bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesenchymal stem cell mediated effects on microglial phenotype in cuprizone‐induced demyelination model
Authors: Barati Shirin , Ragerdi Kashani Iraj , Moradi Fateme , Tahmasebi Fatemeh , Mehrabi Soraya , Barati Mahmood , Joghataei Mohammad Taghi 
Published: April 2019

AbstractMicroglial cells have an essential role in neurodegenerative disorders, such as multiple sclerosis. They are divided into two subgroups: M1 and M2 phenotypes. Mesenchymal stem cells (MSC), with neuroprotective and immunomodulating properties, could improve these diseases. We evaluate the immunomodulating effects of MSC on microglial phenotypes and the improvement of demyelination in a cuprizone (CPZ) model of multiple sclerosis (MS). For inducing the chronic demyelination model, C57BL6 mice were given a diet with 0.2% CPZ (w/w) for 12 weeks. In the MSC group, cells were transplanted into the right lateral ventricle of mice. The expression of targeted genes was assessed by real‐time polymerase chain reaction. M1 and M2 microglial phenotypes were assessed by immunohistochemistry of inducible nitric oxide synthase (iNOS) and Arg‐1, respectively. Remyelination was studied by luxal fast blue (LFB) staining and electron microscopy (EM). We found that MSC transplantation reduced the expression level of M1‐specific messenger RNA (mRNA; iNOS and CD86) but increased the expression level of M2 specific genes (CD206, Arg‐1, and CX3CR1) in comparison to the CPZ group. Moreover, cell therapy significantly decreased the M1 marker (iNOS+ cells), but M2 marker (Arg‐1+ cells) significantly increased in comparison with the CPZ group. In addition, MSC treatment significantly increased the CX3CL1 expression level in comparison with the CPZ group and led to improvement in remyelination, which was confirmed by LFB and EM images. The results showed that MSC transplantation increases the M2 and decreases the M1 phenotype in MS. This change was accompanied by decrease in demyelination and axonal injury and indicated that MSCs have a positive effect on MS by modification of microglia cells.
Oxidative stress upregulates Wnt signaling in human retinal microvascular endothelial cells through activation of disheveled
Authors: Zhang Chi , Tannous Elizabeth , Zheng Jie J. 
Published: April 2019

AbstractAbnormal retinal neovascularization associated with various retinopathies can result in irreversible vision loss. Although the mechanisms involved in this occurrence is unclear, increasing evidence suggests that aberrant Wnt signaling participates in the pathogenesis of abnormal neovascularization. Because Wnt signaling upregulation can be induced by oxidative stress through the activation of disheveled (DVL), a key molecule in the Wnt signaling pathway, we investigated whether oxidative stress can activate Wnt signaling and induce angiogenic phenotypes in human retinal microvascular endothelial cells (HRMECs). We found that increased Wnt signaling activity, as well as enhanced angiogenic phenotypes, such as tube formation and cell migration, were detected in the hydrogen peroxide‐treated HRMECs. Moreover, these effects were effectively suppressed by a small‐molecule Wnt inhibitor targeting the PDZ domain of DVL. Therefore, we propose that targeting abnormal Wnt signaling at the DVL level with a small‐molecule inhibitor may represent a novel approach in retinal neovascularization treatment and prevention.
An endoplasmic reticulum stress regulator, Tmbim6, modulates secretory stage of mice molar
Authors: Aryal Yam Prasad , Neupane Sanjiv , Adhikari Nirpesh , An Chang‐Hyeon , Ha Jung‐Hong , Kwon Tae‐Yub , Yamamoto Hitoshi , Jung Jae‐Kwang , Park Eui‐Kyun , Kim Ji‐Youn , Cho Sung‐Won , Sohn Wern‐Joo , Lee Youngkyun , Chae Han‐Jung , Kim Hyung‐Ryong , Kim Jae‐Young 
Published: April 2019

AbstractTo understand the role of endoplasmic reticulum (ER)‐stress in mice molar development, we studied Tmbim6 that antagonizes the unfolded protein response, using Tmbim6 knockout (KO) mice and in vitro organ cultivation with knocking down using small interfering RNA. During molar development, Tmbim6 is expressed in developing tooth at E14–E16, postnatal0 (PN0), and PN6. Mineral content in Tmbim6 KO enamel was reduced while dentin was slightly increased revealing ultrastructural changes in pattern formation of both enamel and dentin. Moreover, odontoblast differentiation was altered with increased Dspp expression at PN0 followed by altered AMELX localizations at PN5. These results were confirmed by in vitro organ cultivation and showed altered Bmp signaling, proliferation, and actin rearrangement in the presumptive ameloblast and odontoblasts that followed the altered expression of differentiation and ER stress‐related signaling molecules at E16.5. Overall, ER stress modulated by Tmbim6 would play important roles in patterned dental hard tissue formation in mice molar within a limited period of development.
Rapid clinical exome sequencing in a pediatric ICU: Genetic counselor impacts and challenges
Authors: Clowes Candadai Sarah V. , Sikes Megan C. , Thies Jenny M. , Freed Amanda S. , Bennett James T. 
Published: April 2019

AbstractExome sequencing (ES) has revolutionized molecular diagnosis in children with genetic disease over the past decade. However, exome sequencing in the inpatient setting has traditionally been discouraged, in part due to an increased risk of providers failing to retrieve and act upon results, as many patients are discharged before results return. The development of rapid turn‐around‐times (TATs) for genomic testing has begun to shift this paradigm. Rapid exome sequencing (rES) is increasingly being used as a diagnostic tool for critically ill infants with likely genetic disease and presents significant challenges to execute. We implemented a program, entitled the Rapid Inpatient Genomic Testing (RIGhT) project, to identify critically ill children for whom a molecular diagnosis is likely to change inpatient management. Two important goals of the RIGhT project were to provide appropriate genetic counseling, and to develop protocols to ensure efficient test coordination‐ both of which relied heavily on laboratory and clinic‐based genetic counselors (GCs). Here, rES was performed on 27 inpatient trios from October 2016 to August 2018; laboratory and clinical GCs encountered significant challenges in the coordination of this testing. The GCs involved retrospectively reviewed these cases and identified three common challenges encountered during pretest counseling and coordination. The aim of this paper is to define these challenges using illustrative case examples that highlight the importance of including GCs to support rES programs.
Moral emotions: A review and research agenda for management scholarship
Authors: Greenbaum Rebecca , Bonner Julena , Gray Truit , Mawritz Mary 
Published: April 2019

SummaryBy discussing “families” of moral emotions, we synthesize and review the moral emotions literature in an effort to advance organizational scholarship. First, we broadly discuss “what constitutes a moral emotion?” Second, we critically examine each family of moral emotions. We discuss key controversies and debates, particularly in terms of construct overlap, and provide recommendations. Third, we review scholarly work on each family of moral emotions in the workplace and offer ideas for future research. Finally, in our general future directions, we discuss a range of theoretical perspectives that can be used to advance the moral emotions literature in the management field.
Deep eutectic solvent as an operative media on structure‐reactivity relationships
Authors: Harifi‐Mood Ali Reza , Khorshahi Hasan 
Published: April 2019

AbstractDeep eutectic solvents seem to be environmentally friendly solvents, particularly because they are prepared easily and have very low‐vapor pressures under ambient conditions. They are suitable candidates as green solvents for reaction media with special properties. To present this behavior, substitution reactions of some para‐ and meta‐substituted anilines with 1‐fluoro‐2,4‐dinitrobenzene have been spectrophotometrically investigated in varying mole fractions of ethaline as a deep eutectic solvent in dimethyl sulfoxide (DMSO). The measured rate coefficients of the reaction demonstrated a noticeable variation with the increasing mole fraction of ethaline in ethaline‐DMSO mixtures. The linear free energy relationship (LFER) of second‐order rate coefficients based on Hammett's substituent constants demonstrates a reasonably linear straight line with a negative slope in different mole fractions of ethaline‐DMSO mixtures. Another LFER investigation based on the polarity parameters of the media showed a good agreement with hydrogen bond donor and acceptor abilities of the solvent. Non‐LFER assay according to the preferential solvation model confirmed differences between the microsphere solvation of the solute molecules and the bulk composition of the solvents.
Assessing fractional hair cell survival in archival human temporal bones
Authors: Wu Pei‐zhe , Wen Wei‐ping , O'Malley Jennifer T. , Liberman M. Charles 
Published: April 2019

Objectives/HypothesisHistopathological analysis of hair cell survival in human temporal bone sections has historically been binarized such that each hair cell row is rated as either present or absent, thereby greatly underestimating the amount of hair cell loss. Here, we describe and validate a technique to reliably assess fractional hair cell survival in archival sections stained with hematoxylin and eosin (H&E) using high‐resolution light microscopy and optical sectioning.Study DesignTechnique validation.MethodsHair cell counts in archival temporal bone slide sets were performed by several observers using either differential interference contrast (DIC) or confocal microscopy of the endogenous eosin fluorescence in hair cells. As a further cross‐check, additional decelloidinized sections were immunostained with hair cell markers myosin VI and VIIa.ResultsCuticular plates and stereocilia bundles are routinely resolvable in DIC imaging of archival H&E‐stained human material using standard research‐grade microscopes, allowing highly accurate counts of fractional hair cell survival that are reproducible across observer and can be verified by confocal microscopy.ConclusionsReanalysis of cases from the classic temporal bone literature on presbycusis suggests that, contrary to prior reports, differences in audiometric patterns may be well explained by the patterns of hair cell loss.Level of EvidenceNA Laryngoscope, 130:487–495, 2020
Healthy Nordic Diet Modulates the Expression of Genes Related to Mitochondrial Function and Immune Response in Peripheral Blood Mononuclear Cells from Subjects with Metabolic Syndrome–A SYSDIET Sub‐Study
Authors: Myhrstad Mari C. W. , de Mello Vanessa D. , Dahlman Ingrid , Kolehmainen Marjukka , Paananen Jussi , Rundblad Amanda , Carlberg Carsten , Olstad Ole Kristoffer , Pihlajamäki Jussi , Holven Kirsten B. , Hermansen Kjeld , Dragsted Lars O. , Gunnarsdottir Ingibjörg , Cloetens Lieselotte , Storm Matilda Ulmius , Åkesson Björn , Rosqvist Fredrik , Hukkanen Janne , Herzig Karl‐Heinz , Risérus Ulf , Thorsdottir Inga , Poutanen Kaisa S. , Savolainen Markku J , Schwab Ursula , Arner Peter , Uusitupa Matti , Ulven Stine M. 
Published: April 2019

ScopeTo explore the effect of a healthy Nordic diet on the global transcriptome profile in peripheral blood mononuclear cells (PBMCs) of subjects with metabolic syndrome.Methods and resultsSubjects with metabolic syndrome undergo a 18/24 week randomized intervention study comparing an isocaloric healthy Nordic diet with an average habitual Nordic diet served as control (SYSDIET study). Altogether, 68 participants are included. PBMCs are obtained before and after intervention and total RNA is subjected to global transcriptome analysis. 1302 probe sets are differentially expressed between the diet groups (p‐value < 0.05). Twenty‐five of these are significantly regulated (FDR q‐value < 0.25) and are mainly involved in mitochondrial function, cell growth, and cell adhesion. The list of 1302 regulated probe sets is subjected to functional analyses. Pathways and processes involved in the mitochondrial electron transport chain, immune response, and cell cycle are downregulated in the healthy Nordic diet group. In addition, gene transcripts with common motifs for 42 transcription factors, including NFR1, NFR2, and NF‐κB, are downregulated in the healthy Nordic diet group.ConclusionThese results suggest that benefits of a healthy diet may be mediated by improved mitochondrial function and reduced inflammation.
Synthesis and Feasibility Evaluation of a new Trastuzumab Conjugate Integrated with Paclitaxel and 89Zr for Theranostic Application Against HER2‐Expressing Breast Cancers
Authors: Jang Joo Hee , Han Sang Jin , Kim Jung Young , Kim Kwang Il , Lee Kyo Chul , Kang Chi Soo 
Published: April 2019

AbstractThe preparation and in vitro evaluation of a theranostic conjugate composed of trastuzumab, paclitaxel (PTX), and deferoxamine (DFO)‐chelated 89Zr have been reported. These comounds have potential applications against HER2 receptor positive breast cancers. We conjugated DFO and PTX to trastuzumab by exploiting simple conjugation chemistry. The conjugate (DFO‐trastuzumab‐PTX) showed excellent radiolabeling efficiency with 89Zr and the labeled conjugate had high in vitro stability in human serum. Furthermore, DFO‐trastuzumab‐PTX displayed comparable cytotoxicity with PTX and 89Zr‐DFO‐trastuzumab‐PTX exhibited HER2 receptor‐mediated binding on HER2‐positive MDA‐MB‐231 breast cancer cells. The results of our in vitro study indicate high potential of 89Zr‐DFO‐trastuzumab‐PTX to be utilized in the theranostic application against HER2‐postive breast cancers.
Synthesis and Pharmacological Screening of Pyridopyrimidines as Effective Anti‐Diarrheal Agents through the Suppression of Cyclic Nucleotide Accumulation
Authors: Zaminelli Tiago , Magli Elisa , Frecentese Francesco , Lescano Caroline H. , Campos Rafael , Saccone Irene , Corvino Angela , Di Vaio Paola , Giordano Flavia , Luciano Paolo , Fiorino Ferdinando , Perissutti Elisa , Santagada Vincenzo , Severino Beatrice , Caliendo Giuseppe , De Nucci Gilberto 
Published: April 2019

AbstractThe increased levels of cyclic nucleotides (cGMP and cAMP) in enterocytes trigger intracellular mechanisms of ion and fluid secretion into the lumen, causing secretory diarrhea. Twelve novel pyridopyrimidines derived from 5‐(3,5‐bistrifluoromethylphenyl)‐1,3‐dimethyl‐5,11‐dihydro‐1H‐indeno[2,1 : 5,6]pyrido[2,3‐d]pyrimidine‐2,4,6‐trione (FPIPP) were synthesized and evaluated on intracellular cyclic nucleotide accumulation. All compounds had no effect on either cyclic nucleotide basal levels or on pre‐contracted aortic rings. The metabolic activity and viability in T84 cells, assessed by MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide) and the LDH (lactate dehydrogenase) assays, respectively, were not affected by incubation with the compounds (50 μM). Compound VI almost abolished cGMP accumulation (94 % inhibition) induced by STa toxin in T834 cells and significantly reduced (69 %) forskolin‐induced cAMP accumulation in Jurkat cells. Compound VI was active in an in vivo model for diarrhea in rabbits. These results prompted us to perform a microscopic histopathological analysis of intestinal tissues, showing that only compound VI preserves the intestine without significant pathological changes and with a decreased inflammatory pattern in comparison to FPIPP. In vitro stability test revealed that compound VI is resistant to oxidation promoted by atmospheric oxygen.
Quantifying hydrologic alteration in an area lacking current reference conditions—The Mississippi alluvial plain of the south‐central United States
Authors: Hart Rheannon M. , Breaker Brian K. 
Published: April 2019

AbstractQuantifying hydrologic alteration in the Mississippi Alluvial Plain (MAP) of the south‐central United States is particularly difficult because of the lack of current reference, or even relatively undisturbed, streams and associated streamflow data. Impacts, such as water withdrawals for agriculture, weirs, dams, channelization, and other forms of regulation, within the MAP increased substantially beginning around 1960 suggesting that streamflow has since been altered. Using historical streamflow and climate data and explanatory variables, the U.S. Geological Survey developed random forest regression models to estimate expected reference monthly streamflows (pre‐1960) at 76 sites in the MAP and two adjacent Level III Ecoregions. To compensate for the lack of current reference stream sites in the study area, the pre‐1960 streamflow data were used as a surrogate to estimate current streamflow conditions without anthropogenic influence (inferring current reference conditions). Overall, nearly every site within the study area had less zero‐flow days than what historically has been observed and there were more low‐pulse spells. However, the frequency of floods remained relatively consistent.
A Sensitive Aptasensor Based on a Hemin/G‐Quadruplex‐Assisted Signal Amplification Strategy for Electrochemical Detection of Gastric Cancer Exosomes
Authors: Huang Rongrong , He Lei , Xia Yanyan , Xu Hongpan , Liu Chang , Xie Hui , Wang Su , Peng Lijun , Liu Yufeng , Liu Yuan , He Nongyue , Li Zhiyang 
Published: April 2019

AbstractEmerging evidence indicates that exosomes derived from gastric cancer cells enhance tumor migration and invasion through the modulation of the tumor microenvironment. However, it remains a major problem to detect cancer‐specific exosomes due to technical and biological challenges. Most of the methods reported could not achieve efficient detection of tumor‐derived exosomes in the background of normal exosomes. Herein, a label‐free electrochemical aptasensor is presented for specific detection of gastric cancer exosomes. This platform contains an anti‐CD63 antibody modified gold electrode and a gastric cancer exosome specific aptamer. The aptamer is linked to a primer sequence that is complementary to a G‐quadruplex circular template. The presence of target exosomes could trigger rolling circle amplification and produce multiple G‐quadruplex units. This horseradish peroxidase mimicking DNAzyme could catalyze the reduction of H2O2 and generate electrochemical signals. This aptasensor exhibits high selectivity and sensitivity toward gastric cancer exosomes with a detection limit of 9.54 × 102 mL−1 and a linear response range from 4.8 × 103 to 4.8 × 106 exosomes per milliliter. Therefore, this electrochemical aptasensor is expected to become a useful tool for the early diagnosis of gastric cancer.
Dementia: Paradigm shifting into high gear
Authors: Hachinski Vladimir 
Published: April 2019

AbstractRedressing the rising threat of dementia demands not only an increase, but a diversification of efforts. We need new approaches, trials, and partners. We cannot afford to continue to only round up the usual suspects, β amyloid, and tau and try to stop them with a single drug “silver bullet”. Dementia of late onset is not a disease, but an amalgam of interactive pathologies on the shifting background of aging, requiring multimodal targeting. Cerebrovascular diseases coexist and coact with all major neurodegenerative pathologies, increasing two‐fold the likelihood that they will manifest clinically. Cerebrovascular diseases need to be controlled, to give antidegenerative drugs a chance to succeed. This calls for new types of trials and designs. Stroke doubles the chances of developing dementia and decreases in stroke incidence correlate with decreases in dementia. Ninety percent of strokes are potentially preventable and so are a proportion of dementias. The stroke and dementia communities need to partner and complement the search for silver bullets with the golden opportunity of doing something now.
THE IDENTITY OF IDENTITY: MORAL AND LEGAL ASPECTS OF TECHNOLOGICAL
SELF-TRANSFORMATION
Authors: Shapiro Michael H. 
Published: April 2019

Technologies are being developed for significantly altering the traits
of existing persons (or fetuses or embryos) and of future persons via germ
line modification. The availability of such technologies may affect our
philosophical, legal, and everyday understandings of several important
concepts, including that of personal identity. I consider whether the idea
of personal identity requires reconstruction, revision or abandonment in
the face of such possibilities of technological intervention into the
nature and form of an individual's attributes. This requires an
account of the work done by the concept of personal identity, and an
explanation of what “conceptual impacts of technology” and
“conceptual reconstruction” might mean.Our existing notions of personal identity and related ideas such as
personhood and autonomy may seem unable to comfortably accommodate the
possibilities of technologically directed trait formation and development.
This is a matter of moral and legal importance because the idea of
personal identity embeds major values and reflects value-laden beliefs and
attitudes. The assumed endurance of identity underlies interpersonal
relationships, the assignment of rewards and punishments, and the very
idea of what constitutes an autonomous person. Perhaps radical
restructuring or even abandonment of concepts are sometimes called for
when the world changes drastically, but I suggest that conceptual
modification is not “compelled” for personal identity except
under extreme circumstances—the remote possibility of rapid human
“shape shifting” where physical and mentational attributes can
be transformed quickly and continuously.Efforts to enhance human traits, including merit attributes and other
resource-attractive characteristics (e.g., intellectual and
athletic aptitudes, physical size and appearance), may generate legal
problems wherever the persistence of identity is presupposed. Some advance
speculation is thus warranted on how trait change generally will be
managed within our legal and socioeconomic systems, and more particularly
on rights of access to trait-altering technologies. I mention the possible
distributive effects of enhancing highly-resource attractive traits,
including the strengthening individual powers to acquire still more
increments in such traits in a self-reinforcing cycle. A brief review of
some constitutional issues bearing on trait change completes the
discussion.I conclude that existing and projected technologies do not impel the
abandonment or remodeling of the idea of personal identity. We may,
however, have to reconsider some uses of this concept in different
settings, to rethink our understandings of ideas of merit and desert, and
to deal with the distribution of resources that may enlarge and entrench
the “distances” between social and economic groups.