bluuebunny/crossref_metadata_2025_split huggingface dataset:
Responsive Neurostimulation for People With Drug-Resistant Epilepsy and Autism Spectrum Disorder
Authors: Fields Madeline C. , Marsh Christina , Eka Onome , Johnson Emily A. , Marcuse Lara V. , Kwon Churl-Su , Young James J. , LaVega-Talbott Maite , Kurukumbi Mohankumar , Von Allmen Gretchen , Zempel John , Friedman Daniel , Jette Nathalie , Singh Anuradha , Yoo Ji Yeoun , Blank Leah , Panov Fedor , Ghatan Saadi 
Published: May 2022

Purpose:
Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System.

Methods:
This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and behavioral outcomes were reported. Descriptive statistics were used for analysis.

Results:
Nineteen patients with ASD and DRE had the RNS System placed at 5 centers. Patients were between the ages of 11 and 29 (median 20) years. Fourteen patients were male, whereas five were female. The device was implanted from 1 to 5 years. Sixty-three percent of all patients experienced a >50% seizure reduction, with 21% of those patients being classified as super responders (seizure reduction >90%). For the super responders, two of the four patients had the device implanted for >2 years. The response rate was 70% for those in whom the device was implanted for >2 years. Improvements in behaviors as measured by the Clinical Global Impression Scale-Improvement scale were noted in 79%. No complications from the surgery were reported.

Conclusions:
Based on the authors' experience in this small cohort of patients, the RNS System seems to be a promising surgical option in people with ASD–DRE.
Validation of a Model for Targeted EEG Monitoring Duration in Critically Ill Children
Authors: Fung France W. , Fan Jiaxin , Parikh Darshana S. , Vala Lisa , Donnelly Maureen , Jacobwitz Marin , Topjian Alexis A. , Xiao Rui , Abend Nicholas S. 
Published: May 2022

Purpose:
Continuous EEG monitoring (CEEG) to identify electrographic seizures (ES) in critically ill children is resource intense. Targeted strategies could enhance implementation feasibility. We aimed to validate previously published findings regarding the optimal CEEG duration to identify ES in critically ill children.

Methods:
This was a prospective observational study of 1,399 consecutive critically ill children with encephalopathy. We validated the findings of a multistate survival model generated in a published cohort (N = 719) in a new validation cohort (N = 680). The model aimed to determine the CEEG duration at which there was <15%, <10%, <5%, or <2% risk of experiencing ES if CEEG were continued longer. The model included baseline clinical risk factors and emergent EEG risk factors.

Results:
A model aiming to determine the CEEG duration at which a patient had <10% risk of ES if CEEG were continued longer showed similar performance in the generation and validation cohorts. Patients without emergent EEG risk factors would undergo 7 hours of CEEG in both cohorts, whereas patients with emergent EEG risk factors would undergo 44 and 36 hours of CEEG in the generation and validation cohorts, respectively. The <10% risk of ES model would yield a 28% or 64% reduction in CEEG hours compared with guidelines recommending CEEG for 24 or 48 hours, respectively.

Conclusions:
This model enables implementation of a data-driven strategy that targets CEEG duration based on readily available clinical and EEG variables. This approach could identify most critically ill children experiencing ES while optimizing CEEG use.
A Fast, Provably Accurate Approximation Algorithm for Sparse Principal Component Analysis Reveals Human Genetic Variation Across the World
Authors: Chowdhury Agniva , Bose Aritra , Zhou Samson , Woodruff David P. , Drineas Petros 
Published: May 2022

AbstractPrincipal component analysis (PCA) is a widely used dimensionality reduction technique in machine learning and multivariate statistics. To improve the interpretability of PCA, various approaches to obtain sparse principal direction loadings have been proposed, which are termed Sparse Principal Component Analysis (SPCA). In this paper, we present ThreSPCA, a provably accurate algorithm based on thresholding the Singular Value Decomposition for the SPCA problem, without imposing any restrictive assumptions on the input covariance matrix. Our thresholding algorithm is conceptually simple; much faster than current state-of-the-art; and performs well in practice. When applied to genotype data from the 1000 Genomes Project, ThreSPCA is faster than previous benchmarks, at least as accurate, and leads to a set of interpretable biomarkers, revealing genetic diversity across the world.
Change in stroke presentations during COVID-19 pandemic in South-Western Sydney
Authors: Thomas James , Manser David , Thomas Peter , Moore Nicholas , Middleton Paul , Cordato Dennis , Cappelen-Smith Cecilia , McDougall Alan 
Published: May 2022

AbstractBackgroundAustralia managed relatively well during the global COVID-19 pandemic owing to our swift mandated public health response. During the NSW lockdown restrictions, we noted a decrease in acute stroke presentations at our institution, similar to what was subsequently reported worldwide.AimsWe aimed to test our hypothesis that (i) the true numbers of ischaemic strokes did not change, however patients were presenting later and (ii) the proportion of TIAs decreased.MethodsWe conducted a retrospective audit of all stroke and TIA presentations in 2020 and compared these with data from 2019. We collected information about stroke subtype, severity, time from stroke/TIA onset to presentation and acute reperfusion therapies.ResultsBetween January-February and April-March 2020, there was a 15% drop in acute stroke presentations (128 vs. 109). In the same period “stroke mimic” presentations dropped by 22%. The proportion of patients attending the emergency department within 4.5hrs was only 36% compared with 48% over the similar period in 2019.ConclusionsAlthough the raw numbers of ischemic stroke presentations remained stable during NSW Covid lockdown, the proportion of patients presenting within time window for acute reperfusion therapies fell. The number of TIAs similarly fell suggesting COVID-19 discouraged patients from presenting to hospital which placed them at higher risk of disabling stroke. The opportunity cost of lockdown restrictions on stroke outcome should be considered in future policy directives.
BREEDIT: A novel multiplex genome editing strategy to improve complex quantitative traits in maize (Zea mays L.)
Authors: Lorenzo Christian Damian , Debray Kevin , Herwegh Denia , Develtere Ward , Impens Lennert , Schaumont Dries , Vandeputte Wout , Aesaert Stijn , Coussens Griet , de Boe Yara , Demuynck Kirin , Van Hautegem Tom , Pauwels Laurens , Jacobs Thomas B. , Ruttink Tom , Nelissen Hilde , Inzé Dirk 
Published: May 2022

AbstractEnsuring food security for an ever-growing global population while adapting to climate change is the main challenge for agriculture in the 21st century. Though new technologies are being applied to tackle the problem, we are approaching a plateau in crop improvement using conventional breeding. Recent advances in gene engineering via the CRISPR/Cas technology pave the way to accelerate plant breeding and meet this increasing demand. Here, we present a gene discovery pipeline named ‘BREEDIT’ that combines multiplex genome editing of whole gene families with crossing schemes to improve complex traits such as yield and drought resistance. We induced gene knockouts in 48 growth-related genes using CRISPR/Cas9 and generated a collection of over 1000 gene-edited maize plants. Edited populations displayed, on average, significant increases of 5 to 10% for leaf length and up to 20% for leaf width compared with controls. For each gene family, edits in subsets of genes could be associated with increased traits, allowing us to reduce the gene space needed to focus on for trait improvement. We propose BREEDIT as a gene discovery pipeline which can be rapidly applied to generate a diverse collection of mutants to identify subsets of promising candidates that could be later incorporated in breeding programs.
Development and evaluation of low-volume tests to detect and characterise antibodies to SARS-CoV-2
Authors: Halliday Alice , Long Anna E , Baum Holly E , Thomas Amy C , Shelley Kathryn L , Oliver Elizabeth , Gupta Kapil , Francis Ore , Kavanagh Williamson Maia , di Bartolo Natalie , Randell Matthew J , Ben-Khoud Yassin , Kelland Ilana , Mortimer Georgina , Ball Olivia , Plumptre Charlie , Chandler Kyla , Obst Ulrike , Secchi Massimiliano , Piemonti Lorenzo , Lampasona Vito , Smith Joyce , Gregorova Michaela , Knezevic Lea , Metz Jane , Barr Rachael , Morales-Aza Begonia , Oliver Jennifer , Collingwood Lucy , Hitchings Benjamin , Ring Susan , Wooldridge Linda , Rivino Laura , Timpson Nicholas , McKernon Jorgen , Muir Peter , Hamilton Fergus , Arnold David , Woolfson Derek N , Goenka Anu , Davidson Andrew D. , Toye Ashley M , Berger Imre , Bailey Mick , Gillespie Kathleen M , Williams Alistair JK , Finn Adam 
Published: May 2022

AbstractLow-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings where active testing for virus is limited and remote sampling is optimal. We developed 12 ELISAs detecting total or antibody isotypes to SARS-CoV-2 nucleocapsid, spike protein or its receptor binding domain (RBD), 3 anti-RBD isotype specific luciferase immunoprecipitation system (LIPS) assays and a novel Spike-RBD bridging LIPS total-antibody assay. We utilised pre-pandemic (n=984) and confirmed/suspected recent COVID-19 sera taken pre-vaccination rollout in 2020 (n=269). Assays measuring total antibody discriminated best between pre-pandemic and COVID-19 sera and were selected for diagnostic evaluation. In the blind evaluation, two of these assays (Spike Pan ELISA and Spike-RBD Bridging LIPS assay) demonstrated >97% specificity and >92% sensitivity for samples from COVID- 19 patients taken >21 days post symptom onset or PCR test. These assays offered better sensitivity for the detection of COVID-19 cases than a commercial assay which requires 100-fold larger serum volumes. This study demonstrates that low-volume in- house antibody assays can provide good diagnostic performance, and highlights the importance of using well-characterised samples and controls for all stages of assay development and evaluation. These cost-effective assays may be particularly useful for seroprevalence studies in low and middle-income countries.
SARS-CoV-2 neutralizing antibodies in Chile after a vaccination campaign with five different schemes
Authors: Aguilera Ximena , Hormazabal Juan , Vial Cecilia , Cortes Lina Jimena , Gonzalez Claudia , Rubilar Paola , Apablaza Mauricio , Ramirez-Santana Muriel , Icaza Gloria , Nuñez-Franz Loreto , Castillo-Laborde Carla , Ramirez-Riffo Carolina , Perez Claudia , Quezada-Gate Ruben , Said Macarena , Vial Pablo 
Published: May 2022

AbstractUsing levels of neutralizing antibodies (nAbs), we evaluate the successful Chilean SARS-CoV-2 vaccine campaign, which combines technologies and heterologous boosters. In 120 randomly selected seropositive individuals from a population-based study, we conclude that the booster dose, regardless of vaccine technology or natural infection, and mRNA vaccines significantly improve nAbs response.
Development of Molecular Inversion Probes for Soybean Progeny Genomic Selection Genotyping
Authors: Wang Haichuan , Campbell Benjamin , Happ Mary , McConaughy Samantha , Lorenz Aaron , Amundsen Keenan , Song Qijian , Pantalone Vincent , Hyten David 
Published: May 2022

AbstractIncreasing rate of genetic gain for key agronomic traits through genomic selection requires the development of new molecular methods to run genome-wide single nucleotide polymorphisms (SNPs). The main limitation of current methods is the cost is too high to screen breeding populations. Molecular inversion probes (MIPs) is a targeted genotyping-by-sequencing method that could be used for soybeans that is both cost effective, high-throughput, and provides high data quality to screen breeder’s germplasm for genomic selection. A 1K MIP SNP set was developed for soybean with uniformly distributed markers across the genome. The SNPs were selected to maximize the number of informative markers in germplasm being tested in soybean breeding programs located in the North Central and Mid-South regions of the United States. The 1K SNP MIP set was tested on diverse germplasm and a recombinant inbred line population. Targeted sequencing with MIPs obtained an 85% enrichment for the targeted SNPs. MIP’s genotyping accuracy was 93% overall while homozoygous call accuracy was 98% with less than 10% missing data. The accuracy of MIPs combined with its low per sample cost makes it a powerful tool to enable genomic selection within soybean breeding programs.
Testing the link between isoaspartate and Alzheimer’s disease etiology
Authors: Wang Jijing , Guo Cong , Meng Zhaowei , Zwan Marissa D. , Chen Xin , Seelow Sven , Lundström Susanna L. , Rodin Sergey , Teunissen Charlotte E. , Zubarev Roman A. 
Published: May 2022

ABSTRACTIsoaspartate (isoAsp) is a damaging amino acid residue formed in proteins as a result of spontaneous deamidation. IsoAsp disrupts the secondary and higher order structures of proteins, damaging their functions and making them prone to aggregation. An association has been suggested between isoAsp and Alzheimer’s Disease (AD). Here we strengthened the link between isoAsp and AD by novel approaches to isoAsp analysis in blood human serum albumin (HSA), the most abundant blood protein, a major carrier of amyloid beta (Aß) peptide and phosphorylated tau (pTau) protein in blood and a key participant in their clearance pathway. We discovered a reduced amount of anti-isoAsp antibodies (P < .0001), an elevated isoAsp level in HSA (P < .001), more HSA aggregates (P < .0001) and increased levels of free Aß (P < .01) in AD blood compared to healthy controls. We also found that deamidation significantly reduces HSA capacity to bind with Aß and pTau (P < .05). These findings support the presence in AD of a bottleneck in clearance of Aß and pTau leading to their increased concentrations in brain and facilitating their aggregations there.RESEARCH IN CONTEXTSystematic review:We reviewed the evidence that associates isoaspartate (isoAsp) residue in blood proteins with the etiology of Alzheimer’s disease (AD). However, the link between isoAsp in blood and aggregation of amyloid beta (Aß) peptide and phosphorylated tau (pTau) protein in brain remained unclear.Interpretation:For the first time we demonstrate that isoAsp-containing human serum albumin (HSA) forms aggregates with reduced binding capacity toward Aß peptide and pTau protein. Using a novel ELISA, we discovered in AD blood elevated levels of isoAsp in HSA, together with reduced endogenous anti-isoAsp antibody levels, suggesting hampered Aß and pTau clearance in AD.Future directions:As degradation of the innate anti-isoAsp defenses may take years to develop, investigation of the isoAsp role in early stages of AD is warranted. And enrollment of different neurodegenerative disease cohorts will illustrate if isoAsp is AD-specific or universal to diseases related to aging.Abstract Figure
Co-occurrence patterns and habitat selection of the mountain hare, European hare, and European rabbit in urban areas of Sweden
Authors: Bach Henriette , Escoubet Hannah , Mayer Martin 
Published: May 2022

AbstractAssessing the underlying mechanisms of co-occurrence patterns can be challenging as biotic and abiotic causations are hard to disentangle. To date, few studies have investigated co-occurrence patterns within urban areas that constitute novel habitat to numerous wildlife species. Moreover, as urban areas expand and are increasingly used as habitat by wildlife, there is a need for a better understanding of urban ecology to facilitate human-wildlife coexistence. Here, we investigated co-occurrence patterns and habitat selection of the European hare (Lepus europaeus), mountain hare (L. timidus), and European rabbit (Oryctolagus cuniculus) inside urban areas of Sweden, using joint species distribution models and generalized linear mixed models based on citizen science observations. All three species were observed within urban areas, but European hares and rabbits appear to be more successful urban colonizers compared to mountain hares. Overall, our findings suggested that urban occurrence by all three lagomorphs was related to suitable conditions within the distribution of each species (e.g. climate and elevation), rather than by the presence of other lagomorph species or specific land cover types within urban areas. On a finer spatial scale, our findings suggested facilitation of European hares by rabbits, though the mechanism for this remains unclear. European hares and rabbits generally selected for green urban areas and mountain hares for residential gardens, which likely constitute suitable foraging sites. Our findings contribute to the understanding of urban ecology and provide valuable insight for management measures of the three lagomorphs in urban areas of Sweden.
CHRNA5links chandelier cells to severity of amyloid pathology in aging and Alzheimer’s Disease
Authors: Rybnicek Jonas , Chen Yuxiao , Millic Milos , Tio Earvin , McLaurin JoAnne , Hohman Timothy J. , De Jager Philip L , Schneider Julie A , Wang Yanling , Bennett David A , Tripathy Shreejoy , Felsky Daniel , Lambe Evelyn K 
Published: May 2022

AbstractChanges in high-affinity nicotinic acetylcholine receptors are intricately connected to neuropathology in Alzheimer’s Disease (AD). Protective and cognitive-enhancing roles for the nicotinic α5 subunit have been identified, but this gene has not been closely examined in the context of human aging and dementia. Therefore, we investigate the nicotinic α5 geneCHRNA5and the impact of relevant single nucleotide polymorphisms (SNPs) in prefrontal cortex from 922 individuals with matched genotypic andpost-mortemRNA sequencing in the Religious Orders Study and Memory and Aging Project (ROS/MAP). We find that a genotype robustly linked to increased expression ofCHRNA5(rs1979905A2) predicts significantly reduced cortical β-amyloid load. Intriguingly, co-expression analysis suggestsCHRNA5has a distinct cellular expression profile compared to other nicotinic receptor genes. Consistent with this prediction, single nucleus RNA sequencing from 22 individuals revealsCHRNA5expression is disproportionately-elevated in chandelier neurons, a distinct subtype of inhibitory neuron known for its role in excitatory/inhibitory (E/I) balance. We show that chandelier neurons are enriched in amyloid-binding proteins compared to basket cells, the other major subtype of PVALB-positive interneurons. Consistent with the hypothesis that nicotinic receptors in chandelier cells normally protect against β-amyloid, cell-type proportion analysis from 549 individuals reveals these neurons show amyloid-associated vulnerability only in individuals with impaired function/trafficking of nicotinic α5-containing receptors due to homozygosity of the missenseCHRNA5SNP (rs16969968A2). Taken together, these findings suggest thatCHRNA5and its nicotinic α5 subunit exert a neuroprotective role in aging and Alzheimer’s disease centered on chandelier interneurons.
Hybrid offspring of C57BL/6J mice exhibit improved properties for neurobehavioral research
Authors: Sloin Hadas E. , Bikovski Lior , Levi Amir , Amber-Vitos Ortal , Katz Tomer , Spivak Lidor , Someck Shirly , Gattegno Roni , Sivroni Shir , Sjulson Lucas , Stark Eran 
Published: May 2022

AbstractC57BL/6 is the most commonly used mouse strain in neurobehavioral research, serving as a background for multiple transgenic lines. However, C57BL/6 exhibit behavioral and sensorimotor disadvantages that worsen with age. We bred FVB/NJ females and C57BL/6J males to generate first-generation hybrid offspring, (FVB/NJ x C57BL/6J)F1. The hybrid mice exhibit reduced anxiety-like behavior, improved learning, and enhanced long-term spatial memory. In contrast to both progenitors, older hybrids maintain sensorimotor performance and exhibit improved long-term memory. The hybrids are larger than C57BL/6J, exhibiting enhanced running behavior on a linear track during freely-moving electrophysiological recordings. Hybrids exhibit typical rate and phase coding of space by CA1 pyramidal cells. Hybrids generated by crossing FVB/NJ females with transgenic males of a C57BL/6 background support optogenetic neuronal control in neocortex and hippocampus. The hybrid mice provide an improved model for neurobehavioral studies combining complex behavior, electrophysiology, and genetic tools readily available in C57BL/6 mice.
Online Bayesian Analysis with BEAST 2
Authors: Bouckaert Remco , Collienne Lena , Gavryushkin Alex 
Published: May 2022

AbstractThere are a growing number of areas, e.g. epidemiology and within-organism cancer evolution, where re-analysing all available data from scratch every time new data becomes available or old data is refined is no longer feasible. All these and related areas can benefit from online phylogenetic inference that can booster previous data analyses.Here, we make the case that adding/removing taxa from an analysis can have substantial non-local impact on the tree that is inferred, both in a model based setting, as well as for distance based methods. Consequently, online phylogenetic algorithms may require global updates of the trees and other parameters, a task that in general is highly non-trivial.Motivated by this observation, we designed an online algorithm that benefits from a parallelism in a Bayesian setting that is substantially more efficient than re-running the analysis from scratch. Furthermore, our algorithm is not sensitive to the number of sequences added, allowing the sequence data to grow/be refined iteratively. We show how this approach can be used in a maximum likelihood setting, and – apart from adding/removing new sequences – demonstrate a number of practical alternative use cases of our algorithm, including how to break up a single (offline) large analysis to get results faster.An open source implementation is available under GPL3 license as the ‘online’ package for BEAST 2 athttps://github.com/rbouckaert/onlineand a tutorial athttps://github.com/rbouckaert/online-tutorial.