bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic evaluation of SARS-CoV-2 spike protein derived peptides for diagnosis of COVID-19 patients
Authors: Li Yang , Lai Dan-yun , Lei Qing , Xu Zhao-wei , Hou Hongyan , Chen Lingyun , Wu Jiaoxiang , Ren Yan , Ma Ming-liang , Zhang Bo , Chen Hong , Yu Caizheng , Xue Jun-biao , Zheng Yun-xiao , Wang Xue-ning , Jiang He-wei , Zhang Hai-nan , Qi Huan , Guo Shu-juan , Zhang Yandi , Lin Xiaosong , Yao Zongjie , Pang Pengfei , Shi Dawei , Wang Wei , Yang Xiao , Zhou Jie , Sheng Huiming , Sun Ziyong , Shan Hong , Wang Feng , Fan Xionglin , Tao Sheng-ce 
Published: September 2020

AbstractSerological test plays an essential role in monitoring and combating COVID-19 pandemic. Recombinant spike protein (S protein), especially S1 protein is one of the major reagents for serological tests. However, the high cost in production of S protein, and the possible cross-reactivity with other human coronaviruses poses unneglectable challenges. Taking advantage of a peptide microarray of full spike protein coverage, we analyzed 2,434 sera from 858 COVID-19 patients, sera from 63 asymptomatic patients and 610 controls collected from multiple clinical centers. Based on the results of the peptide microarray, we identified several S protein derived 12-mer peptides that have high diagnosis performance. Particularly, for monitoring IgG response, one peptide (aa 1148-1159 or S2-78) has a comparable sensitivity (95.5%, 95% CI 93.7-96.9%) and specificity (96.7%, 95% CI 94.8-98.0%) to that of S1 protein for detection of both COVID-19 patients and asymptomatic infections. Furthermore, the performance of S2-78 IgG for diagnosis was successfully validated by ELISA with an independent sample cohort. By combining S2-78/ S1 with other peptides, a two-step strategy was proposed to ensure both the sensitivity and specificity of S protein based serological assay. The peptide/s identified in this study could be applied independently or in combination with S1 protein for accurate, affordable, and accessible COVID-19 diagnosis.One Sentence SummaryEight S protein-derived peptides, particularly S2-78 (aa 1148-1159), are of high performance for diagnosis of COVID-19 as well as discrimination of other coronaviruses.
Age-dependence of healthcare interventions for SARS-CoV-2 infection in Ontario, Canada
Authors: Papst Irena , Li Michael , Champredon David , Bolker Benjamin M. , Dushoff Jonathan , Earn David J.D. 
Published: September 2020

AbstractBackgroundPatient age is the most salient clinical indicator of risk from COVID-19. Age-specific distributions of known SARS-CoV-2 infections and COVID-19-related deaths are available for most countries. However, relatively little attention has been given to the age distributions of hospitalizations and serious healthcare interventions administered to COVID-19 patients. We examined these distributions in Ontario, Canada, in order to quantify the age-related impacts of COVID-19, and to identify potential risks should the healthcare system become overwhelmed with COVID-19 patients in the future.MethodsWe analysed known SARS-CoV-2 infection records from the integrated Public Health Information System (iPHIS) and the Toronto Public Health Coronavirus Rapid Entry System (CORES) between 23 January 2020 and 17 June 2020 (N = 30,546), and estimated the age distributions of hospitalizations, ICU admissions, intubations, and ventilations. We quantified the probability of hospitalization given known SARS-CoV-2 infection, and of survival given COVID-19-related hospitalization.ResultsThe distribution of COVID-19-related hospitalizations peaks with a wide plateau covering ages 54-90, whereas deaths are sharply concentrated in very old ages, with a maximum at age 90. The estimated probability of hospitalization given known SARS-CoV-2 infection reaches a maximum of 32.0% at age 75 (95% CI 27.5%-36.7%). The probability of survival given COVID-19-related hospitalization is uncertain for children (due to small sample size), and near 100% for adults younger than 40. After age 40, survival of hospitalized COVID-19 patients declines substantially; for example, a hospitalized 50-year-old patient has a 90.4% chance of surviving COVID-19 (95% CI 81.9%-95.7%).InterpretationConcerted efforts to control the spread of SARS-CoV-2 have kept prevalence of the virus low in the population of Ontario. The healthcare system has not been overstretched, yet the probability of survival given hospitalization for COVID-19 has been lower than is generally recognized for patients over 40. If prevalence of the virus were to increase and healthcare capacities were to be exceeded, survival of individuals in the broad age range requiring acute care would be expected to decrease, potentially expanding the distribution of COVID-19-related deaths toward younger ages.
Investigating post-breeding moult locations and diets of Common Guillemots (Uria aalge) in the North Sea using stable isotope analyses
Authors: Christie Alec P. 
Published: September 2020

AbstractSeabird movements and diet during the non-breeding season are poorly studied, yet understanding these aspects of seabird ecology is extremely important to effectively conserve these protected species. Stable isotope analyses (SIA) provide a cost-effective solution to filling these knowledge gaps, yielding information on diet and foraging locations of animals. This study aimed to use SIA to investigate whether Common Guillemots (Uria aalge) from different age classes and locations in the UK had contrasting diets and foraging areas during the post-breeding moult (July-September). SIA of secondary feathers and a newly-developed North Sea isoscape were used to identify the likeliest foraging areas and diets of deceased guillemots recovered from beaches in eastern Scotland and mixed fisheries in Cornwall and the Celtic Sea. Overall, guillemots foraged widely in the western, eastern and southern North Sea, consuming a variety of clupeid, gadoid and invertebrate prey. There were negligible dietary differences between age classes and birds from different recovery locations. Juveniles showed a wider range in foraging areas, but both age classes foraged in similar parts of the North Sea. Guillemots recovered from Scotland may have foraged further north, only overlapping with guillemots recovered from the southwestern UK in the southern and eastern North Sea. Their winter recovery locations also implied that they exhibited different movement strategies during the non-breeding season, meriting further investigation. Conservation efforts should target foraging areas in the southern and eastern North Sea which are highly threatened by gillnet fishing, shipping traffic and oil infrastructure.
Experimentally disambiguating models of sensory cue integration
Authors: Scarfe Peter 
Published: September 2020

AbstractSensory cue integration is one of the primary areas in which a normative mathematical framework has been used to define the “optimal” way in which to make decisions based upon ambiguous sensory information and compare these predictions to behaviour. The conclusion from such studies is that sensory cues are integrated in a statistically optimal fashion. However, numerous alternative computational frameworks exist by which sensory cues could be integrated, many of which could be described as “optimal” based on different criteria. Existing studies rarely assess the evidence relative to different candidate models, resulting in an inability to conclude that sensory cues are integrated according to the experimenter’s preferred framework. The aims of the present paper are to summarise and highlight the implicit assumptions rarely acknowledged in testing models of sensory cue integration, as well as to introduce an unbiased and principled method by which to determine, for a given experimental design, the probability with which a population of observers behaving in accordance with one model of sensory integration can be distinguished from the predictions of a set of alternative models.
The Epidermal Barrier is Indispensable for Systemic Energy Homeostasis
Authors: Kruse Vibeke , Neess Ditte , Marcher Ann-Britt , Wæde Mie Rye , Vistisen Julie , Møller Pauline M. , Petersen Rikke , Brewer Jonathan R. , Ma Tao , Colleluori Georgia , Severi Ilenia , Cinti Saverio , Gerhart-Hines Zach , Mandrup Susanne , Færgeman Nils J. 
Published: September 2020

ABSTRACTObjectivesHomeostatic regulation of body temperature is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and neuronal regulators. Although the skin is the largest sensory organ of the human body, and plays a fundamental role in regulating body temperature, it is surprising that adaptive alterations in skin functions and morphology only vaguely have been associated with physiological responses to cold stress or sensation of ambient temperatures.MethodsTo unravel the physiological responses to a compromised epidermal barrier in detail we have used animal models with either defects in skin lipid metabolism (ACBP-/-and skin-specific ACBP-/-knockout mice) or defects in skin structural proteins (ma/ma Flgft/ft). The primary objective was to clarify how defects in epidermal barrier function affect 1) energy expenditure by indirect calorimetry, 2) response to high fat feeding and a high oral glucose load and 3) expression of brown-selective gene programs by quantitative PCR in inguinal WAT (iWAT).ResultsWe show that mice with a compromised epidermal barrier function exhibit increased energy expenditure, increased food intake, browning of the iWAT, and resistance to diet-induced obesity. The metabolic phenotype, including browning of the iWAT, is reversed by housing the mice at thermoneutrality (30°C) or by pharmacological β-adrenergic blocking. These findings show that a compromised epidermal barrier induces a β-adrenergic response that increases energy expenditure and browning of the white adipose tissue to maintain a normal body temperature.ConclusionOur findings show that the epidermal barrier plays a key role in maintaining systemic metabolic homeostasis.HighlightsEnergy expenditure is significantly augmented in mice with impaired epidermal barrier.Mice with compromised barrier display increased food intake while maintaining normal bodyweight.Mice with an impaired epidermal barrier are resistant to diet-induced obesity and insulin resistance.Compromised barrier function induces expression of brown-selective gene programs in iWAT.Thermoneutral housing or blocking β-adrenergic signaling prevents induction of brite-selective genes in iWAT and reverses food intake.
ASO-basedPKMSplice-switching Therapy Inhibits Hepatocellular Carcinoma Cell Growth
Authors: Ma Wai Kit , Voss Dillon M. , Scharner Juergen , Costa Ana S. H. , Lin Kuan-Ting , Jeon Hyun Yong , Wilkinson John E. , Jackson Michaela , Rigo Frank , Bennett C. Frank , Krainer Adrian R. 
Published: September 2020

AbstractThe M2 pyruvate kinase (PKM2) isoform is upregulated in most cancers and plays a crucial role in the Warburg effect, which is characterized by the preference for aerobic glycolysis for energy metabolism. PKM2 is an alternative-splice isoform of thePKMgene and is a potential therapeutic target. Previously, we developed antisense oligonucleotides (ASOs) that switchPKMsplicing from the cancer-associatedPKM2to thePKM1isoform and induce apoptosis in cultured glioblastoma cells. Here, we explore the potential of ASO-basedPKMsplice-switching as a targeted therapy for liver cancer. We utilize a more potent lead cEt/DNA ASO and demonstrate that it inducesPKMsplice-switching and inhibits the growth of cultured hepatocellular-carcinoma (HCC) cells. ThisPKMisoform switch increases pyruvate-kinase activity and alters glucose metabolism. The lead ASO and a second ASO targeting a non-overlapping site inhibit tumorigenesis in an orthotopic-xenograft HCC mouse model. Finally, a surrogate mouse-specific ASO inducesPkmsplice-switching and inhibits HCC growth, without observable toxicity, in a genetic HCC mouse model. These results lay the groundwork for a potential ASO therapy for HCC.Statement of significanceAntisense oligonucleotides are used to force a change inPKMisoform usage in HCC, reversing the Warburg effect and inhibiting tumorigenesis.
The Effect of Population Structure on Murine Genome-Wide Association Studies
Authors: Wang Meiyue , Fang Zhuoqing , Yoo Boyoung , Bejerano Gill , Peltz Gary 
Published: September 2020

AbstractPopulation structure (PS) has been shown to cause false positive signals in genome-wide association studies (GWAS). Since PS correction is routinely used in human GWAS, it was assumed that it also should be utilized for murine GWAS using inbred strains. Nevertheless, there are fundamental differences between murine and human GWAS, and the impact of PS on murine GWAS results has not been thoroughly investigated. To assess the impact of PS on murine GWAS, we examined 8223 datasets that characterized biomedical responses in panels of inbred mouse strains. Surprisingly, we found that the PS had a minimal impact on datasets characterizing responses in ≤20 strains; and relatively little impact on the majority of datasets characterizing >20 strains. Moreover, there were examples where association signals within known causative genes could be rejected if PS correction methods were utilized. PS assessment should be carefully used and should be considered in conjunction with other criteria when assessing the candidate genes identified in GWAS using inbred mouse strains.
Manipulation of IRE1-dependent MAPK signaling by a Vibrio agonist-antagonist effector pair
Authors: De Nisco Nicole J. , Casey Amanda K. , Kanchwala Mohammed , Lafrance Alexander E. , Coskun Fatma S. , Kinch Lisa N. , Grishin Nick V. , Xing Chao , Orth Kim 
Published: September 2020

AbstractDiverse bacterial pathogens employ effector delivery systems to disrupt vital cellular processes in the host (1). The type III secretion system 1 of the marine pathogen,Vibrio parahaemolyticus, utilizes the sequential action of four effectors to induce a rapid, pro-inflammatory cell death uniquely characterized by a pro-survival host transcriptional response (2, 3). Herein, we show that this pro-survival response is caused by the action of the channel-forming effector VopQ that targets the host V-ATPase resulting in lysosomal deacidification and inhibition of lysosome-autophagosome fusion. Recent structural studies have shown how VopQ interacts with the V-ATPase and, while in the ER, a V-ATPase assembly intermediate can interact with VopQ causing a disruption in membrane integrity. Additionally, we observe that VopQ-mediated disruption of the V-ATPase activates the IRE1 branch of the unfolded protein response (UPR) resulting in an IRE1-dependent activation of ERK1/2 MAPK signaling. We also find that this early VopQ-dependent induction of ERK1/2 phosphorylation is terminated by the VopS-mediated inhibitory AMPylation of Rho GTPase signaling. Since VopS dampens VopQ-induced IRE1-dependent ERK1/2 activation, we propose that IRE1 activates ERK1/2 phosphorylation at or above the level of Rho GTPases. This study illustrates how temporally induced effectors can work as in tandem as agonist/antagonist to manipulate host signaling and reveal new connections between V-ATPase function, UPR and MAPK signaling.ImportanceVibrio parahaemolyticus (V. para)is a seafood-borne pathogen that encodes two Type 3 Secretion Systems (T3SS). The first system T3SS1 is thought to be maintained in all strains ofV. parato to maintain survival in the environment, whereas the second sytem T3SS2 is linked to clinical isolates and disease in humans. Herein, we find that first system targets evolutionarily conserved signaling systems to manipulate host cells, eventually causing a rapid, orchestrated cells death within three hours. We have found that the T3SS1 injects virulence factors that temporally manipulate host signaling. Within the first hour of infection, the effector VopQ acts first by activating host surval signals while diminishing the host cell apoptotic machinery. Less than an hour later, another effector VopS reverses activation and inhibition of these signaling systems ultimately leading to death of the host cell. This work provides example of how pathogens have evolved to manipulate the interplay between T3SS effectors to regulate host signaling pathways.
Digital droplet PCR accurately quantifies SARS-CoV-2 viral load from crude lysate without nucleic acid purification
Authors: Vasudevan Harish N. , Xu Peng , Servellita Venice , Miller Steve , Liu Leqian , Gopez Allan , Chiu Charles Y. , Abate Adam R. 
Published: September 2020

AbstractThe COVID-19 pandemic caused by the SARS-CoV-2 virus motivates diverse diagnostic approaches due to the novel causative pathogen, incompletely understood clinical sequelae, and limited availability of testing resources. Given the variability in viral load across and within patients, absolute viral load quantification directly from crude lysate is important for diagnosis and surveillance. Here, we investigate the use of digital droplet PCR (ddPCR) for SARS-CoV-2 viral load measurement directly from crude lysate without nucleic acid purification. We demonstrate ddPCR accurately quantifies SARS-CoV-2 standards from purified RNA and multiple sample matrices, including commonly utilized universal transport medium (UTM). In addition, we find ddPCR functions robustly at low input viral copy numbers on nasopharyngeal swab specimens stored in UTM without upfront RNA extraction. We also show ddPCR, but not qPCR, from crude lysate shows high concordance with viral load measurements from purified RNA. Our data suggest ddPCR offers advantages to qPCR for SARS-CoV-2 detection with higher sensitivity and robustness when using crude lysate rather than purified RNA as input. More broadly, digital droplet assays provide a potential method for nucleic acid measurement and infectious disease diagnosis with limited sample processing, underscoring the utility of such techniques in laboratory medicine.
Real-time monitoring of COVID-19 dynamics using automated trend fitting and anomaly detection
Authors: Jombart Thibaut , Ghozzi Stéphane , Schumacher Dirk , Leclerc Quentin J , Jit Mark , Flasche Stefan , Greaves Felix , Ward Tom , Eggo Rosalind M , Nightingale Emily , Meakin Sophie , Brady Oliver J ,   Centre for Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Medley Graham F , Höhle Michael , Edmunds W John 
Published: September 2020

AbstractAs several countries gradually release social distancing measures, rapid detection of new localised COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (Automatic Selection of Models and Outlier Detection for Epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterise the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggest ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. We illustrate our method using publicly available data of NHS Pathways reporting potential COVID-19 cases in England at a fine spatial scale, for which we provide a template automated analysis pipeline. ASMODEE is implemented in the free R package trendbreaker.
The lower-airway microbiome and metabolome in preterm infants: Identifying potential predictive biomarkers of bronchopulmonary dysplasia
Authors: Xu Qi , Yu Jialin , He Junli , Tan Qi , He Yu 
Published: September 2020

AbstractThe lower-airway microbiome may influence the pathogenesis of lung disease. Bronchopulmonary dysplasia (BPD) is a serious morbidity associated with preterm birth that may be influenced by lower-airway microbial or metabolic alterations. This study used16S rRNA gene sequencing, metabolomic analyses, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to investigate the lower-airway microbiome and metabolome in a cohort of preterm infants with mild, moderate, or severe BPD or no BPD. Differences in the diversity and composition of the infants’ lower airway microbiota, as well as metabolic status, were initially observed, but became less pronounced at 7 days of life. Decreased diversity of the lower-airway microbiome, increased abundance ofStenotrophomonas, and increased level of sn-glycerol 3-phosphoethanolamine were associated with increased BPD severity, and have potential as predictive biomarkers for BPD.Stenotrophomonasmay contribute to the development of BPD and influence the composition of the lower-airway microbiome through its metabolite, sn-glycerol 3-phosphoethanolamine. These findings provide novel insights into the lower-airway microbiome and its role in BPD.
Temporal stability of the ventral attention network and general cognition along the Alzheimer’s disease spectrum
Authors: Chumin Evgeny J. , Risacher Shannon L. , West John D. , Apostolova Liana G. , Farlow Martin R. , McDonald Brenna C. , Wu Yu-Chien , Saykin Andrew J. , Sporns Olaf 
Published: September 2020

AbstractUnderstanding the interrelationships of clinical manifestations of Alzheimer’s disease (AD) and functional connectivity (FC) as the disease progresses is necessary for use of FC as a potential neuroimaging biomarker. Degradation of resting-state networks in AD has been observed when FC is estimated over the entire scan, however, the temporal dynamics of these networks are less studied. We implemented a novel approach to investigate the modular structure of static (sFC) and time-varying (tvFC) connectivity along the AD spectrum in a two-sample Discovery/Validation design (n=80 and 81, respectively). Cortical FC networks were estimated across 4 diagnostic groups (cognitively normal, subjective cognitive decline, mild cognitive impairment, and AD) for whole scan (sFC) and with sliding window correlation (tvFC). Modularity quality (across a range of spatial scales) did not differ in either sFC or tvFC. For tvFC, group differences in temporal stability within and between multiple resting state networks were observed; however, these differences were not consistent between samples. Correlation analyses identified a relationship between global cognition and temporal stability of the ventral attention network, which was reproduced in both samples. While the ventral attention system has been predominantly studied in task-evoked designs, the relationship between its intrinsic dynamics at-rest and general cognition along the AD spectrum highlights its relevance regarding clinical manifestation of the disease.