bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serotonin stimulated parathyroid hormone related protein induction in the mammary epithelia by transglutaminase-dependent serotonylation
Authors: Sheftel Celeste M. , Hernandez Laura L. 
Published: March 2020

AbstractMammary-derived serotonin [5HT] has been implicated in breast-to-bone communication during lactation by increasing parathyroid hormone related-peptide [PTHrP] in the mammary gland. It is well-established that PTHrP acts on the bone to liberate calcium for the milk during lactation; however, the mechanism of 5HT’s regulation of PTHrP has not been fully elucidated. Recently, serotonylation, has been shown to be involved in a variety of physiological processes. Therefore, we investigated whether serotonylation is involved in 5HT’s regulation of PTHrP in the mammary gland. Using lactogenic differentiated mouse mammary epithelial cells, we studied the effect of increased intracellular 5HT using the antidepressant, fluoxetine [FLX], or 5-hydroxytryptophan ([5HTP] 5HT precursor) with or without transglutaminase inhibition on PTHrP induction and activity and the potential serotonylation target protein, RhoA. Treatment with FLX or 5HTP significantly increased intracellular 5HT concentration and subsequently increased PTHrP gene expression which was reduced with transglutaminase inhibition. Further, we demonstrated that transglutaminase becomes more active with lactogenic differentiation and with 5HTP or FLX treatment. We examined RhoA, Rac1, and Rab4 as potential serotonylation target proteins and have concluded RhoA is likely a serotonylation target protein. Our data suggest that 5HT regulates PTHrP induction in part through the process of serotonylation during lactation.
CReSCENT: CanceR Single Cell ExpressioN Toolkit
Authors: Mohanraj Suluxan , Díaz-Mejía J. Javier , Pham Martin D. , Elrick Hillary , Husić Mia , Rashid Shaikh , Luo Ping , Bal Prabnur , Lu Kevin , Patel Samarth , Mahalanabis Alaina , Naidas Alaine , Christensen Erik , Croucher Danielle , Richards Laura M. , Shooshtari Parisa , Brudno Michael , Ramani Arun K. , Pugh Trevor J. 
Published: March 2020

ABSTRACTCReSCENTCanceR Single Cell ExpressioN Toolkit (https://crescent.cloud), is an intuitive and scalable web portal incorporating a containerized pipeline execution engine for standardized analysis of single-cell RNA sequencing (scRNA-seq) data. While scRNA-seq data for tumour specimens are readily generated, subsequent analysis requires high-performance computing infrastructure and user expertise to build analysis pipelines and tailor interpretation for cancer biology. CReSCENT uses public data sets and preconfigured pipelines that are accessible to computational biology non-experts and are user-editable to allow optimization, comparison, and reanalysis for specific experiments. Users can also upload their own scRNA-seq data for analysis and results can be kept private or shared with other users.
Improved characterization of diffusion in normal and cancerous prostate tissue through optimization of the restriction spectrum imaging signal model
Authors: Conlin Christopher Charles , Feng Christine H , RodrÃ-guez-Soto Ana E , Karunamuni Roshan A , Kuperman Joshua M , Holland Dominic , Rakow-Penner Rebecca , Hahn Michael E , Seibert Tyler M , Dale Anders M 
Published: March 2020

AbstractBackgroundOptimizing a restriction spectrum imaging (RSI) model for the prostate could lead to improved characterization of diffusion in the prostate and better discrimination of tumors.PurposeTo determine optimal apparent diffusion coefficients (ADCs) for prostate RSI models and evaluate the number of tissue compartments required to best describe diffusion in prostate tissue.Study TypeRetrospective.Population/SubjectsForty-six patients who underwent an extended MRI examination for suspected prostate cancer; 23 had prostate tumors and 23 had no detectable cancer.Field strength/Sequence3T multi-shell diffusion weighted sequence.AssessmentRSI models with 2-5 tissue compartments were fit to multi-shell DWI data from the prostate to determine optimal compartmental ADCs. Signal contributions from the different tissue compartments were computed using these ADCs and compared between normal tissues (peripheral zone, transition zone, seminal vesicles) and tumors.Statistical TestsThe Bayesian Information Criterion (BIC) was used to evaluate the optimality of different RSI models. Model-fitting residual (as percent variance) was recorded to assess the models’ goodness-of-fit and whether it varied between anatomical regions of the prostate. Two-sample t-tests (α=0.05) were used to determine the statistical significance of any differences observed in compartmental signal-fraction between normal prostate tissue and tumors.ResultsThe lowest BIC was observed from the 4-compartment model. Optimal ADCs for the 4 compartments were 5.2e-4, 1.9e-3, 3.0e-3, and ≫3.0e-3 mm2/s. Tumor tissue showed the largest reduction in fitting residual by increasing model order. Prostate tumors had a significantly (P≪0.05) greater proportion of signal from compartments 1 and 2 than normal tissue. Tumor conspicuity in compartment 1 increased substantially with model order.Data ConclusionAmong the examined RSI models, the 4-compartment model best described the diffusion-signal characteristics of the prostate. Compartmental signal fractions revealed by such a model may improve discrimination between cancerous and benign prostate tissue.
Prediction of the time evolution of the Covid-19 Pandemic in Italy by a Gauss Error Function and Monte Carlo simulations
Authors: Ciufolini Ignazio , Paolozzi Antonio 
Published: March 2020

AbstractIn this paper are presented predictions on the evolution in time of the number of positive cases in Italy of the Covid-19 pandemic based on official data and on the use of a function of the type of a Gauss Error Function as a Cumulative Distribution Function (CDF). We have analyzed the available data for China and Italy. The evolution in time of the number of cumulative diagnosed positive cases of Covid-19 in China very well approximates a distribution of the type of the Error Function, that is, the integral of a normal, Gaussian distribution. We have then used such a function to study the potential evolution in time of the number of positive cases in Italy by performing a number of fits of the official data so far available. We then found a statistical prediction for the day in which the peak of the number of daily positive cases in Italy occurs, corresponding to the flex of the fit, i.e., to the change in sign of its second derivative (that is the change from acceleration to deceleration) as well as of the day in which a substantial attenuation of such number of daily cases is reached. We have then performed 150 Monte Carlo simulations in the attempt to have a more robust prediction of the day of the above-mentioned peak and of the day of the substantial decrease of the number of daily positive cases. Although, official data have been used, these predictions are obtained with a heuristic approach, since those predictions are based on statistical approach and do not take into account either a number of relevant issues (such as medical, social distancing, virologic, epidemiological, etc.) or models of contamination diffusion.
A mathematical model of COVID-19 transmission between frontliners and the general public
Authors: Buhat Christian Alvin H. , Torres Monica C. , Olave Yancee H. , Gavina Maica Krizna A. , Felix Edd Francis O. , Gamilla Gimelle B. , Verano Kyrell Vann B. , Babierra Ariel L. , Rabajante Jomar F. 
Published: March 2020

ABSTRACTThe number of COVID-19 cases is continuously increasing in different countries (as of March 2020) including the Philippines. It is estimated that the basic reproductive number of COVID-19 is around 1.5 to 4. The basic reproductive number characterizes the average number of persons that a primary case can directly infect in a population full of susceptible individuals. However, there can be superspreaders that can infect more than this estimated basic reproductive number. In this study, we formulate a conceptual mathematical model on the transmission dynamics of COVID-19 between the frontliners and the general public. We assume that the general public has a reproductive number between 1.5 to 4, and frontliners (e.g. healthcare workers, customer service and retail personnel, food service crews, and transport or delivery workers) have a higher reproduction number. Our simulations show that both the frontliners and the general public should be protected or resilient against the disease. Protecting only the frontliners will not result in flattening the epidemic curve. Protecting only the general public may flatten the epidemic curve but the infection risk faced by the frontliners is still high, which may eventually affect their work. Our simple model does not consider all factors involved in COVID-19 transmission in a community, but the insights from our model results remind us of the importance of community effort in controlling the transmission of the disease. All in all, the take-home message is that everyone in the community, whether a frontliner or not, should be protected or should implement preventive measures to avoid being infected.
Estimation of protection for COVID-19 in children from epidemiological information and estimate effect of policy in Japan
Authors: Kurita Junko , Sugishita Yoshiyuki , Sugawara Tamie , Ohkusa Yasushi 
Published: March 2020

AbstractBackgroundIncidence in children was much less than in adults during the COVID-19 outbreak. Sports and entertainment events were canceled (VEC) in Japan for two weeks during 26 February – 13 March. Most schools were closed (SC).ObjectWe construct a susceptible–infected–recovered model using three age classes and estimate the basic reproduction number (R0) and protection level among children simultaneously. Then we simulate SC and VEC effects.MethodWe used data of patients with symptoms in Japan during 14 January to assess SC and VEC introduction. Effects of SC and VEC were incorporated into the model through change in the contact pattern or frequencies among age classes.ResultsResults suggest R0 as 2.86 [95%CI of 2.73, 2.97]. The protection level was estimated as 0.4 [0.2, 0.7]. SC and VEC can reduce the total number of patients significantly, by 6–7%.Discussion and ConclusionThe estimated R0 was similar to that found from other studies in China and Japan. We found a significant protection level among children, and by effects of SC and VEC. Introduction
Late diagnosis of infants with PCD and neonatal respiratory distress
Authors: Myrofora Goutaki , Halbeisen Florian S , Angelo Barbato , Suzanne Crowley , Amanda Harris , Hirst Robert A , Bülent Karadag , Vendula Martinu , Lucy Morgan , Chris O’Callaghan , Ugur Ozçelik , Sergio Scigliano , Santiago Ucros , Panayiotis Yiallouros , Schulzke Sven M , Kuehni Claudia E 
Published: March 2020

AbstractNeonatal respiratory distress (NRD) is common among infants with primary ciliary dyskinesia (PCD), but we do not know whether affected neonates are diagnosed timely.We used data from the international PCD cohort study (iPCD), including only participants diagnosed between 2000 and 2019 using current diagnostic criteria. We assessed the proportion of patients with PCD with a history of NRD and their age at diagnosis, stratifying by presence of laterality defects. First we analysed data from the entire cohort and then from a subgroup including children diagnosed using stricter criteria.Among the 1375 patients in the study, 45% had a history of NRD and 42% a laterality defect. Out of the 476 children with definite PCD diagnosis, 55% had a history of NRD and 50% a laterality defect. PCD was diagnosed at a median age of 3.4 years in this group, varying from less than 1 year in Norway and Cyprus to 10 years in Turkey. Overall, 30% of children with PCD were diagnosed during the first 12 months of life. This varied from 13% in those with situs solitus and no NRD, to 21% in those with situs solitus and NRD, 33% in those with situs anomalies but no NRD, and 52% in those with both NRD and situs anomalies.Our results suggest that we need to improve our knowledge of the neonatal presentation of infants with PCD, and apply this knowledge in neonatology so that these patients will receive appropriate care sooner, at the start of their extrauterine life.What is already known on this topic?Many patients with primary ciliary dyskinesia (PCD) present with neonatal respiratory distress (NRD).The neonatal period would therefore be an ideal window of opportunity to diagnose PCD early, before long-term damage to the lungs has occurred.Despite this, PCD is usually diagnosed late in life.What this study adds?55% of children with PCD in this large multinational dataset had a history of NRD.Among these, PCD was diagnosed early in those with laterality defects (median age 0.9 years) but late in those with situs solitus (5.9 years).This suggests that neonatologists and paediatricians do not suspect PCD as a cause of NRD in term infants unless it is accompanied by laterality defects.
The psychological distress and coping styles in the early stages of the 2019 coronavirus disease (COVID-19) epidemic in the general mainland Chinese population: a web-based survey
Authors: Wang Hui-yao , Xia Qian , Xiong Zhen-zhen , Li Zhi-xiong , Xiang Wei-yi , Yuan Yi-wen , Liu Ya-ya , Li Zhe 
Published: March 2020

AbstractBackgroundAs the epidemic outbreak of 2019 coronavirus disease (COVID-19), general population may experience psychological distress. Evidence has suggested that negative coping styles may be related to subsequent mental illness. Therefore, we investigate the general population’s psychological distress and coping styles in the early stages of the COVID-19 outbreak.MethodsA cross-sectional battery of surveys was conducted from February 1-4, 2020. The Kessler 6 psychological distress scale, the simplified coping style questionnaire and a general information questionnaire were administered on-line to a convenience sample of 1599 in China. Spearman’s correlation was used to measure the correlations among category variables.ResultsGeneral population’s psychological distress were significant differences based on age, marriage, epidemic contact characteristics, concern with media reports, and perceived impacts of the epidemic outbreak (all p <0.001) except gender (p=0.316). Those with a history of visiting Wuhan and a history of epidemics occurring in the community, more concern with media reports, perceived more severe impacts and negative coping style had a higher level of psychological distress, which was significantly positively correlated with a history of visiting Wuhan (r=0.548, p<0.001), a history of epidemics occurring in the community (r=0.219, p<0.001), and concern with media reports (r=0.192, p<0.001). Coping styles were significantly different across all category variables (all p <0.001), and negatively correlated with other category variables (all p<0.01) except age and marriage. Psychological distress was significantly negatively correlated with the coping style (r=-0.573, p<0.01).ConclusionsIn the early stages of COVID-19, general population with epidemic contact characteristics, excessive concern with media reports, and perceived more severe impacts have higher levels of psychological distress. Psychological distress was significantly negatively correlated with the coping style. Interventions should be implemented early, especially for those population with a high level of psychological distress and/or with a negative coping style.
DNA methylation classification in diffuse glioma shows little spatial heterogeneity after adjusting for tumor purity
Authors: Verburg N. , Barthel F.B. , Anderson K.J. , Johnson K.C. , Koopman T. , Yaqub M.M. , Hoekstra O.S. , Lammertsma A.A. , Barkhof F. , Pouwels P.J.W. , Reijneveld J.C. , Rozemuller A.J.M. , Boellaard R. , Taylor M.D. , Das S. , Costello J.F. , Vandertop W.P. , Wesseling P. , de Witt Hamer P.C. , Verhaak R.G.W. 
Published: March 2020

AbstractIntratumoral heterogeneity is a hallmark of diffuse gliomas. We used neuronavigation to acquire 133 image-guided and spatially-separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma, which we characterized using DNA methylation arrays. Samples were obtained from regions with and without imaging abnormalities. Methylation profiles were analyzed to devise a three-dimensional reconstruction of genetic and epigenetic heterogeneity. Molecular aberrations indicated that tumor was found outside imaging abnormalities, underlining the infiltrative nature of this tumor and the limitations of current routine imaging modalities. We demonstrate that tumor purity is highly variable between samples and largely explains apparent epigenetic spatial heterogeneity. Indeed, we observed that DNA methylation subtypes are highly conserved in space after adjusting for tumor purity. Genome-wide heterogeneity analysis showed equal or increased heterogeneity among normal tissue when compared to tumor. These findings were validated in a separate cohort of 61 multi-sector tumor and 64 normal samples. Our findings underscore the infiltrative nature of diffuse gliomas and suggest that heterogeneity in DNA methylation is innate to somatic cells and not a characteristic feature of this tumor type.
Chidamide increases the sensitivity of non-small cell lung cancer to crizotinib by decreasing c-METmRNA methylation
Authors: Ding Nan , You Abin , Tian Wei , Gu Liankun , Deng Dajun 
Published: March 2020

ABSTRACTIntroductionCrizotinib is a kinase inhibitor targeting c-MET/ALK/ROS1 used as the first-line chemical for the treatment of non-small cell lung cancer (NSCLC) withALKmutations. Although c-MET is frequently overexpressed in 35-72% of NSCLC, most NSCLCs are primarily resistant to crizotinib treatment.MethodA set of NSCLC cell lines were used to test the effect of chidamide on the crizotinib sensitivityin vitroandin vivo. Relationships between the synergistic effect of chidamide and c-MET expression and RNA methylation were systemically studied with a battery of molecular biological assays.ResultsWe found for the first time that chidamide could increase the crizotinib sensitivity of a set ofALKmutation-free NSCLC cell lines, especially those with high levels of c-METexpression. Notably, chidamide could not increase the crizotinib sensitivity of NSCLC cells cultured in serum-free medium without hepatocyte growth factor (HGF; a c-MET ligand). In contrast, the addition of HGF into the serum-/HGF-free medium could restore the synergistic effect of chidamide. Moreover, the synergistic effect of chidamide could also be abolished either by treatment with c-MET antibody or siRNA-knockdown of c-METexpression. While cells with low or no c-METexpression were primarily resistant to chidamide-crizotinib cotreatment, enforced c-METoverexpression could increase the sensitivity of these cells to chidamide-crizotinib cotreatment. Furthermore, chidamide could decrease c-METexpression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation ofMETTL3andWTAPexpression. Chidamide-crizotinib cotreatment significantly suppressed the activity of c-MET downstream molecules.Conclusionchidamide downregulated c-METexpression by decreasing its mRNA m6A methylation, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.GRAPHIC SUMMARY
Burst activity plays no role for the field-to-field variability and rate remapping of grid cells
Authors: Poth Michaela , Herz Andreas V.M. 
Published: March 2020

AbstractGrid cells in rodent medial entorhinal cortex are thought to play a key role for spatial navigation. When the animal is freely moving in an open arena the firing fields of each grid cell tend to form a hexagonal lattice spanning the environment. Firing rates vary from field to field and change under contextual modifications, whereas the field locations do not shift under such “rate remapping”. The observed differences in firing rate could reflect overall activity changes or changes in the detailed spike-train statistics. As these two alternatives imply distinct neural coding schemes, we investigated whether temporal firing patterns vary from field to field and whether they change under rate remapping. Focusing on short time scales, we found that the proportion of bursts compared to all discharge events is similar in all firing fields of a given grid cell and does not change under rate remapping. Mean firing rates with and without bursts are proportional for each cell. However, this ratio varies across cells. Additionally, we looked at how rate remapping relates to entorhinal theta-frequency oscillations. Theta-phase coding was preserved despite firing-rate changes from rate remapping but we did not observe differences between the first and second half of the theta cycle, as had been reported for CA1. Our results indicate that both, the heterogeneity between firing fields and rate remapping, are not due to altered firing patterns on short time scales but reflect location-specific changes at the firing-rate level.
Prognostic factors for COVID-19 pneumonia progression to severe symptom based on the earlier clinical features: a retrospective analysis
Authors: Huang Huang , Cai Shuijiang , Li Yueping , Li Youxia , Fan Yinqiang , Li Linghua , Lei Chunliang , Tang Xiaoping , Hu Fengyu , Li Feng , Deng Xilong 
Published: March 2020

AbstractApproximately 15-20% of COVID-19 patients will develop severe pneumonia, about 10 % of which will die if not properly managed. Earlier discrimination of the potential severe patients basing on routine clinical and laboratory changes and commencement of prophylactical management will not only save their lives but also mitigate the otherwise overwhelmed health care burden. In this retrospective investigation, the clinical and laboratory features were collected from 125 COVID-19 patients, who were classified into mild (93 cases) or severe (32 cases) groups according to their clinical outcomes after 3 to 7-days post-admission. The subsequent analysis with single-factor and multivariate logistic regression methods indicated that 17 factors on admission differed significantly between mild and severe groups, but that only comorbid with underlying diseases, increased respiratory rate (>24/min), elevated C-reactive protein (CRP >10mg/liter), and lactate dehydrogenase (LDH >250U/liter), were independently associated with the later disease development. Finally, we evaluated their prognostic values with the receiver operating characteristic curve (ROC) analysis and found that the above four factors could not confidently predict the occurrence of severe pneumonia individually, but that a combination of fast respiratory rate and elevated LDH significantly increased the predictive confidence (AUC= 0.944, sensitivity= 0.941, and specificity= 0.902). A combination consisting of 3- or 4-factors could further increase the prognostic value. Additionally, measurable serum viral RNA post-admission independently predicted the severe illness occurrence. In conclusion, a combination of general clinical characteristics and laboratory tests could provide high confident prognostic value for identifying potential severe COVID-19 pneumonia patients.SummaryWith our successful experience of treating COVID-19 patients, we retrospectively found that routine clinical features could reliably predict severe pneumonia development, thus provide quick and affordable references for physicians to save the otherwise fatal patients with the limited medical resource.