bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural signatures of compression in the retelling of past events
Authors: Musz Elizabeth , Chen Janice 
Published: September 2021

AbstractWhen we retell our past experiences, we aim to reproduce some version of the original events; this reproduced version is often temporally compressed relative to the original. How does such compression of memories manifest in brain activity? One possibility is that a compressed retrieved memory manifests as a neural pattern which is more dissimilar to the original, relative to a more detailed or vivid memory. However, we argue that measuring raw dissimilarity alone is insufficient, as it confuses a variety of interesting and uninteresting changes. To address this problem, we examine brain pattern changes that are consistent across people. We show that temporal compression in individuals’ retelling of past events predicts systematic encoding-to-recall transformations in a number of higher associative regions. These findings elucidate how neural representations are not simply reactivated, but can also be transformed due to temporal compression during a universal form of human memory expression: verbal retelling.
Polygenic score accuracy in ancient samples: quantifying the effects of allelic turnover
Authors: Carlson Maryn O. , Rice Daniel P. , Berg Jeremy J. , Steinrücken Matthias 
Published: September 2021

AbstractPolygenic scores link the genotypes of ancient individuals to their phenotypes, which are often unobservable, offering a tantalizing opportunity to reconstruct complex trait evolution. In practice, however, interpretation of ancient polygenic scores is subject to numerous assumptions. For one, the genome-wide association (GWA) studies from which polygenic scores are derived, can only estimate effect sizes for loci segregating in contemporary populations. Therefore, a GWA study may not correctly identify all loci relevant to trait variation in the ancient population. In addition, the frequencies of trait-associated loci may have changed in the intervening years. Here, we devise a theoretical framework to quantify the effect of this allelic turnover on the statistical properties of polygenic scores as functions of population genetic dynamics, trait architecture, power to detect significant loci, and the age of the ancient sample. We model the allele frequencies of loci underlying trait variation using the Wright-Fisher diffusion, and employ the spectral representation of its transition density to find analytical expressions for several error metrics, including the correlation between an ancient individual’s polygenic score and true phenotype, referred to as polygenic score accuracy. Our theory also applies to a two-population scenario and demonstrates that allelic turnover alonemayexplain a substantial percentage of the reduced accuracy observed in cross-population predictions, akin to those performed in human genetics. Finally, we use simulations to explore the effects of recent directional selection, a bias-inducing process, on the statistics of interest. We find that even in the presence of bias, weak selection induces minimal deviations from our neutral expectations for the decay of polygenic score accuracy. By quantifying the limitations of polygenic scores in an explicit evolutionary context, our work lays the foundation for the development of more sophisticated statistical procedures to analyze both temporally and geographically resolved polygenic scores.
Extrasynaptic signaling enables an asymmetric juvenile motor circuit to produce a symmetric undulation
Authors: Lu Yangning , Ahamed Tosif , Mulcahy Ben , Meng Jun , Witvliet Daniel , Guan Sihui Asuka , Holmyard Douglas , Hung Wesley , Wen Quan , Chisholm Andrew D , Samuel Aravinthan DT , Zhen Mei 
Published: September 2021

SummaryIn many animals, there is a direct correspondence between the motor patterns that drive locomotion and the motor neuron innervation onto the muscle groups. For example, the adult C. elegans moves with symmetric and alternating dorsal-ventral bending waves arising from symmetric motor neuron input onto the dorsal and ventral muscles. In contrast to the adult, the C. elegans motor circuit at the juvenile larval stage has asymmetric wiring between motor neurons and muscles, but still generates adult-like bending waves with dorsal-ventral symmetry. We show that in the juvenile circuit, wiring between excitatory and inhibitory motor neurons coordinates the contraction of dorsal muscles with relaxation of ventral muscles, producing dorsal bends. However, ventral bending is not driven by analogous wiring. Instead, ventral muscles are excited uniformly by premotor interneurons through extrasynaptic signaling. Ventral bends occur in anti-phasic entrainment to activity of the same motor neurons that drive dorsal bends. During maturation, the juvenile motor circuit is replaced by two motor subcircuits that separately drive dorsal and ventral bending. Modeling reveals that the juvenile’s immature motor circuit is an adequate solution to generate adult-like dorsal-ventral bending before the animal matures. Developmental rewiring between functionally degenerate circuit solutions, that both generate symmetric bending patterns, minimizes behavioral disruption across maturation.HighlightsC. elegans larvae generate symmetric motor pattern with an asymmetrically wired motor circuit.Synaptic wiring between excitatory and inhibitory motor neurons drives dorsal bending.Extrasynaptic excitation by premotor interneurons entrains ventral muscles for anti-phasic ventral bending.A developmental strategy to enable mature motor pattern before the circuit structurally matures.
Urethane Anesthesia Exhibits Neurophysiological Correlates of Unconsciousness and is Distinct from Sleep
Authors: Mondino Alejandra , González Joaquín , Li Duan , Mateos Diego , Osorio Lucía , Cavelli Matías , Costa Alicia , Vanini Giancarlo , Mashour George , Torterolo Pablo 
Published: September 2021

AbstractUrethane is a general anesthetic widely used in animal research. It is unique among anesthetics because urethane anesthesia alternates between macroscopically distinct electrographic states: a slow-wave state that resembles NREM sleep (NREMure), and an activated state with features of both REM sleep and wakefulness (REMure). However, the relationship between urethane anesthesia and physiological sleep is still unclear. In this study, electroencephalography (EEG) and electromyography were recorded in chronically prepared rats during natural sleep-wake states and during urethane anesthesia. We subsequently analyzed the EEG signatures associated with the loss of consciousness and found that, in comparison to natural sleep-wake states, the power, coherence, directed connectivity and complexity of brain oscillations are distinct during urethane. We also demonstrate that both urethane states have clear EEG signatures of general anesthesia. Thus, despite superficial similarities that have led others to conclude that urethane is a model of sleep, the electrocortical traits of depressed and activated states during urethane anesthesia differ from physiological sleep states.
An 8 week randomized Dietary Guidelines for Americans -based diet intervention improves the omega-3 index of healthy women
Authors: Richardson Christine E. , Krishnan Sridevi , Gray Ira J. , Keim Nancy L. , Newman John W. 
Published: September 2021

AbstractBackgroundThe Dietary Guidelines for Americans (DGA) recommends consuming >1.75g/wk of long-chain omega-3 fatty acids to reduce the risk of cardiovascular disease (CVD) through triglyceride reduction, however individual responses to treatment vary.ObjectiveWe sought to determine if a DGA-conforming diet (DGAD) can increase the omega-3 index (OM3I), a diet-sensitive biomarker of omega-3 fatty acid status, into a health promoting range and reduce fasting triglycerides in 8 weeks. We further explored determinants of the basal OM3I and its response to treatment.DesignThis is a secondary analysis of a randomized, double-blind 8wk dietary intervention of overweight/obese women fed an 8d rotating DGAD (n =22) or typical American diet (TAD; n =20) registered at www.clinicaltrials.gov as NCT02298725. The DGAD and TAD provided individuals with 16 ± 2 g/wk and 1.2 ± 0.12 g/wk of eisocapentaenoic acid (EPA) + docosahexaenoic acid (DHA), respectively. Habitual diet and body composition were determined at baseline. OM3I, fasting triglycerides, glucose and insulin were measured at 0, 2 and 8wk.ResultsBaseline OM3I (5.8 ± 1.3; n =42) was positively correlated to the dietary (EPA+DHA):dietary fat ratio (p =0.006), negatively correlated to the android fat mass (p =0.0007) and was not different between diet groups. At 8wk, while the TAD-group average OM3I was unchanged (5.8 ± 0.76), the DGAD-group OM3I increased (7.33 ± 1.36; p <0.001). In the DGAD-group 9 of 22 (i.e. 41%) participants achieving an OM3I >8%. Subgroup analyses of the DGAD-group revealed that body fat content and distribution influenced the baseline-dependent response to treatment. Fasting triglyceride and OM3I changes did not correlate.ConclusionsAn 8wk TAD stabilized the OM3I in a healthy range, while a DGAD increased the OM3I into a health-promoting range, but did not reduce fasting triglycerides. Fat distribution and basal omega-3 status are primary factors influencing omega-3 efficacy in overweight/obese women.
Automated Multilabel Diagnosis on Electrocardiographic Images and Signals
Authors: Sangha Veer , Mortazavi Bobak J. , Haimovich Adrian D. , Ribeiro Antônio H. , Brandt Cynthia A. , Jacoby Daniel L. , Schulz Wade L. , Krumholz Harlan M. , Ribeiro Antonio Luiz P. , Khera Rohan 
Published: September 2021

ABSTRACTAimsThe application of artificial intelligence (AI) for automated diagnosis of electrocardiograms (ECGs) can improve access to high quality diagnostic care in remote settings but is limited by the reliance on signal-based data that are not routinely available. We sought to develop a multilabel automated diagnosis model for electrocardiographic images, more suitable for broader use.Methods and ResultsA total of 2,228,236 12-lead ECGs from 811 municipalities in Minas Gerais, Brazil were sampled into 90% (training):5%(validation):5%(held-out test), and were transformed to ECG images with varying lead locations and formats. We trained a convolutional neural network (CNN) using an EfficientNet-based architecture on ECG images to identify 6 physician-defined clinical labels spanning rhythm and conduction disorders, as well as a hidden label for gender. We trained another CNN for signal-based classification. The image-based model performed well on the held-out test set (average AUROC 0.99, AUPRC 0.68). This was replicated in a distinct test set from Brazil validated by at least two cardiologists (average AUROC 0.99, AUPRC 0.86) as well as an external validation set of 21,785 ECGs from Germany (average AUROC 0.97, AUPRC 0.73), with performance superior to signal-based models. Expert review of 120 out of 120 high confidence false positive predictions on the held-out and external validation sets were confirmed to be true positives with incorrect labels. The model learned generalizable features, confirmed using Gradient-weighted Class Activation Mapping (Grad-CAM).ConclusionWe developed an externally validated model that extends the automated diagnosis of key rhythm and conduction disorders to printed ECGs as well as to the identification of hidden features, allowing the application of AI to ECGs captured across broad settings.
Integrating genome-wide polygenic risk scores and non-genetic risk to predict colorectal cancer diagnosis: a cohort study in UK Biobank
Authors: Briggs Sarah E.W. , Law Philip , East James E. , Wordsworth Sarah , Dunlop Malcolm , Houlston Richard , Hippisley-Cox Julia , Tomlinson Ian 
Published: September 2021

AbstractObjectivesTo evaluate the benefit of combining polygenic risk scores (PRS) with the QCancer-10 (colorectal cancer) non-genetic risk prediction model to identify those at highest risk of colorectal cancer (CRC).DesignPopulation based cohort study. Six different PRS for CRC were developed (using LDpred2 PRS software, clumping and thresholding approaches, and genome-wide significant models). The top-performing genome-wide and GWAS-significant PRS were then combined with QCancer-10 and performance compared to QCancer-10 alone. Case-control (logistic regression) and time-to-event (Cox proportional hazards) analyses were used to evaluate risk model performance in men and women.Setting and participantsUK Biobank Study. A total of 434587 individuals with complete genetic and QCancer-10 predictor data were included in the QCancer-10+PRS modelling cohorts.Main outcome measuresPrediction of colorectal cancer diagnosis by genetic, non-genetic and combined risk models.FindingsPRS derived using the LDpred2 program performed best, with an odds-ratio per standard deviation of 1.58, and top age- and sex-adjusted C-statistic of 0.733 (95% confidence interval 0.710 to 0.753) in logistic regression models in the validation cohort. Integrated QCancer-10+PRS models out-performed QCancer-10 alone. In men, the integrated LDpred2 (QCancer-10+LDP) model produced a C-statistic of 0.730 (0.720 to 0.741) and explained variation of 28.1% (26.3% to 30.0%), compared with 0.693 (0.682 to 0.704) and 21.0% (18.9% to 23.1%) for QCancer-10 alone. Performance improvements in women were similar. In the top 20% of individuals at highest absolute risk, the sensitivity of QCancer-10+LDP models for predicting CRC diagnosis within 5 years was 47.6% in men and 42.5% in women, with respective 3.49-fold and 2.75-fold absolute increases in the top 5% of risk compared to average. Decision curve analysis showed that adding PRS to QCancer-10 improved net-benefit and interventions avoided, across most probability thresholds.ConclusionsIntegrating PRS with QCancer-10 significantly improves risk prediction over QCancer-10 alone. Evaluation of risk stratified population screening using this approach is warranted.Summary BoxWhat is already known on this topicRisk stratification based on genetic or environmental risk factors could improve cancer screening outcomesNo previously published study has examined integrated models combining genome-wide PRS and non-genetic risk factors beyond ageQCancer-10 (colorectal cancer) is the top-performing non-genetic risk prediction model for CRCWhat this study addsAdding PRS to the QCancer-10 (colorectal cancer) risk prediction model improves performance and clinical benefit, with greatest gain from the LDpred2 genome-wide PRS, to a level that suggests utility in stratifying CRC screening and prevention
Cost-effectiveness of psychosocial assessment for individuals who present to hospital following self-harm in England: a model-based retrospective analysis
Authors: McDaid David , Park A-La , Tsiachristas Apostolos , Brand Fiona , Casey Deborah , Clements Caroline , Geulayov Galit , Kapur Nav , Ness Jennifer , Waters Keith , Hawton Keith 
Published: September 2021

AbstractAimsThere are substantial costs to health care systems and society associated with self-harm. Moreover, individuals who have presented to hospital following self-harm have a much higher risk of suicide within the following year compared to the general population. National guidance in England recommends psychosocial assessment when presenting to hospital following self-harm but adherence to this guidance is variable. There is some limited evidence suggesting that psychosocial assessment is associated with lower risk of subsequent presentation to hospital for self-harm. The aim of this study was to assess the potential cost-effectiveness of psychosocial assessment for hospital-presenting self-harm in England compared to no assessment.MethodsWe constructed a three-state four-cycle Markov model to assess the cost-effectiveness of psychosocial assessment after self-harm compared with no assessment over two years. Data on risk of subsequent self-harm and hospital costs of treating different types of self-harm were drawn from prior analysis of the Multicentre Study of Self-Harm in England, while estimates of the effectiveness of psychosocial assessment on risk of self-harm, quality of life impacts and other costs were supplemented by a literature review. Incremental cost-effectiveness ratios (ICERs) were estimated in terms of cost per Quality Adjusted Life Year (QALY) gained and parameter uncertainty was addressed in univariate and probabilistic sensitivity analyses. Costs were reported in 2020 UK Pounds from the healthcare and societal perspective (that included productivity loss) and a discount rate of 3.5% was applied to future costs and QALYs.ResultsThe cost per QALY gained from psychosocial assessment was £10,962 (95% uncertainty interval (UI) £15,538 - £9,219) from the NHS perspective, and £9,980 (95% UI £14,538, £6,938) from the societal perspective. Baseline results were generally robust to changes in model assumptions; the relative risk of self-harm after psychosocial assessment would have to be 0.73 or lower for the ICER to be below £20,000. The cost-effectiveness acceptability curve showed that the probability of the ICER to be below a £20,000 threshold was 78%, rising to 91% with a £30,000 threshold.ConclusionsPsychosocial assessment as implemented in the English NHS is likely to be cost-effective. This evidence could support adherence to NICE guidelines. However, further evidence is still needed about the precise impact of psychosocial assessment on self-harm repetition and costs to individuals affected by self-harm and their families beyond immediate hospital stay.
Update of transmission modelling and projections of gambiense human African trypanosomiasis in the Mandoul focus, Chad
Authors: Rock Kat S , Huang Ching-I , Crump Ronald E , Bessell Paul R , Brown Paul E , Tirados Inaki , Solano Philippe , Antillon Marina , Picado Albert , Mbainda Severin , Darnas Justin , Crowley Emily H , Torr Steve J , Peka Mallaye 
Published: September 2021

AbstractBackgroundIn recent years, an integrated programme of vector control, screening and treatment of gambiense human African trypanosomiasis (gHAT) infections has led to a rapid decline in cases in the Mandoul disease focus of Chad. In this study, we assess whether elimination of transmission has already been achieved in the region despite low-level case reporting, quantify the role of intensified interventions in transmission reduction, and predict the trajectory of gHAT in Mandoul for the next decade under a range of control scenarios.MethodWe utilise human case data (2000–2019) to update a previous model of transmission of gHAT in Mandoul. We also test the updated model, which now has refined assumptions on diagnostic specificity of the current algorithm and an improved fitting method, via a data censoring approach.ResultsWe conclude that passive detection rates have increased due to improvements in diagnostic availability in fixed health facilities since 2015, by 2.1-fold for stage 1 detection, and by 1.5-fold for stage 2. We find that whilst the diagnostic algorithm for active screening is estimated to be highly specific (99.93%, 95% CI: 99.91–99.95%), the high screening level and limited remaining infection means that some recently reported cases might be false positives, especially the ones that were not parasitologically confirmed. We also find that the focus-wide tsetse vector reduction estimated through model fitting (99.1%, 95% CI: 96.1–99.6%) is comparable to the very high reduction previously measured by the decline in catches of tsetse from monitoring traps. In line with previous results, the model suggests that transmission was likely interrupted in 2015 as a result of intensified interventions.ConclusionsWe recommend that additional confirmatory testing is performed in Mandoul in order that the endgame can be carefully monitored now that infection levels are so low. More specific measurement of cases would better inform when it is safe to stop active screening and vector control.
Periodic attention operates faster during more complex visual search
Authors: Merholz Garance , Grabot Laetitia , VanRullen Rufin , Dugué Laura 
Published: September 2021

AbstractAttention has been found to sample visual information periodically, in a wide range of frequencies below 20 Hz. This periodicity may be supported by brain oscillations at corresponding frequencies. We propose that part of the discrepancy in periodic frequencies observed in the literature is due to differences in attentional demands, resulting from heterogeneity in tasks performed. To test this hypothesis, we used visual search and manipulated task complexity, i.e., target discriminability (high, medium, low) and number of distractors (set size), while electro-encephalography was simultaneously recorded. We replicated previous results showing that the phase of pre-stimulus low-frequency oscillations predicts search performance. Crucially, such effects were observed at increasing frequencies within the theta-alpha range (6-18 Hz) for decreasing target discriminability. In medium and low discriminability conditions, correct responses were further associated with higher post-stimulus phase-locking than incorrect ones, in increasing frequency and latency. Finally, the larger the set size, the later the post-stimulus effect peaked. Together, these results suggest that increased complexity (lower discriminability or larger set size) requires more attentional cycles to perform the task, partially explaining discrepancies between reports of attentional sampling. Low-frequency oscillations structure the temporal dynamics of neural activity and aid top-down, attentional control for efficient visual processing.
Expedited gene delivery for osteochondral defect repair in a rabbit knee model: a one-year investigation
Authors: Nagelli Christopher V. , De La Vega Rodolfo E. , Coenen Michael , de Lopez Consuelo Padilla , Panos Joseph A. , Tovar Alejandro , Müller Sebastian A. , Evans Christopher H. 
Published: September 2021

ABSTRACTObjectiveTo evaluate a single-step, gene-based procedure for repairing osteochondral lesions.DesignOsteochondral lesions were created in the patellar groove of skeletally mature rabbits. Autologous bone marrow aspirates were mixed with adenovirus vectors carrying cDNA encoding green fluorescent protein (Ad.GFP) or transforming growth factor-β1 (Ad.TGF-β1) and allowed to clot. The clotted marrow was press-fit into the defects. Animals receiving Ad.GFP were euthanized at 2 weeks and intra-articular expression of GFP examined by fluorescence microscopy. Animals receiving Ad.TGF-β1 were euthanized at 3 months and 12 months; repair was compared to empty defects using histology and immunohistochemistry. Complementary in vitro experiments assessed transgene expression and chondrogenesis in marrow clots and fibrin gels. In a subsequent pilot study, repair at 3 months using a fibrin gel to encapsulate Ad.TGF-β1 was evaluated.ResultsAt 2 weeks, GFP expression was seen at variable levels within the cartilaginous lesion. At 3 months, there was a statistically significant improvement in healing of lesions receiving Ad.TGF-β1, although variability was high. At 12 months, there was no difference between the empty defects and those receiving Ad.TGF-β1 in overall score and cartilage score, but the bone healing score remained higher. Variability was again high. In vitro experiments suggested that variability reflected variable transduction efficiency and chondrogenic activity of the marrow clots; using fibrin gels instead of marrow provided more uniformity in healing.ConclusionsThis approach to improving the repair of osteochondral lesions holds promise but needs further refinement to reduce variability and provide a more robust outcome.