bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentiation agents increase the potential AraC therapy of AML by reactivating cell death pathways without enhancing ROS generation
Authors: Wang Xuening , Dawod Alaa , Nachliely Matan , Harrison Jonathan S. , Danilenko Michael , Studzinski George P. 
Published: June 2019

AbstractAcute myeloid leukemia (AML) has a poor prognosis and requires new approaches for treatment. We have reported that a combination of vitamin D‐based cell differentiation agents (doxercalciferol/carnosic acid [D2/CA]) added following the cytotoxic drug arabinocytosine (AraC) increases AML cell death (CD), a model for improved therapy of this disease. Because AraC‐induced CD is known to involve reactive oxygen species (ROS) generation, here we investigated if the modulation of cellular REDOX status plays a role in the enhancement of cell death (ECD) by D2/CA. Using thiol antioxidants, such asN‐acetyl cysteine (NAC), we found a significant inhibition of ECD, yet this occurred in the absence of any detectable change in cellular ROS levels. In contrast, NAC reduced the vitamin D receptor (VDR) abundance and its signaling of ECD. Importantly, VDR knockdown and NAC similarly inhibited ECD without producing an additive effect. Thus, the proposed post‐AraC therapy may be compromised by agents that reduce VDR levels in AML blasts.
First‐in‐Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of an Oral Formulation of DS‐1040, an Inhibitor of the Activated Form of Thrombin‐Activatable Fibrinolysis Inhibitor, in Healthy Subjects
Authors: Zhou Jin , Limsakun Tharin , Yin Ophelia , Warren Vance , Zamora Cynthia , Atiee George , Kochan Jarema , Pav Joseph , Kobayashi Fumiaki , Vashi Vijay , Dishy Victor 
Published: June 2019

AbstractDS‐1040, a low‐molecular‐weight imidazole derivative, inhibits the enzymatic activity of thrombin‐activatable fibrinolysis inhibitor (TAFIa), enhancing endogenous tissue plasminogen activator–triggered fibrinolysis. This first‐in‐human, randomized, placebo‐controlled, phase 1 study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of an oral formulation of DS‐1040. Healthy adults (aged 20‐45 years; N = 56) were randomized 3:1 to receive DS‐1040 orally administered as single ascending doses (50, 100, 200, or 400 mg) or placebo, or DS‐1040 multiple ascending doses (100 mg once daily, 200 mg once daily, or 150 mg twice daily) or placebo for 14 days. Safety, PK, and PD parameters were assessed. All doses of DS‐1040 were well tolerated; no serious/severe adverse events (AEs) or discontinuations due to AEs occurred. DS‐1040 had no effect on coagulation parameters, and no treatment‐related trends in the bleeding time were observed. DS‐1040 exposure (peak concentration and area under the concentration‐time curve) increased in a dose‐proportional manner across the single‐dose range. With multiple doses, steady state was achieved by day 7 with minimal accumulation (mean accumulation ratio 1.15‐1.25), and the PK was time‐independent. After 72 hours, approximately 10% of the DS‐1040 400‐mg single dose was recovered in urine as intact parent drug. The mean terminal half‐life ranged from 17.2 to 24.9 hours, which was similar to previous intravenous administration data. Dose‐dependent inhibition of total TAFIa activity was observed following single and multiple doses of oral DS‐1040. The safety and PK/PD profiles of oral DS‐1040 in healthy subjects support further clinical development.
Using national laboratory data to assess cumulative frequency of linkage after transfer to community‐based HIV clinics in South Africa
Authors: Bassett Ingrid V , Huang Mingshu , Cloete Christie , Candy Sue , Giddy Janet , Frank Simone C , Freedberg Kenneth A , Losina Elena , Walensky Rochelle P , Parker Robert A 
Published: June 2019

AbstractIntroductionChanges to the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) funding have led to closures of non‐governmental HIV clinics with patient transfers to government‐funded clinics. We sought to determine the success of transfers in South Africa using a national data source.MethodsAll adults (≥18 years) on antiretroviral therapy (ART) who visited a single PEPFAR‐funded hospital‐based HIV clinic in Durban, South Africa from March to June 2012 were transferred to community‐based clinics. Previously, we matched patient records from the hospital‐based HIV clinic with National Health Laboratory Services (NHLS) Corporate Data Warehouse (CDW) data to estimate the proportion of patients with a CD4 count or viral load (VL) in the CDW during the year before transfer. As a proxy for retention in care, in this study we evaluated whether patients had a CD4 count or VL at another facility within approximately three years of transfer. Patients referred to a private doctor at transfer were excluded from the analysis. We assessed predictors (age, sex, CD4 count, VL status, ART duration and location of future care) of not having post‐transfer laboratory data using Cox proportional hazards models.ResultsOf the 3893 patients referred to a government facility at transfer, 41% were male and median age was 39 years (IQR 34 to 46). There was a post‐transfer CD4 count or VL from another facility for 23% of these individuals within six months, 44% within one year, 57% within two years and 61% within approximately three years. Male sex (aHR 1.20, 95% CI 1.10 to 1.31) and shorter duration on ART (<3 months, aHR 3.80, 95% CI 2.77 to 5.21; three months to one year, aHR 1.32, 95% CI 1.15 to 1.51, each compared with >1 year) were associated with not having a post‐transfer record.ConclusionsUsing data from the NHLS CDW, 61% of patients had evidence of a post‐transfer laboratory record at another facility within approximately three years after closure of a large South African HIV clinic. Males and those with shorter time on ART prior to transfer were at highest risk for lacking follow‐up laboratory data. As patients transfer care, national data sources can be used to evaluate long‐term patient care trajectories.
Odontocete peduncle tendons for possible control of fluke orientation and flexibility
Authors: Adams Danielle S. , Fish Frank E. 
Published: June 2019

AbstractDorso‐ventral oscillations of cetacean caudal flukes generate lift‐based thrust for swimming. Movements of the flukes are actuated by epaxial and hypaxial muscles through caudal tendons inserting onto vertebrate in the peduncle. To determine if the caudal tendons in the peduncle affect the flexibility of the flukes, we must understand how the tendons from axial muscles insert onto the caudal vertebrate. The purpose of this study was to provide a detailed description of the various tendons within the cetacean peduncle with regard to their role in swimming and flexibility. Dissection of the peduncle and flukes of multiple odontocete species showed that there were two distinct epaxial tendon sets within the peduncle: (1) extensor caudae medialis tendon (ECM) and (2) extensor caudae lateralis tendon (ECL). There is one distinct hypaxial tendon set, the medial tendon of the hypaxialis lumborum (MHL). The ECM and MHL tendons inserted serially onto caudal vertebrae while the ECL inserted exclusively onto the terminal vertebrae posterior to the fluke insertion. It is typical that tendons insert onto bone, however, the connection to the core fibrous layer of the flukes suggests an element of active control of the flexibility of the flukes via the axial muscles. Tension from muscular contraction transmitted through the tendons could affect both spanwise and chordwise flexibility. Changing flexibility could modulate thrust and efficiency over an extended operation range of swimming speeds in cetaceans.
Phylogenetic and immunoinformatic analysis of VP4, VP7, and NSP4 genes of rotavirus strains circulating in children with acute gastroenteritis in Indonesia
Authors: Nirwati Hera , Donato Celeste M. , Ikram Aqsa , Aman Abu T. , Wibawa Tri , Kirkwood Carl D. , Soenarto Yati , Pan Qiuwei , Hakim Mohamad S. 
Published: June 2019

AbstractRotavirus is a major cause of diarrhea in Indonesian children. However, rotavirus vaccines have not been introduced in the national immunization program of Indonesia. Understanding the genetic diversity and conserved antigenic regions of circulating strains are therefore essential to assess the potential efficacy of rotavirus vaccines. We collected fecal samples from hospitalized children less than 5 years of age with acute diarrhea. Rotavirus genotyping was performed by reverse transcriptase polymerase chain reaction, followed by sequencing of the VP4, VP7, and NSP4 genes of representative strains. Phylogenetic analysis was performed to investigate their relationship with globally circulating strains. Conservational analysis, immunoinformatics, and epitope mapping in comparison to vaccine strains were also performed. The sequence analyses showed that differences of multiple amino acid residues existed between the VP4, VP7, and NSP4 antigenic regions of the vaccine strains and the Indonesian isolates. However, many predicted conserved epitopes with higher antigenicity were observed in the vaccine and Indonesian strains, conferring the importance of these epitopes. The identified epitopes showed a higher potential of rotavirus vaccine to be employed in Indonesia. It could also be helpful to inform the design of a peptide vaccine based on the conserved regions and epitopes in the viral proteins.
Creative Collaboration in Young Children’s Playful Group Drawing
Authors: Kukkonen Tiina , Chang‐Kredl Sandra , Bolden Benjamin 
Published: June 2019

ABSTRACTCollaborations that lead to creative outputs occur within different group contexts and with diverse populations, including young children. Two cases of collaborative drawing are presented in this article to consider how young children engage in creative collaboration by negotiating meaning with others through open‐ended group drawing. We conceptualize group drawing as a form of social play where children can advance personal creative abilities through interactions and shared understandings with others. The two cases derive from a study that examined young children's group play through drawing. A preschool class of 16 children (aged 4–5) was observed during free play over eight 1‐hour sessions. Children were free to come and go as they pleased from an art station consisting of large drawing surfaces and a variety of drawing materials. Findings from the two selected cases suggest the development of shared meaning supports creative collaboration in group drawing situations, as children use a variety of verbal and non‐verbal strategies to communicate their ideas. Implications are offered for early childhood educators and environments seeking to promote creative collaboration.
Crystallization of single and binary iron‐ and aluminum hydroxides affect phosphorus desorption
Authors: Gypser Stella , Schütze Elisabeth , Freese Dirk 
Published: June 2019

AbstractIn acidic soils, phosphorus availability is affected by its strong affinity for mineral surfaces, especially Fe‐ and Al‐hydroxides. Plant roots have developed adaptive strategies to enhance the availability of phosphorus, including producing and exuding low molecular weight organic acids with a high affinity for phosphorus that competes with high molecular weight organic ligands formed during humification and mineralization. The aim of this study was to characterize the kinetics and mechanism of phosphorus desorption from Fe‐ and Al‐hydroxides of variable crystallinity, as well as binary Fe:Al‐hydroxide mixtures. Long‐term desorption experiments (56 days) were conducted with CaCl2, CaSO4, citric acid, and humic acid as competitive sorptives. CaCl2 and CaSO4 were selected as general inorganic sorptives and citric and humic acids were selected as organic ligands produced by organisms in the rhizosphere or following humification. The cumulative phosphorus desorption increased following the order CaCl2 < CaSO4 < humic acid < citric acid. Amorphous ferrihydrite and Fe‐rich Fe:Al‐hydroxides exhibited much less desorption when exposed to inorganic solutions than the crystalline and Al‐rich Fe:Al‐hydroxide mixtures. Models of the desorption data suggest phosphorus desorption with citric acid is diffusion‐controlled for ferrihydrite and Fe‐rich amorphous Fe:Al‐hydroxides. When humic acid was the sorptive, metal‐organic complexes accumulated in the solution. The results suggest organic compounds, especially citric acid, are more important for liberating phosphorus from Fe‐ and Al‐minerals than inorganic ions present in the soil solution.
Evaluation of Lysophospholipid Measurement in Cerebrospinal Fluid Samples using Liquid Chromatography–Tandem Mass Spectrometry
Authors: Morita Yoshifumi , Kurano Makoto , Sakai Eri , Nishikawa Masako , Sawabe Motoji , Aoki Junken , Yatomi Yutaka 
Published: June 2019

AbstractA quantification system for lysophospholipids (lysoPL) was developed, especially for blood samples, using liquid chromatography–tandem mass spectrometry (LC–MS/MS). However, the lysoPL measurement in cerebrospinal fluid (CSF) has not been validated. Therefore, the present study aimed to validate the lysoPL measurement using CSF samples and to elucidate the possible clinical significance of the lysoPL measurement in CSF. For the validation, we observed a good precision and linearity in a sample with high lysoPL levels. The concentrations of lysoPL changed after incubation but the changes were smaller than those observed for serum samples. Moreover, we observed that the CSF levels of 16:0, 18:0 lysophosphatidylcholine, and 18:0, 18:1, and 20:4 lysophosphatidic acid were significantly higher in subjects with central nervous system invasion caused by hematological malignancies or carcinoma than in subjects with no abnormal CSF test results. In conclusion, an LC–MS/MS quantification system for lysoPL in CSF might be useful and could be applied to clinical laboratory testing.
The rabbit brachial plexus as a model for nerve injury and repair Part 1: Anatomic study of the biceps and triceps innervation
Authors: Kollitz Kathleen M. , Giusti Guilherme , Friedrich Patricia F. , Bishop Allen T. , Shin Alexander Y. 
Published: June 2019

AbstractPurposeAnimal models can be helpful in evaluating new surgical strategies for brachial plexus reconstruction. While several groups have already used the rabbit brachial plexus to model injury, reports conflict in anatomic detail and do not identify a nerve‐muscle pair to measure motor function recovery after reconstruction. The purpose of the current study is to describe the innervations of the biceps and triceps muscles in rabbits, which are both amenable to study in brachial plexus injury models.Materials and MethodsThirteen rabbits weighing 2–2.5 kg were anesthetized. Six rabbits were sacrificed and dissected using loupe and microscope magnification to understand the overall morphology of the brachial plexus. Seven rabbits underwent electrophysiologic investigation. A bipolar nerve stimulator was used to systematically stimulate the roots, trunks and divisions, and nerve branches of the rabbit brachial plexus and compound muscle action potential was used to record muscle response. Nerve length and width measurements were not recorded.ResultsRoots contributing to the brachial plexus were C5, C6, C7, C8, and T1. In contrast to other anatomical studies, T2 did not contribute to the brachial plexus. The triceps was innervated by the radial nerve, which received contributions from C6 (1.6 mA), C7 (1.9 mA), C8, and T1 (12.2 mA).The biceps had dual innervation (proximally and distally). The proximal branch received contributions from C6 (3.5 mA) and C7 (5mA). The distal portion was innervated by a branch from the median nerve, which received innervation from C6, C7, C8, and T1.ConclusionsThe overall structure of rabbit brachial plexus is described and innervation of the biceps and triceps is described in detail. This anatomic investigation will form the basis of a future brachial plexus model of injury and repair.
Essential Amino Acids, Vitamins, and Minerals Moderate the Relationship between the Right Frontal Pole and Measures of Memory
Authors: Key Mickeal N. , Zwilling Christopher E. , Talukdar Tanveer , Barbey Aron K. 
Published: June 2019

ScopeNutrition has increasingly been recognized for its ability to help prevent and protect against disease, inspiring new programs of research that translate findings from nutritional science into innovative assessment tools, technologies, and therapies to advance the practice of modern medicine. A central aim in this effort is to discover specific dietary patterns that promote healthy brain aging and moderate the engagement of neural systems known to facilitate cognitive performance in later life.Methods and ResultsThe present study therefore investigates estimates of nutrient intake derived from food frequency questionnaires, structural measures of brain volume via high‐resolution magnetic resonance imaging, and standardized neuropsychological measures of memory performance in nondemented elders (n = 111) using a moderation analysis. The results reveal that the essential amino acids, vitamins, and minerals nutrient pattern moderates the positive relationship between the volume of the right frontal pole and measures of both delayed and auditory memory.ConclusionsOur findings demonstrate that a nutrient pattern including macro‐ and micronutrients moderate the effect of brain structure on cognitive function in old age and support the efficacy of interdisciplinary methods in nutritional cognitive neuroscience for the study of healthy brain aging.
A novel design method for extending power back‐off range of broadband Doherty power amplifier
Authors: Jin Yi , Dang Ni , Yang Guangwen , Li Mingyu , Yang Zhenxing , Yao Yao 
Published: June 2019

AbstractIn this article, a novel design method for extending the output back‐off (OBO) range of the Doherty power amplifier (DPA) is proposed. The influence of the power ratio of the peaking and carrier power amplifier on the bandwidth of the DPA is analyzed in detail. With the proposed theory, the simplified estimation of the bandwidth of the DPA for a specific OBO range can be carried out. A broadband high‐efficiency DPA working from 1.8 to 2.6 GHz (33% relative bandwidth) with 9 dB OBO level is designed to verify the proposed method. According to the measured results, the DPA achieves 44.6 to 46.8 dBm saturation output power and drain efficiency (DE) of 61% to 74%. And at 9 dB OBO level, the DE varies from 50% to 63% over the operation band. Furthermore, digital predistortion (DPD) measurement results show that the linearized DPA can meet the spectral requirements for modern wireless communication systems.
Association Between Nonalcoholic Fatty Liver Disease and Future Deterioration of Metabolic Health: A Cohort Study
Authors: Hwang You‐Cheol , Ahn Hong‐Yup , Park Cheol‐Young 
Published: June 2019

ObjectiveIt was hypothesized that the presence of nonalcoholic fatty liver disease (NAFLD) at baseline predicts future conversion from the metabolically healthy (MH) to the metabolically unhealthy (MU) phenotype according to body fat mass.MethodsA total of 22,551 Korean participants (13,601 men and 8,950 women) aged 18 to 78 years in the Kangbuk Samsung Health Study cohort were enrolled from 2007 to 2013.ResultsDuring a median of 5.1 years of follow‐up (interquartile range 2.1‐9.8 years), 23.5% (n = 5,298) of MH individuals converted to the MU phenotype. NAFLD at baseline predicted conversion independent of age, sex, BMI, lifestyle factors, individual components of metabolic syndrome, and insulin resistance (HR, 1.29; 95% CI: 1.19‐1.39; P < 0.0001). In participants with lower BMI and fat mass, NAFLD was strongly associated with conversion; however, as BMI and fat mass increased, the risk decreased, and there was no association in participants with higher BMI and fat mass (P < 0.0001 for trend).ConclusionsNAFLD at baseline was independently associated with future conversion from the MH to the MU phenotype.
Does Stimulating Physical Activity Affect School Performance?
Authors: Golsteyn Bart H. H. , Jansen Maria W. J. , Van Kann Dave H. H. , Verhagen Annelore M. C. 
Published: June 2019

AbstractThis paper investigates whether encouraging children to become more physically active in their everyday life affects their primary school performance. We use data from a field quasi‐experiment called the Active Living Program, which aimed to increase active modes of transportation to school and active play among 8‐ to 12‐year‐olds living in low socioeconomic status (SES) areas in the Netherlands. Difference‐in‐differences estimations reveal that while the interventions increase time spent on physical activity during school hours, they negatively affect school performance, especially among the worst‐performing students. Further analyses reveal that increased restlessness during instruction time is a potential mechanism for this negative effect. Our results suggest that the commonly found positive effects of exercising or participating in sports on educational outcomes may not be generalizable to physical activity in everyday life. Policymakers and educators who seek to increase physical activity in everyday life need to weigh the health and well‐being benefits against the probability of increasing inequality in school performance.
Montmorillonite reduces crystallinity of poly‐l‐lactic acid scaffolds to accelerate degradation
Authors: Shuai Cijun , Li Yang , Feng Pei , Yang Wenjing , Zhao Zhenyu , Liu Wei 
Published: June 2019

Poly‐l‐lactic acid (PLLA) is considered as a potential bone scaffold material because of good biocompatibility and bioabsorbability, whereas too slow degradation rate limits its application. In this study, montmorillonite (MMT) was introduced into PLLA scaffolds fabricated via selective laser sintering to accelerate degradation by reducing crystallinity. To be specific, MMT was a layered silicate with large surface area and aspect ratio, which provided nucleation site for the crystallization of PLLA molecular chain along their surface during the sintering process. As the surface of MMT plate was randomly oriented in the matrix, the growth direction of crystallite was also random, which interrupted the orderly crystallization, thus decreasing the overall crystallinity of PLLA. As a result, the crystallinity of PLLA scaffolds was decreased from 32.3% to 27.4% when introducing 4.5% MMT. Accordingly, weight loss was increased from 0.83% to 7.25% after immersing for 4 weeks. Besides, the tensile strength and modulus of the scaffolds increased by 44.1% and 66.9% because of the change of fracture mode from brittle fracture to ductile fracture. In addition, the scaffolds also demonstrated good hydrophilic property and cell compatibility.