bluuebunny/crossref_metadata_2025_split huggingface dataset:
Literature-Based Discovery beyond the ABC paradigm: a contrastive approach
Authors: Moreau Erwan , Hardiman Orla , Heverin Mark , O’Sullivan Declan 
Published: September 2021

AbstractLiterature-Based Discovery (LBD) aims to help researchers to identify relations between concepts which are worthy of further investigation by text-mining the biomedical literature. The vast majority of the LBD research follows the ABC model: a relation (A,C) is a candidate for discovery if there is some intermediate concept B which is related to both A and C. The ABC model has been successful in applications where the search space is strongly constrained, but there is limited evidence about its usefulness when applied in a broader context.Through a case study of 8 recent discoveries related to neurodegenerative diseases (NDs), we show the limitations of the ABC model in an open-ended context. The study emphasizes the impact of the choice of source data and extraction method on the resulting knowledge base: different “views” of the biomedical literature offer different levels of accuracy and coverage. We propose a novel contrastive approach which leverages these differences between “views” in order to target relations between concepts of interest. We explore various parameters and demonstrate the relevance of our approach through quantitative evaluation on the 8 target discoveries.The source data used in this article are publicly available. The different parts of the software used to process the data are published under open-source license and provided with detailed instructions. The main code for this paper is available at https://github.com/erwanm/lbd-contrast (required dependencies are detailed in the documentation). A prototype of the system is also provided as an online exploration tool at brainmend.adaptcentre.ie.
Characterizing pupil dynamics coupling to brain state fluctuation based on lateral hypothalamic activity
Authors: Takahashi Kengo , Sobczak Filip , Pais-Roldán Patricia , Yu Xin 
Published: September 2021

AbstractPupil dynamics presents varied correlation features with brain activity under different vigilant levels. The modulation of brain state changes can arise from the lateral hypothalamus (LH), where diverse neuronal cell types contribute to arousal regulation in opposite directions via the anterior cingulate cortex (ACC). However, the relationship of the LH and pupil dynamics has seldom been investigated. Here, we performed local field potential (LFP) recordings at the LH and ACC, and the whole brain fMRI with simultaneous fiber photometry Ca2+ recording in the ACC, to evaluate their correlation with brain state-dependent pupil dynamics. Both LFP and functional MRI (fMRI) data showed opposite correlation features to pupil dynamics, demonstrating an LH activity-dependent manner. Our results demonstrate that the correlation of pupil dynamics with ACC LFP and whole-brain fMRI signals depends on LH activity, indicating a role of the latter in brain state regulation.
Enculturating a Community of Action (CoA): A qualitative study of health professions educators’ perspectives on teaching with Wikipedia
Authors: Martin Paolo C. , Maggio Lauren A. , Murray Heather , Willinsky John M. 
Published: September 2021

AbstractPurposeThere is a growing desire for health professions educators to engage learners in more meaningful instruction. Many have tapped Wikipedia to offer an applied approach to engage learners, particularly as it relates to evidence-based medicine (EBM). However, little is known about the benefits and challenges of using Wikipedia as a pedagogical tool from the collective experience of educators who have sought to improve their instructional practice with it. This study aims to uncover and synthesize the perspectives of health professions education (HPE) instructors who have incorporated Wikipedia in their HPE courses.MethodsApplying a constructivist approach, the authors conducted semi-structured interviews with 17 participating HPE instructors who had substantively integrated Wikipedia into their curriculum. Participants were interviewed about their experiences of integrating Wikipedia editing into their courses. Thematic analysis was conducted on resulting transcripts.ResultsAuthors observed two broad themes among participants’ expressed benefits of teaching with Wikipedia: 1) provides a meaningful instructional alternative that also benefits society and develops learners’ information literacy and EBM skills, and 2) supports learners’ careers and professional identity formation. Identified challenges included: 1) high effort and time, 2) issues with sourcing references, and 3) challenging interactions with skeptics, editors, and students.DiscussionFindings build on known benefits, such as providing a real-world collaborative project that contextualizes students’ learning experiences. They also echo known challenges, such as the resource-intensive nature of teaching with Wikipedia. At the same time, findings extend the current literature by revealing a potential opportunity to approach crowd-sourced information tools, like Wikipedia, as a vehicle to engage and enculturate HPE students within a situated learning context. These findings present implications for HPE programs considering implementing Wikipedia and faculty development needed to help instructors harness crowd-sourced information tools’ pedagogical opportunities as well as anticipate their challenges.
Tyr is Responsible for the Cctq1a QTL and Links Developmental Environment to Central Corneal Thickness Determination
Authors: Meyer Kacie J. , Larson Demelza R. , Whitmore S. Scott , van der Heide Carly J. , Hedberg-Buenz Adam , Dutca Laura M. , Koli Swanand , Pomernackas Nicholas , Mercer Hannah E. , Mansaray Maurisa N. , Paradee William J. , Wang Kai , Nair K. Saidas , Scheetz Todd E. , Anderson Michael G. 
Published: September 2021

AbstractCentral corneal thickness is a quantitative trait with important associations to human health. In a phenotype-driven approach studying corneal thickness of congenic derivatives of C57BLKS/J and SJL/J mice, the critical region for a quantitative trait locus influencing corneal thickness, Cctq1a, was delimited to a 10-gene interval. Exome sequencing, RNAseq, and studying independent mutations eliminated multiple candidate genes and confirmed one. Though the causative gene, Tyr, has no obvious direct function in the transparent cornea, studies with multiple alleles on matched genetic backgrounds, both in isolation and genetic complementation crosses, confirmed allelism of Tyr-Cctq1a; albino mice lacking Tyr function had thin corneas. Albino mice also had increased axial length. Because albinism exposes eyes to increased light, the effect of dark-rearing was tested and found to rescue central corneal thickness. In sum, the results point to an epiphenomenon; developmental light exposure interacts with genotype as an important determinate of adult corneal thickness.
Peptide fusion improves prime editing efficiency
Authors: Velimirovic Minja , Zanetti Larissa C. , Shen Max W. , Fife James D. , Lin Lin , Cha Minsun , Akinci Ersin , Barnum Danielle , Yu Tian , Sherwood Richard I. 
Published: September 2021

AbstractPrime editing enables search-and-replace genome editing but is limited by low editing efficiency. We present a high-throughput approach, PepSEq, to measure how fusion of 12,000 85-amino acid peptides derived from human DNA repair-related proteins influences prime editing efficiency. We show that peptide fusion can enhance prime editing, prime-enhancing peptides combine productively, and a top dual peptide-prime editor increases prime editing significantly in multiple cell lines across dozens of target sites.
Brain Injury Localization in Electromagnetic Imaging using Symmetric Crossing Lines Method
Authors: Zhu Guohun , Bialkowski Alina , Crozier Stuart , Guo Lei , Nguyen Phong , Stancombe Anthony , Abbosh Amin 
Published: September 2021

AbstractTo avoid death or disability, patients with brain injury should undertake a diagnosis at the earliest time and accept frequent monitoring after starting any medical intervention. This paper presents a novel approach to localize brain injury using the intersection of pairs of signals from symmetrical antennas based on the hypothesis that healthy brains are approximately symmetric that the bleeding targets will lead to significantly different amplitude and phase changes if one of pair of transmit signals cross targets. The scattered signals (S-parameters) are acquired using 100 realistic brain models and 150 experimental data measurements. Firstly, three pair of horizontal antennas are used to detect target crossing which line and in which hemisphere in low frequency bands and estimate the size using high frequency bands. Then, an intersection of two pairs of antennas are identified the position of the target. Finally, a heat map is used to visualise the stroke brain. The results indicate that crossing pairs of antenna signals from the hemisphere with a blood mass exhibit significantly different signal amplitude in the graph features compared to those without the target (p<0.003). The experiments show that our novel localization algorithm can achieve an accuracy of 0.85±0.08 Dice similarity coefficient based on 150 experimental measurements using an elliptical container, which is suitable for brain injury localization.
Nonparametric Interrogation of Transcriptional Regulation in Single-Cell RNA and Chromatin Accessibility Multiomic Data
Authors: Jiang Yuchao , Harigaya Yuriko , Zhang Zhaojun , Zhang Hongpan , Zang Chongzhi , Zhang Nancy R 
Published: September 2021

AbstractEpigenetic control of gene expression is highly cell-type- and context-specific. Yet, despite its complexity, gene regulatory logic can be broken down into modular components consisting of a transcription factor (TF) activating or repressing the expression of a target gene through its binding to a cis-regulatory region. Recent advances in joint profiling of transcription and chromatin accessibility with single-cell resolution offer unprecedented opportunities to interrogate such regulatory logic. Here, we propose a nonparametric approach, TRIPOD, to detect and characterize three-way relationships between a TF, its target gene, and the accessibility of the TF’s binding site, using single-cell RNA and ATAC multiomic data. We apply TRIPOD to interrogate cell-type-specific regulatory logic in peripheral blood mononuclear cells and contrast our results to detections from enhancer databases, cis-eQTL studies, ChIP-seq experiments, and TF knockdown/knockout studies. We then apply TRIPOD to mouse embryonic brain data during neurogenesis and gliogenesis and identified known and novel putative regulatory relationships, validated by ChIP-seq and PLAC-seq. Finally, we demonstrate TRIPOD on SHARE-seq data of differentiating mouse hair follicle cells and identify lineage-specific regulation supported by histone marks for gene activation and super-enhancer annotations.
The necrotrophic effector ToxA fromParastagonospora nodoruminteracts with wheat NHL proteins to facilitateTsn1-mediated necrosis
Authors: Dagvadorj Bayantes , Outram Megan A. , Williams Simon J. , Solomon Peter S. 
Published: September 2021

SummaryThe plant pathogenParastagonospora nodorumsecretes necrotrophic effectors to promote disease. These effectors induce cell death on wheat cultivars carrying dominant susceptibility genes in an inverse gene-for-gene manner. However, the molecular mechanisms underpinning these interactions and resulting cell death remain unclear. Here, we used a yeast-two-hybrid library approach to identify wheat proteins that interact with the necrotrophic effector ToxA. Using this strategy, we identified an interaction between ToxA and a wheat transmembrane NDR/HIN1-like protein (TaNHL10) and confirmed the interaction usingin-plantaco-immunoprecipitation and confocal microscopy co-localization analysis. We showed that the C-terminus of TaNHL10 is extracellular whilst the N-terminus was localized in the cytoplasm. Further analyses using yeast-two-hybrid and confocal microscopy co-localization showed that ToxA interacts with the C-terminal LEA2 extracellular domain of TaNHL10. Random mutagenesis was then used to identify a ToxA mutant, ToxAN109D, which was unable to interact with TaNHL10 in yeast-two-hybrid assays. Subsequent heterologous expression and purification of ToxAN109DinNicotiania benthamianarevealed that the mutated protein was unable to induce necrosis onTsn1-dominant wheat cultivars confirming that the interaction of ToxA with TaNHL10 is required to induce cell death. Collectively, these data advance our understanding on how ToxA induces cell death during infection and further highlights the importance of host cell surface interactions in necrotrophic pathosystems.
Tracing boundaries in Eastern Antarctica: Multi-scale drivers of soil microbial communities across the hyperarid Vestfold Hills
Authors: Zhang Eden , Czechowski Paul , Terauds Aleks , Wong Sin Yin , Chelliah Devan S. , Raven Mark , Tanaka Mark M. , Ferrari Belinda C. 
Published: September 2021

AbstractMicroorganisms are key to sustaining core ecosystem processes across terrestrial Antarctica but they are rarely considered in conservation frameworks. Whilst greater advocacy has been made towards the inclusion of microbial data in this context, there is still a need for better tools to quantify multispecies responses to environmental change. Here, we extend the scope of Gradient Forest modelling beyond macroorganisms and small datasets to the comprehensive polar soil microbiome encompassing >17, 000 sequence variants for bacteria, micro-eukarya and archaea throughout the hyperarid Vestfold Hills of Eastern Antarctica. Quantification of microbial diversity against 79 physiochemical variables revealed that whilst rank-order importance differed, predictors were broadly consistent between domains, with greatest sharing occurring between bacteria and micro-eukarya. Moisture was identified as the most robust predictor for shaping the regional soil microbiome, with highest compositional turnover or “splits” occurring within the 10 – 12 % moisture content range. Often the most responsive taxa were rarer lineages of bacteria and micro-eukarya with phototrophic and nutrient-cycling capacities such as Cyanobacteria (up to 61.81 % predictive capacity), Chlorophyta (62.17 %) and Ochrophyta (57.81 %). These taxa groups are thus at greater risk of biodiversity loss or gain to projected climate trajectories, which will inevitably disturb current ecosystem dynamics. Better understanding of these threshold tipping points will positively aid conservation efforts across Eastern Antarctica. Furthermore, the successful implementation of an improved Gradient Forest model also presents an exciting opportunity to broaden its use on microbial systems globally.
A new class of cell wall-recycling L,D-carboxypeptidase determines β-lactam susceptibility and morphogenesis in Acinetobacter baumannii
Authors: Dai Yunfei , Pinedo Victor , Tang Amy Y. , Cava Felipe , Geisinger Edward 
Published: September 2021

AbstractThe hospital-acquired pathogen Acinetobacter baumannii possesses a complex cell envelope that is key to its multidrug resistance and virulence. The bacterium, however, lacks many canonical enzymes that build the envelope in model organisms. Instead, A. baumannii contains a number of poorly annotated proteins that may allow alternative mechanisms of envelope biogenesis. We demonstrated previously that one of these unusual proteins, ElsL, is required for cell elongation and for withstanding antibiotics that attack the septal cell wall. Curiously, ElsL is composed of a leaderless YkuD-family domain usually found in secreted, cell-wall-modifying L,D-transpeptidases (LDTs). Here, we show that, rather than being an LDT, ElsL is actually a new class of cytoplasmic L,D-carboxypeptidase (LDC) that provides a critical step in cell-wall recycling previously thought to be missing from A. baumannii. Absence of ElsL impairs cell wall integrity, elongation, and intrinsic resistance due to buildup of murein tetrapeptide precursors, toxicity of which is bypassed by preventing muropeptide recycling. Multiple pathways in the cell become sites of vulnerability when ElsL is inactivated, including L,D-crosslink formation, cell division, and outer membrane lipid homoeostasis, reflecting its pleiotropic influence on cell envelope physiology. We thus reveal a novel class of cell-wall-recycling LDC critical to growth and homeostasis of A. baumannii and likely many other bacteria.ImportanceTo grow efficiently, resist antibiotics, and control the immune response, bacteria recycle parts of their cell wall. A key step in the typical recycling pathway is the reuse of cell wall peptides by an enzyme known as an LDC. Acinetobacter baumannii, an “urgent-threat” pathogen causing drug-resistant sepsis in hospitals, was previously thought to lack this enzymatic activity due to absence of a known LDC homolog. Here, we show that A. baumannii possesses this activity in the form of an enzyme class not previously associated with cell wall recycling. Absence of this protein intoxicates and weakens the A. baumannii cell envelope in multiple ways due to the accumulation of dead-end intermediates. Several other organisms of importance to health and disease encode homologs of the A. baumannii enzyme. This work thus reveals an unappreciated mechanism of cell wall recycling, manipulation of which may contribute to enhanced treatments targeting the bacterial envelope.
The Influence of Model Violation on Phylogenetic Inference: A Simulation Study
Authors: Naser-Khdour Suha , Minh Bui Quang , Lanfear Robert 
Published: September 2021

AbstractPhylogenetic inference typically assumes that the data has evolved under Stationary, Reversible and Homogeneous (SRH) conditions. Many empirical and simulation studies have shown that assuming SRH conditions can lead to significant errors in phylogenetic inference when the data violates these assumptions. Yet, many simulation studies focused on extreme non-SRH conditions that represent worst-case scenarios and not the average empirical dataset. In this study, we simulate datasets under various degrees of non-SRH conditions using empirically derived parameters to mimic real data and examine the effects of incorrectly assuming SRH conditions on inferring phylogenies. Our results show that maximum likelihood inference is generally quite robust to a wide range of SRH model violations but is inaccurate under extreme convergent evolution.
Validation of the Panbio™ COVID-19 Antigen Rapid Test (Abbott) to screen for SARS-CoV-2 infection in Sint Maarten: a diagnostic accuracy study
Authors: King Colin , Weever Eva Lista-de , Henry Maria , Steingrover Radjin , Fleming Chérina , Panneflek Richard , van Kampen Sanne 
Published: September 2021

AbstractObjectivesControl of the pandemic has required countries to look for other forms of tests besides the gold standard real-time polymerase chain reaction (RT-PCR). Rapid antigen tests (RAT), though less sensitive than RT-PCR, offer the possibility of rapid, inexpensive and early detection of the most infectious COVID-19 cases. Only very few studies have assessed the performance of the Abbott Panbio COVID-19 RAT among asymptomatic people or in Latin America. This study set out to validate this test among people attending the public test street in Sint Maarten, Dutch Caribbean.MethodsPeople of all ages were recruited from the public COVID-19 test street regardless of COVID-19 symptoms. They received a nasopharyngeal swab for the Abbott Panbio COVID-19 RAT and the RT-PCR Qtower. Diagnostic accuracy of the RAT was compared to the RT-PCR among the overall study population and for subgroups with/without symptoms, with/without close contact and different Ct values.ResultsUsing a RT-PCR Ct cut-off value of <33, 119 out of 1,411 people (8.4%) tested positive for SARS-CoV-2. Most were asymptomatic (59%). The overall sensitivity and specificity of the RAT was 84% (95% CI 76.2-90.1) and 99.9% (95% CI 99.6-100) respectively. The sensitivity reduced to 67.6% (95% CI: 49.5%, 82.6%) among people without symptoms, regardless of whether they were in close contact with a known COVID-19 case. Sensitivity reduced considerably with a Ct cut-off value of <35.ConclusionsThe Abbott Panbio RAT is a valid and cheaper alternative to RT-PCR when used on symptomatic individuals among the general population. However, among asymptomatic people it should not be used as a stand-alone test and negative results should be confirmed with RT-PCR.
Outcomes of gastrointestinal fistulas: Results from a multi-continent, multi-national, multi-center cohort
Authors: Márquez Humberto Arenas , Turcios Correia María Isabel , García Juan Francisco , Prado Roberto Anaya , Vergara Arturo , Garnica Jorge Luis , Cacho Alejandra , Guerra Daniel , Navarrete Miguel Mendoza , Porbén Sergio Santana 
Published: September 2021

SUMMARYRationaleGastrointestinal fistulas (GIF) represent a severe and potentially lethal complication of the hospital surgical activity. However, evidences are lacking about prognosis and outcomes of GIF in Latin America (LATAM) hospitals.ObjectiveTo describe the prognosis and outcomes GIF in LATAM hospitals.Study designProspective, longitudinal, cohort-type study. The cohort fostered three cross-sectional examinations: First examination: On admission of the patient in the study; Second examination: Thirty days later; and Third (and last) examination: Sixty days after patient’s admission.Study serieOne hundred seventy-seven patients (Males: 58.2 %; Average age: 51.0 ± 16.7 years; Ages ≥ 60 years: 36.2 %) diagnosed with, and assisted for, GIF (ECF: Enterocutaneous: 64.9 % vs. EAF: Enteroathmospheric: 35.1 %) in 76 LATAM hospitals (13 countries) and Europe (4).MethodsCondition (Alive vs. Deceased) and hospital status (Hospitalized vs. Discharged) of the patient, and the GFI patency (Closed vs. Non closed) were recorded in each of the cohort’s examination. Indicators of GFI prognosis thus constructed were correlated demographical, sanitary, surgical and nutritional characteristics of the patientsResultsOn conclusion of the study indicators of GIF prognosis behaved as follows: Mortality:14.7 %; Prolonged hospitalization: 47.4 %; Spontaneous closure of GIF: 36.2 %. Type of GIF influenced upon patient’s survival: ECF: 87.0 % vs. EAF: 82.3 % (Δ = +4.7 %; χ2 = 6.787; p < 0.05). In each examination of the cohort, the number of surviving subjects was always greater among those with ECF: After 30 days: ECF: 92.1 % vs. EAF: 83.9 % (Δ = +8.2 %); After 60 days: ECF: 98.1 % vs. EAF: 90.4 % (Δ = +7.7 %; χ2 = 13.764; p < 0.05). On the other hand, hospital stay was prolonged in the subjects of elective surgery (Elective surgery: 61.4 % vs. Emergency surgery: 38.3 % (Δ = +23.1 %; χ2 = 9.064; p < 0.05) and those with a reduced calf circumference (χ2 = 12.655; p < 0.05). Location of the fistula also influenced upon prolongation of hospital stay (χ2 = 7.817; p < 0.05).ConclusionsType of GIF influences upon survival of the patient. On the hand, hospital stay was dependent upon type of surgery previously performed, location of the fistula, and calf circumference value on admission in the study serie.