bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiota-derived Trimethylamine N-oxide Predicts Cardiovascular Risk After STEMI
Authors: Matsuzawa Yasushi , Nakahashi Hidefumi , Konishi Masaaki , Sato Ryosuke , Kawashima Chika , Kikuchi Shinnosuke , Akiyama Eiichi , Iwahashi Noriaki , Maejima Nobuhiko , Okada Kozo , Ebina Toshiaki , Hibi Kiyoshi , Kosuge Masami , Ishigami Tomoaki , Tamura Kouichi , Kimura Kazuo 
Published: August 2019

AbstractTrimethylamine N-oxide (TMAO), a metabolite derived from the gut microbiota, is proatherogenic and associated with cardiovascular events. However, the change in TMAO with secondary prevention therapies for ST-segment elevation acute myocardial infarction (STEMI) remains unclear. The purpose of this study was to investigate the sequential change in TMAO levels in response to the current secondary prevention therapies in patients with STEMI and the clinical impact of TMAO levels on cardiovascular events We included 112 STEMI patients and measured plasma TMAO levels at the onset of STEMI and 10 months later (chronic phase). After the chronic-phase assessment, patients were followed up for cardiovascular events. Plasma TMAO levels significantly increased from the acute phase to the chronic phase of STEMI (median: 5.63 to 6.76 μM, P = 0.048). During a median period of 5.4 years, 17 patients experienced events. The chronic-phase TMAO level independently predicted future cardiovascular events (adjusted hazard ratio for 0.1 increase in log chronic-phase TMAO level: 1.343, 95% confidence interval 1.122–1.636, P = 0.001), but the acute-phase TMAO level did not. This study demonstrated the clinical importance of the chronic-phase TMAO levels on future cardiovascular events in patients after STEMI.
Myeloid maturation potentiates STAT3-mediated atypical IFN-γ signaling and upregulation of PD-1 ligands in AML and MDS
Authors: Yoyen-Ermis Digdem , Tunali Gurcan , Tavukcuoglu Ece , Horzum Utku , Ozkazanc Didem , Sutlu Tolga , Buyukasik Yahya , Esendagli Gunes 
Published: August 2019

AbstractInterferon (IFN)-γ is the major mediator of anti-tumor immune responses; nevertheless, cancer cells use intrigue strategies to alter IFN-γ signaling and avoid elimination. Understanding the immune regulatory mechanisms employed by acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells upon exposure to IFN-γ is critical for development of immunotherapy and checkpoint blockade therapy approaches. This study aims to explore the influence of myeloid maturation on IFN-γ-induced PD-L1 and PD-L2 expression and on pro-leukemogenic transcription factor STAT3 signaling in AML and MDS. Stimulation of myeloid blasts’ maturation by all-trans retinoic acid (ATRA) or 1α,25-dihydroxyvitamin D3 (vitamin D) increased the CD11b+ fraction that expressed PD-1 ligands in response to IFN-γ. Intriguingly, STAT3 pathway was potently induced by IFN-γ and strengthened upon prolonged exposure. Nonetheless, STAT3-mediated atypical IFN-γ signaling appeared as a negligible factor for PD-L1 and PD-L2 expression. These negative influences of IFN-γ could be alleviated by a small-molecule inhibitor of STAT3, stattic, which also inhibited the upregulation of PD-L1. In conclusion, induction of myeloid maturation enhances the responsiveness of AML and MDS cells to IFN-γ. However, these malignant myeloid cells can exploit both STAT3 pathway and PD-1 ligands to survive IFN-γ-mediated immunity and maintain secondary immune resistance.
Development of Gabapentin Expandable Gastroretentive Controlled Drug Delivery System
Authors: Rimawi Issam B. , Muqedi Ramzi H. , Kanaze Feras I. 
Published: August 2019

AbstractExpandable drug delivery systems are one of many gastroretentive delivery systems which have emerged during the last few years. Expandable systems are usually folded in a capsule and expand to dimensions greater than the pyloric sphincter upon contact with gastric fluid. This prevents them from being evacuated by gastric emptying. The main objective of developing such systems is to increase the residence time of a specific drug in stomach; controlling its release, increasing its bioavailability and decreasing its side effects and dosing frequency. An expandable gastroretentive drug delivery system containing Gabapentin was developed using experimental design (D-optimal reduced quadratic design). This system was able to unfold at stomach pH in less than 15 minutes and obtain a controlled release of 78.1 ± 4.7% in 6 hours following zero-order release kinetic model. It is rigid in stomach and its rigidity decreases at intestinal pH. FTIR analysis indicated the occurrence of hydrogen bonding in Gabapentin when present in the developed system, which might be responsible for the drug’s controlled release. XRD analysis indicated that Gabapentin physical properties changed from crystalline in the typical state to amorphous in the developed system.
Link clustering explains non-central and contextually essential genes in protein interaction networks
Authors: Kim Inhae , Lee Heetak , Lee Kwanghwan , Han Seong Kyu , Kim Donghyo , Kim Sanguk 
Published: August 2019

AbstractRecent studies have shown that many essential genes (EGs) change their essentiality across various contexts. Finding contextual EGs in pathogenic conditions may facilitate the identification of therapeutic targets. We propose link clustering as an indicator of contextual EGs that are non-central in protein-protein interaction (PPI) networks. In various human and yeast PPI networks, we found that 29–47% of EGs were better characterized by link clustering than by centrality. Importantly, non-central EGs were prone to change their essentiality across different human cell lines and between species. Compared with central EGs and non-EGs, non-central EGs had intermediate levels of expression and evolutionary conservation. In addition, non-central EGs exhibited a significant impact on communities at lower hierarchical levels, suggesting that link clustering is associated with contextual essentiality, as it depicts locally important nodes in network structures.
Atorvastatin increases the production of proinflammatory cytokines and decreases the survival of Escherichia coli-infected mice
Authors: Hussein Hadi M. , Al-Khoury Diva Kalash , Abdelnoor Alexander M. , Rahal Elias A. 
Published: August 2019

AbstractTo assess whether the immunosuppressive effects of atorvastatin outweigh its antibacterial ones in an infection, mice were infected with Escherichia coli and administered atorvastatin; survival rates were then monitored. Mice treated with atorvastatin post-infection showed a remarkable decrease in their survival rate. On the other hand, the higher the level of serum IFN-γ in the infected mice treated with atorvastatin, the lower was the survival rate. Levels of IL-4 were markedly depressed in all groups infected with E. coli and treated with atorvastatin. Since atorvastatin inhibits IFN-γ expression in the absence of bacterial infection, we examined whether bacterial lipopolysaccharide (LPS) was the element capable of overriding this inhibition. Mouse peripheral blood mononuclear cells were treated with atorvastatin and lipopolysaccharide ex vivo then proinflammatory (IFN-γ, TNFα, IL-6) and prohumoral/regulatory (IL-4, IL-13, IL-10) cytokine levels were analyzed in culture supernatants. While proinflammatory cytokine levels were decreased upon treatment with atorvastatin alone, their levels were markedly elevated by treatment with LPS, bacterial lysate or bacterial culture supernatant. On the other hand, atorvastatin exerted an inhibitory effect on production of the prohumoral/regulatory cytokines. Our data indicates that any consideration for statins as antimicrobial treatment should assess the possible adverse outcomes.
A novel Carcinoembryonic Antigen (CEA)-Targeted Trimeric Immunotoxin shows significantly enhanced Antitumor Activity in Human Colorectal Cancer Xenografts
Authors: Lázaro-Gorines R. , Ruiz-de-la-Herrán J. , Navarro R. , Sanz L. , Álvarez-Vallina L. , Martínez-del-Pozo A. , Gavilanes J. G. , Lacadena J. 
Published: August 2019

AbstractImmunotoxins are chimeric molecules, which combine antibody specificity to recognize and bind with high-affinity tumor-associated antigens (TAA) with the potency of the enzymatic activity of a toxin, in order to induce the death of target cells. Current immunotoxins present some limitations for cancer therapy, driving the need to develop new prototypes with optimized properties. Herein we describe the production, purification and characterization of two new immunotoxins based on the gene fusion of the anti-carcinoembryonic antigen (CEA) single-chain variable fragment (scFv) antibody MFE23 to α-sarcin, a potent fungal ribotoxin. One construct corresponds to a conventional monomeric single-chain immunotoxin design (IMTXCEAαS), while the other one takes advantage of the trimerbody technology and exhibits a novel trimeric format (IMTXTRICEAαS) with enhanced properties compared with their monomeric counterparts, including size, functional affinity and biodistribution, which endow them with an improved tumor targeting capacity. Our results show the highly specific cytotoxic activity of both immunotoxins in vitro, which was enhanced in the trimeric format compared to the monomeric version. Moreover, the trimeric immunotoxin also exhibited superior antitumor activity in vivo in mice bearing human colorectal cancer xenografts. Therefore, trimeric immunotoxins represent a further step in the development of next-generation therapeutic immunotoxins.
Coherent quantum dynamics of systems with coupling-induced creation pathways
Authors: Rogers Steven D. , Graf Austin , Javid Usman A. , Lin Qiang 
Published: August 2019

AbstractMany technologies emerging from quantum information science heavily rely upon the generation and manipulation of entangled quantum states. Here, we propose and demonstrate a new class of quantum interference phenomena that arise when states are created in and coherently converted between the propagating modes of an optical microcavity. The modal coupling introduces several new creation pathways to a nonlinear optical process within the device, which quantum mechanically interfere to drive the system between states in the time domain. The coherent conversion entangles the generated biphotons between propagation pathways, leading to cyclically evolving path-entanglement and the manifestation of coherent oscillations in second-order temporal correlations. Furthermore, the rich device physics is harnessed to tune properties of the quantum states. In particular, we show that the strength of interference between pathways can be coherently controlled, allowing for manipulation of the degree of entanglement, which can even be entirely quenched. The states can likewise be made to flip-flop between exhibiting initially correlated or uncorrelated behavior. The phenomena presented here open a route to creating higher dimensional entanglement and exotic multi-photon states.
Elevated serum macrophage migration inhibitory factor levels correlate with benign paroxysmal positional vertigo and recurrence events
Authors: Cai Hong-Bin , Duan Lei , Tian Ting , Li Zi-Chao , Zhao Chong-Chong , Ge Zhao-Ming 
Published: August 2019

Abstract
Objective: We aimed to assess the possible relations between serum levels of macrophage migration inhibitory factor (MIF), a central cytokine of the innate immunity and inflammatory response, and benign paroxysmal positional vertigo (BPPV) risk and BPPV recurrence events.
Methods: In the present study, 154 patients with BPPV, and 100 age-and sex-matched control subjects were enrolled in the study. All the patients and controls underwent a complete audio-vestibular test battery including the Dix–Hallpike maneuver and supine roll test. In the BPPV group, measurements of MIF levels were repeated 1 month after the vertigo attack. The patients were also divided into the recurrence group and the nonrecurrence group in the 1-year follow-up.
Results: The serum levels of MIF in patients with BPPV were higher than in those controls (13.9[interquartile range {IQR}, 8.9–18.4] ng/ml vs. 9.8[7.8–11.8]; P&lt;0.001). As a continuous variable, MIF was associated with increased risk of BPPV (odds ratio [OR] 1.21, 95% confidence interval [CI]: 1.11–1.39; P=0.004) in multiple regression analyses. Recurrent attacks of BPPV were reported in 35 patients, and those patients had higher levels of MIF than those patients were not recurrence (18.0[IQR, 13.6–22.2] ng/ml vs. 12.6[9.3–16.8] ng/ml). In multivariate models comparing the second (Q2), third (Q3) and fourth(Q4) quartiles against the first (Q1) quartile of MIF, levels of MIF in Q4 were associated with recurrent BPPV, and the odds were increased by approximately 305% (OR = 4.05; 95%CI: 1.65–15.44; P=0.009).
Conclusions: Elevated MIF is positively correlated with BPPV risk and BPPV recurrence events, requiring further efforts to clarify the exact mechanism.
The role of molecular filaments in the origin of the prestellar core mass function and stellar initial mass function
Authors: André Ph. , Arzoumanian D. , Könyves V. , Shimajiri Y. , Palmeirim P. 
Published: August 2019

Context. The origin of the stellar initial mass function (IMF) is one of the most debated issues in astrophysics.
Aims. Here we explore the possible link between the quasi-universal filamentary structure of star-forming molecular clouds and the origin of the IMF.
Methods. Based on our recent comprehensive study of filament properties from Herschel Gould Belt survey observations, we derive, for the first time, a good estimate of the filament mass function (FMF) and filament line mass function (FLMF) in nearby molecular clouds. We use the observed FLMF to propose a simple toy model for the origin of the prestellar core mass function (CMF), relying on gravitational fragmentation of thermally supercritical but virialized filaments.
Results. We find that the FMF and the FLMF have very similar shapes and are both consistent with a Salpeter-like power-law function (dN/dlog Mline ∝ Mline−1.5±0.1) in the regime of thermally supercritical filaments (Mline >  16 M⊙ pc−1). This is a remarkable result since, in contrast, the mass distribution of molecular clouds and clumps is known to be significantly shallower than the Salpeter power-law IMF, with dN/dlog Mcl ∝ Mcl−0.7.
Conclusions. Since the vast majority of prestellar cores appear to form in thermally transcritical or supercritical filaments, we suggest that the prestellar CMF and by extension the stellar IMF are at least partly inherited from the FLMF through gravitational fragmentation of individual filaments.
New Aspects in the Diagnosis and Therapy of Fetal Hypoplastic Left Heart Syndrome
Authors: Graupner Oliver , Enzensberger Christian , Axt-Fliedner Roland 
Published: August 2019

AbstractFetal hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease with a lethal prognosis without postnatal therapeutic intervention or surgery. The aim of this article is to give a brief overview of new findings in the field of prenatal diagnosis and the therapy of HLHS. As cardiac output in HLHS children depends on the right ventricle (RV), prenatal assessment of fetal RV function is of interest to predict poor functional RV status before the RV becomes the systemic ventricle. Prenatal cardiac interventions such as fetal aortic valvuloplasty and non-invasive procedures such as maternal hyperoxygenation seem to be promising treatment options but will need to be evaluated with regard to long-term outcomes. Novel approaches such as stem cell therapy or neuroprotection provide important clues about the complexity of the disease. New aspects in diagnostics and therapy of HLHS show the potential of a targeted prenatal treatment planning. This could be used to optimize parental counseling as well as pre- and postnatal management of affected children.
Opioidsubstitutionsbehandlung und Cannabiskonsum
Authors: Schneider Udo , Schäfer Ingo , Hillemacher Thomas , Cimander Konrad F. , Wedekind Dirk , Weirich Steffen , Havemann-Reinecke Ursula 
Published: August 2019

Zusammenfassung
Ziel der Studie Mehr als 30 % der Patienten in Opioidsubstitutionsbehandlung konsumieren zusätzlich Cannabis. In dem Artikel werden die Auswirkungen des Konsums von Cannabis im Rahmen einer Opioidsubstitutionsbehandlung dargestellt.
Methodik Narrative Literaturrecherche (Medline, PubMed)
Ergebnisse Der Konsum von Cannabis im Rahmen einer Opioidsubstitutionsbehandlung kann negative Folgen nach sich ziehen.
Schlussfolgerung Der Konsum von Cannabis im Rahmen einer Substitutionsbehandlung sollte mit dem Patienten erörtert werden. Cannabiskonsum stellt grundsätzlich keinen Grund für den Abbruch einer Substitutionsbehandlung dar.
Myelon Stent – a New Technical Procedure to Protect the Spinal Cord Against Tumour Compression
Authors: Eysel Peer , Baltin Christoph , Meyer Carolin 
Published: August 2019

AbstractA 59-year-old woman with breast cancer who had undergone chemotherapy, three surgical interventions at the thoracic spine, and radiation since 2012, suffered from progressive ataxia caused by a single relapse metastasis resulting in spinal stenosis at thoracic level 6. Therefore, excessive tumour debulking was performed at thoracic levels 4 to 7 and a fully covered, self-expandable stent was placed around the spinal cord at these levels in order to create a mechanical barrier and to prevent the spinal cord from compression by the tumour. Neuromonitoring was performed before, during, and after surgical procedure. Clinically and electrophysiologically, ataxia appeared improved after intervention. Radiologically, no tumour growth was found at thoracic levels 4 to 7 after the intervention.
Plyometric-based Training for Isokinetic Knee Strength and Jump Performance in Cricket Fast Bowlers
Authors: Krishna Sai Aditya , Alwar Thiagarjan Keddin , Sibeko Sandile , Ranjit Shivani , Sivaraman Arumugam 
Published: August 2019

AbstractCompetitive cricket demands a high level of performance from fast bowlers. Ground reaction forces during the landing phase pose a risk for lower limb and lumbar spine injury. Good dynamic knee strength allows the knee to flex to absorb these forces and extend prior to ball release for maximum efficiency. Plyometric training has been shown to improve dynamic strength. There is a lack of literature on this subject for cricket. This study evaluated the effect of a combined plyometric and strength training program on isokinetic knee strength of fast bowlers. Forty-two professional fast bowlers were randomly assigned to a training group (n=21) and a control group (n=21). Both groups underwent isokinetic knee strength and vertical and standing broad-jump testing. Quadriceps and hamstring concentric and eccentric peak torques, bilateral strength asymmetries (BSAs), and dynamic control ratios (DCRs) were evaluated by isokinetic testing. The study group underwent 12 weeks of plyometric training, whereas the control group continued with their own training methods. The study group showed a significant improvement (p<0.05) in jump performance and eccentric strength. There was a reduction in the proportion of bowlers with poor BSA and DCR. Improving dynamic knee strength through plyometric training reduces injury risk and improves performance in cricket fast bowlers.
Innovative Molecular Testing Strategies for Adjunctive Investigations in Hemostasis and Thrombosis
Authors: Ghorbanpour Elham , Lillicrap David 
Published: August 2019

AbstractClinicians and scientists in the fields of hemostasis and thrombosis have been among those first to integrate new molecular strategies for the purpose of enhancing disease diagnosis and treatment. The molecular diagnosis and introduction of gene therapy approaches for hemophilia are obvious examples of this tendency. In this review, the authors summarize information concerning three molecular technologies that have reached various stages of translational potential for their incorporation into the clinical management of disorders of hemostasis. Chromatin conformation assays are now being used to capture structural knowledge of long-range genomic interactions that can alter patterns of gene expression and contribute to quantitative trait pathogenesis. Liquid biopsies in various forms are providing opportunities for early cancer detection, and in the context of tumor-educated platelets, as described here, can also characterize tumor type and the extent of tumor progression. This technology is already being trialed in patients with unprovoked venous thrombosis to assess the potential for occult malignancies. Lastly, advances in single cell transcriptome analysis, provide opportunities to definitively determine molecular events in rare cells, such as antigen-specific regulatory T cells, within the context of heterogeneous cell populations.
Digitalized service multinationals and international business theory
Authors: Hennart Jean-François 
Published: August 2019

AbstractBanalieva and Dhanaraj argue that digital service multinationals (DSMNCs) possess a new category of firm-specific advantage (FSA), the network advantage, and that, contrary to extant theory, they use networks as a mode of governance. I review the business models used by DSMNCs, compare them to non-digital ones, and explore what we can learn about them from extant IB theory. I conclude that network advantages are not a new category of FSAs, that networks are not a mode of governance, and that their use by DSMNCs is well explained by extant theory.
The Opioid and Related Drug Epidemics in Rural Appalachia: A Systematic Review of Populations Affected, Risk Factors, and Infectious Diseases
Authors: Schalkoff Christine A. , Lancaster Kathryn E. , Gaynes Bradley N. , Wang Vivian , Pence Brian W. , Miller William C. , Go Vivian F. 
Published: August 2019

Background/aims To examine trends in rural Appalachian opioid and related drug epidemics during the past 10 years, including at-risk populations, substance use shifts and correlates, and associated infections. Methods We conducted this review in accordance with the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. Seven databases were searched for quantitative studies, published between January 2006 and December 2017, of drug use, drug-related mortality, or associated infections in rural Appalachia. Results Drug-related deaths increased in study states, and a high incidence of polydrug toxicity was noted. Rural substance use was most common among young, white males, with low education levels. A history of depression/anxiety was common among study populations. Prescription opioids were most commonly used, often in conjunction with sedatives. Women emerged as a distinct user subpopulation, with different routes of drug use initiation and drug sources. Injection drug use was accompanied by risky injection behaviors and was associated with hepatitis C. Conclusions This review can help to inform substance use intervention development and implementation in rural Appalachian populations. Those at highest risk are young, white males who often engage in polysubstance use and have a history of mental health issues. Differences in risk factors among other groups and characteristics of drug use in rural Appalachian populations that are conducive to human immunodeficiency virus (HIV) spread also warrant consideration.