bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results from a 78‐week, single‐arm, open‐label phase 2 study to evaluate UX007 in pediatric and adult patients with severe long‐chain fatty acid oxidation disorders (LC‐FAOD)
Authors: Vockley Jerry , Burton Barbara , Berry Gerard T. , Longo Nicola , Phillips John , Sanchez‐Valle Amarilis , Tanpaiboon Pranoot , Grunewald Stephanie , Murphy Elaine , Bowden Alexandra , Chen Wencong , Chen Chao‐Yin , Cataldo Jason , Marsden Deborah , Kakkis Emil 
Published: February 2019

AbstractLong‐chain fatty acid oxidation disorders (LC‐FAOD) are rare disorders characterized by acute crises of energy metabolism and severe energy deficiency that may present with cardiomyopathy, hypoglycemia, and/or rhabdomyolysis, which can lead to frequent hospitalizations and early death. An open‐label Phase 2 study evaluated the efficacy of UX007, an investigational odd‐carbon medium‐chain triglyceride, in 29 subjects with severe LC‐FAOD. UX007 was administered over 78 weeks at a target dose of 25–35% total daily caloric intake (mean 27.5%). The frequency and duration of major clinical events (hospitalizations, emergency room visits, and emergency home interventions due to rhabdomyolysis, hypoglycemia, and cardiomyopathy) occurring during 78 weeks of UX007 treatment was compared with the frequency and duration of events captured retrospectively from medical records for 78 weeks before UX007 initiation. The mean annualized event rates decreased from 1.69 to 0.88 events/year following UX007 initiation (p = 0.021; 48.1% reduction). The mean annualized duration rate decreased from 5.96 to 2.96 days/year (p = 0.028; 50.3% reduction). Hospitalizations due to rhabdomyolysis, the most common event, decreased from 1.03 to 0.63 events/year (p = 0.104; 38.7% reduction). Initiation of UX007 eliminated hypoglycemia events leading to hospitalization (from 11 pre‐UX007 hospitalizations, 0.30 events/year vs. 0; p = 0.067) and intensive care unit (ICU) care (from 2 pre‐UX007 ICU admissions, 0.05 events/year vs. 0; p = 0.161) and reduced cardiomyopathy events (3 events vs. 1 event; 0.07 to 0.02 events/year; 69.7% decrease). The majority of treatment‐related adverse events (AEs) were mild to moderate gastrointestinal symptoms, including diarrhea, vomiting, and abdominal or gastrointestinal pain, which can be managed with smaller, frequent doses mixed with food.
Evaluation of treatment and outcomes for Hispanic patients with gastric cancer at Commission on Cancer‐accredited centers in the United States
Authors: Zhao Beiqun , Leichman Lawrence P. , Horgan Santiago , Bouvet Michael , Kelly Kaitlyn J. 
Published: February 2019

AbstractBackground and ObjectivesGastric cancer in the Hispanic population commonly presents with poor clinical features. Characteristics of this vulnerable population and optimal therapy for these patients have not been clearly defined.MethodsUsing the National Cancer Database (2004‐2014), we analyzed patient demographics, clinical factors, treatment‐related factors, and outcomes for Hispanic and non‐Hispanic patients with gastric adenocarcinoma in the United States.ResultsA total of 129 666 patients were included in this analysis. Hispanics were younger, more often female, had larger tumors, and were more likely to present with metastatic disease (all P < 0.001). Hispanics were more likely to undergo staging laparoscopy (5.6% vs 4.9%; P = 0.037), gastrectomy (63.5% vs 56.9%; P < 0.001), and ≥ 15 lymph nodes examined (56.1% vs 50.5%; P < 0.001). Hispanics were less likely to have negative margins (91.2% vs 92.8%; P = 0.004). Hispanics with stage II/III disease were less likely to receive neoadjuvant therapy (31.7% vs 38.7%; P < 0.001), but more likely to receive multimodal therapy (48.9% vs 46.1%; P = 0.01). Predictors for improved overall survival in Hispanics included multimodal therapy, negative margins, and treatment at an academic center.ConclusionsEfforts to optimize treatment of this distinct and growing population of gastric cancer patients should focus on earlier diagnosis, referral to academic centers, and high‐quality surgery.
A hierarchical screening method for detection of illegal adulterants in Fur seal ginseng pills by profiling analysis of HPLC multi‐dimensional fingerprints
Authors: Wang Ke , Zeng Huiyun , Zhang Yi , Xie Xiujuan , Yue Zhenfeng , Zhang Wei , Fu Chujun , Luo Laicheng , Fan Huajun 
Published: February 2019

AbstractA novel method for hierarchical screening of illegal adulterants in Fur seal ginseng pills products was developed by multi‐dimensional fingerprint profiling analysis. Fingerprint feature of the samples was acquired by high‐performance liquid chromatography analysis of 11 batches of samples with diode array detector and fluorescence detector, and then potential illegal adulterants including phosphodiesterase type‐5 inhibitors, androgens, α receptor antagonists and yohimbine, were further separated at multiple wavelengths to reduce or remove interferences from sample matrix for highlight their chromatographic characteristics. Accordingly, a hierarchical screening strategy was designed by first‐order and second‐order fingerprints combined with spectral examination to achieve high accuracy and reliability. The method was successfully applied to screening of illegal adulterants in real samples, and it also exhibited good quantification performance through validation tests. From 16 batches of samples, three suspected samples were confirmed to be positive, containing 9.37μg/g of testosterone, 18.8 μg/g of tadalafil, and 48.5 μg/g of sildenafil, respectively. The recoveries and relative standard deviations were in the range of 83.6–103.1% and 4.2–6.8%, respectively. The proposed method provided a simple, efficient and promising alternative to monitoring functional foods.
Well‐posedness of the Laplacian on manifolds with boundary and bounded geometry
Authors: Ammann Bernd , Große Nadine , Nistor Victor 
Published: February 2019

AbstractLet M be a Riemannian manifold with a smooth boundary. The main question we address in this article is: “When is the Laplace–Beltrami operator , , invertible?” We consider also the case of mixed boundary conditions. The study of this main question leads us to the class of manifolds with boundary and bounded geometry introduced by Schick (Math. Nachr. 223 (2001), 103–120). We thus begin with some needed results on the geometry of manifolds with boundary and bounded geometry. Let be an open and closed subset of the boundary of M. We say that has finite width if, by definition, M is a manifold with boundary and bounded geometry such that the distance from a point to is bounded uniformly in x (and hence, in particular, intersects all connected components of M). For manifolds with finite width, we prove a Poincaré inequality for functions vanishing on , thus generalizing an important result of Sakurai (Osaka J. Math, 2017). The Poincaré inequality then leads, as in the classical case to results on the spectrum of Δ with domain given by mixed boundary conditions, in particular, Δ is invertible for manifolds with finite width. The bounded geometry assumption then allows us to prove the well‐posedness of the Poisson problem with mixed boundary conditions in the higher Sobolev spaces , .
The potential role of Annexin 3 in diapause embryo restart of Artemia sinica and in response to stress of low temperature
Authors: Li Na , Yao Feng , Huang Huifang , Zhang Hong , Zhang Wan , Zou Xiangyang , Sui Linlin , Hou Lin 
Published: February 2019

AbstractAnnexins are highly conserved and ubiquitous in various somatic cell types. They are involved in membrane transport and a range of calcium‐regulated activities on the cell membrane surface, including vesicular transport, membrane fusion in exocytosis, signal transduction, and formation of calcium channels. They also regulate inflammatory response, cell differentiation, and interaction between cytoskeletal proteins. In this study, for the first time, an ANX3 gene from Artemia sinica (
As‐anx3) was cloned. The
As‐anx3 full‐length complementary DNA comprises 1,024 bp and has a 948 bp open reading frame encoding a 315‐amino‐acid polypeptide with four ANX domains. The profiles of both
As‐ANX3 mRNA and protein expression exhibited peaks at the 0 hr stage and had the same significant downregulation trend throughout the post‐diapause embryo development stage. The ERK1/2, the phosphorylation levels of ERK1/2, and cell cycle‐related protein (CDK4) expressions were analyzed by western blot analysis. The results showed that CDK4 presented a significantly ascending trend from 0 and 40 hr, although the phosphorylation levels of ERK1/2 did not increase significantly. The transcriptional and protein expressions of
As‐ANX3 were highly upregulated when the temperature was lowered from 25 to 15°C, but the expressions showed a gradual downward trend when the temperature was further lowered to 5°C. These results indicated that
As‐ANX3 plays a crucial role in restarting diapause and low‐temperature stress in
A. sinica.
Conversion from Vancomycin Trough Concentration–Guided Dosing to Area Under the Curve–Guided Dosing Using Two Sample Measurements in Adults: Implementation at an Academic Medical Center
Authors: Meng Lina , Wong Tiffany , Huang Sharon , Mui Emily , Nguyen Vinhkhoa , Espinosa Gabriela , Desai Janjri , Holubar Marisa , Deresinski Stan 
Published: February 2019

Study ObjectiveThe optimal pharmacodynamic parameter for the prediction of efficacy of vancomycin is the area under the concentration–time curve (AUC), and current published data indicate that dosing based on vancomycin trough concentrations is an inaccurate substitute. In this study, our objective was to compare the achievement of therapeutic target attainment after switching from a trough‐based to an AUC‐based dosing strategy as a part of our institution's vancomycin‐per‐pharmacy protocol.DesignProspective observational quality assurance study.SettingAcademic medical center.PatientsA total of 296 hospitalized adults who received vancomycin and monitoring under our institution's vancomycin‐per‐pharmacy protocol were included in the analysis. The preimplementation retrospective comparison group consisted of 179 patients in whom vancomycin was initiated using a trough‐based dosing strategy between November 22, 2017, and January 22, 2018. The postimplementation group included 117 patients in whom vancomycin was initiated using an AUC‐based dosing strategy using two‐point sampling between June 19, 2018, and July 19, 2018, after hospital‐wide implementation of this protocol on June 19, 2018.Measurements and Main ResultsAUC values were calculated from two vancomycin concentrations (peak and trough). The primary outcome was achievement of therapeutic AUC values (400–800 mg·hr/L) in the postimplementation group or therapeutic trough level values (10–20 mg/L) in the preimplementation group. Only 98 (55%) of 179 initial trough values were therapeutic in the preimplementation group (trough‐only dosing method) versus 86 (73.5%) of 117 initial AUC values in the postimplementation group (AUC‐based dosing method) (p=0.0014). A lower proportion of supratherapeutic AUC values was observed in the postimplementation group compared with supratherapeutic trough concentrations in the preimplementation group (1.7% vs 18%, p<0.0001). Overall, 62% of patients with initially therapeutic AUC values had subsequent trough value increases of 25% or greater, occurring at a median of 6 days of vancomycin therapy. Nephrotoxicity occurred in 11% of patients in the preimplementation versus 9.4% in the postimplementation group (p=0.70).ConclusionCompared with a trough concentration–based dosing strategy, AUC‐based dosing using two‐point sampling improved therapeutic target attainment. Implementation is feasible at any hospital that performs vancomycin peak concentration testing and is a workable alternative to using Bayesian software for estimating AUC. This approach should also be directly compared with AUC‐based dosing using Bayesian software.
Congenital diaphragmatic hernia and exercise capacity, a longitudinal evaluation
Authors: Toussaint‐Duyster Leontien C.C. , van der Cammen‐van Zijp Monique H.M. , de Jongste Johan C. , Tibboel Dick , Wijnen Rene M.H. , Gischler Saskia J. , van Rosmalen Joost , IJsselstijn Hanneke 
Published: February 2019

AbstractObjectiveChildren with congenital diaphragmatic hernia (CDH) suffer from long‐term pulmonary morbidity. Longitudinal data of exercise capacity in these children are lacking. We hypothesized that exercise capacity would be impaired in children with CDH and deteriorates over time. We evaluated exercise capacity and its determinants in CDH patients longitudinally until 12 years of age.DesignProspective longitudinal follow‐up study in tertiary university hospital.PatientsOne hundred and fourteen children with CDH born between 1999 and 2012.MethodsExercise capacity was evaluated using the Bruce treadmill‐protocol at the ages of 5, 8, and 12 years. Primary outcome parameter was standard deviation score (SDS) of maximal endurance time. Data were analyzed by using linear mixed models.ResultsA total of 107 children (30 treated with extracorporeal membrane oxygenation [ECMO]) performed 191 reliable exercise tests. At ages 5, 8, and 12 years, the mean (95%CI) SDS endurance time was −0.44 (−0.65 to −0.24); −1.01 (−1.23 to −0.78); −1.10 (−1.40 to −0.80), respectively, all less than zero (P < 0.001). Exercise capacity declined significantly over time irrespective of ECMO‐treatment (5‐12 years: non‐ECMO P = 0.015; ECMO P = 0.006). Duration of initial hospital stay and diffusion capacity corrected for alveolar volume were associated with SDS endurance time (P < 0.001 and P = 0.039).ConclusionsIn CDH patients exercise capacity deteriorates between 5 and 12 years of age, irrespective of ECMO‐treatment. CDH patients may benefit from long‐term assessments of exercise capacity with timely intervention.
The dual functionality of antimicrobial peptides Os and Os‐C in human leukocytes
Authors: Taute Helena , Bester Megan J. , Gaspar Anabella R.M. 
Published: February 2019

Antimicrobial peptides (AMPs), Os and Os‐C, have been identified as multifunctional peptides with antibacterial, antiendotoxin, and anti‐inflammatory properties. For further development of Os and Os‐C as therapeutic peptides, it is essential to evaluate these effects in human mononuclear (MN) and polymorphonuclear (PMN) leukocytes. The cytotoxicity and the effects of both peptides on MN and PMN morphology were determined with the Alamar‐Blue assay and scanning electron microscopy, respectively. The ability of Os and Os‐C to induce reactive oxygen species (ROS) and to protect against 2,2′‐azobis(2‐amidinopropane) dihydrochloride–induced oxidative damage in both cell populations was evaluated using 2′,7′‐dichlorofluorescin diacetate (DCFH‐DA). Using fluorescently labeled peptides, the ability of the peptides to cross the cell membranes of MN and PMN was also evaluated. At the minimum bactericidal concentrations of Os and Os‐C, neither peptide was cytotoxic. Os caused morphological features of toxicity at 100 μM, entered MN cells, and also protected these cells against oxidative damage. Os‐C caused MN and PMN leukocyte activation associated with ROS formation and was unable to penetrate cell membranes, indicating extracellular membrane interactions. This study confirms that both Os and Os‐C at less than 100 μM are not cytotoxic. The MN‐specific uptake of Os identifies it as a cell‐specific cargo‐carrier peptide, with additional anti‐inflammatory properties. In contrast, the ability of Os‐C to activate MN and PMN cells implies that this peptide should be further evaluated as an AMP, which, in addition to its ability to eradicate infection, can further enhance host immunity. These novel characteristics of Os and Os‐C indicate that these AMPs as peptides can be further developed for specific applications.
Ginsenoside Rf relieves mechanical hypersensitivity, depression‐like behavior, and inflammatory reactions in chronic constriction injury rats
Authors: Li Yangyi , Chen Chengbo , Li Shunyuan , Jiang Changcheng 
Published: February 2019

The aim of this study was to investigate whether ginsenoside Rf can effectively relieve pain hypersensitivity in a neuropathic pain rat model. Neuropathic pain was induced in rats by chronic constriction injury (CCI) to the right sciatic nerve. Ginsenoside Rf was administered intraperitoneally after CCI surgery. The von Frey filament test and forced swimming test were performed to examine pain hypersensitivity and depression‐like behavior in rats. Western blot was used to measure the levels of inflammatory cytokines in the dorsal root ganglion (DRG) and the spinal cord. Pretreatment of ginsenoside Rf for 7 days did not affect the onset of mechanical allodynia in CCI rats; however, a single dose of ginsenoside Rf 1 day after surgery attenuated established mechanical allodynia in CCI rats. Additionally, chronic treatment of ginsenoside Rf 1 week before and 2 weeks after CCI surgery diminished mechanical allodynia and depression‐like behavior without affecting spontaneous locomotor activity in CCI rats. Furthermore, in CCI rats, chronic ginsenoside Rf treatment partially reversed the upregulation of proinflammatory cytokines in the spinal cord and/or the DRG but elevated IL‐10, an anti‐inflammatory factor, in the DRG. Ginsenoside Rf alleviated neuropathic pain and its associated depression and restored the balance between proinflammatory and anti‐inflammatory cytokines. Our results suggest that ginsenoside Rf may be a potential therapy for nerve injury‐induced neuropathic pain.
Effect of surface treatments on the localized corrosion resistance of the AA2198‐T8 aluminum lithium alloy welded by FSW process
Authors: de S. C. Machado Caruline , Klumpp Rafael E. , Ayusso Victor H. , Donatus Uyime , Milagre Mariana X. , de S. Araujo João V. , F. Machado Glauson A. , Costa I. 
Published: February 2019

In this work, the effect of eight types of surface treatments on the corrosion resistance of friction stir welded samples of an AA2198‐T8 Al‐Cu‐Li alloy were tested and compared in an attempt to find suitable alternatives to toxic and carcinogenic hexavalent chromium treatments. All the samples were anodized and subjected to different post‐anodizing treatments. The post‐anodizing treatments were (1) hydrothermal treatment in Ce (NO3)3 6H2O solution; (2) hydrothermal treatment in Ce (NO3)3 6H2O solution with H2O2; (3) hydrothermal treatment in boiling water; (4) hexavalent chromium conversion coating; and (5) immersion in BTSE (bis‐1,2‐(triethoxysilyl) ethane. The corrosion resistance of the treated samples was evaluated by immersion tests in sodium chloride solution (0.1 mol L−1 NaCl) and electrochemical impedance spectroscopy (EIS) of the friction stir weldment. The results showed that among the alternative treatments, the Ce‐containing solutions presented the best corrosion resistance, especially when used without peroxide.
Biomacromolecule‐Functionalized AIEgens for Advanced Biomedical Studies
Authors: Wu Feng , Wu Xia , Duan Zhijuan , Huang Yu , Lou Xiaoding , Xia Fan 
Published: February 2019

AbstractThe advances in bioinformatics and biomedicine have promoted the development of biomedical imaging and theranostic systems to respectively extend the endogenous biomarker imaging with high contrast and enhance the therapeutic effect with high efficiency. The emergence of biomacromolecule‐functionalized aggregation‐induced emitters (AIEgens), utilizing AIEgens, and biomacromolecules (nucleic acids, peptides, glycans, and lipids), displays specific targeting ability to cancer cell, improved biocompatibility, reduced toxicity, enhanced therapeutic effect, and so forth. This review summarizes the rational design of biomacromolecule‐functionalized AIEgens and their biomedical applications in recent ten years, including high‐resolution optical imaging of cell, tissue, and small animal model with low background; the biomarker detection for early diagnosis and prognosis; the delivery and monitoring of prodrugs; image‐guide photodynamic therapy and its combination with chemotherapy. Through illustrating their functional mechanisms and application, it is hoped that this review would open up a completely new train of research thought for attracted researchers in various fields.
Light‐Stimulated Synaptic Transistors Fabricated by a Facile Solution Process Based on Inorganic Perovskite Quantum Dots and Organic Semiconductors
Authors: Wang Kai , Dai Shilei , Zhao Yiwei , Wang Yan , Liu Chuan , Huang Jia 
Published: February 2019

AbstractImplementation of artificial intelligent systems with light‐stimulated synaptic emulators may enhance computational speed by providing devices with high bandwidth, low power computation requirements, and low crosstalk. One of the key challenges is to develop light‐stimulated devices that can response to light signals in a neuron‐/synapse‐like fashion. A simple and effective solution process to fabricate light‐stimulated synaptic transistors (LSSTs) based on inorganic halide perovskite quantum dots (IHP QDs) and organic semiconductors (OSCs) is reported. Blending IHP QDs and OSCs not only improves the charge separation efficiency of the photoexcited charges, but also induces delayed decay of the photocurrent in the IHP QDs/OSCs hybrid film. The enhanced charge separation efficiency results in high photoresponsivity, while the induced delayed decay of the photocurrent is critical to achieving light‐stimulating devices with a memory effect, which are important for achieving high synaptic performance. The LSSTs can respond to light signals in a highly neuron‐/synapse‐like fashion. Both short‐term and long‐term synaptic behaviors have been realized, which may lay the foundation for the future implementation of artificial intelligent systems that are enabled by light signals. More significantly, LSSTs are fabricated by a facile solution process which can be easily applied to large‐scale samples.
Phylogeny and evolution of morphological characters in tribe Chamaedoreeae (Arecaceae)
Authors: Cuenca Argelia , Dransfield John B. , Asmussen-Lange Conny B. 
Published: February 2019

AbstractWithin the palm family, molecular analyses have resulted in a need to re­evaluate characters previously considered useful to establish hypotheses of relationships among groups. Recent phylogenetic analyses of tribe Chamaedoreeae have shown that characters traditionally used as strong indicators of relationship, such as presence of solitary flowers and dioecy, are homoplasious within this tribe. In the largest genus, Chamaedorea, published molecular analyses recover well­supported groups not previously proposed based on morphological characters and at the same time resolve some of the current subgenera as polyphyletic. In this study we further explore the phylogenetic relationships in Chamaedoreeae and search for morphological synapomorphies for the monophyletic groups recovered. Phylogenetic analyses of morphological, nuclear (PRK, RPB2), and plastid (matK, ndhF, trnD­trnT, rps16 intron, trnL­trnF) data are performed and morphological characters are subsequently optimized on the resulting topologies. Although most of the morphological characters included are highly homoplasious, the inclusion of morphological characters in the phylogenetic analyses improves the resolution within Chamaedoreeae, particularly among species of Chamaedorea. With the exception of Synechanthus and Wendlandiella, all the genera and subgenera in Chamaedoreeae are defined by a combination of homoplasious characters, none of which is unique within the tribe. Two of the seven subgenera of Chamaedorea included in our analyses, C. subg. Eleutheropetalum and subg. Stephanostachys, are supported as monophyletic with a number of morphological synapomorphies also used in the original descriptions of these subgenera. Some morphological characters not used in the traditional subgeneric classification of Chamaedorea, such as leaf sheath structure and pistillode, gynoecium and filament connation, though homoplasious, are resolved as synapomorphies and, therefore, potentially useful when defining subgenera within this genus.