bluuebunny/crossref_metadata_2025 huggingface dataset:
IL‐20R Activation via rIL‐19 Enhances Hematoma Resolution through the IL‐20R1/ERK/Nrf2 Pathway in an Experimental GMH Rat Pup Model
Authors: Liu Shengpeng , Flores Jerry J. , Li Bo , Deng Shuixiang , Zuo Gang , Peng Jun , Tang Jiping , Zhang John H.
Published: January 2021

Aims. Blood clots play the primary role in neurological deficits after germinal matrix hemorrhage (GMH). Previous studies have shown a beneficial effect in blood clot clearance after hemorrhagic stroke. The purpose of this study is to investigate interleukin‐19’s role in hematoma clearance after GMH and its underlying mechanism of IL‐20R1/ERK/Nrf2 signaling pathway. Methods. A total of 240 Sprague‐Dawley P7 rat pups were used. GMH was induced by intraparenchymal injection of bacterial collagenase. rIL‐19 was administered intranasally 1 hour post‐GMH. IL‐20R1 CRISPR was administered intracerebroventricularly, or Nrf2 antagonist ML385 was administered intraperitoneally 48 hours and 1 hour before GMH induction, respectively. Neurobehavior, Western blot, immunohistochemistry, histology, and hemoglobin assay were used to evaluate treatment regiments in the short‐ and long‐term. Results. Endogenous IL‐19, IL‐20R1, IL‐20R2, and scavenger receptor CD163 were increased after GMH. rIL‐19 treatment improved neurological deficits, reduced hematoma volume and hemoglobin content, reduced ventriculomegaly, and attenuated cortical thickness loss. Additionally, treatment increased ERK, Nrf2, and CD163 expression, whereas IL‐20R1 CRISPR‐knockdown plasmid and ML385 inhibited the effects of rIL‐19 on CD163 expression. Conclusion. rIL‐19 treatment improved hematoma clearance and attenuated neurological deficits induced by GMH, which was mediated through the upregulation of the IL‐20R1/ERK/Nrf2 pathways. rIL‐19 treatment may provide a promising therapeutic strategy for the GMH patient population.
Identification of the Different Gene Expression Characteristics from Liver Cirrhosis to Hepatocellular Carcinoma Using Single-Cell Sequencing Analyses
Authors: Xing Xin , Song Jian
Published: January 2021

The occurrence of hepatocellular carcinoma (HCC) is closely related to the chronic inflammation which caused liver fibrosis and cirrhosis, and the interaction between HCC and its microenvironment further drives tumorigenesis. However, the single-cell resolution in vivo study is lacking, which limits our molecular understanding of tumour biology in the liver. Here, using published single-cell sequencing technology (scRNA-seq) database, we analyzed the liver microenvironment at high resolution in an unbiased manner and demonstrated the transcriptomic comparison between various cell populations and subpopulations in HCC and cirrhosis tissues. We found that eight genes that are specifically expressed in the endothelial cell and stellate cell of the HCC patients and correlated them with their survival rate, which may provide novel diagnosis and treatment targets for the clinical application.
COVID-19 Viral Pneumonia Complicated with Acute Pulmonary Embolism: A Descriptive Study
Authors: Darwish Hoda Salah , Habash Mohamed Yasser , Habash Waleed Yasser
Published: January 2021

Objective. To evaluate acute pulmonary embolism in patients with 2019 novel coronavirus (COVID-19) pneumonia using pulmonary CT angiography. Subjects and Methods. From 95 symptomatic patients confirmed with COVID-19 by RT-PCR from 1 May to 14 July 2020 in Dallah Hospital, Riyadh, Saudi Arabia, CT angiography was done for 25 patients suspected to have pulmonary embolism and have no contraindication for contrast study. 11 cases of them showed CT evidence of acute pulmonary embolism (PE). Retrospectively, CT angiography was analyzed and detailed findings were recorded. This study was approved by the Institutional Review Board of our hospital, and the patient consent was waived. Results. The mean age of the included patients was 49 ± 11 years; the youngest was 22 years, and the oldest was 64 years. Common symptoms in the 25 cases that underwent CT angiography were fever that was noted in 21/25 cases (84%), shortness of breath in 18/25 cases (72%), cough in 16/25 cases (64%), and severe myalgia/body fatigue in 13/25 cases (52%). The less common symptoms were sore throat in 11/25 cases (44%) and headache in 10/25 cases (40%). Regarding CT findings, 4/25 cases (16%) had unilateral lung disease and 21/25 cases (84%) had bilateral disease, with slight predilection for the right lower lobe (10/25 cases, 40%). Pure ground-glass opacity (GGO) was seen in 13/25 cases (52%), and GGO with consolidation was seen in 12/25 cases (48%). Common accompanying CT signs included crazy paving stone sign in 15/25 cases (60%) and air bronchogram in 12/25 cases (48%). From the 25 patients that showed respiratory deterioration and elevated serum D-dimer level, 11 cases confirmed to have acute pulmonary embolism, while 14 cases showed negative result for pulmonary embolism. 6/11 were male and 5/11 were female. Pulmonary embolism was diagnosed at a mean of 21 days from symptom onset. Unilateral acute pulmonary embolism was seen in 3/11 cases, while 8/11 cases showed bilateral distribution. Among 11 cases with acute pulmonary embolism, no emboli at the central level could be seen, but 3 cases showed pulmonary embolism at the lobar level, 3 cases at the segmental level, and 5 cases at lobar, segmental, and subsegmental levels. Conclusion. In patients with confirmed COVID-19, we should maintain a high suspicion for its thromboembolic complications such as acute pulmonary embolism that was mainly diagnosed at the end of 3rd week from symptom onset. We suggest that whenever a CT evaluation of the parenchymal involvement of COVID-19 pneumonia is performed, a simultaneous evaluation of the pulmonary arteries is also essential in order to identify early signs of associated pulmonary embolism.
Quantitative Analysis of Flavonoids in Glycyrrhiza uralensis Fisch by 1H-qNMR
Authors: Yu Ping , Li Qian , Feng Yanmei , Chen Yuying , Ma Sinan , Ding Xiaoqin
Published: January 2021

Objective. To establish a method for simultaneous determination of liquiritin, liquiritigenin, and isoliquiritinin glycyrrhizin using hydrogen nuclear magnetic resonance quantitative technology (1H-qNMR). Methodology. Deuterated dimethyl sulfoxide was used as the solvent, and dichloromethane was used as the internal standard. The probe temperature was 298.0 K, the pulse sequence was Zg30, the number of scans was 16, and relaxation delay (D1) was 10 s. Quantitative characteristic signal peaks were δ 4.891∼4.878 ppm, δ 8.187∼8.172 ppm, and δ 6.790∼6.776 ppm for liquiritin, isoliquiritin, and liquiritigenin, respectively. Results. The experimental result showed that the content of flavonoids in Licorice, from Chifeng, Inner Mongolia, was the highest. Conclusion. In this study, a new method for determination of three flavonoids in Licorice using 1H-qNMR was established. This experimental method has the advantages of accuracy, efficiency, and economy. It lays a foundation for the study on the determination of flavonoids content in licorice by proton nuclear magnetic resonance spectroscopy.
Vulnerability of Submarine Cable Network of Mainland China: Comparison of Vulnerability between before and after Construction of Trans‐Arctic Cable System
Authors: Xie Yongshun , Wang Chengjin
Published: January 2021

The submarine optical‐fiber cable (submarine cable) is a large connectivity infrastructure, which plays an important role in international communication, cyber‐physical systems, and even national security. Although submarine cable network interruption may cause serious consequences, researching its vulnerability has not attracted much attention. This paper proposes a quantitative method to measure the vulnerability of the submarine cable network and evaluates the influence of the upcoming trans‐Arctic cable (TAC) system on the submarine cable network of mainland China. To address this issue, first, the submarine cable network of mainland China is constructed. Further, methodology based on complex network and geospatial perspective is proposed to simulate the changes of network eigenvalues under different attacks and to quantitatively analyze the variation degree of network vulnerability. With the proposed method, the vulnerability of the submarine cable network of mainland China before and after construction of the trans‐Arctic cable system is compared. The results reveal the key node countries and sea channels of the submarine cable network of mainland China and show the significance of the TAC system.
Organizational Performance Influenced by Academic Service Quality: An Investigation in Public Universities in Malaysia
Authors: Sharma Sailesh , Al Sinawi Saleh
Published: January 2021

The influence of service quality on organizational performance has captured a greater attention in corporate and academic world. The public universities in Malaysia are no different than such corporate world in terms of quality, services, and outcome. Hence, investigation of the influence of academic service quality on the organizational performance in public universities in Malaysia is the key attention of this study. A survey was conducted by drawing a sample of 435 international students from three public universities in Malaysia, by using a questionnaire developed by modification of SERVQUAL. The modified questionnaire assessing academic service quality comprises of five dimensions such as academic resources, academic competence, skills development, attitude, and responsiveness. Data obtained were analyzed by using techniques such as principal component analysis, one-way ANOVA, correlation, and multiple regression. Results indicated that the three universities provided the same level of academic service quality. It was also found that all the five dimensions of academic service quality significantly influenced the organizational performance. This study concludes by advocating the need of comparative studies between public and private universities in Malaysia and across countries.
Effects of Curcumin Treatment in a Diabetic Neuropathic Pain Model of Rats: Involvement of c-Jun N-Terminal Kinase Located in the Astrocytes and Neurons of the Dorsal Root Ganglion
Authors: Park Hanwool , Lee Jong-Hyuk , Sim Ji Hoon , Park Jihoon , Choi Seong-Soo , Leem Jeong Gil
Published: January 2021

Curcumin (diferuloylmethane) is a major component of turmeric, which is isolated from the rhizomes of Curcuma longa L. from the family Zingiberaceae. It is used as a dietary pigment for curry and in traditional Indian medicine for its anti-inflammatory and attenuating pain effects. This study aimed to evaluate the beneficial effects of curcumin in a rat model of diabetic neuropathic pain. Additionally, we investigated the involvement of the phosphorylated form of c-Jun N-terminal kinase (pJNK) located in the neurons and astrocytes of the dorsal root ganglion (DRG). To induce diabetic neuropathic pain in rats, 50 mg/kg of streptozotocin (STZ) was intraperitoneally injected. After 4 weeks, rats were administered the vehicle, 10 mg/kg/day curcumin, or 50 mg/kg/day curcumin orally for 4 consecutive weeks. One day after the final drug administration, we performed behavioral tests to measure responses of rats to mechanical, heat, cold, and acetone-induced cold stimuli. After behavioral tests, pJNK expression in the DRG was evaluated using western blot assay and immunohistochemistry. Curcumin treatment for 4 consecutive weeks in STZ-induced diabetic neuropathic pain rats improved behavioral responses to mechanical, cold, and thermal stimuli. Increased pJNK expression in the astrocytes and neurons of the DRG in STZ-induced diabetic neuropathic pain rats was reduced by curcumin treatment for 4 consecutive weeks. We suggest that curcumin can be an option for the treatment of diabetes-related neuropathic pain, and one of the mechanisms that underlie the action of curcumin may involve pJNK expression in the astrocytes and neurons of the DRG.
Comparison between Two Low Doses of Amitriptyline in the Management of Chronic Neck Pain: A Randomized, Double-Blind, Comparative Study
Authors: Mahmoud Atef Mohamed Sayed , Ragab Safaa Gaber , Boules Maged Labib , Botros Joseph Makram
Published: January 2021

Chronic neck pain (CNP) is a major concern for pain therapists. Many drugs including antidepressants such as amitriptyline have been used in the management of CNP. This study compared the efficacy and safety of 2 different doses of amitriptyline (5 mg and 10 mg at bedtime) in patients with CNP. A total of 80 patients of both sexes with idiopathic CNP, ranging in age from 18 to 75 years, were divided into 2 groups that received 5 or 10 mg oral amitriptyline at bedtime for 120 days. The primary outcome measure was neck pain disability index (NPDI). Neck pain intensity, Athens Insomnia Scale score, Hospital Anxiety and Depression Scale (HADS), side effects of the drug, and patient satisfaction were secondary outcome measures. NPDI decreased by 71.9% ± 13.4% in the 10 mg group compared to 47.3% ± 17.3% in the 5 mg group, representing a statistically significant difference (95% confidence interval: 27.3–12.6). Additionally, the 10 mg group showed greater mean reductions in pain score and HADS scores (both the anxiety and depression subscales), as well as improvement in sleep disturbance compared to the 5 mg group. A higher dose (10 mg) of amitriptyline at bedtime significantly reduced neck pain intensity, sleep disturbance, and anxiety and depression compared to a lower dose (5 mg) in patients with idiopathic and nontraumatic CNP after 120 days of treatment, with no significant difference between groups in the rate of side effects.
Construction of Credit Evaluation Index System for Two-Stage Bayesian Discrimination: An Empirical Analysis of Small Chinese Enterprises
Authors: Li Zhanjiang , Guo Lin
Published: January 2021

In China, small enterprises have a direct role in economic growth, but they have difficulty in financing development. To address this problem, this paper creates a small business credit evaluation index using a two-stage Bayesian discriminant model. In the first stage, customers are distinguished by whether they are in default, and in the second stage, customers with continuing default are divided into those with a high default loss rate and those with a low default loss rate. The literature to date has identified a credit index only for the first stage; the credit evaluation index proposed here is based on two stages, which is more sensitive. Then, we conduct an empirical analysis using credit data on 3,111 small enterprises in China with a two-stage nonparametric Bayesian discriminant model and a parametric discriminant model, and then, we test the two indicator systems with discriminant accuracy and an ROC curve; the discriminant accuracy of the established index system is 77.95% and 70.95%, respectively, and their prediction accuracy is 0.902 and 0.866, respectively; they show that the constructed indicator system is robust and effective. Finally, we conduct a comparative analysis of discriminant accuracy in three models, finding that the two-stage nonparametric model is optimal, the two-stage logistic regression model is suboptimal, and the two-stage parametric model is poor.
Intelligent Vehicle Automatic Stop‐and‐Go Task Based on Humanized Learning Control Model
Authors: Sun Tianjun , Gao Zhenhai , Gao Fei , Zhang Tianyao , Ji Di , Chen Siyan
Published: January 2021

The automatic stop‐and‐go task of intelligent vehicles can make the adaptive cruise control system achieve a full‐speed range. However, the conventional design methods mostly focus on functional safety, without considering drivers’ behaviors, thereby leading to a poor driving experience. To improve the situation, a humanized learning control model is used instead of mechanical switching logic. Therefore, first, the common characteristics of human drivers with different driving styles are found by analyzing real drivers’ experiments. Then, the vehicle automatic starting function is designed based on iterative learning control with the fast Fourier transform for acceleration fitting. Next, the vehicle automatic braking function is designed based on dynamic time to collision. Finally, the simulation of the stop‐and‐go scenario is shown in CARSIM, and the real vehicle test is performed under the urban overpass driving condition. Results show that the proposed model can improve the humanization in the vehicle stop‐and‐go task.
Clinical Characteristics and Manifestations of Fungal Esophagitis: A Single-Center Experience in South China
Authors: Zhan Shu-Kai , Wu Xiao-Qin , Zheng Feng-Ping
Published: January 2021

Fungal esophagitis is a common infectious disease, although the pathogenic clinical characteristics remain incompletely clear, especially in South China. The goal of this study was to investigate the pathogenic clinical characteristics of fungal esophagitis and the efficacy of different therapeutic strategies at a tertiary hospital in South China. A retrospective study was conducted from January 2007 to December 2017. Data from 113,390 patients who were treated in the endoscopic unit were retrieved and analyzed. To further understand the pathogen and risk factors for fungal esophagitis, we performed a case-control analysis of 101 patients and 202 controls. Of the 113,390 patients, 932 (0.82%) were positive. The annual detection rate ranged from 0.345% to 1.106%, showing an initially increasing and subsequently decreasing trend. The patients’ median age was 49 years (range from 8 to 85), and most were men (615/932, 65.99%). Candida albicans was found in samples collected from 36 patients, without any drug-resistant strains. Age (

P
=
0.018

), malignancy (

OR
=
4.031

, 95% CI: 1.562~10.407), cigarette smoking (

OR
=
3.017

, 95% CI: 1.645~5.533), and the use of antibiotics (

OR
=
2.178

, 95% CI: 1.078~4.400) or immunosuppressants (

OR
=
6.525

, 95% CI: 1.089~39.105) were independently associated with esophageal candidiasis. Fluconazole had a better curative effect than nystatin (

OR
=
4.047

, 95% CI: 1.282~12.772) or simple observation (

OR
=
8.91

, 95% CI: 2.61~30.49). In conclusion, fungal esophagitis primarily affects men and elderly individuals; it develops in the setting of malignancy, smoking, and certain previous medication use. Candida albicans is the most common pathogen and is sensitive to antifungal agents. Fluconazole has a good therapeutic effect.
Decitabine Downregulates TIGAR to Induce Apoptosis and Autophagy in Myeloid Leukemia Cells
Authors: Li Lanzhu , Liu Wenjie , Sun Qian , Zhu Han , Hong Ming , Qian Sixuan
Published: January 2021

Decitabine (DAC) is a well‐known DNA methyltransferase inhibitor, which has been widely used for the treatment of acute myeloid leukemia (AML). However, in addition to hypomethylation, DAC in AML is also involved in cell metabolism, apoptosis, and immunity. The TP53‐induced glycolysis and apoptosis regulator (TIGAR) functions to inhabit glycolysis and protect cancer cells from reactive oxygen species‐ (ROS‐) associated apoptosis. Our previous study revealed that TIGAR is highly expressed in myeloid leukemia cell lines and AML primary cells and associated with poor prognosis in adult patients with cytogenetically normal AML. In the present study, it was found that in a time‐ and concentration‐dependent manner, DAC downregulates the TIGAR expression, induces ROS production, and promotes apoptosis in HL‐60 and K562 cells. However, blocking the glycolytic pathway partially reversed the combined effects of DAC and TIGAR knockdown on apoptosis, ROS production, and cell cycle arrest, indicating that DAC induced apoptosis through the glycolytic pathway. Furthermore, TIGAR also has a negative impact on autophagy, while DAC treatment upregulates autophagy‐related proteins LC3, Beclin‐1, ATG3, and ATG‐5, downregulates p62, and promotes the formation of autophagosomes, indicating that DAC may activate autophagy by downregulating TIGAR. Taken together, DAC plays an unmethylated role in inducing apoptosis and activating autophagy in myeloid leukemia by downregulating TIGAR.
Effect of Nanoparticles and Base Fluid Types on Natural Convection in a Three-Dimensional Cubic Enclosure
Authors: Dayf Abdellatif , Feddaoui M’barek , Bouchta Said , Charef Adil , El Ihssini Houssine
Published: January 2021

Convective heat transfer using nanofluids play an important role in thermal applications such as heat exchangers, automotive industries, and power generation. In this work, a numerical analysis is conducted to examine the heat transfer of nanofluid in three-dimensional differentially heated cavity. The finite volume method-based SIMPLEC algorithm is used to solve the system of the mass, momentum, and energy transfer governing equations. The left and the right vertical side walls of the cube are maintained at constant temperatures

T

C

and

T

H

, respectively. The remaining walls of the cube are insulated. Effective thermal conductivity and viscosity of the nanofluid are determined using Brinkman and Maxwell models, respectively. Studies are carried out for three types of nanoparticles and volume fractions of nanoparticles (

0

–

5
%

). The effects of two binary liquid mixtures as a base fluid (propylene glycol-water and ethylene glycol-water) are also examined. Results show an enhancement of

13
%

for Al2O3-EG in comparison to pure ethylene glycol in the case of

Ra
=

10

3

. In addition, heat transfer enhancement was increased with the rise of nanoparticle volume fractions.
Entity Linking Based on Sentence Representation
Authors: Jia Bingjing , Wu Zhongli , Zhou Pengpeng , Wu Bin
Published: January 2021

Entity linking involves mapping ambiguous mentions in documents to the correct entities in a given knowledge base. Most existing methods failed to link when a mention appears multiple times in a document, since the conflict of its contexts in different locations may lead to difficult linking. Sentence representation, which has been studied based on deep learning approaches recently, can be used to resolve the above issue. In this paper, an effective entity linking model is proposed to capture the semantic meaning of the sentences and reduce the noise introduced by different contexts of the same mention in a document. This model first uses the symmetry of the Siamese network to learn the sentence similarity. Then, the attention mechanism is added to improve the interaction between input sentences. To show the effectiveness of our sentence representation model combined with attention mechanism, named ELSR, extensive experiments are conducted on two public datasets. Results illustrate that our model outperforms the baselines and achieves the superior performance.
Shaking Table Tests on a New Antislide Pile under Earthquakes
Authors: Lai Jie , Liu Yun , Wang Wei
Published: January 2021

A retaining form of a shock-absorbing antislide pile is proposed for slope engineering. A flexible material (shock-absorption layer) is filled in front of an ordinary antislide pile, which is used to absorb a large amount of seismic energy, thereby decreasing the transmission of seismic energy to the antislide pile. The flexible material thus reduces the seismic response, hence improving the aseismic capacity of the antislide pile. To verify the seismic performance of the shock-absorbing antislide pile, a shaking table contrast test was conducted and the results were compared with those from an ordinary antislide pile. The test results show that the flexible material absorbs a portion of the seismic deformation of the slip mass, decreasing the final displacement of the shock-absorbing antislide pile compared to that of the ordinary antislide pile, thereby reducing the sensitivity of the pile body to the displacement. Under the same conditions, the acceleration response of the slope body at the same height is lower for the shock-absorbing antislide pile than that for the ordinary pile, with the seismic performance of the former being superior to that of the latter. Furthermore, the shock-absorbing antislide pile is similar to the ordinary pile in terms of the dynamic earth pressure distribution form of the pile shaft; however, its value is relatively smaller, and the former exhibits better dynamic stress performance than the latter. The test results should prove useful for aseismic design of slopes.
Current Management of Inherited Retinal Degeneration Patients in Europe: Results of a Multinational Survey by the European Vision Institute Clinical Research Network
Authors: Lorenz Birgit , Tavares Joana , van den Born L. Ingeborgh , Marques João P. , Scholl Hendrik P. N. ,   the EVICR.net Group
Published: January 2021

Purpose: An increasing number of gene therapies are developed for Inherited Retinal Degenerations (IRD). To date, 1 treatment has been approved for clinical use (FDA USA 2017, EMA Europe 2018, MoHAP UAE 2019, SFDA Saudi Arabia 2019, Swiss Medic Switzerland 2020, TGA Australia 2020, and BFR Brazil 2020). While such therapies do not provide complete cure, they may halt degeneration or partially restore function. Identification of well-characterized patients is an emerging need. We conducted the first multinational survey to understand the management of IRDs in Europe. Methods: An electronic survey questionnaire containing 112 questions was developed and sent to the 101 EVICR.net clinical centers (14 European countries and Israel). Results: The overall response rate was 49%. Only 14% of responding centers do not see IRD patients; 52% that manage IRD patients follow ≥200 patients, 16% > 1,000. Databases exist in 86% of the centers; of these, 75% are local files, 28% local Web-based database, and 19% national Web-based. IRD patients are referred to EVICR.net centers mainly by general ophthalmologists, patient self-referrals, and medical retina specialists. Most IRD patients are first seen in adulthood. Most prominent signs and symptoms depend on the age of onset, for example, nystagmus in infancy, or night blindness, and reduced visual acuity at older age. The time from inquiring for first appointment and clinical diagnosis varies among countries: in 29% of centers, the mean time is <4 weeks, although can be up to 35 months in others. The time to genetic diagnosis is ≥4 weeks, the maximum 10 years, likely depending on access to genetic testing, and the improvement of the tests available. Comprehensive eye examination always includes autofluorescence imaging and perimetry (86% static, 76% kinetic, and 21% microperimetry), and frequently optical coherence tomography (OCT) (95%), electroretinography (93%), and fundus photography (93%). Identified genotypes were reported in 40–80% patients by 69% of centers, and in 80–100% by 5%. Genetic testing is provided by public health insurance in 77% of centers, private health insurance in 38%, center budget in 13%, research funds in 18%; and 15% of centers do not have access to genetic testing. Conclusion: At the start of this era of ocular gene therapy for IRD patients, this first international survey on management of IRDs in Europe highlights significant heterogeneity between centers and across countries and provides important baseline data for researchers, clinicians, pharmaceutical companies, and investors.
CRD-733, a Novel PDE9 (Phosphodiesterase 9) Inhibitor, Reverses Pressure Overload–Induced Heart Failure
Authors: Richards Daniel A. , Aronovitz Mark J. , Liu Peiwen , Martin Gregory L. , Tam Kelly , Pande Suchita , Karas Richard H. , Bloomfield Daniel M. , Mendelsohn Michael E. , Blanton Robert M.
Published: January 2021

Background:

Augmentation of NP (natriuretic peptide) receptor and cyclic guanosine monophosphate (cGMP) signaling has emerged as a therapeutic strategy in heart failure (HF). cGMP-specific PDE9 (phosphodiesterase 9) inhibition increases cGMP signaling and attenuates stress-induced hypertrophic heart disease in preclinical studies. A novel cGMP-specific PDE9 inhibitor, CRD-733, is currently being advanced in human clinical studies. Here, we explore the effects of chronic PDE9 inhibition with CRD-733 in the mouse transverse aortic constriction pressure overload HF model.

Methods:

Adult male C57BL/6J mice were subjected to transverse aortic constriction and developed significant left ventricular (LV) hypertrophy after 7 days (
P
<0.001). Mice then received daily treatment with CRD-733 (600 mg/kg per day; n=10) or vehicle (n=17), alongside sham-operated controls (n=10).

Results:

CRD-733 treatment reversed existing LV hypertrophy compared with vehicle (
P
<0.001), significantly improved LV ejection fraction (
P
=0.009), and attenuated left atrial dilation (
P
<0.001), as assessed by serial echocardiography. CRD-733 prevented elevations in LV end diastolic pressures (
P
=0.037) compared with vehicle, while lung weights, a surrogate for pulmonary edema, were reduced to sham levels. Chronic CRD-733 treatment increased plasma cGMP levels compared with vehicle (
P
<0.001), alongside increased phosphorylation of Ser
273
of cardiac myosin binding protein-C, a cGMP-dependent protein kinase I phosphorylation site.

Conclusions:

The PDE9 inhibitor, CRD-733, improves key hallmarks of HF including LV hypertrophy, LV dysfunction, left atrial dilation, and pulmonary edema after pressure overload in the mouse transverse aortic constriction HF model. Additionally, elevated plasma cGMP may be used as a biomarker of target engagement. These findings support future investigation into the therapeutic potential of CRD-733 in human HF.
Medium- and Large-Vessel Vasculitis
Authors: Saadoun David , Vautier Mathieu , Cacoub Patrice
Published: January 2021

Systemic vasculitides are multisystem blood vessel disorders, which are defined by the size of the vessel predominantly affected, namely small, medium, or large vessels. The term “large vessel” relates to the aorta and its major branches; “medium vessel” refers to the main visceral arteries and veins and their initial branches. The most common causes of large-vessel vasculitis are giant cell arteritis and Takayasu arteritis, and those of medium-vessel arteritis are polyarteritis nodosa and Kawasaki disease. However, there is some overlap, and arteries of any size can potentially be involved in any of the 3 main categories of dominant vessel involvement. In addition to multisystem vasculitides, other forms of vasculitis have been defined, including single-organ vasculitis (eg, isolated aortitis). Prompt identification of vasculitides is important because they are associated with an increased risk of mortality. Left undiagnosed or mismanaged, these conditions may result in serious adverse outcomes that might otherwise have been avoided or minimized. The ethnic and regional differences in the incidence, prevalence, and clinical characteristics of patients with vasculitis should be recognized. Because the clinical presentation of vasculitis is highly variable, the cardiovascular clinician must have a high index of suspicion to establish a reliable and prompt diagnosis. This article reviews the pathophysiology, epidemiology, diagnostic strategies, and management of vasculitis.
Early-but Not Late-Onset Hypertension Is Related to Midlife Cognitive Function
Authors: Suvila Karri , Lima Joao A.C. , Yano Yuichiro , Tan Zaldy S. , Cheng Susan , Niiranen Teemu J.
Published: January 2021

Hypertension is related to increased risk of cognitive decline in a highly age-dependent manner. However, conflicting evidence exists on the relation between age of hypertension onset and cognition. Our goal was to investigate the association between early- versus late-onset hypertension and midlife cognitive performance in 2946 CARDIA study (Coronary Artery Risk Development in Young Adults) participants (mean age 55±4, 57% women). The participants underwent 9 repeat examinations, including blood pressure measurements, between 1985 to 1986 and 2015 to 2016. The participants underwent brain magnetic resonance imaging and completed Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Stroop interference test, and the Montreal Cognitive Assessment to evaluate cognitive function at the year 30 exam. We assessed the relation between age of hypertension onset and cognitive function using linear regression models adjusted for cognitive decline risk factors, including systolic blood pressure. We observed that individuals with early-onset hypertension (onset at <35 years) had 0.24±0.09, 0.22±0.10, 0.27±0.09, and 0.19±0.07 lower standardized Z-scores in Digit Symbol Substitution Test, Stroop test, Montreal Cognitive Assessment, and a composite cognitive score than participants without hypertension (
P
<0.05 for all). In contrast, hypertension onset at ≥35 years was not associated with cognitive function (
P 
>0.05 for all). In a subgroup of 559 participants, neither early- nor late-onset hypertension was related to macrostructural brain alterations (
P 
>0.05 for all). Our results indicate that early-onset hypertension is a potent risk factor for midlife cognitive impairment. Thus, age of hypertension onset assessment in clinical practice could improve risk stratification of cognitive decline in patients with hypertension.
Bitenosh’s Orgasm, Galen’s Two Seeds and Conception Theory in the Hebrew Bible
Authors: Quick Laura
Published: January 2021

In the Genesis Apocryphon, Lamech worries that his son is illegitimate and accordingly confronts his wife about her fidelity. Bitenosh answers these accusations with a surprising response: she asks her husband to recall the sexual pleasure that she experienced during their intercourse. Scholars have clarified this rhetorical strategy by connecting the episode to Greco-Roman theories of embryogenesis, in which a woman’s pleasure during intercourse was taken to indicate conception. While this provides a convincing explanation for Bitenosh’s argumentation, in this essay I argue that rather than deriving these ideas from the Greco-Roman world, the conception theory which informed the Genesis Apocryphon is in fact consistent with notions that can already be found in the Hebrew Bible and the wider ancient Near East. By exploring the concept of conception in biblical and ancient Near Eastern texts, I uncover a belief in the necessity for female pleasure during intercourse as well as the existence of female “seed.” These ancient authors were able to develop and promote significant reflections upon medical issues such as conception, and this is recalled in Bitenosh’s speech. This essay therefore has significant implications for understanding concepts of sex and conception in the Genesis Apocryphon, as well as in the Hebrew Bible and the wider ancient Near East more generally.
Afterword
Authors: Reindl-Kiel Hedda
Published: January 2021

The paper questions the function of the anti-Ottoman approach that, until recently, prevailed in Southeastern European historiography. This mindset and its concomitant attitudes were steps in nation building. A short comparison of the Ottoman social system with the social structures of countries in the region that did not come under direct Ottoman rule shows only minor differences. Thus, the adoption of Ottoman cultural practices including material culture was not a difficult choice. At the same time, we see individuals and whole groups whose lifestyles were oriented toward the West. Changing eating habits serve as an illustration for this phenomenon.
Garments, Signatures, and Ottoman Self-Fashioning in the Imperial Periphery: Moldavian Voyvode Ştefan Tomşa II and Ottomanization in the Early Seventeenth Century
Authors: Wasiucionek Michał
Published: January 2021

The paper examines the strategies of self-representation pursued by Moldavian Voyvode Ștefan Tomșa II (r. 1611-1615, 1621-1623). From his ascension to the throne, Tomșa faced accusations of wholesale adoption of Ottoman customs and fashion, and even conversion to Islam. While Romanian scholars have largely dismissed these claims as a product of hostile propaganda, the paper argues that—while remaining an Orthodox Christian—the voyvode deliberately emphasized his affinity to the Ottoman cultural idiom and presented himself to his subjects as a member of the Ottoman ruling class. By examining the nexus between Tomșa’s career, material objects he commissioned, and chancery innovations during his reign, the paper looks into the process of Christian Ottomanization in the Danubian principalities of Moldavia and Wallachia.
France in the Levant: Trade and Immaterial Circulations in the “Long Eighteenth Century”
Authors: Celetti David
Published: January 2021

The article analyzes aspects of French trade in the Levant during the eighteenth century by tracing the link between commercial exchange, institutions, and socio-cultural interaction within the system of French échelles in the Eastern Mediterranean. As the paper argues, this trade not only acquired a primary relevance within Ottoman and French economies but also created institutional and social interdependencies that prefigured nineteenth-century developments. The study discusses how economic, institutional, and social aspects are highly intertwined, each of them playing a core role in explaining the relevance of the French presence in the Early Modern Eastern Mediterranean.
Pandering for the Greater Good? Senate, People, and Politics in Cicero’s de lege agraria 1 and 2
Authors: Krostenko Brian
Published: January 2021

Cicero’s first speeches as consul, de lege agraria I and II, delivered to the senate and the people respectively, are virtually identical in outline and broad argument. That allows the rhetorical technique of individual sections to be compared closely. This article uses such comparisons to probe the tactics and ideology of the speeches. In both Cicero’s choice of word and phrase might suggest that he is simply addressing his audiences as suits their stations. But a consideration of the circumstances of the speeches reveals instead that Cicero is directing his audiences to alternate ways of imagining their social and political positions; in effect, Cicero propounds distinct, principled, and communalist definitions of dignitas and libertas, core values of each audience – though sometimes at the price of distorting the intent of the bill.
Description of Heteracris lecoqi Yetchom-Fondjo & Kekeunou sp. nov. and Heteracris hannai Wandji & Kekeunou sp. nov. and redescription of Heteracris guineensis (Krauss, 1890) (Orthoptera: Acrididae) with comments on its ecology in the Southern part of Cameroon
Authors: WANDJI ALAIN CHRISTEL , YETCHOM-FONDJO JEANNE AGRIPPINE , KEKEUNOU SÉVILOR , KENNE MARTIN , MISSOUP ALAIN DIDIER , TINDO MAURICE , SIMEU-NOUTCHOM ALAIN , MBADJOUN-NZIKE MARCELLE , XU SHENG-QUAN , DJOMNANG-NKWALA ALFIERY LAUREL , FOMENA ABRAHAM
Published: January 2021

The specimens studied were collected with sweep net and pitfall in the forests, agro-forests, herbaceous fallows, and crop fields of 14 localities in the southern part of Cameroon, from August 2015 to February 2018. The results show that Heteracris hannai sp. nov. and Heteracris lecoqi sp. nov. differ from previously known species of the same genus by the pattern of coloration and the details or shape of the phallic complex. H. lecoqi sp. nov. is characterized by light brownish body; male cercus with flattened, downcurved and obtuse apex; lophus strongly curved; interlophal space with V shape; apodeme of cingulum bow, convergent, with V-shape; valve of cingulum in lateral view longer than apical valve of penis; ramus in ventral view joined. H. hannai sp. nov. is distinct to other species by brown to grey body; male cercus with apex rounded, curved inside; lophus curved; interlophal space with U-shape; apodeme of cingulum thick, slightly parallel, with U shape; valve of cingulum in lateral view hardly longer than apical valve of penis; ramus in ventral view opened. The characteristics of H. guineensis are closer to H. hannai sp. nov. than to H. lecoqi sp. nov. H. lecoqi sp. nov. was collected only in the fallows while H. hannai sp. nov. was collected in the forests, agro-forests, fallows, and crop fields. Compared to H. guineensis, both new species are scarce in the natural vegetation and their distribution area is limited to two and four localities respectively for H. lecoqi sp. nov. and H. hannai sp. nov. All these three grasshopper’s species were recorded as accidental species in all types of vegetation.
New species of the monotypic thiratoscirtine genera Ajaraneola and Nimbarus (Araneae: Salticidae: Aelurillini: Thiratoscirtina)
Authors: SZŰTS TAMÁS , MADDISON WAYNE PAUL
Published: January 2021

Two new species of the currently monotypic thiratoscirtine genera Ajaraneola Wesołowska & Russell-Smith, 2011 and Nimbarus Rollard & Wesołowska, 2002 are described from Uganda and Cameroon: Ajaraneola pajakwandy sp. nov. (male) and Nimbarus nimbus sp. nov. (male), respectively. With the new species, previous diagnoses of the genera are re-evaluated and refined. The range of each genus is extended considerably: Ajaraneola is reported from Uganda and Nimbarus from Cameroon for the first time.
Description of a new species of Mauroniscus Bourgeois, 1911 from Chile (Coleoptera: Mauroniscidae)
Authors: ESTRADA PATRICIA , SOLERVICENS JAIME
Published: January 2021

A new species of Mauroniscus Bourgeois, 1911, Mauroniscus chilensis n. sp., from central Chile is described using external characters of the adult male and female including terminal segments of the abdomen and genitalia. The morphological differences of Mauroniscus chilensis n. sp. with M. maculatum Pic, 1927 are discussed
Ultrasound-Mediated Oxygen Delivery for Enhanced Radiotherapy with Ultrasound Imaging Guidance
Authors: Yao Yuanzhi , Xiao Huan , Zhu Lirong , Gao Yang , Xu Juan , Tang Yi , Wang Qiao , Yang Chunjiang
Published: January 2021

As a non-invasive therapeutic, radiotherapy (RT) has been extensively used for solid tumor treatment. However, intratumoral hypoxia leads to severe RT resistance or failure. Moreover, damage from RT to normal tissues limits the application of high doses of radiation to eliminate cancer
cells. Therefore, simultaneously improving the curative efficacy while minimizing the side effects of RT is in pressing need. Hence, the purpose of this study is to use oxygen-based microbubbles (O2 @MBs) combined with ultrasound (US) targeting microbubble destruction (UTMD) technology
to overcome hypoxia prior to RT, evaluate the effects of O2 @MBs on contrast-enhanced ultrasound (CEUS) imaging enhancement, investigate the optimum delivery route of O2 @MBs, and evaluate the therapeutic efficacy. In this study, O2 @MBs were injected intravenously
or locally and the distribution of O2 @MBs in tumors or regions surrounding the tumors are compared by US imaging. The hypoxic status of tumors and their sensitivity to RT were investigated. Our findings suggest that O2 @MBs combined with UTMD can significantly enhance
the effects of RT. In addition, the in vivo biosafety assay demonstrates good biocompatibility, indicating great potential for clinical translation.
The Effect of Magnetic Poly(lactic-co-glycolic acid) Microsphere-Gelatin Hydrogel on the Growth of Pre-Osteoblasts Under Static Magnetic Field
Authors: Wang Jingxi , Li Ping , Li Kun , Xu Junwei , Liu Meili , Fan Yubo
Published: January 2021

A number of bone repair materials are demanded due to bone injury in clinical treatment. Magnetic hydrogels combined with the magnetic field have showed great promoting potential in the field of bone regeneration. Considering the superiority of magnetic microspheres in magnetic localization
and drug release, magnetic poly(lactic-co-glycolic acid) microspheres, obtained by electrospraying, were combined with gelatin hydrogel to construct a magnetic poly(lactic-co-glycolic acid) microsphere-gelatin hydrogel for bone repair in our study. Particularly, we investigated the combined
effect of 20 mT static magnetic field and magnetic poly(lactic-co-glycolic acid) microsphere-gelatin hydrogel on the proliferation of MC3T3-E1 pre-osteoblasts, indicating that it could significantly promote cell growth at a low concentration of Fe3 O4. Furthermore, the
hydrogel containing 400 mg˙ L–1Fe3 O4 presented the highest growth-promoting effect under a 20 mT static magnetic field. Therefore, the magnetic poly(lactic-co-glycolic acid) microsphere-gelatin hydrogel possesses impressive application value in promoting
osteogenesis and bone repair.
Usability of Urban Local Body Websites and Service Quality of E-services
Authors: Doctor Gayatri , Samuel Mercy , Christian Perez , Baradi Manvita
Published: January 2021

Developments in the Information and Communication Technology (ICT) field have brought a significant change in the way citizens can interact with their governments. Traditional governance has been digitalised to what we now know as ‘e-governance’. E-government investments in India had seen a ‘ten-fold increase’ in 2015 with the launch of the Digital India Mission as compared to previous years. Despite this, in 2018, an e-government survey by the United Nations, India’s E-government Development Index (EGDI) was 0.5669, just above the world average of 0.55. As digital literacy is becoming increasingly common in India, along with falling data prices, increasing smartphone and mobile usage, the spotlight of e-government should focus on the usability and quality of its services and platforms.

This article measures the usability of the Municipal or Urban Local Body (ULB) websites and the service quality of its e-services. Separate evaluation frameworks are used to measure the usability of the municipal e-government websites of four Indian cities as well as the service quality of the four most commonly used citizen services, viz. complaint registration, payment of property tax, payment of professional taxes and birth/death registration. For this, a thorough study of existent literature on the subject, comprehensive study of the selected websites and discussions with domain experts have been conducted by the authors. The article also discusses some qualitative issues on the usability of these websites and services that were observed during the evaluation process.
Outsourcing Reproductive Care: The Restrictive Regime of the Japan Society of Obstetrics and Gynaecology
Authors: Croydon Silvia Atanassova
Published: January 2021

Japan is a developed country where many women, having obtained a higher education and entered the labour force, increasingly postpone childbirth and motherhood beyond their most fertile years. Whilst such a trend has been documented almost everywhere in the developed world, what is conspicuous about the particular case of Japan is how limited these women are when it comes to their options to build a family through assisted reproduction. This article puts the spotlight on five kinds of fertility patients in Japan who, by being largely denied access to assisted reproduction domestically, are pushed to seek solutions abroad, driving the regional (and global) demand for such arrangements. The article identifies as instrumental to this trend the restrictive regime created by the Japan Society of Obstetrics and Gynaecology.
Third-party regime type and civil war duration
Authors: Norrevik Sara , Sarwari Mehwish
Published: January 2021

Does the regime type of a foreign intervener influence the duration of civil wars? Existing research has shown that third-party support affects the outcome of a conflict. Moreover, studies show that the type of support offered to conflict actors can determine how a war ends. While this research has offered significant implications on conflict dynamics, extant works have overlooked the importance of characteristics of foreign supporters and how their attributes can impact conflict outcomes. Focusing on foreign troop support and quantities, this article examines the relationship between the regime type of a foreign supporter and the outcome of an armed conflict. We argue that regime type of an external troop sponsor can influence war duration based on two dynamics: selection effects and signaling effects. Specifically, troop assistance provided to warring parties by democracies decreases the length of civil wars and increases the likelihood for a one-sided victory for the supported faction. The empirical findings for all intrastate conflicts during the period 1975–2012 provide evidence for our claims that the regime type of an external intervener influences the outcome of a conflict.