bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mobile Laboratory Measurements of High Surface Ozone Levels and Spatial Heterogeneity During LISTOS 2018: Evidence for Sea Breeze Influence
Authors: Zhang Jie , Ninneman Matthew , Joseph Everette , Schwab Margaret J. , Shrestha Bhupal , Schwab James J. 
Published: May 2020

AbstractThe Long Island Sound Tropospheric Ozone Study (LISTOS) was organized to investigate ozone formation and transport in the New York City metropolitan area and locations downwind. During LISTOS, the University at Albany Atmospheric Sciences Research Center (ASRC) mobile laboratory was used for measuring surface O3, NO2, and aerosol number and mass concentration. Sharp O3 concentration gradients, with ΔO3 Δy−1 over 15 ppb km−1, were measured both at and near the land‐water interface and on the highway on days characterized by high regional O3 concentrations. These large O3 gradients at or near the land‐water interface, and in air masses relatively low in NO2, are shown to be influenced in part by the transport of highly oxidized air masses via sea breeze circulation and convergence with gradient flow. On the highway under regionally high O3 concentrations, strong anticorrelation (R2 = 0.78, p < 0.05) between O3 and NO2 and an absolute slope less than 1 suggested that Ox concentrations (O3 + NO2) increased with increasing NO2. Overall, the on‐road measurements made during LISTOS help to better characterize the interaction between the emitted pollution and the meteorological conditions on Long Island, thereby having potential policy implications.
Reduction of depression-like behavior in rat model induced by ShRNA targeting norepinephrine transporter in locus coeruleus
Authors: Du Xiangdong , Yin Ming , Yuan Lian , Zhang Guangya , Fan Yan , Li Zhe , Yuan Nian , Lv Xiaoli , Zhao Xueli , Zou Siyun , Deng Wei , Kosten Thomas R. , Zhang Xiang Yang 
Published: May 2020

AbstractDepression may be associated with reduced monoamine neurotransmission, particularly serotonin and norepinephrine (NE). Reuptake of NE by the norepinephrine transporter (NET) is the primary mechanism by which many of the antidepressants are high-affinity substrates for NET. This study aimed to examine the effect of lentivirus-mediated shRNA targeting NET in locus coeruleus (LC) on depression-like behaviors of rats. We randomly assigned 60 male Wistar rats to 6 experimental groups: (1) Control group: without chronic unpredictable mild stress (CUMS) and without NET-shRNA treatment; (2) shRNA group: without CUMS + NET-shRNA; (3) CUMS group: 3-week CUMS without NET-shRNA; (4) CUMS + nonsense shRNA group; (5) CUMS + amygdala (Amy)-shRNA group; (6) CUMS+ locus coeruleus (LC)-shRNA group. First, recombinant lentiviral vector expressing shRNA (ShRNA-629, ShRNA-330, ShRNA-1222, ShRNA-1146 or ShRNA- negative control) against NET were produced, and their efficiency in knocking down of NET in PC12 cells were assessed by Q-PCR and western blot analysis. Second, shRNA was injected into the rat LC bilaterally to investigate whether it could prevent the depressive-like behavior induced by 3-week CUMS. Third, we tested the depressive-like behavior of the rats in the forced swimming test, the open field test, the sucrose preference test, as well as the body weight gain at the end of the seventh week. Finally, the protein expressions of NET was measured by western blot and the NE levels were measured by high performance liquid chromatography. Q-PCR and western blot showed that the ShRNA-1146 had the best interference efficiency targeting on NET in PC12 cells (p < 0.01). Compared to the depression model group, the immobility time in the forced swimming test was significantly reduced (p < 0.01), but the sucrose preference and the total scores in the open field test were significantly increased (all p < 0.01) in the group treated with shRNA in LC. Furthermore, compared with the depression model group, NET levels were significantly decreased (p < 0.01), but NE levels were significantly increased in the group treated with shRNA in LC (p < 0.05). Our findings suggest that Lentivirus-mediated shRNA targeting NET in LC downregulated NET both in vitro and in vivo, resulting in a significant decrease in depressive-like behavior of rats.
Impact of numerical variation, allele burden, mutation length and co-occurring mutations on the efficacy of tyrosine kinase inhibitors in newly diagnosed FLT3- mutant acute myeloid leukemia
Authors: Abou Dalle Iman , Ghorab Ahmad , Patel Keyur , Wang Xuemei , Hwang Hyunsoo , Cortes Jorge , Issa Ghayas C. , Yalniz Fevzi , Sasaki Koji , Chihara Dai , Price Allyson , Kadia Tapan , Pemmaraju Naveen , Daver Naval , DiNardo Courtney , Ravandi Farhad , Kantarjian Hagop M. , Borthakur Gautam 
Published: May 2020

AbstractFLT3-ITD mutations in newly diagnosed acute myeloid leukemia (AML) are associated with worse overall survival (OS). FLT3-ITD diversity can further influence clinical outcomes. Addition of FLT3 inhibitors to standard chemotherapy has improved OS. The aim of this study is to evaluate the prognostic impact of FLT3 diversity and identify predictors of efficacy of FLT3 inhibitors. We reviewed prospectively collected data from 395 patients with newly diagnosed FLT3-ITD mutant AML. 156 (39%) patients received FLT3 inhibitors combined with either high or low intensity chemotherapy. There was no statistically significant difference in clinical outcomes among patients treated with FLT3 inhibitors based on FLT3 numerical variation (p = 0.85), mutation length (p = 0.67). Overall, the addition of FLT3 inhibitor to intensive chemotherapy was associated with an improved OS (HR = 0.35, 95% CI: 0.24–0.5, p = 0.0005), but not in combination with lower intensity chemotherapy (HR = 0.98, 95%CI: 0.7–1.36, p = 0.85). A differential effect of FLT3 inhibitor on OS was more pronounced in younger patients with FLT3 allelic ratio ≥0.5 (HR = 0.41, 95% CI: 0.25–0.66, p < 0.001), single ITD mutation (HR = 0.55, 95% CI: 0.34–0.88, p = 0.01), diploid cytogenetics (HR = 0.52, 95% CI: 0.35–0.76, p = 0.001), NPM1 co-mutation (HR = 0.35, 95% CI: 0.19–0.67, p = 0.001). Our analysis identifies predictors of survival among diverse FLT3 related variables in patients treated with FLT3 inhibitor.
Relationship between markers of malnutrition and clinical outcomes in older adults with cancer: systematic review, narrative synthesis and meta-analysis
Authors: Bullock Alex F. , Greenley Sarah L. , McKenzie Gordon A. G. , Paton Lewis W. , Johnson Miriam J. 
Published: May 2020

AbstractMalnutrition predicts poorer clinical outcomes for people with cancer. Older adults with cancer are a complex, growing population at high risk of weight-losing conditions. A number of malnutrition screening tools exist, however the best screening tool for this group is unknown. The aim was to systematically review the published evidence regarding markers and measures of nutritional status in older adults with cancer (age ≥ 70). A systematic search was performed in Ovid Medline, EMBASE, Web of Science, CINAHL, British Nursing Database and Cochrane CENTRAL; search terms related to malnutrition, cancer, older adults. Titles, abstracts and papers were screened and quality-appraised. Data evaluating ability of markers of nutritional status to predict patient outcomes were subjected to meta-analysis or narrative synthesis. Forty-two studies, describing 15 markers were included. Meta-analysis found decreased food intake was associated with mortality (OR 2.15 [2.03–4.20] p = < 0.00001) in univariate analysis. Prognostic Nutritional Index (PNI) was associated with overall survival (HR 1.89 [1.03–3.48] p = 0.04). PNI markers (albumin, total lymphocyte count) could be seen as markers of inflammation rather than nutrition. There a suggested relationship between very low body mass index (BMI) (<18 kg/m2) and clinical outcomes. No tool was identified as appropriate to screen for malnutrition, as distinct from inflammatory causes of weight-loss. Risk of cancer-cachexia and sarcopenia in older adults with cancer limits the tools analysed. Measures of food intake predicted mortality and should be included in clinical enquiry. A screening tool that distinguishes between malnutrition, cachexia and sarcopenia in older adults with cancer is needed.
Efficient correction of a deleterious point mutation in primary horse fibroblasts with CRISPR-Cas9
Authors: Pinzon-Arteaga Carlos , Snyder Matthew D. , Lazzarotto Cicera R. , Moreno Nicolas F. , Juras Rytis , Raudsepp Terje , Golding Michael C. , Varner Dickson D. , Long Charles R. 
Published: May 2020

AbstractPhenotypic selection during animal domestication has resulted in unwanted incorporation of deleterious mutations. In horses, the autosomal recessive condition known as Glycogen Branching Enzyme Deficiency (GBED) is the result of one of these deleterious mutations (102C > A), in the first exon of the GBE1 gene (GBE1102C>A). With recent advances in genome editing, this type of genetic mutation can be precisely repaired. In this study, we used the RNA-guided nuclease CRISPR-Cas9 (clustered regularly-interspaced short palindromic repeats/CRISPR-associated protein 9) to correct the GBE1102C>A mutation in a primary fibroblast cell line derived from a high genetic merit heterozygous stallion. To correct this mutation by homologous recombination (HR), we designed a series of single guide RNAs (sgRNAs) flanking the mutation and provided different single-stranded donor DNA templates. The distance between the Cas9-mediated double-stranded break (DSB) to the mutation site, rather than DSB efficiency, was the primary determinant for successful HR. This framework can be used for targeting other harmful diseases in animal populations.
ATR Inhibition Broadly Sensitizes Soft-Tissue Sarcoma Cells to Chemotherapy Independent of Alternative Lengthening Telomere (ALT) Status
Authors: Laroche-Clary Audrey , Chaire Vanessa , Verbeke Stéphanie , Algéo Marie-Paule , Malykh Andrei , Le Loarer François , Italiano Antoine 
Published: May 2020

AbstractOnly few drugs have shown activity in patients with advanced soft-tissue and the median overall survival is only 18 months. Alterations of genes involved in the DNA damage repair pathway have been associated with sarcoma risk and prognosis. ATR plays a crucial role in maintaining genomic integrity by responding to a large spectrum of DNA damage, including double strand breaks (DSBs) that interfere with replication. The objective of this study is to evaluate the pre-clinical activity of ATR inhibition in soft tissue sarcomas (STS). We explored the ability of the ATR inhibitor, VE-822, to prevent chemotherapy-induced intra-S-phase checkpoint activation and evaluated the antitumor potential of this combination in vitro and in vivo in STS cell lines and in a patient-derived xenograft model. The combination of VE-822 and gemcitabine in vitro was synergistic, inhibited cell proliferation, induced apoptosis, and accumulated in the S phase of the cell cycle with higher efficacy than either single agent alone. The combination also resulted in enhanced γH2AX intranuclear accumulation as a result of DNA damage induction. These effects were unrelated to the alternative lengthening of telomeres pathway. In vivo, the combination of VE-822 and gemcitabine significantly enhanced tumor growth inhibition and progression-free survival in an aggressive model of undifferentiated pleomorphic sarcoma. The combination of ATR inhibitor and chemotherapy is beneficial in pre-clinical models of soft-tissue sarcoma and deserves further exploration in the clinical setting.
Comparative Analyses of the Conformational Dynamics Between the Soluble and Membrane-Bound Cytokine Receptors
Authors: Yang Chao-Yie 
Published: May 2020

AbstractCytokine receptors receive extracellular cues by binding with cytokines to transduce a signaling cascade leading to gene transcription in cells. Their soluble isoforms, functioning as decoy receptors, contain only the ectodomain. Whether the ectodomains of cytokine receptors at the membrane exhibit different conformational dynamics from their soluble forms is unknown. Using Stimulation-2 (ST2) as an example, we performed microsecond molecular dynamics (MD) simulations to study the conformational dynamics of the soluble and the membrane-bound ST2 (sST2 and ST2). Combined use of accelerated and conventional MD simulations enabled extensive sampling of the conformational space of sST2 for comparison with ST2. Using the interdomain loop conformation as the reaction coordinate, we built a Markov State Model to determine the slowest implied timescale of the conformational transition in sST2 and ST2. We found that the ectodomain of ST2 undergoes slower conformational relaxation but exhibits a faster rate of conformational transition in a more restricted conformational space than sST2. Analyses of the relaxed conformations of ST2 further suggest important contributions of interdomain salt-bridge interactions to the stabilization of different ST2 conformations. Our study elucidates differential conformational properties between sST2 and ST2 that may be exploited for devising strategies to selectively target each isoform.
The role of early social rearing, neurological, and genetic factors on individual differences in mutual eye gaze among captive chimpanzees
Authors: Hopkins William D. , Mulholland Michele M. , Reamer Lisa A. , Mareno Mary Catherine , Schapiro Steven J. 
Published: May 2020

AbstractMutual eye gaze plays an important role in primate social development and communication. In the current study, we examined the underlying experiential, genetic, and neuroanatomical basis of mutual eye gaze variation in adult captive chimpanzees. A multivariate analysis of variance revealed a significant rearing effect on bout length, with human-reared chimpanzees engaging in longer bouts of mutual gaze compared to mother-reared and wild-born individuals. Next, we utilized source-based morphometry (SBM) to examine gray matter covariation in magnetic resonance imaging scans and determine the relationship between the resulting gray matter covariation components and mutual eye gaze. One SBM component was negatively correlated with gaze duration (nucleus accumbens and anterior insular cortex), while two components were positively correlated with bout length (posterior cingulate cortex, inferior occipital cortex, middle temporal cortex, hippocampus, and the precentral sulcus). Finally, heritability analyses revealed mutual eye gaze to be modestly heritable and significant genetic correlations between bout length and two gray matter covariation components. This study reveals that non-genetic factors, and to a lesser extent, genetic factors appear to influence mutual eye gaze in adult chimpanzees, and is the first to report neuroanatomical correlates of mutual eye gaze variation in chimpanzees.
Effects of Schizochytrium and micro-minerals on immune, antioxidant, inflammatory and lipid-metabolism status of Micropterus salmoides fed high- and low-fishmeal diets
Authors: Habte-Tsion Habte-Michael , Kolimadu Gagan D. , Rossi Waldemar , Filer Keith , Kumar Vikas 
Published: May 2020

AbstractA 12-week factorial experiment was conducted to investigate the interactive effects of dietary algal meal (Schizochytrium sp., AM) and micro-minerals (MM, either organic [OM] or inorganic [IM]) on the immune and antioxidant status, and the expression of hepatic genes involved in the regulation of antioxidants, inflammatory cytokines, lipid metabolism, and organ growth of largemouth bass (LMB; Micropterus salmoides) fed high-and low-fishmeal (FM) diets. For this purpose, two sets of six iso-nitrogenous (42% crude protein) and iso-lipidic (12% lipid) diets, such as high (35%) and low (10%) FM diets were formulated. Within each FM level, AM was used to replace 50% or 100% of fish oil (FO), or without AM (FO control) and supplemented with either OM or IM (Fe, Zn, Mn, Cu, and Se). Diets were fed to juvenile LMB (initial weight, 25.87 ± 0.08 g) to near satiation twice daily. The results indicated that FO replacement by dietary AM did not change the levels of most biochemical (ALB, AMY, TP and GLOB), antioxidants (SOD, GPx and GSH), and immune (IgM and lysozyme) parameters in LMB, except ALP and CAT. MM affected only hepatic GSH, with lower values in fish fed the OM diets. FM influenced the levels of ALP, AMY, GLOB, IgM, and MDA (P < 0.05). A three-way interactive effect (P = 0.016) was found on IgM only, with lower levels in fish fed diet 12 (low-FM, AM100, OM). Subsequently, the relative expressions of hepatic antioxidants (Cu/Zn-SOD and GPx-4), inflammatory cytokines (TNF-α and TGF-β1), lipid metabolism (FASN and CYP7A1), and organ growth (IGF-I) related genes were affected by the dietary treatments, with interactions being present in Cu/Zn-SOD, TNF-α, TGF-β1, FASN and IGF-I. Overall, dietary AM could be used as an alternative to FO in low-FM diets without compromising the health of LMB, especially when it is supplemented with MM.
Incidence of acute type A aortic dissection in emergency departments
Authors: Wundram Maximilian , Falk Volkmar , Eulert-Grehn Jaime-Jürgen , Herbst Hermann , Thurau Jana , Leidel Bernd A. , Göncz Eva , Bauer Wolfgang , Habazettl Helmut , Kurz Stephan D. 
Published: May 2020

AbstractDue to the symptoms, patients with acute type A aortic dissection are first seen by the ambulance service and diagnosed at the emergency department. How often an aortic dissection occurs in an emergency department per year has been studied. The incidence in the emergency department may be used as a quality marker of differential diagnostics of acute chest pain. A multi-institutional retrospective study with the municipal Berlin hospital chain Vivantes and its Department of Pathology and the Charité - University Medicine Berlin was performed. From the Berlin Hospital Society, the annual numbers of publicly insured emergency patients were obtained. Between 2006 and 2016, 631 aortic dissections were identified. The total number of patients treated in the emergency departments (n = 12,790,577) was used to calculate the “emergency department incidence.” The autopsy data from six clinics allowed an estimate on how many acute type A aortic dissections remained undetected. Across all Berlin hospitals, the emergency department incidence of acute type A aortic dissection was 5.24 cases in 100,000 patients per year. In tertiary referral hospitals and, particularly, in university hospitals the respective incidences were markedly higher (6.7 and 12.4, respectively). Based on the autopsy results, about 50% of the acute type A aortic dissection may remain undetected, which would double the reported incidences. Among different hospital types the emergency department incidences of acute type A aortic dissection vary between 5.93/100,000 and 24.92/100,000. Aortic dissection; Incidence; Emergency Department; Epidemiology
Transcriptome-wide analysis reveals different categories of response to a standardised immune challenge in a wild rodent
Authors: Wanelik Klara M. , Begon Mike , Arriero Elena , Bradley Janette E. , Friberg Ida M. , Jackson Joseph A. , Taylor Christopher H. , Paterson Steve 
Published: May 2020

AbstractIndividuals vary in their immune response and, as a result, some are more susceptible to infectious disease than others. Little is known about the nature of this individual variation in natural populations, or which components of immune pathways are most responsible, but defining this underlying landscape of variation is an essential first step to understanding the drivers of this variation and, ultimately, predicting the outcome of infection. We describe transcriptome-wide variation in response to a standardised immune challenge in wild field voles. We find that genes (hereafter 'markers') can be categorised into a limited number of types. For the majority of markers, the response of an individual is dependent on its baseline expression level, with significant enrichment in this category for conventional immune pathways. Another, moderately sized, category contains markers for which the responses of different individuals are also variable but independent of their baseline expression levels. This category lacks any enrichment for conventional immune pathways. We further identify markers which display particularly high individual variability in response, and could be used as markers of immune response in larger studies. Our work shows how a standardised challenge performed on a natural population can reveal the patterns of natural variation in immune response.
miR-744-5p contributes to ocular inflammation in patients with primary Sjogrens Syndrome
Authors: Pilson Qistina , Smith Siobhan , Jefferies Caroline A. , Ní Gabhann-Dromgoole Joan , Murphy Conor C. 
Published: May 2020

AbstractIn primary Sjögren’s syndrome (pSS) the exocrine glands become infiltrated with lymphocytes instigating severe damage to the salivary and lacrimal glands causing dry eyes and dry mouth. Previous investigations have suggested that dysregulated localized and systemic inflammation contributes to the development and pathogenesis of pSS. A miR microarray performed in primary human conjunctival epithelial cells (PECs) demonstrated significant differences in miR expression at the ocular surface between pSS patients and healthy controls. MicroRNA-744-5p (miR-744-5p) was identified as being of particular interest, as its top predicted target is Pellino3 (PELI3), a known negative regulator of inflammation. Validation studies confirmed that miR-744-5p expression is significantly increased in PECs from pSS patients, whilst PELI3 was significantly reduced. We validated the miR-744 binding site in the 3’ untranslated region (UTR) of PELI3 and demonstrated that increasing PELI3 levels with a miR-744-5p antagomir in an inflammatory environment resulted in reduced levels of IFN dependent chemokines Rantes (CCL5) and CXCL10. These results reveal a novel role for miR-744-5p in mediating ocular inflammation via Pellino3 expression in pSS patients and suggest that miR-744-5p may be a potential therapeutic target for the management of severe dry eye disease and ocular inflammation in pSS patients.
A Complex Life Habitable Zone Based On Lipid Solubility Theory
Authors: Ramirez Ramses M. 
Published: May 2020

AbstractTo find potentially habitable exoplanets, space missions employ the habitable zone (HZ), which is the region around a star (or multiple stars) where standing bodies of water could exist on the surface of a rocky planet. Follow-up atmospheric characterization could yield biosignatures signifying life. Although most iterations of the HZ are agnostic regarding the nature of such life, a recent study argues that a complex life HZ would be considerably smaller than that used in classical definitions. Here, I use an advanced energy balance model to show that such an HZ would be considerably wider than originally predicted given revised CO2 limits and (for the first time) N2 respiration limits for complex life. The width of this complex life HZ (CLHZ) increases by ~35% from ~0.95–1.2 AU to 0.95–1.31 AU in our solar system. Similar extensions are shown for stars with stellar effective temperatures between 2,600–9,000 K. I define this CLHZ using lipid solubility theory, diving data, and results from animal laboratory experiments. I also discuss implications for biosignatures and technosignatures. Finally, I discuss the applicability of the CLHZ and other HZ variants to the search for both simple and complex life.