bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease
Authors: Smith Einar , Ottosson Filip , Hellstrand Sophie , Ericson Ulrika , Orho-Melander Marju , Fernandez Céline , Melander Olle 
Published: October 2019

ObjectivesWe recently identified a health conscious food pattern (HCFP) associated with reduced risk of cardiometabolic disease. However, the molecular events linking the healthy food pattern to reduced risk of cardiometabolic disease are unknown. Our aim was to identify plasma metabolites associated with the HCFP and test if such metabolites predict cardiometabolic disease and mortality.MethodsUsing liquid-chromatography mass-spectrometry, 112 plasma metabolites were measured in 3236 participants without cardiovascular disease (CVD) and diabetes mellitus from the population-based Malmö Diet and Cancer study. Metabolites associated with the HCFP were identified using multivariable adjusted linear regressions followed by Bonferroni correction. The healthy dietary biomarkers were subsequently related to risk of cardiometabolic disease and mortality during long-term follow-up with multivariable adjusted Cox proportional hazards models.ResultsDuring a median follow-up time of 21.4 years, 603 participants developed CVD, 362 developed diabetes mellitus and 843 participants died. Five healthy dietary biomarkers were associated with the HCFP at baseline (p<0.0004) and four predicted at least one of the studied end points (p<0.05). Ergothioneine was the metabolite most strongly connected to the HCFP and was associated with a lower risk of coronary disease (HR per 1 SD increment of ergothioneine, HR=0.85, p=0.01), cardiovascular mortality (HR=0.79, p=0.002) and overall mortality (HR=0.86, p=4e-5).ConclusionsWe identified that higher ergothioneine was an independent marker of lower risk of cardiometabolic disease and mortality, which potentially can be induced by a specific healthy dietary intake.
Population-based prevalence and incidence estimates of primary discoid lupus erythematosus from the Manhattan Lupus Surveillance Program
Authors: Izmirly Peter , Buyon Jill , Belmont H Michael , Sahl Sara , Wan Isabella , Salmon Jane , Askanase Anca , Bathon Joan M , Geraldino-Pardilla Laura , Ali Yousaf , Ginzler Ellen , Putterman Chaim , Gordon Caroline , Helmick Charles , Parton Hilary 
Published: October 2019

ObjectiveEpidemiological data for primary discoid lupus erythematosus (pDLE) remain limited, particularly for racial/ethnic populations in the USA. The Manhattan Lupus Surveillance Program (MLSP) is a population-based retrospective registry of cases with SLE and related diseases including pDLE in Manhattan and was used to provide estimates of the prevalence and incidence of pDLE across major racial/ethnic populations.MethodsMLSP cases were identified from rheumatologists, hospitals and population databases. Two case definitions were used for pDLE: the primary case definition which was any physician diagnosis found in the chart and a secondary case definition which was limited to cases diagnosed by a rheumatologist and/or dermatologist. Rates among Manhattan residents were age-adjusted, and capture–recapture analyses were conducted to assess case under-ascertainment.ResultsBased on the primary definition, age-adjusted overall prevalence and incidence rates of pDLE among Manhattan residents were 6.5 and 0.8 per 100 000 person-years, which increased to 9.0 and 1.3 after capture–recapture adjustment. Prevalence and incidence rates were approximately two and six times higher, respectively, among women compared with men (p<0.0001). Higher prevalence was also found among non-Latino blacks (23.5) and Latinos (8.2) compared with non-Latino whites (1.8) and non-Latino Asians (0.6) (p<0.0001). Incidence was highest among non-Latino blacks (2.4) compared with all other racial/ethnic groups. Similar relationships were observed for the secondary case definition.ConclusionData from the MLSP provide epidemiological estimates for pDLE among the major racial/ethnic populations in the USA and reveal disparities in pDLE prevalence and incidence by sex and race/ethnicity among Manhattan residents.
Eight weeks of fish oil supplementation does not prevent sitting-induced leg endothelial dysfunction
Authors: Morishima Takuma , Tsuchiya Yosuke , Padilla Jaume , Ochi Eisuke 
Published: October 2019

Prolonged sitting impairs leg endothelial function and this impairment is thought to be mediated by a sustained reduction in blood flow-induced shear stress. However, whether nutritional strategies can be used to prevent sitting-induced leg endothelial dysfunction remains unknown. Herein, we tested the hypothesis that 8 weeks of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation would prevent endothelial dysfunction associated with sitting. Nineteen healthy men were randomly assigned to a placebo group or EPA+DHA group in a double-blind fashion. The EPA+DHA group was administered EPA-rich fish oil, containing 600 mg EPA and 260 mg DHA per day for 8 weeks. The placebo group received matching capsules for the same duration of time. Popliteal artery flow-mediated dilation (FMD) was measured at baseline and before and after a 3-h sitting period. During sitting, blood pressure, popliteal artery diameter, and blood velocity were measured every hour. Throughout the sitting period, popliteal artery blood flow and shear rate were markedly and similarly reduced in both groups (P < 0.05). However, counter to the hypothesis, 3 h of sitting impaired popliteal artery FMD to the same extent in both groups (P < 0.05). In conclusion, daily EPA and DHA supplementation is not effective at preventing the detrimental effects of prolonged sitting on leg endothelial function. Novelty We provide evidence that sitting-induced leg endothelial dysfunction in young healthy subjects cannot be remediated by a nutritional strategy known to produce cardiovascular benefits. This could be partially due to the low total dose of EPA and DHA administered.
Mechanical properties of bio-fiber composites reinforced with luffa cylindrica irradiated by electron beam
Authors: Patra Subhashree , Mohanta Kamal Lochan , Parida Chhatrapati 
Published: October 2019

This investigation aims to analyze the effects of electron beam irradiation on the morphological and mechanical properties of green composites synthesized using natural fibers of luffa cylindrica (LC) and biodegradable polymer poly (lactic) acid. This work aims to transform the low priced, readily available, agricultural waste product LC fiber into a high value product. The major challenge during the fabrication of natural fiber composites is the chemical bonding between hydrophilic LC fiber and hydrophobic poly lactic acid (PLA) matrix. Due to the disagreeing chemical nature of fiber and matrix, they are not compatible. The fibers are exposed to physical treatment, i.e., electron beam irradiation of different doses 0.5, 1.0, 2.0, 4.0 and 10.0 Gy using 6 MeV medical linear accelerator to increase the compatibility of LC fiber with PLA. Before irradiation, LC fibers are modified with calcium salts to explore the use of composite materials in biomedical terrain. When PLA is reinforced with irradiated LC fiber, tensile strength increases by 79.87% and flexural strength increases by 177%. Mechanical parameters generated by flexural and tensile tests of this study can be explored to have various clinical applications like bone implant, replacement of cervical cavities, etc.
The dielectric properties and electrical conductivity of LDPE modified by fillers of biological origin
Authors: Gojayev E. M. , Aliyeva Sh. V. , Khalilova X. S. , Jafarova G. S. , Jabarov S. H. 
Published: October 2019

In this work, were investigated about the investigation of the frequency-dependent change in the character of the dielectric permeability and the tangent of dielectric loss angles of the biocomposites type LDPE + x vol.% FB obtained by fish bone fillers adding to the matrix of low density polyethylene and the bionanocomposites type LDPE + x vol.% FB + 1 vol.% Al with adding to this mixture 1 vol.% aluminum nanoparticles size 50 nm, calculation the actual and imaginary parts of the dielectric permeability of these materials, and the investigation of frequency change of electrical conductivity of both bio and bionanocomposites. It has been established that the dielectric permeability of biocomposites practically does not change in the frequency range 0–103 kHz.
Research on the Fluctuation and Factors of China TFP of IT Industry
Authors: Zhang Caiming 
Published: October 2019

The production capacity of the industry itself is booming in the development of the information technology (IT) industry in China. At the same time, we should clearly understand that in the process of industrial development and aggregation, there are very significant features, such as differences in investment in output between software and hardware development, regional differences, and even IT industries in different levels of cities. The development also has a clear division of labor and constraints. Furthermore, it is necessary to study the fluctuations of the total factor productivity (TFP) of the IT industry and the analysis of the influencing factors in China. This is not only a review of the past development of the IT industry of China, but also the IT in the new era and the new situation. The industry gives correspondingly targeted and feasible recommendations for China. This paper attempts to calculate the TFP of the IT industry of the 23 provinces in China from 2007 to 2016, describes the fluctuations of the TFP of IT industry in China, using the decomposition indicators to analyze the constituent factors and make recommendations. After the argumentation, this paper chose the DEA-Malquist index method and uses the Deap2.1 system. The empirical analysis found that the TFP of China’s IT industry fluctuated less, with an average annual growth rate of 10.7%. Its pure technical efficiency continues to be improving, and its scale efficiency is significant, but its regional differences are large. The differences are not only reflected in the relative value of inputs, but also in the progress of the productivity breakdown.
Single-muscle fiber contractile properties in lifelong aerobic exercising women
Authors: Gries Kevin J. , Minchev Kiril , Raue Ulrika , Grosicki Gregory J. , Begue Gwénaëlle , Finch W. Holmes , Graham Bruce , Trappe Todd A. , Trappe Scott 
Published: October 2019

The purpose of this study was to examine the effects of lifelong aerobic exercise on single-muscle fiber performance in trained women (LLE; n = 7, 72 ± 2 yr) by comparing them to old healthy nonexercisers (OH; n = 10, 75 ± 1 yr) and young exercisers (YE; n = 10, 25 ± 1 yr). On average, LLE had exercised ~5 days/wk for ~7 h/wk over the past 48 ± 2 yr. Each subject had a vastus lateralis muscle biopsy to examine myosin heavy chain (MHC) I and IIa single-muscle fiber size and function (strength, speed, power). MHC I fiber size was similar across all three cohorts (YE = 5,178 ± 157, LLE = 4,983 ± 184, OH = 4,902 ± 159 µm2). MHC IIa fiber size decreased ( P < 0.05) 36% with aging (YE = 4,719 ± 164 vs. OH = 3,031 ± 153 µm2), with LLE showing a similar 31% reduction (3,253 ± 189 µm2). LLE had 17% more powerful ( P < 0.05) MHC I fibers and offset the 18% decline in MHC IIa fiber power observed with aging ( P < 0.05). The LLE contractile power was driven by greater strength (+11%, P = 0.056) in MHC I fibers and elevated contractile speed (+12%, P < 0.05) in MHC IIa fibers. These data indicate that lifelong exercise did not benefit MHC I or IIa muscle fiber size. However, LLE had contractile function adaptations that enhanced MHC I fiber power and preserved MHC IIa fiber power through different contractile mechanisms (strength vs. speed). The single-muscle fiber contractile properties observed with lifelong aerobic exercise are unique and provide new insights into aging skeletal muscle plasticity in women at the myocellular level. NEW & NOTEWORTHY This is the first investigation to examine the effects of lifelong exercise on single-muscle fiber physiology in women. Nearly 50 yr of moderate to vigorous aerobic exercise training resulted in enhanced slow-twitch fiber power primarily by increasing force production, whereas fast-twitch fiber power was preserved primarily by increasing contractile speed. These unique muscle fiber power profiles helped offset the effects of fast-twitch fiber atrophy and highlight the benefits of lifelong aerobic exercise for myocellular health.
Cremaster muscle perfusion, oxygenation, and heterogeneity revealed by a new automated acquisition system in a rodent model of prolonged hemorrhagic shock
Authors: Torres Filho Ivo P. , Barraza David , Hildreth Kim , Williams Charnae , Dubick Michael A. 
Published: October 2019

Local blood flow/oxygen partial pressure (Po2) distributions and flow-Po2 relationships are physiologically relevant. They affect the pathophysiology and treatment of conditions like hemorrhagic shock (HS), but direct noninvasive measures of flow, Po2, and their heterogeneity during prolonged HS are infrequently presented. To fill this void, we report the first quantitative evaluation of flow-Po2 relationships and heterogeneities in normovolemia and during several hours of HS using noninvasive, unbiased, automated acquisition. Anesthetized rats were subjected to tracheostomy, arterial/venous catheterizations, cremaster muscle exteriorization, hemorrhage (40% total blood volume), and laparotomy. Control animals equally instrumented were not subjected to hemorrhage/laparotomy. Every 0.5 h for 4.5 h, noninvasive laser speckle contrast imaging and phosphorescence quenching were employed for nearly 7,000 flow/Po2 measurements in muscles from eight animals, using an automated system. Precise alignment of 16 muscle areas allowed overlapping between flow and oxygenation measurements to evaluate spatial heterogeneity, and repeated measurements were used to estimate temporal heterogeneity. Systemic physiological parameters and blood chemistry were simultaneously assessed by blood samplings replaced with crystalloids. Hemodilution was associated with local hypoxia, but increased flow prevented major oxygen delivery decline. Adding laparotomy and prolonged HS resulted in hypoxia, ischemia, decreased tissue oxygen delivery, and logarithmic flow/Po2 relationships in most regions. Flow and Po2 spatial heterogeneities were higher than their respective temporal heterogeneities, although this did not change significantly over the studied period. This quantitative framework establishes a basis for evaluating therapies aimed at restoring muscle homeostasis, positively impacting outcomes of civilian and military trauma/HS victims. NEW & NOTEWORTHY This is the first study on flow-Po2 relationships during normovolemia, hemodilution, and prolonged hemorrhagic shock using noninvasive methods in multiple skeletal muscle areas of monitored animals. Automated flow/Po2 measurements revealed temporal/spatial heterogeneities, hypoxia, ischemia, and decreased tissue oxygen delivery after trauma/severe hemorrhage. Hemodilution was associated with local hypoxia, but hyperemia prevented a major decline in oxygen delivery. This framework provides a quantitative basis for testing therapeutics that positively impacts muscle homeostasis and outcomes of trauma/hemorrhagic shock victims.
A Microbial Siderophore-Inspired Self-Gelling Hydrogel for Noninvasive Anticancer Phototherapy
Authors: Ko Seungbeom , Park Joo Yeon , Oh Yu-Kyoung 
Published: October 2019

Abstract

Microbial carboxyl and catechol siderophores have been shown to have natural iron-chelating abilities, suggesting that hyaluronic acid (HA) and the catechol compound, gallic acid (GA), may have iron-coordinating activities. Here, a photoresponsive self-gelling hydrogel that was both injectable and could be applied to the skin was developed on the basis of the abilities of HA and GA to form coordination bonds with ferric ions (Fe3+). The conjugate of HA and GA (HA–GA) instantly formed hydrogels in the presence of ferric ions and showed near-infrared (NIR)-responsive photothermal properties. Following their subcutaneous injection into mice, HA–GA and ferric ion formed a hydrogel, which remained at the injection site for at least 8 days. Intratumoral injection of HA-GA/Fe hydrogel into mice allowed repeated exposure of the tumor to NIR irradiation. This repeated NIR irradiation resulted in complete tumor ablation in KB carcinoma cell–xenografted mice and suppressed lung metastasis of 4T1-Luc orthotopic breast tumors. Application of HA-GA/Fe hydrogel to the skin of A375 melanoma-xenografted tumor sites, followed by NIR irradiation, also resulted in complete tumor ablation. These findings demonstrate that single applications of HA–GA/Fe hydrogel have photothermal anticancer effects against both solid tumors and skin cancers.

Significance:
These findings provide new insights into noninvasive anticancer phototherapy using self-gelling hydrogels. Application of these hydrogels in preclinical models reduces the sizes of solid tumors and skin cancers without surgery, radiation, or chemotherapy.
Natural Killer Cell–Derived Vesicular miRNAs: A New Anticancer Approach?
Authors: Fabbri Muller 
Published: October 2019

Abstract

Natural killer (NK) cells are cytotoxic lymphocytes targeting virus-infected cells and cancer cells. Specific pro- and antikilling signals modulate the overall ability of NK cells to kill cancer cells, however, several immune-escape mechanisms can be enacted by cancer cells to avoid NK-mediated killing. Recently, increasing evidence has shown that extracellular vesicles (EV) released by NK cells carry proteins and miRNAs able to exert an antitumoral effect, even within a highly immune-suppressive tumor microenvironment. These recent findings suggest a possible use of NK-derived EVs as anticancer agents and propel the development of new strategies to enrich EVs with the most effective anticancer cargo as a promising new anticancer approach.
EGFL7 Antagonizes NOTCH Signaling and Represents a Novel Therapeutic Target in Acute Myeloid Leukemia
Authors: Bill Marius , Pathmanathan Aparna , Karunasiri Malith , Shen Changxian , Burke Matthew H. , Ranganathan Parvathi , Papaioannou Dimitrios , Zitzer Nina C. , Snyder Katiri , LaRocco Allison , Walker Allison E. , Brannan Zachary J. , Nalin Ansel P. , Freud Aharon G. , Dikov Mikhail M. , Zhang Xiaoli , Bloomfield Clara D. , Garzon Ramiro , Dorrance Adrienne M. 
Published: October 2019

Abstract

Purpose:
EGF-like domain 7 (EGFL7) is a secreted protein and recently has been shown to play an important role in acute myeloid leukemia (AML); however, the underlying mechanism by which EGFL7 promotes leukemogenesis is largely unknown.

Experimental Design:
Using an antibody interaction array, we measured the ability of EGFL7 to bind directly approximately 400 proteins expressed by primary AML blasts. Primary patient samples were stimulated in vitro with recombinant EGFL7 (rEGFL7) or anti-EGFL7 blocking antibody to assess alterations in downstream signaling and the ability to effect blast differentiation and survival. We treated three independent AML models with anti-EGFL7 or IgG1 control to determine whether anti-EGFL7 could prolong survival in vivo.

Results:
We found EGFL7 significantly binds several signaling proteins important for normal and malignant hematopoiesis including NOTCH. Stimulation of AML blasts with rEGFL7 reduced NOTCH intracellular domain and NOTCH target gene expression while treatment with an anti-EGFL7 blocking antibody resulted in reactivation of NOTCH signaling, increased differentiation, and apoptosis. Competitive ligand-binding assays showed rEGFL7 inhibits DELTA-like (DLL) 4-mediated NOTCH activation while anti-EGFL7 combined with DLL4 significantly increased NOTCH activation and induced apoptosis. Using three different AML mouse models, we demonstrated that in vivo treatment with anti-EGFL7 alone results in increased survival.

Conclusions:
Our data demonstrate that EGFL7 contributes to NOTCH silencing in AML by antagonizing canonical NOTCH ligand binding. Reactivation of NOTCH signaling in vivo using anti-EGFL7 results in prolonged survival of leukemic mice, supporting the use of EGFL7 as a novel therapeutic target in AML.
Tumor-Specific Regulatory T Cells from the Bone Marrow Orchestrate Antitumor Immunity in Breast Cancer
Authors: Ge Yingzi , Böhm Hans-Henning , Rathinasamy Anchana , Xydia Maria , Hu Xiaoying , Pincha Mudita , Umansky Ludmila , Breyer Christopher , Hillier Michael , Bonertz Andreas , Sevko Alexandra , Domschke Christoph , Schuetz Florian , Frebel Helge , Dettling Steffen , Herold-Mende Christel , Reissfelder Christoph , Weitz Jürgen , Umansky Viktor , Beckhove Philipp 
Published: October 2019

AbstractEndogenous antitumor effector T-cell responses and immune-suppressive regulatory T cells (Treg) critically influence the prognosis of patients with cancer, yet many of the mechanisms of how this occurs remain unresolved. On the basis of an analysis of the function, antigen specificity, and distribution of tumor antigen–reactive T cells and Tregs in patients with breast cancer and transgenic mouse tumor models, we showed that tumor-specific Tregs were selectively activated in the bone marrow (BM) and egressed into the peripheral blood. The BM was constantly depleted of tumor-specific Tregs and was instead a site of increased induction and activity of tumor-reactive effector/memory T cells. Treg egress from the BM was associated with activation-induced expression of peripheral homing receptors such as CCR2. Because breast cancer tissues express the CCR2 ligand CCL2, the activation and egress of tumor antigen–specific Tregs in the BM resulted in the accumulation of Tregs in breast tumor tissue. Such immune compartmentalization and redistribution of T-cell subpopulations between the BM and peripheral tissues were achieved by vaccination with adenoviral vector–encoded TRP-2 tumor antigen in a RET transgenic mouse model of spontaneous malignant melanoma. Thus, the BM simultaneously represented a source of tumor-infiltrating Tregs and a site for the induction of endogenous tumor-specific effector T-cell responses, suggesting that both antitumor immunity and local immune suppression are orchestrated in the BM.
ApoE (Apolipoprotein E) in Brain Pericytes Regulates Endothelial Function in an Isoform-Dependent Manner by Modulating Basement Membrane Components
Authors: Yamazaki Yu , Shinohara Mitsuru , Yamazaki Akari , Ren Yingxue , Asmann Yan W. , Kanekiyo Takahisa , Bu Guojun 
Published: October 2019

Objective:

The ε4 allele of the
APOE
gene (
APOE4
) is the strongest genetic risk factor for Alzheimer disease when compared with the common ε3 allele. Although there has been significant progress in understanding how apoE4 (apolipoprotein E4) drives amyloid pathology, its effects on amyloid-independent pathways, in particular cerebrovascular integrity and function, are less clear.

Approach and Results:
Here, we show that brain pericytes, the mural cells of the capillary walls, differentially modulate endothelial cell phenotype in an apoE isoform-dependent manner. Extracellular matrix protein induction, tube-like structure formation, and barrier formation were lower with endothelial cells cocultured with pericytes isolated from apoE4-targeted replacement (TR) mice compared with those from apoE3-TR mice. Importantly, aged apoE4-targeted replacement mice had decreased extracellular matrix protein expression and increased plasma protein leakages compared with apoE3-TR mice.

Conclusions:
ApoE4 impairs pericyte-mediated basement membrane formation, potentially contributing to the cerebrovascular effects of apoE4.