bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucagon receptor signaling is not required forN-carbamoyl glutamate- andl-citrulline-induced ureagenesis in mice
Authors: Galsgaard Katrine D. , Pedersen Jens , Kjeldsen Sasha A. S. , Winther-Sørensen Marie , Stojanovska Elena , Vilstrup Hendrik , Ørskov Cathrine , Wewer Albrechtsen Nicolai J. , Holst Jens J.
Published: March 2020

Hepatic ureagenesis is essential in amino acid metabolism and is importantly regulated by glucagon, but the exact mechanism is unclear. With the aim to identify the steps whereby glucagon both acutely and chronically regulates ureagenesis, we here show, contrary to our hypothesis, that glucagon receptor-mediated activation of ureagenesis is not required when N-acetylglutamate synthase activity and/or N-acetylglutamate levels are sufficient to activate the first step of the urea cycle in vivo.
UT-A1/A3 knockout mice show reduced fibrosis following unilateral ureteral obstruction
Authors: Rianto Fitra , Kuma Akihiro , Ellis Carla L. , Hassounah Faten , Rodriguez Eva L. , Wang Xiaonan H. , Sands Jeff M. , Klein Janet D.
Published: March 2020

Renal fibrosis is a major contributor to the development and progression of chronic kidney disease. A low-protein diet can reduce the progression of chronic kidney disease and reduce the development of renal fibrosis, although the mechanism is not well understood. Urea reabsorption into the inner medulla is regulated by inner medullary urea transporter (UT)-A1 and UT-A3. Inhibition or knockout of UT-A1/A3 will reduce interstitial urea accumulation, which may be beneficial in reducing renal fibrosis. To test this hypothesis, the effect of unilateral ureteral obstruction (UUO) was compared in wild-type (WT) and UT-A1/A3 knockout mice. UUO causes increased extracellular matrix associated with increases in transforming growth factor-β, vimentin, and α-smooth muscle actin (α-SMA). In WT mice, UUO increased the abundance of three markers of fibrosis: transforming growth factor-β, vimentin, and α-SMA. In contrast, in UT-A1/A3 knockout mice, the increase following UUO was significantly reduced. Consistent with the Western blot results, immunohistochemical staining showed that the levels of vimentin and α-SMA were increased in WT mice with UUO and that the increase was reduced in UT-A1/A3 knockout mice with UUO. Masson’s trichrome staining showed increased collagen in WT mice with UUO, which was reduced in UT-A1/A3 knockout mice with UUO. We conclude that reduced UT activity reduces the severity of renal fibrosis following UUO.
Combinatorial expression of claudins in the proximal renal tubule and its functional consequences
Authors: Curry Joshua N. , Tokuda Shinsaku , McAnulty Patrick , Yu Alan S. L.
Published: March 2020

The proximal renal tubule (PT) is characterized by a highly conductive paracellular pathway, which contributes to a significant amount of solute and water reabsorption by the kidney. Claudins are tight junction proteins that, in part, determine the paracellular permeability of epithelia. In the present study, we determined the expression pattern of the major PT claudins. We found that claudin-2 and claudin-10 are coexpressed throughout the PT, whereas claudin-3 is coexpressed with claudin-2 predominantly in the proximal straight tubule. Additionally, claudin-2 and claudin-3 are expressed separately within mutually exclusive populations of descending thin limbs. We developed a novel double-inducible Madin-Darby canine kidney I cell model to characterize in vitro the functional effect of coexpression of PT claudins. In keeping with previous studies, we found that claudin-2 alone primarily increased cation (Na+and Ca2+) permeability, whereas claudin-10a alone increased anion (Cl−) permeability. Coexpression of claudin-2 and claudin-10a together led to a weak physical interaction between the isoforms and the formation of a monolayer with high conductance but neutral charge selectivity. Claudin-3 expression had a negligible effect on all measures of cell permeability, whether expressed alone or together with claudin-2. In cells coexpressing a claudin-2 mutant, S68C, together with claudin-10a, inhibition of cation permeability through the claudin-2 pore with a thiol-reactive pore blocker did not block anion permeation through claudin-10a. We conclude that claudin-2 and claudin-10a form independent paracellular cation- and anion-selective channels that function in parallel.
Meprin-β activity modulates the β-catalytic subunit of protein kinase A in ischemia-reperfusion-induced acute kidney injury
Authors: Ahmed Faihaa , Mwiza Jean-Marie , Fernander Mizpha , Yahaya Ismaila , Abousaad Shaymaa , Ongeri Elimelda Moige
Published: March 2020

Meprin metalloproteases have been implicated in the progression of kidney injury. Previous work from our group has shown that meprins proteolytically process the catalytic subunit of protein kinase A (PKA-C), resulting in decreased PKA-C kinase activity. The goal of the present study was to determine the PKA-C isoforms impacted by meprin-β and whether meprin-β expression affects downstream mediators of the PKA signaling pathway in ischemia-reperfusion (IR)-induced kidney injury. IR was induced in 12-wk-old male wild-type (WT) and meprin-β knockout (βKO) mice. Madin-Darby canine kidney cells transfected with meprin-β cDNA were also subjected to 2 h of hypoxia. Western blot analysis was used to evaluate levels of total PKA-C, PKA-Cα, PKA-Cβ, phosphorylated (p-)PKA-C, and p-ERK1/2. Meprin-β expression enhanced kidney injury as indicated by levels of neutrophil gelatinase-associated lipocalin and cystatin C. IR-associated decreases were observed in levels of p-PKA-C in kidney tissue from WT mice but not βKO mice, suggesting that meprin-β expression/activity is responsible for the in vivo reduction in kinase activity. Significant increases in levels of PKA-Cβ were observed in kidney lysates for WT mice but not βKO mice at 6 h post-IR. Proximal tubule PKA-Cβ increases in WT but not βKO kidneys were demonstrated by fluorescent microscopy. Furthermore, IR-induced injury was associated with significant increases in p-ERK levels for both genotypes. The present data demonstrate that meprin-β enhances IR-induced kidney injury in part by modulating mediators of the PKA-Cβ signaling pathway.
Synthesis of C-N-S-Tridoped TiO2 from Vietnam Ilmenite Ore and Its Visible Light-Driven-Photocatalytic Activity for Tetracyline Degradation
Authors: Lan Nguyen Thi , Anh Vo Hoang , An Hoang Duc , Hung Nguyen Phi , Nhiem Dao Ngoc , Van Thang Bui , Lieu Pham Khac , Khieu Dinh Quang
Published: March 2020

In this study, C-N-S-tridoped TiO2 composite was fabricated from TiO2 prepared from ilmenite ore and thiourea by means of hydrothermal method. The obtained material was characterized by X-ray diffraction, Raman scattering spectroscopy, UV-Vis diffuse reflectance spectroscopy, nitrogen adsorption-desorption isotherms, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). It was found that C-N-S-tridoped TiO2 material has a large specific surface area, showing good photocatalytic activity on the degradation of antibiotic tetracycline in visible light region. The study on the mechanism of tetracycline photodegradation using the liquid chromatography with mass spectrometry was performed. It was found that tetracycline has been degraded over C-N-S-tridoped TiO2 catalyst into many different intermediates which can eventually be converted into CO2 and H2O. The kinetics of photocatalytic decomposition of tetracycline were investigated. In addition, the obtained material could catalyze well the degradation of other antibiotics (ciprofloxacin and chloramphenicol) and dyes (rhodamine-B, methylene blue, and organe red). The catalyst was stable after five recycles with slight loss of catalytic activity, which indicates great potential for practical application of C-N-S-tridoped TiO2 catalyst in treatment of wastewater containing tetracycline in particular or antibiotics in general.
Molecular Aspects of Colorectal Adenomas: The Interplay among Microenvironment, Oxidative Stress, and Predisposition
Authors: Aceto Gitana Maria , Catalano Teresa , Curia Maria Cristina
Published: March 2020

The development of colorectal cancer (CRC) is a multistep process initiated by a benign polyp that has the potential to evolve into in situ carcinoma through the interactions between environmental and genetic factors. CRC incidence rates are constantly increased for young adult patients presenting an advanced tumor stage. The majority of CRCs arise from colonic adenomas originating from aberrant cell proliferation of colon epithelium. Endoscopic polypectomy represents a tool for early detection and removal of polyps, although the occurrence of cancers after negative colonoscopy shows a significant incidence. It has long been recognized that the aberrant regulation of Wingless/It (Wnt)/β‐Catenin signaling in the pathogenesis of colorectal cancer is supported by its critical role in the differentiation of stem cells in intestinal crypts and in the maintenance of intestinal homeostasis. For this review, we will focus on the development of adenomatous polyps through the interplay between renewal signaling in the colon epithelium and reactive oxygen species (ROS) production. The current knowledge of molecular pathology allows us to deepen the relationships between oxidative stress and other risk factors as lifestyle, microbiota, and predisposition. We underline that the chronic inflammation and ROS production in the colon epithelium can impair the Wnt/β‐catenin and/or base excision repair (BER) pathways and predispose to polyp development. In fact, the coexistence of oxidative DNA damage and errors in DNA polymerase can foster C>T transitions in various types of cancer and adenomas, leading to a hypermutated phenotype of tumor cells. Moreover, the function of Adenomatous Polyposis Coli (APC) protein in regulating DNA repair is very important as therapeutic implication making DNA damaging chemotherapeutic agents more effective in CRC cells that tend to accumulate mutations. Additional studies will determine whether approaches based on Wnt inhibition would provide long‐term therapeutic value in CRC, but it is clear that APC disruption plays a central role in driving and maintaining tumorigenesis.
Characterization and Functional Analysis of Polyadenylation Sites in Fast and Slow Muscles
Authors: Deng Lulu , Li Long , Zou Cheng , Fang Chengchi , Li Changchun
Published: March 2020

Many increasing documents have proved that alternative polyadenylation (APA) events with different polyadenylation sites (PAS) contribute to posttranscriptional regulation. However, little is known about the detailed molecular features of PASs and its role in porcine fast and slow skeletal muscles through microRNAs (miRNAs) and RNA binding proteins (RBPs). In this study, we combined single‐molecule real‐time sequencing and Illumina RNA‐seq datasets to comprehensively analyze polyadenylation in pigs. We identified a total of 10,334 PASs, of which 8734 were characterized by reference genome annotation. 32.86% of PAS‐associated genes were determined to have more than one PAS. Further analysis demonstrated that tissue‐specific PASs between fast and slow muscles were enriched in skeletal muscle development pathways. In addition, we obtained 1407 target genes regulated by APA events through potential binding 69 miRNAs and 28 RBPs in variable 3′ UTR regions and some are involved in myofiber transformation. Furthermore, the de novo motif search confirmed that the most common usage of canonical motif AAUAAA and three types of PASs may be related to the strength of motifs. In summary, our results provide a useful annotation of PASs for pig transcriptome and suggest that APA may serve as a role in fast and slow muscle development under the regulation of miRNAs and RBPs.
Antistaphylococcal Activity of Extracts, Fractions, and Compounds of Acacia polyacantha Wild (Fabaceae)
Authors: Ashu Fred A. , Na-Iya Jean , Wamba Brice E. N. , Kamga Justin , Nayim Paul , Ngameni Bathélémy , Beng Veronique P. , Ngadjui Bonaventure T. , Kuete Victor
Published: March 2020

Acacia polyacantha is a medicinal plant traditionally used to treat livestock diseases and gastrointestinal infections; our study was undertaken to evaluate the antistaphylococcal activities of the methanolic leaf, bark, and root extracts, fractions, and compounds from Acacia polyacantha against a panel of 14 multidrug‐resistant Staphylococcus bacterial strains overexpressing efflux pumps. The study was also extended to investigate two possible modes of action, that is, influence on bacterial growth kinetics and influence on proton‐ATPase pumps, of the most active compound against a reference strain. Materials and Methods. The crude extracts after extraction were subjected to column chromatography. Antibacterial assays of extracts, fractions, and compounds alone and in the presence of efflux pump inhibitors were carried out using the broth microdilution method and the study of two mechanisms of action achieved by standard methods with the most active compound. Results. The phytochemical study of Acacia polyacantha leaves leads to the isolation of stigmasterol (1), β‐amyrin (2), 3‐O‐methyl‐D‐chiro‐inositol (3), epicatechin (4), quercetin‐3‐O‐galactoside (5), 3‐O‐[β‐D‐xylopyranosyl‐(1 ⟶ 4)‐β‐D‐galactopyranosyl]‐oleanolic acid (6), 3‐O‐[β‐galactopyranosyl‐(1⟶ 4)‐β‐D‐galactopyranosyl]‐oleanolic acid (7) and that of leaves lead to the isolation of lupeol (8) 2,3‐dihydroxypropyltetracosanoate (9), and methyl‐gallate (10). Leaf, root, and bark extracts inhibited 92.85% (13/14), 92.85% (13/14), and 71.43 % (10/14) of the tested bacteria strains, respectively, with minimum inhibitory concentration (MIC) varying between 16 and 1024 μg/mL. Fractions exhibited better activities compared to those of their extracts of origin, as their MICs ranged from 16 to 512 μg/mL, with fractions from leaves being more active than those obtained from barks. Compounds had varying activities; MICs varied from 16 to 512 μg/mL with compound 4 presenting the best activity as MICs ≤100 μg/mL were obtained against 11 of the tested bacteria. The activities of extracts, fractions, and compounds were improved in the presence of carbonyl cyanide m‐chlorophenylhydrazone (CCCP) as an efflux pump inhibitor to as much as >128 folds. Meanwhile, in the presence of chlorpromazine as an efflux pump inhibitor, only the activity of compound 10 was improved on 10 of the tested bacteria strains. Compound 4 prolonged the lag phase of the growth kinetic in a concentration‐dependent manner and equally inhibited the proton‐ATPase pumps of the tested bacteria strains. Conclusion. The present study demonstrates the antistaphylococcal potential of Acacia polyacantha and its constituents to combat bacterial infections alone or in combination with efflux pump inhibitors.
An Approach to Improve SSD through Skip Connection of Multiscale Feature Maps
Authors: Zhang Xiaoguo , Gao Ye , Ye Fei , Liu Qihan , Zhang Kaixin
Published: March 2020

SSD (Single Shot MultiBox Detector) is one of the best object detection algorithms and is able to provide high accurate object detection performance in real time. However, SSD shows relatively poor performance on small object detection because its shallow prediction layer, which is responsible for detecting small objects, lacks enough semantic information. To overcome this problem, SKIPSSD, an improved SSD with a novel skip connection of multiscale feature maps, is proposed in this paper to enhance the semantic information and the details of the prediction layers through skippingly fusing high-level and low-level feature maps. For the detail of the fusion methods, we design two feature fusion modules and multiple fusion strategies to improve the SSD detector’s sensitivity and perception ability. Experimental results on the PASCAL VOC2007 test set demonstrate that SKIPSSD significantly improves the detection performance and outperforms lots of state-of-the-art object detectors. With an input size of 300 × 300, SKIPSSD achieves 79.0% mAP (mean average precision) at 38.7 FPS (frame per second) on a single 1080 GPU, 1.8% higher than the mAP of SSD while still keeping the real-time detection speed.
Mathematical Modeling and Dynamic Analysis of Planetary Gears System with Time-Varying Parameters
Authors: Xiao Zhengming , Cao Jinxin , Yu Yinxin
Published: March 2020

Planetary gears are widely used in automobiles, helicopters, heavy machinery, etc., due to the high speed reductions in compact spaces; however, the gear fault and early damage induced by the vibration of planetary gears remains a key concern. The time-varying parameters have a vital influence on dynamic performance and reliability of the gearbox. An analytical model is proposed to investigate the effect of gear tooth crack on the gear mesh stiffness, and then the dynamical model of the planetary gears with time-varying parameters is established. The natural characteristics of the transmission system are calculated, and the dynamic responses of transmission components, as well as dynamic meshing force of each pair of gear are investigated based on varying internal excitations induced by time-varying parameters and tooth root crack. The effects of gear tooth root crack size on the planetary gear dynamics are simulated, and the mapping rules between damage degree and gear dynamics are revealed. In order to verify the theoretical model and simulation results, the planetary gear test rig was built by assembling faulty and healthy gear separately. The failure mechanism and dynamic characteristics of the planetary gears with tooth root crack are clarified by comparing the analytical results and experimental data.
Partially Smoothing and Gradient-Based Algorithm for Optimizing the VMI System with Competitive Retailers under Random Demands
Authors: Deng Hua , Li Yinxue , Wan Zhaoman , Wan Zhong
Published: March 2020

Vendor managed inventory (VMI) is an improved sustainable inventory management system, but it is difficult to establish and solve an integrated Stackelberg game model under the complicated practical environment. In this paper, a bilevel programming model is proposed to formulate the VMI system by taking into account the uncertainty of demand, the competition among retailers, the cooperative advertising, the shortage and holding costs, and the practical constraints. For the established stochastic model being associated with continuously random demands, a deterministic mathematical program with complementarity constraints (MPCC) is first derived by expectation method and the first-order optimality conditions of the lower-level problem. Then, with a partially smoothing technique, the MPCC is solved by transforming it into a series of standard smooth optimization subproblems. Finally, owing to complexity caused by evaluating the integrals with unknown decision variables in the objective function, an efficient algorithm is developed to solve the problem based on the gradient information of model. Sensitivity analysis has been employed to reveal a number of managerial implications from the constructed model and algorithm. (1) The participation rate depends on advertising expenditures from both the manufacturer and the retailer. There exists an optimal threshold of participation rate for the manufacturer, which can be provided by the intersection point of the manufacturer and retailer’s cost-profit curves. (2) The manufacturer’s advertising policy is less sensitive to uncertainty of demand than the change of the retailer’s advertising policy. (3) The manufacturer in the VMI system should concern about the differences caused by symmetric or asymmetric retailers.
Hypercalcemia-Induced ST-Segment Elevation Mimicking Acute Myocardial Injury: A Case Report and Review of the Literature
Authors: Abugroun Ashraf , Tyle Aneesh , Faizan Farah , Accavitti Michael , Ahmed Chaudhary , Wang Theodore
Published: March 2020

ST-segment elevation in absence of acute coronary syndrome can be seen in multiple conditions, including acute pericarditis and coronary vasospasm, but it is rarely seen with severe hypercalcemia. The authors present a case of an 81-year-old female with a history of stage 4 squamous cell cancer of the lung, who presented to the emergency room with profound fatigue, weakness, anorexia, and drowsiness two weeks after her first chemotherapy cycle. Additionally, she had complaints of right-sided chest pain associated with worsening shortness of breath, as well as right arm numbness. An EKG obtained on arrival to the hospital showed diffuse ST-segment elevation (leads V3–V6, I, II, III, and aVF). Basic lab work found a calcium level of 20.4 mg/dl with elevated parathyroid hormone-related protein (PTHrP) of 135 pg/ml. Troponin I remained within normal limits. Serial EKS obtained during the patient’s hospitalization demonstrated resolution of the ST elevation as calcium level normalized. This case emphasizes the importance of hypercalcemia as a differential diagnosis for ST-segment elevation and QT shortening when acute coronary syndrome is not present. Awareness of these EKG changes is critical for early diagnosis, recognition, and appropriate treatment.
Waist-to-Height Ratio (WHtR) in Predicting Coronary Artery Disease Compared to Body Mass Index and Waist Circumference in a Single Center from Saudi Arabia
Authors: Alshamiri Mostafa Q. , Mohd A Habbab Faisal , AL-Qahtani Saad Saeed , Alghalayini Khalil Abdullah , Al-Qattan Omar Mohammed , El-shaer Fayez
Published: March 2020

This study aims to study the efficiency of the Waist-to-Height Ratio (WHtR) for determining coronary artery disease. It compares the frequency of abnormal WHtR, as a proxy for abdominal obesity, to that of body mass index (BMI) and waist circumference (WC). It also relates the findings to other cardiometabolic risk factors in University Hospital patients. A cross-sectional study design was used, where a sample of 200 patients (142 males and 58 females) who attended the adult cardiac clinic were purposively included. BMI, WC, and WHtR were measured, where frequencies of WHtR were compared to those of BMI and WC. The findings were related to the history of coronary artery disease (CAD) and history of cardiometabolic risk factors, including diabetes mellitus (DM), hypertension (HTN), and hyperlipidemia. Majority of the male patients were older, taller, and had a lower BMI value. It also showed that the prevalence of dyslipidemia and CAD was higher in male patients. No significant difference between both genders was noticed for weight, WC, WHtR, hypertension, or DM. BMI was least associated with high-risk cardiac population in both males and females (39.4% and 60.3%), followed by WC (84.5% and 96.6%, respectively). WHtR showed the highest association with gender (male 98.6% and females 98.3%). These findings were noticed in patients with all risk factors. WHtR is superior to BMI and WC for determining the elevated risk of diabetes, hypertension, dyslipidemia, and CAD in a single university institute. The role of WHtR in both normal and diseased Saudi population should be delineated.
Application of Causal Inference Analysis Economic Growth on Labor Production from Foreign Direct Investment
Authors: Ko Po Sheng , Lu Kuo Chih , Wu Cheng Chung , Yuan Tiantong
Published: March 2020

In recent four decades, policy reform has integrated China’s economy into global. Since 1981, foreign direct investment (FDI) has been gradually flowing into the Yangtze River Delta region. As a result, this region has enjoyed strong economic strength based on abundant human resources and convenient transportation network. Shanghai, the key city, has become one of the major cites attracting FDI; meanwhile, FDI also has had a tremendous impact on Shanghai’s economic development, including employment. To sum up, Shanghai has been chosen as the research object in this paper. This research is organized by four parts: firstly, a theoretical analysis of employment effects of FDI is presented; secondly, after combining the actual utilization of FDI and employment in Shanghai, an empirical analysis of the effects of FDI on employment quantity and employment quality is carried out by data and regression models; thirdly, this research found FDI has exerted a negative influence on employment quantity in Shanghai; moreover, FDI also has shown a positive impact on the employment quality; and finally, the paper has proposed some suggestions to FDI’s utility in the future.
The Forgotten Disease: A Case of Lemierre’s Syndrome with Distal Extremity Involvement
Authors: Gaskill John , Aronson Michael
Published: March 2020

Once coined the “Forgotten Disease,” Lemierre’s syndrome is a rare condition that results from oropharyngeal infection with the gram-negative, anaerobic Fusobacterium necrophorum. The typical progression of illness involves spread to adjacent structures such as the internal jugular vein with resulting thrombophlebitis. Septic emboli to distant sites are also a common sequela. Here, we present a case of Lemierre’s syndrome in a 20-year-old, otherwise healthy, male. The patient presented with fever, sore throat, and dysphagia. Imaging revealed peritonsillar multiloculated fluid collections and necrotizing pneumonia with multiple pulmonary abscesses. The patient’s hospital course was complicated by the development of necrotizing fasciitis in his right lower leg, which required incision and drainage with surgical washout. In addition to systemic intravenous antibiotics and anticoagulation, he underwent multiple thoracentesis procedures. The patient was ultimately transferred to a tertiary care center due to persistent fevers and lung abscesses. This case highlights the challenges of initial diagnosis, as well as the treatment choices faced by the attending physicians.
Identification and Resolution of Drug-Related Problems among Childhood Cancer Patients in Ethiopia
Authors: Yismaw Malede Berihun , Adam Haileyesus , Engidawork Ephrem
Published: March 2020

Background. Even though medications play a major role in the cure, palliation, and inhibition of disease, they also expose patients to drug-related problems. Drug-related problems are frequent and may result in reduced quality of life, morbidity, and mortality. Objectives. The study was aimed to identify, characterize, and resolve drug-related problems in the Pediatric Hematology/Oncology ward of Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. Methods. A prospective observational study was conducted from 25 June to 25 October 2018 to assess DRPs on patients admitted at the pediatric hematology/oncology ward of Tikur Anbessa Specialized Hospital, which is the highest level governmental tertiary care hospital in Ethiopia. Data were obtained from patients’ medical charts, physicians, patients/caregivers, pharmacists, and nurses. All the collected data were entered and analyzed using the Statistical Package for the Social Sciences version 25e. Descriptive statistics were used to represent the data. Results. Among the total 156 participants, DRPs were identified in 68.6% of the study subjects. Dosing problems which include dosage too low and high were the top ranking (39.3%) of all DRPs followed by needs additional therapy (27.2%) and nonadherence (14.0%). Systemic anti-infectives were the most common class of drugs involved in DRPs. Trimethoprim-sulfamethoxazole, methotrexate, vincristine, ondansetron, and metoclopramide were frequently involved in DRPs. The addition of drugs and change in drug dose were the two most proposed intervention types. Among the proposed interventions, 223 (92.15%) were fully accepted, 9 (3.72%) partially accepted, and 10 (4.13%) not accepted. Conclusion. DRPs are common among Pediatric Hematology/Oncology ward patients. The hospital should develop a pediatric dosing chart for the commonly prescribed medications to prevent drug-related morbidity and mortality. The integration of clinical pharmacists can mitigate risks associated with DRPs.
Alleviating the Hydrolysis of Carbohydrates, Tangzhiqing (TZQ) Decreased the Postprandial Glycemia in Healthy Volunteers: An Eight‐Period Crossover Study
Authors: Li Yanfen , Li Ziqiang , Wang Ruihua , Mi Bo , Jiang Ting , Lu Meijuan , Liu Jia , Wang Baohe , Zhang Deqin , Xu Qiang , Huang Yuhong
Published: March 2020

Tangzhiqing (TZQ), a Chinese herbal medicine, has been widely used to treat diabetes mellitus in China. TZQ works as a potential α‐glucosidase inhibitor to reduce the absorption of glucose from dietary carbohydrates. The main aim of this study was to investigate the postprandial glucose‐lowering effect of TZQ on the common carbohydrates in healthy humans. Meanwhile, the possible types of the inhibited α‐glucosidase enzymes were predicted in this study. Glucose, sucrose, maltose, maltodextrin, and starch were chosen as investigated carbohydrates. The baseline incremental area under the curve (IAUC) and glycemic index (GI) values of the investigated carbohydrates were evaluated. Then, thirty‐six subjects were randomly assigned to three groups to assess postprandial hypoglycemic effects of 3‐, 6‐, and 9‐tablet TZQ. The subjects in each group were randomized to eight subgroups. An eight‐period, eight‐sequence, crossover design was performed to investigate the postprandial glucose‐lowering effect of TZQ after drinking each carbohydrate. A significant decrease was observed on the postprandial glucose IAUCs (279.41 ± 111.31 vs. 203.86 ± 61.08) and GIs (124.91 ± 48.54 vs. 91.69 ± 27.47) of maltose after oral administration of 6‐tablet TZQ, as well as IAUCs (145.05 ± 55.01 vs. 110.23 ± 57.03) and GIs (84.87 ± 33.40 vs. 65.50 ± 33.89) of sucrose after administration of 3‐tablet TZQ. The glucose IAUCs (109.15 ± 55.92 vs. 57.68 ± 46.09) and GIs (49.09 ± 25.15 vs. 25.94 ± 20.73) of starch statistically reduced following the administration of 6‐tablet TZQ. The lowering postprandial blood glucose effect of TZQ did not increase proportionally with increasing doses in humans. There were no significant changes in the glucose‐lowering effect of glucose and maltodextrin after the administration of 3‐, 6‐, or 9‐tablet TZQ, respectively. TZQ is a potential treatment for postprandial hyperglycemia, which can probably make α‐glucosidases inhibit maltase, sucrase, and α‐amylase in the digestive organs.
Antiangiogenesis Roles of Exosomes with Fei‐Liu‐Ping Ointment Treatment are Involved in the Lung Carcinoma with the Lewis Xenograft Mouse Model
Authors: Zheng Qi , Liu Haolong , Fan Huiting , Zhang Ying , Hou Wei
Published: March 2020

Exosomes display efficient biocompatibility and represent valuable vehicles for drug or effective material delivery in a tumour‐therapeutic approach. Following treatment with Fei‐Liu‐Ping (FLP) ointment, a traditional Chinese herbal formula, which is used for treating lung cancer patients, could inhibit lung carcinoma growth in clinical and animal studies. In the present study, the values of VEGF and PDGF, which were closely related to angiogenesis, were estimated in serum and carcinoma tissue exosomes to unveil the FLP effects on angiogenesis. The common inflammatory factors of IL‐6, IL‐1β, TNF‐α, and TGF‐β in serum exosomes were also detected with the Lewis xenograft model. Methods. Male C57BL/6 mice were randomly divided into four groups, namely, normal, model, cyclophosphamide (CTX), and FLP treatment groups. Histological structures were observed and imaged by H&E. CD31 expressions in tumour tissues were detected by immunofluorescence (IF) and western blot (WB). VEGF, PDGF, and PDGFR levels in exosomes, serum, tumour, and lung tissues were detected by enzyme‐linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and WB, respectively. IL‐6, IL‐1β, TNF‐α, and TGF‐β levels in exosomes were measured by multiplex immunoassay panels. Results. The results showed that FLP had tumour growth inhibition rate (39.31%). CD31 protein expression was obviously decreased in tumour tissues of CTX‐ and FLP‐treated MO mice, compared to that of MO mice (P < 0.05 or P < 0.001). VEGF, PDGF, and PDGFR expression levels with FLP treatment were downregulated in exosomes, serum, tumour, and lung tissues compared to model group (P < 0.05 or P < 0.01). The expressions of IL‐6, IL‐1β, and TNF‐α were downregulated in exosomes compared to the model group (P < 0.05 or P < 0.01). Conclusions. This study suggested that FLP had the ability of inhibiting tumourigenesis in a Lewis lung xenograft mouse model, whose therapeutic mechanisms might relate with the downregulation of angiogenesis factor and tumour inflammatory cytokines levels.
Isoliquiritigenin Attenuates Anxiety‐Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to Nicotine
Authors: Wang Yuhua , Kim Sang Chan , Wu Tong , Jiao Yu , Jin Haifeng , Hyo Lee Bong , Lee Chul Won , Fan Yu , Kim Hee Young , Yang Chae Ha , Zhao Zhenglin , Zhao Rongjie
Published: March 2020

As important components of positive and negative reinforcement, locomotor sensitization and withdrawal anxiety following repeated exposure to nicotine (NIC) constitute crucial risk factors for relapse to NIC use after abstinence. Glycyrrhiza radix (G. radix), an important tonic used in traditional Oriental medicine, has not only anxiolytic effects but also reduces NIC‐induced locomotor sensitization. Isoliquiritigenin (ISL), a bioactive ingredient of G. radix, also exhibits neuropharmacological effects, including anxiolytic action. Previously, we reported that ISL suppressed cocaine‐induced extracellular dopamine release in the nucleus accumbens shell (NaccSh) and attenuated methamphetamine‐induced neurotoxicity. The present study was performed to evaluate the effects of ISL on both NIC withdrawal anxiety and locomotor sensitization. Adult male rats received subcutaneous administration of NIC hydrogen tartrate (0.4 mg/kg, twice a day) for 7 days followed by 4 days of withdrawal. During the period of NIC withdrawal, the rats received four intragastric treatments with ISL (3, 10, or 30 mg/kg/day). All three doses of ISL significantly inhibited NIC withdrawal‐induced anxiety‐like behaviors in the elevated plus maze (EPM) test, but only the 10 mg/kg/day and 30 mg/kg/day ISL doses attenuated locomotor sensitization induced by a challenge dose of NIC. Intracerebroventricular ISL also inhibited both NIC‐induced withdrawal anxiety and locomotor sensitization, but intra‐NaccSh injection of ISL blocked only NIC locomotor sensitization, which was abolished by post‐ISL infusion of tert‐butyl hydroperoxide (an oxidant) or N‐methyl‐d‐aspartate (NMDA) into the NaccSh. Moreover, there was increased protein expression of phosphorylated Erk1/2 in the NIC‐sensitized NaccSh, which was suppressed by ISL. Taken together, these results suggest that ISL can inhibit repeated NIC‐induced withdrawal anxiety and locomotor sensitization, and the latter is mediated by antagonizing accumbal reactive oxygen species and NMDA receptor signaling.
Product Dictionary Learning-Based SAR Target Configuration Recognition
Authors: Liu Ming , Chen Shichao , Lu Fugang , Liu Junsheng
Published: March 2020

Dictionary construction is a key factor for the sparse representation- (SR-) based algorithms. It has been verified that the learned dictionaries are more effective than the predefined ones. In this paper, we propose a product dictionary learning (PDL) algorithm to achieve synthetic aperture radar (SAR) target configuration recognition. The proposed algorithm obtains the dictionaries from a statistical standpoint to enhance the robustness of the proposed algorithm to noise. And, taking the inevitable multiplicative speckle in SAR images into account, the proposed algorithm employs the product model to describe SAR images. A more accurate description of the SAR image results in higher recognition rates. The accuracy and robustness of the proposed algorithm are validated by the moving and stationary target acquisition and recognition (MSTAR) database.
Early Exposure to Gut Microbiome Reduces Hepatocellular Carcinoma Risks in Mice
Authors: Lee Yang-Ming , Chang Wei-Chun , Lei Fu-Ju , Kor Chew-Teng , Lai Hsueh-Chou , Chen Yao-Li , Ma Wen-Lung
Published: March 2020

Aims. Liver cancer is a multietiological disease that has multiple factors contributing to the hepatocarcinogenic process, e.g., hepatitis viruses, carcinogens, male sex, or metabolic factors. Notably, emerging evidence reported that gut microbiota is crucial to the pathogenesis of hepatocellular carcinoma (HCC) via activation of innate immunity. However, the effect of time to gut microbiota exposure after birth is unknown. Using a germ‐free animal housing environment, instead of antibiotics, we examined the effects of various time‐to‐exposure (TTE) to gut microbiota durations on HCC risk. Methods. HBV or carcinogen‐mediated spontaneous HCC models were implemented in this study. The HCC incidence rates in mice either kept germ‐free (GF; that is, with no exposure to gut microbiota) or exposed to gut microbiota after being moved to a specific pathogen‐free (SPF) housing environment and with various time‐to‐exposure (TTE) durations, namely, 5 weeks after birth, 10 weeks after birth, or since conception (that is, 5‐week TTE group, 10‐week TTE group, and SPF group, respectively), were recorded. The mice were sacrificed at 30 or 40 weeks after birth, and macro‐/microscopic observations and pathological diagnosis were performed. Results. The incidence of liver tumors among the male mice was higher than that among the female mice in the carcinogen‐induced HCC mice sacrificed at 40 weeks after birth (with P = 0.011, 0.035, 0.0003, and 0.012, respectively, in the GF group, 5‐week TTE group, 10‐week TTE group, and SPF group). Similarly, in the HBV‐HCC model, the incidence of liver tumors among the male mice was significantly higher than that among the female mice (with P = 0.013, 0.020, 0.012, and 0.002, respectively, in the GF group, 5‐week TTE group, 10‐week TTE group, and SPF group). These results suggest that gut microbiota exposure is irrelevant to the male sex preference of HCC. Surprisingly, when comparing carcinogen‐induced HCC male mice in the 10‐week TTE group (90%; n = 10), 5‐week TTE group (56%; n = 9), and SPF group (30%; n = 10) (P = 0.020), we found that the incidence of liver tumors was higher in the mice with later exposure to gut microbiome. Similarly, when comparing HBV‐HCC male mice in the 10‐week TTE group (100%; n = 11), 5‐week TTE group (70%; n = 10), and SPF group (33%; n = 9) (P = 0.080), we also found that the incidence of liver tumors was higher in the mice with later exposure to gut microbiome. Conclusions. Early (prepubertal) exposure to gut microbiome reduces the risk of HCC development, indicating a potentially important factor for cancer surveillance. Exploring the mechanisms by which such exposure affects HCC risk might lead to novel cancer vaccines.
Infiltrating Mast Cell–Mediated Stimulation of Estrogen Receptor Activity in Breast Cancer Cells Promotes the Luminal Phenotype
Authors: Majorini Maria Teresa , Cancila Valeria , Rigoni Alice , Botti Laura , Dugo Matteo , Triulzi Tiziana , De Cecco Loris , Fontanella Enrico , Jachetti Elena , Tagliabue Elda , Chiodoni Claudia , Tripodo Claudio , Colombo Mario P. , Lecis Daniele
Published: March 2020

Tumor growth and development is determined by both cancer cell–autonomous and microenvironmental mechanisms, including the contribution of infiltrating immune cells. Because the role of mast cells (MC) in this process is poorly characterized and even controversial, we investigated their part in breast cancer. Crossing C57BL/6 MMTV-PyMT mice, which spontaneously develop mammary carcinomas, with MC-deficient C57BL/6-KitW-sh/W-sh (Wsh) mice, showed that MCs promote tumor growth and prevent the development of basal CK5-positive areas in favor of a luminal gene program. When cocultured with breast cancer cells in vitro, MCs hindered activation of cMET, a master regulator of the basal program, and simultaneously promoted expression and activation of estrogen receptor (ESR1/ER) and its target genes (PGR, KRT8/CK8, BCL2), which are all luminal markers. Moreover, MCs reduced ERBB2/HER2 levels, whose inhibition further increased ESR1 expression. In vivo and in silico analysis of patients with breast cancer revealed a direct correlation between MC density and ESR1 expression. In mice engrafted with HER2-positive breast cancer tumors, coinjection of MCs increased tumor engraftment and outgrowth, supporting the link between MCs and increased risk of relapse in patients with breast cancer. Together, our findings support the notion that MCs influence the phenotype of breast cancer cells by stimulating a luminal phenotype and ultimately modifying the outcome of the disease.

Significance:

Mast cells impact breast cancer outcome by directly affecting the phenotype of tumor cells through stimulation of the estrogen receptor pathway.
Diabetes, Glycated Hemoglobin, and Risk of Cancer in the UK Biobank Study
Authors: Peila Rita , Rohan Thomas E.
Published: March 2020

Background:

Evidence suggest that diabetes and glycated hemoglobin (HbA1c) levels are associated with cancer risk. However, previous studies have been limited variably by failure to adjust for cancer-specific risk factors (e.g., body mass index), inattention to diabetes duration and use of antidiabetic medications, and failure to stratify by obesity.

Methods:

We examined the association between diabetes, HbA1c, and cancer risk in the UK Biobank, using data from 476,517 participants (54% women), followed for an average period of 7.1 years. Diabetes was defined on the basis of baseline self-reported diagnosis of diabetes and/or use of diabetes medication, while HbA1c measured at baseline was categorized as low (<31 mmol/mol), normal (31–<39 mmol/mol), increased risk (39–<48 mmol/mol), and high risk for diabetes (≥48 mmol/mol). Multivariable Cox proportional hazards models were used to estimate the association of diabetes and cancer at different anatomical sites, with adjustment for cancer-specific risk factors.

Results:

Diabetes was associated with increased risk of cancers of the stomach, liver, bladder, endometrium, and lung among smokers, and with decreased risk of prostate cancer. Compared with the normal HbA1c category, the increased risk category was positively associated with risk of cancers of the colon, liver, bladder, and lung among smokers, and the high-risk category was associated with increased risk of cancers of the esophagus, liver, pancreas, and bladder, and with decreased risk of prostate cancer.

Conclusions:

These results suggest that both diabetes and/or elevated HbA1c are associated with risk of cancer at several anatomic sites.

Impact:

The associations of diabetes and HbA1c levels with cancer suggest their importance in cancer prevention.
A New DARS2 Mutation Discovered in an Adult Patient
Authors: N’Gbo N’Gbo Ikazabo Rosy , Mostosi Christian , Jissendi Patrice , Labaisse Marie-Anne , Vandernoot Isabelle
Published: March 2020

We report a case of an adult patient suffering from leukoencephalopathy with brainstem and spinal cord involvement and elevated white matter lactate (LBSL) caused by a DARS2 polymorphism. DARS2 mutation was identified by combining MRI and genetic analysis. Our patient was affected by compound heterozygosity for a pathogenic mutation and a common variant, but with reduced aspartyl-tRNA synthetase activity. Brain and spinal cord magnetic resonance imaging revealed extensive white matter abnormalities; spectroscopy revealed no lactate elevation. A new compound heterozygous DARS2 variant combined with a polymorphism in the other allele in an adult patient with LBSL was identified, resulting in reduced DARS2 activity. This combination is rare and has consequences on how we should consider benign variant polymorphisms in the future.
Ultrasound Guidance to Reduce Vascular and Bleeding Complications of Percutaneous Transfemoral Transcatheter Aortic Valve Replacement: A Propensity Score–Matched Comparison
Authors: Vincent Flavien , Spillemaeker Hugues , Kyheng Maéva , Belin‐Vincent Cassandre , Delhaye Cédric , Piérache Adeline , Denimal Tom , Verdier Basile , Debry Nicolas , Moussa Mouhamed , Schurtz Guillaume , Porouchani Sina , Cosenza Alessandro , Juthier Francis , Pamart Thibault , Richardson Marjorie , Coisne Augustin , Hertault Adrien , Sobocinski Jonathan , Modine Thomas , Pontana François , Duhamel Alain , Labreuche Julien , Van Belle Eric
Published: March 2020

Background

Ultrasound (
US
) guidance provides the unique opportunity to control the puncture zone of the artery during transfemoral transcatheter aortic valve replacement and may decrease major vascular complications (
VC
) and life‐threatening or major bleeding complications. This study aimed to evaluate the clinical impact of
US
guidance using a propensity score–matched comparison.

Methods and Results

US
guidance was implemented as the default approach for all transfemoral transcatheter aortic valve replacement cases in our institution in June 2013. We defined 3 groups of consecutive patients according to the method of puncture (fluoroscopic/
US
guidance) and the use of a transcatheter heart valve. Patients in the
US
‐guided second‐generation group (Sapien
XT
[Edwards Lifesciences, Irvine, CA], Corevalve [Medtronic, Dublin, Ireland]) were successfully 1:1 matched with patients in the fluoroscope‐guided second‐generation group (n=95) with propensity score matching. In a second analysis we described the consecutive patients of the
US
‐guided third‐generation group (Evolut‐R [Medtronic], Sapien 3 [Edwards Lifesciences], n=308). All vascular and bleeding complications were reduced in the
US
‐guided second‐generation group compared with the fluoroscope‐guided second‐generation group:
VC
(16.8% versus 6.3%;
P
=0.023); life‐threatening or major bleeding (22.1% versus 6%;
P
=0.004); and
VC
related to vascular access (12.6% versus 4.2%;
P
=0.052). In the
US
‐guided third‐generation group the rates of major
VC
and life‐threatening or major bleeding were 3.2% (95%
CI
, 1.6% to 5.9%) and 3.6% (95%
CI
, 1.8% to 6.3%). In the overall population (n=546), life‐threatening or major bleeding was associated with a 1.7‐fold increased mortality risk (
P
=0.02).

Conclusions

We demonstrated that
US
guidance effectively reduced
VC
and bleeding complications for transfemoral transcatheter aortic valve replacement and should be considered the standard puncture method.

Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02628509.
Understanding Households' Choice of Cooking Fuels: Evidence from Urban Households in Pakistan
Authors: Rahut Dil Bahadur , Ali Akhter , Mottaleb Khondoker Abdul , Aryal Jeetendra Prakash
Published: March 2020

Households in developing countries predominantly rely on solid fuel for cooking, which is injurious to both the environment and human health. The provision of clean energy for cooking, therefore, is essential for safeguarding the environment and human health, primarily of women and children in developing countries. Using the 2014–2015 Pakistan Social and Living Standards Measurement Survey and robust econometric methods, this study analyzes different types of energy used for cooking among urban households in Pakistan. The study shows that although urban households in Pakistan mostly use gas for cooking, the use of solid fuels, particularly among poor and relatively less educated households, is pervasive. The econometric findings confirm that households with a higher level of education and wealthy families mainly use clean energy, such as gas, and are less likely to use dirty solid fuels, such as cake dung and crop residue for cooking. Considering the expansion of middle-class households and anticipating their demand for clean fuel for cooking, this study suggests ensuring an adequate supply of clean sources of energy to meet future demand as well as augmenting the affordability and awareness among households who are still dependent on solid fuels.