bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammation Drives Alternative First Exon usage to Regulate Immune Genes including a Novel Iron Regulated Isoform of Aim2
Authors: Robinson Elektra K. , Jagannatha Pratibha , Covarrubias Sergio , Cattle Matthew , Safavi Rojin , Song Ran , Viswanathan Kasthuribai , Shapleigh Barbara , Abu-Shumays Robin , Jain Miten , Cloonan Suzanne M. , Wakeland Edward , Akeson Mark , Brooks Angela N. , Carpenter Susan 
Published: July 2020

AbstractDetermining the layers of gene regulation within the innate immune response is critical to our understanding of the cellular responses to infection and dysregulation in disease. We identified a conserved mechanism of gene regulation in human and mouse via changes in alternative first exon (AFE) usage following inflammation, resulting in changes to isoform usage. Of these AFE events, we identified 50 unannotated transcription start sites (TSS) in mice using Oxford Nanopore native RNA sequencing, one of which is the cytosolic receptor for dsDNA and known inflammatory inducible gene,Aim2. We show that this unannotated AFE isoform ofAim2is the predominant isoform transcribed during inflammation and contains an iron-responsive element in its 5′UTR enabling mRNA translation to be regulated by iron levels. This work highlights the importance of examining alternative isoform changes and translational regulation in the innate immune response and uncovers novel regulatory mechanisms ofAim2.Summary SentenceAlternative first exon usage was the major splicing event observed in macrophages during inflammation, which resulted in the elucidation of a novel isoform and iron mediated regulatory mechanism of the protein coding gene,Aim2.
Discovery of Drug-like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3
Authors: Virdi Rajdeep S. , Bavisotto Robert V. , Hopper Nicholas C. , Vuksanovic Nemanja , Melkonian Trevor R. , Silvaggi Nicholas R. , Frick David N. 
Published: July 2020

ABSTRACTSmall molecules that bind the SARS-CoV-2 non-structural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to coronavirus’ ability to evade cellular detection. A high-throughput assay based on differential scanning fluorimetry (DSF) was therefore optimized and used to identify possible Mac1 ligands in small libraries of drugs and drug-like compounds. Numerous promising compounds included nucleotides, steroids, beta-lactams, and benzimidazoles. The main drawback to this approach was that a high percentage of compounds in some libraries were found to influence the observed Mac1 melting temperature. To prioritize DSF screening hits, the shapes of the observed melting curves and initial assay fluorescence were examined, and the results were compared with virtual screens performed using Autodock VINA. The molecular basis for alternate ligand binding was also examined by determining a structure of one of the hits, cyclic adenosine monophosphate, with atomic resolution.
Growth of tumor emboli within a vessel model reveals dependence on the magnitude of mechanical constraint
Authors: Kulwatno Jonathan , Gearhart Jamie , Gong Xiangyu , Herzog Nora , Getzin Matthew , Skobe Mihaela , Mills Kristen L. 
Published: July 2020

ABSTRACTTumor emboli – aggregates of tumor cell within vessels – pose a clinical challenge as they are associated with increased metastasis and tumor recurrence. When growing within a vessel, tumor emboli are subject to a unique mechanical constraint provided by the tubular geometry of the vessel. Current models of tumor emboli use unconstrained multicellular tumor spheroids, which neglect this mechanical interplay. Here, we modelled a lymphatic vessel as a 200 μm-diameter channel in either a stiff or soft, bioinert agarose matrix, and we modelled colon or breast cancer tumor emboli with aggregates of HCT116 or SUM149PT cells, respectively. The stiff vessel model constrained the tumor emboli to the cylindrical geometry, which led to continuous growth of the emboli, in contrast to the growth plateau that unconstrained spheroids exhibit. Emboli morphology in the soft vessel model, however, was dependent on the magnitude of mechanical mismatch between the vessel matrix and the cell aggregates. In general, when the elastic modulus of the vessel was greater than the emboli (Eves/Eemb> 1), the emboli were constrained to grow within the vessel geometry, and when the elastic modulus of the vessel was less than the emboli (0 <Eves/Eemb< 1), the emboli bulged into the matrix. Inhibitors of myosin-related force generation decreased the elastic modulus and/or increased the stress relaxation of the tumor cell aggregates, effectively increasing the mechanical mismatch. The increased mechanical mismatch after drug treatment was correlated with increased confinement of tumor emboli growth along the vessel, which may translate to increased tumor burden due to the increased tumor volume within the diffusion distance of nutrients and oxygen.INSIGHT BOXThe growth of tumor emboli—aggregates of tumor cells within vessels—is associated with aggressive cancer progression and metastasis. Models of their growth have not taken into account their biomechanical context, where radial expansion is constrained, but lengthwise expansion is free in the vessel. Here, we modelled the vessel geometry with a cylindrical microchannel in a hydrogel. In contrast to unconstrained or fully embedded aggregates, vessel-like constraint promotes growth of emboli in our model. The growth advantage is increased when the matrix is stiffened or actomyosin contractility weakened, both of which effectively increase the magnitude of mechanical constraint. This study sheds light on increased tumor burden in vessel-based growth and indicates a need to study tumor progression in similar environments.
Passive Monitoring of Physiological Data and Self-reported Symptoms to Detect Clusters of People with COVID-19
Authors: Quer Giorgio , Radin Jennifer M. , Gadaleta Matteo , Baca-Motes Katie , Ariniello Lauren , Ramos Edward , Kheterpal Vik , Topol Eric J. , Steinhubl Steven R 
Published: July 2020

ABSTRACTTraditional screening for COVID-19 typically includes survey questions about symptoms, travel history, and sometimes temperature measurements. We explored whether longitudinal, personal sensor data can help identify subtle changes which may indicate an infection, such as COVID-19. To do this we developed an app that collects smartwatch and activity tracker data, as well as self-reported symptoms and diagnostic testing results from participants living in the US. We assessed whether symptoms and sensor data could differentiate COVID-19 positive versus negative cases in symptomatic individuals. Between March 25 and June 7, 2020, we enrolled 30,529 participants, of whom 3,811 reported symptoms, 54 reported testing positive for COVID-19, and 279 negative. We found that a combination of symptom and sensor data resulted in an AUC=0.80 [0.73 – 0.86] which was significantly better (p < 0.01) than a model which just considered symptoms alone (AUC=0.71 [0.63 – 0.79]) in the discrimination between symptomatic individuals positive or negative for COVID-19. Such orthogonal, continuous, passively captured data may be complementary to virus testing that is generally a one-off, or infrequent, sampling assay.
Reopening universities during the COVID-19 pandemic: A testing strategy to minimize active cases and delay outbreaks
Authors: Rennert Lior , Kalbaugh Corey A. , Shi Lu , McMahan Christopher 
Published: July 2020

AbstractBackgroundUniversity campuses present an ideal environment for viral spread and are therefore at extreme risk of serving as a hotbed for a COVID-19 outbreak. While active surveillance throughout the semester such as widespread testing, contact tracing, and case isolation, may assist in detecting and preventing early outbreaks, these strategies will not be sufficient should a larger outbreak occur. It is therefore necessary to limit the initial number of active cases at the start of the semester. We examine the impact of pre-semester NAT testing on disease spread in a university setting.MethodsWe implement simple dynamic transmission models of SARS-CoV-2 infection to explore the effects of pre-semester testing strategies on the number of active infections and occupied isolation beds throughout the semester. We assume an infectious period of 3 days and vary R0 to represent the effectiveness of disease mitigation strategies throughout the semester. We assume the prevalence of active cases at the beginning of the semester is 5%. The sensitivity of the NAT test is set at 90%.ResultsIf no pre-semester screening is mandated, the peak number of active infections occurs in under 10 days and the size of the peak is substantial, ranging from 5,000 active infections when effective mitigation strategies (R0 = 1.25) are implemented to over 15,000 active infections for less effective strategies (R0 = 3). When one NAT test is mandated within one week of campus arrival, effective (R0 = 1.25) and less effective (R0 = 3) mitigation strategies delay the onset of the peak to 40 days and 17 days, respectively, and result in peak size ranging from 1,000 to over 15,000 active infections. When two NAT tests are mandated, effective (R0 = 1.25) and less effective (R0 = 3) mitigation strategies delay the onset of the peak through the end of fall semester and 20 days, respectively, and result in peak size ranging from less than 1,000 to over 15,000 active infections. If maximum occupancy of isolation beds is set to 2% of the student population, then isolation beds would only be available for a range of 1 in 2 confirmed cases (R0 = 1.25) to 1 in 40 confirmed cases (R0 = 3) before maximum occupancy is reached.ConclusionEven with highly effective mitigation strategies throughout the semester, inadequate pre-semester testing will lead to early and large surges of the disease and result in universities quickly reaching their isolation bed capacity. We therefore recommend NAT testing within one week of campus return. While this strategy is sufficient for delaying the timing of the outbreak, pre-semester testing would need to be implemented in conjunction with effective mitigation strategies to reduce the outbreak size.
Predicted effects of summer holidays and seasonality on the SARS-Cov-2 epidemic in France
Authors: Duchemin Louis , Paris Mathilde , Boussau Bastien 
Published: July 2020

1AbstractThe SARS-CoV-2 epidemic in France has had a large death toll. It has not affected all regions similarly, since the death rate can vary several folds between regions where the epidemic has remained at a low level and regions where it got an early burst. The epidemic has been slowed down by a lockdown that lasted for almost eight weeks, and individuals can now move between metropolitan French regions without restriction. In this report we investigate the effect on the epidemic of summer holidays, during which millions of individuals will move between French regions. Additionally, we evaluate the effect of strong or weak seasonality and of several values for the reproduction number on the epidemic, in particular on the timing, the height and the spread of a second wave. To do so, we extend a SEIR model to simulate the effect of summer migrations between regions on the number and distribution of new infections. We find that the model predicts little effect of summer migrations on the epidemic, because the number of migrating infectious individuals are low as a consequence of the lockdown. However, all the reproduction numbers above 1.0 and the seasonality parameters we tried result in a second epidemic wave, with a peak date that can vary between October 2020 and April 2021. If the sanitary measures currently in place manage to keep the reproduction number below 1.0, the second wave will be avoided. If they keep the reproduction number at a low value, for instance at 1.1 as in one of our simulations, the second wave is flattened and could be similar to the first wave.
COVID-19 presenting as anosmia and dysgeusia in New York City emergency departments, March - April, 2020
Authors: Wang Tina Z. , Sell Jessica , Weiss Don , Lall Ramona 
Published: July 2020

AbstractBackgroundIncreasing evidence has been emerging of anosmia and dysgeusia as frequently reported symptoms in COVID-19. Improving our understanding of these presenting symptoms may facilitate the prompt recognition of the disease in emergency departments and prevent further transmission.MethodsWe examined a cross-sectional cohort using New York City emergency department syndromic surveillance data for March and April 2020. Emergency department visits for anosmia and/or dysgeusia were identified and subsequently matched to the Electronic Clinical Laboratory Reporting System to determine testing results for SARS-CoV-2.ResultsOf the 683 patients with anosmia and/or dysgeusia included, SARS-CoV-2 testing was performed for 232 (34%) and 168 (72%) were found to be positive. Median age of all patients presenting with anosmia and/or dysgeusia symptoms was 38, and 54% were female. Anosmia and/or dysgeusia was the sole complaint of 158 (23%) patients, of whom 35 were tested for SARS-CoV-2 and 23 (66%) were positive. While the remaining patients presented with at least one other symptom, nearly half of all patients (n=334, 49%) and more than a third of those who tested positive (n=62, 37%) did not have any of the CDC-established symptoms used for screening of COVID-19 such as fever, cough, shortness of breath, or sore throat.Conclusions and RelevanceAnosmia and/or dysgeusia have been frequent complaints among patients presenting to emergency departments during the COVID-19 pandemic, and, while only a small proportion of patients ultimately underwent testing for SARS-CoV-19, the majority of patients tested have been positive. Anosmia and dysgeusia likely represent underrecognized symptoms of COVID-19 but may have important future implications in disease diagnosis and surveillance.
Long-term PM2.5 exposure and depressive symptoms in China: a quasi-experimental study
Authors: Xue Tao , Guan Tianjia , Zheng Yixuan , Geng Guannan , Zhang Qiang , Yao Yao , Zhu Tong 
Published: July 2020

AbstractBackgroundAir pollutants, particularly fine particulate matters (PM2.5) have been associated with mental disorder such as depression. Clean air policy (CAP, i.e., a series of emission-control actions) has been shown to reduce the public health burden of air pollutions. There were few studies on the health effects of CAP on mental health, particularly, in low-income and middle-income countries (LMICs). We investigated the association between a stringent CAP and depressive symptoms among general adults in China.MethodsWe used three waves (2011, 2013 and 2015) of the China Health and Retirement Longitudinal Study (CHARLS), a prospective nationwide cohort of the middle-aged and older population in China. We assessed exposure to PM2.5 through a satellite-retrieved dataset. We implemented a difference-in-differences (DID) approach, under the quasi-experimental framework of the temporal contrast between 2011 (before the CAP) and 2015 (after the CAP), to evaluate the effect of CAP on depressive symptoms. The association was further explored using a mixed-effects model of the three waves. To increase the interpretability, the estimated impact of PM2.5 was compared to that of aging, an established risk factor for depression.FindingsOur analysis included 15,954 participants. In the DID model, we found a 10-μg/m3 reduction of PM2.5 concentration was associated with a 4.14% (95% CI: 0.41–8.00%) decrement in the depressive score. The estimate was similar to that from the mixed-effects model (3.63% [95% CI, 2.00–5.27%]). We also found improved air quality during 2011-2015 offset the negative impact from 5-years’ aging.InterpretationThe findings suggest that implementing CAP may improve mental wellbeing of adults in China and other LMICs.FundingNational Natural Science Foundation and Ministry of Science and Technology of China, and Energy Foundation.
COVID-19 incidence trends between April and June 2020: A global analysis
Authors: Amanor-Boadu Vincent , Ross Kara 
Published: July 2020

AbstractThe study sought to investigate how the number of confirmed cases of COVID-19 have evolved in the most recent three months across the world, and what insights the trends may provide about the second half of the pandemic’s first year using a situation analysis approach based on national income, temperature, trade intensity with China, and location defined by longitude and latitude. The study confirmed the negative relationship between COVID-19 cases and temperature. It contributed to the resolution of the conflicting results about latitude after organizing it into a categorical variable instead of its continuous form. This approach works because the average temperature in the 15°S to 15°N region remains similar to the average temperatures in both the Above 15°N region and the Below 15°S region during their summer months because the 15°S to 15°N region does not experience the marked seasonal changes in temperature. Given the negative association between temperature and case numbers, this suggests that countries in the 15°S to 15°N region might continue exhibiting the low numbers they have thus far exhibited through the second half of this year, even as numbers climb in the Below 15°S region. To succeed, their policymakers must control importation of the disease by implementing effective testing, quarantining, and contact tracing for people entering their borders. Policymakers in countries Below 15°S region may manage their inherent risks by applying lessons learned from countries in the Above 15°N region during these past months. Such preventative measures may allow the world to avoid the drastic lockdown policies and facilitate rapid global economic recovery from this pandemic.
Comparative conventional extraction methods of ethanolic extracts of Clinacanthus nutans leaves on antioxidant activity and toxicity
Authors: Chuah Pei Ni , Nyanasegaram Dhalini , Yu Ke-Xin , Mohamed Razik Rasny , Al-Dhalli Samer , Kue Chin Siang , Shaari Khozirah , Ng Chean Hui 
Published: July 2020

PurposeThe purpose of this paper is to evaluate the antioxidant activity and toxicity of Clinacanthus nutans leaves from three conventional extraction methods, i.e. maceration, Soxhlet and magnetic stirring.Design/methodology/approachTotal flavonoid content (TFC) and phenolic content (TPC) were determined using colorimetric method of aluminum chloride and Folin-Ciocalteu (FC) assay, respectively. Antioxidant property of C. nutans was evaluated using 2,2'-diphenyl-1-pierylhydrazyl (DPPH) free radical scavenging assay. Cytotoxic activity of C. nutans against brine shrimp was evaluated based on LC50 (lethality concentration) after 24 h exposure to the plant extract.FindingsThe highest TPC of C. nutans was observed with Soxhlet extraction method (98.87 ± 10.43 mg of gallic acid equivalents (GAE/g) followed by maceration (68.77 ± 2.45 mg of GAE/g) and magnetic stirring (46.75 ± 2.45 mg of GAE/g). Interestingly, remarkable highest TFC was observed with magnetic stirring (568.90 ± 4.85 mg of rutin equivalent (RE)/g) followed by maceration (249.60 ± 2.79 mg of RE/g) and Soxhlet (174.8 ± 1.74 mg of RE/g). On the other hands, the extract obtained using maceration method showed the highest antioxidant activity (IC50: 14.18 mg/mL compared to ascorbic acid 144.36 µg/mL). Cytotoxicity of C. nutans from all extraction methods showed similar LC50 values with maceration (3.81 mg/mL), Soxhlet (2.61 mg/mL) and magnetic stirring (4.56 mg/mL), respectively.Originality/valueBoth phenolic and flavonoids are responsible for the antioxidant activity, of C. nutans extracts. Based on Meyer's toxicity index, all extracts were nontoxic (LC50>1 mg/mL).
Factors driving indebtedness among small- and medium-sized dairy companies
Authors: Mazzoleni Alberto , Pollonini Enrica 
Published: July 2020

PurposeWe developed a model to demonstrate how multiple interrelated aspects of a firm influence its recourse to third-party financing, which frequently depends on the characteristics of each food production chain.Design/methodology/approachWe conducted an empirical research on a relevant sample of small- and medium-sized Italian dairy firms. Our research methodology is inspired by the grounded theory (Glaser and Strauss, 1967).FindingsOur findings illustrated that firm indebtedness is the result of intertwined variables, linked to different firm dimensions, including growth, financial structure and economic dynamics.Research limitations/implicationsA portion of the analysed phenomenon is not explained using the sample and econometric tools.Practical implicationsThere are practical implications for the decision-makers in a firm (in particular, the managers and the shareholders) as the model allows to evaluate the influence of a set of mutually interdependent firm variables for the indebtedness level.Originality/valueFirst, we considered the recourse to third-party financing within the context of the systems theory (Millová and Blatný, 2015) and from the perspective of linked causes and mutually connected variables. Second, our research focussed on a well-defined food chain and on features of firms operating in this context. Last, our model considered the impact of the recent economic crisis, which motivated us to review the existing models.
Innovation within the food companies: how creative partnerships may conduct to better performances?
Authors: Ferraris Alberto , Vrontis Demetris , Belyaeva Zhanna , De Bernardi Paola , Ozek Hande 
Published: July 2020

PurposeThis is one of the first empirical studies aimed at analyzing the interrelation between creative partnerships (CPs), absorptive (AC), knowledge application (KA) capacities and innovation performance in food companies.Design/methodology/approachWe tested this on a sample of 112 Italian medium-sized food firms that established CPs through a partial least square (PLS) structural equation model (SEM) approach.FindingsResults are in favor of an important role of CPs in the innovation process of food firms analyzed only if combined with the development of the two internal capacities investigated (AC and KA).Research limitations/implicationsImplications are provided in order to stimulate new and more forms of collaboration between CIs and food firms as well as more empirical studies on this topic.Originality/valueFew studies in food companies keep into account the role of internal capacities that firms have to build with the aim of acquiring external knowledge through partnerships, in particular in the specific context of CPs. These specific kinds of partnerships are becoming increasingly important because they provide key nonoverlapping knowledge and propose new creative methods, ways and answers that differentiate the innovation process of food firms.