bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medical Exemptions to Vaccination — Riverside County, California, 2016–2019
Authors: Kaiser Cameron , Geiger Tonya , Lynch Cassandra , Rivera Anna 
Published: April 2022

AbstractObjectivesTo review the nature and clinical reasoning of medical exemptions to vaccination received in Riverside County, CA after California Senate Bill 277 eliminated personal belief exemptions statewide.Methods614 deduplicated medical exemptions to vaccination from 156 providers were reviewed from August 2016 to August 2019. Exemptions covering all vaccines were additionally coded for number and category of medical justification.Results81.3% of reviewed exemptions were for all vaccines, 91.0% were permanent or indefinite, and 74.9% were for all vaccines and permanent or indefinite. Of the 490 evaluated all-vaccine exemptions, a median of two and maximum of ten justifications were cited per exemption, most often a family history of autoimmune disease other than allergy. Three providers wrote more than 70 exemptions each.ConclusionsThe number and nature of the exemptions reviewed here raise concerns over their impact on immunization rates, and future policies may need to ensure additional oversight.
How does target lesion selection affect RECIST? A computer simulation study
Authors: Bucho Teresa T. , Tissier Renaud , Lipman Kevin Groot , Bodalal Zuhir , Pizzi Andrea Delli , Nguyen-Kim Thi Dan Linh , Beets-Tan Regina , Trebeschi Stefano 
Published: April 2022

AbstractRECIST is grounded on the assumption that target lesion selection is objective and representative of the change in total tumor burden during therapy. A computer simulation model was designed to challenge this assumption, focusing on a particular aspect of subjectivity: target lesion selection. Disagreement among readers, and between readers and total tumor burden was analyzed, as a function of the total number of lesions, affected organs, and lesion growth. Disagreement aggravates when the number of lesions increases, when lesions are concentrated on few organs, and when lesion growth borders the thresholds of progressive disease and partial response. An intrinsic methodological error is observed in the estimation of total tumor burden (TTB) via RECIST. In a metastatic setting, RECIST displays a non-linear, unpredictable behavior. Our results demonstrate that RECIST can deliver an accurate estimate of total tumor burden in localized disease, but fails in cases of distal metastases and multiple organ involvement. This is worsened by the “selection of the largest lesions”, which introduce a bias that makes it hardly possible to perform an accurate estimate of the total tumor burden. Including more (if not all) lesions in the quantitative analysis of tumor burden is desirable.
Top-down modulation and cortical-AMG/HPC interaction in familiar face processing
Authors: Fan Xiaoxu , Guo Qiang , Zhang Xinxin , Fei lingxia , He Sheng , Weng Xuchu 
Published: April 2022

AbstractHumans can accurately recognize familiar faces in only a few hundred milliseconds, but the underlying neural mechanism remains unclear. Here we recorded intracranial electrophysiological signals from ventral temporal cortex (VTC), superior/middle temporal cortex (STC/MTC), medial parietal cortex (MPC) and amygdala/hippocampus (AMG/HPC) in 20 epilepsy patients while they viewed faces of famous people and strangers as well as common objects. In posterior VTC and MPC, familiarity-sensitive responses emerged significantly later than initial face-selective responses, suggesting that familiarity enhances face representations after they are first being extracted. Moreover, viewing famous faces increased the coupling between cortical areas and AMG/HPC in multiple frequency bands. These findings imply that the top-down modulation in local face-selective response and interactions between cortical face areas and AMG/HPC contribute to the superior recognition of familiar faces.TeaserTop-down modulation and cortical-AMG/HPC interactions contribute to the superior processing of familiar faces.
Exact polynomial-time graph canonisation and isomorphism testing through comparison of ordered vertex eigenprojections
Authors: O’Shea Robert John 
Published: April 2022

AbstractMotivationGraph canonisation and isomorphism testing representation are fundamental computational problems, whose complexity has remained unsolved to date. This study examines graph eigenprojections, demonstrating that linear-ordering transformations induce canonical properties therein to yield polynomial-time canonisation and isomorphism testing in all undirected graphs.ResultsThis study presents an exact method to identify analogous vertices in isomorphic graphs, through comparison of vertices’ eigenprojection matrices, which are shown to be related by a linear permutation. Systematic perturbation strategies are developed to reduce degeneracy whilst conserving isomorphism, through the addition of characteristically weighted self-loops to analogous vertices. Repeated iterations of analogy testing and perturbation deliver canonical vertex labelling and recovery of isomorphic mappings in time in all graphs. Analytical proofs are provided to support claims and experimental performance is demonstrated in biological and synthetic data, with comparison to a commonly used heuristic algorithm.Availability and ImplementationSource code is provided at github.com/robertoshea/graph_isomorphism.Contactrobert.1.oshea@kcl.ac.ukSupplementary Data.Not applicable.
Bidirectional alterations in brain temperature profoundly modulate spatiotemporal neurovascular responses in-vivo: Implications for theragnostics
Authors: Boorman Luke W. , Harris Samuel S. , Shabir Osman , Lee Llywelyn , Eyre Beth , Howarth Clare , Berwick Jason 
Published: April 2022

AbstractNeurovascular coupling (NVC) is a mechanism that, amongst other known and latent critical functions, ensures activated brain regions are adequately supplied with oxygen and glucose. This biological phenomenon underpins non-invasive perfusion-related neuroimaging techniques and recent reports have implicated NVC impairment in several neurodegenerative disorders. Yet, much remains unknown regarding NVC in health and disease, and only recently has there been burgeoning recognition of a close interplay with brain thermodynamics. Accordingly, we developed a novel multi-modal approach to systematically modulate cortical temperature and interrogate the spatiotemporal dynamics of sensory-evoked NVC. We show that changes in cortical temperature profoundly and intricately modulate NVC, with low temperatures associated with diminished oxygen delivery, and high temperatures inducing a distinct vascular oscillation. These observations provide novel insights into the relationship between NVC and brain thermodynamics, with important implications for brain-temperature related therapies, functional biomarkers of elevated brain temperature, and in-vivo methods to study neurovascular coupling.
Cooperative ectodomain interaction among TCRαβ, CD3γε, and CD3δε enhances TCR mechanotransduction
Authors: Yuan Zhou , Cong Peiwen , Natarajan Aswin , Ge Chenghao , Travaglino Stefano , Beesam Saikiran , Grazette Danielle , Krogsgaard Michelle , Zhu Cheng 
Published: April 2022

ABSTRACTThe T-cell receptor (TCR) complex comprises TCRαβ, CD3γε, CD3δε, and CD3ζζ. TCRαβ engagement with peptide-bound major histocompatibility complex (pMHC) triggers CD3 phosphorylation, which is regulated by mechanical force. However, the inner workings of the TCR mechanotransduction machinery remains unclear. TCR ectodomain (ECD) interactions have been inferred from structural and mutagenesis studies. Due to their extreme weakness, however, direct measurements of affinity had failed and of force regulation have never been attempted. Here we measured two-dimensional affinities and force-dependent lifetimes of interactions among TCRαβ, CD3γε, and CD3δε ECDs, showing a cooperative CD3δε–TCRαβ–CD3γε catch bond with longer- lasting lifetime that exceeds the TCR–pMHC bond lifetime. Molecular dynamics stimulations revealed a central interacting region surrounded by TCR ECDs and identified critical interacting residues at their interfaces. Interfering TCR ECD interactions by antibodies impaired TCR–pMHC interaction and T cell function. Mutating residues that mediate TCR ECD cis-interactions with CD3s altered the catch bond of TCR–pMHC trans-interaction, which correlates with changed T cell cytokine production. Thus, TCR mechanotransduction is supported by cooperative TCR ECD interactions, which regulates T cell function. Our results provide a missing link between pMHC ligation and CD3 signaling and may guide future TCR engineering design for immunotherapies.
WNT5A-RHOA axis is a new vulnerability in small-cell lung cancer
Authors: Kim Kee-Beom , Kim Dong-Wook , Kim Youngchul , Tang Jun , Kirk Nicole , Gan Yongyu , Fang Bingliang , Park Jae-Il , Zheng Yi , Park Kwon-Sik 
Published: April 2022

AbstractWNT signaling presents an attractive target for cancer therapy due to its widespread oncogenic role. However, the molecular players involved in WNT signaling and the impact of their perturbation remain unknown for numerous recalcitrant cancers including small-cell lung cancer (SCLC). Here we show that beta-catenin, a master mediator of canonical WNT signaling, is not required for SCLC development in genetically engineered mouse models (GEMMs) and its transcriptional program is largely silenced during tumor development. Instead, inactivation of p130 in SCLC cells induces expression of WNT5A, a ligand for beta-catenin-independent WNT pathways. WNT5A is both sufficient and required for SCLC development and cell proliferation and selectively induces Rhoa transcription and activates RHOA protein to drive SCLC. Rhoa knockout suppresses SCLC development in vivo, and chemical perturbation of RHOA selectively inhibits SCLC cell proliferation. These findings suggest a novel requirement for the WNT5A-RHOA axis in SCLC that is distinct from other noncanonical WNT pathways. This vulnerability of p130-WNT5A-RHOA pathway provides critical insight into the development of novel therapeutic strategies for the recalcitrant cancer, as well as the stratification of patients who may benefit from them. This study also sheds new light on the heterogeneity of WNT signaling and the molecular determinants of its cell-type specificity.
Integrative chromatin domain annotation through graph embedding of Hi-C data
Authors: Shokraneh Neda , Arab Mariam , Libbrecht Maxwell 
Published: April 2022

AbstractMotivationThe organization of the genome into domains plays a central role in gene expression and other cellular activities. Researchers identify genomic domains mainly through two views: 1D functional assays such as ChIP-seq, and chromatin conformation assays such as Hi-C. Fully understanding domains requires integrative modeling that combines these two views. However, the predominant form of integrative modeling uses segmentation and genome annotation (SAGA) along with the rigid assumption that loci in contact are more likely to share the same domain type, which is not necessarily true for epigenomic domain types and genome-wide chromatin interactions.ResultsHere, we present an integrative approach that annotates domains using both 1D functional genomic signals and Hi-C measurements of genome-wide 3D interactions without the use of a pairwise prior. We do so by using a graph embedding to learn structural features corresponding to each genomic region, then inputting learned structural features along with functional genomic signals to a SAGA algorithm. We show that our domain types recapitulate well-known subcompartments with an additional granularity that distinguishes a combination of the spatial and functional states of the genomic regions. In particular, we identified a division of the previously-identified A2 subcompartment such that the divided domain types have significantly varying expression levels.Availabilityhttps://github.com/nedashokraneh/IChDAContactmaxwl@sfu.caSupplementary information
Infected I. scapularis nymphs maintained in prolonged questing under optimal environmental conditions for one year can transmit B. burgdorferi to uninfected hosts
Authors: Samanta Kamalika , Azevedo Jose F. , Nair Nisha , Kundu Suman , Gomes-Solecki Maria 
Published: April 2022

ABSTRACTIn recent decades, Lyme disease has been expanding to previous non-endemic areas. We hypothesized that infected I. scapularis nymphs that retain host-seeking behavior under optimal environmental conditions are fit to fulfil their transmission role in the enzootic cycle of B. burgdorferi. To test this hypothesis, we produced nymphal ticks in the laboratory under controlled temperature (22-25°C), humidity (80-90%) and natural daylight cycle conditions to allow them to retain host-seeking/questing behavior for 1 year. We then analyzed differences in B. burgdorferi infection prevalence in questing and diapause nymphs at 6 weeks post-molting (prime questing) as well as differences in infection prevalence of questing nymphs maintained under prolonged environmental induced questing over 12 months (prolonged questing). Lastly, we analyzed the fitness of nymphal ticks subjected to prolonged questing in transmission of B. burgdorferi to naïve mice over the course of the year. Our study shows that B. burgdorferi infected unfed I. scapularis nymphal ticks maintained under optimal environmental conditions in the laboratory not only survived for a year in a developmental state of prolonged questing (host-seeking), as they retained an infection prevalence sufficient to effectively fulfil transmission of B. burgdorferi to uninfected mice after tick challenge. Our study is important for understanding and possibly modeling Lyme disease expansion into former non-endemic regions due to global warming.IMPORTANCELyme disease is rapidly spreading from its usual endemic areas in the Northeast, Midwest and Midatlantic states into neighboring areas which could be due to changing climate patterns. Our study shows that unfed I. scapularis nymphal ticks kept under optimal environmental conditions in the laboratory survived for a year while exhibiting aggressive host-seeking behavior and they maintained a B. burgdorferi infection prevalence which was sufficient to infect naïve reservoir hosts after tick challenge. Our study raises important questions regarding prolonged survival of B. burgdorferi infected host-seeking nymphal I. scapularis ticks that can potentially increase the risk of Lyme disease incidence, if conditions of temperature and humidity become amenable to the enzootic cycle of B. burgdorferi in regions currently classified as non-endemic.
Roseoflavin, a natural riboflavin analogue, possesses in vitro and in vivo antiplasmodial activity
Authors: Hemasa Ayman , Mack Matthias , Saliba Kevin J. 
Published: April 2022

AbstractThe ability of the human malaria parasite Plasmodium falciparum to access and utilise vital nutrients is critical to its growth and proliferation. Molecules that interfere with these process could potentially serve as antimalarials. We found that two riboflavin analogues, roseoflavin and 8-aminoriboflavin, inhibit malaria parasite proliferation by targeting riboflavin metabolism and/or the utilisation of the riboflavin metabolites flavin mononucleotide and flavin adenine dinucleotide. An additional eight riboflavin analogues were evaluated, but none were found to be more potent than roseoflavin, nor was their activity on target. Focussing on roseoflavin, we tested its antimalarial activity in vivo against Plasmodium vinckei vinckei in mice. We found that roseoflavin decreased the parasitemia by 46-fold following a 4 day suppression test and, on average, increased the survival of mice by 4-5 days. Our data are consistent with riboflavin metabolism and/or the utilisation of riboflavin-derived cofactors being viable drug targets for the development of new antimalarials and that roseoflavin could serve as a potential starting point.
Using a real-world network to model the tradeoff between stay-at-home restriction, vaccination, social distancing and working hours on COVID-19 dynamics
Authors: Nashebi Ramin , Sari Murat , Kotil Seyfullah 
Published: April 2022

AbstractBackgroundHuman behavior, economic activity, vaccination, and social distancing are inseparably entangled in epidemic management. This study aims to investigate the effects of various parameters such as stay-at-home restrictions, work hours, vaccination and social distance on the containment of pandemics such as COVID-19.MethodsTo achieve this, we developed an agent-based model based on a time-dynamic graph with stochastic transmission events. The graph is constructed from a real-world social network. The graph’s edges have been categorized into three categories: home, workplaces, and social environment. The conditions needed to mitigate the spread of wild-type (WT) COVID-19 and the delta variant have been analyzed. Our purposeful agent-based model has carefully executed tens of thousands of individual-based simulations. We propose simple relationships for the trade-offs between effective reproduction number (Re), transmission rate, work hours, vaccination, and stay at home restrictions.ResultsFor the WT, it has been found that a 13% increase in vaccination impacts the reproduction number, like the magnitude of decreasing nine hours of work to four and a single day of stay-at-home order. For the delta, 16% vaccination has the same effect. Also, since we can keep track of household and non-household infections, we observed that the change in household transmission rate does not significantly alter theRe. Household infections are not limited by transmission rate due to the high frequency of connections. For COVID-19’s specifications, theRedepends on the non-household transmissions rate.ConclusionsAll measures are worth considering. Vaccination and transmission reduction are almost interchangeable. Without vaccination or teaching people how to lower their transmission probability significantly, changing work hours or weekend restrictions will only make people more frustrated
Effectiveness of ChAdOx1 nCoV-19 Corona Virus Vaccine (Covishield™) in preventing SARS-CoV2 infection, Chennai, Tamil Nadu, India, 2021
Authors: Murali Sharan , Sakthivel Manikandanesan , P Kamaraj , Venkataswamy Vettrichelvan , Thangaraj Jeromie Wesley Vivian , Shete Anita , John Alby , Arjun Jaganathan , C P Girish Kumar , Yadav Pragya D , Sahay Rima , Majumdar Triparna , Dhudhmal Manisha , Sivalingam Azhagendran , D Sudha Rani , D Augustine , R Vijayaprabha , M Murali Mohan , A Suresh , M Punita , G Elavarasu , C Prabhakaran , S Dhana Priya Vadhani , M Prakash , P Ezhil , Parasuraman Ganeshkumar , M Jagadeesan , Narnaware Manish S , Bedi Gagandeep Singh , Kaur Prabhdeep , Murhekar Manoj V 
Published: April 2022

AbstractBackgroundIndia experienced the second wave of the COVID-19 pandemic in March 2021, driven by the delta variant. Apprehensions around the usefulness of vaccines against delta variant posed a risk to the vaccination program. Therefore, we estimated the effectiveness of two doses of the ChAdOx1 nCoV-19 (Covishield) vaccine against COVID-19 infection among individuals ≥45 years in Chennai, India.MethodsA community-based cohort study was conducted from May to September 2021 in a selected geographic area in Chennai, Tamil Nadu. The estimated sample size was 10,232. We enumerated individuals from all eligible households and periodically updated vaccination and COVID-19 infection data. We computed vaccine effectiveness with its 95% confidence interval for two doses of the Covishield vaccine against any COVID-19 infection.ResultsWe enrolled 69,435 individuals, of which 21,793 were above 45 years. Two dose coverage of Covishield in the 18+ and 45+ age group was 18% and 31%, respectively. The overall incidence of COVID-19 infection was 1099 per 100,000 population. The vaccine effectiveness against COVID-19 disease in the ≥45 age group was 61.3% (95% CI: 43.6 - 73.4) at least two weeks after receiving the second dose of Covishield. Genomic analysis of 74 (28 with two doses, 15 with one dose, and 31 with zero dose) out of the 90 aliquots collected from the 303 COVID-19 positive individuals in the 45+ age group showed delta variants and their sub-lineages.ConclusionWe demonstrated the effectiveness of two doses of the ChAdOx1 vaccine against the delta variant in the general population of Chennai. We recommend similar future studies considering emerging variants and newer vaccines. Two-dose vaccine coverage could be ensured to protect against COVID-19 infection.
A needle in a haystack: metagenomic DNA sequencing to quantify Mycobacterium tuberculosis DNA and diagnose tuberculosis
Authors: Chang Adrienne , Mzava Omary , Kounatse Liz-Audrey Djomnang , Lenz Joan , Burnham Philip , Kaplinsky Peter , Andama Alfred , Connelly John , Bachman Christine M. , Cattamanchi Adithya , Steadman Amy , De Vlaminck Iwijn 
Published: April 2022

ABSTRACTBackgroundTuberculosis (TB) remains a significant cause of mortality worldwide. Metagenomic next-generation sequencing has the potential to reveal biomarkers of active disease, identify coinfection, and improve detection for sputum-scarce or culture-negative cases.MethodsWe conducted a large-scale comparative study of 427 plasma, urine, and oral swab samples from 334 individuals from TB endemic and non-endemic regions to evaluate the utility of a shotgun metagenomic DNA sequencing assay for tuberculosis diagnosis.FindingsWe found that the choice of a negative, non-TB control cohort had a strong impact on the measured performance of the diagnostic test: the use of a control patient cohort from a nonendemic region led to a test with nearly 100% specificity and sensitivity, whereas controls from TB endemic regions exhibited a high background of nontuberculous mycobacterial DNA, limiting the diagnostic performance of the test. Using mathematical modeling and quantitative comparisons to matched qPCR data, we found that the burden of Mycobacterium tuberculosis DNA constitutes a very small fraction (0.04 or less) of the total abundance of DNA originating from mycobacteria in samples from TB endemic regions.InterpretationOur findings suggest that the utility of a metagenomic sequencing assay for tuberculosis diagnostics is limited by the low burden of M. tuberculosis in extrapulmonary sites and an overwhelming biological background of nontuberculous mycobacterial DNA.FundingThis work was supported by the National Institutes of Health, the Rainin Foundation, the National Science Foundation, and the Bill and Melinda Gates Foundation.
Effectiveness of COVID-19 mRNA vaccine booster dose relative to primary series during a period of Omicron circulation
Authors: Petrie Joshua G. , King Jennifer P. , McClure David L. , Rolfes Melissa A. , Meece Jennifer K. , Belongia Edward A. , McLean Huong Q. 
Published: April 2022

ABSTRACTDuring a period of Omicron variant circulation, we estimated relative VE of COVID-19 mRNA booster vaccination versus primary two-dose series in an ongoing community cohort. Relative VE was 66% (95% CI: 46%, 79%) favoring the booster dose compared to primary series vaccination. Our results support current booster recommendations.