bluuebunny/crossref_metadata_2025_split huggingface dataset:
An electronic nose using a single graphene FET and machine learning for water, methanol, and ethanol
Authors: Hayasaka Takeshi , Lin Albert , Copa Vernalyn C. , Lopez Lorenzo P. , Loberternos Regine A. , Ballesteros Laureen Ida M. , Kubota Yoshihiro , Liu Yumeng , Salvador Arnel A. , Lin Liwei 
Published: May 2020

AbstractThe poor gas selectivity problem has been a long-standing issue for miniaturized chemical-resistor gas sensors. The electronic nose (e-nose) was proposed in the 1980s to tackle the selectivity issue, but it required top-down chemical functionalization processes to deposit multiple functional materials. Here, we report a novel gas-sensing scheme using a single graphene field-effect transistor (GFET) and machine learning to realize gas selectivity under particular conditions by combining the unique properties of the GFET and e-nose concept. Instead of using multiple functional materials, the gas-sensing conductivity profiles of a GFET are recorded and decoupled into four distinctive physical properties and projected onto a feature space as 4D output vectors and classified to differentiated target gases by using machine-learning analyses. Our single-GFET approach coupled with trained pattern recognition algorithms was able to classify water, methanol, and ethanol vapors with high accuracy quantitatively when they were tested individually. Furthermore, the gas-sensing patterns of methanol were qualitatively distinguished from those of water vapor in a binary mixture condition, suggesting that the proposed scheme is capable of differentiating a gas from the realistic scenario of an ambient environment with background humidity. As such, this work offers a new class of gas-sensing schemes using a single GFET without multiple functional materials toward miniaturized e-noses.
KSHV infection skews macrophage polarisation towards M2-like/TAM and activates Ire1 α-XBP1 axis up-regulating pro-tumorigenic cytokine release and PD-L1 expression
Authors: Gilardini Montani Maria Saveria , Falcinelli Luca , Santarelli Roberta , Granato Marisa , Romeo Maria Anele , Cecere Nives , Gonnella Roberta , D’Orazi Gabriella , Faggioni Alberto , Cirone Mara 
Published: May 2020

AbstractBackgroundKaposi’s Sarcoma Herpesvirus (KSHV) is a gammaherpesvirus strongly linked to human cancer. The virus is also able to induce immune suppression, effect that contributes to onset/progression of the viral-associated malignancies. As KSHV may infect macrophages and these cells abundantly infiltrate Kaposi’s sarcoma lesions, in this study we investigated whether KSHV-infection could affect macrophage polarisation to promote tumorigenesis.MethodsFACS analysis was used to detect macrophage markers and PD-L1 expression. KSHV infection and the molecular pathways activated were investigated by western blot analysis and by qRT-PCR while cytokine release was assessed by Multi-analyte Kit.ResultsWe found that KSHV infection reduced macrophage survival and skewed their polarisation towards M2 like/TAM cells, based on the expression of CD163, on the activation of STAT3 and STAT6 pathways and the release of pro-tumorigenic cytokines such as IL-10, VEGF, IL-6 and IL-8. We also found that KSHV triggered Ire1 α-XBP1 axis activation in infected macrophages to increase the release of pro-tumorigenic cytokines and to up-regulate PD-L1 surface expression.ConclusionsThe findings that KSHV infection of macrophages skews their polarisation towards M2/TAM and that activate Ire1 α-XBP1 to increase the release of pro-tumorigenic cytokines and the expression of PD-L1, suggest that manipulation of UPR could be exploited to prevent or improve the treatment of KSHV-associated malignancies.
miR-622 is a novel potential biomarker of breast carcinoma and impairs motility of breast cancer cells through targeting NUAK1 kinase
Authors: Orlandella Francesca Maria , Mariniello Raffaela Mariarosaria , Mirabelli Peppino , De Stefano Anna Elisa , Iervolino Paola Lucia Chiara , Lasorsa Vito Alessandro , Capasso Mario , Giannatiempo Rosa , Rongo Maria , Incoronato Mariarosaria , Messina Francesco , Salvatore Marco , Soricelli Andrea , Salvatore Giuliana 
Published: May 2020

Abstract
Background
Aberrant expression of microRNAs (miR) has been proposed as non-invasive biomarkers for breast cancers. The aim of this study was to analyse the miR-622 level in the plasma and in tissues of breast cancer patients and to explore the role of miR-622 and its target, the NUAK1 kinase, in this context.

Methods
miR-622 expression was analysed in plasma and in tissues samples of breast cancer patients by q-RT-PCR. Bioinformatics programs, luciferase assay, public dataset analysis and functional experiments were used to uncover the role of miR-622 and its target in breast cancer cells.

Results
miR-622 is downregulated in plasma and in tissues of breast cancer patients respect to healthy controls and its downregulation is significantly associated with advanced grade and high Ki67 level. Modulation of miR-622 affects the motility phenotype of breast cancer cells. NUAK1 kinase is a functional target of miR-622, it is associated with poor clinical outcomes of breast cancer patients and is inversely correlated with miR-622 level.

Conclusions
miR-622/NUAK1 axis is deregulated in breast cancer patients and affects the motility phenotype of breast cancer cells. Importantly, miR-622 and NUAK1 hold promises as biomarkers and as targets for breast cancers.
Identification of EMT-related high-risk stage II colorectal cancer and characterisation of metastasis-related genes
Authors: Wang Kai , Song Kai , Ma Zhigang , Yao Yang , Liu Chao , Yang Jing , Xiao Huiting , Zhang Jiashuai , Zhang Yanqiao , Zhao Wenyuan 
Published: May 2020

Abstract
Background
Our laboratory previously reported an individual-level prognostic signature for patients with stage II colorectal cancer (CRC). However, this signature was not applicable for RNA-sequencing datasets. In this study, we constructed a robust epithelial-to-mesenchymal transition (EMT)- related gene pair prognostic signature.

Methods
Based on EMT-related genes, metastasis-associated gene pairs were identified between metastatic and non-metastatic samples. Then, we selected prognosis-associated gene pairs, which were significantly correlated with disease-free survival of stage II CRC using multivariate Cox regression model, as the EMT-related prognosis signature.

Results
An EMT-related signature composed of fifty-one gene pairs (51-GPS) for prediction-relapse risk of patients with stage II CRC was developed, whose prognostic efficiency was validated in independent datasets. Moreover, 51-GPS achieved better predictive performance than other reported signatures, including a commercial signature Oncotype Dx colon cancer and an immune-related gene pair signature. Besides, EMT-related functional gene sets achieved high enrichment scores in high-risk samples. Especially, loss-of-function antisense approach showed that DEGs between the predicted two clusters were metastasis-related.

Conclusions
The EMT-related gene pair signature can identify the high relapse-risk patients with stage II CRC, which can facilitate individualised management of patients.
Testing the carbohydrate-insulin model of obesity in a 5-month feeding study: the perils of post-hoc participant exclusions
Authors: Ludwig David S. , Greco Kimberly F. , Ma Clement , Ebbeling Cara B. 
Published: May 2020

AbstractA large feeding study reported that total energy expenditure (TEE) was greater on a low- versus high-carbohydrate diet, supporting the carbohydrate-insulin model of obesity. Recently, the validity of this finding was challenged in a post-hoc analysis excluding participants with putative non-adherence to the study diets. Here, we show why that analysis, based on a post-randomization variable linked to the outcome, introduced severe confounding bias. With control for confounding, the diet effect on TEE remained strong in a reanalysis. Together with sensitivity analyses demonstrating robustness to plausible levels of non-adherence, these data provide experimental support for a potentially novel metabolic effect of macronutrients that might inform the design of more effective obesity treatment.
ERK Activity in Immature Leukemic Cells Drives Clonal Selection during Induction Therapy for Acute Myeloid Leukemia
Authors: Hayun Michal , Zaatra Maria , Itzkovich Chen , Sahar Dvora , Rosenberg Dina , Filatova Margarita , Ringelstein-Harlev Shimrit , Baris Hagit , Moustafa-Hawash Nivin , Louria-Hayon Igal , Ofran Yishai 
Published: May 2020

AbstractSelection of resistant clones following intensive chemotherapy is a common obstacle for cure in many cancers, particularly in acute myeloid leukemia (AML). In AML, clone-specific sensitivity to chemotherapy varies even within the same patient. Multiple mutations and genetic aberrations are associated with clones surviving chemotherapy. The current study explored the role of activated signaling pathways in chemoresistance as a function of cell maturation, reflected by CD34 expression. In-vitro, Kasumi-1 leukemic cell line, sorted by CD34 expression, showed increased apoptosis only in the CD34− subpopulation after exposure to cytosine arabinoside (Ara-C) or daunorubicin. The resistant CD34+ subset demonstrated higher expression of ERK1/2 and BCL-2 proteins than CD34− cells. MEK1/2 inhibition elevated Ara-C ability to induce apoptosis in CD34+ cells, suggesting that MEK1/2-ERK1/2 is surviving signaling, which correlates to cell maturation levels and plays a role in chemoresistance. Deep sequencing of sorted CD34+/− populations, both derived from the same patient samples, demonstrated various subclonal distribution of NPM1, DNMT3A and FLT3-ITD mutations. Interestingly, in these samples, p-ERK levels and apoptosis rates following chemotherapy exposure significantly differed between CD34+/− populations. Hence, clones may be selected due to their ability to escape apoptosis rather than a direct effect of chemotherapy on a specific mutated clone.
Administration of apo A-I (Milano) nanoparticles reverses pathological remodelling, cardiac dysfunction, and heart failure in a murine model of HFpEF associated with hypertension
Authors: Mishra Mudit , Muthuramu Ilayaraja , Kempen Herman , De Geest Bart 
Published: May 2020

AbstractTherapeutic interventions with proven efficacy in heart failure with reduced ejection fraction (HFrEF) have been unsuccessful in heart failure with preserved ejection fraction (HFpEF). The modifiable risk factor with the greatest impact on the development of HFpEF is hypertension. The objectives of this study were to establish a murine model of HFpEF associated with hypertension and to evaluate the effect of apo A-IMilano nanoparticles (MDCO-216) on established HFpEF in this model. Subcutaneous infusion of angiotensin II in combination with 1% NaCl in the drinking water was started at the age of 12 weeks in male C57BL/6 N mice and continued for the entire duration of the experiment. Treatment with MDCO-216 partially reversed established cardiac hypertrophy, cardiomyocyte hypertrophy, capillary rarefaction, and perivascular fibrosis in this model. Pressure-volume loop analysis was consistent with HFpEF in hypertension mice as evidenced by the preserved ejection fraction and a significant reduction of cardiac output (7.78 ± 0.56 ml/min versus 10.5 ± 0.7 ml/min; p < 0.01) and of the peak filling rate (p < 0.05). MDCO-216 completely reversed cardiac dysfunction and abolished heart failure as evidenced by the normal lung weight and normal biomarkers of heart failure. In conclusion, apo A-IMilano nanoparticles constitute an effective treatment for established hypertension-associated HFpEF.
Partial Scanning Transmission Electron Microscopy with Deep Learning
Authors: Ede Jeffrey M. , Beanland Richard 
Published: May 2020

AbstractCompressed sensing algorithms are used to decrease electron microscope scan time and electron beam exposure with minimal information loss. Following successful applications of deep learning to compressed sensing, we have developed a two-stage multiscale generative adversarial neural network to complete realistic 512 × 512 scanning transmission electron micrographs from spiral, jittered gridlike, and other partial scans. For spiral scans and mean squared error based pre-training, this enables electron beam coverage to be decreased by 17.9× with a 3.8% test set root mean squared intensity error, and by 87.0× with a 6.2% error. Our generator networks are trained on partial scans created from a new dataset of 16227 scanning transmission electron micrographs. High performance is achieved with adaptive learning rate clipping of loss spikes and an auxiliary trainer network. Our source code, new dataset, and pre-trained models are publicly available.
Automated detection of the head-twitch response using wavelet scalograms and a deep convolutional neural network
Authors: Halberstadt Adam L. 
Published: May 2020

AbstractHallucinogens induce the head-twitch response (HTR), a rapid reciprocal head movement, in mice. Although head twitches are usually identified by direct observation, they can also be assessed using a head-mounted magnet and a magnetometer. Procedures have been developed to automate the analysis of magnetometer recordings by detecting events that match the frequency, duration, and amplitude of the HTR. However, there is considerable variability in the features of head twitches, and behaviors such as jumping have similar characteristics, reducing the reliability of these methods. We have developed an automated method that can detect head twitches unambiguously, without relying on features in the amplitude-time domain. To detect the behavior, events are transformed into a visual representation in the time-frequency domain (a scalogram), deep features are extracted using the pretrained convolutional neural network (CNN) ResNet-50, and then the images are classified using a Support Vector Machine (SVM) algorithm. These procedures were used to analyze recordings from 237 mice containing 11,312 HTR. After transformation to scalograms, the multistage CNN-SVM approach detected 11,244 (99.4%) of the HTR. The procedures were insensitive to other behaviors, including jumping and seizures. Deep learning based on scalograms can be used to automate HTR detection with robust sensitivity and reliability.
The fornix acts as a permissive corridor for septal neuron migration beyond the diencephalic-telencephalic boundary
Authors: Watanabe Keisuke , Takebayashi Hirohide , Sato Noboru 
Published: May 2020

AbstractNeuronal migration is essential for constructing functional neural networks. Two posterior septal (PS) nuclei, the triangular septal nucleus and bed nuclei of the anterior commissure, are involved in fear and anxiety. During development, glutamatergic PS neurons undergo long-distance rostrodorsal migration from the thalamic eminence (TE) of the diencephalon, then settle in the caudalmost telencephalon. However, the developmental behavior of PS neurons and the guidance structures facilitating their migration remain unknown. We previously demonstrated the migration of PS neurons along the fornix, a major efferent pathway from the hippocampal formation. Here, we show that the postcommissural fornix is essential for PS neuron migration which is largely confined to its axonal tract, which grows in the opposite direction as PS neuron migration. Fornical axons reach the TE prior to initiation of PS neuron rostrodorsal migration. Ectopic expression of Semaphorin 3 A in the dorsomedial cortex resulted in defective fornix formation. Furthermore, loss of the postcommissural fornix stalled PS neuron migration resulting in abnormal accumulation near their origin. This suggests that PS neurons utilize the postcommissural fornix as a permissive corridor during migration beyond the diencephalic-telencephalic boundary. This axonal support is essential for the functional organization of the heterogeneous septal nuclear complex.
Universal layer number in graphite
Authors: Sasaki K. , Hitachi K. 
Published: May 2020

AbstractGraphene absorbs light in accordance with the fine-structure constant α ≃ 1/137. The α value is universal in the sense that it is unrelated to material parameters but solely related to the elementary charge, which is a fundamental constant governing the coupling of light and matter. A new universality governed only by α has yet to be discovered in graphene optics. However, since α is a dimensionless quantity, it can be anticipated that the reciprocal of α appears as a characteristic number of layers in the light absorptance of an N-layer graphene. Here, we report that this number is 2/πα. We show simultaneously that for light in the infrared to visible range, an N-layer graphene with N above 1500 may be regarded as graphite. This also enables us to obtain the simplest expression for the optical constants of graphite, which is written in terms of α and interlayer distance only.
Overcoming off-targets: assessing Western blot signals for Bcnt/Cfdp1, a tentative component of the chromatin remodeling complex
Authors: Iwashita Shintaro , Suzuki Takehiro , Kiriyama Yoshimitsu , Dohmae Naoshi , Ohoka Yoshiharu , Song Si-Young , Nakashima Kentaro 
Published: May 2020

Abstract
The Bucentaur (BCNT) protein family is characterized by a conserved amino acid sequence at the C-terminus (BCNT-C domain) and plays an essential role in gene expression and chromosomal maintenance in yeast and Drosophila. The mammalian Bucentaur/Craniofacial developmental protein 1 (Bcnt/Cfdp1) is also a tentative component of the SNF2-related CBP activator protein (Srcap) chromatin remodeling complex, but little is known about its properties, partly because few antibodies are available to examine the endogenous protein. In this paper, we assigned the Western blot signal against the mouse Bcnt/Cfdp1 as a doublet of approximately 45 kDa using anti-Bcnt/Cfdp1 antibodies, which were generated against either of two unrelated immunogens, BCNT-C domain or mouse N-terminal peptide, and in addition, the Cfdp1 knockdown mouse ES cell line and bovine tissue were used as potential negative controls. Moreover, LC-MS/MS analysis of the corresponding doublet to the Flag-tagged mouse Bcnt/Cfdp1 that was constitutively expressed in a HEK293 cell exhibited that the upper band was much more phosphorylated than the lower band with preferential Ser phosphorylation in the WESF motif of BCNT-C domain. Western blot analysis with these evaluated antibodies indicated a preferential expression of Bcnt/Cfdp1 in the early stages of brain development of mouse and rat, which is consistent with a data file of the expression of Bcnt/Cfdp1 mRNA.
Praticiens de terrain et responsabilité sociale en santé : enjeux et attentes
Authors: Millette Bernard , Cauli Marie , Merimi Sanaa , Pestiaux Dominique 
Published: May 2020

Problématique :  La responsabilité sociale en santé (RSS) a d’abord été définie en lien avec les institutions de formation des professionnels de santé. Mais, que signifie être socialement responsable pour un intervenant de proximité ? Quelles sont les compétences pour une pratique socialement responsable au niveau « micro », celui de la rencontre patient-professionnel de santé ? Tels sont les enjeux que cet article explore. Exégèse : À partir de deux vignettes de consultation, les auteurs abordent plusieurs questions-clés en lien avec la RSS des professionnels de proximité (actions et attitudes du praticien, impacts des déterminants sociaux de la santé, questions vives de société tel l’accès aux soins pour les démunis, l’observation de maltraitance, les dilemmes de l’euthanasie…). Des réponses socialement responsables à ces enjeux sont évoquées (compétence professionnelle, habiletés communicationnelles, mais aussi pertinence d’une anamnèse sociale pour identifier et agir en fonction des déterminants sociaux influençant la santé des patients…). Discussion : Les auteurs questionnent la volonté des professionnels de santé de répondre aux défis de la RSS. L’enjeu de la formation à la RSS est aussi évoqué en proposant que des stratégies soient développées pour favoriser l’intégration progressive de la valeur « RSS » à l’identité professionnelle. Conclusion : Le professionnel de santé socialement responsable agit, informe, met en lien les uns souffrant avec les autres qui peuvent les aider. Il participe aux plaidoyers et actions pour réduire ou faire disparaître certains obstacles sociaux à la santé des individus et communautés. Il est prêt à évaluer et, au besoin, modifier ses pratiques et son environnement.
Arzneimittelinteraktionen in der Notfallmedizin
Authors: Hofmann Tobias , Hachenberg Thomas 
Published: May 2020

ZusammenfassungUnerwünschte Arzneimittelwirkungen treten bei der Behandlung von Notfällen auf, können aber auch einen Notarzteinsatz auslösen und sind für eine große Zahl von Klinikeinweisungen verantwortlich. Man unterscheidet dabei pharmakodynamische und -kinetische Wechselwirkungen. Ihre Wahrscheinlichkeit steigt mit der Anzahl der eingenommenen Medikamente. Zu ihrer Vermeidung können elektronische Datenbanken und Smartphone-Apps hilfreich sein.
Therapeutische Apherese
Authors: Klingel Reinhard , Fassbender Cordula , Heibges Andreas , Schettler Volker J. J. 
Published: May 2020

ZUSAMMENFASSUNGIn Deutschland ist der Einsatz der therapeutischen Apherese (TA) vorrangig ein nephrologisches Therapieangebot. International ist der Fachbezug heterogener. Abhängig von Zulassungsstatus und Erfahrungswerten werden bei gleicher Indikation unterschiedliche Methoden bevorzugt. Der unselektive Plasmaaustausch ist in weiten Teilen der Welt unverändert das Standardverfahren. Deutschland und Japan sind die Pioniere der selektiven Verfahren wie der Immunadsorption und Doppelfiltrations-Plasmapherese. Unter den interdisziplinären Leitlinien zum Einsatz der TA sind für die Praxis in Deutschland der Apherese-Standard der Deutschen Gesellschaft für Nephrologie (DGfN) und die Leitlinien der American Society for Apheresis (ASFA) hervorzuheben. Die Leitlinien der Deutschen Gesellschaft für Neurologie e. V. (DGN) sind als nationale fachbezogene Leitlinien zu erwähnen, da die TA bei vielen neurologischen Erkrankungen zum Einsatz kommt und sehr differenziert empfohlen wird. Das neurologische Konsensuspapier zur TA fasst dies aktuell zusammen. Im Jahr 2019 wurden die 3 Werke aktualisiert bzw. erstmals vorgelegt.
Uveitis bei Behçet-Syndrom in Deutschland – Prognose unter aktueller Therapie
Authors: Stübiger Nicole , Deuter Christoph , Doycheva Deshka 
Published: May 2020

ZusammenfassungDas Behçet-Syndrom (BS) ist eine entzündliche Systemerkrankung, die mit multiplen Organmanifestationen einhergeht. Häufigste Krankheitssymptome sind orale Aphthen, genitale Ulzerationen, Hauteffloreszenzen und Augenmanifestationen. Die Diagnose des Behçet-Syndroms wird anhand klinischer Symptome gestellt. Typische okuläre Präsentation beim Behçet-Syndrom ist die rezidivierende nicht granulomatöse Panuveitis mit okklusiver retinaler Vaskulitis. Früher waren systemische Steroide und konventionelle Immunsuppressiva die einzige therapeutische Option beim Behçet-Syndrom. Unter dieser Therapie konnte jedoch häufig keine stabile Remission der Augenbeteiligung erreicht werden und die Prognose der Behçet-Uveitis, insbesondere bei Vorliegen einer okklusiven retinalen Vaskulitis, galt lange Zeit als äußerst schlecht. In den letzten Jahren hat die Einführung der Biologika die Therapie des Behçet-Syndroms revolutioniert und die Visusprognose der Patienten deutlich verbessert.