bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracerebral Hemorrhage Detection in Computed Tomography Scans Through Cost-Sensitive Machine Learning
Authors: Goyal Rushank 
Published: October 2021

AbstractPurposeIntracerebral hemorrhage is the most severe form of stroke, with a greater than 75% likelihood of death or severe disability, and half of its mortality occurs in the first 24 hours. The grave nature of intracerebral hemorrhage and the high cost of false negatives in its diagnosis are representative of many medical tasks.ApproachCost-sensitive machine learning has shown promise in various studies as a method of minimizing unwanted results. In this study, 6 machine learning models were trained on 160 computed tomography brain scans both with and without utility matrices based on penalization, an implementation of cost-sensitive learning.ResultsThe highest-performing model was the support vector machine, which obtained an accuracy of 97.5%, sensitivity of 95% and specificity of 100% without penalization, and an accuracy of 92.5%, sensitivity of 100% and specificity of 85% with penalization, on a dataset of 40 scans. In both cases, the model outperforms a range of previous work using other techniques despite the small size of, and high heterogeneity in, the dataset.ConclusionUtility matrices demonstrate strong potential for sensitive yet accurate artificial intelligence techniques in medical contexts and workflows where a reduction of false negatives is crucial.
High prevalence of an alpha variant lineage with a premature stop codon in ORF7a in Iraq, winter 2020-2021
Authors: Al-Rashedi Nihad A.M , Alburkat Hussein , Hadi Abas O. , Munahi Murad G. , Jasim Ali , Hameed Alaa , Oda Basel Saber , Lilo Kareem Moamin , AlObaidi Laith A.H. , Vapalahti Olli , Sironen Tarja , Smura Teemu 
Published: October 2021

AbstractBackgroundSince the first reported case of coronavirus disease 2019 (COVID-19) in China, SARS-CoV-2 has been spreading worldwide. Genomic surveillance of SARS-CoV-2 has had a critical role in tracking the emergence, introduction, and spread of new variants, which may affect transmissibility, pathogenicity, and escape from infection or vaccine-induced immunity. As anticipated, the rapid increase in COVID-19 infections in Iraq in February 2021 is due to the introduction of variants of concern during the second wave of the COVID-19 pandemic.AimTo understand the molecular epidemiology of SARS-CoV-2 during the second wave in Iraq (2021),MethodWe sequenced 76 complete SARS-CoV-2 genomes using NGS technology and identified genomic mutations and proportions of circulating variants among these. Also, we performed an in silico study to predict the effect of the truncation of NS7a protein (ORF7a) on its functionResultsWe detected nine different lineages of SARS-CoV-2. The B.1.1.7 lineage was predominant (78.9%) from February to May 2021, while only one B.1.351 strain was detected. Interestingly, the phylogenetic analysis showed that multiple strains of the B.1.1.7 lineage clustered closely with those from European countries. A high frequency (88%) of stop codon mutation (NS7a Q62stop) was detected among the B.1.1.7 lineage sequences. In silico analysis of NS7a with Q62stop found that this stop codon had no significant effect on the function of NS7a.ConclusionThis work provides molecular epidemiological insights into the spread variants of SARS-CoV-2 in Iraq, which are most likely imported from Europe.
Markerless mouse tracking for social experiments
Authors: Le Van Anh , Sterley Toni-Lee , Cheng Ning , Bains Jaideep S. , Murari Kartikeya 
Published: October 2021

AbstractAutomated behavior quantification requires accurate tracking of animals. Simultaneous tracking of multiple animals, particularly those lacking visual identifiers, is particularly challenging. Problems of mistaken identities and lost information on key anatomical features are common in existing methods. Here we propose a markerless video-based tool to simultaneously track two socially interacting mice of the same appearance. It incorporates conventional handcrafted tracking and deep learning based techniques, which are trained on a small number of labeled images from a very basic, uncluttered experimental setup. The output consists of body masks and coordinates of the snout and tail-base for each mouse. The method was tested on a series of cross-setup videos recorded under commonly used experimental conditions including bedding in the cage and fiberoptic or headstage implants on the mice. Results obtained without any human intervention showed the effectiveness of the proposed approach, evidenced by a near elimination of identities switches and a 10% improvement in tracking accuracy over a pure deep-learning-based keypoint tracking approach trained on the same data. Finally, we demonstrated an application of this approach in studies of social behaviour of mice, by using it to quantify and compare interactions between pairs of mice in which some are anosmic, i.e. unable to smell. Our results indicated loss of olfaction impaired typical snout-directed social recognition behaviors of mice, while non-snout-directed social behaviours were enhanced. Together, these results suggest that the hybrid approach could be valuable for studying group behaviors in rodents, such as social interactions.
Endoplasmic Reticulum Chaperone Genes Encode Effectors of Long-Term Memory
Authors: Chatterjee Snehajyoti , Bahl Ethan , Mukherjee Utsav , Walsh Emily N. , Shetty Mahesh Shivarama , Yan Amy L. , Vanrobaeys Yann , Lederman Joseph D. , Giese K. Peter , Michaelson Jacob , Abel Ted 
Published: October 2021

AbstractThe mechanisms underlying memory loss associated with Alzheimer’s disease and related dementias (ADRD) remain unclear, and no effective treatments exist. Fundamental studies have shown that a set of transcriptional regulatory proteins of the nuclear receptor 4a (Nr4a) family serve as molecular switches for long-term memory. Here, we show that Nr4a proteins regulate the transcription of a group of genes encoding chaperones that localize to the endoplasmic reticulum (ER), which function to traffic plasticity-related proteins to the cell surface during long lasting forms of synaptic plasticity and memory. Nr4a transcription factors and ER chaperones are linked to ADRD in human samples as well as mouse models, and overexpressing Nr4a1 or the ER chaperone Hspa5 ameliorates the long-term memory deficits in a tau-based mouse model of ADRD, pointing towards novel therapeutic approaches for treating memory loss. Thus, our findings establish protein folding in the ER as a novel molecular concept underlying long-term memory, providing new insights into the mechanistic basis of cognitive deficits in dementia.One-Sentence SummaryMolecular approaches establish protein folding in the endoplasmic reticulum as a novel molecular concept underlying synaptic plasticity and memory, serving as a switch to regulate protein folding and trafficking, and driving cognitive deficits in neurodegenerative disorders.
Moran Process Version of the Tug-of-War Model: Complex Behavior Revealed by Mathematical Analysis and Simulation Studies
Authors: Bobrowski Adam , Kimmel Marek , Kurpas Monika K. , Ratajczyk Elżbieta 
Published: October 2021

AbstractIn a series of publications McFarland and co-authors introduced the tug-of-war model of evolution of cancer cell populations. The model is explaining the joint effect of rare advantageous and frequent slightly deleterious mutations, which may be identifiable with driver and passenger mutations in cancer. In this paper, we put the Tug-of-War model in the framework of a denumerable-type Moran process and use mathematics and simulations to understand its behavior. The model is associated with a time-continuous Markov Chain (MC), with a generator that can be split into a sum of the drift and selection process part and of the mutation process part. Operator semigroup theory is then employed to prove that the MC does not explode, as well as to characterize a strong-drift limit version of the MC which displays “instant fixation” effect, which was an assumption in the original McFarland’s model. Mathematical results are fully confirmed by simulations of the complete and limit versions. They also visualize complex stochastic transients and genealogies of clones arising in the model.
Mining of thousands of prokaryotic genomes reveals high abundance of prophage signals
Authors: López-Leal Gamaliel , Camelo-Valera Laura Carolina , Hurtado-Ramírez Juan Manuel , Verleyen Jérôme , Castillo-Ramírez Santiago , Reyes-Muñoz Alejandro 
Published: October 2021

AbstractPhages and prophages are one of the principal modulators of microbial populations. However, much of their diversity is still poorly understood. Here, we extracted 33,624 prophages from 13,713 complete prokaryotic genomes in order to explore the prophage diversity and their relationships with their host. Our results reveal that prophages were present in 75% of the genomes studied. In addition, Enterobacterales were significantly enriched in prophages. We also found that pathogens are a significant reservoir of prophages. Finally, we determined that the prophage relatedness and the range of genomic hosts were delimited by the evolutionary relationships of their hosts. On a broader level, we got insights into the prophage population, identified in thousands of publicly available prokaryotic genomes, by comparing the prophage distribution and relatedness between them and their hosts.
First characterisation of antimicrobial susceptibility and resistance of Neisseria gonorrhoeae isolates in Qatar, 2017-2020
Authors: Al-Maslamani Muna , Ibrahim Elmagboul Emad Bashier , Puthiyottil Aslam , Chemaitelly Hiam , Varghese Manoj Kizhakkepeedikayil , Al Romaihi Hamad Eid , Al-Thani Mohamed H. , Khal Abdullatif Al , Unemo Magnus , Abu-Raddad Laith J. 
Published: October 2021

ABSTRACTLimited data are available regarding antimicrobial resistance in Neisseria gonorrhoeae strains circulating in WHO Eastern Mediterranean Region (EMR). We investigated the antimicrobial susceptibility/resistance of N. gonorrhoeae isolates to five antimicrobials (ceftriaxone, azithromycin, ciprofloxacin, tetracycline, and benzylpenicillin) currently or previously used for gonorrhoea treatment in Qatar, 2017-2020. Minimum inhibitory concentrations (MICs; mg/L) of antimicrobials were determined using Etest on gonococcal isolates collected during January 1, 2017-August 30, 2020 at Hamad Medical Corporation, a national public healthcare provider. During 2017-2020, resistance in isolates from urogenital sites of 433 patients was 64.7% (95% CI: 59.5-69.6%; range: 43.9-78.7%) for ciprofloxacin, 50.7% (95% CI: 45.3-56.1%; range: 41.3-70.4%) for tetracycline, and 30.8% (95% CI: 26.3-35.6%; range: 26.7-35.8%) for benzylpenicillin. Percentage of isolates non-susceptible to azithromycin was 4.1% (95% CI: 2.0-7.4%; range: 2.7-4.8%) and all (100%) isolates were susceptible to ceftriaxone. Two (1.6%) isolates from 2019 and one (2.2%) isolate from 2020 had high-level resistance to azithromycin (MIC≥256 mg/L). Overall, 1.0% (4/418) of isolates had a ceftriaxone MIC of 0.25 mg/L, which is at the ceftriaxone susceptibility breakpoint (MIC≤0.25 mg/L). Treatment with ceftriaxone 250 mg plus azithromycin 1 g can continuously be recommended for gonorrhoea therapy in Qatar. Continued quality-assured gonococcal AMR surveillance is warranted in EMR.
Using a novel echo-marker to identify high mortality risk patients with moderate aortic stenosis
Authors: Chao Chieh-Ju , Agasthi Pradyumma , Barry Timothy , Girardo Marlene , Seri Amith R. , Shanbhag Anusha , Wang Yuxiang , Lester Steven J. , Alsidawi Said , Freeman William K , Naqvi Tasneem Z. , Eleid Mackram , Fortuin David , Sweeney John P. , Pollak Peter , Sabbagh Abdallah El , Sell-Dottin Kristen , Majdalany David , Larsen Carolyn , Holmes David R , Oh Jae K. , Appleton Christopher P. , Arsanjani Reza 
Published: October 2021

AbstractBackgroundRecent studies have shown that patients with moderate aortic stenosis and reduced left ventricular ejection fraction may benefit from earlier intervention instead of periodic surveillance. Identifying patients at higher risk is therefore warranted concerning the possibility of expanding aortic valve replacement indication.ObjectiveWe aim to investigate the usefulness of a novel echo-marker, augmented mean arterial pressure (AugMAP), in identifying high-risk patients with moderate aortic stenosis.MethodsAdult patients with moderate aortic stenosis (aortic valve area 1.0-1.5 cm2) at Mayo Clinic sites in 1/2010-12/2020 were identified. Baseline demographics, echocardiography, and all-cause mortality data were retrieved. Patients were grouped into higher and lower AugMAP groups using a cutoff of 80 mmHg for analysis. Kaplan-Meier and Cox regression analyses were used to assess the performance of AugMAP.ResultsA total of 4,563 patients with moderate aortic stenosis were included. The mean age was 73.7±12.5 years and 60.5 % were male. The median follow-up was 2.5 years, and 36.0% of patients died. The mean LVEF was 60.1 ± 11.4%, and the mean AugMAP was 99.1 ± 13.1 mmHg. Patients in the lower AugMAP group, with either preserved or reduced LVEF, had significantly worse survival performance (all p< 0.0001). Multivariate Cox regression showed that AugMAP was independently associated with all-cause mortality after adjusting for age, sex, and LVEF (HR: 0.99 per unit increase, 95%CI: 0.978-0.996, p=0.01).ConclusionAugMAP is a simple and effective echo-maker beyond LVEF to identify high-risk moderate aortic stenosis patients who may benefit more from earlier intervention.Condensed abstractPatients with moderate aortic stenosis and reduced left ventricular ejection fraction may benefit from earlier intervention. We aim to validate the usefulness of a novel echo-marker, augmented mean arterial pressure (AugMAP), in identifying high-risk patients with moderate aortic stenosis. AugMAP can identify patients at higher mortality risk within the first two years after the diagnosis of moderate aortic stenosis, regardless of LVEF. AugMAP was also independently associated with all-cause mortality after adjusting for age, sex, and LVEF. AugMAP is a simple and effective novel echo-maker beyond LVEF to identify high-risk moderate aortic stenosis patients who may benefit from earlier intervention.
Molecular-scale 3D visualisation of the cardiac ryanodine receptor clusters and the molecular-scale fraying of dyads
Authors: Sheard Thomas M. D. , Hurley Miriam E. , Smith Andrew J. , Colyer John , White Ed , Jayasinghe Izzy 
Published: October 2021

AbstractClusters of ryanodine receptor calcium channels (RyRs) form the primary molecular machinery in cardiomyocytes. Various adaptations of super-resolution microscopy have revealed intricate details of the structure, molecular composition and locations of these couplons. However, most optical super-resolution techniques lack the capacity for three-dimensional (3D) visualisation. Enhanced Expansion Microscopy (EExM) offers resolution (in-plane and axially) sufficient to spatially resolve individual proteins within peripheral couplons and within dyads located in the interior. We have combined immunocytochemistry and immunohistochemistry variations of EExM with 3D visualisation to examine the complex topologies, geometries and molecular sub-domains within RyR clusters. We observed that peripheral couplons exhibit variable co-clustering ratios and patterns between RyR and the structural protein, junctophilin-2 (JPH2). Dyads possessed sub-domains of JPH2 which occupied the central regions of the RyR cluster, whilst the poles were typically devoid of JPH2 and broader, and likely specialise in turnover and remodelling of the cluster. In right ventricular myocytes from rats with monocrotaline-induced right ventricular failure, we observed hallmarks of RyR cluster fragmentation accompanied by similar fragmentations of the JPH2 sub-domains. We hypothesise that the frayed morphology of RyRs in close proximity to fragmented JPH2 structural sub-domains may form the primordial foci of RyR mobilisation and dyad remodelling.
Population genomics of ancient and modernTrichuris trichiura
Authors: Doyle Stephen R. , Søe Martin Jensen , Nejsum Peter , Betson Martha , Cooper Philip J. , Peng Lifei , Zhu Xing-Quan , Sanchez Ana , Matamoros Gabriela , Fontecha Sandoval Gustavo Adolfo , Cutillas Cristina , Tchuenté Louis-Albert Tchuem , Mekonnen Zeleke , Ame Shaali M. , Namwanje Harriet , Levecke Bruno , Berriman Matthew , Fredensborg Brian Lund , Outzen Kapel Christian Moliin 
Published: October 2021

AbstractThe neglected tropical disease trichuriasis is caused by the whipwormTrichuris trichiura, a soil-transmitted helminth that has infected humans for millennia. Today,T. trichiurainfects as many as 500 million people, predominantly in communities with poor sanitary infrastructure enabling sustained faecal-oral transmission. Using whole-genome sequencing of geographically distributed worms collected from human and other primate hosts, together with ancient samples preserved in archaeologically-defined latrines and deposits dated up to one thousand years old, we present the first population genomics study ofT. trichiura. We describe the continent-scale genetic structure between whipworms infecting humans and baboons relative to those infecting other primates. Admixture and population demographic analyses support a stepwise distribution of genetic variation that is highest in Uganda, consistent with an African origin and subsequent translocation with human migration. Finally, genome-wide analyses between human samples and between human and non-human primate samples reveal local regions of genetic differentiation between geographically distinct populations. These data provide insight into zoonotic reservoirs of human-infectiveT. trichiuraand will support future efforts toward the implementation of genomic epidemiology of this globally important helminth.
Within-generation and transgenerational social plasticity interact during rapid adaptive evolution
Authors: Sturiale Samantha L. , Bailey Nathan W. 
Published: October 2021

AbstractThe role of within-generation phenotypic plasticity (WGP) versus transgenerational plasticity (TGP) during evolutionary adaptation are not well understood, particularly for socially-cued TGP.We tested how genetics, WGP, and TGP jointly influence expression of fitness traits facilitating adaptive evolution in the field cricketTeleogryllus oceanicus. A male-silencing mutation (“flatwing”) spread to fixation in ca. 50 generations in a Hawaiian cricket population attacked by acoustically-orienting parasitoids. This rapid loss of song caused the social environment to dramatically change.Juveniles carrying theflatwing(fw) genotype exhibited greater locomotive activity than those carrying thenormal-wing(nw) allele, consistent with genetic coupling of increased locomotion withfw.Consistent with adaptive WGP, homozygousfwfemales developing in the absence of song showed reduced body condition and reproductive investment at adulthood.Adult but not juvenile offspring exhibited TGP in response to maternal social environment for structural size, somatic condition, and reproductive investment, whereas adult locomotion and flight was only influenced by WGP. WGP and TGP interacted to shape multiple traits at adulthood, though effect sizes were modest.Interactions between genetic effects and social plasticity within and across generations are likely to have influenced the evolutionary spread of flatwing crickets. However, interactions among these effects can be complex, and it is notable that TGP manifested most strongly later in development. Our findings stress the importance of evaluating trait plasticity at different developmental stages and across generations when studying phenotypic plasticity’s role in evolution.
Autopolyploid establishment depends on life history strategy and the mating outcomes of clonal architecture
Authors: Van Drunen Wendy E. , Friedman Jannice 
Published: October 2021

ABSTRACTPolyploidy is a significant component in the evolution of many taxa, particularly plant groups. However, the mechanisms promoting or preventing initial polyploid establishment in natural populations are often unclear. We develop spatially explicit agent-based simulation models to explore how perennial life history and clonal propagation influence the early stages of polyploid establishment. Our models show that polyploid establishment is unlikely among short-lived plants. Polyploids have increased establishment probability when both diploid and polyploid lifespans are long, especially when unreduced gamete production is non-zero. Further, polyploids that combine sexual and clonal reproduction can establish across a wide range of life history strategies. Polyploid genets containing many, far spreading ramets are most successful, but genets with tightly clumped ramets have similar establishment probability when pollen dispersal is local and rates of self-fertilization are high. Clonal architecture has a substantial impact on the spatial structure of the mixed cytotype population during establishment; altering patterns of mating within or between cytotypes, the mechanisms through which polyploid establishment proceeds, and the final composition of the polyploid population after successful establishment. Overall, our findings provide insight into the complex relationship between polyploidy, perenniality, and clonal reproduction, and offer testable predictions for future empirical work.
Readers move their eyes mindlessly using midbrain visuo-motor principles
Authors: Vitu Françoise , Adeli Hossein , Zelinsky Gregory J. 
Published: October 2021

AbstractSaccadic eye movements rapidly shift our gaze over 100,000 times daily, enabling countless tasks ranging from driving to reading. Long regarded as a window to the mind1and human information processing2, they are thought to be cortically/cognitively controlled movements aimed at objects/words of interest3–10. Saccades however involve a complex cerebral network11–13wherein the contribution of phylogenetically older sensory-motor pathways14–15remains unclear. Here we show using a neuro-computational approach16that mindless visuo-motor computations, akin to reflexive orienting responses17in neonates18–19and vertebrates with little neocortex15,20, guide humans’ eye movements in a quintessentially cognitive task, reading. These computations occur in the superior colliculus, an ancestral midbrain structure15, that integrates retinal and (sub)cortical afferent signals13over retinotopically organized, and size-invariant, neuronal populations21. Simply considering retinal and primary-visual-cortex afferents, which convey the distribution of luminance contrast over sentences (visual-saliency map22), we find that collicular population-averaging principles capture readers’ prototypical word-based oculomotor behavior2, leaving essentially rereading behavior unexplained. These principles reveal that inter-word spacing is unnecessary23–24, explaining metadata across languages and writing systems using only print size as a predictor25–26. Our findings demonstrate that saccades, rather than being a window into cognitive/linguistic processes, primarily reflect rudimentary visuo-motor mechanisms in the midbrain that survived brain-evolution pressure27.