bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anticancer effects of chemokine-directed antigen delivery to a cross-presenting dendritic cell subset with immune checkpoint blockade
Authors: Mizumoto Yuki , Hemmi Hiroaki , Katsuda Masahiro , Miyazawa Motoki , Kitahata Yuji , Miyamoto Atsushi , Nakamori Mikihito , Ojima Toshiyasu , Matsuda Kenji , Nakamura Masaki , Hayata Keiji , Fukuda-Ohta Yuri , Sugiyama Masanaka , Ohta Tomokazu , Orimo Takashi , Okura Soichiro , Sasaki Izumi , Tamada Koji , Yamaue Hiroki , Kaisho Tsuneyasu 
Published: February 2020

AbstractBackgroundCancer peptide vaccines show only marginal effects against cancers. Immune checkpoint inhibitors (ICIs) show significant curative effects in certain types of cancers, but the response rate is still limited. In this study, we aim to improve cancer peptide vaccination by targeting Ag peptides selectively to a dendritic cell (DC) subset, XCR1-expressing DCs (XCR1+DCs), with high ability to support CD8+T-cell responses.MethodsWe have generated a fusion protein, consisting of an Ag peptide presented with MHC class I, and an XCR1 ligand, XCL1, and examined its effects on antitumour immunity in mice.ResultsThe fusion protein was delivered to XCR1+DCs in an XCR1-dependent manner. Immunisation with the fusion protein plus an immune adjuvant, polyinosinic:polycytidylic acids (poly(I:C)), more potently induced Ag-specific CD8+T-cell responses through XCR1 than the Ag peptide plus poly(I:C) or the Ag protein plus poly(I:C). The fusion protein plus poly(I:C) inhibited the tumour growth efficiently in the prophylactic and therapeutic tumour models. Furthermore, the fusion protein plus poly(I:C) showed suppressive effects on tumour growth in synergy with anti-PD-1 Ab.ConclusionsCancer Ag targeting to XCR1+DCs should be a promising procedure as a combination anticancer therapy with immune checkpoint blockade.
Sestrin2 protects dendritic cells against endoplasmic reticulum stress-related apoptosis induced by high mobility group box-1 protein
Authors: Wang Li-Xue , Zhu Xiao-Mei , Luo Yi-Nan , Wu Yao , Dong Ning , Tong Ya-lin , Yao Yong-Ming 
Published: February 2020

AbstractSestrin2 (SESN2) is a highly evolutionary conserved protein and involved in different cellular responses to various stresses. However, the potential function of SESN2 in immune system remains unclear. The present study was designed to test whether dendritic cells (DCs) could express SESN2, and investigate the underlying molecular mechanism as well as its potential significance. Herein, we firstly reported that SESN2 was expressed in DCs after high mobility group box-1 protein (HMGB1) stimulation and the apoptosis of DCs was obviously increased when SESN2 gene silenced by siRNA. Cells undergone SESN2-knockdown promoted endoplasmic reticulum (ER) stress (ERS)-related cell death, markedly exacerbated ER disruption as well as the formation of dilated and aggregated structures, and they significantly aggravated the extent of ERS response. Conversely, overexpressing SESN2 DCs markedly decreased apoptotic rates and attenuated HMGB1-induced ER morphology fragment together with inhibition of ERS-related protein translation. Furthermore, sesn2−/−-deficient mice manifested increased DC apoptosis and aggravated ERS extent in septic model. These results indicate that SESN2 appears to be a potential regulator to inhibit apoptotic ERS signaling that exerts a protective effect on apoptosis of DCs in the setting of septic challenge.
Inhibition of IκBα phosphorylation potentiates regulated cell death induced by azidothymidine in HTLV-1 infected cells
Authors: Matteucci Claudia , Marino-Merlo Francesca , Minutolo Antonella , Balestrieri Emanuela , Valletta Elena , Macchi Beatrice , Mastino Antonio , Grelli Sandro 
Published: February 2020

AbstractAdult T cell leukemia/lymphoma (ATL) can be susceptible, at least transiently, to treatments with azidothymidine (AZT) plus IFNα and/or arsenic trioxide. However, the real role of AZT in this effect is still unclear. In fact, while reverse transcriptase (RT) inhibition could explain reduction of clonal expansion and of renewal of HTLV-1 infected cells during ATL progression, this effect alone seems insufficient to justify the evident and prompt decrease of the pro-viral load in treated patients. We have previously demonstrated that AZT is endowed with an intrinsic pro-apoptotic potential towards both peripheral blood mononuclear cells from healthy donors or some tumor cell lines, but this cytotoxic potential cannot be fully achieved unless IκBα phosphorylation is inhibited. Since the constitutive activation of NF-kappa B (NF-κB) appears a common biological basis of HTLV-1-infected cells, a pharmacological inhibition of IκBα phosphorylation seems a potential strategy for treating and preventing HTLV-1 related pathologies. In this study, we have demonstrated that a combination treatment with the IκBα phosphorylation inhibitor Bay 11-7085 and AZT induced increased levels of regulated cell death (RCD) by apoptosis compared to the single treatments in HTLV-1 infected cells of different origin. Importantly, levels of RCD were considerably higher in infected cells in comparison with the uninfected ones. Inhibition of NF-κB activation following the combined treatment was confirmed by analysis of both gel-shift and functional activity of the NF-κB complex proteins, p65/p52. Moreover, a transcriptional analysis revealed that the addition of Bay 11-7085 to AZT treatment in HTLV-1-infected cells modified their transcriptional profile, by inducing the upregulation of some pro-apoptotic genes together with the downregulation of some anti-apoptotic genes. Our data suggest that addition of adequate concentrations of IκBα phosphorylation inhibitor to therapeutic regimens including AZT could be a promising strategy in ATL.
Assessment of modelling strategies for drug response prediction in cell lines and xenografts
Authors: Kurilov Roman , Haibe-Kains Benjamin , Brors Benedikt 
Published: February 2020

AbstractData from several large high-throughput drug response screens have become available to the scientific community recently. Although many efforts have been made to use this information to predict drug sensitivity, our ability to accurately predict drug response based on genetic data remains limited. In order to systematically examine how different aspects of modelling affect the resulting prediction accuracy, we built a range of models for seven drugs (erlotinib, pacliatxel, lapatinib, PLX4720, sorafenib, nutlin-3 and nilotinib) using data from the largest available cell line and xenograft drug sensitivity screens. We found that the drug response metric, the choice of the molecular data type and the number of training samples have a substantial impact on prediction accuracy. We also compared the tasks of drug response prediction with tissue type prediction and found that, unlike for drug response, tissue type can be predicted with high accuracy. Furthermore, we assessed our ability to predict drug response in four xenograft cohorts (treated either with erlotinib, gemcitabine or paclitaxel) using models trained on cell line data. We could predict response in an erlotinib-treated cohort with a moderate accuracy (correlation ≈ 0.5), but were unable to correctly predict responses in cohorts treated with gemcitabine or paclitaxel.
Effect of nanoencapsulation on volatile constituents, and antioxidant and anticancer activities of Algerian Origanum glandulosum Desf. essential oil
Authors: Ali Hatem , Al-Khalifa Abdel Rahman , Aouf Abdelhakim , Boukhebti Habiba , Farouk Amr 
Published: February 2020

AbstractNanoencapsulation is an attractive novel technique used for incorporating essential oils in food preparations and pharmaceutical formulae. This study investigated the effect of nanoencapsulation on the composition of volatile compounds, as well as the antioxidant and anticancer activities of hydrodistilled (HD)Origanum glandulosumDesf. Oil, which was encapsulated into nanocapsules via High Speed Homogenization (HSH) and into nanoemulsions through High Pressure Homogenization (HPH). Thirty-two volatile components were identified using Gas Chromatography-Mass Spectrometry analysis (GC-MS) in HD essential oil representing 99.04% of the total oil content. GC-MS analysis showed that the use of HPH to prepare nanoemulsions negatively affected the active compounds present in HD oil, particularly carvacrol and thymol, whereas the use of HSH led to significant quantitative differences in the composition of volatiles between HD oil and nanocapsules but generated the same profile. Consistent with the differences in total phenolics, total flavonoids, and volatiles identified in HD and nanoparticles, HD essential oil exhibited a higher antioxidant activity (IC504.22 mg/mL) than nanocapsules (IC5057.51 mg/mL) and nanoemulsion (IC5078.50 mg/mL), while nanocapsules showed the strongest cytotoxic effect on liver cancer cell line Hep-G2 (54.93 μg/mL) in comparison to HD oil (73.13 μg/mL) and nanoemulsions (131.6 μg/mL).
Reduced micromorphic model in orthogonal curvilinear coordinates and its application to a metamaterial hemisphere
Authors: El Dhaba A. R. 
Published: February 2020

AbstractThe reduced micromorphic model (RMM) is used to study the effect of the applied force on a hemisphere made of phononic crystals that belongs to the metamaterials group. The strain tensor, the micro-strain tensor and the coupling between them are the kinematic relations used to measure the deformation and micro-deformation of the representative volume element of these materials. The free energy function, the constitutive relations, the field equations, and the boundary conditions are presented firstly in the Cartesian coordinate. Then, the orthogonal curvilinear coordinates are introduced as a general coordinate to describe the physical quantities included in the RMM. The spherical coordinates are deduced as a special case from the curvilinear coordinates to study the deformation and micro-deformation for the hemisphere. The kinematic relations and the governing equations of the model are considered to changing with the radius of the hemisphere only. The analytical solutions of the field equations are also obtained by using the Frobenius series satisfying the given boundary conditions and consequently the value of the physical constants of the problem is determined. Numerical applications for the obtained results are introduced with discussion. The results showed that the displacement has a greater effect rather than the micro-strain, when it is measured relative to the classical physical quantities while the micro-strain has a greater effect rather than the displacement, when it is measured relative to the nanoscale physical quantities.
Transcriptome Analysis Reveals Biosynthesis of Important Bioactive Constituents and Mechanism of Stem Formation of Dendrobium huoshanense
Authors: Zhou Peina , Pu Tianzhen , Gui Chun , Zhang Xiuqiao , Gong Ling 
Published: February 2020

AbstractThe stem of Dendrobium huoshanense C.Z. Tang and S.J. Cheng was widely used as a medicinal herb in health care products due to its broad pharmacological activities. However, the molecular regulation mechanism of stem development and biosynthetic pathways of important bioactive substances are still unclear in D. huoshanense. In this study, the bioactive compounds in leaves, stems and roots, and the identification of candidate genes involved in stem formation and biosynthesis of active compounds via transcriptome sequence were analyzed. The accumulation of total polysaccharides and flavonoids were varied significantly in different tissues. A comparative transcriptomic analysis revealed several differentially expressed genes (DEGs) involved in polysaccharides biosynthesis (103 genes), including fructose and mannose related genes (29 genes) and glycosyltransferase genes (74 genes), and flavonoids biosynthesis (15 genes). Some candidate genes that participated in photoperiod regulation (27 genes), starch and sucrose metabolism (46 genes), and hormone-induced activation of signaling pathways (38 genes) may be involved in stem formation. In sum, this study provides a foundation for investigating the molecular processes in the biosynthesis of active compounds and stem development. The transcriptome data presented here provides an important resource for the future studies of the molecular genetics and functional genomics in D. huoshanense and optimized control of the active compounds produced by D. huoshanense.
Turbulent viscosity and magnetic Prandtl number from simulations of isotropically forced turbulence
Authors: Käpylä P. J. , Rheinhardt M. , Brandenburg A. , Käpylä M. J. 
Published: February 2020

Context.Turbulent diffusion of large-scale flows and magnetic fields plays a major role in many astrophysical systems, such as stellar convection zones and accretion discs.Aims.Our goal is to compute turbulent viscosity and magnetic diffusivity which are relevant for diffusing large-scale flows and magnetic fields, respectively. We also aim to compute their ratio, which is the turbulent magnetic Prandtl number, Pmt, for isotropically forced homogeneous turbulence.Methods.We used simulations of forced turbulence in fully periodic cubes composed of isothermal gas with an imposed large-scale sinusoidal shear flow. Turbulent viscosity was computed either from the resulting Reynolds stress or from the decay rate of the large-scale flow. Turbulent magnetic diffusivity was computed using the test-field method for a microphysical magnetic Prandtl number of unity. The scale dependence of the coefficients was studied by varying the wavenumber of the imposed sinusoidal shear and test fields.Results.We find that turbulent viscosity and magnetic diffusivity are in general of the same order of magnitude. Furthermore, the turbulent viscosity depends on the fluid Reynolds number (Re) and scale separation ratio of turbulence. The scale dependence of the turbulent viscosity is found to be well approximated by a Lorentzian. These results are similar to those obtained earlier for the turbulent magnetic diffusivity. The results for the turbulent transport coefficients appear to converge at sufficiently high values of Re and the scale separation ratio. However, a weak trend is found even at the largest values of Re, suggesting that the turbulence is not in the fully developed regime. The turbulent magnetic Prandtl number converges to a value that is slightly below unity for large Re. For small Re we find values between 0.5 and 0.6 but the data are insufficient to draw conclusions regarding asymptotics. We demonstrate that our results are independent of the correlation time of the forcing function.Conclusions.The turbulent magnetic diffusivity is, in general, consistently higher than the turbulent viscosity, which is in qualitative agreement with analytic theories. However, the actual value of Pmtfound from the simulations (≈0.9−0.95) at large Re and large scale separation ratio is higher than any of the analytic predictions (0.4−0.8).
Prophylactic surgical drainage is associated with increased infection following intramedullary nailing of diaphyseal long bone fractures: A prospective cohort study in Nigeria
Authors: Oguzie Gerald Chukwuemeka , Albright Patrick , Ali Syed Haider , Duru Ndubuisi E. , Iyidobi Emmanuel Chino , Lasebikan Omolade Ayoola , Chukwumam Denning C. , Wu Hao-Hua , Ikpeme Ikpeme A. 
Published: February 2020

Introduction: Prophylactic surgical drains are commonly used in Nigeria following intramedullary nailing (IMN) of long bone diaphyseal fractures. However, evidence in the literature suggests that drains do not confer any benefit and predispose clean wounds to infection. This study compares outcomes between patients treated with and without prophylactic surgical drainage following diaphyseal long bone fractures treated with IMN.Methods: A prospective cohort study with randomization was conducted at a tertiary referral center in Enugu, Nigeria. Investigators included skeletally mature patients with diaphyseal long bone (femur, tibia, humerus) fractures treated with SIGN IMN. Patients followed-up at 5, 14, and 30 days post-operatively. The primary outcome was surgical site infection (SSI) rate. Secondary outcomes included post-operative pain at 6 and 12 h, need for blood transfusion, wound characteristics (swelling, ecchymosis, and gaping), need for dressing changes, and length of hospital stay.Results: Of the enrolled patients, 76 (96%) of 79 completed 30-day follow-up. SSI rate was associated with patients who received a prophylactic drain versus those who did not (23.7% vs. 10.5%,p = 0.007). There were no significant differences in transfusion need (p = 0.22), wound swelling (p = 0.74), wound ecchymosis (p = 1.00), wound gaping (p = 1.00), dressing change need (p = 0.31), post-operative pain at 6 h (p = 0.25) or 12 h (p = 0.57), or length of stay (p = 0.95).Discussion: Surgical drain placement following IMN of diaphyseal long bone fractures is associated with a significantly higher risk of SSI. Reducing surgical drain use following orthopaedic injuries in lower resource settings may translate to reduced infection rates.
Ernährungsperiodisierung im Sport
Authors: Hottenrott Kuno 
Published: February 2020

SummarySportler, die ihre Ernährung an das Training anpassen, können ihre Leistungsfähigkeit erhöhen und die Regeneration verbessern. Eine Ernährungsperiodisierung wie das Intervallfasten oder der vorübergehende Verzicht auf eine energetisch ausreichende Nahrungsaufnahme, kann die Reizwirksamkeit des Trainings erhöhen. Davon profitieren insbesondere Sportler, die eine Veränderung der Körperzusammensetzung bewirken wollen.
Die DFG Nachwuchsakademie 2017 – Wissenschaftliche
Nachwuchsförderung in der Versorgungsforschung
Authors: Herber Oliver Rudolf , Wilm Stefan , Fiege Annett , Ernstmann Nicole , Pfaff Holger , Icks Andrea 
Published: February 2020

ZusammenfassungDie vierte Nachwuchsakademie „Versorgungsforschung“ wurde 2017
erneut von der Deutschen Forschungsgemeinschaft (DFG) finanziell
gefördert. Initiator war das Centre for Health and Society (chs) der
Heinrich-Heine-Universität in Düsseldorf unter Beteiligung des
Zentrums für Versorgungsforschung Köln (ZVFK), der
Forschungsstelle für Gesundheitskommunikation und Versorgungsforschung
(CHSR) der Klinik und Poliklinik für Psychosomatische Medizin und
Psychotherapie des Universitätsklinikums Bonn, des
Interdisziplinären Zentrums für Versorgungsforschung im
Gesundheitswesen (IZVF) in Witten und des Instituts für
Versorgungsforschung und Klinische Epidemiologie (IVE) der Universität
Marburg. Ziele der Nachwuchsakademie umfassen die Vermittlung von Kompetenzen im
Entwickeln und Ausarbeiten von innovativen Projektideen, die Erhöhung
der Anzahl der Anträge aus dem Bereich der Versorgungsforschung an die
DFG, die Stärkung der Grundlagenforschung innerhalb der
Versorgungsforschung in Deutschland und die Vernetzung der wissenschaftlichen
Community. Nachwuchswissenschaftlerinnen und -wissenschaftler aus dem gesamten
Bundesgebiet konnten sich mit einem Antragsexposé um die Teilnahme an
der Nachwuchsakademie bewerben. Aus den insgesamt 83 eingegangenen
Bewerbungsanträgen wurden in einem 2-stufigen Begutachtungsprozess die
21 aussichtsreichsten BewerberInnen (14 Frauen und 7 Männer)
ausgewählt, von denen 20 die Nachwuchsakademie durchliefen. Nach einem
eintägigen Vorbereitungs-Workshop, der Erstellung und Begutachtung eines
Probeantrags, einer Akademie-Woche sowie einer Finalisierungsphase wurden alle
Anträge fristgerecht bei der DFG eingereicht. Von diesen
Anträgen werden 9 von der DFG gefördert. Im Juli 2019 fand das
erste Alumnitreffen in Düsseldorf statt.
Delphi-Konsens der Deutschen Gesellschaft für Thoraxchirurgie über das perioperative Management bei onkologischen anatomischen Lungenresektionen
Authors: Koryllos Aris , Ludwig Corinna , Hecker Erich , Leschber Gunda 
Published: February 2020

Zusammenfassung
Einleitung Die anatomische Lungenresektion zur kurativen Behandlung einer malignen Grunderkrankung ist die am häufigsten durchgeführte elektive Operation in der onkologischen Thoraxchirurgie. Ziel dieses Projektes war die Erarbeitung eines Konsenses bez. der am häufigsten gestellten Fragen zum Thema perioperatives Management für elektive onkologische Lungenresektionen.
Methodik Die Arbeitsgruppe erarbeitete 2 elektronische Delphi-Fragerunden. Als Konsens wurde eine Übereinstimmung in ≥ 75% definiert. Nach der statistischen Auswertung der Ergebnisse der elektronischen Fragerunde erfolgte eine Expertenkonferenz, die in einer finalen Delphi-Abstimmung versucht hat, weiteren Konsens über strittige Themen zu erreichen.
Ergebnisse 14 Fragen bez. des perioperativen Managements für elektive onkologische Lungenresektionen konnten formuliert und abgestimmt werden. Konsens konnte für folgende Themen erreicht werden: präoperatives infektiologisches Screening, erweiterte lungenfunktionelle Diagnostik bei eingeschränkter Lungenfunktion, Verwendung eines validierten Cardiac-Risk-Assessment-Algorithmus, Überwachung des Patienten postoperativ, Thromboembolieprophylaxe, Kontrollbronchoskopie nach Bronchusmanschettenresektionen oder nach Pneumonektomie sowie Blutgasanalyse vor Entlassung. Für folgende Themen konnte kein Konsens erreicht werden: präoperative endobronchiale mikrobiologische Diagnostik, Spülung der Thoraxhöhle, standardisierte laborchemische Untersuchungen postoperativ.
Fazit Die vorliegende Arbeit fasste die Ergebnisse eines Delphi-Prozesses zusammen, der 2018/2019 mit Experten aus zertifizierten Kliniken oder hochvolumigen thoraxchirurgischen Einheiten geführt wurde. Insgesamt zeigte sich eine sehr hohe Konsensrate bez. des perioperativen Managements bei onkologischen anatomischen selektiven Lungenresektionen. Die präoperative mikrobiologische endobronchiale Diagnostik war der Hauptpunkt, wo ein Konsens nicht erreicht werden konnte.