bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of SARS-CoV-2 serology and clinical phenotype amongst hospitalised children in a tertiary children’s hospital in India
Authors: Venkataraman Aishwarya , Balasubramanian S , Putilibai Sulochana , Lakshan Raj S , Amperayani Sumanth , Senthilnathan S , Manoharan Anand , Sophi Arokia , Amutha R , Sadasivam Kalaimaran , Goenka Anu , Ramanan A V 
Published: February 2021

AbstractIntroductionChildren usually present with minimal or no symptoms of SARS-CoV-2 infection. Antibody responses to SARS-CoV-2 in children from low- and middle-income countries (LMIC) have not been well described. We describe the prevalence of anti-SARS-CoV-2 antibodies and clinical phenotype of seropositive children admitted to a tertiary children’s hospital in South India.MethodsTo determine the seropositivity and describe the clinical characteristics of SARS-CoV-2 infection amongst hospitalised children, we performed a prospective clinical data collection and blood sampling of children admitted to Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India over 4 months of the COVID-19 pandemic. In seropositive children, we compared antibody titres between children with and without PIMS-TS.ResultsOf 463 children, 91 (19.6%) were seropositive. The median (range) age of seropositive children was 5 years (1 month - 17 years). Clinical presentation was consistent with Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS) in 48% (44/91) of seropositive children. The median (range) antibody titre was 54.8 (11.1–170.9) AU/ml among all seropositive children. The median antibody titre among the children with PIMS-TS (60.3 AU/mL) was significantly (p=0.01) higher when compared to the children without PIM-TS (54.8 AU/mL).ConclusionWe describe the antibody responses to SARS-CoV-2 amongst hospitalised children in a LMIC tertiary children’s hospital. Almost half of the seropositive children had PIMS-TS. Antibody levels may be helpful in the diagnosis and disease stratification of PIMS-TS.Lay summaryChildren usually present with minimal or no symptoms of SARS-CoV-2 infection. However, Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS) has emerged as a distinctive paediatric illness related to SARS-CoV-2. Recently, antibody testing for SARS-CoV-2 is being used increasingly as a diagnostic test for PIMS-TS. However, data on the antibody responses to SARS-CoV-2 in children is sparse. We therefore, attempted to identify the seropositivity and describe the clinical spectrum of SARS-CoV-2 infection amongst infants and children getting hospitalised in a children’s hospital in south India. Nearly one-fifth of the hospitalised children tested serology positive over 4 months. Antibody levels in children with PIMS-TS were significantly higher in comparison to the other two groups (acute SARS-CoV-2 infection and children without PIMS-TS). Results from our study suggest that all children are at risk of SARS-CoV-2 infection though they may present with mild illness or no symptoms. We also observed that antibody testing may have a possible role in diagnosis of PIMS-TS.
MOATAI-VIR - an AI algorithm that predicts severe adverse events and molecular features for COVID-19’s complications
Authors: Astore Courtney , Zhou Hongyi , Jacob Joshy , Skolnick Jeffrey 
Published: February 2021

AbstractFollowing SARS-CoV-2 infection, some COVID-19 patients experience severe adverse events caused by pathogenic host responses. To treat these complications, their underlying etiology must be identified. Thus, a novel AI-based methodology, MOATAI-VIR, which predicts disease-protein-pathway relationships for 22 clinical manifestations attributed to COVID-19 was developed. SARS-CoV-2 interacting human proteins and GWAS identified respiratory failure associated risk genes provide the input from which the mode-of-action (MOA) proteins/pathways of the resulting disease comorbidities are predicted. These comorbidities are then mapped to their clinical manifestations. Three uncharacterized manifestation categories are found: neoplasms, mental and behavioral disorders, and congenital malformations, deformations, and chromosomal abnormalities. The prevalence of neoplasms suggests a possible association between COVID-19 and cancer, whether by shared molecular mechanisms between oncogenesis and viral replication, or perhaps, SARS-CoV-2 is an oncovirus. To assess the molecular basis of each manifestation, the proteins shared across each group of comorbidities were prioritized and subject to global pathway analysis. From these most frequent pathways, the molecular features associated with hallmark COVID-19 phenotypes, such as loss of sense of smell/taste, unusual neurological symptoms, cytokine storm, and blood clots were explored. Results of MOATAI-VIR are available for academic users at: http://pwp.gatech.edu/cssb/MOATAI-VIR/.
How best do we engage the general population in testing for COVID-19?
Authors: Watson Daniella , Baralle Natalia Laverty , Alagil Jawahr , Anil Krithika , Ciccognani Sandy , Dewar-Haggart Rachel , Fearn Sarah , Groot Julia , Knowles Kathryn , Meagher Claire , McGrath Carmel , Muir Sarah , Musgrove Jo , Glyn-Owen Kate , Woods-Townsend Kath , Mortimore Andrew , Roderick Paul , Baird Janis , Inskip Hazel , Godfrey Keith , Barker Mary 
Published: February 2021

AbstractThe UK Scientific Advisory Group for Emergencies (SAGE) emphasises the need for high levels of engagement with communities and individuals to ensure the effectiveness of any COVID-19 testing programme. A novel pilot health surveillance programme to assess the feasibility of weekly mass RT-LAMP testing for the SARS-CoV-2 virus using saliva samples collected at home was developed and piloted by the University of Southampton and Southampton City Council. Rapid qualitative evaluation was conducted to explore experiences of those who took part in the programme, of those who declined and of those in the educational and healthcare organisations involved in the pilot testing who were responsible for roll-out. This included 77 interviews and 20 focus groups with 223 staff, students, pupils and household members from four schools, one university, and one community healthcare NHS trust. Conversations revealed that high levels of communication, trust and convenience were necessary to ensure people’s engagement with the programme. This suggests community leaders and stakeholder organisations should be involved throughout programme development and implementation to optimise these features of the testing. Participants’ and stakeholders’ motivations, challenges and concerns need to be understood and these insights used to modify the programme in a continuous, real-time process to ensure and sustain engagement with testing over the extended period necessary.
Illusory social agents within and beyond voices: a computational linguistics analysis of the experience of psychosis
Authors: Shiel Lisha , Demjén Zsófia , Bell Vaughan 
Published: February 2021

AbstractAimsPsychosis has a strong social component and often involves the experience of being affected by ‘illusory social agents’. However, this experience remains under-characterised, particularly for social agents in delusions and non-vocal hallucinations. One useful approach is a form of computational linguistics called corpus linguistics that studies texts to identify patterns of meaning encoded in both the semantics and linguistic structure of the text.MethodsTwenty people living with psychosis were recruited from community and inpatient services. They participated in open-ended interviews on their experiences of social agents in psychosis and completed a measure of psychotic symptoms. Corpus linguistics analysis was used to identify key phenomenological features of vocal and non-vocal social agents in psychosis.ResultsSocial agents are i) represented with varying levels of richness in participants’ experiences, ii) are attributed with different kinds of identities including physical characteristics and names, iii) are perceived to have internal states and motivations that are different from those of the participants, and iv) interact with participants in various ways including through communicative speech acts, affecting participants’ bodies and moving through space. These representation were equally rich for agents associated with hallucinated voices and those associated with non-vocal hallucinations and delusions.ConclusionsWe show that the experience of illusory social agents is a rich and complex social experience reflecting many aspects of genuine social interaction and is not solely present in auditory hallucinations, but also in delusions and non-vocal hallucinations.
Testing out of quarantine
Authors: McGowan Lucy D’Agostino , Lee Elizabeth C. , Grantz Kyra H. , Kucirka Lauren M. , Gurley Emily S. , Lessler Justin 
Published: February 2021

AbstractSince SARS-CoV-2 emerged, a 14-day quarantine has been recommended based on COVID-19”s incubation period. Using an RT-PCR or rapid antigen test to “test out” of quarantine is a frequently proposed strategy to shorten duration without increasing risk. We calculated the probability that infected individuals test negative for SARS-CoV-2 on a particular day post-infection and remain symptom free for some period of time. We estimate that an infected individual has a 20.1% chance (95% CI 9.8-32.6) of testing RT-PCR negative on day five post-infection and remaining asymptomatic until day seven. We also show that the added information a test provides decreases as we move further from the test date, hence a less sensitive test that returns rapid results is often preferable to a more sensitive test with a delay.
Targeted screening for Alzheimer’s disease clinical trials using data-driven disease progression models
Authors: Oxtoby Neil P. , Shand Cameron , Cash David M. , Alexander Daniel C. , Barkhof Frederik ,   for the Alzheimer’s Disease Neuroimaging Initiative,   the Alzheimer’s Disease Cooperative Study
Published: February 2021

ABSTRACTHeterogeneity in Alzheimer’s disease progression contributes to the ongoing failure to demonstrate efficacy of putative disease-modifying therapeutics that have been trialled over the past two decades. Any treatment effect present in a subgroup of trial participants (responders) can be diluted by non-responders who ideally should have been screened out of the trial. How to identify (screen-in) the most likely potential responders is an important question that is still without an answer. Here we pilot a computational screening tool that leverages recent advances in data-driven disease progression modelling to improve stratification. This aims to increase the sensitivity to treatment effect by screening out non-responders, which will ultimately reduce the size, duration, and cost of a clinical trial. We demonstrate the concept of such a computational screening tool by retrospectively analysing a completed double-blind clinical trial of donepezil in people with amnestic mild cognitive impairment (clinicaltrials.gov: NCT00000173), identifying a data-driven subgroup having more severe cognitive impairment who showed clearer treatment response than observed for the full cohort.
A mathematical model to estimate percentage secondary infections from margin of error of diagnostic sensitivity: Useful tool for regulatory agencies to assess the risk of propagation due to false negative outcome of diagnostics
Authors: Azhahianambi P , Karthik K , Aravindh Babu RP , Senthil kumar TMA , Balachandran C , Dhinakar Raj G 
Published: February 2021

AbstractFalse negative outcome of a diagnosis is one the major reasons for the dissemination of the diseases with high risk of propagation. Diagnostic sensitivity and the margin of error determine the false negative outcome of the diagnosis. A mathematical model had been developed to estimate the mean % secondary infections based on the margin of error of diagnostic sensitivity, % prevalence and R0 value. This model recommends a diagnostic test with diagnostic sensitivity ≥ 96% and at least 92% lower bound limit of the 95% CI or ≤ 4% margin of error for a highly infectious diseases like COVID-19 to curb the secondary transmission of the infection due to false negative cases. Positive relationship was found between mean % secondary infection and margin of error of sensitivity suggesting greater the margin of error of a diagnostic test sensitivity, higher the number of secondary infections in a population due to false negative cases. Negative correlation was found between number of COVID-19 test kits (>90% sensitivity) with regulatory approval and margin of error (R= −0.92, p=0.023) suggesting lesser the margin of error of a diagnostic test, higher the chances of getting approved by the regulatory agencies. However, there are no specific regulatory standards available for margin of error of the diagnostic sensitivity of COVID-19 diagnostic tests. Highly infectious disease such as COVID-19, certainly need specific regulatory standards on margin of error or 95% CI of the diagnostic sensitivity to curb the dissemination of the disease due to false negative cases and our model can be used to set the standards such as sensitivity, margin of error or lower bound limit of 95% CI.
Neptune: An environment for the delivery of genomic medicine
Authors: Venner Eric , Yi Victoria , Murdock David , Kalla Sara E. , Wu Tsung-Jung , Sabo Aniko , Li Shoudong , Meng Qingchang , Tian Xia , Murugan Mullai , Cohen Michelle , Kovar Christie , Wei Wei-Qi , Chung Wendy K. , Weng Chunhua , Wiesner Georgia L. , Jarvik Gail P. , Muzny Donna , Gibbs Richard A. ,   eMERGE Consortium
Published: February 2021

AbstractPurposeGenomic medicine holds great promise for improving healthcare, but integrating searchable and actionable genetic data into electronic health records remains a challenge. Here, we describe Neptune, a system for managing the interaction between a clinical laboratory and an electronic health record system.MethodsWe developed Neptune and applied it to two clinical sequencing projects that required report customization, variant reanalysis and EHR integration.ResultsNeptune enabled the analysis of data for generation of and delivery to EHR systems of over 15,000 clinical genomic reports. These projects demanded customizable clinical reports that contained a variety of genetic data types including SNVs, CNVs, pharmacogenomics and polygenic risk scores. Two variant reanalysis activities were also supported, highlighting this important workflow.ConclusionsMethods are needed for delivering structured genetic data to EHRs. This need extends beyond developing data formats to providing infrastructure that manages the reporting process itself. Neptune was successfully applied on two high-throughput clinical sequencing projects to build and deliver clinical reports to EHR systems. The software is open and available athttps://gitlab.com/bcm-hgsc/neptune.
3-D optogenetic control of arteriole diameter in vivo
Authors: O’Herron Philip J. , Hartmann David A. , Xie Kun , Kara Prakash , Shih Andy Y. 
Published: February 2021

AbstractModulation of brain arteriole diameter is critical for maintaining cerebral blood pressure and controlling regional hyperemia during neural activity. However, studies of hemodynamic function in health and disease have lacked a method to control arteriole diameter independently with high spatiotemporal resolution. Here, we describe an all-optical approach to manipulate and monitor brain arteriole contractility in 3-dimensions using combined in vivo two-photon optogenetics and imaging. The expression of the red-shifted excitatory opsin, ReaChR, in vascular smooth muscle cells enabled rapid and repeated vasoconstriction controlled by brief light pulses. Two-photon activation of ReaChR using a spatial light modulator produced highly localized constrictions when targeted to individual arterioles within the neocortex. We demonstrate the utility of this method for examining arteriole contractile dynamics and creating transient focal blood flow reductions. Additionally, we show that optogenetic constriction can be used to reshape vasodilatory responses to sensory stimulation, providing a valuable tool to dissociate blood flow changes from neural activity.
Integrative phenotypic and genomic analyses reveal strain-dependent responses to acute ozone exposure and their associations with airway macrophage transcriptional activity
Authors: Tovar Adelaide , Crouse Wesley L. , Smith Gregory J. , Thomas Joseph M. , Keith Benjamin P. , McFadden Kathryn M. , Moran Timothy P. , Furey Terrence S. , Kelada Samir N. P. 
Published: February 2021

AbstractAcute ozone (O3) exposure is associated with multiple adverse cardiorespiratory outcomes, the severity of which varies across human populations and rodent models from diverse genetic backgrounds. However, molecular determinants of response, including biomarkers that distinguish which individuals will develop more severe injury and inflammation (i.e., high responders), are poorly characterized. Here, we exposed adult, female and male mice from 6 strains, including 5 Collaborative Cross (CC) strains, to filtered air (FA) or 2 ppm O3for 3 hours, and measured several inflammatory and injury parameters 21 hours later. Additionally, we collected airway macrophages and performed RNA-seq analysis to investigate influences of strain, treatment, and strain-by-treatment interactions on gene expression as well as transcriptional correlates of lung phenotypes. Animals exposed to O3developed airway neutrophilia and lung injury, with varying degrees of severity. We identified many genes that were altered by O3exposure across all strains, and examination of genes whose expression was influenced by strain-by-treatment interactions revealed prominent differences in response between the CC017/Unc and CC003/Unc strains, which were low- and high-responders, respectively (as measured by cellular inflammation and injury). Further investigation of this contrast indicated that baseline gene expression differences likely contribute to their divergent post-O3exposure transcriptional responses. We also observed alterations in chromatin accessibility that differed by strain and with strain-by-treatment interactions, lending further plausibility that baseline differences can modulate post-exposure responses. Together, these results suggest that aspects of the respiratory response to O3exposure may be mediated through altered airway macrophage transcriptional signatures, and further confirms the importance of gene-by-environment interactions in mediating differential responsiveness to environmental agents.
Family dynamics reveal that female house mice preferentially breed in their maternal community
Authors: Evans Julian C. , Lindholm Anna K. , König Barbara 
Published: February 2021

AbstractWhether females breed in their natal group is an important factor in the evolution of extended families in animal sociality. Breeding in natal groups comes with clear costs and benefits, depending on size of the group and presence of older relatives, including mothers. Studying individual decisions about whether to stay or leave can provide insight into the mechanisms and trade-offs governing the formation and structure of family groups. We investigated the family dynamics of a large population of free-ranging commensal house mice. Using dynamic community detection on long term datasets, we determined which females first bred in their natal group. We then looked at how this influenced breeding success. We found most females (77%) exhibited strong philopatry, breeding in their natal groups. Whether a female bred elsewhere was only predictable when natal groups were extremely small and related or large and unrelated. Despite this preference, breeding elsewhere made no difference in how quickly and successfully a female bred. However, presence of their mother did lead females to breed sooner when born during high breeding activity, when competition over reproduction is high. Based on these results, potential loss of fitness does not seem to be the main driver of philopatry in female house mice. The effect of the presence of mothers may indicate retaining prior social connections is an important benefit of breeding in the natal group. Mothers providing benefits also suggests lack of conflict between generations, which is likely an important attribute in the development of extended family groups.Lay summaryWhether animals breed in the group they are born in influences how they form extended family groups. Whether females stay will depend on properties such as presence of older relatives, including mothers. Using long-term wild mouse data, we track groups and which group females bred in. Most stayed, but leaving didn’t reduce breeding success. Presence of mother, who generally stayed, did lead to earlier breeding. This might be a key advantage to remaining to breed.
GraphUnzip: unzipping assembly graphs with long reads and Hi-C
Authors: Faure Roland , Guiglielmoni Nadège , Flot Jean-François 
Published: February 2021

AbstractLong reads and Hi-C have revolutionized the field of genome assembly as they have made highly continuous assemblies accessible for challenging genomes. As haploid chromosome-level assemblies are now commonly achieved for all types of organisms, phasing assemblies has become the new frontier for genome reconstruction. Several tools have already been released using long reads and/or Hi-C to phase assemblies, but they all start from a linear sequence, and are ill-suited for non-model organisms with high levels of heterozygosity. We present GraphUnzip, a fast, memory-efficient and accurate tool to unzip assembly graphs into their constituent haplotypes using long reads and/or Hi-C data. As GraphUnzip only connects sequences in the assembly graph that already had a potential link based on overlaps, it yields high-quality gap-less supercontigs. To demonstrate the efficiency of GraphUnzip, we tested it on a simulated diploidEscherichia coligenome, and on two real datasets for the genomes of the rotiferAdineta vagaand the potatoSolanum tuberosum. In all cases, GraphUnzip yielded highly continuous phased assemblies.
Gut regulates brain synaptic assembly through neuroendocrine signaling pathway
Authors: Shi Yanjun , Qin Lu , Shao Zhiyong 
Published: February 2021

ABSTRACTThe gut-brain axis plays an essential role in regulating neural development in response to environmental stimuli, such as microbes or nutrients. Defects in gut-brain communication can lead to various neurological disorders. However, it remains unknown whether gut plays any intrinsic role in regulating neuronal development. Through a genetic screen inC. elegans, we uncovered that an intrinsic Wnt-endocrine pathway in gut regulates synaptic development and neuronal activity in brain. Specifically, the Wnt signaling upregulates the expression of the neuropeptide NLP-40 in the gut, which then facilitates presynaptic assembly through the neuronal expressed GPCR AEX-2 receptor during development. The NLP-40 acts most likely through modulating neuronal activity and promoting synaptic protein trafficking. Therefore, this study reveals a novel role of gut in synaptic development in the brain.