bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of a serological diagnostic kit of SARS-CoV-2 availble in Iran
Authors: Shamsollahi Hamid Reza , Amini Mostafa , Alizadeh Shaban , Nedjat Saharnaz , Akbari-Sari Ali , Rezaei Mehdi , Allameh Seyed Farshad , Fotouhi Akbar , Yunesian Masud 
Published: May 2020

AbstractBackgroundThe SARS-CoV-2 epidemic broke out in December 2019 and now is characterized as a pandemic. The effective control of this infectious disease requires access to diagnostic techniques, both for case finding and epidemic size estimation. The molecular technique is routinely being used worldwide. Although it is the “standard” case detection and management method, it has its own shortcomings. Thus, some easy-to-use rapid serological tests were developed.MethodsOne hundred and fourteen positive RT-PCR-diagnosed patients were tested by VivaDiag Kit, a brand of rapid serological kits available in hospitals affiliated to Tehran University of Medical Sciences (TUMS), Tehran, Iran. Frozen serum specimens taken from healthy people in summer and autumn 2019, were also tested as negative controls.ResultsThe test sensitivity was 47.9% (95% confidence interval [CI]: 38.8-56.9) for IgM and 47.0% (95% CI: 38.0-56.0) for IgG. There was no difference between IgG and IgM seropositivity except in one case. Specificity was calculated as 99.0% (95% CI: 96.4-99.9) for IgM and of 100.0% (95% CI: 0.98.2-100.0) for IgG. Sensitivity was higher in men and older participants.ConclusionThis test can be used for epidemiological investigations especially for the estimation of the level of infection in the community, after it is properly corrected for sensitivity and specificity. The low sensitivity could be attributed to the technical limitation of the kits or low levels of antibodies after infection. The different sensitivity in age and sex groups supports the hypothesis that different people show different immune responses to this virus.
Significance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio for predicting clinical outcomes in COVID-19
Authors: Huang Shaoping , Liu Min , Li Xiaolu , Shang Zhiyin , Zhang Ting , Lu Hongzhou 
Published: May 2020

AbstractBackgroundThe epidemic of 2019 novel coronavirus (COVID-19) struck China in late December, 2019, resulting in about 200000 deaths all over the world. Numerous observational studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) and lymphocyte proportion and the platelet-to-lymphocyte ratio (PLR) are inflammatory markers. Our study aimed to detect the role of NLR, PLR in predicting the prognosis of COVID-19.MethodsFour hundred and fifteen consecutive patients were enrolled in Shanghai Public Health Clinical Center affiliated to Fudan University, between 20 January and 11 April 2020 with confirmed COVID-19. Epidemiology, symptoms, signs, and laboratory examinations during the hospital stay were collected and compared between non-severe and severe patients. Statistical analysis was performed by SPSS 25.0 software.ResultsFour hundred and fifteen laboratory-confirmed COVID-19 patients were included in our study, among which 386 (93%) patients were not severe, and 27 (7%) were severe. The proportion of males in severe cases is higher than in non-severe cases (75.86% vs. 50.52%, P=0.008). The age between the two groups is different (p=0.022). Compared with non-severe patients, severe patients exhibited more comorbidities, including hypertension (48.28% vs. 19.43%, p<0.001), diabetes (20.69% vs. 6.99%, p=0.009), chronic obstructive pulmonary disease (51.72% vs. 6.22%, p<0.001), and fatty liver (37.93% vs. 15.8%, p=0.002), respectively. NLR and PLR showed significant difference (p<0.001). Diabetes (OR 0.28; 95% CI 15.824-187.186), fatty liver (OR 21.469; 95% CI 2.306-199.872), coronary heart disease (OR 18.157; 95% CI 2.085-158.083), NLR (OR 1.729; 95% CI 1.050-2.847) were significantly associated with severe cases with COVID-19. The NLR of patients in severe group had a 1.729-fold higher than that of no-severe group (OR 1.729; 95% CI 1.050-2.847, P=0.031).ConclusionsNLR is an independent risk factor of severe COVID-19 patients. PLR, NLR were significantly different between severe and non-severe patients, so assessment of NLR, PLR may help identify high risk cases with COVID-19.
Segmentation and shielding of the most vulnerable members of the population as elements of an exit strategy from COVID-19 lockdown
Authors: van Bunnik Bram A.D. , Morgan Alex L.K. , Bessell Paul R. , Calder-Gerver Giles , Zhang Feifei , Haynes Samuel , Ashworth Jordan , Zhao Shengyuan , Cave Nicola Rose , Perry Meghan R. , Lepper Hannah C. , Lu Lu , Kellam Paul , Sheikh Aziz , Medley Graham F. , Woolhouse Mark E.J. 
Published: May 2020

AbstractIn this study we demonstrate that the adoption of a segmenting and shielding (S&S) strategy could increase scope to partially exit COVID-19 lockdown while limiting the risk of an overwhelming second wave of infection.The S&S strategy has an antecedent in the “cocooning” of infants by immunisation of close family members (Forsyth et al., 2015), and forms a pillar of infection, prevention and control (IPC) strategies (RCN, 2017). We are unaware of it being proposed as a major public health initiative previously.We illustrate the S&S strategy using a mathematical model that segments the vulnerable population and their closest contacts, the “shielders”. We explore the effects on the epidemic curve of a gradual ramping up of protection for the vulnerable population and a gradual ramping down of restrictions on the non-vulnerable population over a period of 12 weeks after lockdown.The most important determinants of outcome are: i) post-lockdown transmission rates within the general population segment and between the general and vulnerable segments; ii) the fraction of the population in the vulnerable and shielder segments; iii) adherence with need to be protected; and iv) the extent to which population immunity builds up in all segments.We explored the effects of extending the duration of lockdown and faster or slower transition to post-lockdown conditions and, most importantly, the trade-off between increased protection of the vulnerable segment and fewer restrictions on the general population.We illustrate how the potential for the relaxation of restrictions interacts with specific policy objectives. We show that the range of options for relaxation in the general population can be increased by maintaining restrictions on the shielder segment and by intensive routine screening of shielders.We find that the outcome of any future policy is strongly influenced by the contact matrix between segments and the relationships between physical distancing measures and transmission rates. These relationships are difficult to quantify so close monitoring of the epidemic would be essential during and after the exit from lockdown.More generally, S&S has potential applications for any infectious disease for which there are defined proportions of the population who cannot be treated or who are at risk of severe outcomes.
Allochronic Divergence Driven by Spatial Asynchrony in Precipitation in Neotropical Frogs?
Authors: Guarnizo Carlos E. , Montoya Paola , Quintero Ignacio , Cadena Carlos Daniel 
Published: May 2020

AbstractThe role of geographic barriers in promoting reproductive isolation across space is well understood. Isolation by the time of breeding, however, may also promote population divergence when populations reproduce asynchronically in space, even in the absence of geographic barriers. Few examples exist of divergence due to breeding allochrony, particularly in vertebrates. We tested whether in Neotropical frogs’ asynchrony in precipitation patterns promotes intraspecific genetic divergence, speciation, and regional accumulation of diversity. We assessed the relationship between spatial asynchrony in precipitation and genetic divergence controlling for ecological connectivity across 48 Neotropical frog species. In addition, we examined whether regions within which precipitation regimes are more asynchronous across space have higher species richness and have experienced greater speciation rates. Beyond a generalized expected effect of ecological connectivity on intraspecific genetic divergence, we found that asynchrony in precipitation is positively associated with genetic differentiation in 31% of the species tested, resulting in a significantly positive cross-species effect of asynchrony in precipitation on genetic divergence in a meta-analysis. However, the effect of asynchrony in precipitation on population divergence seems not to scale to macroevolutionary patterns because spatial asynchrony in precipitation was not associated with geographical patterns of species richness or speciation rates. Our results indicate that genetic divergence can be promoted by asynchronous breeding lag in the absence of geographic barriers in species where breeding is associated with water availability, but such effects may not be stable enough through time to influence macroevolutionary patterns.
Towards understanding predictability in ecology: A forest gap model case study
Authors: Raiho Ann , Dietze Michael , Dawson Andria , Rollinson Christine R. , Tipton John , McLachlan Jason 
Published: May 2020

AbstractUnderestimation of uncertainty in ecology runs the risk of producing precise, but inaccurate predictions. Most predictions from ecological models account for only a subset of the various components of uncertainty, making it diffcult to determine which uncertainties drive inaccurate predictions. To address this issue, we leveraged the forecast-analysis cycle and created a new state data assimilation algorithm that accommodates non-normal datasets and incorporates a commonly left-out uncertainty, process error covariance. We evaluated this novel algorithm with a case study where we assimilated 50 years of tree-ring-estimated aboveground biomass data into a forest gap model. To test assumptions about which uncertainties dominate forecasts of forest community and carbon dynamics, we partitioned hindcast variance into five uncertainty components. Contrary to the assumption that demographic stochasticity dominates forest gap dynamics, we found that demographic stochasticity alone massively underestimated forecast uncertainty (0.09% of the total uncertainty) and resulted in overconfident, biased model predictions. Similarly, despite decades of reliance on unconstrained “spin-ups” to initialize models, initial condition uncertainty declined very little over the forecast period and constraining initial conditions with data led to large increases in prediction accuracy. Process uncertainty, which up until now had been diffcult to estimate in mechanistic ecosystem model projections, dominated the prediction uncertainty over the forecast time period (49.1%), followed by meteorological uncertainty (32.5%). Parameter uncertainty, a recent focus of the modeling community, contributed 18.3%. These findings call into question our conventional wisdom about how to improve forest community and carbon cycle projections. This foundation can be used to test long standing modeling assumptions across fields in global change biology and specifically challenges the conventional wisdom regarding which aspects dominate uncertainty in the forest gap models.
Effectiveness of 2ndSkull Products in Reducing Head Impact in Simulated Sports
Authors: Ritchie Marina , Lin Honghuang , Au Rhoda 
Published: May 2020

AbstractCumulative effects of repetitive head impact have been highly associated with short and long term neurological conditions. Despite high rates of head injuries, many people in the U.S. and around the world continue to participate in collision sports. As one approach to address this concern, 2ndSkull has developed supplemental protective headgears including a skull cap, scrum cap and headband that can be utilized in both helmet and non-helmet sports. To test the effectiveness of 2ndSkull products as an adjunctive tool to reduce the severity of head impact, data were extracted from a series of tests completed at four sites under laboratory conditions using linear, projectile and rotational impactor to simulate blows to the head in sports. The majority of test cases showed the same pattern of reduced impact severity with the addition of 2ndSkull padding. It remains to be seen if these laboratory results will translate to the field.
Mechano-Chemo Signaling Interactions Modulate Matrix Production by Cardiac Fibroblasts
Authors: Rogers Jesse D. , Holmes Jeffrey W. , Saucerman Jeffrey J. , Richardson William J. 
Published: May 2020

AbstractExtracellular matrix remodeling after myocardial infarction occurs in a dynamic environment in which local mechanical stresses and biochemical signaling species stimulate the accumulation of collagen-rich scar tissue. It is well-known that cardiac fibroblasts regulate post-infarction matrix turnover by secreting matrix proteins, proteases, and protease inhibitors in response to both biochemical stimuli and mechanical stretch, but how these stimuli act together to dictate cellular responses is still unclear. We developed a screen of cardiac fibroblast-secreted proteins in response to combinations of biochemical agonists and cyclic uniaxial stretch in order to elucidate the relationships between stretch, biochemical signaling, and cardiac matrix turnover. We found that stretch significantly synergized with biochemical agonists to inhibit the secretion of matrix metalloproteinases, with stretch either amplifying protease suppression by individual agonists or antagonizing agonist-driven upregulation of protease expression. Stretch also modulated fibroblast sensitivity towards biochemical agonists by either sensitizing cells towards agonists that suppress protease secretion or de-sensitizing cells towards agonists that upregulate protease secretion. These findings suggest that the mechanical environment can significantly alter fibrosis-related signaling in cardiac fibroblasts, suggesting caution when extrapolatingin vitrodata to predict effects of fibrosis-related cytokines in situations like myocardial infarction where mechanical stretch occurs.
Skin Delivery of Modified Vaccinia Ankara Viral Vectors Generates Superior T Cell Immunity Against a Respiratory Viral Challenge
Authors: Pan Youdong , Liu Luzheng , Tian Tian , Zhao Jingxia , Park Chang Ook , Lofftus Serena Y. , Stingley Claire A. , Mei Shenglin , Liu Xing , Kupper Thomas S. 
Published: May 2020

AbstractModified Vaccinia Ankara (MVA) was recently approved as a Smallpox vaccine. Transmission of Variola is by respiratory droplets, and MVA delivered by skin scarification (s.s.) protected mice far more effectively against lethal respiratory challenge with VACV than any other route of delivery, and at much lower doses. Comparisons of s.s. with intradermal, subcutaneous or intramuscular routes showed that MVAOVAs.s.-generated T cells were both more abundant and transcriptionally distinct. MVAOVAs.s. produced greater numbers of lung Ova-specific CD8+TRMand was superior in protecting mice against lethal VACVOVArespiratory challenge. Nearly as many lung TRMwere generated with MVAOVAs.s. compared to direct pulmonary immunization with MVAOVA, and both routes vaccination protected mice against lethal pulmonary challenge with VACVOVA. Strikingly, MVAOVAs.s.-generated effector T cells exhibited overlapping gene transcriptional profiles to those generated via direct pulmonary immunization. Overall, our data suggest that heterologous MVA vectors delivered via s.s. are uniquely well-suited as vaccine vectors for respiratory pathogens like COVID-19. In addition, MVA delivered via s.s. could represent a more effective dose-sparing smallpox vaccine.
Prokaryotic Argonaute fromArchaeoglobus fulgidusinteracts with DNA as a homodimer
Authors: Golovinas Edvardas , Rutkauskas Danielis , Manakova Elena , Jankunec Marija , Silanskas Arunas , Sasnauskas Giedrius , Zaremba Mindaugas 
Published: May 2020

ABSTRACTBackgroundArgonaute (Ago) proteins are found in all three domains of life. The best characterized group is eukaryotic Argonautes (eAgos), which are the core of RNA interference. The best understood prokaryotic Ago (pAgo) proteins are full-length pAgos. They are monomeric proteins, all composed of four major structural/functional domains (N, PAZ, MID and PIWI) and thereby closely resemble eAgos. It is believed that full-length pAgos function as prokaryotic antiviral systems, with the PIWI domain performing cleavage of invading nucleic acids. However, the majority of identified pAgos are shorter and catalytically inactive (encode just MID and inactive PIWI domains), thus their action mechanism and function remain unknown.ResultsIn this work we focus on AfAgo, a short pAgo protein encoded by an archaeonArchaeoglobus fulgidus. We find that in all previously solved AfAgo structures, its two monomers form substantial dimerization interfaces involving the C-terminal β-sheets. Led by this finding, we have employed various biochemical and biophysical assays, including single-molecule FRET, SAXS and AFM, to test the possible dimerization of AfAgo. SAXS results confirm that WT AfAgo, but not the dimerization surface mutant AfAgoΔ, forms a homodimer both in the apo-form and when bound to a nucleic acid. Single molecule FRET and AFM studies demonstrate that the dimeric WT AfAgo binds two ends of a linear DNA fragment, forming a relatively stable DNA loop.ConclusionOur results show that contrary to other characterized Ago proteins, AfAgo is a stable homodimer in solution, which is capable of simultaneous interaction with two DNA molecules. This finding broadens the range of currently known Argonaute-nucleic acid interaction mechanisms.
Nighttime gibberellin biosynthesis is influenced by fluctuating environmental conditions and contributes to growth adjustments of Arabidopsis leaves
Authors: Prasetyaningrum Putri , Mariotti Lorenzo , Valeri Maria Cristina , Novi Giacomo , Dhondt Stijn , Inzé Dirk , Perata Pierdomenico , van Veen Hans 
Published: May 2020

AbstractOptimal plant growth performance requires that the action of growth signals, such as gibberellins (GA), are coordinated with the availability of photo-assimilates. Here, we studied the links between gibberellin biosynthesis and carbon availability, and the subsequent effects on growth. The results presented here show that carbon availability, light and dark cues, and the clock ensure the timing and magnitude of gibberellin biosynthesis and that disruption of these mechanisms results in reduced gibberellin levels and expression of downstream genes. Carbon dependent nighttime induction of GIBBERELLIN 3-BETA-DIOXYGENASE 1 (GA3ox1) was severely hampered when preceded by a day of lowered light availability, leading specifically to reduced bioactive GA4 levels, and coinciding with a decline in leaf expansion rate during the night. We attribute this decline in leaf expansion mostly to reduced photo-assimilates. However, plants where gibberellin limitation was alleviated had significantly improved expansion demonstrating the relevance of gibberellins in growth control under varying carbon availability. Carbon dependent expression of upstream gibberellin biosynthesis genes (KAURENE SYNTHASE, KS and GIBBERELLIN 20 OXIDASE 1, GA20ox1) was not translated into metabolite changes within this short timeframe. We propose a model where the extent of nighttime biosynthesis of bioactive GA4 by GA3ox1 is determined by starch, as the nighttime carbon source, and so provides day-to-day adjustment of gibberellin responses.
Independent somatic evolution underlies clustered neuroendocrine tumors in the human small intestine
Authors: Elias Erik , Ardalan Arman , Lindberg Markus , Reinsbach Susanne , Muth Andreas , Nilsson Ola , Arvidsson Yvonne , Larsson Erik 
Published: May 2020

AbstractBackgroundSmall intestine neuroendocrine tumor (SI-NET), the most common cancer of the small bowel, often displays a curious multifocal phenotype with several intestinal tumors centered around a regional lymph node metastasis. Although SI-NET patients often present with metastatic disease at the time of diagnosis, there is an unusual absence of somatic driver mutations explaining tumor initiation and metastatic spread. The evolutionary trajectories that underlie multifocal SI-NET lesions could provide insight into the underlying tumor biology, but this question remains unresolved. Here, we determined the complete genome sequences of 65 tumor and tissue samples from 11 patients with multifocal SI-NET, allowing for elucidation of phylogenetic relationships between tumors within individual patients. Intra-individual comparisons of whole genome sequences revealed a lack of shared somatic single-nucleotide variants and copy number alterations among the sampled intestinal lesions, supporting that they were of independent clonal origin. Furthermore, each metastasis originated from a single intestinal tumor, and in three of the patients, two independent tumors had metastasized. We conclude that primary multifocal SI-NETs generally arise from clonally independent cells, suggesting a contribution from of a cancer-priming local factor.
Role ofDrosophilaRap/Fzr (DCdh1) in Retinal Axon Targeting and its Interactions with Loco and Liprin-alpha
Authors: Grońska-Pęski Marta , Venkatesh Tadmiri R. 
Published: May 2020

AbstractThe development of the wild typeDrosophilacompound eye involves stereotypical targeting of photoreceptor axons to the specific layers of the optic ganglion, medulla and lamina, in the third instar larvae. To test the hypothesis that ubiquitin ligases play an important role during retinal axon targeting we have examined the patterns of axon targeting in the developing eye of theretina aberrant in pattern (rap/fzr)mutants. Rap/Fzr is a homolog of mammalian Cdh1, an activator of anaphase promoting complex (APC), a multi-subunit E3 ubiquitin ligase, regulating the cell cycle progression. Previous work has shown that Rap/Fzr is required during eye development for proper cell cycle regulation, glia differentiation and pattern formation. It was also necessary for proper neuromuscular junction development and circadian rhythms. Our results show that Rap/Fzr is required for proper retinal axon targeting in the developing eye. Usingro-tau-lacZ, we show that the R2-R5 axons fail to stop in the lamina and mis-target to the medulla levels. Also, mosaic analyses experiments using FLP-FRT and GAL4-UAS techniques show that Rap/Fzr functions in a cell autonomous manner. To test for possible role of other signalling molecules and interactions with Rap/Fzr, we have examinedrap/fzraxon projection phenotypes in double mutant combinations with the RGS protein,locomotion defective(loco) mutants and a scaffolding protein, Liprin-α. Our studies suggest that Rap/Fzr is required for proper axon targeting duringDrosophilavisual system development, and the phenotype is enhanced in double mutants with eitherlocoor Liprin-α. These results are consistent with other mammalian studies reporting a role of Cdh1 in axon growth and targeting and provides further insights into neuronal functions of the ubiquitin ligase APC/CCdh1.HighlightsLoss ofrap/fzrin the third instar Drosophila eye disc leads to photoreceptor axon overgrowthOverexpression ofrap/fzrleads to photoreceptor axon leads to axon shortening and clumpingLoss ofLocoP452leads to photoreceptor overgrowthDouble mutants ofrapandlocoorrapandLiprin-αshow axon enhancement of the axon targeting defects in theDrosophilathird instar larvae eye imaginal discs.