bluuebunny/crossref_metadata_2025 huggingface dataset:
Carrageenan-containing over-the-counter nasal and oral sprays inhibit SARS-CoV-2 infection of airway epithelial cultures
Authors: Schütz Desiree , Conzelmann Carina , Fois Giorgio , Groß Rüdiger , Weil Tatjana , Wettstein Lukas , Stenger Steffen , Zelikin Alexander , Hoffmann Thomas K. , Frick Manfred , Müller Janis A. , Münch Jan
Published: February 2021

Pharmaceutical interventions are urgently needed to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission. As SARS-CoV-2 infects and spreads via the nasopharyngeal airways, we analyzed the antiviral effect of selected nasal and oral sprays on virus infection in vitro. Two nose sprays showed virucidal activity but were cytotoxic precluding further analysis in cell culture. One nasal and one mouth spray suppressed SARS-CoV-2 infection of TMPRSS2-expressing Vero E6 cells and primary differentiated human airway epithelial cultures. The antiviral activity in both sprays could be attributed to polyanionic ι- and κ-carrageenans. Thus, application of carrageenan-containing nasal and mouth sprays may reduce the risk of acquiring SARS-CoV-2 infection and may limit viral spread, warranting further clinical evaluation.
Subdirect Sums of Doubly Strictly Diagonally Dominant Matrices
Authors: Li Yating , Chen Xiaoyong , Liu Yi , Gao Lei , Wang Yaqiang
Published: February 2021

In this paper, the question of when the subdirect sum of two doubly strictly diagonally dominant (DSDDs) matrices is addressed. Some sufficient conditions are given, and these sufficient conditions only depend on the elements of the given matrices. Moreover, examples are presented to illustrate the corresponding results.
Effect of Concentration and Suspension Agent (HPMC) on Properties of Coal Gangue and Fly Ash Cemented Filling Material
Authors: Yang Baogui , Jin Junyu , Yin Xindong , Wang Xiaoyu , Yang Hongliang
Published: February 2021

Cemented coal gangue‐fly ash backfill (CGFB) mixtures are utilized as the filling materials for backfilling the underground openings in coal mines. The freshly prepared CGFB slurries are commonly transported into the gobs through a pipeline. The mixture ratio of slurry concentration and suspending agent (HPMC) plays an essential role in transporting the slurry to goaf smoothly and efficiently. In this paper, the influence of slurry concentration and HPMC on the performance of coal gangue‐fly ash cemented filling material was studied based on the response surface method. The prediction model of CGFB slurry slump flow, segregation rate, and bleeding rate was constructed. It is concluded that the segregation rate and slump flow of slurry are more sensitive to the variation of concentration. On the other hand, the bleeding rate of slurry is more sensitive to the change of HPMC content. Based on the established model, the reasonable mix proportion range of slurry concentration and suspending agent (HPMC) was obtained. In addition, three new CGFB mixtures have been tested, and the experimental results are in good agreement with the predicted values.
Quantitative Evaluation of SRS Similarity for Aerospace Testing Applications
Authors: Adebolu Ibukun O. , Masui Hirokazu , Cho Mengu
Published: February 2021

The similarity between a shock response spectrum (SRS) and a target shock specification is essential in evaluating the success of a qualification test of a space component. Qualification testing facilities often utilize shock response databases for rapid testing. Traditionally, the comparison of two shocks (SRS) depends on visual evaluation, which is, at best, subjective. This paper compares five different quantitative methods for evaluating shock response similarity. This work aims to find the most suitable metric for retrieving an SRS from a pyroshock database. The five methods are the SRS difference, mean acceleration difference, average SRS ratio, dimensionless SRS coefficients, and mean square goodness‐of‐fit method. None of the similarity metrics account for the sign of the deviation between the target SRS and database SRS, making it challenging to satisfy the criteria for a good shock test. We propose a metric (the weighted distance) for retrieving the most similar SRS to a target SRS specification from a shock database in this work. The weighted distance outperforms the mean square goodness‐of‐fit and other metrics in database SRS retrieval for rapid qualification testing.
The Antioxidant Enzyme PON1: A Potential Prognostic Predictor of Acute Ischemic Stroke
Authors: Xu Yuzhen , Wang Kai , Wang Qian , Ma Yihong , Liu Xueyuan
Published: February 2021

Objective. Paraoxonase 1 (PON1) is an antioxidant enzyme, which has been proved to be involved in the pathophysiological process of oxidative stress and various neurological diseases in recent years. Although reduced PON1 activity has been reported in patients with acute ischemic stroke (AIS), the prognostic value of PON1 in AIS has not been clearly established. The purpose of this study was to determine whether the baseline serum PON1 activity level is related to the functional outcome of AIS patients. Methods. From July 2017 to June 2020, AIS patients within 3 days of symptom onset were continuously prospectively included in the study. On admission, clinical and laboratory data were recorded, and serum PON1 activity was tested. The National Institute of Health Stroke Scale (NIHSS) score was used to evaluate the initial neurologic deficit at admission, and the modified Rankin scale (mRS) was used to evaluate the functional outcome at 3 months. A multiple logistic regression model was used to analyze the relationship between the baseline PON1 activity level and the prognosis of AIS. Results. A total of 336 AIS patients were finally included in this study. The serum PON1 activity of AIS patients with good outcomes was significantly higher than that of patients with poor outcomes (193.4 ± 16.3 U/mL vs. 127.2 ± 14.9 U/mL, p < 0.001). However, the comparison of other clinical and laboratory data between AIS patients with good and poor outcomes was not significant (p > 0.05). There was a significant decrease in the mRS score in patients with AIS across serum PON1 quartiles (3.0 ± 1.6, 2.6 ± 1.5, 2.4 ± 1.4, and 2.4 ± 1.3, p = 0.007). Multivariate logistic regression analysis showed that the 3‐month functional outcome of AIS patients was significantly correlated with the quartile of serum PON1 activity. Conclusions. This study suggests that the serum PON1 activity may be an independent predictor of the functional outcome of AIS patients.
A Generic Embedding Class-I Model via Karmarkar Condition in
f

ℛ
,
T

Gravity
Authors: Zubair M. , Waheed Saira , Javaid Hina
Published: February 2021

In the present work, we investigate the existence of compact star model in the background of

f

ℛ
,
T

gravity theory, where

ℛ

represents the Ricci scalar and

T

refers to the energy-momentum tensor trace. Here, we use Karmarkar condition for the interior stellar setup so that a complete and precise model following the embedding class-I strategy can be obtained. For this purpose, we assume anisotropic matter contents along with static and spherically symmetric geometry of compact star. As Karmarkar embedding condition yields a relationship of metric potentials, therefore we assume a suitable form for one of the metric components as

e

ϕ

=
a

r

2

+

b

n
−
1

r

n

+
1

, where

a

and

b

represent constants and

n

is a free parameter, and evaluate the other. We approximate the values of physical parameters like

a
,
A

, and

B

by utilizing the known values of mass and radius for the compact star Vela X-1. The validity of the acquired model is then explored for different values of coupling parameter

λ

graphically. It is found that the resulting solution is physically interesting and well-behaved.
Vibration Characteristics of Subway Tunnel Structure in Viscous Soil Medium
Authors: Ren Dawei , Shao Shengjun , Cao Xiaoshan , Hu Yifeng
Published: February 2021

Based on research on subway tunnels in a viscous soil medium, this paper establishes the vibration equation of a tunnel structure by using the theory of moderately thick cylindrical shells and the method of wave propagation. The soil around the tunnel is represented in simplified form as an isotropic viscoelastic medium to obtain the equation of motion of the soil, and the vibration control equation of the tunnel under the influence of viscous soil is obtained by coupling. By numerical calculations, the variation trends in the natural vibration frequency of the tunnel and attenuation affected by soil viscosity under different modes are given. Furthermore, the influences of the tunnel radius, wall thickness, and length on the vibration characteristics of a tunnel structure in viscous soil are discussed. This study will provide a reference for the design of subway vehicles and the antivibration design of subway tunnel structures.
Model Test on the Vibration Reduction Characteristics of a Composite Foundation with Gravel Cushion under Different Seismic Wave Amplitudes
Authors: Zhao Yingying , Gong Weiming , Ling Xianzhang , Li Peng , Wang Ziyu , Fan Hong
Published: February 2021

Gravel cushions have been introduced as a practical and efficient seismic isolation technology to ensure the safety of nuclear power plants. This study investigated the seismic isolation effect of a gravel cushion by conducting a series of shaking table tests on a model foundation with a cushion built of three different types of graded aggregates (single‐sized (2–5 mm), two‐sized (2–5 mm:5–10 mm = 3 : 1), and continuously graded) under input El Centro seismic waves with three different peak accelerations (0.1 g, 0.2 g, and 0.3 g). The testing results showed that the seismic isolation effect of the gravel cushion increased with the peak seismic acceleration. The gravel cushion built with single‐sized aggregates had better seismic isolation performance than gravel cushions built with two‐sized or continuously graded aggregates. Under input seismic waves with 0.1 g peak acceleration, the single‐sized aggregate gravel cushion still had a seismic isolation effect with a vibration reduction rate of approximately 11.81%, whereas the other two gravel cushions had no effect. Under input seismic waves with peak accelerations of 0.2 g and 0.3 g, all three gravel cushions had seismic isolation effects with vibration reduction rates of approximately 18.63% and 17.92%, respectively. An empirical model is proposed for predicting the vibration reduction rate of the cushion. Under input seismic waves with 0.3 g peak acceleration, the ultimate vibration reduction rate of the gravel cushion fell between 20.44% and 31.33%. The gravel cushion is an excellent option for nuclear power plant foundations with high requirements for seismic isolation, provided that the required bearing capacity is satisfied.
Motor Sequence Learning across Multiple Sessions Is Not Facilitated by Targeting Consolidation with Posttraining tDCS in Patients with Progressive Multiple Sclerosis
Authors: Seelmann-Eggebert Harald , Stoppe Muriel , Then Bergh Florian , Classen Joseph , Rumpf Jost-Julian
Published: February 2021

Compared to relapsing-remitting multiple sclerosis (MS), progressive MS is characterized by a lack of spontaneous recovery and a poor response to pharmaceutical immunomodulatory treatment. These patients may, therefore, particularly benefit from interventions that augment training-induced plasticity of the central nervous system. In this cross-sectional double-blind cross-over pilot study, effects of transcranial direct current stimulation (tDCS) on motor sequence learning were examined across four sessions on days 1, 3, 5, and 8 in 16 patients with progressive MS. Active or sham anodal tDCS of the primary motor cortex was applied immediately after each training session. Participants took part in two experiments separated by at least four weeks, which differed with respect to the type of posttraining tDCS (active or sham). While task performance across blocks of training and across sessions improved significantly in both the active and sham tDCS experiment, neither online nor offline motor learning was modulated by the type of tDCS. Accordingly, the primary endpoint (task performance on day 8) did not differ between stimulation conditions. In sum, patients with progressive MS are able to improve performance in an ecologically valid motor sequence learning task through training. However, even multisession posttraining tDCS fails to promote motor learning in progressive MS.
Comparative Regression Analysis for Estimating Resonant Frequency of C-Like Patch Antennas
Authors: Özkaya Umut , Yiğit Enes , Seyfi Levent , Öztürk Şaban , Singh Dilbag
Published: February 2021

This study provides a comparative analysis of regression techniques to estimate the operating frequency of the C-like microstrip antenna. The performance of well-known regression techniques such as linear regression (LR), regression tree (RT), support vector regression (SVR), Gaussian regression (GR), and artificial neural network (ANN) is tested. For this purpose, 160 C-like microstrip antennas are simulated, of which 145 are used for training of regression techniques and 15 for testing. From the evaluated results, it is found that the pure quadratic Gaussian regression (PQGR) technique has the lowest error rates with 0.0109 mean absolute error (MAE), 0.0087 median error (ME), 0.0002 mean squared error (MSE), 0.0156 root mean squared error (RMSE), and 0.5981 average percentage error (APE). As can be seen in the comparative analysis, the PQGR method outperforms other regression methods on simulation and measurement data. Experimental analysis shows that the resonant frequency of the C-like patch antennas can be calculated very close to measurements.
Correlation of Total Polyphenolic Content with Antioxidant Activity of Hydromethanolic Extract and Their Fractions of the Salvia officinalis Leaves from Different Regions of Morocco
Authors: Khiya Zakaria , Oualcadi Yassine , Gamar Abderrahmane , Berrekhis Fatima , Zair Touria , Hilali Fatima EL
Published: February 2021

The purpose of this study is to determine the total content of phenols, flavonoids, and condensed tannins, as well as on the antioxidant activity of the extract, and their fractions were measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), phosphomolybdate reduction (or total antioxidant capacity), and cyclic voltammetry (CV). The hydromethanolic extract of Salvia officinalis showed the highest values of total phenolic (176 mgGAE/g of extract) and condensed tannins (162.53 mgEC/g of extract) from the Boulemane and Khenifra regions, respectively. The results showed that the best DPPH assay was found in the ethyl acetate fraction of Salvia officinalis leaves of the Boulemane region (IC50 = 0.002 mg/ml). For the ethyl acetate and butanolic fractions of Salvia officinalis leaves, those collected from different regions have a better reducing capacity (EC50 = 0.021 mg/ml, respectively). For the total antioxidant capacity, the best activity was found in the aqueous fraction of Salvia officinalis leaves of the Boulemane region (108 mgGAE/g of extract). By the cyclic voltammetry method, hydromethanolic extract of Salvia officinalis leaves from the Boulemane region showed an important result (288.8 mgGAE/g). There was a positive correlation between total phenol content (TPC), condensed tannin content (TCT), and total antioxidant capacity (TAC) (r = 0.932, r = 0.896, respectively). The main compounds that have been identified in the hydromethanolic extract of Salvia officinalis are ascorbic acid, gallic acid, 4-hydroxybenzoic acid, tannic acid, and rutin. Due to their antioxidant property, the leaf extracts from Salvia officinalis are used as natural preservative ingredients in food and/or pharmaceutical industries.
Comparison of In Vitro Endocrine Activity of Phthalates and Alternative Plasticizers
Authors: Moche Hélène , Chentouf Aouatif , Neves Sergio , Corpart Jean-Marc , Nesslany Fabrice
Published: February 2021

Because of the deleterious effects of phthalates, regulations have been taken to decrease their use, and the needs for alternatives are increasing. Due to the concerns about the endocrine-disrupting properties of phthalates, it was deemed necessary to particularly investigate these effects for potential substitutes. In this study, we compared the in vitro endocrine activity of several already used potential alternative plasticizers (DEHT, DINCH, and TOTM) or new substitutes (POLYSORB® isosorbide and POLYSORB® ID 46) to one of 2 phthalates, DEHP and DINP. Effects of these chemicals on 3 common mechanisms of endocrine disruption, i.e., interaction with estrogen receptors (ER), androgen receptors (AR), or steroidogenesis, were studied using extensively used in vitro methods. In the E-Screen assay, only DEHP moderately induced MCF-7 cell proliferation; none of the other tested substances were estrogenic or antiestrogenic. No androgenic or antiandrogenic activity in MDA-kb2 cells was shown for any of the tested phthalates or alternatives. On the other hand, both DEHP and DINP, as well as DEHT, DINCH, and TOTM, disrupted steroidogenesis in the H295R assay, mainly by inducing an increase in estradiol synthesis; no such effect was observed for POLYSORB® isosorbide and POLYSORB® ID 46.
Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy
Authors: Ayala-Mar Sergio , Donoso-Quezada Javier , González-Valdez José
Published: February 2021

Inhibiting the programmed cell death ligand-1 (PD-L1)/programmed cell death receptor-1 (PD-1) signaling axis reinvigorates the antitumor immune response with remarkable clinical efficacy. Yet, low response rates limit the benefits of immunotherapy to a minority of patients. Recent studies have explored the importance of PD-L1 as a transmembrane protein in exosomes and have revealed exosomal PD-L1 as a mechanism of tumor immune escape and immunotherapy resistance. Exosomal PD-L1 suppresses T cell effector function, induces systemic immunosuppression, and transfers functional PD-L1 across the tumor microenvironment (TME). Because of its significant contribution to immune escape, exosomal PD-L1 has been proposed as a biomarker to predict immunotherapy response and to assess therapeutic efficacy. In this review, we summarize the immunological mechanisms of exosomal PD-L1, focusing on the factors that lead to exosome biogenesis and release. Next, we review the effect of exosomal PD-L1 on T cell function and its role across the TME. In addition, we discuss the latest findings on the use of exosomal PD-L1 as a biomarker for cancer immunotherapy. Throughout this review, we propose exosomal PD-L1 as a critical mediator of tumor progression and highlight the clinical implications that follow for immuno-oncology, discussing the potential to target exosomes to advance cancer treatment.
Study on Irrigation Water Quality in the Rift Valley Areas of Awash River Basin, Ethiopia
Authors: Aregahegn Zeyede , Zerihun Mulate
Published: February 2021

Awash River water has been impaired by various types of pollution owing to waste released from different socioeconomic activities in its basin. This study aimed to evaluate the water quality of the Awash River and its tributaries in the basin used for irrigation purposes. Sampling sites were identified based on the pollution sources, accessibility, and land-use coverage. A total of 17 sampling sites were chosen along the Awash River, and samplings were collected four times a year through different seasons. The overall water quality and suitability for irrigation are explained using multiple water quality parameters such as pH, EC, SAR, RSC, Na+, K+, Ca + Mg, CO32−, HCO3−, and Cl−. The obtained results showed that all quality parameters at Beseka Lake exceed the maximum permissible limit of suitability for irrigation. It is generally conceivable that the physicochemical characteristic of the Awash River varies in different water quality parameters at different sites. Only Beseka Lake and Meteka hot spring water exceeded pH and SAR permissible limit, and EC at Mojo, Wonji, Beseka, Melkasedi, Werer, Ambash, Meteka, and Meteka hot spring shows medium-to-high salinity scale, while RSC was very high at Beseka, Melkasedi, Meteka hot spring, Ambash, Meteka Mojo, Werer, Assayta, Wonji, Dupty, Tibila, Metehara, and Afambo, respectively. The establishment of wastewater treatment plants for industries and stormwater quality management at hotspot areas are recommended to improve the water quality, and dispatch proportion needs to be considered in the future.
Positive Associations between Adipocyte Fatty Acid-Binding Protein Level and Central Arterial Stiffness in Peritoneal Dialysis Patients
Authors: Sung Cheng-Hao , Hsu Bang-Gee , Tasi Jen-Pi , Wang Chih-Hsien , Kuo Chiu-Huang
Published: February 2021

Background. Adipocyte fatty acid-binding protein (A-FABP) plays essential roles in lipolysis, insulin resistance, and atherosclerosis. This study aimed to evaluate the relationship between serum A-FABP levels and carotid-femoral pulse wave velocity (cfPWV) in peritoneal dialysis (PD) patients. Methods. This study obtained fasting blood samples from 76 PD patients. A validated tonometry system was used to measure cfPWV. Patients with cfPWV values >10 m/s were classified into the high arterial stiffness group, whereas patients with values ≤10 m/s were classified into the low arterial stiffness group, according to the ESH-ESC 2013 guidelines. Serum A-FABP levels were measured using a commercial enzyme-linked immunosorbent assay kit. Results. Twenty-five (32.9%) of the 76 PD patients were classified in the high arterial stiffness group. Compared with the patients in the low arterial stiffness group, the high arterial stiffness group was older (P = 0.002) and had a longer PD vintage (P = 0.011), higher diastolic blood pressure (DBP,P = 0.036), higher fasting glucose levels (P = 0.012), higher serum C reactive protein levels (P = 0.001), and higher serum A-FABP levels (P < 0.001). A multivariate logistic regression analysis of the factors significantly associated with central arterial stiffness revealed that A-FABP (odds ratio (OR): 1.165, 95% confidence interval (CI): 1.056–1.284,P = 0.002), age (OR: 1.423, 95% CI: 1.153–1.757,P = 0.001), PD vintage (OR: 1.049, 95% CI: 1.015–1.085,P = 0.005), and DBP (OR: 1.152, 95% CI: 1.033–1.285,P = 0.011) were independent predictors of central arterial stiffness in PD patients. Furthermore, serum A-FABP levels (β = 0.476, adjusted R2 change: 0.197,P < 0.001) were significantly positively correlated with cfPWV according to the multivariable forward stepwise linear regression analysis. Conclusions. A-FABP levels are an independent marker of central arterial stiffness in PD patients.
Study on the Water‐Physical Properties of the Cement‐Plaster Bonded Rock‐Like Materials
Authors: Zhang Yong , Cao Zhiguo , Shi Xiaomeng
Published: February 2021

The cement‐plaster bonded rock‐like material is one of the most commonly used materials to simulate different rocks in physical model tests. However, the applicability of this material in solid‐fluid coupling model tests is not clear because there are few research studies on the water‐physical properties of this material and its similarity to the actual rock is uncertain. This paper presents a systemic experimental study on the water‐physical properties of the cement‐plaster bonded rock‐like materials. The parameters of rock‐like materials, including water absorption, softening coefficient, and permeability coefficient, were compared with those of actual rocks to analyse the applicability of such material. Then, the influence of proportion on the water‐physical properties of this material was discussed. By multiple regression analysis of the test results, empirical equations between the water‐physical parameters and proportions were proposed. The equations can be used to estimate the water‐physical properties of cement‐plaster bonded rock‐like materials with specific proportion and thus to select suitable materials in the solid‐fluid coupling physical model tests.
Prevalence and Nonpharmacological Interventions for Sarcopenia among Cirrhotic Patients
Authors: Abdelbasset Walid Kamal , Nambi Gopal , Elsayed Shereen H. , Moawd Samah A. , Ibrahim Ahmed A. , Verma Anju , Tantawy Sayed A. , Kamel Dalia M. , Saleh Ayman K. , Aldhafian Osama R. , Nwihadh Naif Bin
Published: February 2021

Sarcopenia is the most common feature of hepatic cirrhosis characterized by progressive loss of muscle mass and function and increases permanently the mortality and morbidity rates among those patients. The incidence of sarcopenia in cirrhotic patients ranged 40-70% associating with impaired quality of life and augmented rates of infection. Based on these issues, this review is aimed at determining the prevalence and main causes of sarcopenia among cirrhotic patients and recognizing the recent diagnostic and physical treatment modalities that prevent risk factors for sarcopenia in those patients. No ideal modality is currently demonstrated for diagnosing sarcopenia in hepatic diseases, particularly cirrhosis; however, recent studies reported different diagnostic modalities for muscle function in different individuals including handgrip strength, skeletal muscle index, six-min walk test, liver frailty index, short physical performance battery, and radiological assessments for quadriceps and psoas muscles. Exercise training and therapeutic nutrition are strongly recommended for controlling sarcopenia in cirrhotic patients. The exercise program is designed and carried out on a frequent basis within an extensive scheduled time aimed at improving functional performance, aerobic capacity, and healthy conditions. Finally, a combination of exercise training and therapeutic nutrition is powerfully recommended to control sarcopenia in cirrhosis.
Serum Metabolites as an Indicator of Developing Gestational Diabetes Mellitus Later in the Pregnancy: A Prospective Cohort of a Chinese Population
Authors: Tian Mengyuan , Ma Shujuan , You Yiping , Long Sisi , Zhang Jiayue , Guo Chuhao , Wang Xiaolei , Tan Hongzhuan
Published: February 2021

Objective. Gestational diabetes mellitus (GDM) is a common metabolic disorder with onset during pregnancy. However, the etiology and pathogenesis of GDM have not been fully elucidated. In this study, we used a metabolomics approach to investigate the relationship between maternal serum metabolites and GDM in early pregnancy. Methods. A nested case-control study was performed. To establish an early pregnancy cohort, pregnant women in early pregnancy (10‐13+6weeks) were recruited. In total, 51 patients with GDM and 51 healthy controls were included. Serum samples were analyzed using an untargeted high-performance liquid chromatography mass spectrometry metabolomics approach. The relationships between metabolites and GDM were analyzed by an orthogonal partial least-squares discriminant analysis. Differential metabolites were evaluated using a KEGG pathway analysis. Results. A total of 44 differential metabolites were identified between GDM cases and healthy controls during early pregnancy. Of these, 26 significant metabolites were obtained in early pregnancy after false discovery rate (FDR<0.1) correction. In the GDM group, the levels of L-pyroglutamic acid, L-glutamic acid, phenylacetic acid, pantothenic acid, and xanthine were significantly higher and the levels of 1,5-anhydro-D-glucitol, calcitriol, and 4-oxoproline were significantly lower than those in the control group. These metabolites were involved in multiple metabolic pathways, including those for amino acid, carbohydrate, lipid, energy, nucleotide, cofactor, and vitamin metabolism. Conclusions. We identified significant differentially expressed metabolites associated with the risk of GDM, providing insight into the mechanisms underlying GDM in early pregnancy and candidate predictive markers.
The IKZF1–IRF4/IRF5 Axis Controls Polarization of Myeloma-Associated Macrophages
Authors: Mougiakakos Dimitrios , Bach Christian , Böttcher Martin , Beier Fabian , Röhner Linda , Stoll Andrej , Rehli Michael , Gebhard Claudia , Lischer Christopher , Eberhardt Martin , Vera Julio , Büttner-Herold Maike , Bitterer Katrin , Balzer Heidi , Leffler Magdalena , Jitschin Simon , Hundemer Michael , Awwad Mohamed H.S. , Busch Martin , Stenger Steffen , Völkl Simon , Schütz Christian , Krönke Jan , Mackensen Andreas , Bruns Heiko
Published: February 2021

The bone marrow niche has a pivotal role in progression, survival, and drug resistance of multiple myeloma cells. Therefore, it is important to develop means for targeting the multiple myeloma bone marrow microenvironment. Myeloma-associated macrophages (MAM) in the bone marrow niche are M2 like. They provide nurturing signals to multiple myeloma cells and promote immune escape. Reprogramming M2-like macrophages toward a tumoricidal M1 phenotype represents an intriguing therapeutic strategy. This is especially interesting in view of the successful use of mAbs against multiple myeloma cells, as these therapies hold the potential to trigger macrophage-mediated phagocytosis and cytotoxicity. In this study, we observed that MAMs derived from patients treated with the immunomodulatory drug (IMiD) lenalidomide skewed phenotypically and functionally toward an M1 phenotype. Lenalidomide is known to exert its beneficial effects by modulating the CRBN-CRL4 E3 ligase to ubiquitinate and degrade the transcription factor IKAROS family zinc finger 1 (IKZF1). In M2-like MAMs, we observed enhanced IKZF1 levels that vanished through treatment with lenalidomide, yielding MAMs with a bioenergetic profile, T-cell stimulatory properties, and loss of tumor-promoting capabilities that resemble M1 cells. We also provide evidence that IMiDs interfere epigenetically, via degradation of IKZF1, with IFN regulatory factors 4 and 5, which in turn alters the balance of M1/M2 polarization. We validated our observations in vivo using the CrbnI391V mouse model that recapitulates the IMiD-triggered IKZF1 degradation. These data show a role for IKZF1 in macrophage polarization and can provide explanations for the clinical benefits observed when combining IMiDs with therapeutic antibodies.

See related Spotlight on p. 254
Maternal Citicoline-Supplemented Diet Improves the Response of the Immature Hippocampus to Perinatal Asphyxia in Rats
Authors: Isac Sebastian , Panaitescu Anca Maria , Iesanu Mara Ioana , Zeca Vlad , Cucu Natalia , Zagrean Leon , Peltecu Gheorghe , Zagrean Ana-Maria
Published: February 2021

Background: Citicoline represents a dietary source of choline, an essential nutrient, and precursor of cell membrane components, highly required during development and post-injury recovery. Objectives: We previously showed that perinatal asphyxia (PA) induces hippocampal neuroinflammation and injury that are subject to epigenetic change by maternal diet. The present study investigates maternal citicoline-supplemented diet (CSD) impact on offspring hippocampal response to PA. Methods: Six-day-old Wistar rats from mothers with standard-diet or CSD were exposed to PA. The hippocampal inflammation and injury were assessed by interleukin-1 beta (IL-1b), tumor necrosis factor-alpha (TNFα), and S-100B protein (S-100B), 24–48 h post-asphyxia. The microRNAs species miR124, miR132, miR134, miR146, and miR15a were measured from the hippocampus 24 h post-asphyxia, to investigate its epigenetic response to PA and maternal diet. At maturity, the offspring’s behavior was analyzed using open field (OFT), T-maze (TMT), and forced swimming (FST) tests. Results: Our data show that the maternal CSD decreased IL-1b (p = 0.02), TNFα (p = 0.007), and S100B (p = 0.01) at 24 h postexposure, upregulated miR124 (p = 0.03), downregulated miR132 (p = 0.002) and miR134 (p = 0.001), shortened the immobility period in FST (p = 0.01), and increased the percentage of passed trials in TMT (p = 0.01) compared to standard-diet. Conclusions: Maternal CSD reduces hippocampal inflammation and S100B level, triggers epigenetic changes related to homeostatic synaptic plasticity, memory formation, and neuronal tolerance to asphyxia, decreases the depressive-like behavior, and improves the lucrative memory in offspring subjected to PA. Thus, citicoline could be valuable as a maternal dietary strategy in improving the brain response to PA.
Daprodustat Compared with Epoetin Beta Pegol for Anemia in Japanese Patients Not on Dialysis: A 52-Week Randomized Open-Label Phase 3 Trial
Authors: Nangaku Masaomi , Hamano Takayuki , Akizawa Tadao , Tsubakihara Yoshiharu , Nagai Reiko , Okuda Nobuhiko , Kurata Kyo , Nagakubo Takashi , Jones Nigel P. , Endo Yukihiro , Cobitz Alexander R.
Published: February 2021

Background: Daprodustat is an oral agent that stimulates erythropoiesis by inhibiting the prolyl hydroxylases which mark hypoxia-inducible factor for degradation through hydroxylation. Its safety and efficacy (noninferiority) were assessed in this 52-week, open-label study. Methods: Japanese patients not on dialysis (ND) (N = 299) with anemia of CKD (stages G3, G4, and G5) with iron parameters of ferritin >100 ng/mL or transferrin saturation >20% at screening were randomized to daprodustat or epoetin beta pegol (continuous erythropoietin receptor activator [CERA], also known as methoxy polyethylene glycol-epoetin beta). After initiation of the study, the daprodustat starting dose for erythropoiesis-stimulating agent (ESA)-naïve participants was revised, and daprodustat was started at 2 or 4 mg once daily depending on baseline hemoglobin. ESA users switched to daprodustat 4 mg once daily. CERA was started at 25 μg every 2 weeks for ESA-naïve patients and 25–250 μg every 4 weeks for ESA users based on previous ESA dose. In both treatment groups, dose was adjusted every 4 weeks based on hemoglobin level and changed according to a prespecified algorithm. The primary endpoint was mean hemoglobin level during weeks 40–52 in the intention-to-treat (ITT) population. ESA-naïve patients who entered before the protocol amendment revising the daprodustat starting dose were excluded from the ITT population. Results: Mean hemoglobin levels during weeks 40–52 were 12.0 g/dL in the daprodustat group (n = 108; 95% confidence interval [CI], 11.8–12.1) and 11.9 g/dL for CERA (n = 109; 95% CI 11.7–12.0); the difference between the groups was 0.1 g/dL (95% CI −0.1 to 0.3 g/dL). The lower limit of the 95% CI of the difference was greater than the prespecified margin of −1.0 g/dL. The mean hemoglobin level was within the target range (11.0–13.0 g/dL) during weeks 40–52 for 92% of participants in both groups. There was no meaningful difference in the frequencies of adverse events. Conclusions: Oral daprodustat was noninferior to CERA in achieving and maintaining target hemoglobin levels in Japanese ND patients. Daprodustat was well tolerated, with no new safety concerns identified.
Reflux Symptoms – Functional and Structural Diseases: The Approach from the General Practitioner
Authors: Herszényi László
Published: February 2021

A primary care management strategy of gastroesophageal reflux disease (GERD) should pay attention to the epidemiology, prevalence, and distribution of reflux-like symptoms in the community and to the special characteristics of patients presenting for the first time with reflux symptoms in primary care. General practitioners (GPs) encounter daily challenges to make cost-effective differential diagnostic and therapeutic decisions, avoiding needless and costly investigation or referral. They should provide long-term effective control of symptoms and esophageal healing in a personalized, symptom-based, patient-centered, and evidence-based manner. GPs should use a practical system of triage in order to distinguish the high majority of patients with self-limiting conditions from the minority with alarm symptoms with potentially severe disorder. They should also discriminate between troublesome and nontroublesome reflux symptoms. Most GERD is uncomplicated and can be treated using management algorithms that make the best use of resources. Some strategies such as “step-down,” “intermittent,” or “on-demand” therapy can cost-effectively improve the long-term management and quality of life of patients with recurrent GERD. The accurate interpretation of “step-down” therapeutic strategy and a careful interpretation of proton pump inhibitor refractoriness are also essential.
Estimation of a Heterogeneous Demand Function with Berkson Errors
Authors: Blundell Richard , Horowitz Joel , Parey Matthias
Published: February 2021

Berkson errors are commonplace in empirical microeconomics. In consumer demand, this form of measurement error occurs when the price an individual pays is measured by the (weighted) average price paid by individuals in a group (e.g., a county) rather than the true transaction price. We show the importance of Berkson errors for demand estimation with nonseparable unobserved heterogeneity. We develop a consistent estimator using external information on the true price distribution. Examining gasoline demand in the United States, we document substantial within-market price variability. Accounting for Berkson errors is quantitatively important. Imposing the Slutsky shape constraint reduces sensitivity to Berkson errors.
Vitexin Inhibits the Proliferation and Promotes the Apoptosis of Gastric Cancer Cells via Phosphatidylinositol-3-Kinase (PI3K)/Protein Kinase B (Akt)/The Mammalian Target of Rapamycin (mTOR) Signaling Pathway
Authors: Jiashu Lu M. M. , Lei Yu M. M. , Ying Ma M. M. , Jie Li M. M.
Published: February 2021

Gastric cancer (GC) is a kind of digestive tract malignancy that has very high morbidity and mortality, making it crucial to find new drug treatments. Vitexin is a kind of flavonoid compound, which has anti-tumor, anti-inflammatory, analgesic and antiviral effects, etc. However, the
specific role of vitexin in GC is still unclear. In this study, the expression of the survival rate and apoptosis was detected by CCK-8 and flow cytometry after vitexin acted on cells. Plasmid transfection technique was used to overexpress PI3K. Expression of PI3K/AKT/mTOR pathway-related
proteins, autophagic-related proteins (Atg14, beclin-1, P62) and apoptotic-related proteins (bcl-2, Bax, cleaved caspase3) were detected by Western blot. We found that the cell survival rate decreased with the increasing time and dosage of vitexin. When vitexin acted on cells, the expression
of p-PI3K, p-AKT and p-mTOR was significantly decreased, the degree of autophagy was increased, and the apoptosis rate was obviously increased. However, the overexpression of PI3K, the level of autophagy and apoptosis rate of cells which were given vitexin significantly decreased. In conclusion,
Vitexin induces autophagy by inhibiting PI3K/AKT/mTOR signaling pathway, thereby inhibiting proliferation and promoting apoptosis of GC cells.
Progranulin Promotes Osteogenic Differentiation and Osteosynthesis of Bone Marrow Mesenchymal Stem Cells and Alleviates Osteoporosis Through Phosphatidylinositol 3-Kinase/Protein Kinase B/Peroxisome Proliferator-Activated Receptor γ Pathway
Authors: Ying Yang , Zhao Binghao , Qian Wei , Xu Li
Published: February 2021

Bone marrow mesenchymal stem cells (BMSCs) have self-renewal potential with multi-directional differentiation. Progranulin prevents bone degradation, inhibits inflammation and protects bone tissue. However, the role of Progranulin in osteoporotic BMSCs is unclear. Osteoporosis (OP)
rat models were prepared by ovarian removal and treated with different doses (5 and 10 μM) of Progranulin followed by analysis of BMP-2 level by ELISA, bone mineral density and ALP activity. OP rat BMSCs were isolated and assigned into control group and Progranulin group followed
by analysis of Progranulin level by ELISA, cell proliferation by MTT assay, RUNX2 and COL1A1 mRNA level by Real time PCR, and PI3K/Akt/PPARγ signaling protein level by Western blot. Progranulin treatment of OP rats dose-dependently increased BMP-2 expression, bone density and
ALP activity. Compared with OP group, there were significant differences (P <0.05). Progranulin expression and BMSCs proliferation was increased, and RUNX2 and COL1A1 mRNA expression was elevated in Progranulin-treated OP group along with increased PI3K/Akt expression and decreased
PPARγ protein expression. Compared with OP group, the difference was statistically significant, and the change was more significant with increasing concentration (P <0.05). Progranulin promotes BMSCs osteogenic differentiation and proliferation by regulating PI3K/Akt/PPARγ
signaling pathway, which is beneficial for OP rats’ bone synthesis.
Who Did the Top Media From Spain Started Following on Twitter? An Exploratory Data Analysis Case Study
Authors: Israel-Turim Verónica , Micó-Sanz Josep Lluís , Ordeix-Rigo Enric
Published: February 2021

The digital sphere and social media platforms have prompted new logics regarding information access and influence flows among media, politicians, and citizens. In this exploratory study, via a machine learning software and with data visualization methods, we analyzed social media data in order to find patterns that can contribute to comprehend the new dynamics of influence between the media, politicians, and citizenship in the context of social media and digital communication, specifically on Twitter. We analyzed who the top 50 Spanish generalist media with most followers started following in 2017, 2018, and 2019 on Twitter, the quintessential informational network. To do so, we melded data visualization computational and manual methods. We used an artificial intelligence big data analysis software to visualize the network of media from Spain in order to identify the sample. Afterward, we extracted the top followed accounts by the sample and categorized them in types of accounts, institution/citizenship, country, number of followers, and gender, to proceed with the data visualization to identify trends and patterns. The results show that these media accounts started following mainly accounts that belonged to male politicians from Spain. We could also spot among the years of the study an inversely proportional trend from the media that went from following mainly institutions to following a majority of citizens, and to start following more accounts with a smaller number of followers every year. The tendency to follow accounts from Spain that belong to men grew or remained a majority among the years of the study.
Step on up! A multi-component health promotion intervention to promote stair climbing
Authors: Ly Hieu , Irwin Jennifer D
Published: February 2021

Objectives:

To study the influence of a multi-component poster-based intervention to promote stair climbing in a library on a Canadian university campus.

Participants:

Adults who ascended to upper levels via staircase/elevator.

Methods:

Individuals who used the staircase/elevators were counted by observers for 28 days, while either in the absence/presence of a poster-based intervention. Chi-square tests were used to compare staircase versus elevator use before, during and after the poster-based intervention. Data from weekdays and weekends were analysed separately.

Results:

A total of 7,663 stair climbers and elevator users were observed. Compared to the baseline period, the frequency of staircase use on weekdays was significantly higher during the intervention and follow-up periods. This effect was not found at weekends.

Conclusion:

This study provides evidence that a multi-component poster-based intervention can result in increased staircase use. The increase observed in this study is similar to that in previous research using point-of-choice prompts only.
Cognitive illness representations among Israeli Arabs diagnosed with depression and their relationship with health-related quality of life
Authors: Abo-Rass Fareeda , Werner Perla , Shinan-Altman Shiri
Published: February 2021

Background:

The number of studies that have assessed cognitive illness representations among people diagnosed with depression, and their relationship to health outcomes, has clearly grown. Nevertheless, the relationship between cognitive illness representations and health-related quality of life (HRQoL) has received very little research attention.

Aims:

This study examined cognitive illness representations, based on the self-regulation model (SRM), and the contribution of each dimension of these cognitive illness representations to health-related quality of life (HRQoL) among Israeli Arabs diagnosed with depression.

Methods:

A convenience sample of 160 Israeli Arabs with depression completed measures of cognitive illness representations (identity, timeline, consequences, personal control, treatment control, and coherence), HRQoL, and sociodemographic and health characteristics.

Results:

Participants reported high levels of negative perceptions in the identity, timeline, and consequences dimensions, and moderate levels in the dimensions of personal control, treatment control, and coherence. Also, participants reported low levels of HRQoL. Identity, consequences, and coherence were found to be the main determinants of HRQoL.

Conclusion:

This study underlines the crucial role of the identity, consequences, and coherence dimensions in the HRQoL of individuals diagnosed with depression. The findings indicate that clinical interventions targeting cognitive illness representations of individuals with depression, and in particular identity, consequences, and coherence, might be helpful in improving the HRQoL of this population.
Mental health-related stigma and attitudes toward patient care among providers of mental health services in a rural Chinese county
Authors: Deng Yuer , Wang An-Li , Frasso Rosemary , Ran Mao-Sheng , Zhang Tian-Ming , Kong Dexia , Wong Yin-Ling Irene
Published: February 2021

Background and aims:

The increasing prevalence of mental illness and low treatment rate presents a pressing public health issue in China. Pervasive stigma is a significant barrier to mental health recovery and community inclusion. In particular, stigmatizing or supportive attitudes held by healthcare providers could either perpetuate or mitigate self-stigma of people with mental illness. Moreover, mental health resources are unevenly distributed in China, with most of them concentrated in urban centers and provincial capitals. This study explores healthcare providers’ attitudes toward mental illness and the challenges they faced at work in a rural Chinese county.

Method:

Four focus groups were conducted with 36 healthcare providers from a three-tier mental healthcare system in a rural county in southwestern China. Focus group discussions were recorded and transcribed verbatim. The team employed a conventional content analysis approach for data analysis. All transcripts were double-coded by three bilingual team members who are native Chinese speakers. Coding discrepancies were resolved by consensus.

Results:

Healthcare providers recruited from the county, township, and village levels varied in educational background, professional qualification, and experience of working with people with mental illness. Five thematic categories identified across four groups include (1) barriers to mental healthcare delivery, (2) keys to mental health recovery, (3) providers’ attitudes toward providing care, (4) providers’ perception toward patients and family members, and (5) providers’ perception of training needs.

Conclusions:

This is a unique study that included healthcare providers from a three-tier healthcare system. Findings signal the importance of understanding healthcare practitioners’ experiences and views to inform the design of training initiatives in rural or low-resource communities.