bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety Profile of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Disproportionality Analysis of FDA Adverse Event Reporting System
Authors: Huang Jing , Meng Long , Yang Bing , Sun Shusen , Luo Zhigang , Chen Hong 
Published: March 2020

AbstractAdverse event reports submitted to the US Food and Drug Administration (FDA) were analyzed to map the safety profile of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). We conducted a disproportionality analysis of the adverse events (AEs) of EGFR-TKIs (gefitinib, erlotinib, afatinib, osimertinib) by data mining using the FDA adverse event reporting system (AERS) database, and by calculating the reporting odds ratios (ROR) with 95% confidence intervals. The FDA AERS database contained 27,123 EGFR-TKI-associated AERs within the reporting period from January 1, 2004 to March 31, 2018. Thirty-three preferred terms (PTs) were selected for analysis, and significant RORs were most commonly observed in the skin, nail, gastrointestinal tract, hepatic, eyes, and lungs. Unexpected adverse drug reactions were found in the “intestinal obstruction” and “hypokalaemia” in gefitinib and erlotinib, “hyponatraemia” in gefitinib, erlotinib and afatinib, “alopecia”in erlotinib, “hair growth abnormal” in afatinib, but not in “nausea” and “vomiting” listed on drug labels. The results of this study are consistent with clinical observation, suggesting the usefulness of pharmacovigilance research should be corroborated with the real-world FAERS data.
Myocardial Minimal Damage After Rapid Ventricular Pacing – the prospective randomized multicentre MyDate-Trial
Authors: Semmler Verena , Deutschmann Clara , Haller Bernhard , Lennerz Carsten , Brkic Amir , Grebmer Christian , Blazek Patrick , Weigand Severin , Karch Martin , Busch Sonia , Kolb Christof 
Published: March 2020

AbstractTherapy of choice for the primary and secondary prevention of sudden cardiac death is the implantation of an implantable cardioverter defibrillator (ICD). Whereas appropriate and inappropriate ICD shocks lead to myocardial microdamage, this is not known for antitachycardia pacing (ATP). In total, 150 ICD recipients (66 ± 12 years, 81.3% male, 93.3% primary prevention, 30.0% resynchronization therapy) were randomly assigned to an ICD implantation with or without intraoperative ATP. In the group with ATP, the pacing maneuver was performed twice, each time applying 8 impulses à 6 Volt x 1.0 milliseconds to the myocardium. High sensitive Troponin T (hsTnT) levels were determined prior to the implantation and thereafter. There was no significant difference in the release of hsTnT between the two randomization groups (delta TnT without ATP in median 0.010 ng/ml [min. −0.016 ng/ml–max. 0.075 ng/ml] vs. with ATP in median 0.013 ng/ml [min. −0.005–0.287 ng/ml], p = 0.323). Setting a hsTnT cutoff of 0.059 ng/dl as a regularly augmented postoperative hsTnT level, no relevant difference between the two groups regarding the postoperative hsTnT levels above this cutoff could be identified (without ATP n = 10 [14.7%] vs. with ATP n = 16 [21.9%], p = 0.287). There was no significant difference in the release of high sensitive Troponin between patients without intraoperative ATP compared to those with intraoperative ATP. Hence, antitachycardia pacing does not seem to cause significant myocardial microdamage. This may further support its use as a painless and efficient method to terminate ventricular tachycardia in high-risk patients.
Generation and Manipulation of Superoscillatory Hotspots Using Virtual Fourier Filtering and CTF Shaping
Authors: Sanjeev Abhijit , Shabairou Nadav , Attar Arrad , Scherbaum Daniel , Kapellner Yuval , Sinvani Moshe , Zalevsky Zeev 
Published: March 2020

AbstractSuperoscillation is a technique that is used to produce a spot of light (known as ‘hotspot’) which is smaller than the conventional diffraction limit of a lens and even smaller than the optical wavelength. Over the past few years, several techniques have been realized for the generation of the superoscillatory hotspot. In this article, for the first time to the best of our knowledge, we propose a novel and a more efficient technique for producing superoscillation in microscopic imaging by shaping the Coherent Transfer Function (CTF) of a lens via virtual Fourier filtering followed by a phase retrieval algorithm. We design and realize a phase mask which when placed at the pupil plane of a diffraction-limited lens produces a superoscillatory hotspot with sidelobes properly matched to the field of view (FOV) required in microscopic imaging applications, i.e. hotspot always coexists with huge intense rings known as ‘sidebands’ close to it and hence limiting the FOV. Our technique is also capable of extending the FOV with minimal loss in resolution of the hotspot generated and considerable ratio between the intensity of the hotspot to that of the side lobes while optimizing the obtainable FOV to the requirement of microscopy.
Modulation of glycine receptor single-channel conductance by intracellular phosphorylation
Authors: Moraga-Cid Gustavo , San Martín Victoria P. , Lara Cesar O. , Muñoz Braulio , Marileo Ana M. , Sazo Anggelo , Muñoz-Montesino Carola , Fuentealba Jorge , Castro Patricio A. , Guzmán Leonardo , Burgos Carlos F. , Zeilhofer Hanns U. , Aguayo Luis G. , Corringer Pierre-Jean , Yévenes Gonzalo E. 
Published: March 2020

AbstractGlycine receptors (GlyRs) are anion-permeable pentameric ligand-gated ion channels (pLGICs). The GlyR activation is critical for the control of key neurophysiological functions, such as motor coordination, respiratory control, muscle tone and pain processing. The relevance of the GlyR function is further highlighted by the presence of abnormal glycinergic inhibition in many pathophysiological states, such as hyperekplexia, epilepsy, autism and chronic pain. In this context, previous studies have shown that the functional inhibition of GlyRs containing the α3 subunit is a pivotal mechanism of pain hypersensitivity. This pathway involves the activation of EP2 receptors and the subsequent PKA-dependent phosphorylation of α3GlyRs within the intracellular domain (ICD), which decrease the GlyR-associated currents and enhance neuronal excitability. Despite the importance of this mechanism of glycinergic dis-inhibition associated with dysfunctional α3GlyRs, our current understanding of the molecular events involved is limited. Here, we report that the activation of PKA signaling pathway decreases the unitary conductance of α3GlyRs. We show in addition that the substitution of the PKA-targeted serine with a negatively charged residue within the ICD of α3GlyRs and of chimeric receptors combining bacterial GLIC and α3GlyR was sufficient to generate receptors with reduced conductance. Thus, our findings reveal a potential biophysical mechanism of glycinergic dis-inhibition and suggest that post-translational modifications of the ICD, such as phosphorylation, may shape the conductance of other pLGICs.
Identifying mutation hotspots reveals pathogenetic mechanisms of KCNQ2 epileptic encephalopathy
Authors: Zhang Jiaren , Kim Eung Chang , Chen Congcong , Procko Erik , Pant Shashank , Lam Kin , Patel Jaimin , Choi Rebecca , Hong Mary , Joshi Dhruv , Bolton Eric , Tajkhorshid Emad , Chung Hee Jung 
Published: March 2020

AbstractKv7 channels are enriched at the axonal plasma membrane where their voltage-dependent potassium currents suppress neuronal excitability. Mutations in Kv7.2 and Kv7.3 subunits cause epileptic encephalopathy (EE), yet the underlying pathogenetic mechanism is unclear. Here, we used novel statistical algorithms and structural modeling to identify EE mutation hotspots in key functional domains of Kv7.2 including voltage sensing S4, the pore loop and S6 in the pore domain, and intracellular calmodulin-binding helix B and helix B-C linker. Characterization of selected EE mutations from these hotspots revealed that L203P at S4 induces a large depolarizing shift in voltage dependence of Kv7.2 channels and L268F at the pore decreases their current densities. While L268F severely reduces expression of heteromeric channels in hippocampal neurons without affecting internalization, K552T and R553L mutations at distal helix B decrease calmodulin-binding and axonal enrichment. Importantly, L268F, K552T, and R553L mutations disrupt current potentiation by increasing phosphatidylinositol 4,5-bisphosphate (PIP2), and our molecular dynamics simulation suggests PIP2 interaction with these residues. Together, these findings demonstrate that each EE variant causes a unique combination of defects in Kv7 channel function and neuronal expression, and suggest a critical need for both prediction algorithms and experimental interrogations to understand pathophysiology of Kv7-associated EE.
Congruency and reactivation aid memory integration through reinstatement of prior knowledge
Authors: van Kesteren Marlieke T. R. , Rignanese Paul , Gianferrara Pierre G. , Krabbendam Lydia , Meeter Martijn 
Published: March 2020

AbstractBuilding knowledge schemas that organize information and guide future learning is of great importance in everyday life. Such knowledge building is suggested to occur through reinstatement of prior knowledge during new learning, yielding integration of new with old memories supported by the medial prefrontal cortex (mPFC) and medial temporal lobe (MTL). Congruency with prior knowledge is also known to enhance subsequent memory. Yet, how reactivation and congruency interact to optimize memory integration is unknown. To investigate this question, we used an adapted AB-AC inference paradigm in combination with functional Magnetic Resonance Imaging (fMRI). Participants first studied an AB-association followed by an AC-association, so B (a scene) and C (an object) were indirectly linked through A (a pseudoword). BC-associations were either congruent or incongruent with prior knowledge (e.g. bathduck or hammer in a bathroom), and participants reported subjective B-reactivation strength while learning AC. Behaviorally, both congruency and reactivation enhanced memory integration. In the brain, these behavioral effects related to univariate and multivariate parametric effects in the MTL, mPFC, and Parahippocampal Place Area (PPA). Moreover, mPFC exhibited larger PPA-connectivity for more congruent associations. These outcomes provide insights into the neural mechanisms underlying memory enhancement, which has value for educational learning.
Dynamic FoxP2 levels in male zebra finches are linked to morphology of adult-born Area X medium spiny neurons
Authors: Kosubek-Langer Jennifer , Scharff Constance 
Published: March 2020

AbstractThe transcription factor FOXP2 is crucial for the formation and function of cortico-striatal circuits. FOXP2 mutations are associated with specific speech and language impairments. In songbirds, experimentally altered FoxP2 expression levels in the striatal song nucleus Area X impair vocal learning and song production. Overall FoxP2 protein levels in Area X are low in adult zebra finches and decrease further with singing. However, some Area X medium spiny neurons (MSNs) express FoxP2 at high levels (FoxP2high MSNs) and singing does not change this. Because Area X receives many new neurons throughout adulthood, we hypothesized that the FoxP2high MSNs are newly recruited neurons, not yet integrated into the local Area X circuitry and thus not active during singing. Contrary to our expectation, FoxP2 protein levels did not predict whether new MSNs were active during singing, assayed via immediate early gene expression. However, new FoxP2high MSNs had more complex dendrites, higher spine density and more mushroom spines than new FoxP2low MSNs. In addition, FoxP2 expression levels correlated positively with nucleus size of new MSNs. Together, our data suggest that dynamic FoxP2 levels in new MSNs shape their morphology during maturation and their incorporation into a neural circuit that enables the maintenance and social modulation of adult birdsong.
A Switchable High-Performance RF-MEMS Resonator with Flexible Frequency Generations
Authors: Chen Zeji , Kan Xiao , Yuan Quan , Wang Tianyun , Yang Jinling , Yang Fuhua 
Published: March 2020

AbstractResonators with multi-frequency generations at the device-level are highly desired in the future multi-band, reconfigurable, and compact wireless communications. In this work, a switchable radio frequency micro-electro-mechanical system (RF-MEMS) resonator with multiple electrodes is presented. The resonator is designed to operate at the whispering gallery modes (WGMs). Simultaneous excitations of the second to seventh modes with high Q values are implemented within a single device using a pair of electrodes for driving and sensing. For effective multi-frequency excitations, the electrode span angle is optimized. The frequencies of the 37 μm and 18 μm-radius resonators range from 53 MHz to 176 MHz and 112 MHz to 366 MHz, respectively. The Q values in each mode are over 104. Moreover, with the multi-electrode configurations, the specific mode can be enhanced with other modes suppressed. A more than 6 dB improvement of the spectrum peak is realized and the high Q values are maintained. A comprehensive theory is built up to clarify the driving/sensing principles under different electrode configurations. Furthermore, the air damping is found to have a significant effect on Q values for resonator with high stiffness vibrating in all the WGMs. The Q values in vacuum have at least two times improvement. The high-performance switchable resonator could dramatically reduce the power consumption, simplify the processing circuits, and occupy less footprint, which has great potential applications in future advanced RF front end systems.
Metabolomics-based study reveals the effect of lead (Pb) in the culture environment on Whitmania pigra
Authors: Luo Xuemei , Meng Jieqin , Chen Xiufen , Cheng Liangke , Yan Shaopeng , Gao Luying , Xue Miao , Yang Yaojun 
Published: March 2020

AbstractWhitmania pigra, called Mahuang (MH) in Chinese, has been used as a traditional Chinese medicine for many years and is susceptible to Pb exposure in aquaculture environments. To understand the impact of Pb in the culture environment on MHs, we carried out a 50-day culture of MHs in environments with different levels of Pb pollution. Then, tissue samples of MHs reared in the different Pb-polluted environments were collected and analysed by UPLC-Q/TOF-MS. The results showed that the Pb residue in MHs increased with increasing Pb in the culture environment. There was no significant difference in MH Pb content (P < 0.05) between the low-Pb residue group (PbL) and the blank control group (BC), and those of the middle-Pb residue group (PbM) and the high-Pb residue group (PbH) were significantly different from that of the BC group. Metabolomics results showed significant changes in 24 metabolites in the PbL, PbM and PbH groups, some of which were dose-dependent. These metabolites were mainly lipids, nucleotides, and dipeptides, which are involved in metabolic pathways such as glycerophospholipid metabolism, sphingolipid metabolism, and nucleotide metabolism. Overall, the results proved that metabolomics can be an effective tool to understand the effects of Pb on the metabolic responses of MHs.
Introspective and Neurophysiological Measures of Mind Wandering in Schizophrenia
Authors: Iglesias-Parro S. , Soriano M. F. , Prieto M. , Rodríguez I. , Aznarte J. I. , Ibáñez-Molina A. J. 
Published: March 2020

AbstractPatients with schizophrenia have often been considered to be “in their own world”. However, this casual observation has not been proven by scientific evidence so far. This can be explained because scientific research has usually addressed cognition related to the processing of external stimuli, but only recently have efforts been made to explain thoughts, images and feelings not directly related to the external environment. This internally directed cognition has been called mind wandering. In this paper, we have explored mind wandering in schizophrenia under the hypothesis that a predominance of mind wandering would be a core dysfunction in this disorder. To this end, we collected verbal reports and measured electrophysiological signals from patients with schizophrenia spectrum disorders and matched healthy controls while they were presented with segments of films. The results showed that mind wandering was more frequent in patients than in controls. This higher frequency of mind wandering did not correlate with deficits in attentional, memory or executive functioning. In addition, mind wandering in patients was characterized by a different pattern of Electroencephalography (EEG) complexity in patients than in controls, leading to the suggestion that mind wandering in schizophrenia could be of a different nature. These findings could have relevant implications for the conceptualization of this severe mental disorder.
Transcriptome signature analysis repurposes trifluoperazine for the treatment of fragile X syndrome in mouse model
Authors: Ding Qi , Sethna Ferzin , Wu Xue-Ting , Miao Zhuang , Chen Ping , Zhang Yueqi , Xiao Hua , Feng Wei , Feng Yue , Li Xuan , Wang Hongbing 
Published: March 2020

AbstractFragile X syndrome (FXS) is a prevailing genetic disorder of intellectual disability and autism. There is no efficacious medication for FXS. Through in silico screening with a public database, computational analysis of transcriptome profile in FXS mouse neurons predicts therapeutic value of an FDA-approved drug trifluoperazine. Systemic administration of low-dose trifluoperazine at 0.05 mg/kg attenuates multiple FXS- and autism-related behavioral symptoms. Moreover, computational analysis of transcriptome alteration caused by trifluoperazine suggests a new mechanism of action against PI3K (Phosphatidylinositol-4,5-bisphosphate 3-kinase) activity. Consistently, trifluoperazine suppresses PI3K activity and its down-stream targets Akt (protein kinase B) and S6K1 (S6 kinase 1) in neurons. Further, trifluoperazine normalizes the aberrantly elevated activity of Akt and S6K1 and enhanced protein synthesis in FXS mouse. Together, our data demonstrate a promising value of transcriptome-based computation in identification of therapeutic strategy and repurposing drugs for neurological disorders, and suggest trifluoperazine as a potential treatment for FXS.
The construction and analysis of tumor-infiltrating immune cells and ceRNA networks in metastatic adrenal cortical carcinoma
Authors: Huang Runzhi , Liu Ziqi , Tian Tingli , Song Dianwen , Yan Penghui , Yin Huabin , Hu Peng , Zhu Xiaolong , Liu Yihan , Li Zhenyu , Meng Tong , Zhang Jie , Huang Zongqiang 
Published: March 2020

Abstract
Purpose: To construct and analyze tumor-infiltrating immune cell and ceRNA (competitive endogenous RNA) networks in metastatic adrenal cortical carcinoma (ACC).
Methods: A ceRNA network was established to identify the ceRNAs involved in metastasis of ACC based on 92 samples from TCGA, including 18 cases of metastasis and 74 cases of non-metastatic primary tumors. And the algorithm “cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT)” was used to quantify the proportion of immune cells in ACC. In addition, predictive nomograms based on the types of important immune cells or ceRNAs were constructed to predict ACC prognosis. Moreover, we evaluated the relationships between metastatic ACC-specific immune cells and ceRNA networks to identify the potential immune gene characteristics.
Results: Ten prognostic biomarkers were identified as key members of the ceRNA network and three tumor-infiltrating immune cells were identified by CIBERSORT algorithm. Some important co-expression patterns between immune cells and ceRNAs network indicate significant correlation between Macrophages M0 and hsa-miR-130b-3p (P &lt; 0.001), Macrophages M0 and H2AFX (P = 0.003).
Conclusions: The present study inferred that the metastasis-related ceRNAs of H2AFX, hsa-miR-130b-3p and Macrophages M0 might play important roles in ACC metastasis.
Spectroscopic patch model for massive stars using PHOEBE II and FASTWIND
Authors: Abdul-Masih Michael , Sana Hugues , Conroy Kyle E. , Sundqvist Jon , Prša Andrej , Kochoska Angela , Puls Joachim 
Published: March 2020

Context. Massive stars play an important role in the mechanical and chemical evolution of galaxies. Understanding the internal processes of these stars is vital to our understanding of their evolution and eventual end products. Deformations from spherical geometry are common for massive stars; however, the tools that are currently available for the study of these systems are almost exclusively one-dimensional.
Aims. We present a new spectroscopic analysis tool tailored for massive stars that deviate from spherical symmetry. This code (entitled SPAMMS) is a spectroscopic patch model that takes the three-dimensional surface geometry of the system into account to produce spectral profiles at given phases and orientations.
Methods. In using the Wilson–Devinney-like code PHOEBE in combination with the nonlocal thermodynamic equilibrium radiative transfer code FASTWIND, we created a three-dimensional mesh that represents the surface geometry of our system and we assigned FASTWIND emergent intensity line profiles to each mesh triangle, which take the local parameters such as temperature, surface gravity, and radius into account. These line profiles were then integrated across the visible surface, where their flux contribution and radial velocity are taken into account, thus returning a final line profile for the visible surface of the system at a given phase.
Results. We demonstrate that SPAMMS can accurately reproduce the morphology of observed spectral line profiles for overcontact systems. Additionally, we show how line profiles of rapidly-rotating single stars differ when taking rotational distortion into account, and the effects that these can have on the determined parameters. Finally, we demonstrate the code’s ability to reproduce the Rossiter–Mclaughlin and Struve–Sahade effects.
Qualität in der Kopf-Hals-Onkologie
Authors: Wiegand Susanne , Dietz Andreas 
Published: March 2020

ZusammenfassungEine fachlich-qualifizierte, patienten- und bedarfsgerechte, wirtschaftliche,
qualitativ hochwertige Versorgung von Patienten mit Kopf-Hals-Karzinomen ist
eine Herausforderung. Basis der Qualitätsoptimierung in der deutschen
Kopf-Hals-Onkologie sind qualitätsfördernde Rahmenbedingungen,
wie der Nationale Krebsplan, der Ausbau klinischer Krebsregister und das
Vorhandensein evidenzbasierter Leitlinien, die im Rahmen des 2008 initiierten
„Leitlinienprogramms Onkologie“ erstellt wurden (S3-Leitlinien
Mundhöhlenkarzinom und Larynxkarzinom). Aktuell gibt es in Deutschland
56 zertifizierte Kopf-Hals-Tumorzentren mit dem Ziel einer objektivierbaren
Qualitätssteigerung der Behandlung und einer Verbesserung des Outcomes
der Patienten. Verschiedene Qualitätsindikatoren wurden erarbeitet, es
gibt Programme zur Qualitätssicherung der Therapie sowie innerhalb von
Studien. Ziel des Referates ist es, Qualitätsstandards in der
Kopf-Hals-Onkologie darzustellen.