bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opto-E-Dura: a Soft, Stretchable ECoG Array for Multimodal, Multi-scale Neuroscience
Authors: Renz Aline F. , Lee Jihyun , Tybrandt Klas , Brzezinski Maciej , Lorenzo Dayra A. , Cheraka Mouna Cerra , Lee Jaehong , Helmchen Fritjof , Vörös Janos , Lewis Christopher M. 
Published: June 2020

AbstractSoft, stretchable materials hold great promise for the fabrication of biomedical devices due to their capacity to integrate gracefully with and conform to biological tissues. Conformal devices are of particular interest in the development of brain interfaces where rigid structures can lead to tissue damage and loss of signal quality over the lifetime of the implant. Interfaces to study brain function and dysfunction increasingly require multimodal access in order to facilitate measurement of diverse physiological signals that span the disparate temporal and spatial scales of brain dynamics. Here we present the Opto-e-Dura, a soft, stretchable, 16-channel electrocorticography array that is optically transparent. We demonstrate its compatibility with diverse optical and electrical readouts enabling multimodal studies that bridge spatial and temporal scales. The device is chronically stable for weeks, compatible with wide-field and 2-photon calcium imaging and permits the repeated insertion of penetrating multi-electrode arrays. As the variety of sensors and effectors realizable on soft, stretchable substrates expands, similar devices that provide large-scale, multimodal access to the brain will continue to improve fundamental understanding of brain function.
PD-L1hiplasmablasts limit the T cell response during the acute phase of parasite infections
Authors: Serrán Melisa Gorosito , Vernengo Facundo Fiocca , Almada Laura , Beccaria Cristian G , Canete Pablo F , Alegre Jonathan Rocco , Boari Jimena Tosello , Ramello Maria Cecilia , Wehrens Ellen , Cai Yeping , Zuniga I Elina , Montes Carolina L , Rodriguez Eva V Acosta , Cockburn Ian A. , Vinuesa Carola G , Gruppi Adriana 
Published: June 2020

ABSTRACTDuring infections with protozoan parasites or virus, T cell immunosuppression is generated simultaneously with a high B cell activation. Here, we show that inT. cruziinfection, all plasmablasts detected had higher surface expression of PD-L1, than other mononuclear cells. PD-L1hiplasmablasts were inducedin vivoin an antigen-specific manner and required help from Bcl-6+CD4+T cells. PD-L1hiexpression was not a characteristic of all antibody-secreting cells since plasma cells found during the chronic phase of infection express PD-L1 but at lower levels. PD-L1hiplasmablasts were also present in mice infected withPlasmodiumor with lymphocytic choriomeningitis virus, but not in mice with autoimmune disorders or immunized with T cell-dependent antigens. PD-L1hiplasmablasts suppressed T cell response, via PD-L1,in vitroandin vivo. Thus, this study reveals that extrafollicular PD-L1hiplasmablasts, which precede the germinal center (CG) response, are a suppressive population in infections that may influence T cell response.Brief summaryPathogens develop different strategies to settle in the host. We identified a plasmablats population induced by pathogens in acute infections which suppress T cell response.
A distributed network of noise-resistant neurons in the central auditory system
Authors: Souffi S. , Lorenzi C. , Huetz C. , Edeline J.-M. 
Published: June 2020

AbstractBackground noise strongly penalizes auditory perception of speech in humans or vocalizations in animals. Despite this, auditory neurons successfully detect and discriminate behaviorally salient sounds even when the signal-to-noise ratio is quite poor. Here, we collected neuronal recordings in cochlear nucleus, inferior colliculus, auditory thalamus, primary and secondary auditory cortex in response to vocalizations presented either against a stationary or a chorus noise. Using a clustering approach, we provide evidence that five behaviors exist at each level of the auditory system from neurons with high fidelity representations of the target, named target-specific neurons, mostly found in inferior colliculus and thalamus, to neurons with high fidelity representations of the noise, named masker-specific neurons mostly found in cochlear nucleus in stationary noise but in similar proportions in each structure in chorus noise. This indicates that the neural bases of auditory perception in noise rely on a distributed network along the auditory system.
Emotional Metacognition: Stimulus Valence Modulates Cardiac Arousal and Metamemory
Authors: Legrand Nicolas , Engen Sebastian Scott , Correa Camile Maria Costa , Mathiasen Nanna Kildahl , Nikolova Niia , Fardo Francesca , Allen Micah 
Published: June 2020

AbstractEmotion alters how we feel, see, and experience the world. In the domain of memory, the emotional valence and arousal of memorised stimuli can modulate both the acuity and content of episodic recall. However, no experiment has investigated whether arousal and valence also influence metacognition for memory (i.e., the process of self-monitoring memories). In a pre-registered study, we applied a novel psychophysiological design together with computational models of metacognition to assess the influence of stimulus valence and arousal on the sensitivity, bias, and efficiency of metamemory. To estimate the role of physiological arousal in mediating these effects, we recorded cardiac measures through pulse oximetry. We found that negative valence substantially decreased both memory performance and subjective confidence, in particular for low arousal words. Simultaneously, we found that emotional valence modulated both heart rate and heart-rate variability (HRV) during recognition memory. Exploratory trial-level analyses further revealed that subjective confidence was encoded in instantaneous heart-rate fluctuations and that this relationship was also modulated by emotional valence. Our results demonstrate that recognition memory and metacognition are influenced by the emotional valence of encoded items and that this correlation is in part related to cardiac activity.
Rich resource environment of fish farms facilitates phenotypic variation and virulence in an opportunistic fish pathogen
Authors: Pulkkinen Katja , Ketola Tarmo , Laakso Jouni , Mappes Johanna , Sundberg Lotta-Riina 
Published: June 2020

SummaryPhenotypic variation allows adaptation of opportunistic pathogens to variable conditions in the outside-host environment with strong effects on their epidemiology and pathogenicity in hosts. Here we found that the isolates of an opportunistic fish pathogenFlavobacterium columnarefrom fish farming environment had higher phenotypic variation between two morphotypes in growth, as compared to the isolates from the natural water environment. The rough morphotypes had higher growth rate than the rhizoid morphotypes especially in the higher resource concentrations and in the higher temperature, but only if the isolate was originating from the fish farms. Rhizoid morphotype was more virulent than the rough type regardless of their origin. However, the virulence of the rough type increased sharply with the size of the fish, and the bacterial isolates from the gills of diseased fish were rhizoid type, indicating a reversal of the rough morphotype into rhizoid in contact with the fish. The high growth rate of the rough morphotype combined with the morphotype reversibility could increase the probability of columnaris epidemics at fish farms. Our findings suggest that intensive farming imposes different selection pressures on bacterial survival in the outside-host environment and its transmission compared to the natural water environment.
Phox2a defines a developmental origin of the anterolateral system in mice and humans
Authors: Roome R. Brian , Bourojeni Farin B. , Mona Bishakha , Rastegar-Pouyani Shima , Blain Raphael , Dumouchel Annie , Salesse Charleen , Thompson W. Scott , Brookbank Megan , Gitton Yorick , Tessarollo Lino , Goulding Martyn , Johnson Jane E. , Kmita Marie , Chédotal Alain , Kania Artur 
Published: June 2020

SummaryAnterolateral system neurons relay pain, itch and temperature information from the spinal cord to pain-related brain regions, but the differentiation of these neurons and their specific contribution to pain perception remain poorly defined. Here, we show that virtually all mouse spinal neurons that embryonically express the autonomic system-associated Paired-like homeobox 2A (Phox2a) transcription factor innervate nociceptive brain targets, including the parabrachial nucleus and the thalamus. We define Phox2a anterolateral system neuron birth order, migration and differentiation, and uncover an essential role for Phox2a in the development of relay of nociceptive signals from the spinal cord to the brain. Finally, we also demonstrate that the molecular identity of Phox2a neurons is conserved in the human foetal spinal cord. The developmental expression of Phox2a as a uniting feature of anterolateral system neurons suggests a link between nociception and autonomic nervous system function.
Estimating the COVID-19 epidemic trajectory and hospital capacity requirements in South West England: a mathematical modelling framework
Authors: Booton Ross D. , MacGregor Louis , Vass Lucy , Looker Katharine J. , Hyams Catherine , Bright Philip D. , Harding Irasha , Lazarus Rajeka , Hamilton Fergus , Lawson Daniel , Danon Leon , Pratt Adrian , Wood Richard , Brooks-Pollock Ellen , Turner Katherine M.E. 
Published: June 2020

AbstractObjectivesTo develop a regional model of COVID-19 dynamics, for use in estimating the number of infections, deaths and required acute and intensive care (IC) beds using the South West of England (SW) as an example case.DesignOpen-source age-structured variant of a susceptible-exposed-infectious-recovered (SEIR) deterministic compartmental mathematical model. Latin hypercube sampling and maximum likelihood estimation were used to calibrate to cumulative cases and cumulative deaths.SettingSW at a time considered early in the pandemic, where National Health Service (NHS) authorities required evidence to guide localised planning and support decision-making.ParticipantsPublicly-available data on COVID-19 patients.Primary and secondary outcome measuresThe expected numbers of infected cases, deaths due to COVID-19 infection, patient occupancy of acute and IC beds and the reproduction (“R”) number over time.ResultsSW model projections indicate that, as of the 11th May 2020 (when ‘lockdown’ measures were eased), 5,793 (95% credible interval, CrI, 2,003 – 12,051) individuals were still infectious (0.10% of the total SW England population, 95%CrI 0.04 – 0.22%), and a total of 189,048 (95%CrI 141,580 – 277,955) had been infected with the virus (either asymptomatically or symptomatically), but recovered, which is 3.4% (95%CrI 2.5 – 5.0%) of the SW population. The total number of patients in acute and IC beds in the SW on the 11th May 2020 was predicted to be 701 (95%CrI 169 – 1,543) and 110 (95%CrI 8 – 464) respectively. The R value in SW England was predicted to be 2.6 (95%CrI 2.0 – 3.2) prior to any interventions, with social distancing reducing this to 2.3 (95%CrI 1.8 – 2.9) and lockdown/ school closures further reducing the R value to 0.6 (95CrI% 0.5 – 0.7).ConclusionsThe developed model has proved a valuable asset for local and regional healthcare services. The model will be used further in the SW as the pandemic evolves, and – as open source software – is portable to healthcare systems in other geographies.Future work/ applicationsOpen-source modelling tool available for wider use and re-use.Customisable to a number of granularities such as at the local, regional and national level.Supports a more holistic understanding of intervention efficacy through estimating unobservable quantities, e.g. asymptomatic population.While not presented here, future use of the model could evaluate the effect of various interventions on transmission of COVID-19.Further developments could consider the impact of bedded capacity in terms of resulting excess deaths.
Low rate of daily smokers in patients with symptomatic COVID-19
Authors: Miyara Makoto , Tubach Florence , Pourcher Valérie , Morélot-Panzini Capucine , Pernet Julie , Haroche Julien , Lebbah Said , Morawiec Elise , Gorochov Guy , Caumes Eric , Hausfater Pierre , Combes Alain , Similowski Thomas , Amoura Zahir 
Published: June 2020

AbstractBackgroundIdentification of prognostic factors in COVID-19 remains a global challenge. The role of smoking is still controversial.ObjectiveTo evaluate the rate of daily smokers in patients with COVID-19.MethodsCOVID-19 in-and outpatients from a large French university hospital were systematically interviewed for their smoking status, use of e-cigarette and nicotinic substitutes. The rates of daily smokers in in-and outpatients were compared to those in the 2019 French general population, after standardization for sex and age.ResultsThe inpatient group was composed of 340 patients, median age 66 years: 203 men (59.7%) and 137 women (40.3%), median age for both 66 years, with a daily smokers rate of 4.1 % CI95% [2.3–6.9] (5.4% of men, 2.2% of women). The outpatient group was composed of 139 patients, median age 44 years: 62 men (44.6%, median age 43 years), and 77 women (55.4%, median age 44 years). The daily smoker rate was 6.1 % CI 95% [2.7 - 11.6] (5.1% of men, 6.8% of women). In the 2019 French population, the daily smoker rate was 24.0% (27.5% of men, 20.7% of women). Among inpatients, daily smokers represented 2.2% and 3.4% of the 45 dead patients and of the 29 patients transferred to ICU, respectively.The rate of daily smokers was significantly lower in COVID-19 patients, as compared to that in the French general population after standardization by age and sex, with Standardized Incidence Ratios of 0.24 [0.12-0.48] for outpatients and 0.24 [0.14-0.40] for inpatients.ConclusionDaily smokers rate in patients with symptomatic COVID-19 is lower as compared to the general population
Delayed Discharges: Does Staff Well-Being Matter?
Authors: Ali Manhal , Salehnejad Reza 
Published: June 2020

AbstractDelayed discharges of patients from hospitals, also known as “bed–blocking” is a long standing policy concern. Such delays can increase hospital treatment costs and may also lead to poorer patient health and experience. Prior research indicates that external factors, such as, greater availability and better affordability of long term care associated with lower delays. Using theories from Economics, this study examines the role of within–hospital factors, namely, staff well–being in alleviating hospital delayed days. We use a new panel database of delays in all English hospital trusts from 2011/12 to 2014/15. Employing longitudinal count data models, the paper finds that staff well–being is associated with lower hospital delayed discharges controlling for long–term factors and management quality. The findings are robust to alternative methods and measures of delayed discharges.
Self-reported changes in energy balance behaviors during COVID-19 related home confinement: A Cross-Sectional Study
Authors: Bhutani Surabhi , Cooper Jamie A , Vandellen Michelle R 
Published: June 2020

ABSTRACTBackgroundThe COVID-19 pandemic has caused people to shelter-at-home for an extended period, resulting in a sudden rise in unstructured time. This unexpected disruption in everyday life has raised concerns about weight management, especially in high-risk populations of women and individuals with overweight and obesity. This study aimed to investigate the changes in behaviors that may impact energy intake and/or energy expenditure in U.S. adults during the home confinement.MethodsCross-sectional data from 1,779 adults were collected using an online Qualtrics survey between April 24th and May 4th, 2020. Self-reported data on demographics, eating behaviors, physical activity, sleep, screen time, takeout food intake, and food purchasing behaviors were collected. Chi-Square analyses were conducted to evaluate differences in the percent of participants reporting increasing, decreasing, or staying the same in each health behavior since the COVID-19 outbreak in their area. Each analysis was followed by comparing whether increases or decreases were more likely for each health behavior. Similar comparisons were made between male and female participants and between body mass index (BMI) categories.ResultsWe observed an increase in the intake of both healthy and energy-dense unhealthy foods and snacks during the home confinement. Participants also reported increases in sedentary activities and decrease in physical activity, alcohol intake, and consumption of takeout meals during this time. In women, several behavioral changes support greater energy intake and less energy expenditure than men. No clear difference in patterns was observed across BMI status.ConclusionAcute changes in behaviors underscore the significance of a sudden increase in unstructured time at home on potential weight gain. Our findings support the need to implement and support measures that promote strategies to maintain body weight and establish a methodology to collect body weight data at multiple time points to longitudinally assess the dynamic relationship between behaviors and body weight change.
Persistent SARS-CoV-2 replication in severe COVID-19
Authors: Folgueira María Dolores , Luczkowiak Joanna , Lasala Fátima , Pérez-Rivilla Alfredo , Delgado Rafael 
Published: June 2020

AbstractBackgroundThe diagnosis of SARS-CoV-2 infection is based on viral RNA detection by real-time RT-PCR (rRT-PCR) in respiratory samples. This detection can remain positive for weeks without implying virus viability.MethodsWe have performed cell culture to assess viral replication in 106 respiratory samples rRT-PCR positive for SARS-CoV-2 from 105 patients with COVID-19. Fifty were samples from 50 patients with mild forms of COVID-19 who did not require hospital admission. Fifty-six samples were obtained from 55 hospitalized patients with severe pneumonia. Samples were obtained at different time points covering the time from clinical diagnosis to the follow up during hospital care.ResultsIn 49 samples (49/106, 46.2%) a cytopathic effect (CPE) was detected in cell culture. Our study demonstrates that while in patients with mild COVID-19, viral viability is maintained in fact up to 10 days in patients with severe COVID-19 the virus can remain viable for up to 32 days after the onset of symptoms. Patients with severe COVID-19 as compared with mild cases, presented infective virus in a significantly higher proportion in samples with moderate or low viral load (Ct value > 26): 22/46 (47.8%) versus 7/38 (18.4%), (p<0.01), respectively.ConclusionsPersistent SARS-CoV-2 replication could be demonstrated in severe COVID-19 cases for periods up to 32 days after the onset of symptoms and even at high Ct values. COVID-19 severity is a more determining factor for viral viability than the time elapsed since the onset of symptoms or the Ct value obtained in the RT-PCR assay.
Loss of TP53 mediates suppression of Macrophage Effector Function via Extracellular Vesicles and PDL1 towards Resistance against Chemoimmunotherapy in B-cell malignancies
Authors: Izquierdo Elena , Vorholt Daniela , Sackey Benedict , Nolte Janica L. , Blakemore Stuart , Schmitz Jan , Barbarino Verena , Nickel Nadine , Bachurski Daniel , Lobastova Ludmila , Nikolic Milos , Michalik Michael , Brinker Reinhild , Merkel Olaf , Neuhaus René , Koch Maximilian , Knittel Gero , Frenzel Lukas , Reinhardt Hans Christian , Peifer Martin , Rebollido-Rios Rocio , Bruns Heiko , Krüger Marcus , Hallek Michael , Pallasch Christian 
Published: June 2020

SummaryChemoimmunotherapy (CIT) is the standard of care in B-cell malignancies. It is relying on synergistic effects of alkylating chemotherapy and monoclonal antibodies via secretory crosstalk with effector macrophages. Here, we observed that loss of p53 function mediates resistance to CIT by suppressing macrophage phagocytic function.Loss of p53 leads to an upregulation of PDL1 and an increased formation of extracellular vesicles (EVs). EVs directly inhibit macrophage phagocytosis by PDL1 surface expression. Suppression of phagocytic function by lymphoma cell-derived EVs could be abrogated by pre-incubation of EVs with anti-PDL1 antibodies, CRISPR-KO ofPDL1and abrogation of EV formation byRAB27A-KO in lymphoma cells. Immune checkpoint inhibition represents a viable strategy to overcome EV-mediated resistance to chemoimmunotherapy in lymphoma.SignificanceLoss ofTP53mediates cell autonomous resistance to genotoxic chemotherapy, moreover non-cell autonomous effects may cause therapy resistance mediated by the tumor microenvironment. We identify aTP53-dependent mechanism that mediates resistance to synergistic chemoimmunotherapy by increasing formation of EVs and expression of the PDL1 immune checkpoint. PDL1 on EVs is directly responsible for macrophage suppression, preventing the exertion of the essential effector function of antibody-dependent cellular phagocytosis. This novel mechanism of resistance is in turn targetable by PDL1 checkpoint inhibition. Enhanced EV-release and immune checkpoint expression in lymphoma are novel mechanisms of macrophage modulation in the lymphoma microenvironment. We provide a novel principle of resistance to chemoimmunotherapy (CIT) representing of immediate relevance to treatment of refractory B-cell lymphoma.HighlightsLoss ofTP53in B-cell lymphoma induces resistance towards chemoimmunotherapy (CIT) by inhibition of macrophage effector function through PDL1 upregulationLoss ofTP53increases formation of extracellular vesicles (EVs) carrying PDL1EVs inhibit antibody-mediated cellular phagocytosis (ADCP), a key macrophage effector function in CITTargeting PDL1 on EVs with immune checkpoint inhibitors overcomesTP53-mediated resistance to CIT
Microvillar cartography: a super-resolution single-molecule imaging method to map the positions of membrane proteins with respect to cellular surface topography
Authors: Ghosh Shirsendu , Alon Ronen , Alcover Andres , Haran Gilad 
Published: June 2020

AbstractWe introduce Microvillar Cartography (MC), a method to map proteins on cellular surfaces with respect to the membrane topography. The surfaces of many cells are not smooth, but are rather covered with various protrusions such as microvilli. These protrusions may play key roles in multiple cellular functions, due to their ability to control the distribution of specific protein assemblies on the cell surface. Thus, for example, we have shown that the T-cell receptor and several of its proximal signaling proteins reside on microvilli, while others are excluded from these projections. These results have indicated that microvilli can function as key signaling hubs for the initiation of the immune response. MC has facilitated our observations of particular surface proteins and their specialized distribution on microvillar and non-microvillar compartments. MC combines membrane topography imaging, using variable-angle total internal microscopy, with stochastic localization nanoscopy, which generates deep sub-diffraction maps of protein distribution. Since the method is based on light microscopy, it avoids some of the pitfalls inherent to electron-microscopy-based techniques, such as dehydration, carbon coating and immunogold clustering, and is amenable to future developments involving e.g. live-cell imaging. This Protocol details the procedures we developed for MC, which can be readily adopted to study a broad range of cell surface molecules and dissect their distribution within distinct surface assemblies under multiple cell activation states.