bluuebunny/crossref_metadata_2025_split huggingface dataset:
High complexity cellular barcoding and clonal tracing reveals stochastic and deterministic parameters of radiation resistance
Authors: Wursthorn Anne , Schwager Christian , Kurth Ina , Peitzsch Claudia , Herold-Mende Christel , Debus Jürgen , Abdollahi Amir , Nowrouzi Ali 
Published: October 2020

AbstractThe impact of functional heterogeneity in response to radiation therapy is poorly understood to the present. It remains elusive whether clonal selection of tumor cells in response to ionizing radiation (IR) is a deterministic or stochastic process. We applied high-resolution lentiviral cellular barcoding for quantitative clonal tracking and deconvolution of clonal dynamics in response to IR. Clonal tracking of over 400.000 HNSCC patient-derived tumor cells and the analyses of over 1500 million sequencing reads in clonogenic survival assays reveals that fractionated IR induced a strong selective pressure for clonal reduction. This significantly exceeded uniform clonal survival probabilities indicative for a strong clone-to clone difference within tumor cell lines. IR induced clonal reduction affected the majority of tumor cells ranging between 96-75% and correlated to the degree of radiation sensitivity. Survival and clonogenicity is characterized by an intensive clonal distortion and dominance of individual tumor cells. Survival to IR is driven by a deterministic clonal selection of a smaller population which commonly survives radiation, while increased clonogenic capacity is a result of clonal competition of cells which have been selected stochastically. A 2-fold increase in radiation resistance results in a 4-fold (p<0.05) higher deterministic clonal selection showing that the ratio of these parameters is amenable to radiation sensitivity which correlates to prognostic biomarkers of HNSCC. Evidence for the existence of a rare subpopulation with an intrinsically radiation resistant phenotype commonly surviving IR was found at a frequency of 0.6-3.3% (p<0.001, FDR 3%). With cellular barcoding we introduce a novel functional heterogeneity associated qualitative readout for tracking dynamics of clonogenic survival in response to radiation. This enables the quantification of intrinsically radiation resistant tumor cells from patient samples and reveals the contribution of stochastic and deterministic clonal selection processes in response to IR.
Enrichment for Cases of African-American Patients with Pathogenic TTR V142I Variant in the TOPCAT Trial
Authors: Papoutsidakis Nikolaos , Gandotra Neeru , Miller Edward , Murray Michael F. , Scharfe Curt , Jacoby Daniel 
Published: October 2020

AbstractTransthyretin cardiac amyloidosis (ATTR-CA) is a treatable cause of heart failure with a hereditary form that disproportionally affects patients of West African ancestry. The clinical management of ATTR-CA has dramatically changed in the past five years, with rapidly evolving diagnostic approaches and life-prolonging therapies. The TTR variant c.424G>A, p.V142I (aka V122I) is pathogenic and occurs in 3-4% of individuals of West African ancestry. Despite its high frequency, V142I ATTR-CA is often unrecognized due to variable clinical penetrance, limited knowledge, and lack of inexpensive non-invasive diagnostic tests. Currently unknown is which TTR V142I carriers will progress to heart failure and at what age. Here we studied the prevalence of TTR V142I among a random cohort of African-American patients enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT). Three of the 26 HFpEF patients (11.5%) studied carried the pathogenic TTR V142I variant. While we cannot conclude at this point that TTR V142I was the underlying cause of the clinical phenotype in these patients, our results suggest that rapid TTR V142I genotyping, in combination with heart imaging, could have immediate clinical utility for identifying under-/mis-diagnosed HFpEF patients.
Microscale dynamics of electrophysiological markers of epilepsy
Authors: Yang Jimmy C. , Paulk Angelique C. , Lee Sang Heon , Ganji Mehran , Soper Daniel J. , Salami Pariya , Cleary Daniel , Simon Mirela , Maus Douglas , Lee Jong Woo , Nahed Brian , Jones Pamela , Cahill Daniel P. , Cosgrove Garth Rees , Chu Catherine J. , Williams Ziv , Halgren Eric , Dayeh Shadi , Cash Sydney S. 
Published: October 2020

AbstractObjectiveInterictal discharges (IIDs) and high frequency oscillations (HFOs) are neurophysiologic biomarkers of epilepsy. In this study, we use custom poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) microelectrodes to better understand their microscale dynamics.MethodsElectrodes with spatial resolution down to 50µm were used to record intraoperatively in 30 subjects. For IIDs, putative spatiotemporal paths were generated by peak-tracking, followed by clustering. For HFOs, repeating patterns were elucidated by clustering similar time windows. Fast events, consistent with multi-unit activity (MUA), were covaried with either IIDs or HFOs.ResultsIIDs seen across the entire array were detected in 93% of subjects. Local IIDs, observed across <50% of the array, were seen in 53% of subjects. IIDs appeared to travel across the array in specific paths, and HFOs appeared in similar repeated spatial patterns. Finally, microseizure events were identified spanning 50-100µm. HFOs covaried with MUA, but not with IIDs.ConclusionsOverall, these data suggest micro-domains of irritable cortex that form part of an underlying pathologic architecture that contributes to the seizure network.SignificanceMicroelectrodes in cases of human epilepsy can reveal dynamics that are not seen by conventional electrocorticography and point to new possibilities for their use in the diagnosis and treatment of epilepsy.HighlightsPEDOT:PSS microelectrodes with at least 50µm spatial resolution uniquely reveal spatiotemporal patterns of markers of epilepsyHigh spatiotemporal resolution allows interictal discharges to be tracked and reveal cortical domains involved in microseizuresHigh frequency oscillations detected by microelectrodes demonstrate localized clustering on the cortical surface
ATTENTIONAL MODULATION OF NEURAL DYNAMICS IN TACTILE PERCEPTION OF COMPLEX REGIONAL PAIN SYNDROME PATIENTS
Authors: Defina Serena , Niedernhuber Maria , Shenker Nicholas , Brown Christopher , Bekinschtein Tristan A. 
Published: October 2020

AbstractBody perceptual disturbances are an increasingly acknowledged set of symptoms and possible clinical markers of Complex Regional Pain Syndrome (CRPS), but the neurophysiological and neurocognitive changes that underlie them are still far from being clear. We adopted a multivariate and neurodynamical approach to the analysis of EEG modulations evoked by touch to highlight differences between patients and healthy controls, between affected and unaffected side of the body, and between “passive” (i.e. no task demands and equiprobable digit stimulation) and “active” tactile processing (i.e. where a digit discrimination task was administered and spatial probability manipulated). When correct identifications are considered, an early reduction in cortical decodability (28–56 ms) distinguishes CRPS patients from healthy volunteers. However, when error trials are included in the classifier’s training, there is an unexpected increased decodability in the CRPS group compared to healthy volunteers (280–320 ms). These group differences in neural processing seemed to be driven by the affected rather than the unaffected side. We corroborated these findings with several exploratory analyses of neural representation dynamics and behavioural modelling, highlighting the need for single participant analyses. Although several limitations impacted the robustness and generalizability of these comparisons, the proposed analytical approach yielded promising insights (as well as possible biomarkers based on neural dynamics) into the relatively unexplored alterations of tactile decision-making and attentional control mechanisms in chronic CRPS.
Novel Machine-Learned Approach for COVID-19 Resource Allocation: A Tool for Evaluating Community Susceptibility
Authors: Kale Neil 
Published: October 2020

AbstractDespite worldwide efforts to develop an effective COVID vaccine, it is quite evident that initial supplies will be limited. Therefore, it is important to develop methods that will ensure that the COVID vaccine is allocated to the people who are at major risk until there is a sufficient global supply. Herein, I developed a machine-learning tool that could be applied to assess the risk in communities based on social, medical, and lifestyle risk factors. As a “proof of concept,” I modeled COVID risk in the Massachusetts communities using 29 risk factors, including the prevalence of preexisting comorbid conditions like COPD and social factors such as racial composition. Of the 29 factors, 14 were found to be significant (p < 0.1) indicators: poverty, food insecurity, lack of high school education, lack of health insurance coverage, premature mortality, population, population density, recent population growth, Asian percentage, high-occupancy housing, and preexisting prevalence of cancer, COPD, overweightness, and heart attacks. The machine-learning approach finds the 9 highest risk communities in the state of Massachusetts: Lynn, Brockton, Revere, Randolph, Lowell, New Bedford, Everett, Waltham, and Fitchburg. The 5 most at-risk counties are Suffolk, Middlesex, Bristol, Norfolk, and Plymouth. With appropriate data, the tool could evaluate risk in other communities, or even enumerate individual patient susceptibility. A ranking of communities by risk may help policymakers ensure equitable allocation of limited doses of the COVID vaccine.
Physiological and psychosocial correlates of cancer related fatigue
Authors: Brownstein Callum G , Twomey Rosemary , Temesi John , Wrightson James G , Martin Tristan , Medysky Mary E. , Culos-Reed S. Nicole , Millet Guillaume Y 
Published: October 2020

ABSTRACTCancer-related fatigue (CRF) is a common and distressing symptom of cancer and its treatments that may persist for years following treatment completion in approximately one-third of cancer survivors. Despite its high prevalence, little is known about the pathophysiology of CRF. Using a comprehensive group of physiological and psychosocial variables, the aim of the present study was to identify correlates of CRF in a heterogenous group of cancer survivors. Ninety-three cancer survivors (51 fatigued, 42 non-fatigued, with grouping based on validated cut-off scores derived from The Functional Assessment of Chronic Illness Therapy - Fatigue scale) completed assessments of performance fatigability (i.e. the change in maximal force-generating capacity, contractile function and capacity of the central nervous system to activate muscles caused by cycling exercise), cardiopulmonary exercise testing, venous blood samples for whole blood cell count and inflammatory markers and body composition. Participants also completed questionnaires measuring demographic, treatment-related, and psychosocial variables. The results showed that performance fatigability (decline in muscle strength during exercise), time-to-task-failure, peak oxygen uptake , tumor necrosis factor-α (TNF-α), body fat percentage and lean mass index were associated with CRF severity. Performance fatigability, , TNF-α and age explained 35% of the variance in CRF severity. Furthermore, those with clinically-relevant CRF reported more pain, more depressive symptoms, less social support, and were less physically active than non-fatigued cancer survivors. Given the association between CRF and numerous physical activity related measures, including performance fatigability, cardiorespiratory fitness, and anthropometric measures, the present study identifies potential biomarkers by which the mechanisms underpinning the effect of physical activity interventions on CRF can be investigated.
Leave-one-out cross-validation and linear modeling of visuospatial memory to predict long-term motor skill retention in individuals with and without chronic stroke: A short report
Authors: VanGilder Jennapher Lingo , Hooyman Andrew , Bosch Pamela R. , Schaefer Sydney Y. 
Published: October 2020

AbstractMotor learning is fundamental to motor rehabilitation outcomes and has been associated with visuospatial memory function in previous studies. Current predictive models of motor recovery of individuals with stroke generally exclude cognitive measures, overlooking the connection between motor learning and visuospatial memory. Recent work has demonstrated that a clinical test of visuospatial memory (Rey-Osterrieth Complex Figure Delayed Recall) may predict one-month skill learning in older adults, but if this relationship persists in individuals with chronic stroke remains unknown. The purpose of this short report was to extend these findings by evaluating the extent these test scores impacted prediction in older adults and determine if this relationship generalized to individuals with stroke pathology. To address these questions, we trained two regression models (one including Delayed Recall scores and one without) using data from non-stroke older adults. To determine the extent to which Delayed Recall test scores impacted prediction accuracy of one-month skill learning in older adults, we used leave-one-out cross-validation to evaluate the prediction error between models. To determine if this predictive relationship persisted in individuals with chronic ischemic stroke, we then tested each trained model on an independent stroke dataset. Results indicated that in both stroke and non-stroke datasets, inclusion of Delayed Recall scores explained significantly more variance of one-month skill performance than models that included age, education, and baseline motor performance alone. This proof-of-concept suggests that the relationship between delayed visuospatial memory and one-month motor skill performance generalizes to individuals with chronic stroke and supports the idea that visuospatial testing may provide prognostic insight into motor rehabilitation outcomes.
Polygamous breeding system identified in the distylous genusPsychotria:P. manillensisin the Ryukyu archipelago, Japan
Authors: Watanabe Kenta , Shimizu Akira , Sugawara Takashi 
Published: October 2020

AbstractDistyly is a genetic polymorphism composed of long- and short-styled flowers in a population. The evolutionary breakdown of distyly has been reported in many taxa, and mainly involves a shift toward monomorphism or dioecism. However, a shift toward monoecism has not been reported in distylous species.Psychotria(Rubiaceae), one of the world largest genera, consists of distylous species and their derivatives. In our preliminary study, however, we identified some monoecious individuals in a population ofPsychotria manillensis. To understand the breeding system and reproductive biology ofP. manillensis, we investigated floral traits, open fruit set, and flower visitors, and performed hand pollination and bagging experiments in five populations of Okinawa and Iriomote islands, Ryukyu Islands, Japan. The populations ofP. manillensiswere composed mainly of monoecious individuals (54%), followed by female (30%), male (14%), and hermaphroditic (2%) individuals at the time of flower collection. Of the collected flowers, 93% were functionally unisexual (male or female), whereas only 6.5% were perfect (hermaphroditic). However, some individuals changed sex mainly towards increasing femaleness during the flowering period. Moreover, 35% of the studied plants changed their sexual expression over the years.P. manillensisshowed self-compatibility and no agamospermy. The fruit set under open pollination varied among populations and years (1.8–21.9%), but it was significantly higher than that of auto-selfing (0.68–1.56%). Wasps and flies were the main flower visitors and probably the main pollinators of the species. In conclusion,P. manillensiswas revealed to be polygamous, involving monoecious, female, male, and hermaphroditic individuals. This is the first report of the polygamous breeding system not only in the genusPsychotria, but also in all heterostylous taxa.
Macroevolutionary Analyses Provide New Evidences of Phasmid Wings Evolution as a Reversible Process
Authors: Forni Giobbe , Martelossi Jacopo , Valero Pablo , Hennemann Frank H. , Conle Oskar , Luchetti Andrea , Mantovani Barbara 
Published: October 2020

AbstractThe concept that complex ancestral traits can never be re-acquired after their loss has grown popular since its initial formulation and it’s often referred to as Dollo’s law. Nonetheless, several macroevolutionary evidences - along with molecular ones - suggest instances where complex phenotypes could have been lost throughout a clade evolutionary history and subsequently reverted to their former state in derived lineages. One of the first and most notable rejection of Dollo’s law is represented by wing evolution in phasmids: this polyneopteran order of insects - which comprises stick and leaf insects - has played a central role in initiating a long-standing debate on the topic. In this study, a novel and comprehensive time-tree - including over 300 Phasmatodea species - is used as a framework for investigating wing’s evolutionary patterns in the clade. Despite accounting for several possible biases and sources of uncertainty, macroevolutionary analyses consistently support a dynamic and reversible evolution of wings, with multiple transitions to ancestral states taking place after their loss. Our findings suggest that wings and flight are decoupled from Phasmatodea diversification dynamics and that brachyptery is an unstable state, unless when co-opted for non-aerodynamic adaptations. We also explored how different assumptions of wings’ reversals probability could impact their inference: we found that until reversals are assumed to be over 30 times more unlikely than losses, they are consistently retrieved despite uncertainty in tree and model parameters. Our findings demonstrate that wings evolution can be a reversible and dynamic process in phasmids and contribute to shape our understanding of how complex phenotypes evolve.
A Boolean Model of the Formation of Tumour Associated Macrophages in anin-vitroModel of Chronic Lymphocytic Leukaemia
Authors: Marku Malvina , Raynal Flavien , Verstraete Nina , Domagala Marcin , Madrid-Mencía Miguel , Poupot Mary , Fournié Jean-Jacques , Ysebaert Loïc , Pancaldi Vera 
Published: October 2020

AbstractThe tumour microenvironment is the collection of cells in and surrounding cancer cells in a tumour including a variety of immune cells, especially neutrophils and monocyte-derived macrophages. In a tumour setting, macrophages encompass a spectrum between a tumour-suppressive (M1) or tumour-promoting (M2) state. The biology of macrophages found in tumours (Tumour Associated Macrophages) remains unclear, but understanding their impact on tumour progression is highly important. In this paper, we perform a comprehensive analysis of a macrophage polarization network, following two lines of enquiry:(i)we reconstruct the macrophage polarization network based on literature, extending it to include important stimuli in a tumour setting, and(ii)we build a dynamical model able to reproduce macrophage polarization in the presence of different stimuli, including the contact with cancer cells. Our simulations recapitulate the documented macrophage phenotypes and their dependencies on specific receptors and transcription factors, while also elucidating the formation of a special type of tumour associated macrophages in anin-vitromodel of chronic lymphocytic leukaemia. This model constitutes the first step towards elucidating the cross-talk between immune and cancer cells inside tumours, with the ultimate goal of identifying new therapeutic targets that could control the formation of tumour associated macrophages in patients.
Immersive virtual reality interferes with default head-trunk coordination strategies in young children
Authors: Miehlbradt Jenifer C. , Cuturi Luigi F. , Zanchi Silvia , Gori Monica , Micera Silvestro 
Published: October 2020

AbstractThe acquisition of postural control is an elaborate process, which relies on the balanced integration of multisensory inputs. Current models suggest that young children rely on an ‘en-block’ control of their upper body before sequentially acquiring a segmental control around the age of 7, and that they resort to the former strategy under challenging conditions. While recent works suggest that a virtual sensory environment alters visuomotor integration in healthy adults, little is known about the effects on younger individuals.Here we show that this coordination pattern is disrupted by an immersive virtual reality framework where a steering role is assigned to the trunk, which causes 6- to 8-year-olds to employ an ill-adapted segmental strategy. These results provide an alternate trajectory of motor development and emphasize the immaturity of postural control at these ages.
A Connectome-wide Functional Signature of Trait Anger
Authors: Justin Kim M. , Elliott Maxwell L. , Knodt Annchen R. , Hariri Ahmad R. 
Published: October 2020

AbstractPast research on the brain correlates of trait anger has been limited by small sample sizes, a focus on relatively few regions-of-interest, and poor test-retest reliability of functional brain measures. To address these limitations, we conducted a data-driven analysis of variability in connectome-wide general functional connectivity, which has good test-retest reliability, in a sample of 1,048 young adult volunteers. Multi-dimensional matrix regression analysis showed that individual differences in self-reported trait anger maps onto variability in the whole-brain functional connectivity patterns of three brain regions that serve action-related functions: bilateral supplementary motor area (SMA) and the right lateral frontal pole. Follow-up seed-based analysis confirmed that high trait anger is associated with hyperconnectivity between these three regions and the somatomotor network as well as hyperconnectivity and hypoconnectivity between SMA and default mode and visual networks, respectively. Supplementary targeted analyses based on theoretical and empirical grounds further revealed that high trait anger is associated with hyperconnectivity between the amygdala and dorsomedial prefrontal cortex, dorsal anterior cingulate cortex, and striatum. These patterns suggest that the dispositional tendency to more easily experience frustration and anger is associated with variability in the functional connectivity of brain networks supporting somatomotor, affective, self-referential, and visual information processes. The emergence of action-related brain regions from our connectome-wide analysis is consistent with trait anger as reflecting a greater propensity to provoked action.