bluuebunny/crossref_metadata_2025_split huggingface dataset:
β-Elemene Selectively Inhibits the Proliferation of Glioma Stem-Like Cells Through the Downregulation of Notch1
Authors: Feng Hai-bin , Wang Jing , Jiang Hao-ran , Mei Xin , Zhao Yi-ying , Chen Fu-rong , Qu Yue , Sai Ke , Guo Cheng-cheng , Yang Qun-ying , Zhang Zong-ping , Chen Zhong-ping 
Published: October 2016

Abstract
Glioma is the most frequent primary central nervous system tumor. Although the current first-line medicine, temozolomide (TMZ), promotes patient survival, drug resistance develops easily. Thus, it is important to investigate novel therapeutic reagents to solidify the treatment effect. β-Elemene (bELE) is a compound from a Chinese herb whose anticancer effect has been shown in various types of cancer. However, its role in the inhibition of glioma stem-like cells (GSLCs) has not yet been reported. We studied both the in vitro and the in vivo inhibitory effect of bELE and TMZ in GSLCs and parental cells and their combined effects. The molecular mechanisms were also investigated. We also optimized the delivery methods of bELE. We found that bELE selectively inhibits the proliferation and sphere formation of GSLCs, other than parental glioma cells, and TMZ exerts its effects on parental cells instead of GSLCs. The in vivo data confirmed that the combination of bELE and TMZ worked better in the xenografts of GSLCs, mimicking the situation of tumorigenesis of human cancer. Notch1 was downregulated with bELE treatment. Our data also demonstrated that the continuous administration of bELE produces an ideal effect to control tumor progression. Our findings have demonstrated, for the first time, that bELE could compensate for TMZ to kill both GSLCs and nonstem-like cancer cells, probably improving the prognosis of glioma patients tremendously. Notch1 might be a downstream target of bELE. Therefore, our data shed light on improving the outcomes of glioma patients by combining bELE and TMZ.
Human Stem Cell-Derived Endothelial-Hepatic Platform for Efficacy Testing of Vascular-Protective Metabolites from Nutraceuticals
Authors: Narmada Balakrishnan Chakrapani , Goh Yeek Teck , Li Huan , Sinha Sanjay , Yu Hanry , Cheung Christine 
Published: October 2016

Abstract
Atherosclerosis underlies many cardiovascular and cerebrovascular diseases. Nutraceuticals are emerging as a therapeutic moiety for restoring vascular health. Unlike small-molecule drugs, the complexity of ingredients in nutraceuticals often confounds evaluation of their efficacy in preclinical evaluation. It is recognized that the liver is a vital organ in processing complex compounds into bioactive metabolites. In this work, we developed a coculture system of human pluripotent stem cell-derived endothelial cells (hPSC-ECs) and human pluripotent stem cell-derived hepatocytes (hPSC-HEPs) for predicting vascular-protective effects of nutraceuticals. To validate our model, two compounds (quercetin and genistein), known to have anti-inflammatory effects on vasculatures, were selected. We found that both quercetin and genistein were ineffective at suppressing inflammatory activation by interleukin-1β owing to limited metabolic activity of hPSC-ECs. Conversely, hPSC-HEPs demonstrated metabolic capacity to break down both nutraceuticals into primary and secondary metabolites. When hPSC-HEPs were cocultured with hPSC-ECs to permit paracrine interactions, the continuous turnover of metabolites mitigated interleukin-1β stimulation on hPSC-ECs. We observed significant reductions in inflammatory gene expressions, nuclear translocation of nuclear factor κB, and interleukin-8 production. Thus, integration of hPSC-HEPs could accurately reproduce systemic effects involved in drug metabolism in vivo to unravel beneficial constituents in nutraceuticals. This physiologically relevant endothelial-hepatic platform would be a great resource in predicting the efficacy of complex nutraceuticals and mechanistic interrogation of vascular-targeting candidate compounds.
Safety and Efficacy of Megakaryocytes Induced from Hematopoietic Stem Cells in Murine and Nonhuman Primate Models
Authors: Guan Xin , Qin Meng , Zhang Yu , Wang Yanan , Shen Bin , Ren Zhihua , Ding Xinxin , Dai Wei , Jiang Yongping 
Published: October 2016

Abstract
Because of a lack of platelet supply and a U.S. Food and Drug Administration-approved platelet growth factor, megakaryocytes have emerged as an effective substitute for alleviating thrombocytopenia. Here, we report the development of an efficient two-stage culture system that is free of stroma, animal components, and genetic manipulations for the production of functional megakaryocytes from hematopoietic stem cells. Safety and functional studies were performed in murine and nonhuman primate models. One human cryopreserved cord blood CD34+ cell could be induced ex vivo to produce up to 1.0 × 104 megakaryocytes that included CD41a+ and CD42b+ cells at 82.4% ± 6.1% and 73.3% ± 8.5% (mean ± SD), respectively, yielding approximately 650-fold higher cell numbers than reported previously. Induced human megakaryocytic cells were capable of engrafting and producing functional platelets in the murine xenotransplantation model. In the nonhuman primate model, transplantation of primate megakaryocytic progenitors increased platelet count nadir and enhanced hemostatic function with no adverse effects. In addition, primate platelets were released in vivo as early as 3 hours after transplantation with autologous or allogeneic mature megakaryocytes and lasted for more than 48 hours. These results strongly suggest that large-scale induction of functional megakaryocytic cells is applicable for treating thrombocytopenic blood diseases in the clinic.
Cited references and Medical Subject Headings (MeSH) as two different knowledge representations: clustering and mappings at the paper level
Authors: Leydesdorff Loet , Comins Jordan A. , Sorensen Aaron A. , Bornmann Lutz , Hellsten Iina 
Published: October 2016

AbstractFor the biomedical sciences, the Medical Subject Headings (MeSH) make available a rich feature which cannot currently be merged properly with widely used citing/cited data. Here, we provide methods and routines that make MeSH terms amenable to broader usage in the study of science indicators: using Web-of-Science (WoS) data, one can generate the matrix of citing versus cited documents; using PubMed/MEDLINE data, a matrix of the citing documents versus MeSH terms can be generated analogously. The two matrices can also be reorganized into a 2-mode matrix of MeSH terms versus cited references. Using the abbreviated journal names in the references, one can, for example, address the question whether MeSH terms can be used as an alternative to WoS Subject Categories for the purpose of normalizing citation data. We explore the applicability of the routines in the case of a research program about the amyloid cascade hypothesis in Alzheimer’s disease. One conclusion is that referenced journals provide archival structures, whereas MeSH terms indicate mainly variation (including novelty) at the research front. Furthermore, we explore the option of using the citing/cited matrix for main-path analysis as a by-product of the software.
Quadriparesis Caused by Lead Poisoning Nine Years After a Gunshot Wound With Retained Bullet Fragments: A Case Report
Authors: Nally Emma , Jelinek James , Bunning Robert D. 
Published: October 2016

AbstractLead toxicity in adults is characterized by nonspecific symptoms of abdominal pain, vomiting, constipation, fatigue, and weight loss. We present a case of severe lead toxicity that developed subacutely, causing quadriparesis 9 years after a gunshot wound with retained bullet fragments. The onset of symptoms may have been related to the development of a pseudocyst. The long interval between the gunshot wound and the onset of symptoms contributed to a delay in suspecting that the retained bullet was a source of lead toxicity. The patient's symptoms gradually improved after chelation therapy, removal of the bullet fragment, and an extended program of acute inpatient rehabilitation.Level of EvidenceV
Lumbar Muscle Cross‐Sectional Areas Do Not Predict Clinical Outcomes in Adults With Spinal Stenosis: A Longitudinal Study
Authors: Gellhorn Alfred C. , Suri Pradeep , Rundell Sean D. , Olafsen Nathan , Carlson M. Jake , Johnson Steve , Fry Adrielle , Annaswamy Thiru M. , Gilligan Christopher , Comstock Bryan , Heagerty Patrick , Friedly Janna , Jarvik Jeffrey G. 
Published: October 2016

AbstractBackgroundMinimal longitudinal data exist regarding the role of lumbar musculature in predicting back pain and function. In cross‐sectional study designs, there is often atrophy of the segmental multifidus muscle in subjects with low back pain compared with matched controls. However, the cross‐sectional design of these studies prevents drawing conclusions regarding whether lumbar muscle characteristics predict or modify future back pain or function.ObjectiveThe primary objective of this study is to determine whether the cross‐sectional area (CSA) of lumbar muscles predict functional status or back pain at 6‐ or 12‐month follow‐up in older adults with spinal degeneration. The secondary objective is to evaluate whether these muscle characteristics improve outcome prediction above and beyond the prognostic information conferred by demographic and psychosocial variables.DesignSecondary analysis of a randomized controlled trial.ParticipantsA total of 209 adults aged 50 years and older with clinical and radiographic spinal stenosis from the Lumbar Epidural steroid injection for Spinal Stenosis (LESS) trial.MethodsUsing baseline magnetic resonance images, we calculated CSAs of the lumbar multifidus, psoas, and quadratus lumborum muscles using a standardized protocol by manually tracing the borders of each of the muscles. The relationship between lumbar muscle CSAs and baseline measures was assessed with Pearson or Spearman correlation coefficients. The relationship between lumbar muscle characteristics and 6‐ and 12‐month Roland Morris Disability Questionnaire (RDQ) and back pain Numeric Rating Scale (NRS) responses was further evaluated with multivariate linear regression. A hierarchical approach to the regression was performed: a basic model with factors of conceptual importance including age, gender, BMI, and baseline RDQ score formed the first step. The second and third steps evaluated whether psychosocial variables or muscle measures conferred additional prognostic information to the basic model.Main Outcome MeasuresFunction as measured by the RDQ and back pain as measured by the NRS at 6‐ and 12‐month follow‐up.ResultsLumbar muscle CSA was not a significant predictor of 6‐ or 12‐month RDQ or pain score in multivariate analyses.ConclusionsCross‐sectional areas of lumbar muscles do not predict function or pain at medium‐ and long‐term follow‐up in adults with lumbar spinal stenosis.Level of EvidenceIII
RELATIVIZING OPERATIONAL SET THEORY
Authors: JÄGER GERHARD 
Published: October 2016

AbstractWe introduce a way of relativizing operational set theory that also takes care of application. After presenting the basic approach and proving some essential properties of this new form of relativization we turn to the notion of relativized regularity and to the system OST (LR) that extends OST by a limit axiom claiming that any set is element of a relativized regular set. Finally we show that OST (LR) is proof-theoretically equivalent to the well-known theory KPi for a recursively inaccessible universe.
Oral supplementation of healthy adults with 2′-O-fucosyllactose and lacto-N-neotetraose is well tolerated and shifts the intestinal microbiota
Authors: Elison Emma , Vigsnaes Louise K. , Rindom Krogsgaard Laura , Rasmussen Julie , Sørensen Nikolaj , McConnell Bruce , Hennet Thierry , Sommer Morten O. A. , Bytzer Peter 
Published: October 2016

AbstractThe gut microbiota has been established as an important player influencing many aspects of human physiology. Breast milk, the first diet for an infant, contains human milk oligosaccharides (HMO) that shape the infant’s gut microbiota by selectively stimulating the growth of specific bacteria, especially bifidobacteria. In addition to their bifidogenic activity, the ability of HMO to modulate immune function and the gut barrier makes them prime candidates to restore a beneficial microbiota in dysbiotic adults and provide health benefits. We conducted a parallel, double-blind, randomised, placebo-controlled, HMO-supplementation study in 100 healthy, adult volunteers, consuming chemically produced 2′-O-fucosyllactose (2′FL) and/or lacto-N-neotetraose (LNnT) at various daily doses and mixes or placebo for 2 weeks. All participants completed the study without premature discontinuation. Supplementation of 2′FL and LNnT at daily doses up to 20 g was shown to be safe and well tolerated, as assessed using the gastrointestinal symptoms rating scale. 16S rRNA sequencing analysis showed that HMO supplementation specifically modified the adult gut microbiota with the primary impact being substantial increases in relative abundance of Actinobacteria andBifidobacteriumin particular and a reduction in relative abundance of Firmicutes and Proteobacteria. This study provides the first set of data on safety, tolerance and impact of HMO on the adult gut microbiota. Collectively, the results from this study show that supplementing the diet with HMO is a valuable strategy to shape the human gut microbiota and specifically promote the growth of beneficial bifidobacteria.
Morphological and molecular identification of cryptic species in theSergentomyia bailyi(Sinton, 1931) complex in Sri Lanka
Authors: Tharmatha T. , Gajapathy K. , Ramasamy R. , Surendran S.N. 
Published: October 2016

AbstractThe correct identification of sand fly vectors of leishmaniasis is important for controlling the disease. Genetic, particularly DNA sequence data, has lately become an important adjunct to the use of morphological criteria for this purpose. A recent DNA sequencing study revealed the presence of two cryptic species in theSergentomyia bailyispecies complex in India. The present study was undertaken to ascertain the presence of cryptic species in theSe. bailyicomplex in Sri Lanka using morphological characteristics and DNA sequences from cytochrome c oxidase subunits. Sand flies were collected from leishmaniasis endemic and non-endemic dry zone districts of Sri Lanka. A total of 175Se. bailyispecimens were initially screened for morphological variations and the identified samples formed two groups, tentatively termed asSe. bailyispecies A and B, based on the relative length of the sensilla chaeticum and antennal flagellomere. DNA sequences from the mitochondrial cytochrome c oxidase subunit I (COI) and subunit II (COII) genes of morphologically identifiedSe. bailyispecies A and B were subsequently analyzed. The two species showed differences in theCOIandCOIIgene sequences and were placed in two separate clades by phylogenetic analysis. An allele specific polymerase chain reaction assay based on sequence variation in theCOIgene accurately differentiated species A and B. The study therefore describes the first morphological and genetic evidence for the presence of two cryptic species within theSe. bailyicomplex in Sri Lanka and a DNA-based laboratory technique for differentiating them.
COST-EFFECTIVENESS OF STRUCTURED EDUCATION IN CHILDREN WITH TYPE-1 DIABETES MELLITUS
Authors: Basarir Hasan , Brennan Alan , Jacques Richard , Pollard Daniel , Stevens Katherine , Freeman Jennifer , Wales Jerry , Price Katherine 
Published: October 2016

Objectives: Kids in Control OF Food (KICk-OFF) is a 5-day structured education program for 11- to 16-year-olds with type 1 diabetes mellitus (T1DM) who are using multiple daily insulin injections. This study evaluates the cost-effectiveness of the KICk-OFF education program compared with the usual care using data from the KICk-OFF trial.Methods: The short-term within-trial analysis covers the 2-year postintervention period. Data on glycated hemoglobin (HbA1c), severe hypoglycemia, and diabetic ketoacidosis (DKA) were collected over a 2-year follow-up period. Sub-group analyses have been defined on the basis of baseline HbA1c being below 7.5 percent (58.5 mmol/mol) (low group), between 7.5 percent and 9.5 percent (80.3 mmol/mol) (medium group), and over 9.5 percent (high group). The long-term cost-effectiveness evaluation has been conducted by using The Sheffield Type 1 Diabetes Policy Model, which is a patient-level simulation model on T1DM. It includes long-term microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular (myocardial infarction, stroke, revascularization, and angina) diabetes-related complications and acute adverse events (severe hypoglycemia and DKA).Results: The most favorable within-trial scenario for the KICk-OFF arm led to an incremental cost-effectiveness ratio (ICER) of £23,688 (base year 2009) with a cost-effectiveness probability of 41.3 percent. Simulating the long-term complications using the full cohort data, the mean ICER for the base case was £28,813 (base year 2011) and the probability of the KICk-OFF intervention being cost-effective at £20,000/QALY threshold was 42.6 percent, with considerable variation due to treatment effect duration. For the high HbA1c sub-group, the KICk-OFF arm was “dominant” (meaning it provided better health gains at lower costs than usual care) over the usual care arm in each scenario considered.Conclusions: For the whole study population, the cost-effectiveness of KICk-OFF depends on the assumption for treatment effect duration. For the high baseline HbA1c sub-group, KICk-OFF arm was estimated to be dominant over the usual care arm regardless of the assumption on the treatment effect duration.
Probing the spinor nature of electronic states in nanosize non-collinear magnets
Authors: Fischer Jeison A. , Sandratskii Leonid M. , Phark Soo-Hyon , Ouazi Safia , Pasa André A. , Sander Dirk , Parkin Stuart S. P. 
Published: October 2016

AbstractNon-collinear magnetization textures provide a route to novel device concepts in spintronics. These applications require laterally confined non-collinear magnets (NCM). A crucial aspect for potential applications is how the spatial proximity between the NCM and vacuum or another material impacts the magnetization texture on the nanoscale. We focus on a prototypical exchange-driven NCM given by the helical spin order of bilayer Fe on Cu(111). Spin-polarized scanning tunnelling spectroscopy and density functional theory reveal a nanosize- and proximity-driven modification of the electronic and magnetic structure of the NCM in interfacial contact with a ferromagnet or with vacuum. An intriguing non-collinearity between the local magnetization in the sample and the electronic magnetization probed above its surface results. It is a direct consequence of the spinor nature of electronic states in NCM. Our findings provide a possible route for advanced control of nanoscale spin textures by confinement.
Global and hepatocyte-specific ablation of Bmal1 induces hyperlipidaemia and enhances atherosclerosis
Authors: Pan Xiaoyue , Bradfield Christopher A. , Hussain M. Mahmood 
Published: October 2016

AbstractCircadian rhythms controlled by clock genes affect plasma lipids. Here we show that global ablation of Bmal1 in Apoe−/− and Ldlr−/− mice and its liver-specific ablation in Apoe−/− (L-Bmal1−/−Apoe−/−) mice increases, whereas overexpression of BMAL1 in L-Bmal1−/−Apoe−/− and Apoe−/−mice decreases hyperlipidaemia and atherosclerosis. Bmal1 deficiency augments hepatic lipoprotein secretion and diminishes cholesterol excretion to the bile. Further, Bmal1 deficiency reduces expression of Shp and Gata4. Reductions in Shp increase Mtp expression and lipoprotein production, whereas reductions in Gata4 diminish Abcg5/Abcg8 expression and biliary cholesterol excretion. Forced SHP expression normalizes lipoprotein secretion with no effect on biliary cholesterol excretion, while forced GATA4 expression increases cholesterol excretion to the bile and reduces plasma lipids in L-Bmal1−/−Apoe−/− and Apoe−/− mice. Thus, our data indicate that Bmal1 modulates lipoprotein production and biliary cholesterol excretion by regulating the expression of Mtp and Abcg5/Abcg8 via Shp and Gata4.
Separating mitochondrial protein assembly and endoplasmic reticulum tethering by selective coupling of Mdm10
Authors: Ellenrieder Lars , Opaliński Łukasz , Becker Lars , Krüger Vivien , Mirus Oliver , Straub Sebastian P. , Ebell Katharina , Flinner Nadine , Stiller Sebastian B. , Guiard Bernard , Meisinger Chris , Wiedemann Nils , Schleiff Enrico , Wagner Richard , Pfanner Nikolaus , Becker Thomas 
Published: October 2016

AbstractThe endoplasmic reticulum–mitochondria encounter structure (ERMES) connects the mitochondrial outer membrane with the ER. Multiple functions have been linked to ERMES, including maintenance of mitochondrial morphology, protein assembly and phospholipid homeostasis. Since the mitochondrial distribution and morphology protein Mdm10 is present in both ERMES and the mitochondrial sorting and assembly machinery (SAM), it is unknown how the ERMES functions are connected on a molecular level. Here we report that conserved surface areas on opposite sides of the Mdm10 β-barrel interact with SAM and ERMES, respectively. We generated point mutants to separate protein assembly (SAM) from morphology and phospholipid homeostasis (ERMES). Our study reveals that the β-barrel channel of Mdm10 serves different functions. Mdm10 promotes the biogenesis of α-helical and β-barrel proteins at SAM and functions as integral membrane anchor of ERMES, demonstrating that SAM-mediated protein assembly is distinct from ER-mitochondria contact sites.
Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury
Authors: Embree Mildred C. , Chen Mo , Pylawka Serhiy , Kong Danielle , Iwaoka George M. , Kalajzic Ivo , Yao Hai , Shi Chancheng , Sun Dongming , Sheu Tzong-Jen , Koslovsky David A. , Koch Alia , Mao Jeremy J. 
Published: October 2016

AbstractTissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage. We identify FCSCs residing within the superficial zone niche in the temporomandibular joint (TMJ) condyle. A single FCSC spontaneously generates a cartilage anlage, remodels into bone and organizes a haematopoietic microenvironment. Wnt signals deplete the reservoir of FCSCs and cause cartilage degeneration. We also show that intra-articular treatment with the Wnt inhibitor sclerostin sustains the FCSC pool and regenerates cartilage in a TMJ injury model. We demonstrate the promise of exploiting resident FCSCs as a regenerative therapeutic strategy to substitute cell transplantation that could be beneficial for patients suffering from fibrocartilage injury and disease. These data prompt the examination of utilizing this strategy for other musculoskeletal tissues.