bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long noncoding RNA NEAT1 suppresses hepatocyte proliferation in fulminant hepatic failure through increased recruitment of EZH2 to the LATS2 promoter region and promotion of H3K27me3 methylation
Authors: Wang Qiang , Liu Lian , Zhang Sheng , Ming Yingzi , Liu Shu , Cheng Ke , Zhao Yujun 
Published: March 2020

AbstractFulminant hepatic failure (FHF) refers to the rapid development of severe acute liver injury with impaired synthetic function and encephalopathy in people with normal liver or well-compensated liver disease. This study aimed to investigate the function of long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) on the proliferation and apoptosis of hepatocytes in FHF. Our results revealed that lncRNA NEAT1 was upregulated in cell and animal models of FHF induced by D-galactosamine (D-GalN)/lipopolysaccharide (LPS). Overexpression of lncRNA NEAT1 resulted in elevated hepatocyte apoptosis and impaired large tumor-suppressor kinase 2 (LATS2) expression and proliferation. Functional analysis revealed that knockdown of lncRNA NEAT1 inhibited hepatocyte apoptosis and induced proliferation both in vitro and in vivo. RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA NEAT1 recruited enhancer of zeste homolog 2 (EZH2) to the LATS2 promoter and repressed LATS2 expression. Furthermore, ectopic expression of LATS2 increased proliferation and inhibited hepatocyte apoptosis by regulating the Hippo/Yes-associated protein (YAP) signaling pathway. Taken together, our findings indicate that lncRNA NEAT1 might serve as a novel target for FHF therapy due to its regulation of H3K27me3 methylation-dependent promotion of LATS2.
Pembrolizumab monotherapy in patients with previously treated metastatic high-grade neuroendocrine neoplasms: joint analysis of two prospective, non-randomised trials
Authors: Vijayvergia Namrata , Dasari Arvind , Deng Mengying , Litwin Samuel , Al-Toubah Taymeyah , Alpaugh R. Katherine , Dotan Efrat , Hall Michael J. , Ross Nicole M. , Runyen Melissa M. , Denlinger Crystal S. , Halperin Daniel M. , Cohen Steven J. , Engstrom Paul F. , Strosberg Jonathan R. 
Published: March 2020

AbstractBackgroundMetastatic high-grade neuroendocrine neoplasms (G3NENs) have limited treatment options after progression on platinum-based therapy. We addressed the role of Pembrolizumab in patients with previously treated metastatic G3NENs.MethodsTwo open-label, phase 2 studies enrolled patients with G3NEN (Ki-67 > 20%) to receive Pembrolizumab at 200 mg I.V. every 3 weeks. Radiographic evaluation was conducted every 9 weeks with overall response rate as the primary endpoint.ResultsBetween November 2016 and May 2018, 29 patients (13 males/16 females) with G3NENs were enrolled. One patient (3.4%) had an objective response and an additional six patients (20.7%) had stable disease, resulting in a disease control rate of 24.1%. Disease control rate (DCR) at 18 weeks was 10.3% (3/29). There was no difference in the DCR, PFS or OS between the PD-L1-negative and -positive groups (p0.56, 0.88 and 0.55, respectively). Pembrolizumab was well tolerated with only 9 grade 3, and no grade 4 events considered drug-related.ConclusionsPembrolizumab can be safely administered to patients with G3NENs but has limited activity as a single agent. Successful completion of our trials suggest studies in G3NENs are feasible and present an unmet need. Further research to identify active combination therapies should be considered.Clinical trial registration numberNCT02939651 (10/20/2016).
Cytoplasmic m1A reader YTHDF3 inhibits trophoblast invasion by downregulation of m1A-methylated IGF1R
Authors: Zheng Qingliang , Gan Haili , Yang Fenglian , Yao Yongli , Hao Fan , Hong Ling , Jin Liping 
Published: March 2020

AbstractN1-methyladenosine (m1A) is one of the important post-transcriptional modifications in RNA and plays an important role in promoting translation or decay of m1A-methylated messenger RNA (mRNA), but the “reader” protein and the exact biological role of m1A remain to be determined. Here, we identified that nine potential m1A “reader” proteins including YTH domain family and heterogeneous nuclear ribonucleoprotein by mass spectrometry, and among them, YTH domain-containing protein 3 (YTHDF3), could bind directly to m1A-carrying RNA. YTHDF3 was then identified to negatively regulate invasion and migration of trophoblast. Mechanistically, we found that the m1A “reader” YTHDF3 bound to certain m1A-methylated transcripts, such as insulin-like growth factor 1 receptor (IGF1R), with the combination of iCLIP-seq (individual-nucleotide resolution ultraviolet crosslinking and immunoprecipitation high-throughput sequencing) and m1A-seq. Furthermore, YTHDF3 could promote IGF1R mRNA degradation and thus inhibit IGF1R protein expression along with its downstream matrix metallopeptidase 9 signaling pathway, consequently decreasing migration and invasion of trophoblast. Thus, we demonstrated that YTHDF3 as an m1A reader decreased invasion and migration of trophoblast by inhibiting IGF1R expression. Our study outlines a new m1A epigenetic way to regulate the trophoblast activity, which suggests a novel therapeutic target for trophoblast-associated pregnancy disorders.
Acute increases in brain-derived neurotrophic factor in plasma following physical exercise relates to subsequent learning in older adults
Authors: Nilsson Jonna , Ekblom Örjan , Ekblom Maria , Lebedev Alexander , Tarassova Olga , Moberg Marcus , Lövdén Martin 
Published: March 2020

AbstractMultidomain lifestyle interventions represents a promising strategy to counteract cognitive decline in older age. Brain-derived neurotrophic factor (BDNF) is essential for experience-dependent plasticity and increases following physical exercise, suggesting that physical exercise may facilitate subsequent learning. In a randomized-controlled trial, healthy older adults (65–75 years) completed a 12-week behavioral intervention that involved either physical exercise immediately before cognitive training (n = 25; 13 females), physical exercise immediately after cognitive training (n = 24; 11 females), physical exercise only (n = 27; 15 females), or cognitive training only (n = 21; 12 females). We hypothesized that cognition would benefit more from cognitive training when preceded as opposed to followed by physical exercise and that the relationship between exercise-induced increases in peripheral BDNF and cognitive training outcome would be greater when cognitive training is preceded by physical exercise. Greater increases of plasma BDNF were associated with greater cognitive training gains on trained task paradigms, but only when such increases preceded cognitive training (ß = 0.14, 95% CI [0.04, 0.25]). Average cognitive training outcome did not differ depending on intervention order (ß = 0.05, 95% CI [−0.10, 0.20]). The study provides the first empirical support for a time-critical but advantageous role for post-exercise increases in peripheral BDNF for learning at an interindividual level in older adults, with implications for future multidomain lifestyle interventions.
Probing the Possibilities of Ergodicity in the 1D Spin-1/2 XY Chain with Quench Dynamics
Authors: Cheraghi Hadi , Mahdavifar Saeed 
Published: March 2020

AbstractErgodicity sits at the heart of the connection between statistical mechanics and dynamics of a physical system. By fixing the initial state of the system into the ground state of the Hamiltonian at zero temperature and tuning a control parameter, we consider the occurrence of the ergodicity with quench dynamics in the one-dimensional (1D) spin-1/2 XY model in a transverse magnetic field. The ground-state phase diagram consists of two ferromagnetic and paramagnetic phases. It is known the magnetization in this spin system is non-ergodic. We set up two different experiments as we call them single and double quenches and test the dynamics of the magnetization along the Z-axis and the spin-spin correlation function along the X-axis which are the order parameters of the zero-temperature phases . Our exact results reveal that for single quenches at zero-temperature, the ergodicity depends on the initial state and the order parameter. In single quenches for a given order parameter, ergodicity will be observed with an ergodic-region for quenches from another phase, non-correspond to the phase of the order parameter, into itself. In addition, a quench from a ground-state phase point corresponding to the order parameter into or very close to the quantum critical point, hc = 1.0, discloses an ergodic behavior. Otherwise, for all other single quenches, the system behaves non-ergodic. Interestingly on the other setup, a double quench on a cyclic path, ergodicity is completely broken for starting from the phase corresponding to the order parameter. Otherwise, it depends on the first quenched point, and the quench time T when the model spent before a second quench in the way back which gives an ability to controlling the ergodicity in the system. Therefore, and contrary to expectations, in the mentioned model the ergodicity can be observed with probing quench dynamics at zero-temperature. Our results provide further insight into the zero-temperature dynamical behavior of quantum systems and their connections to the ergodicity phenomenon.
Downregulation of respiratory complex I mediates major signalling changes triggered by TOR activation
Authors: Perez-Gomez Raquel , Magnin Valentina , Mihajlovic Zorana , Slaninova Vera , Krejci Alena 
Published: March 2020

AbstractMitochondrial dysfunctions belong amongst the most common metabolic diseases but the signalling networks that lead to the manifestation of a disease phenotype are often not well understood. We identified the subunits of respiratory complex I, III and IV as mediators of major signalling changes during Drosophila wing disc development. Their downregulation in larval wing disc leads to robust stimulation of TOR activity, which in turn orchestrates a complex downstream signalling network. Specifically, after downregulation of the complex I subunit ND-49 (mammalian NDUFS2), TOR activates JNK to induce cell death and ROS production essential for the stimulation of compensatory apoptosis-induced proliferation within the tissue. Additionally, TOR upregulates Notch and JAK/STAT signalling and it directs glycolytic switch of the target tissue. Our results highlight the central role of TOR signalling in mediating the complex response to mitochondrial respiratory dysfunction and they provide a rationale why the disease symptoms associated with respiratory dysfunctions are often alleviated by mTOR inhibitors.
The usefulness of endotracheal tube twisting in facilitating tube delivery to glottis opening during GlideScope intubation in infants: randomized trial
Authors: Min Jeong Jin , Oh Eun Jung , Shin Young Hee , Kwon Eunjin , Jeong Ji Seon 
Published: March 2020

AbstractDespite an excellent view of the glottis, technical difficulties with endotracheal tube delivery remains in GlideScope intubation. We evaluated whether a spiral-shape twisted tube can facilitate placement of the tracheal tube tip at the center of glottis opening compared to conventional tube for GlideScope intubation in infants. Eighty-six infants were randomly placed in either the conventional tube group (group C) or the twist tube group (group T). In group T, the shaft of the tube was manually twisted into a loose spiral shape. The primary outcome was the initial center location of the tube tip at the glottis opening, and the secondary outcome was total tube handling time. The initial center location rate of the tube tip at the glottis opening was significantly higher in group T than in group C (88% [38/43] vs. 47% [20/43], P < 0.001). In addition, total tube handling time (sec) was significantly shorter in group T than in group C (15.4 ± 4.7 vs. 18.2 ± 5.3, P = 0.012). In this study, the spiral shape twist tube successfully improved the rate of initial center location of the tube tip at glottis opening and facilitated tube delivery in GlideScope intubation in infants.
Non-dimensional groups for electrospray modes of highly conductive and viscous nanoparticle suspensions
Authors: Castillo-Orozco Eduardo , Kar Aravinda , Kumar Ranganathan 
Published: March 2020

AbstractMultiple modes of atomization in electrosprays are affected by viscosity, surface tension and electrical conductivity of the semiconductor nanosuspensions. While the effect of gravity is dominant in the dripping mode, the electric field degenerates the electrospray mechanism into a microdripping mode that can potentially allow the deposition of semiconductor nanodots on a substrate. Drop size and frequency of droplet formation are obtained as functions of non-dimensional parameters, which agree well with experimental data. The analysis shows that it is possible to produce the desired size and frequency of ejection of monodisperse droplets by manipulating the electrode voltage for any nanosuspension.
Neutrophil Volume, conductivity and scatter (VCS) as a screening tool in neonatal sepsis
Authors: Nesargi Prerana , Niranjan H. S. , Bandiya Prathik , Benakappa Naveen 
Published: March 2020

AbstractThe initial evaluation of a suspected sepsis in a neonate is always challenging. There are many methods to screen a neonate with suspected sepsis. One of newer method is to assess the changes in neutrophil volume conductivity and scatter. The objective of this study was to establish changes in Neutrophil volume conductivity scatter (VCS) in neonatal sepsis and to determine appropriate cut off levels using receiver operating characteristic (ROC) curves. Neonates with suspected sepsis were evaluated with blood counts, culture and neutrophil VCS parameters. Based on these parameters neonates were classified into sepsis group (Blood culture positive), Probable sepsis group (clinical course consistent with sepsis and positive sepsis screen and negative blood culture), No sepsis group (Clinical course not suggestive of sepsis with negative sepsis screen and blood culture). A total of 304 neonates were included in the study of which 144 were in sepsis group and 160 in no sepsis group respectively. Among the neutrophil VCS parameters there was significant difference between the groups with respect to mean neutrophil volume (MNV) and volume distribution width (VDW) (180 vs 163 vs 150) (p < 0.01). MNV and VDW had good sensitivity (95%, 82%) and specificity (86%, 74%) for diagnosis of sepsis. In conclusion, Neutrophil VCS parameters, especially MNV, can be incorporated with other sepsis screen parameters in diagnosis of neonatal sepsis.
Pan-cancer diagnostic consensus through searching archival histopathology images using artificial intelligence
Authors: Kalra Shivam , Tizhoosh H. R. , Shah Sultaan , Choi Charles , Damaskinos Savvas , Safarpoor Amir , Shafiei Sobhan , Babaie Morteza , Diamandis Phedias , Campbell Clinton J. V. , Pantanowitz Liron 
Published: March 2020

AbstractThe emergence of digital pathology has opened new horizons for histopathology. Artificial intelligence (AI) algorithms are able to operate on digitized slides to assist pathologists with different tasks. Whereas AI-involving classification and segmentation methods have obvious benefits for image analysis, image search represents a fundamental shift in computational pathology. Matching the pathology of new patients with already diagnosed and curated cases offers pathologists a new approach to improve diagnostic accuracy through visual inspection of similar cases and computational majority vote for consensus building. In this study, we report the results from searching the largest public repository (The Cancer Genome Atlas, TCGA) of whole-slide images from almost 11,000 patients. We successfully indexed and searched almost 30,000 high-resolution digitized slides constituting 16 terabytes of data comprised of 20 million 1000 × 1000 pixels image patches. The TCGA image database covers 25 anatomic sites and contains 32 cancer subtypes. High-performance storage and GPU power were employed for experimentation. The results were assessed with conservative “majority voting” to build consensus for subtype diagnosis through vertical search and demonstrated high accuracy values for both frozen section slides (e.g., bladder urothelial carcinoma 93%, kidney renal clear cell carcinoma 97%, and ovarian serous cystadenocarcinoma 99%) and permanent histopathology slides (e.g., prostate adenocarcinoma 98%, skin cutaneous melanoma 99%, and thymoma 100%). The key finding of this validation study was that computational consensus appears to be possible for rendering diagnoses if a sufficiently large number of searchable cases are available for each cancer subtype.
Spatial and temporal tracking of cardiac exosomes in mouse using a nano-luciferase-CD63 fusion protein
Authors: Luo Weijia , Dai Yuan , Chen Zhishi , Yue Xiaojing , Andrade-Powell Kelsey C. , Chang Jiang 
Published: March 2020

AbstractExosomes are secreted extracellular vesicles with lipid bilayer membranes. They are emerging as a new category of messengers that facilitate cross-talk between cells, tissues, and organs. Thus, a critical demand arises for the development of a sensitive and non-invasive tracking system for endogenous exosomes. We have generated a genetic mouse model that meets this goal. The Nano-luciferase (NanoLuc) reporter was fused with the exosome surface marker CD63 for exosome labeling. The cardiomyocyte-specific αMHC promoter followed by the loxP-STOP-loxP cassette was engineered for temporal and spatial labeling of exosomes originated from cardiomyocytes. The transgenic mouse was bred with a tamoxifen-inducible Cre mouse (Rosa26Cre-ERT2) to achieve inducible expression of CD63NanoLuc reporter. The specific labeling and tissue distribution of endogenous exosomes released from cardiomyocytes were demonstrated by luciferase assay and non-invasive bioluminescent live imaging. This endogenous exosome tracking mouse provides a useful tool for a range of research applications.
An integrative analysis of 5HTT-mediated mechanism of hyperactivity to non-threatening voices
Authors: Chen Chenyi , Martínez Róger M. , Liao Tsai-Tsen , Chen Chin-Yau , Yang Chih-Yung , Cheng Yawei 
Published: March 2020

AbstractThe tonic model delineating the serotonin transporter polymorphism’s (5-HTTLPR) modulatory effect on anxiety points towards a universal underlying mechanism involving a hyper-or-elevated baseline level of arousal even to non-threatening stimuli. However, to our knowledge, this mechanism has never been observed in non-clinical cohorts exhibiting high anxiety. Moreover, empirical support regarding said association is mixed, potentially because of publication bias with a relatively small sample size. Hence, how the 5-HTTLPR modulates neural correlates remains controversial. Here we show that 5-HTTLPR short-allele carriers had significantly increased baseline ERPs and reduced fearful MMN, phenomena which can nevertheless be reversed by acute anxiolytic treatment. This provides evidence that the 5-HTT affects the automatic processing of threatening and non-threatening voices, impacts broadly on social cognition, and conclusively asserts the heightened baseline arousal level as the universal underlying neural mechanism for anxiety-related susceptibilities, functioning as a spectrum-like distribution from high trait anxiety non-patients to anxiety patients.
Missing water in Class I protostellar disks
Authors: Harsono D. , Persson M. V. , Ramos A. , Murillo N. M. , Maud L. T. , Hogerheijde M. R. , Bosman A. D. , Kristensen L. E. , Jørgensen J. K. , Bergin E. A. , Visser R. , Mottram J. C. , van Dishoeck E. F. 
Published: March 2020

Context. Water is a key volatile that provides insight into the initial stages of planet formation. The low water abundances inferred from water observations toward low-mass protostellar objects may point to a rapid locking of water as ice by large dust grains during star and planet formation. However, little is known about the water vapor abundance in newly formed planet-forming disks.
Aims. We aim to determine the water abundance in embedded Keplerian disks through spatially-resolved observations of H218O lines to understand the evolution of water during star and planet formation.
Methods. We present H218O line observations with ALMA and NOEMA millimeter interferometers toward five young stellar objects. NOEMA observed the 31,3–22,0 line (Eup∕kB = 203.7 K) while ALMA targeted the 41,4–32,1 line (Eup∕kB = 322.0 K). Water column densities were derived considering optically thin and thermalized emission. Our observations were sensitive to the emission from the known Keplerian disks around three out of the five Class I objects in the sample.
Results. No H218O emission is detected toward any of our five Class I disks. We report upper limits to the integrated line intensities. The inferred water column densities in Class I disks are NH218O < 1015 cm−2 on 100 au scales, which include both the disk and envelope. The upper limits imply a disk-averaged water abundance of ≲10−6 with respect to H2 for Class I objects. After taking the physical structure of the disk into account, the upper limit to the water abundance averaged over the inner warm disk with T > 100 K is between ~10−7 and 10−5.
Conclusions. Water vapor is not abundant in warm protostellar envelopes around Class I protostars. Upper limits to the water vapor column densities in Class I disks are at least two orders of magnitude lower than values found in Class 0 disk-like structures.
Supporting Students with TBI: A Clinically Focused Tutorial for Speech-Language Pathologists
Authors: Coreno Alyssa , Ciccia Angela H. 
Published: March 2020

AbstractAttention to pediatric traumatic brain injury (TBI) has grown in recent years, likely due to the increased awareness of mild TBI (mTBI) in contact sports. With this increased attention, along with an increased diagnosis of injury, more students with TBI need services, especially as they return to the classroom environment and progress through school. Support of students with TBI of all severities requires an interdisciplinary team with the school-based speech-language pathologist playing a critical role. The purpose of this tutorial is to provide a clinically focused summary of the complexities that exist for students with TBI of all severities and practical steps that can be implemented in clinical practice to enhance service provision for students with TBI.