bluuebunny/crossref_metadata_2025_split huggingface dataset:
CN-105 in Participants with Acute SupraTentorial IntraCerebral Hemorrhage (CATCH) Trial
Authors: James Michael L. , Troy Jesse , Nowacki Nathaniel , Komisarow Jordan , Swisher Christa B. , Tucker Kristi , Hatton Kevin , Babi Marc A. , Worrall Bradford B. , Andrews Charles , Woo Daniel , Kranz Peter G. , Lascola Christopher , Maughan Maureen , Laskowitz Daniel T. ,   for the CATCH Investigators
Published: October 2020

AbstractBackgroundEndogenous apoliloprotein E mediates neuroinflammatory responses and recovery after brain injury. Exogenously administered apolipoprotein E-mimetic peptides can effectively penetrate the brain and down-regulate acute inflammation. CN-105 is a novel apolipoprotein E-mimetic pentapeptide with excellent preclinical evidence as an acute intracerebral hemorrhage (ICH) therapeutic. TheCN-105 in participants withAcute supraTentorial intraCerebralHemorrhage (CATCH) trial is a first-in-disease-state, multi-center, open-label trial evaluating safety and feasability of CN-105 administration in patients with acute primary supratentorial ICH.MethodsEligible patients were age 30-80 years, had confirmed primary supratentorial ICH, and able to intiate CN-105 administration (1.0 mg/kg every 6 hours for 72 hours) within 12 hours of symptom onset.A prioridefined safety endpoints, including hematoma volume, pharmacokinetics, and 30-day neurological outcomes were analyzed. For comparisons, CATCH participants were matched 1:1 with a contemporary ICH cohort through random selection. Hematoma volumes determined from computed tomography images on Days 0, 1, 2, and 5 and ordinal modified Rankin Score at 30 days after ICH were compared.ResultsIn 39 participants enrolled across six study sites in the United States, adverse events occurred at expected rate without increase in hematoma expansion or neurological deterioration or significant serum accumulation. CN-105 treatment had an odds ratio (95% confidence interval) of 2.69 (1.31–5.51) for lower 30-day mRS, after adjustment for ICH Score, sex, and race/ethnicity, compared to matched contemporary cohort.ConclusionCN-105 administration represents an excellent translational candidate as an actue ICH therapeutic due to its safety, dosing feasibility, favorable pharmacokinetics, and evidence of improved neurological recovery.
Knowledge and practices towards COVID-19 among Palestinians during the COVID-19 outbreak: A second round cross-sectional survey
Authors: Qutob Nouar , Awartani Faisal , Asia Mohammad , Khader Imad Abu 
Published: October 2020

AbstractCoronavirus disease 2019 (COVID-19) is a highly transmissible illness that spreads rapidly through human-to-human transmission. To assess the knowledge and practices of Palestinians towards COVID-19 after the ease of movement restrictions, we collected data from Palestinian adults between June 15thand June 30th2020. The participants’ pool represented a stratified sample of 1355 adults from Palestinian households across 11 governorates in the West Bank. The questionnaire included 7 demographic questions, 13 questions about participants’ knowledge and awareness of COVID–19, and 4 questions regarding the participants’ safety measures that had been taken in the last three months. Based on the results of this study, we conclude that the majority of participants have a good knowledge about COVID-19, but were not adequately committed to the infection control measures necessary to protect themselves and others. The findings may provide valuable feedback to lawmakers and health administrators to prevent the spread of the epidemic.
Parental acceptance toward behavior guidance techniques for pediatric dental visits: a meta-analysis
Authors: Massignan Carla , Soares Josiane Pezzini , de Souza Pires Maria Marlene , Dick Bruce D. , Porporatti André Luís , De Luca Canto Graziela , Bolan Michele 
Published: October 2020

AbstractObjectiveThe systematic review aimed to compare agreement with behavior guidance techniques (BGT) between parents of children with special health care needs (SHCN) and those non-SHCN.MethodsA structured search of Cochrane Library, Latin American and Caribbean Health Sciences, PubMed, PsycInfo, Scopus, Web of Science, ProQuest Dissertations and Theses Database, Opengrey and Google Scholar was taken up to October 2020. Two authors selected studies independently, extracted the data, assessed the studies’ methodological quality using the Joanna Briggs scale and the Recommendations, Assessment, Development and Evaluation (GRADE).ResultsForty-eight studies covering the parents’ agreement with BGT were included and 41 were retained for random-effects proportion meta-analysis. The methodological quality assessment varied from low to high. Among the parents of non-SHCN children, the agreement with BGT varied from 84.1% (95% CI: 75.8-90.9; p<0.001; I2 93.3%) for tell-show-do to 25.7% (95% CI: 17.8-34.4; p<0.001; I2 90.4%) for passive protective stabilization, without hand-over-mouth. Among the parents of children with SHCN, the acceptance of BGT varied from 89.1% (95% CI: 56.1-99.7; p<0.001; I2 95.7%) for tell-show-do to 29.1% (95% CI: 11.8-50.0; p=0.001; I2 84.8%) to general anesthesia.ConclusionThere is very low certainty in evidence that both the parents of children SHCN and non-SHCN were more likely to agree with basic BGT and that they were less likely to agree with the advanced ones.
Local and Distant responses to single pulse electrical stimulation reflect different forms of connectivity
Authors: Crocker Britni , Ostrowski Lauren , Williams Ziv M. , Dougherty Darin D. , Eskandar Emad N. , Widge Alik S. , Chu Catherine J. , Cash Sydney S. , Paulk Angelique C. 
Published: October 2020

AbstractBackgroundMeasuring connectivity in the human brain can involve innumerable approaches using both noninvasive (fMRI, EEG) and invasive (intracranial EEG or iEEG) recording modalities, including the use of external probing stimuli, such as direct electrical stimulation.Objective/HypothesisTo examine how different measures of connectivity correlate with one another, we compared ‘passive’ measures of connectivity during resting state conditions map to the more ‘active’ probing measures of connectivity with single pulse electrical stimulation (SPES).MethodsWe measured the network engagement and spread of the cortico-cortico evoked potential (CCEP) induced by SPES at 53 total sites across the brain, including cortical and subcortical regions, in patients with intractable epilepsy (N=11) who were undergoing intracranial recordings as a part of their clinical care for identifying seizure onset zones. We compared the CCEP network to functional, effective, and structural measures of connectivity during a resting state in each patient. Functional and effective connectivity measures included correlation or Granger causality measures applied to stereoEEG (sEEGs) recordings. Structural connectivity was derived from diffusion tensor imaging (DTI) acquired before intracranial electrode implant and monitoring (N=8).ResultsThe CCEP network was most similar to the resting state voltage correlation network in channels near to the stimulation location. In contrast, the distant CCEP network was most similar to the DTI network. Other connectivity measures were not as similar to the CCEP network.ConclusionsThese results demonstrate that different connectivity measures, including those derived from active stimulation-based probing, measure different, complementary aspects of regional interrelationships in the brain.
Pharmacological inhibition of nonsense-mediated RNA decay augments HLA class I-mediated presentation of neoepitopes in MSI CRC
Authors: Becker Jonas P. , Helm Dominic , Rettel Mandy , Stein Frank , Hernandez-Sanchez Alejandro , Urban Katharina , Gebert Johannes , Kloor Matthias , Neu-Yilik Gabriele , von Knebel Doeberitz Magnus , Hentze Matthias W. , Kulozik Andreas E. 
Published: October 2020

AbstractMicrosatellite-unstable (MSI) colorectal cancer is characterized by the accumulation of somatic insertion/deletion (InDel) mutations potentially generating tumor-specific, frameshifted protein sequences. Such mutations typically generate premature translation termination codons targeting the affected mRNAs to degradation by nonsense-mediated RNA decay (NMD), limiting the synthesis and HLA class I-mediated presentation of tumor-specific InDel neoepitopes. We reasoned that the NMD inhibitor 5-azacytidine (5AZA) could serve to increase the expression of NMD-sensitive neoepitopes and analyzed the immunopeptidome of MSI HCT-116 cells using a proteogenomic approach. After immunoprecipitation of HLA:peptide complexes, we identified more than 10,000 HLA class I-presented peptides by LC-MS/MS including five InDel neoepitopes. The InDel neoepitopes were verified on the genomic, transcriptomic, and peptidomic level. Treatment with 5AZA increased the expression of the corresponding frameshift- and premature termination codon-bearing mRNAs and enhanced the presentation of peptides originating from known NMD targets and one of the identified InDel neoepitopes. By analyzing an array of MSI colorectal cancer cell lines and patient samples, we found the underlying frameshift mutation to be highly recurrent and immunization with the corresponding neoepitope induced strong CD8+ T cell responses in an HLA-A*02:01 transgenic mouse model. Our data directly show that peptides originating from frameshifted open reading frames due to InDel mutations in mismatch repair-deficient cells are presented on the cell surface via HLA class I. Moreover, we demonstrate the utility of NMD inhibitor-enhanced HLA class I-mediated presentation of InDel neoepitopes as well as their immunogenicity, uncovering the clinical potential of NMD inhibition in anti-cancer immunotherapy strategies.One Sentence SummaryImmunopeptidomics identified increased HLA class I-mediated presentation of immunogenic, frameshift-derived neoepitopes following NMD inhibition.
DIMA: Data-driven selection of a suitable imputation algorithm
Authors: Egert Janine , Warscheid Bettina , Kreutz Clemens 
Published: October 2020

AbstractMotivationImputation is a prominent strategy when dealing with missing values (MVs) in proteomics data analysis pipelines. However, the performance of different imputation methods is difficult to assess and varies strongly depending on data characteristics. To overcome this issue, we present the concept of adata-driven selection of a suitable imputation algorithm(DIMA).ResultsThe performance and broad applicability of DIMA is demonstrated on 121 quantitative proteomics data sets from the PRIDE database and on simulated data consisting of 5 – 50% MVs with different proportions of missing not at random and missing completely at random values. DIMA reliably suggests a high-performing imputation algorithm which is always among the three best algorithms and results in a root mean square error difference (ΔRMSE) ≤ 10% in 84% of the cases.Availability and ImplementationSource code is freely available for download atgithub.com/clemenskreutz/OmicsData.
Detecting changes in dynamical structures in synchronous neural oscillations using probabilistic inference
Authors: Yokoyama Hiroshi , Kitajo Keiichi 
Published: October 2020

AbstractRecent neuroscience studies have suggested that cognitive functions and learning capacity are reflected in the time-evolving dynamics of brain networks. However, an efficient method to detect changes in dynamical brain structures using neural data has yet to be established. To address this issue, we developed a new model-based approach to detect change points in dynamical network structures by combining the model-based network estimation with a phase-coupled oscillator model and sequential Bayesian inference. By giving the model parameter as the prior distribution, applying Bayesian inference allows the extent of temporal changes in dynamic brain networks to be quantified by comparing the prior distribution with posterior distribution using information theoretical criteria. For this, we used the Kullback-Leibler divergence as an index of such changes. To validate our method, we applied it to numerical data and electroencephalography data. As a result, we confirmed that the Kullback-Leibler divergence only increased when changes in dynamical network structures occurred. Our proposed method successfully estimated both directed network couplings and change points of dynamical structures in the numerical and electroencephalography data. These results suggest that our proposed method can reveal the neural basis of dynamic brain networks.
Opening the Pig to Comparative Neuroimaging: A Common Space Approach Contextualizes the Pig and Human Structural Connectome
Authors: Benn R. Austin , Mars Rogier B. , Xu Ting , Yee Jason R. , Rodríguez-Esparragoza Luis , Montesinos Paula , Manzano-Patron J.P , Lopez-Martin Gonzalo , Fuster Valentin , Sanchez-Gonzalez Javier , Duff Eugene P. , Ibañez Borja 
Published: October 2020

AbstractNeuroimaging’s capability to quickly and rapidly phenotype the cortical organization of the whole brain brings with it the possibility to extend our understanding of cortical organization across the mammalian lineage. However, neuroimaging has thus far generally limited itself to a small number of species, with most animal studies being performed in either rodents or Non-Human Primates. Here we perform a first pass characterization of an animal which has recently seen its stock rise in the neuroscience community with the development of new models of neurological disease; the domestic pig. Characterizing the structural connectome of the pig, we create a white matter atlas, and an anatomical template which we use to build a horizontal translation between the pig and human based on a connectivity blueprint approach. We find that conserved trends of structural connectivity across species enabled spatial prediction of regions of interest between the pig and human, showing the potential horizontal translations have as a tool to assess the translational validity of porcine models of neurological disease. Releasing the anatomical template, white matter atlas, and connectivity blueprints, we hope to ease and promote the acceptance of the pig as an alternative large-animal model by the neuroimaging community.
ACIS, A Novel KepTide™, Binds to ACE-2 Receptor and Inhibits the Infection of SARS-CoV2 Virus in vitro in Primate Kidney Cells: Therapeutic Implications for COVID-19
Authors: Gottschalk Gunnar , Keating James , Kessler Kris , Luan Chi-Hao , Knox Konstance , Roy Avik 
Published: October 2020

AbstractCoronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome (SARS) caused by a virus known as SARS-Coronavirus 2 (SARS-CoV2). Without a targeted-medicine, this disease has been causing a massive humanitarian crisis not only in terms of mortality, but also imposing a lasting damage to social life and economic progress of humankind. Therefore, an immediate therapeutic strategy needs to be intervened to mitigate this global crisis. Here, we report a novel KepTide™ (Knock-End Peptide) therapy that nullifies SARS-CoV2 infection. SARS-CoV2 employs its surface glycoprotein “spike” (S-glycoprotein) to interact with angiotensin converting enzyme-2 (ACE-2) receptor for its infection in host cells. Based on our in-silico-based homology modeling study validated with a recent X-ray crystallographic structure (PDB ID:6M0J), we have identified that a conserved motif of S-glycoprotein that intimately engages multiple hydrogen-bond (H-bond) interactions with ACE-2 enzyme. Accordingly, we designed a peptide, termed as ACIS (ACE-2 Inhibitory motif of Spike), that displayed significant affinity towards ACE-2 enzyme as confirmed by biochemical assays such as BLItz and fluorescence polarization assays. Interestingly, more than one biochemical modifications were adopted in ACIS in order to enhance the inhibitory action of ACIS and hence called as KEpTide™. Consequently, a monolayer invasion assay, plaque assay and dual immunofluorescence analysis further revealed that KEpTide™ efficiently mitigated the infection of SARS-CoV2 in vitro in VERO E6 cells. Finally, evaluating the relative abundance of ACIS in lungs and the potential side-effects in vivo in mice, our current study discovers a novel KepTide™ therapy that is safe, stable, and robust to attenuate the infection of SARS-CoV2 virus if administered intranasally.
Rapid Development of Neutralizing and Diagnostic SARS-COV-2 Mouse Monoclonal Antibodies
Authors: Chapman Asheley P. , Tang Xiaoling , Lee Joo R. , Chida Asiya , Mercer Kristina , Wharton Rebekah E. , Kainulainen Markus , Harcourt Jennifer L. , Martines Roosecelis B. , Schroeder Michelle , Zhao Liangjun , Bryksin Anton , Zhou Bin , Bergeron Eric , Bollweg Brigid C. , Tamin Azaibi , Thornburg Natalie , Wentworth David E. , Petway David , Bagarozzi Dennis , Finn M.G. , Goldstein Jason M. 
Published: October 2020

AbstractThe need for high-affinity, SARS-CoV-2-specific monoclonal antibodies (mAbs) is critical in the face of the global COVID-19 pandemic, as such reagents can have important diagnostic, research, and therapeutic applications. Of greatest interest is the ~300 amino acid receptor binding domain (RBD) within the S1 subunit of the spike protein because of its key interaction with the human angiotensin converting enzyme 2 (hACE2) receptor present on many cell types, especially lung epithelial cells. We report here the development and functional characterization of 29 nanomolar-affinity mouse SARS-CoV-2 mAbs created by an accelerated immunization and hybridoma screening process. Differing functions, including binding of diverse protein epitopes, viral neutralization, impact on RBD-hACE2 binding, and immunohistochemical staining of infected lung tissue, were correlated with variable gene usage and sequence.
Transcript-specific determinants of pre-mRNA splicing revealed throughin vivokinetic analyses of the 1stand 2ndchemical steps
Authors: Gildea Michael A. , Dwyer Zachary W. , Pleiss Jeffrey A. 
Published: October 2020

SummaryUnderstanding how the spliceosome processes its composite of substrates through the two chemical steps required for mRNA production will be essential to deciphering splicing regulation and mis-regulation. Here we measure thein vivorates of these steps across the genome by coupling metabolic RNA labeling, targeted sequencing, and first order kinetic modeling. We reveal a wide variety of rates by which introns are removed, that splice site sequences are primary determinants of 1ststep rates, and that the 2ndstep is generally faster than the 1ststep. We show that ribosomal protein genes (RPGs) are spliced faster than non-RPGs at each step, and that RPGs share evolutionarily conserved cis-features which facilitate their splicing. A genetic variant defective at the 1ststep shows the expected defect in the 1ststep, but an unexpected change in the 2ndstep which suggests how co-transcriptional splicing functions as an important determinant of splicing rates.
Computational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair
Authors: Lo Chen Hao , Baratchart Etienne , Basanta David , Lynch Conor C 
Published: October 2020

ABSTRACTBone-forming osteoblasts and -resorbing osteoclasts control bone injury repair, and myeloid-derived cells such as monocytes and macrophages are known to influence their behavior. However, precisely how these multiple cell types coordinate and regulate each other over time to repair injured bone is difficult to dissect using biological approaches. Conversely, mathematical modeling lends itself well to this challenge. Therefore, we generated an ordinary differential equation (ODE) model powered by experimental data (osteoblast, osteoclast, bone volume, pro- and anti-inflammatory myeloid cells) obtained from intra-tibially injured mice. Initial ODE results using only osteoblast/osteoclast populations demonstrated that bone homeostasis could not be recovered after injury, but this issue was resolved upon integration of pro- and anti-inflammatory myeloid population dynamics. Surprisingly, the ODE revealed temporal disconnects between the peak of total bone mineralization/resorption, and osteoblast/osteoclast numbers. Specifically, the model indicated that osteoclast activity must vary greatly (>17-fold) to return the bone volume to baseline after injury and suggest that osteoblast/osteoclast number alone is insufficient to predict bone the trajectory of bone repair. Importantly, the values of osteoclast activity fall within those published previously. These data underscore the value of mathematical modeling approaches to understand and reveal new insights into complex biological processes.
Diazepam attenuates the effects of cocaine on locomotion, 50-kHz ultrasonic vocalizations and phasic dopamine release in the nucleus accumbens of rats
Authors: Sanchez William N. , Pochapski Jose A. , Jessen Leticia F. , Ellenberger Marek , Schwarting Rainer K. , Robinson Donita L. , Andreatini Roberto , Cunha Claudio Da 
Published: October 2020

AbstractBackground and PurposeCurrently, no effective drug exists to treat cocaine use disorders, which affect millions of people worldwide. Benzodiazepines are potential therapeutic candidates, as microdialysis and voltammetry studies have shown that they can decrease dopamine release in the nucleus accumbens of rodents. In addition, we have recently shown that diazepam blocks the increase in dopamine release and the affective marker 50-kHz ultrasonic vocalizations (USV) induced by DL-amphetamine in rats.Experimental ApproachHere we tested whether administration of 2.5 mg·kg−1diazepam (i.p.) in adult male Wistar rats could block the effects of 20 mg·kg−1cocaine (i.p.) on electrically evoked phasic dopamine release in the nucleus accumbens measured by fast-scan cyclic voltammetry, as well as 50-kHz USV and locomotor activity.Key ResultsCocaine injection increased evoked dopamine release up to 3-fold within 5 min and the increase was significantly higher than baseline for at least 90 min. The injection of diazepam 15 min later attenuated the cocaine effect by nearly 50% and this attenuation was maintained for at least 30 min. Stimulant drugs, natural rewards and reward predictive cues are known to evoke 50-kHz USV in adult rats. In the present study, cocaine increased the number of 50-kHz USV of the flat, step, trill, and mixed kinds by 12-fold. This effect was at maximum 5 min after cocaine injection, decreased with time and lasted at least 40 min. Diazepam significantly blocked this effect for the entire duration of the session. The distance travelled by control rats during a 40-min session of exploration in an open field was at maximum in the first 5 min and decayed progressively until the end of the session. Cocaine-treated rats travelled significantly longer distances when compared to the control group, while diazepam significantly attenuated cocaine-induced locomotion by up to 50%.Conclusions and implicationThese results suggest that the neurochemical, affective, and stimulant effects of cocaine can be mitigated by diazepam.What is already knownDiazepam decreases dopamine release in the rodent nucleus accumbens (NAc) and reduces some effects produced by DL-amphetamine.What this study addsDiazepam attenuated the increase in phasic dopamine release caused by cocaine.Diazepam blocked the effect of cocaine on 50-kHz USV and locomotor activity.Clinical significanceThis study demonstrates that diazepam can block specific effects of cocaine that likely contribute to addiction.