bluuebunny/crossref_metadata_2025 huggingface dataset:
Can ocular dominance plasticity provide a general index to visual plasticity to personalize treatment in amblyopia?
Authors: Tao Chunwen , He Zhifen , Chen Yiya , Zhou Jiawei , Hess Robert F.
Published: March 2020

Purpose

Recently, Lunghi et al showed that amblyopic eye’s visual acuity per se after 2 months of occlusion therapy could be predicted by a homeostatic plasticity, i.e., the temporary shift of ocular dominance observed after a 2-hour monocular deprivation, in children with anisometropic amblyopia(Lunghi et al., 2016). In this study, we assess whether the visual acuity improvement of the amblyopic eye measured after 2 months of occlusion therapy could be predicted by this plasticity.

Methods

Seven children (6.86 ± 1.46 years old; SD) with anisometropic amblyopia participated in this study. All patients were newly diagnosed and had no treatment history before participating in our study. They had finished 2 months of refractive adaptation and then received a 4-hour daily fellow eye patching therapy with an opaque patch for a 2-month period. Best-corrected visual acuity of the amblyopic eye was measured before and after the patching therapy. The homeostatic plasticity was assessed by measuring the temporary shift of ocular dominance observed after 2 hours of occlusion for the amblyopic eye before the treatment started. A binocular phase combination paradigm was used for this test.

Results

We found that there was no significant correlation between the temporary shift of ocular dominance observed after 2 hours of occlusion for the amblyopic eye before the treatment started and the visual acuity gain obtained by the amblyopic eye from 2-month of classical patching therapy. This result involving the short-term patching of the amblyopic eye is consistent with a reanalysis of Lunghi et al’ s data.

Conclusions

Ocular dominance plasticity does not provide an index of cortical plasticity in the general sense such that it could be used to predict acuity outcomes from longer term classical patching.
Homeostatic control of synaptic rewiring in recurrent networks induces the formation of stable memory engrams
Authors: Gallinaro Júlia V. , Gašparović Nebojša , Rotter Stefan
Published: March 2020

Brain networks store new memories using functional and structural synaptic plasticity. Memory formation is generally attributed to Hebbian plasticity, while homeostatic plasticity is thought to have an ancillary role in stabilizing network dynamics. Here we report that homeostatic plasticity alone can also lead to the formation of stable memories. We analyze this phenomenon using a new theory of network remodeling, combined with numerical simulations of recurrent spiking neural networks that exhibit structural plasticity based on firing rate homeostasis. These networks are able to store repeatedly presented patterns and recall them upon the presentation of incomplete cues. Storage is fast, governed by the homeostatic drift. In contrast, forgetting is slow, driven by a diffusion process. Joint stimulation of neurons induces the growth of associative connections between them, leading to the formation of memory engrams. These memories are stored in a distributed fashion throughout connectivity matrix, and individual synaptic connections have only a small influence. Although memory-specific connections are increased in number, the total number of inputs and outputs of neurons undergo only small changes during stimulation. We find that homeostatic structural plasticity induces a specific type of “silent memories”, different from conventional attractor states.
Soybean Yellow Stripe-like7 is a symbiosome membrane peptide transporter essential for nitrogen fixation
Authors: Gavrin A , Loughlin PC , Brear EM , Griffith OW , Bedon F , Suter Grotemeyer M , Escudero V , Reguera M , Qu Y , Mohd-Noor SN , Chen C , Osorio MB , Rentsch D , González-Guerrero M , Day DA , Smith PMC
Published: March 2020

Legumes form a symbiosis with rhizobia that convert atmospheric nitrogen (N2) to ammonia which they provide to the plant in return for a carbon and nutrient supply. Nodules, developed as part of the symbiosis, harbor rhizobia which are enclosed in the plant-derived symbiosome membrane (SM), to form a symbiosome. In the mature nodule all exchanges between the symbionts occur across the SM. Here we characterize GmYSL7, a member of Yellow stripe-like family which is localized to the SM in soybean nodules. It is expressed specifically in nodule infected cells with expression peaking soon after nitrogenase becomes active. Although most members of the family transport metal complexed with phytosiderophores, GmYSL7 does not. It transports oligopeptides of between four and 12 amino acids. Silencing of GmYSL7 reduces nitrogenase activity and blocks development when symbiosomes contain a single bacteroid. RNAseq of nodules in which GmYSL7 is silenced suggests that the plant initiates a defense response against the rhizobia. There is some evidence that metal transport in the nodules is dysregulated, with upregulation of genes encoding ferritin and vacuolar iron transporter family and downregulation of a gene encoding nicotianamine synthase. However, it is not clear whether the changes are a result of the reduction of nitrogen fixation and the requirement to store excess iron or an indication of a role of GmYSL7 in regulation of metal transport in the nodules. Further work to identify the physiological substrate for GmYSL7 will allow clarification of this role.

One sentence summary

GmYSL7 is a symbiosome membrane peptide transporter that is essential for symbiotic nitrogen fixation that when silenced blocks symbiosome development.
Differential Effects of Propofol and Ketamine on Critical Brain Dynamics
Authors: Varley Thomas F. , Sporns Olaf , Puce Aina , Beggs John
Published: March 2020

Whether the brain operates at a critical ‘‘tipping” point is a long standing scientific question, with evidence from both cellular and systems-scale studies suggesting that the brain does sit in, or near, a critical regime. Neuroimaging studies of humans in altered states of consciousness have prompted the suggestion that maintenance of critical dynamics is necessary for the emergence of consciousness and complex cognition, and that reduced or disorganized consciousness may be associated with deviations from criticality. Unfortunately, many of the cellular-level studies reporting signs of criticality were performed in non-conscious systems (in vitro neuronal cultures) or unconscious animals (e.g. anaesthetized rats). Here we attempted to address this knowledge gap by exploring critical brain dynamics in invasive ECoG recordings from multiple sessions with a single macaque as the animal transitioned from consciousness to unconsciousness under different anaesthetics (ketamine and propofol). We use a previously-validated test of criticality: avalanche dynamics to assess the differences in brain dynamics between normal consciousness and both drug-states. Propofol and ketamine were selected due to their differential effects on consciousness (ketamine, but not propofol, is known to induce an unusual state known as ‘dissociative anaesthesia”). Our analyses indicate that propofol dramatically restricted the size and duration of avalanches, while ketamine allowed for more awake-like dynamics to persist. In addition, propofol, but not ketamine, triggered a large reduction in the complexity of brain dynamics. All states, however, showed some signs of persistent criticality when testing for exponent relations and universal shape-collapse. Further, maintenance of critical brain dynamics may be important for regulation and control of conscious awareness.

Author summary

Here we explore how different anaesthetic drugs change the nature of brain dynamics, using neural activity recorded from sub-dural electrophysiological arrays implanted in a macaque brain. Previous research has suggested that loss of consciousness under anaesthesia is associated with a movement away from critical brain dynamics, towards a less flexible regime. When comparing ketamine and propofol, two anaesthetics with largely different effects on consciousness, we find that propofol, but not ketamine, produces a dramatic reduction in the complexity of brain activity and restricts the range of scales where critical dynamics are plausible. These results suggest that maintenance of critical dynamics may be important for regulation and control of conscious awareness.
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

Mammary-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

CReSCENT

CanceR 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

Background

Optimizing a restriction spectrum imaging (RSI) model for the prostate could lead to improved characterization of diffusion in the prostate and better discrimination of tumors.

Purpose

To 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 Type

Retrospective.

Population/Subjects

Forty-six patients who underwent an extended MRI examination for suspected prostate cancer; 23 had prostate tumors and 23 had no detectable cancer.

Field strength/Sequence

3T multi-shell diffusion weighted sequence.

Assessment

RSI 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 Tests

The 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.

Results

The 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 Conclusion

Among 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

In 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

The 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

Background

Incidence 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).

Object

We 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.

Method

We 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.

Results

Results 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 Conclusion

The 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

Neonatal 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

Background

As 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.

Methods

A 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.

Results

General 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).

Conclusions

In 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

Intratumoral 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

Introduction

Crizotinib 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.

Method

A 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.

Results

We 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.

Conclusion

chidamide 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

Grid 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

Approximately 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.

With 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.
China’s fight against COVID-19: What we have done and what we should do next?
Authors: Cheng Sixiang , Zhao Yuxin , Kaminga Atipatsa Chiwanda , Zhang Pingxin , Xu Huilan
Published: March 2020

Background

On 12 March, the World Health Organization Director-General declared that “the threat of a global pandemic has become a reality”, and the disease caused by the novel coronavirus, known as COVID-19, has become a global concern. Chinese efforts in curbing the virus have widely been recognized. Even the WHO has lauded the efforts of the Chinese government and advised the world to learn from China in fighting the disease. Since the outbreak of COVID-19, to curb the spread of the epidemic, the Chinese government has implemented unprecedented prevention interventions at the nationwide level. Currently, the outbreak in Wuhan is changing in a positive direction and has been effectively controlled. However, it is not clear what these measures were and how these measures changed to curb the outbreak of COVID-19 quickly. This study explored the characteristics and identified that China’s control strategies have changed the epidemiological curve of rapidly rising new confirmed cases of COVID-19. This study also seeks to expand the experiences and lessons from this outbreak.

Methods

We collected public health interventions measures from Jan 20, 2020, to 5 March 2020, and data from COVID-19 daily newly confirmed cases and daily cumulates cases to compare the control effects and changing trends. We performed a retrospective description of these intervention strategies from three stages. Besides, from the perspective of public health, the experiences and lessons exposed by this outbreak were roughly summarized.

Results

These non-pharmacology interventions measures adopted by the Chinese government by the instruction and spirit of President Xi Jinping were timely and efficient.

Conclusions

The present study was conducted to comprehensively analyze from a social epidemiology context. The results confirmed that these radical interventions taken by the Chinese government were effective, ambitious, and agile. However, we must be aware that the epidemic situation in Wuhan is still challenging.
Monitoring phagocytic uptake of amyloid β into glial cell lysosomes in real time
Authors: Prakash Priya , Jethava Krupal P. , Korte Nils , Izquierdo Pablo , Favuzzi Emilia , Rose Indigo , Guttenplan Kevin , Dutta Sayan , Rochet Jean-Christophe , Fishell Gordon , Liddelow Shane , Attwell David , Chopra Gaurav
Published: March 2020

Phagocytosis by glial cells is essential to regulate brain function during development and disease. Given recent interest in using amyloid β (Aβ)-targeted antibodies as a therapy for patients with Alzheimer’s disease, removal of Aβ by phagocytosis is likely protective early in Alzheimer’s disease, but remains poorly understood. Impaired phagocytic function of glial cells surrounding Aβ plaques during later stages in Alzheimer’s disease likely contributes to worsened disease outcomes, but the underlying mechanisms of how this occurs remain unknown. We have developed a human Aβ1-42analogue (AβpH) that exhibits green fluorescence upon internalization into the acidic phagosomes of cells but is non-fluorescent at physiological pH. This allowed us to image, for the first time, glial uptake of AβpHin real time in live animals. Microglia phagocytose more AβpHthan astrocytes in culture, in brain slices andin vivo. AβpHcan be used to investigate the phagocytic mechanisms removing Aβ from the extracellular space, and thus could become a useful tool to study Aβ clearance at different stages of Alzheimer’s disease.
Predicting cell-type-specific non-coding RNA transcription from genome sequence
Authors: Koido Masaru , Hon Chung-Chau , Koyama Satoshi , Kawaji Hideya , Murakawa Yasuhiro , Ishigaki Kazuyoshi , Ito Kaoru , Sese Jun , Kamatani Yoichiro , Carninci Piero , Terao Chikashi
Published: March 2020

Transcription is regulated through complex mechanisms involving non-coding RNAs (ncRNAs). However, because transcription of ncRNAs, especially enhancer RNAs, is often low and cell type-specific, its dependency on genotype remains largely unexplored. Here, we developedmutationeffect prediction onncRNAtranscription (MENTR), a quantitative machine learning framework reliably connecting genetic associations with expression of ncRNAs, resolved to the level of cell type. MENTR-predicted mutation effects on ncRNA transcription were concordant with estimates from previous genetic studies in a cell type-dependent manner. We inferred reliable causal variants from 41,223 GWAS variants, and proposed 7,775 enhancers and 3,548 long-ncRNAs as complex trait-associated ncRNAs in 348 major human primary cells and tissues, including plausible enhancer-mediated functional alterations in single-variant resolution in Crohn’s disease. In summary, we present new resources for discovering causal variants, the biological mechanisms driving complex traits, and the sequence-dependency of ncRNA regulation in relevant cell types.
SARS-CoV-2 asymptomatic and symptomatic patients and risk for transfusion transmission
Authors: Corman Victor M. , Rabenau Holger F. , Adams Ortwin , Oberle Doris , Funk Markus B. , Keller-Stanislawski Brigitte , Timm Jörg , Drosten Christian , Ciesek Sandra
Published: March 2020

Oral swabs, sputum and blood samples from 18 patients with SARS-CoV-2 infection were examined using real-time reverse transcription polymerase chain reaction (RT-PCR) testing. Whereas oral swabs or sputum from the lower respiratory tract were tested RT-PCR positive in all patients, RNAemia was neither detected in 3 patients without symptoms nor in 14 patients with flu-like symptoms, fever or pneumonia. The only patient with RNAemia suffered from acute respiratory distress syndrome (ARDS) and was artificially ventilated in an intensive care unit. Risk for SARS-CoV-2 transmission through blood components in asymptomatic SARS-CoV-2 infected individuals therefore seems negligible but further studies are needed.
How to evaluate the success of the COVID-19 measures implemented by the Norwegian government by analyzing changes in doubling time
Authors: Stangeland Biljana
Published: March 2020

Doubling Time (DT) is typically calculated for growth curves that show exponential growth, such as the cumulative number of COVID-19 cases day by day. DT represents the time it takes before the number of COVID-19 cases, in a certain country or area, doubles.

Throughout the ongoing COVID-19 outbreak, DT values are continually changing. These changes are influenced by the measures that are recommended by the health authorities and implemented by governments.

After the government-imposed shutdowns of Nordic Countries that were announced around the 12th of March 2020, we followed the development of the DT in the region. Governments put in place measures never before experienced during peace time; working from home, closed schools and kindergartens, travel bans and social distancing. We conducted analyses to evaluate the effectiveness of these measures. Does it work? The initial set of results following the shutdown are encouraging, demonstrating a trend towards slower growth; however, this could be reversed if the measures that are in place now are abandoned too early. Premature optimism can be very costly. In this report we describe a method for monitoring the epidemic in real time and evaluating the effectiveness of the implemented measures.
COVID-19 Modelling: the Effects of Social Distancing
Authors: Bendtsen Cano Oliva , Cano Morales Sabrina , Bendtsen Claus
Published: March 2020

The purpose of this article is to reach all those who find it difficult to become well informed about the repercussions of a lockdown strategy to tackle the COVID-19 pandemic and to spark discussion and thought. Here we use simple stochastic simulations to evaluate different approaches taken to tackle the crisis, along with the efficiency they will hold and the number of casualties they may incur. It is clear that the less strict the social distancing the more time it will take for life to return to normal, and the more lives will be at risk. This is shown through simulations formed by an open sourced code, which allows evaluation of the outcomes from different intervention scenarios or conditions.
MinION-in-ARMS: Nanopore Sequencing To Expedite Barcoding Of Specimen-Rich Macrofaunal Samples From Autonomous Reef Monitoring Structures
Authors: Chang Jia Jin Marc , Ip Yin Cheong Aden , Bauman Andrew G. , Huang Danwei
Published: March 2020

Autonomous Reef Monitoring Structure (ARMS) are standardised devices for sampling biodiversity in complex marine benthic habitats such as coral reefs. When coupled with DNA sequencing, these devices greatly expand our ability to document marine biodiversity. Unfortunately, the existing workflow for processing macrofaunal samples (>2-mm) in the ARMS pipeline—which involves Sanger sequencing—is expensive, laborious, and thus prohibitive for ARMS researchers. Here, we propose a faster, more cost-effective alternative by demonstrating a successful application of the MinION-based barcoding approach on the >2mm-size fraction of ARMS samples. All data were available within 3.5–4 h, and sequencing costs relatively low at approximately US$3 per MinION barcode. We sequenced the 313-bp fragment of the cytochrome c oxidase subunit I (COI) for 725 samples on both MinION and Illumina platforms, and retrieved 507–584 overlapping barcodes. MinION barcodes were highly accurate (~99.9%) when compared with Illumina reference barcodes. Molecular operational taxonomic units inferred between MinION and Illumina barcodes were consistently stable, and match ratios demonstrated highly congruent clustering patterns (≥0.96). Our method would make ARMS more accessible to researchers, and greatly expedite the processing of macrofaunal samples; it can also be easily applied to other small-to-moderate DNA barcoding projects (<10,000 specimens) for rapid species identification and discovery.
Physical interventions to interrupt or reduce the spread of respiratory viruses. Part 1 - Face masks, eye protection and person distancing: systematic review and meta-analysis
Authors: Jefferson T , Jones MA , Al-Ansary L , Bawazeer GA , Beller EM , Clark J , Conly JM , Del Mar C , Dooley E , Ferroni E , Glasziou P , Hoffmann T , Thorning S , van Driel ML
Published: March 2020

OBJECTIVE

To examine the effectiveness of eye protection, face masks, or person distancing on interrupting or reducing the spread of respiratory viruses.

DESIGN

Update of a Cochrane review that included a meta-analysis of observational studies during the SARS outbreak of 2003.

DATA SOURCES

Eligible trials from the previous review; search of Cochrane Central Register of Controlled Trials, PubMed, Embase and CINAHL from October 2010 up to 1 April 2020; and forwardand backward citation analysis.

DATA SELECTION

Randomised and cluster-randomised trials of people of any age, testing the use ofeye protection, face masks, or person distancing against standard practice, or a similar physical barrier. Outcomes included any acute respiratory illness and its related consequences.

DATA EXTRACTION AND ANALYSIS

Six authors independently assessed risk of bias using the Cochrane tool and extracted data. We used a generalised inverse variance method for pooling using a random-effects model and reported results with risk ratios and 95% Confidence Intervals (CI).

RESULTS

We included 15 randomised trials investigating the effect of masks (14 trials) in healthcare workers and the general population and of quarantine (1 trial). We found no trials testing eye protection. Compared to no masks there was no reduction of influenza-like illness (ILI) cases (Risk Ratio 0.93, 95%CI 0.83 to 1.05) or influenza (Risk Ratio 0.84, 95%CI 0.61-1.17) for masks in the general population, nor in healthcare workers (Risk Ratio 0.37, 95%CI 0.05 to 2.50). There was no difference between surgical masks and N95 respirators: for ILI (Risk Ratio 0.83, 95%CI 0.63 to 1.08), for influenza (Risk Ratio 1.02, 95%CI 0.73 to 1.43). Harms were poorly reported and limited to discomfort with lower compliance. The only trial testing quarantining workers with household ILI contacts found a reduction in ILI cases, but increased risk of quarantined workers contracting influenza. All trials were conducted during seasonal ILI activity.

CONCLUSIONS

Most included trials had poor design, reporting and sparse events. There was insufficient evidence to provide a recommendation on the use of facial barriers without other measures. We found insufficient evidence for a difference between surgical masks and N95 respirators and limited evidence to support effectiveness of quarantine. Based on observational evidence from the previous SARS epidemic included in the previous version of our Cochrane review we recommend the use of masks combined with other measures.
Determinants of customers' choice of dining-related services: the case of Taipei City
Authors: Cheng Ching-Chan , Wu Hung-Che , Tsai Ming-Chun , Chang Yu-Yuan , Chen Cheng-Ta
Published: March 2020

Purpose

This study aims to extract determinants of customers' choice of dining-related services (CDS) to understand their attitudes and habits for dining-related services. Moreover, it classifies restaurant customers into several clusters based on their CDS factors and further analyzes the differences in the preferences and habits for dining-related services among various clusters.

Design/methodology/approach

This study extracts the CDS factors using principal component analysis and identifies construct validity of the CDS factors through the results of confirmatory factor analysis. Then, it divides the restaurant customers in Taipei City into different clusters through cluster analysis to explore the habits and preferences for dining-related services in each cluster.

Findings

The study results show that the extracted six CDS factors, including service commitment, dietary preferences, design styles, additional value, delicate information collection, and dining environments. Dietary preferences, service commitment and additional value factor are the most important CDS factors for restaurant customers in Taipei City. This study divides 1,029 restaurant customers in Taipei City into three clusters based on the CDS factors through cluster analysis. The differences in the preferences and habits for dining services among three clusters have been discussed in the context in detail. Finally, this study develops eight service strategies and determines the order of execution of the eight service strategies for each cluster of customers.

Originality/value

The findings will help restaurant operators segment the market, target market customers, carry out service positioning and develop marketing strategies to respond to the highly competitive restaurant market and achieve sustainable restaurant operations.