bluuebunny/crossref_metadata_2025_split huggingface dataset:
Point of care microspirometry to facilitate the COPD diagnostic process in primary care: a clustered randomised trial
Authors: Schermer Tjard R. , Vatsolaki Maria , Behr Robbert , Grootens Joke , Cretier Riet , Akkermans Reinier , Denis Joke , Poels Patrick , van den Bemt Lisette 
Published: May 2018

AbstractWe studied if pre-bronchodilator FEV1/FEV6 determinations with microspirometers by GPs improve the diagnostic process for COPD in a 6–8 month clustered randomised controlled trial in Dutch general practices (http://www.trialregister.nl: NTR4041). GPs allocated to microspirometry (MI) used COPD-6® microspirometers in patients ≥50 years old with a smoking history and respiratory complaints that could indicate undiagnosed COPD and ask to refer patients for full spirometry if MI was positive (FEV1/FEV6 <0.73). Introduction of the COPD-6® was postponed in the usual care (UC) group. GPs of both study arms were asked to list all patients that fulfilled study criteria and at the end of the study we screened the electronic medical record system for number of patients that fulfilled study criteria and visited their GP within the study period. Main end point was a documented diagnostic conclusion of COPD within 3 months after the patient’s visit. We used multilevel logistic regression with correction for relevant covariates. Next, we described the process of care. 21 practices (88 GPs) participated and 416 possible undiagnosed COPD patient visited these practices in the study period. 78 (of 192 visiting) subjects were listed by MI GPs and diagnostic conclusions were documented in 77%, compared to 61 listed (of 224 visiting) subjects and 44% with documented diagnostic conclusions by UC GPs (Odds Ratio: OR: 4.3, 95%CI: 1.6–11.5). Microspirometry improved the diagnostic process for possible underlying COPD in patients who consulted their GP with respiratory symptoms, but the majority of possible undiagnosed COPD patients remained unrecognised by GPs.
A novel extracellular vesicle-associated endodeoxyribonuclease helps Streptococcus pneumoniae evade neutrophil extracellular traps and is required for full virulence
Authors: Jhelum Hina , Sori Hema , Sehgal Devinder 
Published: May 2018

AbstractStreptococcus pneumoniae (pneumococcus) is a major bacterial pathogen that causes pneumonia and septicemia in humans. Pneumococci are cleared from the host primarily by antibody dependent opsonophagocytosis by phagocytes like neutrophils. Neutrophils release neutrophil extracellular traps (NETs) on contacting pneumococci. NETs immobilize pneumococci and restrict its dissemination in the host. One of the strategies utilized by pneumococci to evade the host immune response involves use of DNase(s) to degrade NETs. We screened the secretome of autolysin deficient S. pneumoniae to identify novel DNase(s). Zymogram analysis revealed 3 bands indicative of DNase activity. Mass spectrometric analysis led to the identification of TatD as a potential extracellular DNase. Recombinant TatD showed nucleotide sequence-independent endodeoxyribonuclease activity. TatD was associated with extracellular vesicles. Pneumococcal secretome degraded NETs from human neutrophils. Extracellular vesicle fraction from tatD deficient strain showed little NET degrading activity. Recombinant TatD efficiently degraded NETs. tatD deficient pneumococci showed lower bacterial load in lungs, blood and spleen in a murine sepsis model compared to wildtype strain, and showed less severe lung pathology and compromised virulence. This study provides insights into the role of a novel extracellular DNase in evasion of the innate immune system.
Alterations in serum kynurenine pathway metabolites in individuals with high neocortical amyloid-β load: A pilot study
Authors: Chatterjee Pratishtha , Goozee Kathryn , Lim Chai K. , James Ian , Shen Kaikai , Jacobs Kelly R. , Sohrabi Hamid R. , Shah Tejal , Asih Prita R. , Dave Preeti , ManYan Candice , Taddei Kevin , Lovejoy David B. , Chung Roger , Guillemin Gilles J. , Martins Ralph N. 
Published: May 2018

AbstractThe kynurenine pathway (KP) is dysregulated in neuroinflammatory diseases including Alzheimer’s disease (AD), however has not been investigated in preclinical AD characterized by high neocortical amyloid-β load (NAL), prior to cognitive impairment. Serum KP metabolites were measured in the cognitively normal KARVIAH cohort. Participants, aged 65–90 y, were categorised into NAL+ (n = 35) and NAL− (n = 65) using a standard uptake value ratio cut-off = 1.35. Employing linear models adjusting for age and APOEε4, higher kynurenine and anthranilic acid (AA) in NAL+ versus NAL− participants were observed in females (kynurenine, p = 0.004; AA, p = 0.001) but not males (NALxGender, p = 0.001, 0.038, respectively). To evaluate the predictive potential of kynurenine or/and AA for NAL+ in females, logistic regressions with NAL+/− as outcome were carried out. After age and APOEε4 adjustment, kynurenine and AA were individually and jointly significant predictors (p = 0.007, 0.005, 0.0004, respectively). Areas under the receiver operating characteristic curves were 0.794 using age and APOEε4 as predictors, and 0.844, 0.866 and 0.871 when kynurenine, AA and both were added. Findings from the current study exhibit increased KP activation in NAL+ females and highlight the predictive potential of KP metabolites, AA and kynurenine, for NAL+. Additionally, the current study also provides insight into he influence of gender in AD pathogenesis.
The Diversity of Chemoprotective Glucosinolates in Moringaceae (Moringa spp.)
Authors: Fahey Jed W. , Olson Mark E. , Stephenson Katherine K. , Wade Kristina L. , Chodur Gwen M. , Odee David , Nouman Wasif , Massiah Michael , Alt Jesse , Egner Patricia A. , Hubbard Walter C. 
Published: May 2018

AbstractGlucosinolates (GS) are metabolized to isothiocyanates that may enhance human healthspan by protecting against a variety of chronic diseases. Moringa oleifera, the drumstick tree, produces unique GS but little is known about GS variation within M. oleifera, and even less in the 12 other Moringa species, some of which are very rare. We assess leaf, seed, stem, and leaf gland exudate GS content of 12 of the 13 known Moringa species. We describe 2 previously unidentified GS as major components of 6 species, reporting on the presence of simple alkyl GS in 4 species, which are dominant in M. longituba. We document potent chemoprotective potential in 11 of 12 species, and measure the cytoprotective activity of 6 purified GS in several cell lines. Some of the unique GS rank with the most powerful known inducers of the phase 2 cytoprotective response. Although extracts of most species induced a robust phase 2 cytoprotective response in cultured cells, one was very low (M. longituba), and by far the highest was M. arborea, a very rare and poorly known species. Our results underscore the importance of Moringa as a chemoprotective resource and the need to survey and conserve its interspecific diversity.
A correlative and quantitative imaging approach enabling characterization of primary cell-cell communication: Case of human CD4+ T cell-macrophage immunological synapses
Authors: Kasprowicz Richard , Rand Emma , O’Toole Peter J. , Signoret Nathalie 
Published: May 2018

AbstractCell-to-cell communication engages signaling and spatiotemporal reorganization events driven by highly context-dependent and dynamic intercellular interactions, which are difficult to capture within heterogeneous primary cell cultures. Here, we present a straightforward correlative imaging approach utilizing commonly available instrumentation to sample large numbers of cell-cell interaction events, allowing qualitative and quantitative characterization of rare functioning cell-conjugates based on calcium signals. We applied this approach to examine a previously uncharacterized immunological synapse, investigating autologous human blood CD4+T cells and monocyte-derived macrophages (MDMs) forming functional conjugatesin vitro. Populations of signaling conjugates were visualized, tracked and analyzed by combining live imaging, calcium recording and multivariate statistical analysis. Correlative immunofluorescence was added to quantify endogenous molecular recruitments at the cell-cell junction. By analyzing a large number of rare conjugates, we were able to define calcium signatures associated with different states of CD4+T cell-MDM interactions. Quantitative image analysis of immunostained conjugates detected the propensity of endogenous T cell surface markers and intracellular organelles to polarize towards cell-cell junctions with high and sustained calcium signaling profiles, hence defining immunological synapses. Overall, we developed a broadly applicable approach enabling detailed single cell- and population-based investigations of rare cell-cell communication events with primary cells.
Giant photovoltaic response in band engineered ferroelectric perovskite
Authors: Pal Subhajit , Swain Atal Bihari , Biswas Pranab Parimal , Murali D. , Pal Arnab , Nanda B. Ranjit K. , Murugavel Pattukkannu 
Published: May 2018

AbstractRecently the solar energy, an inevitable part of green energy source, has become a mandatory topics in frontier research areas. In this respect, non-centrosymmetric ferroelectric perovskites with open circuit voltage (VOC) higher than the bandgap, gain tremendous importance as next generation photovoltaic materials. Here a non-toxic co-doped Ba1−x(Bi0.5Li0.5)
x
TiO3 ferroelectric system is designed where the dopants influence the band topology in order to enhance the photovoltaic effect. In particular, at the optimal doping concentration (x
opt
~ 0.125) the sample reveals a remarkably high photogenerated field EOC = 320 V/cm (VOC = 16 V), highest ever reported in any bulk polycrystalline non-centrosymmetric systems. The band structure, examined through DFT calculations, suggests that the shift current mechanism is key to explain the large enhancement in photovoltaic effect in this family.
Ring quantum cascade lasers with twisted wavefronts
Authors: Szedlak Rolf , Hisch Thomas , Schwarz Benedikt , Holzbauer Martin , MacFarland Donald , Zederbauer Tobias , Detz Hermann , Andrews Aaron Maxwell , Schrenk Werner , Rotter Stefan , Strasser Gottfried 
Published: May 2018

AbstractWe demonstrate the on-chip generation of twisted light beams from ring quantum cascade lasers. A monolithic gradient index metamaterial is fabricated directly into the substrate side of the semiconductor chip and induces a twist of the light’s wavefront. This significantly influences the obtained beam pattern, which changes from a central intensity minimum to a maximum depending on the discontinuity count of the metamaterial. Our design principle provides an interesting alternative to recent implementations of microlasers operating at an exceptional point.
Microbial production of novel sulphated alkaloids for drug discovery
Authors: Matsumura Eitaro , Nakagawa Akira , Tomabechi Yusuke , Ikushiro Shinichi , Sakaki Toshiyuki , Katayama Takane , Yamamoto Kenji , Kumagai Hidehiko , Sato Fumihiko , Minami Hiromichi 
Published: May 2018

AbstractNatural products from plants are useful as lead compounds in drug discovery. Plant benzylisoquinoline alkaloids (BIAs) exhibit various pharmaceutical activities. Although unidentified BIAs are expected to be of medicinal value, sufficient quantities of such BIAs, for biological assays, are sometimes difficult to obtain due to their low content in natural sources. Here, we showed that high productivity of BIAs in engineered Escherichia coli could be exploited for drug discovery. First, we improved upon the previous microbial production system producing (S)-reticuline, an important BIA intermediate, to obtain yields of around 160 mg/L, which was 4-fold higher than those of the previously reported highest production system. Subsequently, we synthesised non-natural BIAs (O-sulphated (S)-reticulines) by introducing human sulphotransferases into the improved (S)-reticuline production system. Analysis of human primary cells treated with these BIAs demonstrated that they affected a biomarker expression in a manner different from that by the parent compound (S)-reticuline, suggesting that simple side-chain modification altered the characteristic traits of BIA. These results indicated that highly productive microbial systems might facilitate the production of scarce or novel BIAs and enable subsequent evaluation of their biological activities. The system developed here could be applied to other rare natural products and might contribute to the drug-discovery process as a next-generation strategy.
A study of wound repair in Dictyostelium cells by using novel laserporation
Authors: Pervin Mst. Shaela , Itoh Go , Talukder Md. Shahabe Uddin , Fujimoto Koushiro , Morimoto Yusuke V. , Tanaka Masamitsu , Ueda Masahiro , Yumura Shigehiko 
Published: May 2018

AbstractWe examined the mechanism of cell membrane repair in Dictyostelium cells by using a novel laser-based cell poration method. The dynamics of wound pores opening and closing were characterized by live imaging of fluorescent cell membrane proteins, influx of fluorescent dye, and Ca2+ imaging. The wound closed within 2–4 sec, depending on the wound size. Cells could tolerate a wound size of less than 2.0 µm. In the absence of Ca2+ in the external medium, the wound pore did not close and cells ruptured. The release of Ca2+ from intracellular stores also contributed to the elevation of cytoplasmic Ca2+ but not to wound repair. Annexin C1 immediately accumulated at the wound site depending on the external Ca2+ concentration, and annexin C1 knockout cells had a defect in wound repair, but it was not essential. Dictyostelium cells were able to respond to multiple repeated wounds with the same time courses, in contrast to previous reports showing that the first wound accelerates the second wound repair in fibroblasts.
Glioblastoma single-cell microRaman analysis under stress treatments
Authors: Ricci Maria , Ragonese Francesco , Gironi Beatrice , Paolantoni Marco , Morresi Assunta , Latterini Loredana , Fioretti Bernard , Sassi Paola 
Published: May 2018

AbstractGlioblastoma multiforme (GBM) is the most frequent malignant brain tumor characterized by highly heterogeneous subpopulations. In order to reveal the heterogeneous cell response, single cell analysis is an essential requirement. In this study, optical microscopy and Raman microspectroscopy were used to follow the stress response of U251 single cells adherent on a silicon substrate. Cultured cells on silicon substrate were treated with hydrogen peroxide to promote apoptosis. Under these conditions expected changes occurred after a few hours and were revealed by the reduction of cytochrome c, lipid, nucleic acid and protein Raman signals: this ensured the possibility to analyse U251 cell line as grown on Si substrate, and to monitor the response of single cells to stress conditions. As a consequence, we used microRaman to monitor the effects induced by nutrient depletion: a fast change of Raman spectra showed two different sub-populations of sensible and resistant U251 cells. Furthermore, spectral variations after DMSO addition were associated to volume changes and confirmed by morphological analysis. Thus, our results highlight the sensitivity of Raman microspectroscopy to detect rapid variations of macromolecule concentration due to oxidative stress and/or cell volume changes at the single cell level.
Non-coding RNAs in Various Stages of Liver Disease Leading to Hepatocellular Carcinoma: Differential Expression of miRNAs, piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs
Authors: Koduru Srinivas V. , Leberfinger Ashley N. , Kawasawa Yuka I. , Mahajan Milind , Gusani Niraj J. , Sanyal Arun J. , Ravnic Dino J. 
Published: May 2018

AbstractHepatocellular carcinoma (HCC) was the fifth leading cause of cancer death in men and eighth leading cause of death in women in the United States in 2017. In our study, we sought to identify sncRNAs in various stages of development of HCC. We obtained publicly available small RNA-seq data derived from patients with cirrhosis (n = 14), low-grade dysplastic nodules (LGDN, n = 9), high grade dysplastic nodules (HGDN, n = 6), early hepatocellular carcinoma (eHCC, n = 6), and advanced hepatocellular carcinoma (HCC, n = 20), along with healthy liver tissue samples (n = 9). All samples were analyzed for various types of non-coding RNAs using PartekFlow software. We remapped small RNA-seq to miRBase to obtain differential expressions of miRNAs and found 87 in cirrhosis, 106 in LGDN, 59 in HGDN, 80 in eHCC, and 133 in HCC. Pathway analysis of miRNAs obtained from diseased samples compared to normal samples showed signaling pathways in the microRNA dependent EMT, CD44, and others. Additionally, we analyzed the data sets for piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs. We validated the in silico data using human HCC samples with NanoString miRNA global expression. Our results suggest that publically available data is a valuable resource for sncRNA identification in HCC progression (FDR set to <0.05 for all samples) and that a data mining approach is useful for biomarker development.
An Intrinsic Role of Beta Oscillations in Memory for Time Estimation
Authors: Wiener Martin , Parikh Alomi , Krakow Arielle , Coslett H. Branch 
Published: May 2018

AbstractThe neural mechanisms underlying time perception are of vital importance to a comprehensive understanding of behavior and cognition. Recent work has suggested a supramodal role for beta oscillations in measuring temporal intervals. However, the precise function of beta oscillations and whether their manipulation alters timing has yet to be determined. To accomplish this, we first re-analyzed two, separate EEG datasets and demonstrate that beta oscillations are associated with the retention and comparison of a memory standard for duration. We next conducted a study of 20 human participants using transcranial alternating current stimulation (tACS), over frontocentral cortex, at alpha and beta frequencies, during a visual temporal bisection task, finding that beta stimulation exclusively shifts the perception of time such that stimuli are reported as longer in duration. Finally, we decomposed trialwise choice data with a drift diffusion model of timing, revealing that the shift in timing is caused by a change in the starting point of accumulation, rather than the drift rate or threshold. Our results provide evidence for the intrinsic involvement of beta oscillations in the perception of time, and point to a specific role for beta oscillations in the encoding and retention of memory for temporal intervals.
Multitasking of Hsp70 chaperone in the biogenesis of bacterial functional amyloids
Authors: Sugimoto Shinya , Arita-Morioka Ken-ichi , Terao Akari , Yamanaka Kunitoshi , Ogura Teru , Mizunoe Yoshimitsu 
Published: May 2018

AbstractBiofilms are intricate communities of microorganisms embedded in a self-produced matrix of extracellular polymer, which provides microbes survival advantages in stressful environments and can cause chronic infections in humans. Curli are functional amyloids that assemble on the extracellular surface of enteric bacteria such asEscherichia coliduring biofilm development and colonization. The molecular chaperone DnaK, a bacterial Hsp70 homologue, promotes curli biogenesis via unknown mechanism(s). Here we show that DnaK increases the expression of CsgA and CsgB—the major and minor structural components of curli, respectively—via a quantity and quality control of RpoS, a stationary phase-specific alternative sigma factor regulating bacterial transcription, and CsgD, the master transcriptional regulator of curli formation. DnaK also keeps CsgA and CsgB in a translocation-competent state by binding to their signal peptides prone to aggregation. Our findings suggest that DnaK controls the homoeostasis of curli biogenesis at multiple stages to organize the biofilm matrix.
Stadtteildeprivation und Lebensmittelumwelt: Zusammenhänge von sozialen und baulichen Merkmalen der Wohnumgebung und Lebensmittelverfügbarkeit
Authors: Latawitz Toni , Spielau Ulrike , Lipek Tobias , Gausche Ruth , Lück Martina , Kiess Wieland , Grande Gesine , Igel Ulrike 
Published: May 2018

Zusammenfassung
Ziel der Studie Ernährungsgewohnheiten werden maßgeblich durch den individuellen Sozialstatus beeinflusst. Unklar ist, welcher Zusammenhang zwischen der Wohnumgebung und Lebensmittelverfügbarkeit besteht. Ziel der Studie war es, die Lebensmittelumwelt in sozial und baulich verschiedenen Stadtteilen zu untersuchen.
Methodik Anhand offizieller Daten der Stadt Leipzig wurden 3 exemplarische Stadtteile ausgewählt, die sich hinsichtlich ihrer sozialen (2 depriviert, 1 privilegiert) und baulichen Struktur (2 Altbau, 1 Plattenbau) unterscheiden. Über Feldbeobachtungen wurden alle Lebensmittelanbieter kartiert und kategorisiert.
Ergebnisse Soziale und bauliche Merkmale sind mit der Lebensmittelverfügbarkeit assoziiert. Der Anteil an Fast-Food-Anbietern ist in den deprivierten Gebieten mehr als doppelt so hoch als im privilegierten Vergleichsgebiet (25%, 30,4% vs. 13,5%). Altbauquartiere verfügen über eine 70% höhere Angebotsvielfalt als das Plattenbaugebiet.
Schlussfolgerung Die erhöhte Verfügbarkeit von ungesunden Lebensmitteln in deprivierten Gebieten kann zur Entstehung von Adipositas beitragen. Präventionsmaßnahmen sollten den räumlichen und sozialen Kontext berücksichtigen.
Die Rolle der elektiven Neck dissection bei Salvage Laryngektomie – eine retrospektive Analyse
Authors: Hussain Timon , Kanaan Oliver , Höing Benedikt , Dominas Nina , Lang Stephan , Mattheis Stefan 
Published: May 2018

ZusammenfassungIm Rahmen der Salvage Laryngektomie (SLE) bei Rezidivkarzinomen des Larynx und Hypopharynx wird häufig, wie bei der primären Laryngektomie (LE), eine elektive
beidseitige Neck dissection durchgeführt. Der therapeutische Nutzen muss angesichts des potentiell höheren Morbiditätsrisikos nach definitiver
Radiochemotherapie gegenüber den Risiken abgewogen werden.In einer retrospektiven Analyse wurden onkologische Parameter von Patienten erfasst, welche bei Rezidivkarzinomen des Larynx und Hypopharynx nach primärer
Radiochemotherapie eine SLE mit beidseitiger Neck dissection erhielten. Zum Vergleich wurden Daten von Patienten mit primärer LE und beidseitiger Neck
dissection bei Larynx- und Hypopharynxkarzinomen erfasst.19 Patienten mit SLE und 83 Patienten mit LE wurden in die Analyse eingeschlossen. Bei der Mehrzahl der Patienten waren sowohl das initiale Tumorstadium als auch
das Rezidiv-Tumorstadium vor SLE fortgeschritten. Vor SLE wiesen 5 % der Patienten (n = 1) klinisch metastasensuspekte Lymphknoten auf, vor LE 47 % (n = 39).
Bei 17 % (n = 14) der Patienten mit LE wurden okkulte Lymphknotenmetastasen nachgewiesen, bei SLE lediglich bei 5 % der Patienten (n = 1). Insgesamt ergab sich
ein pN+ -Stadium in 55 % (LE, n = 44) bzw. 10 % (SLE, n = 2) der Fälle. Die Gesamtzahl der entfernten Lymphknoten bei LE war höher als bei SLE (37,3 vs. 18,7, p
< 0,001). Das 5-Jahres-Gesamtüberleben der Patienten lag nach LE bei 50,0 %, nach SLE bei 33,3 %.Patienten, welche bei Rezidivkarzinomen des Larynx oder Hypopharynx nach primärer Bestrahlung eine SLE erhalten, weisen selten Lymphknotenmetastasen auf. Dennoch
kommt es in Einzelfällen zu einer okkulten Metastasierung. Bei der Planung der letzten kurativen Therapieoption sollte dies in Betracht gezogen werden.