bluuebunny/crossref_metadata_2025 huggingface dataset:
Rastall gravity extension of the standard $$\Lambda $$CDM model: theoretical features and observational constraints
Authors: Akarsu Özgür , Katırcı Nihan , Kumar Suresh , Nunes Rafael C. , Öztürk Burcu , Sharma Shivani
Published: November 2020

We present a detailed investigation of the Rastall gravity extension of the standard $$\Lambda $$
Λ
CDM model. We review the model for two simultaneous modifications of different nature in the Friedmann equation due to the Rastall gravity: the new contributions of the material (actual) sources (considered as effective source) and the altered evolution of the material sources. We discuss the role/behavior of these modifications with regard to some low redshift tensions, including the so-called $$H_0$$

H
0

tension, prevailing within the standard $$\Lambda $$
Λ
CDM. We constrain the model at the level of linear perturbations, and obtain the first constraints through a robust and accurate analysis using the latest full Planck cosmic microwave background (CMB) data, with and without including baryon acoustic oscillations (BAO) data. We find that the Rastall parameter $$\epsilon $$
ϵ
(null for general relativity) is consistent with zero at 68% CL (with a tendency towards positive values, $$-0.0001< \epsilon < 0.0007$$

-
0.0001
<
ϵ
<
0.0007

(CMB+BAO) at 68% CL), which in turn implies no significant statistical evidence for deviation from general relativity, and also a precision of $$\mathcal {O}(10^{-4})$$

O
(

10

-
4

)

for the coefficient $$-1/2$$

-
1
/
2

of the term $$g_{\mu \nu }R$$

g

μ
ν

R

in the Einstein field equations of general relativity (guaranteeing the local energy-momentum conservation). We explore the consequences led by the Rastall gravity on the cosmological parameters in the light of the observational analyses. It turns out that the effective source, with a present-day density parameter $$\Omega _\mathrm{X0}=-0.0010\pm 0.0013$$

Ω

X
0

=
-
0.0010
±
0.0013

(CMB+BAO, 68% CL), dynamically screens the usual vacuum energy at high redshifts, but this mechanism barely works due to the opposition by the altered evolution of cold dark matter. Consequently, two simultaneous modifications of different nature in the Friedmann equation by the Rastall gravity act against each other, and do not help to considerably relax the low redshift tensions, including the so-called $$H_0$$

H
0

tension. Our results may offer a guide for the research community that studies the Rastall gravity in various aspects of gravitation and cosmology.
Revisiting the production of $$J/\psi $$ pairs at the LHC
Authors: Prokhorov A. A. , Lipatov A. V. , Malyshev M. A. , Baranov S. P.
Published: November 2020

We consider the prompt double$$J/\psi $$J/ψproduction inppcollisions at the LHC in the framework of$$k_T$$kT-factorization QCD approach. Using the fragmentation mechanism, we evaluate the color octet contributions to the production cross sections taking into account the combinatorial effects of multiple gluon radiation in the initial state driven by the Ciafaloni–Catani–Fiorani–Marchesini evolution equation. We demonstrate the importance of these contributions in a certain kinematical region covered by the CMS and ATLAS measurements. On the other hand, the experimental data taken by the LHCb Collaboration at forward rapidities and moderate transverse momenta can be described well by$${{{\mathcal {O}}}}(\alpha _s^4)$$O(αs4)color singlet terms and contributions from the double parton scattering mechanism. The extracted value of the effective cross section is compatible with many other estimations based on different final states.
Super Ginsparg–Wilson algebra and Dirac operator on the super fuzzy Euclidean hyperboloid EAdSF(2|2)
Authors: Lotfizadeh M.
Published: November 2020

In this paper, we construct super fuzzy Dirac and chirality operators on the super fuzzy Euclidean hyperboloid [Formula: see text] in-instanton and no-instanton sectors. Using the super pseudo-projectors of the noncompact first Hopf fibration, we construct the Ginsparg–Wilson algebra in instanton and no-instanton sectors. Then, using the generators of this algebra, we construct pseudo super-Dirac and chirality operators in both sectors. We also construct pseudo super-Dirac and chirality operators corresponding to the case in which our theory includes gauge fields. We show that they have correct commutative limit in the limit case when the noncommutative parameter [Formula: see text] tends to infinity.
Gross misinterpretation of a conditionally solvable eigenvalue equation
Authors: Amore Paolo , Fernández Francisco M.
Published: November 2020

We solve an eigenvalue equation that appears in several papers about a wide range of physical problems. The Frobenius method leads to a three-term recurrence relation for the coefficients of the power series that, under suitable truncation, yields exact analytical eigenvalues and eigenfunctions for particular values of a model parameter. From these solutions some researchers have derived a variety of predictions like allowed angular frequencies, allowed field intensities and the like. We also solve the eigenvalue equation numerically by means of the variational Ritz method and compare the resulting eigenvalues with those provided by the truncation condition. In this way we prove that those physical predictions are merely artifacts of the truncation condition.
Dynamical transition from a naked singularity to a black hole
Authors: Hioki Kenta , Harada Tomohiro
Published: November 2020

We show that a Reissner–Nordström (RN) black hole can be formed by dropping a charged thin dust shell onto a RN naked singularity. This is in contrast to the fact that a RN naked singularity is prohibited from forming by dropping a charged thin dust shell onto a RN black hole. This implies the strong tendency of the RN singularity to be covered by a horizon in favor of cosmic censorship. We show that an extreme RN black hole can also be formed from a RN naked singularity by the same process in a finite advanced time. We also discuss the evolution of the charged thin dust shells and the causal structure of the resultant space–times. a

a The statements expressed in this paper are those of the authors and do not represent the views of Sumitomo Mitsui Banking Corporation or its staff.
Sub-cycle dynamics of nonsequential double ionization of Ar atom by few-cycle counter-rotating two-color circularly polarized laser fields
Authors: Pang Huiling , Huang Xuefei , Huang Cheng
Published: November 2020

We have investigated the sub-cycle correlated electron dynamics of nonsequential double-ionization (NSDI) of Ar atom by few-cycle counter-rotating two-color circularly polarized (TCCP) laser fields using a three-dimensional classical ensemble model. Numerical results indicate that NSDI probability sensitively depends on the relative phase of the two components and achieves its maximum at the relative phase 0.7[Formula: see text]. Back analysis of NSDI trajectories shows that the return angle of the electron is closely related to the relative phase of the two components and can continuously be controlled by changing the relative phase. Furthermore, the relative phase also influences the relative contribution of recollision-induced direct ionization (RII) and recollision-induced excitation with subsequent field ionization (RESI) to NSDI and the final emitted direction of the electrons.
Electron-ion dynamics of hydroperoxyl radical under intense femtosecond laser pulses
Authors: Wang Zhiping , Xu Xuefen , Zhang Fengshou , Qian Chaoyi
Published: November 2020

The electron-ion dynamics of hydroperoxyl radical in intense femtosecond laser pulses is studied by using time-dependent density functional theory combined with molecular dynamics approach. We calculate the optimized structure, the ionization energy, and the optical absorption strength. The results are in good agreement with experiments. The irradiation dynamics of HO2 including the ionization, the dipole moment, the bond lengths, the kinetic energies, and the level depletion is explored by varying the laser frequency. Computational results indicate that the excitation behaviors are distinct due to different frequencies. Furthermore, the angular dependence of the total ionization and the orbital ionization yields of HO2 are explored. The calculated result predicts a maximum around [Formula: see text] and [Formula: see text] for the total ionization and the angular dependence of the total ionization reflects the symmetry of the HOMO.
Synthesis of Sm3+ and Gd3+ Ions Embedded in Nano-Structure Barium Titanate Prepared by Sol-Gel Technique: Terahertz, Dielectric and Up-Conversion Study
Authors: Hameed Talaat A. , Mohamed F. , Mansour A. M. , Battisha I. K.
Published: November 2020

Nano-structure Barium Titanate (BaTiO3) doped with 1 mole% Sm3+ and Gd3+ ions have been synthesized by modified sol-gel process. The tetragonal perovskite structure has been demonstrated by means of X-ray diffraction and selected area electron diffraction obtained by high resolution transmission microscopy. The XRD and HRTEM have been used for estimation the grain size, which found to be around 38.36 and 33.26 nm. The scanning electron microscope micrographs asserted the formation of agglomerated particles, which is characteristic of many nano-systems. The green emission has been observed at 528, 567 and 597 nm, whereas red group emission at 604, 611, 632, 643, 660, 672, 688, 716 and 732. The thermal stability and the purity of the synthesized material were confirmed by the results of Thermogravimetric Analysis (TGA) and differential scanning calorimetry (DSC). Two relaxation processes were observed in the dielectric loss εʹ as well as in the modulus spectra of both samples. The dielectric behavior was further discussed in the range of terahertz by using the time domain terahertz spectrophotometer. the refractive index in terahertz were found to be dwindle, whereas the absorption coefficient improved upon increasing THz frequencies.
A Systematic Review on Traditional Uses, Sources, Phytochemistry, Pharmacology, Pharmacokinetics, and Toxicity of Fritillariae Cirrhosae Bulbus
Authors: Chen Ting , Zhong Furong , Yao Cheng , Chen Jia , Xiang Yiqing , Dong Jijing , Yan Zhuyun , Ma Yuntong
Published: November 2020

Fritillariae Cirrhosae Bulbus (known as chuanbeimu in Chinese, FCB) is a famous folk medicine which has been widely used to relieve cough and eliminate phlegm for thousands of years in China. The medicine originates from dried bulbs of six species of Fritillaria which are distributed in the temperate zone of the Northern Hemisphere. Increasing attention has been paid to FCB because of its excellent medicinal value such as being antitussive, expectorant, analgesic, anticancer, anti‐inflammatory, and antioxidative. During the past years, a large number of research studies have been conducted to investigate the phytochemistry, pharmacology, and pharmacokinetics of FCB. A range of compounds have been isolated and identified from FCB, including alkaloids, saponins, nucleosides, organic acids, terpenoids, and sterols. Among them, alkaloids as the main active ingredient have been illustrated to exert significant therapeutic effects on many diseases such as cancer, acute lung injury, chronic obstructive pulmonary disease, asthma, Parkinson’s disease, and diabetes. Due to the excellent medical value and low toxicity, FCB has a huge market all over the world and triggers a growing enthusiasm among researchers. However, there is still a lack of systematic review. Hence, in this work, we reviewed the FCB‐based articles published in Sci Finder, Web of Science, PubMed, Google Scholar, CNKI, and other databases in the recent years. The traditional uses, sources, phytochemistry, pharmacology, pharmacokinetics, and toxicity of FCB were discussed in the review, which aims to provide a reference for further development and utilization of FCB.
On the Multiwavelets Galerkin Solution of the Volterra–Fredholm Integral Equations by an Efficient Algorithm
Authors: Jebreen H. Bin
Published: November 2020

We develop the multiwavelet Galerkin method to solve the Volterra–Fredholm integral equations. To this end, we represent the Volterra and Fredholm operators in multiwavelet bases. Then, we reduce the problem to a linear or nonlinear system of algebraic equations. The interesting results arise in the linear type where thresholding is employed to decrease the nonzero entries of the coefficient matrix, and thus, this leads to reduction in computational efforts. The convergence analysis is investigated, and numerical experiments guarantee it. To show the applicability of the method, we compare it with other methods and it can be shown that our results are better than others.
Recursive State and Random Fault Estimation for Linear Discrete Systems under Dynamic Event-Based Mechanism and Missing Measurements
Authors: Tian Xuegang , Wang Shaoying
Published: November 2020

This paper is concerned with the event-based state and fault estimation problem for a class of linear discrete systems with randomly occurring faults (ROFs) and missing measurements. Different from the static event-based transmission mechanism (SETM) with a constant threshold, a dynamic event-based mechanism (DETM) is exploited here to regulate the threshold parameter, thus further reducing the amount of data transmission. Some mutually independent Bernoulli random variables are used to characterize the phenomena of ROFs and missing measurements. In order to simultaneously estimate the system state and the fault signals, the main attention of this paper is paid to the design of recursive filter; for example, for all DETM, ROFs, and missing measurements, an upper bound for the estimation error covariance is ensured and the relevant filter gain matrix is designed by minimizing the obtained upper bound. Moreover, the rigorous mathematical analysis is carried out for the exponential boundedness of the estimation error. It is clear that the developed algorithms are dependent on the threshold parameters and the upper bound together with the probabilities of missing measurements and ROFs. Finally, a numerical example is provided to indicate the effectiveness of the presented estimation schemes.
Follicle-Stimulating Hormone Positively Associates with Metabolic Factors in Perimenopausal Women
Authors: Zhang Chen , Zhao Meng , Li Zhengyang , Song Yongfeng
Published: November 2020

Objective. Menopause is associated with the increased risk of metabolic syndrome (MetS) and cardiovascular (CV) disease. Most studies have focused the postmenopausal women and the relationships among estrogen, androgen, and Mets risk. The main aim of the study was to investigate the Mets risk in perimenopausal women and whether the variation of FSH is associated with metabolic factors. Methods. A single-center cross-sectional retrospective analysis including 154 premenopausal women and 124 perimenopausal women was performed. Results. The prevalence of Mets in the perimenopausal group was much higher than the premenopausal group (49.19% vs. 35.71%,

p
=
0.023

). The prevalence of central obesity and NAFLD also increased in the perimenopausal group than in the premenopausal group. We grouped the population by FSH tertiles; compared with women in the lowest tertile, women in the highest tertile had higher age, WC, serum TC, LDL-C, AST, ALT, and creatine levels. The prevalence of hypertriglyceridemia, raised BP and Mets also increased in the highest tertile group. Further, we subdivided the perimenopausal women according to FSH tertiles. Compared with perimenopausal women in the lowest tertile, the prevalence of raised BP significantly increased in the highest tertile. Conclusions. The risk of Mets increased in perimenopausal females than in premenopausal women. And a higher FSH level was associated with higher WC, TG, BPs, and the risk of Mets in perimenopausal women. Elevated FSH level appears to be a risk factor of MetS biomarkers in perimenopausal women.
Pain Experiences and Their Relation to Opioid Misuse Risk and Emotion Dysregulation
Authors: Nauser Jonathan W. , Nelson Cecelia I. , Gross Richard T. , Vargovich Alison M.
Published: November 2020

Pain is a complex, multidimensional experience but often is measured as a unidimensional experience. This study aimed to separately assess the sensory and affective components of pain and identify their relations to important pain-related outcomes, particularly in terms of opioid misuse risk and emotion dysregulation among patients with chronic pain receiving treatment in Appalachia. Two hundred and twelve patients presenting to a multidisciplinary pain center completed the Difficulties in Emotion Regulation Scale (DERS-18), Screener and Opioid Assessment for Patients with Pain—Revised (SOAPP-R), and short-form McGill Pain Questionnaire (SF-MPQ). The sensory experience of pain was unrelated to emotion dysregulation (r = 0.06,

p
=
0.57

) and weakly related to opioid misuse risk (r = 0.182,

p
<
0.05

). In contrast, the affective experience of pain was moderately related to emotion dysregulation (r = 0.217,

p
<
0.05

) and strongly related to opioid misuse risk (r = 0.37,

p
<
0.01

). In addition, emotion dysregulation predicted variance in opioid misuse risk above and beyond the affective and sensory experiences of pain ((b = 0.693,

p
<
0.001

). The results suggest patients with a strong affective experience versus sensory experience of pain and challenges with emotion regulation may require a more comprehensive intervention to address these underlying components in order to reduce their risk of misusing opioid medications.
Potential Roles of the Renin‐Angiotensin System in the Pathogenesis and Treatment of COVID‐19
Authors: Lu Ling , Liu Xiaomei , Jin Rong , Guan Renzheng , Lin Rongjun , Qu Zhenghai
Published: November 2020

The spread of pathogenic severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) poses a global health emergency. Based on the symptomatic treatment and supporting therapy, prevention of complications is the major treatment option. Therefore, it is necessary to illustrate the potential mechanisms for the pathogenesis of COVID‐19. Angiotensin‐converting enzyme 2 (ACE2), the major receptor of SARS‐CoV‐2, is one of the major members of the renin‐angiotensin system (RAS). In this review, we aimed to summarize the crucial roles of ACE2 in the pathogenesis of COVID‐19, followed by illustrating potential treatment options relating to ACE2 and the RAS.
An Experimental and Numerical Investigation on the Initiation and Interaction of Double Cracks in Rocks under Hydromechanical Coupling
Authors: Mei Jie , Zhang Wanzhi
Published: November 2020

The growth of double cracks is the main factor leading to progressive rock failure under hydromechanical coupling. The initiation modes and interaction behaviors of double cracks were investigated by using laboratory tests, and the influences of water pressure were analyzed. The maximum energy release rate criterion was modified to determine the crack growth characteristics. A numerical model was established and then verified by the test results. Based on the simulation, the distribution of stress fields and key fracture parameters of double cracks was investigated. Then, initiation characteristics and interaction behaviors of parallel and nonparallel cracks were quantitatively analyzed. The results indicate that the increase in water pressure leads to the crack initiation being inclined to the original surfaces and the growth length along the crack fronts tending to be uniform; the small tensile stress zones are formed close to the crack tips, and significant compressive stress zones are formed at both sides of the crack surfaces; stress superposition and interaction occur when crack spacing is less than 2.5a; the interactive weakening effect is mainly present in the inner side (rock bridge zone) of cracks, while a certain degree of interactive enhancement effect exhibits in the outer sides; the cracks are much easier to initiate at the outer wing cracks when the spacing is less than the critical length (0.5a); and cracks with a dip angle of 45° are much easier to initiate at the endpoints of long axis. The research results provide certain theoretical guidance for the safety assessment of underground engineering.
Moving Vehicle Tracking Optimization Method Based on SPF
Authors: Lv Caixia , Zhang Xuejing
Published: November 2020

In the intelligent transportation system, the license information can be automatically recognized by the computer and the vehicle can be tracked. Red light running, illegal change of lanes, vehicle retrograde, and other illegal driving events are reasonably recorded. This is undoubtedly an effective help for the traffic police to relieve the huge work pressure. However, in China, a considerable number of vehicle tracking methods have certain limitations in resisting complex external environmental influences. The external environmental factors include but not limited to variable factors such as camera movement, jitter, and severe rain and snow. These factors cannot be controlled well, so the tracking accuracy is greatly reduced. In regard to this, this paper proposes an optimization method for moving vehicle tracking based on SPF. First, according to the size of the overlapping area of the motion area between the two images, the researcher can construct and simplify the vertex adjacency matrix that reflects the characteristics of the undirected bipartite graph. Then according to the corresponding relationship between the vertex adjacency matrix and the regional behavior and vehicle behavior, the researcher completes the regional behavior analysis and vehicle behavior analysis. On this basis, a particle filter vehicle tracking algorithm based on segmentation compensation is introduced, and the vector sum of the tracked segmentation area is used as the final position of the target vehicle. In this way, as many scattered particles fall on the target area as possible, which will greatly improve the efficiency of particle utilization, enhance tracking accuracy, and avoid the problem of tracking failure caused by too fast vehicle movement. Through experimental simulation, it can be seen that the method proposed in this paper can greatly enhance the vehicle tracking ability when tracking vehicles in “complex environments.”
Wireless Network Indoor Positioning Method Using Nonmetric Multidimensional Scaling and RSSI in the Internet of Things Environment
Authors: Wang Shuxia
Published: November 2020

Aiming at the problem that the indoor target location algorithm based on received signal strength (RSSI) in the IoT environment is susceptible to interference and large fluctuations, an indoor localization algorithm combining RSSI and nonmetric multidimensional scaling (NMDS) is proposed (RSSI- NMDS). First, Gaussian filtering is performed on the received plurality of sets of RSSI signals to eliminate abnormal fluctuations of the RSSI. Then, based on the RSSI data, the dissimilarity matrix is constructed, and the relative coordinates of the nodes in the low-dimensional space are obtained by NMDS solution. Finally, according to the actual coordinates of the reference node, the coordinate transformation is performed by the planar four-parameter model, and the position of the node in the actual coordinate system is obtained. The simulation results show that the proposed method has strong anti-RSSI perturbation and high positioning accuracy.
Prevalence and Factors Associated with Sexually Transmitted Infections among Jimma University Students, Southwest Ethiopia
Authors: Tamrat Rahel , Kasa Tesfaye , Sahilemariam Zewdineh , Gashaw Mulatu
Published: November 2020

Background. Globally, one-third of new sexually transmitted infection (STI) cases occur in people under 25 years of age every year. University students are in the youth age category and are exposed to risky sexual behaviors such as unprotected sexual intercourse leading to STIs. Therefore, this study was aimed to assess the prevalence and associated factors of STI among Jimma University students. Method. A health facility-based cross-sectional study was conducted at Jimma University students’ clinic from April 2017 to October 2017 among students with STI syndromes. Urethral, endocervical, and vaginal discharge swabs were collected by attending nurses. Standard protocol was followed to detect the etiologies of STI. Data were entered and analyzed using SPSS Version 20. Results. The overall prevalence of STIs among clinically suspected university students was 14.3%. The predominant causes of STI were Neisseria gonorrhoeae (7.4%) followed by T. vaginalis (4.8%) and T. pallidum (3.7%). Having had sex after taking alcohol was significantly associated with STIs (P≤0.000). All N. gonorrhoeae isolates were found to be resistant to penicillin and tetracycline. Conclusion. In this study, the prevalence of STI was relatively high. The isolated N. gonorrhoeae was resistant to commonly prescribed antibiotics. Therefore, evidence-based treatment and proper reproductive health education for youth are highly recommended.
Rosanortriterpenes A–B, Two Promising Agents from Rosa laevigata var. leiocapus, Alleviate Inflammatory Responses and Liver Fibrosis in In Vitro Cell Models
Authors: Li Bai-Lin , Hu Juan-Juan , Xie Jin-Dan , Ni Chen , Liang Hui-Jun , Li Qian-Ran , Yuan Jie , Wu Jie-Wei
Published: November 2020

Rosanortriterpenes A–B (RTA and RTB), two nortriterpenoids, are characteristic constituents in the fruits of Rosa laevigata var. leiocapus. However, pharmacological studies on these compounds are still scarce. In the present study, we aim to investigate the anti‐inflammatory mechanisms associated with the effects of RTA–B in RAW264.7 macrophages and LO2 cells by detecting cell viabilities, nitric oxide (NO) production, tumour necrosis factor‐alpha (TNF‐α), and interleukin‐6 (IL‐6) production. Simultaneously, the anti‐inflammatory action mechanisms of these two compounds were illustrated through western blot assay. Besides, the antihepatic fibrosis activities of these compounds have also been explored. The results demonstrated that RTA and RTB inhibited the production of NO, TNF‐α, and IL‐6 and suppressed liver fibrosis. RTA and RTB treatment also greatly inhibited the activation of NF‐kappaB (NF‐κB) pathway. Our study confirmed the promising anti‐inflammatory and anti‐liver fibrosis actions of RTA–B, suggesting that they might be developed as alternative and promising drugs for the treatment of hepatic inflammatory and fibrotic diseases.
A CRISPR Screen Reveals Resistance Mechanisms to CD3-Bispecific Antibody Therapy
Authors: Liu Si-Qi , Grantham Alyssa , Landry Casey , Granda Brian , Chopra Rajiv , Chakravarthy Srinivas , Deutsch Sabine , Vogel Markus , Russo Katie , Seiss Katherine , Tschantz William R. , Rejtar Tomas , Ruddy David A. , Hu Tiancen , Aardalen Kimberly , Wagner Joel P. , Dranoff Glenn , D'Alessio Joseph A.
Published: November 2020

CD3-bispecific antibodies represent an important therapeutic strategy in oncology. These molecules work by redirecting cytotoxic T cells to antigen-bearing tumor cells. Although CD3-bispecific antibodies have been developed for several clinical indications, cases of cancer-derived resistance are an emerging limitation to the more generalized application of these molecules. Here, we devised whole-genome CRISPR screens to identify cancer resistance mechanisms to CD3-bispecific antibodies across multiple targets and cancer types. By validating the screen hits, we found that deficiency in IFNγ signaling has a prominent role in cancer resistance. IFNγ functioned by stimulating the expression of T-cell killing–related molecules in a cell type–specific manner. By assessing resistance to the clinical CD3-bispecific antibody flotetuzumab, we identified core fucosylation as a critical pathway to regulate flotetuzumab binding to the CD123 antigen. Disruption of this pathway resulted in significant resistance to flotetuzumab treatment. Proper fucosylation of CD123 was required for its normal biological functions. In order to treat the resistance associated with fucosylation loss, flotetuzumab in combination with an alternative targeting CD3-bispecific antibody demonstrated superior efficacy. Together, our study reveals multiple mechanisms that can be targeted to enhance the clinical potential of current and future T-cell–engaging CD3-bispecific antibody therapies.
Susceptibility of Dental Enamel of Different Ages to Caries-Like Lesion Development
Authors: Barreto de Oliveira Renata D. , de Sousa Frederico Barbosa , Algarni Amnah A. , Eckert George J. , Hara Anderson T.
Published: November 2020

This study investigated the impact of estimated age, anatomical location, and the presence of wear facets on the susceptibility of enamel to develop caries-like lesions. Extracted human premolars (n = 261) had their age estimated between 10 and 93 years old, using established forensic methods. Specimens of enamel (4 × 4 mm) were prepared from the middle of the buccal surfaces, preserving the outer surface layer. The central area of the block (4 × 1 mm) was protected with nail polish and used as an internal control. The specimens were demineralized for 8 days (with 0.1 M acetic acid, 1.28 mM Ca, 0.74 mM Pi, and 0.03 µg F/mL, pH 5.0), to simulate caries-like lesion development. They were then scanned individually using microtomography, and digital 2D images were used to calculate the outcomes of integrated mineral concentration loss (ΔZ in µm/g/cm3) and lesion depth (LD in µm) at 3 locations, i.e., the cervical, middle, and occlusal thirds. The presence of natural surface wear facets was considered in the analysis. Data were evaluated using a linear mixed-effects models (α = 0.05). ΔZ increased significantly as a function of estimated tooth age at all 3 locations, and this increase was greater after the age of 30 years (p < 0.001), when a higher ΔZ was found in the occlusal third than in the middle and cervical thirds (p < 0.001). LD increased only in the occlusal third before the age of 30 years (p = 0.039) and this increase was significantly greater after 30 years at all 3 locations (p < 0.01), with no differences among them (p > 0.15). The presence of wear facets significantly increased ΔZ and LD (p < 0.001 for both). Overall, we concluded that the susceptibility of enamel to developing caries-like lesions increased with estimated dental age. This effect was more pronounced after the estimated age of 30 years and in the presence of natural tooth wear facets.
Impact of Extrahepatic Metastases on Overall Survival in Patients with Advanced Liver Dominant Hepatocellular Carcinoma: A Subanalysis of the SORAMIC Trial
Authors: Schütte Kerstin , Schinner Regina , Fabritius Mathias P. , Möller Melina , Kuhl Christiane , Iezzi Roberto , Öcal Osman , Pech Maciej , Peynircioglu Bora , Seidensticker Max , Sharma Rohini , Palmer Daniel , Bronowicki Jean-Pierre , Reimer Peter , Malfertheiner Peter , Ricke Jens
Published: November 2020

Introduction: Extrahepatic spread is reported as a prognostic factor in patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. However, clinical studies have reported conflicting results for the clinical impact of the pattern of tumor progression during treatment and the role of new extrahepatic metastases in length of survival. Objective: To evaluate the impact of extrahepatic metastases on survival in patients with HCC treated with sorafenib or with a combination of sorafenib and selective internal radiation treatment (SIRT). Methods: SORAMIC is a randomized, controlled trial comprising diagnostic, local ablation, and palliative cohorts. In the palliative cohort, patients not eligible for transarterial chemoembolization (TACE) were randomized 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. This exploratory subanalysis evaluated the impact of extrahepatic metastases on survival. Results: In the intent-to-treat cohort, 216 patients were randomized to SIRT + sorafenib and 208 to sorafenib alone. Seventeen patients with distant organ metastases (bone, n = 11; adrenal glands, n = 5; peritoneum, n = 1) and 262 without distant metastases at study entry were analyzed in this substudy. Patients with (Group A) and without (Group B) distant organ metastases at study entry presented with a median survival of 11.3 and 14.8 months, respectively (p = 0.2807). During follow-up of patients with no organ metastases at baseline, extrahepatic disease progression occurred in 50 patients (19.1%). No statistically significant difference in survival was observed between patients without extrahepatic progression and those with new extrahepatic disease during treatment (14.8 vs. 14.9 months; p = 0.6483). Development of new pulmonary metastases during treatment significantly shortened median survival (7.6 vs. 15.0 months, p = 0.0060). Conclusions: This subanalysis of the SORAMIC trial suggests that in patients with liver-dominant advanced HCC, metastases to distant organs with the exception of pulmonary metastases do not in general exert a negative impact on patient prognosis. The choice of palliative treatment should incorporate a personalized analysis of the pattern of tumor distribution.
Prospective Nanotechnology-Based Strategies for Enhanced Intra- and Transdermal Delivery of Antifungal Drugs
Authors: Lengert Ekaterina V. , Talnikova Ekaterina E. , Tuchin Valery V. , Svenskaya Yulia I.
Published: November 2020

Topical therapy of superficial fungal infections allows the prevention of systemic side effects and provides drug targeting at the site of disease. However, an appropriate drug concentration in these sites should be provided to ensure the efficacy of such local treatment. The enhancement of intra- and transdermal penetration and accumulation of antifungal drugs is an important aspect here. The present overview is focused on novel nano-based formulations served to improve antimycotic penetration through the skin. Furthermore, it summarizes various approaches towards the stimulation of drug penetration through and into the stratum corneum and hair follicles, which are considered to be promising for the future improvement of superficial antifungal therapy as providing the drug localization and prolonged storage property at the targeted area.
The Experience of Lived Time in People with Dementia: A Systematic Meta-Synthesis
Authors: Eriksen Siren , Bartlett Ruth Louise , Grov Ellen Karine , Ibsen Tanja Louise , Telenius Elisabeth Wiken , Mork Rokstad Anne Marie
Published: November 2020

Introduction: For people with dementia, lived time is important to understand, as the condition affects memory, perceptions of time, and life expectancy. The aim of this study was to locate, interpret, and synthesize the experience of lived time for people with dementia. Method: This article presents a qualitative systematic meta-synthesis. The theoretical framework of lifeworlds by van Manen provided the context for the study. The Critical Appraisal Skills Programme criteria for qualitative studies were used to appraise the studies. Sixty-one qualitative research studies based on interviews with people with dementia were included in the review. The analysis followed the principles of interpretive synthesis. Results: Four categories were revealed: (1) rooted in the past – “I am the same as before”; (2) focussing on the present – “Nobody has tomorrow”; (3) thinking about the future – “What is going to happen to me?”; and (4) changes in the experience of self over time – “I used to….” The latent overall meaning was expressed as “being engaged with the dimensions of time.” Discussion/Conclusion: The experience of lived time is an active and important one, enabling people to manage the dementia journey. Future work involving people with dementia should foreground the experience of lived time.
Aggravation of Food Allergy by Skin Sensitization via Systemic Th2 Enhancement
Authors: Koshiba Risa , Oba Takafumi , Fuwa Arisa , Arai Katsuhiko , Sasaki Nobumitsu , Kitazawa Genki , Hattori Makoto , Matsuda Hiroshi , Yoshida Tadashi
Published: November 2020

Background: Recently, the relationship between antigen contact via skin (skin sensitization) and the development of food allergies has gained increasing attention. However, few studies have examined the effects of skin sensitization on healthy skin. Objective: To examine the effect of sensitization in healthy skin on IgE and cytokine production during food allergy development. Methods: The effect of skin sensitization on food allergy was evaluated using DO11.10 mice whose T cells express ovalbumin (OVA)-specific T-cell receptors. OVA was applied to the back skin of mice dehaired by various methods, and then food allergy was induced by providing them with an OVA-containing diet. OVA-specific IgE production in the sera and decreases in body temperature due to anaphylactic reaction were measured as indicators of food allergy. In addition, IL-4 production and proliferation of splenocytes were measured in mice with food allergy after skin sensitization. Results: Skin sensitization in healthy skin increased IgE production and exacerbated anaphylactic symptoms induced by ingesting the antigen. Moreover, skin sensitization enhanced IL-4 production from splenocytes during the onset of food allergy. In contrast, oral tolerance was induced even after establishing skin sensitization. Conclusion: Skin sensitization temporarily exacerbated food allergy by enhancing systemic Th2 responses. These findings will help identify the mechanisms involved in food allergy and help develop treatments.
Lapatinib Decreases the Preimplantation Aneuploidy Rate of in vitro Fertilized Mouse Embryos without Affecting Completion of Preimplantation Development
Authors: Maleki Parvaneh , Gourabi Hamid , Tahmaseb Mohammad , Golkar-Narenji Afsaneh , Bazrgar Masood
Published: November 2020

One of the major reasons for implantation failure and spontaneous abortion is a high incidence of preimplantation chromosomal aneuploidy. Lapatinib simultaneously inhibits EGFR and HER2, leading to apoptosis. We hypothesized a higher sensitivity for aneuploid cells in preimplantation embryos to lapatinib based on reports of aneuploid cell lines being sensitive to some anticancer drugs. Late 2-cell mouse embryos were treated with lapatinib after determining a nontoxic dose. Morphologies were recorded 24, 48, and 60 hours later. The effect of lapatinib on the aneuploidy rate was evaluated by studying blastocyst cells using FISH. Although the rate of development to 8-cell and morula stage was higher in the control group (p < 0.05), there was no difference in development to the blastocyst stage at the same studied intervals between lapatinib-treated and control groups (p = 0.924). The mean number of cells in morula and blastocyst stages were not different between the groups (p = 0.331 and p = 0.175, respectively). The frequency of aneuploid cells and diploid embryos was, respectively, significantly lower and higher in lapatinib-treated embryos, (p < 0.001). Since lapatinib treatment reduced the aneuploidy rate without impact on the development of mouse preimplantation embryos to the blastocyst stage and number of total cells, lapatinib seems useful for prevention of preimplantation aneuploidy in in vitro fertilization.
Intralymphatic Administration of Metagonimus yokogawai-Extracted Protein Attenuates Experimental Murine Allergic Rhinitis Model
Authors: Yang Hyung Chae , Won Eun Jeong , Kim Moon-Ju , Sung Chung Man , Rhee Joon Haeng , Nam Kwang Il
Published: November 2020

Objectives: This study aimed to evaluate potential therapeutic effect of Metagonimus yokogawai on the OVA-induced allergic rhinitis model. Methods: OVA-sensitized mice were used to assess potential therapeutic effect of the extract protein of M. yokogawai (My-TP). My-TP was administrated via the intralymphatic route to cervical lymph nodes. The frequencies of sneezing or nasal rubbing were recorded. Histopathologic evaluation was performed for eosinophil infiltrations in the tissues of the nasal mucosa and skin. The mRNA relative expressions of the cytokine profiles including Th1, Th2, Th17, and Treg subsets in the nasal mucosa, cervical lymph nodes, and spleen were analyzed by quantitative real-time reverse-transcriptase polymerase chain reaction. The potential underlying mechanism was investigated by examining cytokine profiles including IL-4 and Treg subsets from lymphocytes of the spleen by flow cytometry. Results: Intralymphatic injection of My-TP reduced allergic symptoms and eosinophil infiltration in the nasal mucosa. My-TP-treated group showed markedly decreased levels of OVA-specific IgE and WBC counts in nasal lavage. My-TP-treated group showed the decreased expression levels of IL-4, while those of IL-10 were increased in both the nasal mucosa. The levels of IFN-γ and IL-17 were also decreased in the nasal mucosa and cervical lymph nodes. The immunological mechanism may involve the downregulation of Th2 response and upregulation of Tregs in the nasal mucosa and cervical lymph nodes. Conclusions: Our results provide the first evidence of potential therapeutic effect of M. yokogawai in OVA-sensitized allergic rhinitis mice, suggesting that a Treg/Th2 reorganization may play a role in clinical course of allergic rhinitis.
Multifocal Motor Neuropathy with Persistent Conduction Block: The Seminal Case
Authors: Ochsner François , Tatu Laurent
Published: November 2020

Although multifocal motor neuropathy (MMN) is now recognized as a distinct, albeit rare, neurological condition, the path to its recognition was long and winding. This article provides an insight into the medical history of MMN “patient zero” and the first scientific publication that led to the recognition of MMN by the medical community. Multifocal motor neuropathy is nowadays recognized as a disease that produces asymmetric muscle weakness and cramping, with spontaneous motor unit activity (fasciculations and myokymia) but without sensory disorder. From an electrophysiological point of view, the neuropathy is characterized by persistent conduction blocks that usually initially affect the proximal upper extremity. The path to recognizing this rare entity was long and winding. In this article, we describe the first known patient suffering from this disease and the scientific context of its emergence, leading to the first publication on the subject, written by Gérard Roth (1923–2006) and his colleagues at the Neurology Department of Geneva University Hospital (Switzerland) [Eur Neurol. 1986;25(6):416–23].
Hybrid Convergent Procedure for the Treatment of Persistent and Long-Standing Persistent Atrial Fibrillation
Authors: DeLurgio David B. , Crossen Karl J. , Gill Jaswinder , Blauth Christopher , Oza Saumil R. , Magnano Anthony R. , Mostovych Mark A. , Halkos Michael E. , Tschopp David R. , Kerendi Faraz , Taigen Tyler L. , Shults Christian C. , Shah Manish H. , Rajendra Anil B. , Osorio Jose , Silver Jonathan S. , Hook Bruce G. , Gilligan David M. , Calkins Hugh
Published: November 2020

Background:

The limited effectiveness of endocardial catheter ablation (CA) for persistent and long-standing persistent atrial fibrillation (AF) treatment led to the development of a minimally invasive epicardial/endocardial ablation approach (Hybrid Convergent) to achieve a more comprehensive lesion set with durable transmural lesions. The multicenter randomized controlled CONVERGE trial (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent AF) evaluated the safety of Hybrid Convergent and compared its effectiveness to CA for persistent and long-standing persistent AF treatment.

Methods:

One-hundred fifty-three patients were randomized 2:1 to Hybrid Convergent versus CA. Primary effectiveness was freedom from AF/atrial flutter/atrial tachycardia absent new/increased dosage of previously failed/intolerant class I/III antiarrhythmic drugs through 12 months. Primary safety was major adverse events through 30 days. CONVERGE permitted left atrium size up to 6 cm and imposed no limits on AF duration, making it the only ablation trial to substantially include long-standing persistent–AF, that is, 42% patients with long-standing persistent–AF.

Results:

Of 149 evaluable patients at 12 months, primary effectiveness was achieved in 67.7% (67/99) patients with Hybrid Convergent and 50.0% (25/50) with CA (
P
=0.036) on/off previously failed antiarrhythmic drugs and in 53.5% (53/99) versus 32.0% (16/50;
P
=0.0128) respectively off antiarrhythmic drugs. At 18 months using 7-day Holter, 74.0% (53/72) Hybrid Convergent and 55% (23/42) CA patients experienced ≥90% AF burden reduction. A total of 2.9% (3/102) patients had primary safety events within 7 days, and 4.9% (5/102) between 8 and 30 days postprocedure. No deaths, cardiac perforations, or atrioesophageal fistulas occurred. All but one primary safety event resolved.

Conclusions:

The Hybrid Convergent procedure has superior effectiveness compared to the CA for the treatment of persistent and long-standing persistent atrial fibrillation.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01984346.
Intracellular β
1
-Adrenergic Receptors and Organic Cation Transporter 3 Mediate Phospholamban Phosphorylation to Enhance Cardiac Contractility
Authors: Wang Ying , Shi Qian , Li Minghui , Zhao Meimi , Reddy Gopireddy Raghavender , Teoh Jian-Peng , Xu Bing , Zhu Chaoqun , Ireton Kyle E. , Srinivasan Sanghavi , Chen Shaoliang , Gasser Paul J. , Bossuyt Julie , Hell Johannes W. , Bers Donald M. , Xiang Yang K.
Published: November 2020

Rationale:

β
1
ARs (β
1
-adrenoceptors) exist at intracellular membranes and OCT3 (organic cation transporter 3) mediates norepinephrine entry into cardiomyocytes. However, the functional role of intracellular β
1
AR in cardiac contractility remains to be elucidated.

Objective:

Test localization and function of intracellular β
1
AR on cardiac contractility.

Methods and Results:

Membrane fractionation, super-resolution imaging, proximity ligation, coimmunoprecipitation, and single-molecule pull-down demonstrated a pool of β
1
ARs in mouse hearts that were associated with sarco/endoplasmic reticulum Ca
2+
-ATPase at the sarcoplasmic reticulum (SR). Local PKA (protein kinase A) activation was measured using a PKA biosensor targeted at either the plasma membrane (PM) or SR. Compared with wild-type, myocytes lacking OCT3 (OCT3-KO [OCT3 knockout]) responded identically to the membrane-permeant βAR agonist isoproterenol in PKA activation at both PM and SR. The same was true at the PM for membrane-impermeant norepinephrine, but the SR response to norepinephrine was suppressed in OCT3-KO myocytes. This differential effect was recapitulated in phosphorylation of the SR-pump regulator phospholamban. Similarly, OCT3-KO selectively suppressed calcium transients and contraction responses to norepinephrine but not isoproterenol. Furthermore, sotalol, a membrane-impermeant βAR-blocker, suppressed isoproterenol-induced PKA activation at the PM but permitted PKA activation at the SR, phospholamban phosphorylation, and contractility. Moreover, pretreatment with sotalol in OCT3-KO myocytes prevented norepinephrine-induced PKA activation at both PM and the SR and contractility.

Conclusions:

Functional β
1
ARs exists at the SR and is critical for PKA-mediated phosphorylation of phospholamban and cardiac contractility upon catecholamine stimulation. Activation of these intracellular β
1
ARs requires catecholamine transport via OCT3.