II Study of Allogeneic GM-CSF–Transfected Pancreatic Tumor Vaccine (GVAX) with Ipilimumab as Maintenance Treatment for Metastatic Pancreatic Cancer
Authors: Wu Annie A. , Bever Katherine M. , Ho Won Jin , Fertig Elana J. , Niu Nan , Zheng Lei , Parkinson Rose M. , Durham Jennifer N. , Onners Beth , Ferguson Anna K. , Wilt Cara , Ko Andrew H. , Wang-Gillam Andrea , Laheru Daniel A. , Anders Robert A. , Thompson Elizabeth D. , Sugar Elizabeth A. , Jaffee Elizabeth M. , Le Dung T.
Published: June 2020

Purpose:

This phase II study tested granulocyte-macrophage colony-stimulating factor (GM-CSF)-allogeneic pancreatic tumor cells (GVAX) and ipilimumab in metastatic pancreatic ductal adenocarcinoma (PDA) in the maintenance setting.

Patients and Methods:

Patients with PDA who were treated with front-line chemotherapy consisting of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) in the metastatic setting and had ongoing response or stable disease after 8–12 doses were eligible. Patients were randomized 1:1 to treatment with GVAX and ipilimumab given every 3 weeks for four doses then every 8 weeks (Arm A) or to FOLFIRINOX continuation (Arm B). The primary objective was to compare overall survival (OS) between the two arms.

Results:

Eighty-two patients were included in the final analysis (Arm A: 40; Arm B: 42). The study was stopped for futility after interim analysis. Median OS was 9.38 months [95% confidence interval (CI), 5.0–12.2] for Arm A and 14.7 months (95% CI, 11.6–20.0) for Arm B (HR, 1.75; P = 0.019). Using immune-related response criteria, two partial responses (5.7%) were observed in Arm A and four (13.8%) in Arm B. GVAX + ipilimumab promoted T-cell differentiation into effector memory phenotypes both in the periphery and in the tumor microenvironment and increased M1 macrophages in the tumor.

Conclusions:

GVAX and ipilimumab maintenance therapy did not improve OS over continuation of chemotherapy and resulted in a numerically inferior survival in metastatic PDA. However, clinical responses and biological effects on immune cells were observed. Further study of novel combinations in the maintenance treatment of metastatic PDA is feasible.