bluuebunny/crossref_metadata_2025 huggingface dataset:
America's Pragmatic Role?
Authors: Avant Deborah
Published: September 2020

What has made the United States a global leader? Though analysts often attribute American success to a combination of resources and ideas, a subtle undercurrent in these arguments points to pragmatism and the creativity it often generates as an important part of the story. First theorized by American philosophers in the nineteenth and early twentieth centuries, pragmatism emphasizes that creativity can reshape how we see norms and interests to make cooperation more likely. After discussing the basic elements of pragmatism and its intersection with prominent international relations arguments, I show how the creativity that pragmatism envisions appears in each of these books. Though the collected authors do not label themselves as pragmatists, piecing these pragmatic elements together demonstrates the importance of creativity for key global leadership moments in the twentieth century, as well as important, if under-appreciated, governance innovations in the twenty-first century. It also offers insights into how the United States might move into the future.
Successful Integrated Pest Management Minimizes the Economic Impact of Diatraea saccharalis (Lepidoptera: Crambidae) on the Louisiana Sugarcane Industry
Authors: Wilson Blake E
Published: September 2020

The sugarcane borer, Diatraea saccharalis (F.), is the primary pest of sugarcane, Saccharum spp., in Louisiana. Recent evidence suggests an integrated pest management (IPM) program has reduced the pest’s impact, but the success of this program has not been assessed across the industry. The level of D. saccharalis injury present at harvest was recorded from 388 billet samples from five sugar mills from 2017 to 2019. These results were used to estimate direct and indirect revenue losses from D. saccharalis on the Louisiana sugarcane industry. Insecticide use records were used to estimate control costs and determine total economic impact. The mean percentage of bored internodes was 1.1, 0.3, and 1.7% for 2017, 2018, and 2019, respectively. Direct losses from reduced sugar yield averaged US$4.6 million across years. Indirect losses across years accounted for US$3.0 million and $463,000 for insecticidal control costs and reduced milling efficiency, respectively. The total economic impact of D. saccharalis averaged $8.0 million annually during the three-year study period. This study demonstrates the efficacy of pest management implementation in reducing D. saccharalis injury and highlights the value of IPM. Our findings provide new support for the emergence of D. saccharalis management in the Louisiana sugarcane industry as a modern IPM success story.
The Effect of Iterative Learning Control on the Force Control of a Hydraulic Cushion
Authors: Trojaola Ignacio , Elorza Iker , Irigoyen Eloy , Pujana-Arrese Aron , Calleja Carlos
Published: September 2020

An iterative learning control (ILC) algorithm is presented for the force control circuit of a hydraulic cushion. A control scheme consisting of a PI controller, feed-forward (FF) and feedback-linearization is first derived. The uncertainties and nonlinearities of the proportional valve, the main system actuator, prevent the accurate tracking of the pressure reference signal. Therefore, an extra ILC FF signal is added to counteract the valve model uncertainties. The unknown valve dynamics are attenuated by adding a fourth-order low-pass filter to the iterative learning control design, which is split up into two second-order low-pass filters to carry out forward and backward filtering and obtain zero-phase filtering. The addition of the ILC signal presents significant improvements in terms of settling time and overshoot of the pressure signal in the cylinder.
Uncertainty estimation in the forecasting of the 222Rnradiation level time series at the Canfranc Underground Laboratory
Authors: Cárdenas-Montes Miguel
Published: September 2020

Nowadays decision making is strongly supported by the high-confident point estimations produced by deep learning algorithms. In many activities, they are sufficient for the decision-making process. However, in some other cases, confidence intervals are required too for an appropriate decision-making process. In this work, a first attempt to generate point estimations with confidence intervals for the $^{222}$Rn radiation level time series at Canfranc Underground Laboratory is presented. To predict the low-radiation periods allows correctly scheduling the unshielded periods for maintenance operations in the experiments hosted in this facility. This should minimize the deposition of radioactive dust on the exposed surfaces during these unshielded periods. An approach based on deep learning with stochastic regulation is evaluated in the forecasting of point estimations and confidence intervals of the $^{222}$Rn time series and compared with a second approach based on Gaussian processes. As a consequence of this work, an evaluation of the capacity of Gaussian process and deep learning with stochastic regularization for generating point estimations and their confidence intervals for this time series is stated.
The significant effects of stellar mass estimation on galaxy pair fractions.
Authors: Grylls Philip J , Shankar F , Conselice C J
Published: September 2020

Theoretical models suggest that galaxy mergers may have profoundly shaped galaxy morphologies through cosmic time. However, observational estimates of galaxy pair fractions, and implied galaxy mergers, still do not converge, suggesting different numbers and redshift evolution. This paper explores the connection between stellar mass estimation and the pair fraction of galaxies using $\rm {\small STEEL}$, the Statistical sEmi-Emprical modeL, in which galaxies are mapped on to host dark matter haloes via a stellar mass–halo mass (SMHM) relation. As haloes of different mass are predicted to undergo, on average, different degrees of mergers, we expect that galaxy merger rates at fixed stellar mass will also vary depending on the shape of the input SMHM relation. Using a variety of input SMHM relations, also including one that matches the outputs of the Illustris TNG simulation, we thoroughly explore how systematic variations in the stellar mass functions propagate on to the normalization and redshift dependence of the galaxy pair fraction. We find that (i) stellar mass functions characterized by larger number densities of massive galaxies and thus a steeper SMHM relation, result in a substantial reduction of the pair fractions of massive galaxies; (ii) a time-varying SMHM relation produces galaxy pair fractions that can have varied redshift evolutions. We argue that in a hierarchical, dark matter dominated Universe, stellar mass estimates are a considerable cause of bias that must be accounted for when comparing pair fractions from different data sets or from theoretical models developed independently of the fitted survey data.
Eclipse time variations in the post-common envelope binary V470 Cam
Authors: Sale O , Bogensberger D , Clarke F , Lynas-Gray A E
Published: September 2020

Linear or quadratic relations fitted to the time-dependence of post-common envelope binary eclipse times generally give residuals exhibiting a cyclic variation. Among several possible explanations is the presence of one or more orbiting circumbinary objects causing a reflex motion of the binary centre-of-mass, thereby altering the light-travel-time.Twenty new eclipse times for the post-common envelope binary V470 Cam have been obtained; with these and 380 useable eclipse times in the literature, two circumbinary brown dwarfs having orbital periods of 7.87 ± 0.08 and 13.27 ± 0.16 yr were found to give an excellent fit to cyclic residuals resulting from a quadratic ephemeris fit. Irrespective of the excellent fit, it would be premature to claim that the V470 Cam binary is accompanied by two orbiting brown dwarfs; at the very least more eclipse times are needed to confirm the result and other plausible explanations, such as the Applegate mechanism, need eliminating.
SIMPLEs: a single-cell RNA sequencing imputation strategy preserving gene modules and cell clusters variation
Authors: Hu Zhirui , Zu Songpeng , Liu Jun S
Published: September 2020

A main challenge in analyzing single-cell RNA sequencing (scRNA-seq) data is to reduce technical variations yet retain cell heterogeneity. Due to low mRNAs content per cell and molecule losses during the experiment (called ‘dropout’), the gene expression matrix has a substantial amount of zero read counts. Existing imputation methods treat either each cell or each gene as independently and identically distributed, which oversimplifies the gene correlation and cell type structure. We propose a statistical model-based approach, called SIMPLEs (SIngle-cell RNA-seq iMPutation and celL clustErings), which iteratively identifies correlated gene modules and cell clusters and imputes dropouts customized for individual gene module and cell type. Simultaneously, it quantifies the uncertainty of imputation and cell clustering via multiple imputations. In simulations, SIMPLEs performed significantly better than prevailing scRNA-seq imputation methods according to various metrics. By applying SIMPLEs to several real datasets, we discovered gene modules that can further classify subtypes of cells. Our imputations successfully recovered the expression trends of marker genes in stem cell differentiation and can discover putative pathways regulating biological processes.
CD62L on blood basophils: a first pre-treatment predictor of remission in severe lupus nephritis
Authors: Halfon Matthieu , Bachelet Delphine , Hanouna Guillaume , Dema Barbara , Pellefigues Christophe , Manchon Pauline , Laouenan Cedric , Charles Nicolas , Daugas Eric
Published: September 2020

Background

Basophils were recently shown to contribute to lupus nephritis (LN). This study assessed blood basophil activation markers (BAMs) for the diagnosis of LN severity and as pre-treatment prognostic markers of the response to treatment in patients with severe LN.

Method

The diagnostic study included all the patients of a monocentric prospective observational cohort built with consecutive patients diagnosed with LN on the basis of a renal biopsy. The prognostic study selected patients of this cohort according to the following inclusion criteria: ≥18 years old, Class III or IV A ± C ± Class V or pure Class V LN at the time of inclusion and treated with an induction treatment for LN. Clinical data and BAMs were obtained at the time of the kidney biopsy. LN remission status was recorded 12 months after induction therapy initiation. Associations between baseline data and histological severity of LN or LN remission were assessed using logistic regression.

Results

No significant association was found between BAMs and the histological severity of LN in 101 patients. Among the 83 patients included in the prognostic study, 64 reached renal remission. CD62L expression on blood basophils at baseline was independently negatively associated with remission at 12 months [odds ratio = 0.26, 95% confidence interval 0.08–0.82, P = 0.02 for quantitative CD62L expression >105 (geometric fluorescent intensity) gMFI]. CD62L <105 gMFI was associated with a probability of 0.87 of LN remission in the next 12 months after the start of induction therapy.

Conclusion

Pre-treatment CD62L expression on blood basophils could be a first predictive biomarker of renal response to induction therapy at 12 months in patients with severe LN.
Tuskegee as a History Lesson, Tuskegee as Metaphor: Addressing Discrimination as a Social Determinant of Health in the Classroom
Authors: Vijayan Tara , Cortés-Penfield Nicolás , Harris Christina
Published: September 2020

While basic science and social medicine are fundamental to the practice of medicine, the former is often prioritized in preclinical medical education at the expense of the latter. In this perspective, we discuss ways to introduce the concept of interpersonal, institutional, and structural discrimination as social determinants of health (SDOH) into a preclinical microbiology and infectious diseases medical course. We offer 5 specific steps to creating a comprehensive curriculum on discrimination as a social determinant of health: define and use standardized terminology; integrate the concept of SDOH throughout the course; encourage critical appraisal of lay and medical resources; encourage student feedback; and provide faculty development supported by key faculty stakeholders that focuses on increasing comfort and facility with teaching such concepts. This approach offers a template for ongoing discussion in the setting of curricular reform.
The impact of health literacy on self-medication: a cross-sectional outpatient study
Authors: Muflih Suhaib M , Bashir Hadeel N , Khader Yousef S , Karasneh Reema A
Published: September 2020

Although health literacy practices have been increasingly recommended in public health literature, there is a lack of studies that examine the relationships between health literacy and self-medication.

Background

This research project aims to measure and evaluate the impact of health literacy on self-medication and to achieve a better understating of patients’ behaviors.

Methods

A cross-sectional approach was conducted and participants were recruited outpatient clinics through convenience sampling. Health literacy was measured by Single Item Literacy Screener.

Results

A total of 194 participants agreed to participate (63.9% were females). The results showed that more than half (57.2%) had adequate health literacy. Almost 30% of the participants were over the age of 50. The prevalence of self-medication was 74.2%. Nearly, two-thirds of the total participants reported self-administration of antibiotics. There was a significant relationship between the overall health literacy level and practice of self-medication.

Conclusions

Improving the health literacy level of the public can reduce inappropriate self-medication, especially the self-medication with antibiotics, which represented a high prevalence situation in our sample. Appropriate reading skills are important for accessing health information, using health care services, and achieving desirable health outcomes.
Trade and Domestic Production Networks
Authors: Dhyne Emmanuel , Kikkawa Ayumu Ken , Mogstad Magne , Tintelnot Felix
Published: September 2020

We examine how many and what kind of firms ultimately rely on foreign inputs, sell to foreign markets, and are affected by trade shocks. To capture that firms can trade indirectly by buying from or selling to domestic firms that import or export, we use Belgian data with information on both domestic firm-to-firm sales and foreign trade transactions. We find that most firms use a lot of foreign inputs, but only a small number of firms show that dependence through direct imports. While direct exporters are rare, a majority of firms are indirectly exporting. In most firms, however, indirect export is quantitatively modest, and sales at home are the key source of revenue. We show that what matters for the transmission of foreign demand shocks to a firm’s revenue is how much the firm ultimately sells to foreign markets, not whether these sales are from direct or indirect export.
Learning to game the system
Authors: Li Jin , Mukherjee Arijit , Vasconcelos Luis
Published: September 2020

An agent may privately learn which aspects of his job are more important by shirking on some of them, and use that information to shirk more effectively in the future. In a model of long-term employment relationship, we characterize the optimal relational contract in the presence of such learning-by-shirking and highlight how the performance measurement system can be managed to sharpen incentives. Two related policies are studied: intermittent replacement of existing measures, and adoption of new ones. In spite of the learning-by-shirking effect, the optimal contract is stationary, and may involve stochastic replacement/adoption policies that dilute the agent’s information rents from learning how to game the system.
Inter-brain synchrony in teams predicts collective performance
Authors: Reinero Diego A , Dikker Suzanne , Van Bavel Jay J
Published: September 2020

Despite decades of research in economics and psychology attempting to identify ingredients that make up successful teams, neuroscientists have only just begun to study how multiple brains interact. Recent research has shown that people’s brain activity becomes synchronized with others’ (inter-brain synchrony) during social engagement. However, little is known as to whether inter-brain synchrony relates to collective behavior within teams. Here, we merge the nascent field of group neuroscience with the extant literature of team dynamics and collective performance. We recruited 174 participants in groups of 4 and randomly assigned them to complete a series of problem-solving tasks either independently or as a team, while simultaneously recording each person’s brain activity using an electroencephalography hyperscanning setup. This design allowed us to examine the relationship between group identification and inter-brain synchrony in explaining collective performance. As expected, teammates identified more strongly with one another, cooperated more on an economic game, and outperformed the average individual on most problem-solving tasks. Crucially, inter-brain synchrony, but not self-reported group identification, predicted collective performance among teams. These results suggest that inter-brain synchrony can be informative in understanding collective performance among teams where self-report measures may fail to capture behavior.
Sec-Delivered Effector 1 (SDE1) of ‘Candidatus Liberibacter asiaticus’ Promotes Citrus Huanglongbing
Authors: Clark Kelley J. , Pang Zhiqian , Trinh Jessica , Wang Nian , Ma Wenbo
Published: September 2020

Sec-delivered effector 1 (SDE1) from the huanglongbing (HLB)-associated bacterium ‘Candidatus Liberibacter asiaticus’ was previously characterized as an inhibitor of defense-related, papain-like cysteine proteases in vitro and in planta. Here, we investigated the contributions of SDE1 to HLB progression. We found that SDE1 expression in the model plant Arabidopsis thaliana caused severe yellowing in mature leaves, reminiscent of both ‘Ca. L. asiaticus’ infection symptoms and accelerated leaf senescence. Induction of senescence signatures was also observed in the SDE1-expressing A. thaliana lines. These signatures were apparent in older leaves but not in seedlings, suggesting an age-associated effect. Furthermore, independent lines of transgenic Citrus paradisi (L.) Macfadyen (Duncan grapefruit) that express SDE1 exhibited hypersusceptibility to ‘Ca. L. asiaticus’. Similar to A. thaliana, transgenic citrus expressing SDE1 showed altered expression of senescence-associated genes, but only after infection with ‘Ca. L. asiaticus’. These findings suggest that SDE1 is a virulence factor that contributes to HLB progression, likely by inducing premature or accelerated senescence in citrus. This work provides new insight into HLB pathogenesis.

[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
GENESIS OF RETINAL–CHOROIDAL ANASTOMOSIS IN MACULAR TELANGIECTASIA TYPE 2
Authors: Breazzano Mark P. , Yannuzzi Lawrence A. , Spaide Richard F.
Published: September 2020

Purpose:

To longitudinally characterize structural/angiographic findings of retinal–choroidal anastomosis (RCA) in macular telangiectasia Type 2 (MacTel2).

Methods:

A combined retrospective/prospective review of patients with MacTel2 with >2 visits and >2 months follow-up, including examination, fundus photography, fluorescein angiography, spectral-domain optical coherence tomography, and projection-resolved optical coherence tomography angiography.

Results:

There were 24 eyes of 12 patients with a mean age of 61.1 (±7.3 [SD]) years and median follow-up of 447 (range 81–1,511) days. There were five eyes diagnosed with new RCA after not having any previously. Retinal–choroidal anastomosis was diagnosed in 8 (33%) eyes initially and eventually 13 (54%). In the eight eyes initially diagnosed with RCA, the number of RCAs and outer retinal hyperrflective lesions increased over the follow-up. The RCAs were found in clusters, generally temporal to the fovea. Retinal–choroidal anastomosis was uniformly associated with complete retinal subsidence, defined as the loss of outer nuclear layer substance such that the middle retinal layers sank down toward the retinal pigment epithelium (RPE), and was also present in each case. Each RCA colocalized with a region of hyperreflectivity, previously termed an outer retinal hyperreflective lesion. There was a lack of fluorescein leakage, lipid, hemorrhage, or any structural correlates with fluid exudation, and no signs of subretinal/subretinal pigment epithelium neovascularization.

Conclusion:

De novo RCA development seems to be associated with retinal subsidence, and after RCAs form, they increase in number and topographic distribution over time. Initially after formation, there was no sign of exudation. These data suggest the descent of the deep capillary plexus occurs with RCA, devoid of subretinal/subretinal pigment epithelium neovascularization in MacTel2.
Reperfusion of Free Full-Thickness Skin Grafts in Periocular Reconstructive Surgery Monitored Using Laser Speckle Contrast Imaging
Authors: Berggren Johanna , Castelo Nazia , Tenland Kajsa , Dahlstrand Ulf , Engelsberg Karl , Lindstedt Sandra , Sheikh Rafi , Malmsjö Malin
Published: September 2020

Purpose:

Free skin grafts are frequently used in reconstructive surgery. However, little is known about the course of reperfusion due to the previous lack of reliable perfusion monitoring techniques. The aim of this study was to use state-of-the-art laser speckle contrast imaging to monitor free skin grafts in the periocular area.

Methods:

Seven patients needing surgery due to tumor removal or cicatricial ectropion in the periocular region underwent reconstructive surgery using free skin grafts from either the contralateral upper eyelid or the upper inner arm. The free skin grafts measured 10–30 mm horizontally and 9–30 mm vertically. Blood perfusion was monitored using laser speckle contrast imaging immediately postoperatively (0 weeks) and at follow-up after 1, 3, and 7 weeks.

Results:

All grafts were reperfused gradually during healing, the median value being 46% in the central part of the graft after 1 week and 79% after 3 weeks. The grafts were completely reperfused after 7 weeks. No difference was observed in the rate of reperfusion between the center and periphery of the grafts (p = not significant). The cosmetic and functional outcome was excellent in all but 1 patient, who developed ectropion that had to be surgically corrected.

Conclusions:

Skin grafts in the periorbital area are fully reperfused after 7 weeks. The periocular area is known to be well-vascularized and thus forgiving to reconstructive surgery. Future investigations of the reperfusion of free skin grafts in other parts of the body or in higher-risk populations should be carried out.
Triggering Receptor Expressed on Myeloid Cells-2 Protects Aged Mice Against Sepsis by Mitigating the IL-23/IL-17A Response
Authors: Chen QiXing , Yang Yang , Wu XiaoLiang , Yang ShiYue , Zhang Yan , Shu Qiang , Fang XiangMing
Published: September 2020

Background:

Advancing age is an independent predictor of mortality in septic patients. Recent animal studies were unable to reflect this clinical pathophysiological process, largely hampering the development of new efficacious therapies. Triggering receptor expressed on myeloid cells-2 (TREM-2) is a novel immune regulator with multiple activities. However, very little is known about the regulatory role of TREM-2 in sepsis upon aging.

Methods:

Blood samples were collected from septic patients within 24 h after intensive care unit admission. The patients were preselected into two groups based on the age (age with ≥60 years old and age with <60 years old). Sepsis in aged mice was induced by cecal ligation and puncture. The expression of TREM-2 was evaluated in septic patients and aged septic mice. Aged macrophages overexpressing TREM-2 and green fluorescent protein (GFP) were administered to aged septic mice after cecal ligation and puncture. Survival rate was monitored, and bacterial load and inflammatory mediators levels were evaluated. In vivo IL-23 function was blocked using appropriate monoclonal antibodies.

Results:

The expression levels of TREM-2 were downregulated in both aged septic patients and aged septic mice. The administration of TREM-2-overexpressing macrophages significantly prolonged survival and alleviated organ injury in the aged septic mice. The protective effect did not affect host bacterial burden, but markedly inhibited the host IL-17A response, as determined by a multiplex cytokine assay. Screening the expression of IL-17A-related activating factors revealed that the IL-23 level in TREM-2-overexpressing macrophages was significantly lower than that in GFP-expressing macrophages. Blocking IL-23 after the administration of GFP-expressing macrophages protected aged mice against sepsis.

Conclusions:

TREM-2 prolonged survival of aged mice from sepsis by finely modulating the IL-23/IL-17A immune pathway. These results provide previously unidentified mechanistic insight into immune regulation by TREM-2 and new therapeutic targets in sepsis upon aging.
Cytotoxicity of the 42 kDa SMase C sphingomyelinase secreted by Leptospira interrogans serovar Pomona on Vero cells
Authors: Chaurasia Reetika , Sritharan Manjula
Published: September 2020

Sphingomyelinases produced by the pathogenic members of the genusLeptospiraare implicated in the haemorrhagic manifestations seen in the severe form of leptospirosis. With multiple sphingomyelinase genes present in the genome of pathogenicLeptospira, much remains to be understood about these molecules. They include factors regulating their expression, post-translational modifications, and release of the biologically active forms of these molecules. In this study, serovar Pomona was chosen as it is reported to express high levels of sphingomyelinase that explained the haemolytic activity seen in experimental animals infected with this pathogen. Here, we demonstrate the cytotoxicity of a 42 kDa sphingomyelinase secreted byLeptospira interrogansserovar Pomona strain Pomona upon infecting Vero cells. This sphingomyelinase detected using specific anti-sphingomyelinase antibodies, exhibited haemolytic and sphingomyelinase activities that caused host-cell damage evident from the confocal images and scanning electron micrographs. The implications of these findings and the detection of a 42 kDa sphingomyelinase in the urine of human patients with leptospirosis in our earlier study is discussed with an emphasis on the potential of these sphingomyelinases as candidate markers for the early diagnosis of leptospirosis.
Association of cannabis use-related predictor variables and self-reported psychotic disorders: US adults, 2001-2002 and 2012-2013
Authors: Livne Ofir , Shmulewitz Dvora , Sarvet Aaron L. , Hasin Deborah S.
Published: September 2020

Objective

To determine the association of cannabis use-related variables and self-reported psychotic disorders during two time periods (2001-2002; 2012-2013).

Methods

Logistic regression was used to analyze data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, 2001-2002; N=43,093) and NESARC-III (2012-2013; N=36,309). Among those with and without cannabis predictors (any and frequent [≥3 times a week] non-medical use, DSM-IV cannabis use disorders [CUD], cannabis dependence [CD]), standardized prevalence of past-year self-reported psychotic disorders were estimated. Association was indicated by within-survey differences in psychotic disorders by cannabis-related predictor status. Whether associations changed over time was indicated by difference-in-difference tests (contrasts between the surveys).

Results

In both surveys, self-reported psychotic disorders were significantly more prevalent in those with than those without any non-medical cannabis use (2001-2002: 1.65% vs 0.27%; 2012-2013: 1.89% vs. 0.68%), with similar associations in both periods. Self-reported psychotic disorders were unrelated to frequent non-medical use in 2001-2002 but were significantly more prevalent in those with than without frequent non-medical use in 2012-2013 (2.68% vs. 0.71%), with no significant difference over time. In both surveys, self-reported psychotic disorders were significantly more prevalent in those with than without CUD (2001-2002: 2.43% vs. 0.30%; 2012-2013: 3.26% vs. 0.72%), with no significant differences in the associations over time. Self-reported psychotic disorders were unrelated to CD in 2001-2002 but were significantly more prevalent in those with than without CD in 2012-2013 (8.54% vs. 0.73%), showing a significantly stronger relationship in 2012-2013; similarly, among past-year non-medical cannabis users, the association was significantly stronger in 2012-2013.

Conclusions

Cannabis-related variables, especially cannabis dependence, remain related to self-reported psychotic disorders. Therefore, clinicians should closely monitor cannabis-dependent users and assess the need for preventive and therapeutic interventions for these individuals.
The quantitative landscape of the neutralizing antibody response to SARS-CoV-2
Authors: Padmanabhan Pranesh , Desikan Rajat , Dixit Narendra M.
Published: September 2020

Neutralizing antibodies (NAbs) appear promising interventions against SARS-CoV-2 infection. Over 100 NAbs have been identified so far and several are in clinical trials. Yet, which NAbs would be the most potent remains unclear. Here, we analysed reported in vitro dose-response curves (DRCs) of >70 NAbs and estimated corresponding 50% inhibitory concentrations, slope parameters, and instantaneous inhibitory potentials (IIPs), presenting a comprehensive quantitative landscape of NAb responses to SARS-CoV-2. NAbs with high IIPs are likely to be potent. To assess the applicability of the landscape in vivo, we analysed available DRCs of NAbs from individual patients and found that the responses closely resembled the landscape. Further, we created virtual patient plasma samples by randomly sampling NAbs from the landscape and found that they recapitulated plasma dilution assays from convalescent patients. The landscape thus offers a facile tool for benchmarking NAbs and would aid the development of NAb-based therapies for SARS-CoV-2 infection.
Plant Prionome maps reveal specific roles of prion-like proteins in stress and memory
Authors: Garai Sampurna , Citu  , Pandey Jyotsna , Singla-Pareek Sneh L. , Sopory Sudhir K. , Kaur Charanpreet , Yadav Gitanjali
Published: September 2020

Prions can be considered as molecular memory devices, generating reproducible memory of a conformational change. Prion-like proteins (PrLPs) have been demonstrated to be present in plants, but their role in plant stress and memory remains largely unexplored. In this work, we report the widespread presence of PrLPs in plants through a comprehensive analysis of 39 genomes representing major taxonomic groups. We find diverse functional roles associated with plant ‘prionomes’. Investigation of the rice transcriptome further delineated the role of PrLPs in stress and developmental responses, leading us to explore whether and to what extent PrLPs may build stress memory. The rice prionome is significantly enriched for Transposons/Retrotransposons (Ts/RTRs), and we derived transcriptional regulatory inferences from diurnal gene expression revealing a complex regulatory network between PrLPs, transcription factors and genes known to be involved in stress priming, as well as transient and trans-generational plant memory. Overall, our data suggest that plant memory mechanisms may rely upon protein-based signals embedded in PrLPs, in addition to chromatin-based epigenetic signals and provides important insights into the anticipated role of prions in stress and memory.
Improving drug safety predictions by reducing poor analytical practices
Authors: Lazic Stanley E. , Williams Dominic P.
Published: September 2020

Predicting the safety of a drug from preclinical data is a major challenge in drug discovery, and progressing an unsafe compound into the clinic puts patients at risk and wastes resources. In drug safety pharmacology and related fields, methods and analytical decisions known to provide poor predictions are common and include creating arbitrary thresholds, binning continuous values, giving all assays equal weight, and multiple reuse of information. In addition, the metrics used to evaluate models often omit important criteria and models’ performance on new data are often not assessed rigorously. Prediction models with these problems are unlikely to perform well, and published models suffer from many of these issues. We describe these problems in detail, demonstrate their negative consequences, and propose simple solutions that are standard in other disciplines where predictive modelling is used.
Clinical Course And Risk Factors For In-hospital Death In Critical COVID-19 In Wuhan, China
Authors: Li Fei , Cai Yue , Gao Chao , Zhou Lei , Chen Renjuan , Zhang Kan , Li Weiqin , Zhang Ruining , Zhang Xijing , Wang Duolao , Liu Yi , Tao Ling
Published: September 2020

BACKGROUND

The risk factors for mortality of COVID-19 classified as critical type have not been well described.

OBJECTIVES

This study aimed to described the clinical outcomes and further explored risk factors of in-hospital death for COVID-19 classified as critical type.

METHODS

This was a single-center retrospective cohort study. From February 5, 2020 to March 4, 2020, 98 consecutive patients classified as critical COVID-19 were included in Huo Shen Shan Hospital. The final date of follow-up was March 29, 2020. The primary outcome was all-cause mortality during hospitalization. Multivariable Cox regression model was used to explore the risk factors associated with in-hospital death.

RESULTS

Of the 98 patients, 43 (43.9%) died in hospital, 37(37.8%) discharged, and 18(18.4%) remained in hospital. The mean age was 68.5 (63, 75) years, and 57 (58.2%) were female. The most common comorbidity was hypertension (68.4%), followed by diabetes (17.3%), angina pectoris (13.3%). Except the sex (Female: 68.8% vs 49.1%, P=0.039) and angina pectoris (20.9% vs 7.3%, P = 0.048), there was no difference in other demographics and comorbidities between non-survivor and survivor groups. The proportion of elevated alanine aminotransferase, creatinine, D-dimer and cardiac injury marker were 59.4%, 35.7%, 87.5% and 42.9%, respectively, and all showed the significant difference between two groups. The acute cardiac injury, acute kidney injury (AKI), and acute respiratory distress syndrome (ARDS) were observed in 42.9%, 27.8% and 26.5% of the patients. Compared with survivor group, non-survivor group had more acute cardiac injury (79.1% vs 14.5%, P<0.0001), AKI (50.0% vs 10.9%, P<0.0001), and ARDS (37.2% vs 18.2%, P=0.034). Multivariable Cox regression showed increasing hazard ratio of in-hospital death associated with acute cardiac injury (HR, 6.57 [95% CI, 1.89-22.79]) and AKI (HR, 2.60 [95% CI, 1.15-5.86]).

CONCLUSIONS

COVID-19 classified as critical type had a high prevalence of acute cardiac and kidney injury, which were associated with a higher risk of in-hospital mortality.
Estimation of the fraction of COVID-19 infected people in U.S. states and countries worldwide
Authors: Noh Jungsik , Danuser Gaudenz
Published: September 2020

Since the beginning of the COVID-19 pandemic, daily counts of confirmed cases and deaths have been publicly reported in real-time to control the virus spread. However, substantial undocumented infections have obscured the true prevalence of the virus. A machine learning framework was developed to estimate time courses of actual new COVID-19 cases and current infections in 50 countries and 50 U.S. states from reported test results and deaths, as well as published epidemiological parameters. Severe under-reporting of cases was found to be universal. Our framework projects for countries like Belgium, Brazil, and the U.S. ∼10% of the population has been once infected. In the U.S. states like Louisiana, Georgia, and Florida, more than 4% of the population is estimated to be currently infected, as of September 3, 2020, while in New York the fraction is 0.12%. The estimation of the actual fraction of currently infected people is crucial for any definition of public health policies, which up to this point may have been misguided by the reliance on confirmed cases.
Development of the Brain Functional Connectome Follows Puberty-Dependent Nonlinear Trajectories
Authors: Gracia-Tabuenca Zeus , Moreno Martha Beatriz , Barrios Fernando , Alcauter Sarael
Published: September 2020

Adolescence is a developmental period that dramatically impacts body and behavior, with pubertal hormones playing an important role not only in the morphological changes in the body but also in brain structure and function. Understanding brain development during adolescence has become a priority in neuroscience because it coincides with the onset of many psychiatric and behavioral disorders. However, little is known about how puberty influences the brain functional connectome. In this study, taking a longitudinal human sample of typically developing children and adolescents (of both sexes), we demonstrate that the development of the brain functional connectome better fits pubertal status than chronological age. In particular, centrality, segregation, efficiency, and integration of the brain functional connectome increase after the onset of the pubertal markers. We found that these effects are stronger in attention and task control networks. Lastly, after controlling for this effect, we showed that functional connectivity between these networks is related to better performance in cognitive flexibility. This study points out the importance of considering longitudinal nonlinear trends when exploring developmental trajectories, and emphasizes the impact of puberty on the functional organization of the brain in adolescence.

Significance Statement

Understanding the brain organization along development is a crucial challenge for Neuroscience. In particular, during adolescence there is a great impact in body and cognitive functions as well as substantial incidence of mental health disruptions. Here, we tested how brain organization changes along this period based on the properties of the functional connectome in a longitudinal pediatric sample. We found a nonlinear increase in the connectivity and the brain network efficiency, particularly after the onset of puberty. These effects were more prominent in association networks. In addition, higher connectivity in those areas was associated with better performance in cognitive flexibility. These results demonstrate the importance of considering pubertal assessment as well as nonlinear trends in developmental studies.
Comparing Theories for the Maintenance of Late LTP and Long-Term Memory: Computational Analysis of the Roles of Kinase Feedback Pathways and Synaptic Reactivation
Authors: Smolen Paul , Baxter Douglas A. , Byrne John H.
Published: September 2020

A fundamental problem in neuroscience is how memories are maintained from days to a lifetime, given turnover of proteins that underlie expression of long-term synaptic potentiation (LTP) or ‘tag’ synapses as eligible for LTP. One likely solution relies on synaptic positive feedback loops, prominently including persistent activation of Ca2+/calmodulin kinase II (CaMKII) and self-activated synthesis of protein kinase M ζ (PKMζ). Recent studies also suggest positive feedback based on recurrent synaptic reactivation within neuron assemblies, or engrams, is necessary to maintain memories. The relative importance of these feedback mechanisms is controversial. To explore the likelihood that each mechanism is necessary or sufficient to maintain memory, we simulated maintenance of LTP with a simplified model incorporating persistent kinase activation, synaptic tagging, and preferential reactivation of strong synapses, and analyzed implications of recent data. We simulated three model variants, each maintaining LTP with one feedback loop: autonomous, self-activated PKMζ synthesis (model variant I); self-activated CamKII (model variant II); and recurrent reactivation of strengthened synapses (model variant III). Variant I requires and predicts that, for successful maintenance, PKMζ must contribute to synaptic tagging. Variant II maintains LTP and suggests persistent CaMKII activation could maintain PKMζ activity, a feedforward interaction not previously considered. However we note data challenging this feedback loop. In Variant III synaptic reactivation drives, and thus predicts, recurrent or persistent activity elevations of CamKII and other necessary kinases, plausibly contributing to empirically persistent elevation of PKMζ levels. Reactivation is thus predicted to sustain recurrent rounds of synaptic tagging and incorporation of plasticity-related proteins. We also suggest (model variant IV) that synaptic reactivation and autonomous kinase activation could synergistically maintain LTP. We propose experiments that could discriminate these maintenance mechanisms.
Excess Risk of COVID-19 to University Populations Resulting from In-Person Sporting Events
Authors: Johnson Stephanie S. , Jackson Katelin C. , Mietchen Matthew S. , Sbai Samir , Schwartz Elissa J. , Lofgren Eric T.
Published: September 2020

Background

One of the consequences of COVID-19 has been the cancelation of in-person collegiate sporting events. We explore the impact of having in-person sports on COVID-19 transmission on a college campus, specifically the excess cases within the campus community can be anticipated.

Methods

Using a stochastic compartmental model representing the interactions between the university community, we model the impact of transient influxes of visitors attending sporting events and ancillary activities (bars, dining out, etc.). We consider a number of scenarios, varying the extent to which visitors interact with the campus, the number of infectious visitors, and the extent to which the campus has controlled COVID-19 absent events. We also conducted a sensitivity analysis, exploring the model’s outcomes over a wide range of uncertainty.

Results

Events caused an increase in the number of cases among the campus community, ranging from a 25% increase in a scenario where the campus already had an uncontrolled COVID-19 outbreak and visitors had a low prevalence of COVID-19 and mixed lightly with the campus community to an 822% increase where the campus had controlled their COVID-19 outbreak and visitors had both a high prevalence of COVID-19 and mixed heavily with the campus community. The model was insensitive to parameter uncertainty, save for the duration a symptomatic individual was infectious.

Conclusion

In-person sporting events represent a threat to the health of the campus community. This is the case even in circumstances where COVID-19 seems controlled both on-campus and among the larger population visitors are drawn from.
Scrutinizing the Spread of Covid-19 in Madagascar
Authors: Narison S. , Maltezos S.
Published: September 2020

We scrutinize the evolution of Covid-19 in Madagascar by comparing results from three approaches (cubic polynomial, semi-gaussian and gaussian-like models) which we use to provide an analytical form of the spread of the pandemic. In so doing, we introduce (for the first time) the ratio of the cumulative and daily numbers of infected persons over the corresponding one of tests which are expected to be less sensitive to the number of the tests because the credibility of the results based only on the absolute numbers often raises some criticisms. We also give and compare the reproduction number Reff from different approaches and with the ones with the ones of some European countries with a small number of population (Greece, Switzerland) and some other African countries. Finally, we show and comment the evolution of the total number of deaths and of the per cent number of cured persons and discuss the performance of the medical care.
Dorsal and ventral mossy cells differ in their long-range axonal projections throughout the dentate gyrus of the mouse hippocampus
Authors: Botterill Justin J. , Gerencer Kathleen J. , Vinod K. Yaragudri , Alcantara-Gonzalez David , Scharfman Helen E.
Published: September 2020

Glutamatergic hilar mossy cells (MCs) have axons that terminate both near and far from their cell body but stay within the DG, making synapses in the inner molecular layer primarily. The long-range axons are considered the primary projection, and extend throughout the DG ipsilateral to the soma, and project to the contralateral DG. The specificity of long-range MC axons for the inner molecular layer (IML) has been considered to be a key characteristic of the DG. In the present study we made the surprising finding that dorsal MC axons are an exception to this rule. We used two mouse lines that allow for Cre-dependent viral labeling of MCs and their axons: dopamine receptor d2 (Drd2-Cre) and calcitonin receptor-like receptor (Crlr-Cre). A single viral injection into the dorsal DG to label dorsal MCs resulted in labeling of MC axons in both the IML and middle molecular layer (MML). Interestingly, this broad termination of MC axons applied to all long-range axons. In contrast, long-range axons of ventral MCs mainly terminated in the IML, consistent with the literature. Taken together, these results suggest that dorsal and ventral MCs differ significantly in their axonal projections, and the difference is primarily in their long-range projections. Since those projections are thought to terminate primarily on GCs, the results suggest a dorsal-ventral difference in MC activation of GCs. The surprising difference in dorsal and ventral MC projections should therefore be considered when evaluating dorsal-ventral differences in DG function.