bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced asthma-related fibroblast to myofibroblast transition is the result of profibrotic TGF-β/Smad2/3 pathway intensification and antifibrotic TGF-β/Smad1/5/(8)9 pathway impairment
Authors: Wnuk Dawid , Paw Milena , Ryczek Karolina , Bochenek Grażyna , Sładek Krzysztof , Madeja Zbigniew , Michalik Marta 
Published: October 2020

AbstractAirway remodelling with subepithelial fibrosis, which abolishes the physiological functions of the bronchial wall, is a major issue in bronchial asthma. Human bronchial fibroblasts (HBFs) derived from patients diagnosed with asthma display in vitro predestination towards TGF-β1-induced fibroblast-to-myofibroblast transition (FMT), a key event in subepithelial fibrosis. As commonly used anti-asthmatic drugs do not reverse the structural changes of the airways, and the molecular mechanism of enhanced asthma-related TGF-β1-induced FMT is poorly understood, we investigated the balance between the profibrotic TGF-β/Smad2/3 and the antifibrotic TGF-β/Smad1/5/9 signalling pathways and its role in the myofibroblast formation of HBF populations derived from asthmatic and non-asthmatic donors. Our findings showed for the first time that TGF-β-induced activation of the profibrotic Smad2/3 signalling pathway was enhanced, but the activation of the antifibrotic Smad1/5/(8)9 pathway by TGF-β1was significantly diminished in fibroblasts from asthmatic donors compared to those from their healthy counterparts. The impairment of the antifibrotic TGF-β/Smad1/5/(8)9 pathway in HBFs derived from asthmatic donors was correlated with enhanced FMT. Furthermore, we showed that Smad1 silencing in HBFs from non-asthmatic donors increased the FMT potential in these cells. Additionally, we demonstrated that activation of antifibrotic Smad signalling via BMP7 or isoliquiritigenin [a small-molecule activator of the TGF-β/Smad1/5/(8)9 pathway] administration prevents FMT in HBFs from asthmatic donors through downregulation of profibrotic genes, e.g., α-SMA and fibronectin. Our data suggest that influencing the balance between the antifibrotic and profibrotic TGF-β/Smad signalling pathways using BMP7-mimetic compounds presents an unprecedented opportunity to inhibit subepithelial fibrosis during airway remodelling in asthma.
Theory of optical tweezing of dielectric microspheres in chiral host media and its applications
Authors: Ali Rfaqat , Dutra Rafael S. , Pinheiro Felipe A. , Rosa Felipe S. S. , Maia Neto Paulo A. 
Published: October 2020

AbstractWe report for the first time the theory of optical tweezers of spherical dielectric particles embedded in a chiral medium. We develop a partial-wave (Mie) expansion to calculate the optical force acting on a dielectric microsphere illuminated by a circularly-polarized, highly focused laser beam. When choosing a polarization with the same handedness of the medium, the axial trap stability is improved, thus allowing for tweezing of high-refractive-index particles. When the particle is displaced off-axis by an external force, its equilibrium position is rotated around the optical axis by the mechanical effect of an optical torque. Both the optical torque and the angle of rotation are greatly enhanced in the presence of a chiral host medium when considering radii a few times larger than the wavelength. In this range, the angle of rotation depends strongly on the microsphere radius and the chirality parameter of the host medium, opening the way for a quantitative characterization of both parameters. Measurable angles are predicted even in the case of naturally occurring chiral solutes, allowing for a novel all-optical method to locally probe the chiral response at the nanoscale.
Berberine affects mitochondrial activity and cell growth of leukemic cells from chronic lymphocytic leukemia patients
Authors: Ravera Silvia , Ghiotto Fabio , Tenca Claudya , Gugiatti Elena , Santamaria Sara , Ledda Bernardetta , Ibatici Adalberto , Cutrona Giovanna , Mazzarello Andrea N. , Bagnara Davide , Cardillo Martina , Zarcone Daniela , Darzynkiewicz Zbigniew , Ciccone Ermanno , Fais Franco , Bruno Silvia 
Published: October 2020

AbstractB-cell chronic lymphocytic leukemia (CLL) results from accumulation of leukemic cells that are subject to iterative re-activation cycles and clonal expansion in lymphoid tissues. The effects of the well-tolerated alkaloid Berberine (BRB), used for treating metabolic disorders, were studied on ex-vivo leukemic cells activated in vitro by microenvironment stimuli. BRB decreased expression of survival/proliferation-associated molecules (e.g. Mcl-1/Bcl-xL) and inhibited stimulation-induced cell cycle entry, irrespective of TP53 alterations or chromosomal abnormalities. CLL cells rely on oxidative phosphorylation for their bioenergetics, particularly during the activation process. In this context, BRB triggered mitochondrial dysfunction and aberrant cellular energetic metabolism. Decreased ATP production and NADH recycling, associated with mitochondrial uncoupling, were not compensated by increased lactic fermentation. Antioxidant defenses were affected and could not correct the altered intracellular redox homeostasis. The data thus indicated that the cytotoxic/cytostatic action of BRB at 10–30 μM might be mediated, at least in part, by BRB-induced impairment of oxidative phosphorylation and the associated increment of oxidative damage, with consequent inhibition of cell activation and eventual cell death. Bioenergetics and cell survival were instead unaffected in normal B lymphocytes at the same BRB concentrations. Interestingly, BRB lowered the apoptotic threshold of ABT-199/Venetoclax, a promising BH3-mimetic whose cytotoxic activity is counteracted by high Mcl-1/Bcl-xL expression and increased mitochondrial oxidative phosphorylation. Our results indicate that, while CLL cells are in the process of building their survival and cycling armamentarium, the presence of BRB affects this process.
New semi-analytical solution of the problem of vapor bubble growth in superheated liquid
Authors: Chernov A. A. , Pil’nik A. A. , Vladyko I. V. , Lezhnin S. I. 
Published: October 2020

AbstractThis paper presents a mathematical model of the vapor bubble growth in an initially uniformly superheated liquid. This model takes into account simultaneously the dynamic and thermal effects and includes the well-known classical equations: the Rayleigh equation and the heat conductivity equation, written with consideration of specifics associated with the process of liquid evaporation. We have obtained a semi-analytical solution to the problem, which consists in reducing the initial boundary value problem with a moving boundary to a system of ordinary differential equations of the first order, valid in a wide range of operating parameters of the process at all its stages: from inertial to thermal, including the transitional one. It is shown that at large times this solution is consistent with the known solutions of other authors obtained in the framework of the energy thermal model, in particular, for the high Jacob numbers, it is consistent with the Plesset–Zwick solution.
Characterization of the biofilm matrix composition of psychrotrophic, meat spoilage pseudomonads
Authors: Wickramasinghe Nirmani N. , Hlaing Mya M. , Ravensdale Joshua T. , Coorey Ranil , Chandry P. Scott , Dykes Gary A. 
Published: October 2020

AbstractPsychrotrophic Pseudomonas species are the key spoilage bacteria of aerobically stored chilled meat. These organisms readily form biofilms on meat under refrigerated conditions leading to consumer rejection and associated economic losses. Limited information is available on the matrix composition of the biofilms formed by these bacteria. We quantified and characterized the main components of the matrix of mono-species biofilms of selected Pseudomonas fragi and Pseudomonas lundensis strains using chemical analysis and Raman spectroscopy. The biofilms were grown at 10 °C and 25 °C on nitro-cellulose membranes placed on surface sterilized beef cuts. Extra-cellular polymeric substances of the matrix were extracted in soluble and bound forms and were chemically assessed for total carbohydrates, proteins and extra-cellular DNA. Both Pseudomonas species showed a significant increase in total carbohydrates and total proteins when grown at 10 °C as compared to 25 °C. Extra-cellular DNA did not show a strong correlation with growth temperature. Raman spectra were obtained from planktonic bacteria and membrane grown biofilms at 10 °C and 25 °C. Higher levels of guanine were detected in planktonic cells as compared to biofilm cells. This study suggests that psychrotrophic Pseudomonas species may respond to cold stress by increasing extra-cellular polymer secretions.
Spred2-deficiency enhances the proliferation of lung epithelial cells and alleviates pulmonary fibrosis induced by bleomycin
Authors: Kawara Akina , Mizuta Ryo , Fujisawa Masayoshi , Ito Toshihiro , Li Chunning , Nakamura Kaoru , Sun Cuiming , Kuwabara Masaki , Kitabatake Masahiro , Yoshimura Teizo , Matsukawa Akihiro 
Published: October 2020

AbstractThe mitogen-activated protein kinase (MAPK) pathways are involved in many cellular processes, including the development of fibrosis. Here, we examined the role of Sprouty-related EVH-1-domain-containing protein (Spred) 2, a negative regulator of the MAPK-ERK pathway, in the development of bleomycin (BLM)-induced pulmonary fibrosis (PF). Compared to WT mice, Spred2−/− mice developed milder PF with increased proliferation of bronchial epithelial cells. Spred2−/− lung epithelial cells or MLE-12 cells treated with spred2 siRNA proliferated faster than control cells in vitro. Spred2−/− and WT macrophages produced similar levels of TNFα and MCP-1 in response to BLM or lipopolysaccharide and myeloid cell-specific deletion of Spred2 in mice had no effect. Spred2−/− fibroblasts proliferated faster and produced similar levels of MCP-1 compared to WT fibroblasts. Spred2 mRNA was almost exclusively detected in bronchial epithelial cells of naïve WT mice and it accumulated in approximately 50% of cells with a characteristic of Clara cells, 14 days after BLM treatment. These results suggest that Spred2 is involved in the regulation of tissue repair after BLM-induced lung injury and increased proliferation of lung bronchial cells in Spred2−/− mice may contribute to faster tissue repair. Thus, Spred2 may present a new therapeutic target for the treatment of PF.
High frequency acoustic cell stimulation promotes exosome generation regulated by a calcium-dependent mechanism
Authors: Ambattu Lizebona August , Ramesan Shwathy , Dekiwadia Chaitali , Hanssen Eric , Li Haiyan , Yeo Leslie Y. 
Published: October 2020

AbstractExosomes are promising disease diagnostic markers and drug delivery vehicles, although their use in practice is limited by insufficient homogeneous quantities that can be produced. We reveal that exposing cells to high frequency acoustic irradiation stimulates their generation without detriment to cell viability by exploiting their innate membrane repair mechanism, wherein the enhanced recruitment of calcium ions from the extracellular milieu into the cells triggers an ESCRT pathway known to orchestrate exosomal production. Given the high post-irradiation cell viabilities (≈95%), we are able to recycle the cells through iterative irradiation and post-excitation incubation steps, which facilitate high throughput production of a homogeneous population of exosomes—a particular challenge for translating exosome therapy into clinical practice. In particular, we show that approximately eight- to ten-fold enrichment in the number of exosomes produced can be achieved with just 7 cycles over 280 mins, equivalent to a yield of around 1.7–2.1-fold/h.
The relationship between intestinal goblet cells and the immune response
Authors: Zhang Mingming , Wu Chenchen 
Published: October 2020

Abstract
Goblet cells (GCs) are single-cell glands that produce and secrete mucin. Mucin forms a mucus layer, which can separate the materials in cavities from the intestinal epithelium and prevent the invasion of pathogenic microorganisms in various ways. GCs can also participate in the immune response through nonspecific endocytosis and goblet cell-associated antigen passages (GAPs). GCs endocytose soluble substances from the lumen and transmit antigens to the underlying antigen-presenting cells (APCs). A variety of immuno-regulatory factors can promote the differentiation, maturation of GCs, and the secretion of mucin. The mucin secreted by GCs forms a mucus layer, which plays an important role in resisting the invasion of foreign bacteria and intestinal inherent microorganisms, regulating the immune performance of the body. Therefore, the present study mainly reviews the barrier function of the mucus layer, the mucus secreted by goblet cells, the protective effect against pathogenic bacteria, the delivery of luminal substances through GAPs and the relationship between GCs and the immune response.
Prematurity negatively affects regenerative properties of human amniotic epithelial cells in the context of lung repair
Authors: Zhu Dandan , Kusuma Gina D. , Schwab Renate , Chan Siow Teng , Tan Jean , Saad Mohamed I. , Leeman Kristen T. , Kim Carla , Wallace Euan M. , Lim Rebecca 
Published: October 2020

Abstract
There is a growing appreciation of the role of lung stem/progenitor cells in the development and perpetuation of chronic lung disease including idiopathic pulmonary fibrosis. Human amniotic epithelial cells (hAECs) were previously shown to improve lung architecture in bleomycin-induced lung injury, with the further suggestion that hAECs obtained from term pregnancies possessed superior anti-fibrotic properties compared with their preterm counterparts. In the present study, we aimed to elucidate the differential effects of hAECs from term and preterm pregnancies on lung stem/progenitor cells involved in the repair. Here we showed that term hAECs were better able to activate bronchioalveolar stem cells (BASCs) and type 2 alveolar epithelial cells (AT2s) compared with preterm hAECs following bleomycin challenge. Further, we observed that term hAECs restored TGIF1 and TGFβ2 expression levels, while increasing c-MYC expression despite an absence of significant changes to Wnt/β-catenin signaling. In vitro, term hAECs increased the average size and numbers of BASC and AT2 colonies. The gene expression levels of Wnt ligands were higher in term hAECs, and the expression levels of BMP4, CCND1 and CDC42 were only increased in the BASC and AT2 organoids co-cultured with hAECs from term pregnancies but not preterm pregnancies. In conclusion, term hAECs were more efficient at activating the BASC niche compared with preterm hAECs. The impact of gestational age and/or complications leading to preterm delivery should be considered when applying hAECs and other gestational tissue-derived stem and stem-like cells therapeutically.
Reconciling escape fractions and observed line emission in Lyman-continuum-leaking galaxies
Authors: Ramambason L. , Schaerer D. , Stasińska G. , Izotov Y. I. , Guseva N. G. , Vílchez J. M. , Amorín R. , Morisset C. 
Published: October 2020

Context. Finding and elucidating the properties of Lyman-continuum(LyC)-emitting galaxies is an important step in improving our understanding of cosmic reionization.
Aims. Although the z ∼ 0.3 − 0.4 LyC emitters found recently show strong optical emission lines, no consistent quantitative photoionization model taking into account the escape of ionizing photons and inhomogenous interstellar medium (ISM) geometry of these galaxies has yet been constructed. Furthermore, it is unclear to what extent these emission lines can be used to distinguish LyC emitters.
Methods. To address these questions we construct one- and two-zone photoionization models accounting for the observed LyC escape, which we compare to the observed emission line measurements. The main diagnostics used include lines of [O III], [O II], and [O I] plus sulfur lines ([S II], [S III]) and a nitrogen line ([N II]), which probe regions of different ionization in the ISM.
Results. We find that single (one-zone) density-bounded photoionization models cannot reproduce the emission lines of the LyC leakers, as pointed out by earlier studies, because they systematically underpredict the lines of species of low ionization potential, such as [O I] and [S II]. Introducing a two-zone model, with differing ionization parameter and a variable covering fraction and where one of the zones is density-bounded, we show that the observed emission line ratios of the LyC emitters are well reproduced. Furthermore, our model yields LyC escape fractions, which are in fair agreement with the observations and independent measurements. The [O I] λ6300 excess, which is observed in some LyC leakers, can be naturally explained in this model, for example by emission from low-ionization and low-filling-factor gas. LyC emitters with a high escape fraction (fesc ≳ 38%) are deficient both in [O I] λ6300 and in [S II] λλ6716,6731. We also confirm that a [S II] λλ6716,6731 deficiency can be used to select LyC emitter candidates, as suggested earlier. Finally, we find indications for a possible dichotomy in terms of escape mechanisms for LyC photons between galaxies with relatively low (fesc ≲ 10%) and higher escape fractions.
Conclusions. We conclude that two-zone photoionization models are sufficient and required to explain the observed emission line properties of z ∼ 0.3 − 0.4 LyC emitters. This is in agreement with UV absorption line studies, which also show the co-existence of regions with high hydrogen column density (i.e., no escape of ionizing photons) and density-bounded or very low column density regions responsible for the observed escape of LyC radiation. These simple but consistent models provide a first step towards the use of optical emission lines and their ratios as quantitative diagnostics of LyC escape from galaxies.
Die Kosten des Schlaganfalls in Deutschland: eine systematische Übersichtsarbeit
Authors: Düvel Juliane A. , Damm Oliver , Greiner Wolfgang 
Published: October 2020

Zusammenfassung
Zielsetzung Ziel dieser Studie war es, eine umfassende Übersicht über die Literatur zu Kosten des Schlaganfalls oder der transitorischen ischämischen Attacke (TIA) in Deutschland zu geben.
Methodik Es wurde eine systematische Literaturrecherche in PubMed und Embase durchgeführt, um kostenberichtende Studien zu Schlaganfall und TIA, die vor Juni 2019 veröffentlicht wurden, zu identifizieren. Studien wurden eingeschlossen, sofern die Gesamtkosten, eine spezifische Kostenkategorie oder mindestens eine Behandlungsphase nach einem Schlaganfall oder einer TIA dargestellt wurde. Dagegen wurden Studien ausgeschlossen, die den Schlaganfall lediglich als Folge einer anderen Erkrankung oder eines Risikofaktors berücksichtigt haben, soweit dort keine separate Beschreibung der schlaganfallspezifischen Kosten vorgenommen wurde. Um die Vergleichbarkeit der Studienergebnisse zu gewährleisten, wurden alle Kostenschätzungen mithilfe des Verbraucherpreisindex des Statistischen Bundesamtes auf das einheitliche Preisjahr 2018 angepasst.
Ergebnisse Die Suchen in den Datenbanken ergaben 482 Treffer zuzüglich 3 Handrechercheartikeln, von denen 66 Studien für die Volltextüberprüfung ausgewählt wurden. Davon wurden schlussendlich 16 Studien in die Ergebnissynthese eingeschlossen. Die durchschnittlichen direkten Kosten lagen zwischen 14 240 € und 44 060 € pro Patient. Wenn indirekte Kosten erhoben wurden, lagen diese zwischen 2470 € und 17 860 €. Im ersten Jahr nach einem Schlaganfall stellten die stationären Kosten den größten Kostenblock dar, während die ambulanten Behandlungs- und Pflegekosten insbesondere in den Folgejahren dominierten.
Schlussfolgerung Die Ergebnisse der Studien betonen die monetäre Relevanz des Schlaganfalls für das deutsche Gesundheitssystem. Daneben verdeutlicht die Übersichtsarbeit die Notwendigkeit einheitlicher Ansätze zur Erhebung und Analyse von Krankheitskosten, um eine Vergleichbarkeit zu gewährleisten und Handlungsbedarf anhand kostentreibender Aspekte identifizieren zu können.
Vestibular Schwannoma Tumor Size and Growth Rate Predict Response with Gamma Knife Stereotactic Radiosurgery
Authors: Killeen Daniel E. , Tolisano Anthony M. , Isaacson Brandon , Kutz J Walter , Barnett Samuel , Wardak Zabi , Hunter Jacob B. 
Published: October 2020

Abstract
Objective The aim of this study is to determine if pretreatment growth of sporadic vestibular schwannomas (VS) predicts postradiosurgery response.
Methods This study was a retrospective chart review at a tertiary referral center of patients with VS that had at least two pretreatment magnetic resonance imaging (MRI) studies at least 6 months apart and underwent Gamma Knife radiosurgery with a minimum of 14 months postradiosurgery imaging surveillance. Tumor linear measurements and volumetric segmentation were assessed before and after radiosurgery. The main outcome measure was persistent enlargement following radiosurgery, defined as 2 mm enlargement in greatest axial diameter or 20% enlargement in volume without size regression.
Results Thirty-five patients met the inclusion criteria. Patients were observed for median pre- and posttreatment intervals of 29.5 and 40.6 months, respectively. Median dose to the tumor margin was 13 Gy. Postradiosurgery enlargement occurred in six (17.1%) and nine (25.7%) patients based on linear and volumetric enlargement definitions, respectively. Pseudoprogression—defined as tumor enlargement—followed by linear or volumetric regression that occurred in 34.3% of tumors, reaching a maximum size at a median time of 6.3 months (3.3–8.4) postradiosurgery. When controlling for age, gender, and radiation dose, preradiosurgery tumor volume less than 0.3 cm3 (odds ratio [OR]: 59.7, p = 0.012) and preradiosurgery tumor diameter growth rate greater than or equal to 2.5 mm/year (OR: 19.3, p = 0.045) were associated with persistent postradiosurgery tumor enlargement.
Conclusion Smaller pretreatment tumor volume and greater linear tumor growth rates were associated with postradiosurgery tumor enlargement when controlling for age, gender, and radiation dose.
Level of Evidence This study indicates that the level of evidence is V.
Erythrocyte Complement Receptor 1 Gene Polymorphisms and Neonatal Respiratory Distress Syndrome
Authors: Rabie Walaa , Al-Taweel Ahmed , Abuelhamd Walaa A. , Shahin Walaa , Nazeer Marian , Aly Hany 
Published: October 2020

AbstractTo evaluate the role of erythrocyte complement receptor 1 (ECR1) gene in the predisposition to respiratory distress syndrome (RDS), we studied 50 infants with RDS and 50 controls. Real-time polymerase chain reaction allelic discrimination analysis of A3650G (rs2274567) and genotyping of the alleles (HindIII) were performed. Allele L of HindIII restricted single nucleotide polymorphism (SNP) associated with the severity of RDS. Duration of oxygen and ventilation in genotypes AA and AG of A3650G SNP was longer than genotype GG (17.6 ± 19.4 and 8.6 ± 4.5 days, p = 0.01) and (8.9 ± 11.9 and 3.9 ± 3.53 days, p = 0.03), respectively. A3650G and HINDIII digested gene polymorphisms of ECR1 may be of little importance for RDS.
The tabloidization of the Brexit campaign
Authors: Zappettini Franco 
Published: October 2020

Abstract
Consistent with a populist script, evoking the people has been a nodal point in the discursive unfolding of Brexit and its
legitimation. This paper focuses on the mediatization of the Brexit referendum campaign in a corpus of online British tabloids to address
the critical question of how the people in whose name Brexit was (de)legitimised were discursively constructed and mobilized. The argument
put forward is that the legitimation of Brexit was achieved through exclusionary definitions of the people and through strategies of fear,
resentment and empowerment. This discursive framing points to the wider question of the instrumental role that a large section of the
British tabloid press has had not simply in the contingency of referendum but also in the longer-term legitimation chain of Brexit and in
its institutionalization and more generally in the historical priming of their readership with negative coverage of the UK/EU
relationship.