bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multiparameter Flow Cytometry Analysis Panel to Assess CD163 mRNA and Protein in Monocyte and Macrophage Populations in Hyperinflammatory Diseases
Authors: Thornton Sherry , Tan Rachel , Sproles Alyssa , Do Thuy , Schick Jonathan , Grom Alexei A. , DeLay Monica , Schulert Grant S. 
Published: January 2019

Abstract
CD163 facilitates regulation and resolution of inflammation and removal of free hemoglobin and is highly expressed in myeloid cells from patients with inflammatory disorders, such as systemic juvenile idiopathic arthritis (SJIA) and macrophage activation syndrome (MAS). Our recent studies indicate that regulation of CD163 mRNA expression is a key functional property of polarized monocytes and macrophages and is mediated at the transcriptional and posttranscriptional level, including via microRNAs. The goal of the current study is to develop a multiparameter flow cytometry panel incorporating detection of CD163 mRNA for polarized monocyte and macrophage populations in disorders such as SJIA and MAS. THP-1 cells and CD14+ human monocytes were stained using fluorochrome-conjugated Abs to myeloid surface markers, along with CD163 mRNA. Staining for mRNA could reliably detect CD163 expression while simultaneously detecting different macrophage populations using Abs targeting CD14, CD64, CD80, CD163, and CD209. This approach was found to be highly sensitive for increased mRNA expression when macrophages were polarized with IL-10 [M(IL-10)], with a strong signal over a broad range of IL-10 concentrations, and showed distinct kinetics of CD163 mRNA and protein induction upon IL-10 stimulation. Finally, this panel demonstrated clear changes in polarization markers in unstimulated monocytes from patients with SJIA and MAS, including upregulated CD163 mRNA and increased CD64 expression. This approach represents a robust and sensitive system for RNA flow cytometry, useful for studying CD163 expression as part of a multimarker panel for human monocytes and macrophages, with broad applicability to the pathogenesis of hyperinflammatory diseases.
Re Carla: An Error in Judgment
Authors: Richards Bernadette J , Wisdom Travis Leal Couto 
Published: January 2019

As Justice Brennan succinctly explained in Department of Health and Community Services v JWB & SMB (Marion’s Case),[1] every person has a unique character and dignity that warrants respect and protection under the law. This extends to every member of society, whatever their race, gender, sexual orientation, sex characteristics or religion. If dignity is to be respected then the affected person should be at the centre of any enquiry, their preferences heard and their interests protected. Sadly however this ideal does not always translate into practice and a recent decision regarding surgical interventions on intersex children is an example of a situation in which the affected person’s rights and future interests were not afforded clear priority. The decision of Re: Carla (Medical Procedure) [2016] FamCA 7 (‘Re: Carla’) saw the Court handing full authority for decision-making to the parents and the medical fraternity. This withdrawal of the need for external scrutiny of an invasive and potentially non-therapeutic medical procedure signalled a retreat by the judiciary from any meaningful engagement with the child’s future preferences. In this article, we argue that this decision, whilst well intentioned is, quite simply, an error in judgment.

[1] Ibid.
Emotions, Feelings, and Social Change: Love, Anger, and Solidarity in Black Women’s AIDS Activism
Authors: Harris Angelique 
Published: January 2019

AbstractThis paper examines the emotions and feelings that influence AIDS activism work among a sample of black women. HIV/AIDS has disproportionately impacted black communities—black women, in particular. Not only do black women have the highest infection rates among women, but they are also often charged with caring for those infected. Consequently, black women have taken important steps in addressing HIV/AIDS in their communities, yet little is known about the emotions that motivate this activism work. Womanism—and its focus on intersecting identities, spirituality, and social justice—serves as the theoretical framework to examine the thoughts and related emotions expressed during interviews conducted with a sample of 36 activists from across the United States. Findings indicate these women’s activism was often fueled and maintained by feelings of love, anger, and solidarity.
Raziskovanje v družinski medicini v Sloveniji
Authors: Petek Šter Marija , Švab Igor , Petek Davorina 
Published: January 2019

Primarni nivo zdravstvenega varstva predstavlja vstopno mesto v zdravstveni sistem in od njega je v veliki meri odvisna kakovost in stroškovna vzdržnost zdravstvenega sistema. Raziskovanje je gonilo strokovnega razvoja v skrbi za čim boljšo kakovost oskrbe pacientov.Družinska medicina (DM) v Sloveniji predstavlja največjo specialnost na primarnem nivoju zdravstvenega varstva, ki je na področju raziskovanja v zadnjih desetletjih dosegla velike uspehe.V preglednem prispevku bodo prikazane značilnosti raziskovanja v družinski medicini, predstavljena vključenost raziskovanja v različne nivoje izobraževalnega procesa in delo v praksi ter nakazani izzivi, ki družinsko medicino kot znanstveno in raziskovalno vedo čakajo v prihodnje.
Oxytocin promotes coordinated out-group attack during intergroup conflict in humans
Authors: Zhang Hejing , Gross Jörg , De Dreu Carsten , Ma Yina 
Published: January 2019

Intergroup conflict contributes to human discrimination and violence, but persists because individuals make costly contributions to their group’s fighting capacity. Yet how group members effectively coordinate their contributions during intergroup conflict remains poorly understood. Here we examine the role of oxytocin for (the coordination of) contributions to group attack or defense in a multi-round, real-time feedback economic contest. In a double-blind placebo-controlled study with N=480 males in an Intergroup Attacker-Defender contest game, we found that oxytocin reduced contributions to attack and over time increased attacker’s within-group coordination of contributions. However, rather than becoming peaceful, attackers given oxytocin better tracked their rival’s historical defense and coordinated their contributions into well-timed and hence more profitable attacks. Our results reveal coordination of contributions as a critical component of successful attacks and subscribe to the possibility that oxytocin enables individuals to contribute to in-group efficiency and prosperity even when doing so implies outsiders are excluded or harmed.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).
Periventricular white matter changes in idiopathic intracranial hypertension
Authors: Sarica Alessia , Curcio Maria , Rapisarda Laura , Cerasa Antonio , Quattrone Aldo , Bono Francesco 
Published: January 2019

AbstractObjectiveTo evaluate whether increased cerebrospinal fluid (CSF) pressure causes alteration of periventricular white matter (WM) microstructure in patients with idiopathic intracranial hypertension (IIH).MethodsIn a prospective study, patients with refractory chronic headache with and without IIH performed a neuroimaging study including 3T MRI, 3D Phase Contrast MR venography, and diffusion tensor imaging (DTI) of the brain. Whole‐brain voxel‐wise comparisons of DTI abnormalities of WM were performed using tract‐based spatial statistics. A correlation analysis between DTI indices and CSF opening pressure, highest peak, and mean pressure was also performed in patients with IIH.ResultsWe enrolled 62 consecutive patients with refractory chronic headaches. Thirty‐five patients with IIH, and 27 patients without increased intracranial pressure. DTI analysis revealed no fractional anisotropy changes, but decreased mean, axial, and radial diffusivity in body (IIHMD = 0.80 ± 0.04, non‐IIHMD = 0.84 ± 0.4, IIHAD = 1.67 ± 0.07, non‐IIHAD = 1.74 ± 0.05, IIHRD = 0.38 ± 0.04, non‐IIHRD = 0.42 ± 0.05 [mm2/sec × 10−3]) of corpus callosum, and in right superior corona radiata (IIHMD = 0.75 ± 0.04, non‐IIHMD = 0.79 ± 0.05, IIHAD = 1.19 ± 0.07, non‐IIHAD = 1.28 ± 0.09, IIHRD = 0.59 ± 0.03, non‐IIHRD = 0.53 ± 0.03 [mm2/sec × 10−3]) of 35 patients with IIH compared with 27 patients without increased intracranial pressure. DTI indices were negatively correlated with high CSF pressures (P < 0.05). After medical treatment, eight patients showed incremented MD in anterior corona radiata left and right and superior corona radiata right.ConclusionsThere is significant DTI alteration in periventricular WM microstructure of patients with IIH suggesting tissue compaction correlated with high CSF pressure. This periventricular WM change may be partially reversible after medical treatment.
Real‐Time Interrogation of Aspirin Reactivity, Biochemistry, and Biodistribution by Hyperpolarized Magnetic Resonance Spectroscopy
Authors: Zacharias Niki M. , Ornelas Argentina , Lee Jaehyuk , Hu Jingzhe , Davis Jennifer S. , Uddin Nasir , Pudakalakatti Shivanand , Menter David G. , Karam Jose A. , Wood Christopher G. , Hawk Ernest T. , Kopetz Scott , Vilar Eduardo , Bhattacharya Pratip K. , Millward Steven W. 
Published: January 2019

AbstractHyperpolarized magnetic resonance spectroscopy enables quantitative, non‐radioactive, real‐time measurement of imaging probe biodistribution and metabolism in vivo. Here, we investigate and report on the development and characterization of hyperpolarized acetylsalicylic acid (aspirin) and its use as a nuclear magnetic resonance (NMR) probe. Aspirin derivatives were synthesized with single‐ and double‐13C labels and hyperpolarized by dynamic nuclear polarization with 4.7 % and 3 % polarization, respectively. The longitudinal relaxation constants (T1) for the labeled acetyl and carboxyl carbonyls were approximately 30 seconds, supporting in vivo imaging and spectroscopy applications. In vitro hydrolysis, transacetylation, and albumin binding of hyperpolarized aspirin were readily monitored in real time by 13C‐NMR spectroscopy. Hyperpolarized, double‐labeled aspirin was well tolerated in mice and could be observed by both 13C‐MR imaging and 13C‐NMR spectroscopy in vivo.
Photoredox‐Catalyzed Cyclobutane Synthesis by a Deboronative Radical Addition–Polar Cyclization Cascade
Authors: Shu Chao , Noble Adam , Aggarwal Varinder K. 
Published: January 2019

AbstractPhotoredox‐catalyzed methylcyclobutanations of alkylboronic esters are described. The reactions proceed through single‐electron transfer induced deboronative radical addition to an electron‐deficient alkene followed by single‐electron reduction and polar 4‐exo‐tet cyclization with a pendant alkyl halide. Key to the success of the methodology was the use of easily oxidizable arylboronate complexes. Structurally diverse cyclobutanes are shown to be conveniently prepared from readily available alkylboronic esters and a range of haloalkyl alkenes. The mild reactions display excellent functional group tolerance, and the radical addition‐polar cyclization cascade also enables the synthesis of 3‐, 5‐, 6‐, and 7‐membered rings.
Molecular characterization and expression patterns of Phenacoccus solenopsis (Hemiptera: Pseudococcidae) heat shock protein genes and their response to host stress
Authors: Liu Dan , Dang Xiangli , Song Wei , Xi Lingyu , Wang Qi , Zhang Shaobing , Miao Yong , Li Guiting , Jiang Junqi 
Published: January 2019

AbstractAs a polyphagous insect, little is known at the molecular level about the effects of different host plants on physiological changes in Phenacoccus solenopsis. In this study, four heat shock protein (Hsp) genes (PsHsp60, PsHsp70, PsHsp90, and PsHsp20.7) were identified from the transcriptome of P. solenopsis. Analysis of Hsp expression levels revealed significant differences in Hsp gene expression levels in P. solenopsis fed on different host plants. In host conversion tests, the expression levels of PsHsp90 and PsHsp60 were upregulated after transfer of second instar nymphs from tomato to cotton. The expression levels of PsHsp70 and PsHsp20.7 were, respectively, significantly upregulated at 9 and 48 hr after transfer from tomato to Hibiscus. The results of this study aid molecular characterization and understanding of the expression patterns of Hsp genes during different developmental stages and host transfer of P. solenopsis.
Exploiting the Aromatic Chameleon Character of Fulvenes for Computational Design of Baird‐Aromatic Triplet Ground State Compounds
Authors: Yadav Sangeeta , El Bakouri Ouissam , Jorner Kjell , Tong Hui , Dahlstrand Christian , Solà Miquel , Ottosson Henrik 
Published: January 2019

AbstractDue to the reversal in electron counts for aromaticity and antiaromaticity in the closed‐shell singlet state (normally ground state, S0) and lowest ππ* triplet state (T1 or T0), as given by Hückel's and Baird's rules, respectively, fulvenes are influenced by their substituents in the opposite manner in the T1 and S0 states. This effect is caused by a reversal in the dipole moment when going from S0 to T1 as fulvenes adapt to the difference in electron counts for aromaticity in various states; they are aromatic chameleons. Thus, a substituent pattern that enhances (reduces) fulvene aromaticity in S0 reduces (enhances) aromaticity in T1, allowing for rationalizations of the triplet state energies (ET) of substituted fulvenes. Through quantum chemical calculations, we now assess which substituents and which positions on the pentafulvene core are the most powerful for designing compounds with low or inverted ET. As a means to increase the π‐electron withdrawing capacity of cyano groups, we found that protonation at the cyano N atoms of 6,6‐dicyanopentafulvenes can be a route to on‐demand formation of a fulvenium dication with a triplet ground state (T0). The five‐membered ring of this species is markedly Baird‐aromatic, although less than the cyclopentadienyl cation known to have a Baird‐aromatic T0 state.
Engineering the migration and attachment behaviour of primary dermal fibroblasts
Authors: García‐Gareta Elena , Levin Alexandra , Hook Lilian 
Published: January 2019

AbstractThe availability of primary cells present in pathological conditions is often very limited due to stringent ethical regulation and patient consent. One such condition is chronic wounds, where dermal fibroblasts show a deficient migration. In vitro models with cellular tools that mimic the in vivo scenario would be advantageous to test new therapies for these challenging wounds. Since the availability of primary dermal fibroblasts present in chronic wounds is restricted and their “shelf‐life” limited due to the increased senescence, our aim was to engineer human dermal fibroblasts with impaired migration using synthetic Arg‐Gly‐Asp (RGD) peptides. We studied fibroblast behaviour on three different two dimensional (2D) surfaces, representative of the dermal extracellular matrix and the materials used in the development of dermal scaffolds, in addition to commercially available, collagen‐based 3D dermal scaffolds, demonstrating that the concentration of synthetic RGD peptides necessary to impair migration of dermal fibroblasts should be tailored to the particular surface/material and cell population used. The described technology could be translated to other cell types including established cell lines. A wide range of synthetic peptides exists, which differ in the amino acid sequence, thus increasing the possibilities of this technology.
Generation of site‐distinct N‐glycan variants for in vitro bioactivity testing
Authors: Brühlmann David , Vuillemin Thomas , Satwekar Abhijeet , Galano Eugenio , Palmese Angelo , D'Angelo Alessandra , Manco Zeynep , Souquet Jonathan , Broly Hervé , Sauer Markus , Hemberger Jürgen , Jordan Martin 
Published: January 2019

AbstractGlycosylation, a critical product quality attribute, may affect the efficacy and safety of therapeutic proteins in vivo. Chinese hamster ovary fed‐batch cell culture batches yielded consistent glycoprofiles of a Fc‐fusion antibody comprizing three different N‐glycosylation sites. By adding media supplements at specific concentrations in cell culture and applying enzymatic glycoengineering, a diverse N‐glycan variant population was generated, including high mannose, afucosylated, fucosylated, agalactosylated, galactosylated, asialylated, and sialylated forms. Site‐specific glycosylation profiles were elucidated by glycopeptide mapping and the effect of the glycosylation variants on the FcγRIIIa receptor binding affinity and the biological activity (cell‐based and surface plasmon resonance) was assessed. The two fusion body glycosylation sites were characterized by a high degree of sialic acid, more complex N‐glycan structures, a higher degree of antennarity, and a site‐specific behavior in the presence of a media supplement. On the other hand, the media supplements affected the Fc‐site glycosylation heterogeneity similarly to the various studies described in the literature with classical monoclonal antibodies. Enzymatic glycoengineering solely managed to generate high levels of galactosylation at the fusion body sites. Variants with low core fucosylation, and to a lower extent, high mannose glycans exhibited increased FcγRIIIa receptor binding affinity. All N‐glycan variants exhibited weak effects on the biological activity of the fusion body. Both media supplementation and enzymatic glycoengineering are suitable to generate sufficient diversity to assess the effect of glycostructures on the biological activity.
Engineering Escherichia coli as a platform for the in vivo synthesis of prenylated aromatics
Authors: Qian Shuai , Clomburg James M. , Gonzalez Ramon 
Published: January 2019

AbstractPrenylated aromatics (PAs) are an important class of natural products with valuable pharmaceutical applications. To address current limitations of their sourcing from plants, here, we present a microbial platform for the in vivo synthesis of PAs based on the aromatic prenyltransferase NphB from Streptomyces sp. strain CL190. As proof of concept, we targeted the prenylation of phenolic/phenolcarboxylic acids, including orsellinic (OSA), divarinolic (DVA), and olivetolic (OLA) acids, whose prenylated products have important biopharmaceutical applications. Although the ability of wild‐type NphB to catalyze the prenylation reaction with each acid was validated by in vitro characterization, improvement of product titers in vivo required protein modeling and rational design to engineer NphB variants with increased activity and product selectivity. When a designed NphB variant with eightfold improved catalytic efficiency toward OSA was expressed in an Escherichia coli host engineered to generate geranyl pyrophosphate at high flux through the mevalonate pathway, we observed up to 300 mg/L prenylated products by exogenously supplying OSA. The improved properties of engineered NphB were also utilized to demonstrate the diversification of this in vivo platform by using both different aromatic acceptors and different prenyl donors to generate various PA compounds, including medicinally important compounds such as cannabigerovarinic, cannabigerolic, and grifolic acids.
Local direction change of surface gliding microtubules
Authors: Li Feiran , Pan Jing , Choi Jong Hyun 
Published: January 2019

AbstractIn vitro gliding assay, microtubule translocation by kinesin motor proteins on a surface, has been used as an engineering tool in analyte detection, molecular cargo transport, and other applications. Although controlling the moving direction is often necessary to realize these applications, current direction control methods focus largely on lithographic microfabrication of tracks or external fields on the microtubules. These methods are effective, but are relatively complicated. In addition, they cannot target particular microtubules without affecting others. In this study, we propose a facile approach that can make local direction changes for selected microtubules using a polystyrene particle as a circular motion center and a DNA double helix with streptavidin as a capture arm. The DNA arm captures a microtubule in the close proximity of the immobilized particle via biotin–streptavidin interaction and changes the moving direction ~10° on average. In contrast, no significant direction changes are observed other than random variations with streptavidin‐less DNA arms (normal distribution centered at 0°), similar to regular motility assay. The particle‐assisted local direction change scheme is compared with a flow field‐based ensemble method. The combination of flow and kinesin interactions with each microtubule exerts a force to change the direction, ultimately aligning it to the flow field, regardless of its initial direction. A simple model based on the force balance predicts the time needed for such an alignment. Overall, the particle‐based local scheme is distinct and different from ensemble methods such as crossflow that changes directions of all microtubules in the field, thus offering unique utility in engineering applications.
Prognostic significance of PD‐L2 expression in patients with oral squamous cell carcinoma—A comparison to the PD‐L1 expression profile
Authors: Weber Manuel , Wehrhan Falk , Baran Christoph , Agaimy Abbas , Büttner‐Herold Maike , Kesting Marco , Ries Jutta 
Published: January 2019

AbstractBackgroundDespite the observed association of increased PD‐L1 expression in peripheral blood of oral squamous cell carcinoma (OSCC) patients with histomorphologic parameters, the role of the PD1 ligands—PD‐L1 and PD‐L2—is insufficiently understood. Aim of the study was to investigate whether the alterations of PD‐L1 and PD‐L2 expression in blood are associated with survival and could serve as immune monitoring parameter. Moreover, it should be analyzed if PD‐L2 is differentially expressed in tissue and blood samples of OSCC patients compared to healthy controls and if there is an association of PD‐L2 expression with histomorphologic and prognostic tumor parameters.MethodsPD‐L2 mRNA expression was analyzed in tumors and healthy oral mucosa specimens and in corresponding peripheral blood samples of 48 OSCC patients and 26 healthy controls using RT‐qPCR. A cutoff point (COP) was determined and a chi‐square test (χ2 test) was carried out. Survival analysis of PD‐L2 and previously reported PD‐L1 expression data was performed using Kaplan‐Meier analysis (Log‐rank test).ResultsPD‐L2 expression in tissue samples was significantly (P < 0.001) higher in OSCC patients compared to healthy controls. A significant association of PD‐L2 expression above the COP (positive) with malignancy was ascertained (P < 0.001). A significant (P = 0.01) association of previously reported PD‐L1 expression rates in peripheral blood with survival could be shown.ConclusionPeripheral blood PD‐L1 expression might be a prognostic marker for OSCC patients and a possible parameter to monitor immune dysfunction in malign diseases. In the peripheral blood, PD‐L1 might be more relevant for immune tolerance than PD‐L2. Local PD‐L2 expression in tissue samples might be useful as a diagnostic parameter for malignancy and could contribute to the immunosuppressive local microenvironment in OSCC.