bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aspartame effect in sickle cell anemia
Authors: Manion Carl V. , Howard Jessica , Ogle Brandi , Parkhurst Joan , Edmundson Allen 
Published: July 2002

ObjectiveTo examine the in vitro and in vivo attributes of aspartame and to determine its efficacy for treating sickle cell anemia.RationaleAspartame (L‐aspartyl‐L‐phenylalanine methyl ester) binds with 2 human Bence Jones proteins. The proteins (Mcg and Sea) showed phenylalanine penetrating into hydrophobic binding sites. This aspartame property suggested a potential to interfere with sickle hemoglobin fibril formation.MethodsFor the in vitro studies, blood from 20 subjects monitored for sickle cell anemia was collected in heparinized tubes. Specimens were divided in thirds and aspartame was added to 2 tubes to yield a 1 mg/mL or 2 mg/mL concentration. Sickled cells that were present after a drop from each aliquot was added to a fresh 2% metabisulfite solution were counted 3 times. For the in vivo studies, 23 subjects from the Sickle Cell Clinic (University of Oklahoma Health Sciences Center, Oklahoma City, Okla) consented to participate in a randomized single‐dose administration of 1.5, 3.0, or 6 mg/kg aspartame. Heparinized blood was obtained at 0, 30, 60, 120, 240, 480, and 1440 minutes after aspartame administration. Specimens were counted in a blinded manner by means of the technique used for the in vitro method, but a photomicrograph of 1 field from each triplicate count was made. The pictures were marked and were computer counted.ResultsFor the in vitro studies, sickled cells decreased from 28% to <14% when 1 mg/mL aspartame was added and decreased further with 2 mg/mL. For the in vivo studies, a decreased number of sickled cells in homozygous blood (HbSS) were observed after oral administration of aspartame. Sickling was inhibited by 6 mg/kg aspartame for at least 6 hours in 15 subjects with HbSS anemia.ConclusionsFurther evaluations of the efficacy of aspartame for sickle crisis and crisis prevention appears to be warranted.Clinical Pharmacology & Therapeutics (2001) 69, 346–355; doi: 10.1067/mcp.2001.115141
Removal of digoxin by column for specific adsorption of β2‐microglobulin: A potential use for digoxin intoxication
Authors: Tsuruoka Shuichi , Osono Eiichi , Nishiki Kenta , Kawaguchi Atsuhiro , Arai Tatsuhiko , Furuyoshi Sigeo , Saito Tetsuo , Takata Satoru , Sugimoto Koichi , Kurihara Satoshi , Fujimura Akio 
Published: July 2002

BackgroundA β2‐microglobulin adsorption column used for the treatment of dialysis‐related amyloidosis removes serum β2‐microglobulin by recognition of lipophilic residue in the protein. No data are available for the adsorption of the highly lipophilic drug digoxin.MethodsIn vivo clearance of digoxin with the β2‐microglobulin column was measured by a single use of the column in 8 patients receiving hemodialysis with a therapeutic level of digoxin. In vitro adsorption was evaluated by use of incubation with adsorbent of the column and digoxin or ranitidine, a hydrophilic drug. Clearance with the β2‐microglobulin column was further compared with that obtained by use of activated charcoal in the dogs intoxicated with digoxin.ResultsDigoxin concentration was reduced from 1.11 ± 0.25 ng/mL to 0.57 ± 0.15 ng/mL at 240 minutes after initiation of hemoperfusion with the column in the patients. Digoxin clearance with the β2‐microglobulin column was about 145 ± 20 mL/min, with a blood flow rate of 160 to 220 mL/min (80% of plasma flow rate). Eighty‐five percent of digoxin was adsorbed in vitro, and the capacity of the β2‐microglobulin column was not saturated until a toxic level was reached (50 ng/mL). This value was higher than that obtained with use of charcoal. In dogs with digoxin intoxication, digoxin clearance was 38.9 ± 1.5 mL/min, with a blood flow rate of 50 mL/min (95% of plasma flow rate), which was almost twice as that achieved with charcoal. The degree of thrombocytopenia and leukopenia was small with use of the β2‐microglobulin column.ConclusionThese data suggested that the β2‐microglobulin column selectively adsorbs digoxin. This column is a promising tool for the treatment of digoxin intoxication, especially in patients undergoing hemodialysis.Clinical Pharmacology & Therapeutics (2001) 69, 422–430; doi: 10.1067/mcp.2001.116061
Designing Copper‐Based Catalysts for Efficient Carbon Dioxide Electroreduction
Authors: Wang Yuhang , Liu Junlang , Zheng Gengfeng 
Published: April 2021

AbstractThe electroreduction of carbon dioxide (CO2) has been emerging as a high‐ potential approach for CO2 utilization using renewables. When copper (Cu) based catalysts are used, this platform can produce multi‐carbon (C2+) fuels and chemicals with almost net‐zero emission, contributing to the closure of the anthropogenic carbon cycle. Nonetheless, the rational design and development of Cu‐based catalysts are critical toward the realization of highly selective and efficient CO2 electroreduction. In this review, first the latest advances in Cu‐catalyzed CO2 electroreduction in the product selectivity and electrocatalytic activity are briefly summarized. Then, recent theoretical and mechanistic studies of CO2 electroreduction on Cu‐based catalysts are investigated, which serve as programs to design catalysts. Strategies for devising Cu catalysts that aim at promoting different key elementary steps for hydrocarbon and C2+ oxygenates production are further summarized. Moreover, challenges in understanding the mechanism, operando investigation of Cu catalysts and reactions, and systems’ influences are also presented. Finally, the future prospects of CO2 electroreduction are discussed.
Preparation and properties of styrene ethylene butylene styrene / polypropylene thermoplastic elastomer powder for selective laser sintering 3D printing
Authors: He Zuhan , Ren Chuanzheng , Zhang Aimin , Bao Jianjun 
Published: April 2021

AbstractAs one of the most important thermoplastic elastomer materials, the application of styrene ethylene butylene styrene (SEBS) in selective laser sintering (SLS) has not been reported. In this study, SEBS and polypropylene (PP) are blended and then pulverized at low temperatures. We find that SEBS with high molecular weight and styrene segment content is difficult to melt and flow under laser irradiation, which is not suitable for SLS 3D printing. SEBS with low molecular weight can be printed, and its tensile properties can reach 2.1Mpa and 134% elongation at break. We test the enhanced absorption effect of two different infrared absorbers and find that graphene (GE) can enhance absorption mainly rely on its special structure to increase the optical path of the laser. The absorption enhancement effect of each enhancer rises first and then decreases. 0.4‰ addition of GE can bring 22.5% enhancement. With the enhancement of GE, we get a product of 2.8 MPa tensile strength and 176% elongation at break.
Exploring the structure–function relationship in a hypothetical membrane protein from a nucleotide sequence
Authors: Osorio Manuel I. , Salinas Dino G. 
Published: April 2021

AbstractAn educational activity is proposed that uses software for proteomic analysis and databases available for free on the Internet to estimate the structure and function of a hypothetical protein from its coding nucleotide sequence. This bioinformatics activity is recommended for integrated introductory courses that address the structure function relationship in proteins.
Gluconeogenesis is reduced from alanine, lactate and pyruvate, but maintained from glycerol, in liver perfusion of rats with early and late sepsis
Authors: de Souza Galia Winny Beatriz , Biazi Giuliana Regina , Frasson‐Uemura Isabele Gonçalves , Miksza Daniele Romani , Zaia Cássia Thaïs Bussamra Vieira , Zaia Dimas Augusto Morozin , de Souza Helenir Medri , Bertolini Gisele Lopes 
Published: April 2021

Sepsis induces several metabolic abnormalities, including hypoglycaemia in the most advanced stage of the disease, a risk factor for complications and death. Although hypoglycaemia can be caused by inhibition of hepatic gluconeogenesis, decreased and increased gluconeogenesis were reported in sepsis. Furthermore, gluconeogenesis from glycerol was not yet evaluated in this disease. The main purpose of this study was to investigate the gluconeogenesis from alanine, lactate, pyruvate and glycerol in rats with early (8 hours) and late (18 hours) sepsis. Parameters related to the characterization of sepsis were also evaluated. Sepsis was induced by cecal ligation and puncture and gluconeogenesis was assessed in liver perfusion. Rats with early and late sepsis showed increased lactataemia, depletion of liver glycogen and peripheral insulin resistance, characterizing the establishment of sepsis. Rats with early and late sepsis showed decreased gluconeogenesis from alanine, lactate and pyruvate. Interestingly, gluconeogenesis from glycerol, a precursor that enters in the pathway at a later step, subsequent to the entry of alanine, lactate and pyruvate, was maintained in rats with early and late sepsis. In conclusion, gluconeogenesis is decreased from alanine, lactate and pyruvate, but maintained from glycerol, in liver perfusion of rats with early and late sepsis.Significance of the studyThe maintenance of gluconeogenesis from glycerol, but not from alanine, lactate and pyruvate, together with the liver glycogen depletion, points the glycerol as an important precursor for the maintenance of glycaemic homeostasis in sepsis. The findings open the possibility of further investigation on the administration of glycerol in the treatment of hypoglycaemia associated with more advanced sepsis.
Localised release of matrix metallopeptidase 8 in fatal cerebral malaria
Authors: Georgiadou Athina , Naidu Praveena , Walsh Sophie , Kamiza Steve , Barrera Valentina , Harding Simon P , Moxon Christopher A , Cunnington Aubrey J 
Published: April 2021

AbstractObjectiveCerebral malaria (CM) is a complication of Plasmodium falciparum malaria, in which progressive brain swelling is associated with sequestration of parasites and impaired barrier function of the cerebral microvascular endothelium. To test the hypothesis that localised release of matrix metallopeptidase 8 (MMP8) within the retina is implicated in microvascular leak in CM, we examined its expression and association with extravascular fibrinogen leak in a case–control study of post‐mortem retinal samples from 13 Malawian children who met the clinical case definition of CM during life. Cases were seven children who were found on post‐mortem examination to have ‘true‐CM’ (parasite sequestration in brain blood vessels), whilst controls were six children who had alternative causes of death (‘faux‐CM’, no parasite sequestration in blood vessels).MethodsWe used immunofluorescence microscopy and independent scoring, by two assessors blinded to the CM status, to assess MMP8 expression, extravascular fibrinogen as an indicator of vascular leak and their co‐localisation in the retinal microvasculature.ResultsIn ‘true‐CM’ subjects, MMP8 staining was invariably associated with sequestered parasites and a median of 88% (IQR = 74–91%) of capillaries showed MMP8 staining, compared with 14% (IQR = 3.8–24%) in ‘faux‐CM’ (P‐value = 0.001). 41% (IQR = 28–49%) of capillaries in ‘true‐CM’ subjects showed co‐localisation of extravascular fibrinogen leak and MMP8 staining, compared with 1.8% of capillaries in ‘faux‐CM’ (IQR = 0–3.9%, P‐value = 0.01). Vascular leak was rare in the absence of MMP8 staining.ConclusionMatrix metallopeptidase 8 was extensively expressed in retinal capillaries of Malawian children with malarial retinopathy and strongly associated with vascular leak. Our findings implicate MMP8 as a cause of the vascular endothelial barrier disruption in CM, which may precipitate fatal brain swelling.
Optimal power allocation‐based novel control jamming scheme for nonorthogonal multiple access enabled decode‐and‐forward relay network
Authors: Narasimha Nayak V. , Gurrala Kiran Kumar 
Published: April 2021

SummaryIn this work, a new control jamming (CJ) scheme has been proposed for a cooperative nonorthogonal multiple access (NOMA) network with optimal power allocation factors by employing decode‐and‐forward (DF) relay. Maximization of secrecy rate at both NOMA users with the aid of CJ under total transmit power constraint is considered as an optimization problem. In this regard, invasive weed optimization (IWO) algorithm‐based approach is proposed to facilitate optimal power allocation for the considered network. In this analysis, performance metric secrecy rate is analyzed with CJ at both NOMA users by varying the location of eavesdropper with respect to the relay and jammer. In addition, the performance of fixed power allocation (FPA) and proposed power allocation (PPA) schemes is investigated with CJ and compared with jamming (J) and without jamming (WJ) conditions. Simulation result analysis specifies that secrecy performance is enhanced remarkably by CJ and PPA outperforms the FPA.
Site‐specific liquefaction fragility analysis: Cloud, stripe, and incremental approaches
Authors: Bullock Zach , Liel Abbie B. , Porter Keith A. , Dashti Shideh 
Published: April 2021

AbstractThis article adapts a handful of procedures from performance‐based earthquake engineering for use in estimating the probability of liquefaction triggering. The resulting approach, defined as liquefaction fragility analysis (LFA), produces site‐specific fragility functions for liquefaction. These fragility functions incorporate site‐specific, system‐level effects not captured by existing, broader methods, but require more detailed knowledge of both the subsurface conditions and the seismic hazard at the site. LFA accounts for system‐level effects such as pore pressure migration, dynamic layer‐to‐layer interaction, and partial saturation to the extent that these phenomena can be captured in the constitutive models used in nonlinear site response analyses. Multiple approaches for selecting ground motions for LFA are discussed and illustrated using a case study of a site in Los Angeles, California. The computational expense of using LFA for probabilistic estimate of future liquefaction seismic performance is also discussed.
Population Pharmacokinetic‐Pharmacodynamic Modeling and Covariate Analyses of Neutropenia and Thrombocytopenia in Patients With Solid Tumors Treated With Lurbinectedin
Authors: Fernández‐Teruel Carlos , Lubomirov Rubin , Fudio Salvador 
Published: April 2021

AbstractLurbinectedin is a selective inhibitor of oncogenic transcription. Reversible myelosuppression is its most relevant toxicity. Pharmacokinetic‐pharmacodynamic analyses were conducted to characterize the time course of absolute neutrophil count and platelet count recovery and to detect and quantify the effect of relevant covariates in patients with advanced solid tumors treated with lurbinectedin. Absolute neutrophil count, platelet count, and lurbinectedin total plasma concentration were assessed in 244 patients treated with lurbinectedin with varied dosing schedules and doses. A reference extended semimechanistic pharmacokinetic‐pharmacodynamic model of myelosuppression was used. Granulocyte colony‐stimulating factor (G‐CSF) administration was modeled as a dichotomous covariate, and platelet transfusions were included as a bolus dose into the last compartment of the model, representing the central circulation. Final models were suitable to describe the time course of absolute neutrophil count and platelet count recovery. A lurbinectedin dose of 3.2 mg/m2 every 3 weeks can be administered without primary prophylaxis with G‐CSF. G‐CSF followed by ≤2 dose reductions of 20%, if needed, gradually reduced grade 4 neutropenia from cycle 3 onward. BSA‐based dosing reduced the incidence of grade ≥ 3 thrombocytopenia. One‐week dose delays because of low absolute neutrophil count occurred in 3.5% of patients, thus supporting every‐3‐week administration. CYP3A inhibitors produced absolute 11.0% and 6.2% increases in grade ≥ 3 neutropenia and thrombocytopenia, respectively. Neutropenia and thrombocytopenia after lurbinectedin administration to cancer patients are noncumulative, reversible, short lasting, and clinically manageable with secondary prophylaxis of G‐CSF or platelet transfusion and, if needed, dose reductions.
Evaluation of the effects of two different indirect bonding methods on strength of the brackets in mandibular model of severe anterior crowding
Authors: Yuzbasioglu Ertugrul Betul , Alkan Özer 
Published: April 2021

AbstractAn indirect bonding method was developed to solve the problems likely to be encountered during proper positioning of the brackets. The aim of this study is to compare two different indirect bonding methods on the bond strength of the brackets. A 160 extracted human lower incisors were assigned into two groups. Transparent silicone material and bioplast material were used in transfer tray preparation in groups 1 and 2, respectively. Transbond XT adhesive system was used to bond brackets to teeth in both groups. A high intensity LED light source was used for 3 s for adhesive polymerization. Brackets were subjected to shear forces with universal test machine under 0.5 mm/min crosshead speed until failure. Adhesive Remnant Index was used to assess the amount of adhesive remnant on enamel surface after shear test under 10× magnification. Two subjects from both groups were evaluated for enamel surface characteristics with scanning electron microscope (SEM). Mean shear bond strengths were found to be 5.13 ± 1.8 MPa and 5.93 ± 2.19 MPa for silicone and bioplast groups, respectively. Bioplast group showed significantly greater shear bond strength than that of the silicone group. Maximum ARI score, assessed under ×10 magnification was 3 in both groups. A score of 3 was significantly more frequent in bioplast group. Differences were seen between the groups in terms of enamel surface characteristics under SEM evaluation. It was determined that bioplast material, which is considered to be the gold standard for the indirect bonding method, has greater shear bond strength than silicone material.
The virulence factor GroEL directs the osteogenic and adipogenic differentiation of human periodontal ligament stem cells through the involvement of JNK/MAPK and NF‐κB signaling
Authors: Zhang Li , Cheng Lei , Cui Yujia , Wu Zuping , Cai Linyi , Yang Liu , Duan Mengmeng , Zhang Demao , Zhou Chenchen , Xie Jing 
Published: April 2021

AbstractBackgroundGroEL, a bacterial metabolite, is an important stimulator of inflammation. The aim of this study is to confirm the effect of the virulence factor GroEL on differentiation potential of periodontal ligament (PDL) stem cells (PDLSCs) and the potential mechanisms.MethodsPDLSCs were obtained from extracted human premolars. GroEL was administered to osteogenic‐ and adipogenic‐induced hPDLSCs. Alkaline phosphatase (ALP) staining, Alizarin Red staining and Oil Red staining were performed. Gene and protein expression were separately measured by qPCR and Western blotting. The expression and localization of activated signaling factors were confirmed by immunofluorescence staining. The inhibitors of myeloid differentiation factor 88 (MyD88, an adaptor protein of TLRs), JNK/MAPK and NF‐κB signaling were used to verify their specific effects.ResultsFirst, we found that GroEL inhibited the osteogenic differentiation and enhanced the adipogenic differentiation of hPDLSCs. Next, we found that GroEL increased the expression of TLR2 and TLR4 and GroEL activated JNK/MAPK and NF‐κB signaling, which can be blocked by inhibition of MyD88. Finally, we found that inhibition of MyD88 restored GroEL‐induced osteogenic and adipogenic differentiation and blocking JNK/MAPK or NF‐κB signaling partly restored GroEL effects.ConclusionIn the current study, we revealed a potential interaction between bacteria and host cells by showing that GroEL directs the osteogenic and adipogenic differentiation of hPDLSCs by the involvement of JNK/MAPK and NF‐κB signaling. This study provides evidence that bacterial products can influence the differentiation of stem cells and reveals potential effect of GroEL on the context of tissue regeneration.
UPLC‐MS/MS‐based plasma lipidomics reveal a distinctive signature in systemic lupus erythematosus patients
Authors: Chen Jiaxi , Liu Chong , Ye Shenyi , Lu Ruyue , Zhu Hongguo , Xu Jiaqin 
Published: April 2021

AbstractGlobal lipidomics is of considerable utility for exploring altered lipid profiles and unique diagnostic biomarkers in diseases. We aim to apply ultra‐performance liquid chromatography‐tandem mass spectrometry to characterize the lipidomics profile in systemic lupus erythematosus (SLE) patients and explore the underlying pathogenic pathways using the lipidomics approach. Plasma samples from 18 SLE patients, 20 rheumatoid arthritis (RA) patients, and 20 healthy controls (HC) were collected. A total of 467 lipids molecular features were annotated from each sample. Orthogonal partial least square‐discriminant analysis, K‐mean clustering analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated disrupted lipid metabolism in SLE patients, especially in phospholipid, glycerol, and sphingolipid metabolism. The area under curve (AUC) of lipid metabolism biomarkers was better than SLE inflammation markers that ordinarily used in the clinic. Proposed model of monoglyceride (MG) (16:0), MG (18:0), phosphatidylethanolamine (PE) (18:3–16:0), PE (16:0–20:4), and phosphatidylcholine (PC) (O‐16:2–18:3) yielded AUC 1.000 (95% CI, 1.000–1.000), specificity 100% and sensitivity 100% in the diagnosis of SLE from HC. A panel of three lipids molecular PC (18:3‐18:1), PE (20:3–18:0), PE (16:0–20:4) permitted to accurately diagnosis of SLE from RA, with AUC 0.921 (95% CI, 0.828–1.000), 70% specificity, and 100% sensitivity. The plasma lipidomics signatures could serve as an efficient and accurate tool for early diagnosis and provide unprecedented insight into the pathogenesis of SLE.
Characterization of kaposiform lymphangiomatosis tissue‐derived cells
Authors: Nozawa Akifumi , Ozeki Michio , Yasue Shiho , Endo Saori , Noguchi Kei , Kanayama Tomohiro , Tomita Hiroyuki , Aoki Yoko , Ohnishi Hidenori 
Published: April 2021

AbstractBackgroundKaposiform lymphangiomatosis (KLA) is a recently characterized systemic lymphatic anomaly. Activation of RAS/MAPK and PI3K/AKT/mTOR pathways may affect KLA pathogenesis, but the cellular basis of KLA is unclear. Abnormal‐spindle endothelial cells that express lymphatic endothelial cell (LEC) markers are characteristic of KLA histopathology. This study evaluated patient‐derived KLA cells to establish their morphological and biological characteristics.ProcedureWe established cell lines from primary KLA tissues of two patients with KLA and examined their morphological and functional characteristics, messenger RNA and protein expression profiles, gene mutations, and responses to inhibitors of the RAS/MAPK and PI3K/AKT/mTOR pathways.ResultsBoth KLA cell lines showed spindle‐shaped morphology, stained positive for podoplanin (PDPN), and exhibited impaired tube‐formation properties. They expressed LEC marker PDPN and mesenchymal stem cell markers (CD90, CD105) in the absence of endothelial cell markers (CD34, CD31, VWF), per real‐time polymerase chain reaction. Both mTOR inhibitor rapamycin and MEK inhibitor trametinib inhibited growth of the two cell lines. A NRAS p.Q61R variant was found in one of two independent KLA tissue samples, but not in the KLA cells (per targeted next‐generation sequencing); and KLA cells with this variant had elevated AKT phosphorylation levels. ERK phosphorylation levels were undetectable in both KLA cell lines.ConclusionsInhibition of the RAS/MAPK and PI3K/AKT/mTOR pathways may represent potential therapeutic targets in KLA. These patient‐derived KLA cell lines will be useful research tools to elucidate KLA etiology, and could pave the way for basic, translational, and preclinical studies of this disease.