bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring brain integrity using MRI: a novel biomarker for Alzheimer’s disease using T2 relaxometry
Authors: Wearn Alfie R. , Nurdal Volkan , Saunders-Jennings Esther , Knight Michael J. , Isotalus Hanna K. , Dillon Serena , Tsivos Demitra , Kauppinen Risto A. , Coulthard Elizabeth J. 
Published: May 2020

AbstractEarly Alzheimer’s disease diagnosis is vital for development of disease-modifying therapies. Prior to significant loss of brain tissue, several microstructural changes take place as a result of Alzheimer’s pathology. These include deposition of amyloid, tau and iron, as well as altered water homeostasis in tissue and some cell death. T2 relaxation time, a quantitative MRI measure, is sensitive to these changes and may be a useful non-invasive, early marker of tissue integrity which could predict conversion to dementia. The different factors that affect T2 may cause it to increase, as in the case of free water, or decrease, as in the case of iron, amyloid and tau. Thus, tissue affected by early Alzheimer’s disease could become more heterogeneous yet show no change in average T2. We hypothesise that T2 heterogeneity in regions affected early in Alzheimer’s disease (hippocampus and thalamus) may present a sensitive early marker of microstructural changes in Alzheimer’s disease.In this cohort study, we tested 97 healthy older controls, 49 people with mild cognitive impairment (MCI) and 10 with a diagnosis of Alzheimer’s disease. All participants underwent structural MRI including multi-echo sequence for assessing quantitative T2. Cognitive change over one year was assessed in participants with MCI. Hippocampus and thalamus were automatically masked using ASHS and Freesurfer, respectively. T2 distributions were modelled using log-logistic distribution giving measures of log-median value (midpoint; T2μ) and distribution width (heterogeneity; T2σ).We show an increase in heterogeneity (T2σ; p<.0001) in MCI compared to healthy controls, which was not seen with midpoint (T2μ; p=.149) in the hippocampus and thalamus. Hippocampal T2 heterogeneity predicted cognitive decline over one year in MCI participants (p=.018), but midpoint (p=.132) and volume (p=.315) did not. Age affects T2, but the effects described here are significant even after correcting for age.We show that T2 heterogeneity can identify subtle changes in microstructural integrity of brain tissue in prodromal Alzheimer’s disease. We describe a new model that takes into account the competing effects of factors that both increase and decrease T2. These two opposing forces act in opposition and mean that previous human literature focusing on midpoint T2 has obscured the true potential of T2 as an early marker of Alzheimer’s disease. In fact, T2 heterogeneity outperforms midpoint and volumetry in predicting cognitive decline in those with MCI. We propose that T2 heterogeneity reflects microstructural integrity with potential to be a widely used early biomarker of Alzheimer’s disease.
Derivation and validation of a prognostic model for predicting in-hospital mortality in patients admitted with COVID-19 in Wuhan, China: the PLANS (Platelet Lymphocyte Age Neutrophil Sex) model
Authors: Li Jiong , Chen Yuntao , Chen Shujing , Wang Sihua , Zhang Dingyu , Wang Junfeng , Postmus Douwe , Zeng Hesong , Qin Guoyou , Shen Yin , Jiang Jinjun , Yu Yongfu 
Published: May 2020

AbstractOBJECTIVETo develop and validate a prognostic model for in-hospital mortality in COVID-19 patients using routinely collected demographic and clinical characteristics.DESIGNMulticenter, retrospective cohort study.SETTINGJinyintan Hospital, Union Hospital, and Tongji Hosptial in Wuhan, China.PARTICIPANTSA pooled derivation cohort of 1008 COVID-19 patients from Jinyintan Hospital, Union Hospital in Wuhan and an external validation cohort of 1031 patients from Tongji Hospital in Wuhan, China.MAIN OUTCOME MEASURESOutcome of interest was in-hospital mortality, treating discharged alive from hospital as the competing event. Fine-Gray models, using backward elimination for inclusion of predictor variables and allowing non-linear effects of continuous variables, were used to derive a prognostic model for predicting in-hospital mortality among COVID-19 patients. Internal validation was implemented to check model overfitting using bootstrap approach. External validation to a separate hospital was implemented to evaluate the generalizability of the model.RESULTSThe derivation cohort was a case-mix of mild-to-severe hospitalized COVID-19 patients (n=1008, 43.6% females, median age 55). The final model (PLANS), including five predictor variables of platelet count, lymphocyte count, age, neutrophil count, and sex, had an excellent predictive performance (optimism-adjusted C-index: 0.85, 95% CI: 0.83 to 0.87; averaged calibration slope: 0.95, 95% CI: 0.82 to 1.08). Internal validation showed little overfitting. External validation using an independent cohort (n=1031, 47.8% female, median age 63) demonstrated excellent predictive performance (C-index: 0.87, 95% CI: 0.85 to 0.89; calibration slope: 1.02, 95% CI: 0.92 to 1.12). The averaged predicted survival curves were close to the observed survival curves across patients with different risk profiles.CONCLUSIONSThe PLANS model based on the five routinely collected demographic and clinical characteristics (platelet count, lymphocyte count, age, neutrophil count, and sex) showed excellent discriminative and calibration accuracy in predicting in-hospital mortality in COVID-19 patients. This prognostic model would assist clinicians in better triaging patients and allocating healthcare resources to reduce COVID-19 fatality.
National estimates of critical care capacity in 54 African countries
Authors: Craig Jessica , Kalanxhi Erta , Hauck Stephanie 
Published: May 2020

AbstractThe COVID-19 pandemic is an emerging threat across the African continent where critical care capacity is underdeveloped or unknown. In this paper, we describe national critical care capacity including number of ICU beds, number of ventilators, and number of physician and non-physician anesthesia providers for 54 African countries. Data was compiled from a variety of resources including World Bank databases, local and international news media, government reports, local healthcare workers, and published scientific literature. Overall, data on number of physicians, hospital beds, and ICU beds were available for over 90% of countries. Data on number of ventilators, number of physician anesthesia providers (PAP) and non-PAP were available for 46 (85%), 47 (87%) and 37 (69%) countries, respectively. Across all 54 countries included in the analysis, there was an average of 3.10 ICU beds and 0.97 ventilators per 100,000 people, and an average of 2.42 total (physician and non-physician) anesthesia providers per 100,000 people. The purpose of this analysis was to fill in knowledge gaps around current critical care capacity across the African continent and to inform national, regional, and international pandemic preparation and response efforts.
Measuring Metacognition of Direct and Indirect Parameters of Voluntary Movement
Authors: Arbuzova Polina , Peters Caroline , Röd Lukas , Koß Christina , Maurer Heiko , Maurer Lisa K. , Müller Hermann , Verrel Julius , Filevich Elisa 
Published: May 2020

AbstractWe can make exquisitely precise movements without the apparent need for conscious monitoring. But can we monitor the low-level movement parameters when prompted? And what are the mechanisms that allow us to monitor our movements? To answer these questions, we designed a semi-virtual ball throwing task. On each trial, participants first threw a virtual ball by moving their arm (with or without visual feedback, or replayed from a previous trial) and then made a two-alternative forced choice on the resulting ball trajectory. They then rated their confidence in their decision. We measured metacognitive efficiency usingmeta-d’/d’ and compared it between different informational domains of the first-order task (motor, visuomotor or visual information alone), as well as between two different versions of the task based on different parameters of the movement: proximal (position of the arm) or distal (resulting trajectory of the ball thrown).We found that participants were able to monitor their performance based on distal motor information as well as when proximal information was available. Their metacognitive efficiency was also equally high in conditions with different sources of information available. The analysis of correlations across participants revealed an unexpected result: while metacognitive efficiency correlated between informational domains (which would indicate domain-generality of metacognition), it did not correlate across the different parameters of movement. We discuss possible sources of this discrepancy and argue that specific first-order task demands may play a crucial role in our metacognitive ability and should be considered when making inferences about domain-generality based on correlations.
Enzymatic dissociation induces transcriptional and proteotype bias in brain cell populations
Authors: Mattei Daniele , Ivanov Andranik , van Oostrum Marc , Pantelyushin Stanislav , Richetto Juliet , Mueller Flavia , Beffinger Michal Matheus , Schellhammer Linda , vom Berg Johannes , Wollscheid Bernd , Beule Dieter , Paolicelli Rosa Chiara , Meyer Urs 
Published: May 2020

AbstractDifferent cell isolation techniques exist for transcriptomic and proteotype profiling of brain cells. Here, we provide a systematic investigation of the influence of different cell isolation protocols on transcriptional and proteotype profiles in mouse brain tissue by taking into account single-cell transcriptomics of brain cells, proteotypes of microglia and astrocytes, and flow cytometric analysis of microglia. We show that standard enzymatic digestion of brain tissue at 37°C induces profound and consistent alterations in the transcriptome and proteotype of neuronal and glial cells, as compared to an optimized mechanical dissociation protocol at 4°C. These findings emphasize the risk of introducing technical biases and biological artefacts when implementing enzymatic digestion-based isolation methods for brain cell analyses.
A Novel System for The Comprehensive Collection of Nonvolatile Molecules from Human Exhaled Breath
Authors: Chen Dapeng , Bryden Wayne A , McLoughlin Michael 
Published: May 2020

AbstractCharacterization of nonvolatile molecules in exhaled breath particles can be used for respiratory disease monitoring and diagnosis. Conventional methods for the collection of nonvolatile molecules in breath heavily rely on the physical properties of exhaled breath particles. Strategies taking advantage of their chemical properties have not yet been explored. In the present study, we developed a column system in which the surface chemistry between organic nonvolatile molecules and octadecyl carbon chain was exploited for the comprehensive collection of metabolites, lipids, and proteins. We demonstrated that the collection system had the capture efficiency of 99% and the capacity to capture representative nonvolatile molecules. The collection system was further evaluated using human subjects and proteins collected from human exhaled breath were characterized and identified using gel electrophoresis and bottom-up proteomics. The identified 303proteins from mass spectrometry were further searched against reported bronchoalveolar lavage fluid proteomes and it was shown that 60 proteins have the tissue origin of lower respiratory airways. In summary, we demonstrate that our collection system can collect nonvolatile molecules from human exhaled breath in an efficient and comprehensive manner and has the potential to be used for the study of respiratory diseases.
Automated Quantification of Mitochondrial Fragmentation in an In-Vitro Parkinson’s Disease Model
Authors: Rees Daniel J. , Roberts Luke , Carisi M. Carla , Morgan Alwena H. , Brown M. Rowan , Davies Jeffrey S. 
Published: May 2020

AbstractNeuronal mitochondrial fragmentation is a phenotype exhibited in models of neurodegeneration such as Parkinson’s Disease. Delineating the dysfunction in mitochondrial dynamics found in diseased states can aid our understanding of underlying mechanisms for disease progression and possibly identify novel therapeutic approaches. Advances in microscopy and the availability of intuitive open-access software has accelerated the rate of image acquisition and analysis, respectively. These developments allow routine biology researchers to rapidly turn hypotheses into results. In this protocol, we describe the utilisation of cell culture techniques, high-content imaging (HCI), and subsequent open-source image analysis pipeline for the quantification of mitochondrial fragmentation in the context of an in-vitro Parkinson’s Disease model.
Cell size statistics in cell lineages and population snapshots with different growth regimes and division strategies
Authors: Totis Niccolò , Nieto César , Küper Armin , Vargas-García César , Singh Abhyudai , Waldherr Steffen 
Published: May 2020

AbstractGrowing populations of bacteria control their growth and division reaching narrow distributions of cell-sizes. In this paper we explored how different combinations of growth regimes and division mechanisms lead to different cell-size statistics in these populations. Deterministic and stochastic modeling were used to describe the size distribution of a population of cells that is observed from two different perspectives: as single cell lineages, i.e. random paths in the lineage tree, or as snapshots, at given times, of a population in which all descendants of a single ancestor cell are observed. Our time-dependent approaches allowed us to obtain both the transient dynamics and the steady state values for the main statistical moments of the cell-size distribution. Also, we established mathematical relationships among the statistics in the two considered perspectives, thus improving our knowledge of how cells control their growth and proliferation.
Spinal motoneuron firing properties mature from rostral to caudal during post-natal development of the mouse
Authors: Smith Calvin C. , Brownstone Robert M. 
Published: May 2020

AbstractAltricial mammals are born with immature nervous systems comprised of circuits that do not yet have the neuronal properties and connectivity required to produce future behaviours. During the critical period of post-natal development, neuronal properties are tuned to participate in functional circuits. In rodents, cervical motoneurons are born prior to lumbar motoneurons, and spinal cord development follows a sequential rostro-caudal sequence. Here we asked whether birth order is reflected in the post-natal development of electrophysiological properties. We show that motoneurons of both segments have similar properties at birth and follow the same developmental profile, with maximal firing increasing and excitability decreasing into the 3rdpost-natal week. However, these maturative processes occur in cervical prior to lumbar motoneurons, correlating to the timing of arrival of descending systems. These results suggest that motoneuron properties do not mature by cell autonomous mechanisms alone, but rather depend on developing descending and spinal circuits.
Single-cell RNA-sequencing of peripheral neuroblastic tumors reveals an aggressive transitional cell state at the junction of an adrenergic-mesenchymal transdifferentiation trajectory
Authors: Yuan Xiaojun , Seneviratne Janith A. , Du Shibei , Xu Ying , Chen Yijun , Jin Qianya , Jin Xuanxuan , Balachandran Anushree , Huang Shihao , Xu Yanli , Zhai Yue , Lu Liumei , Tang Mengjie , Dong Yushuang , Cheung Belamy B. , Marshall Glenn M. , Shi Weiyang , Zhang Chao , Carter Daniel R. 
Published: May 2020

AbstractPeripheral neuroblastic tumors (PNTs) are the most common extracranial solid tumors in early childhood. They represent a spectrum of neural crest derived tumors including neuroblastoma, ganglioneuroblastoma and ganglioneuroma. PNTs exhibit heterogeneity due to interconverting malignant cell states described as adrenergic/nor-adrenergic or mesenchymal/neural crest cell in origin. The factors determining individual patient levels of tumor heterogeneity, their impact on the malignant phenotype, and the presence of other cell states are unknown. Here, single-cell RNA-sequencing analysis of 4267 cells from 7 PNTs demonstrated extensive transcriptomic heterogeneity. Trajectory modelling showed that malignant neuroblasts move between adrenergic and mesenchymal cell states via a novel state that we termed a “transitional” phenotype. Transitional cells are characterized by gene expression programs linked to a sympathoadrenal development, and aggressive tumor phenotypes such as rapid proliferation and tumor dissemination. Among primary bulk tumor patient cohorts, high expression of the transitional gene signature was highly predictive of poor prognosis when compared to adrenergic and mesenchymal expression patterns. High transitional gene expression in neuroblastoma cell lines identified a similar transitional H3K27-acetylation super-enhancer landscape, supporting the concept that PNTs have phenotypic plasticity and transdifferentiation capacity. Additionally, examination of PNT microenvironments, found that neuroblastomas contained low immune cell infiltration, high levels of non-inflammatory macrophages, and low cytotoxic T lymphocyte levels compared with more benign PNT subtypes. Modeling of cell-cell signaling in the tumor microenvironment predicted specific paracrine effects toward the various subtypes of malignant cells, suggesting further cell-extrinsic influences on malignant cell phenotype. Collectively, our study reveals the presence of a previously unrecognized transitional cell state with high malignant potential and an immune cell architecture which serve both as potential biomarkers and therapeutic targets.
Profiling of small non-coding RNAs across cellular and biofluid compartments: implications for multiple sclerosis immunopathology
Authors: Zheleznyakova Galina Yurevna , Piket Eliane , Needhamsen Maria , Hagemann-Jensen Michael , Ekman Diana , Khademi Mohsen , Nimer Faiez Al , Scicluna Patrick , Faridani Omid R , Olsson Tomas , Piehl Fredrik , Jagodic Maja 
Published: May 2020

AbstractMultiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), is associated with dysregulation of microRNAs (miRNA). We here analyzed all classes of small non-coding RNAs (sncRNAs) in matching peripheral blood mononuclear cells (PBMCs), plasma, cerebrospinal fluid (CSF) cells and cell-free CSF from relapsing-remitting (RRMS, n=12 in relapse, n=11 in remission), secondary progressive (SPMS, n=6) MS patients and non-inflammatory and inflammatory neurological disease controls (NINDC, n=11; INDC, n=5). We show widespread changes in small nuclear, nucleolar, transfer RNAs and miRNAs. In CSF cells, 133/133 and 115/117 differentially expressed sncRNAs are increased in RRMS relapse compared to remission and RRMS compared to NINDC, respectively. In contrast, 65/67 differentially expressed PBMC sncRNAs are decreased in RRMS compared to NINDC. The striking contrast between periphery and CNS suggests that sncRNA-mediated mechanisms, including alternative splicing, RNA degradation and mRNA translation, regulate the transcriptome of pathogenic cells primarily in the target organ.
SYNAPTIC RELEASE POTENTIATION AT AGING AUDITORY RIBBON SYNAPSES
Authors: Peineau Thibault , Belleudy Séverin , Pietropaolo Susanna , Bouleau Yohan , Dulon Didier 
Published: May 2020

ABSTRACTAge-related hidden hearing loss is often described as a cochlear synaptopathy that results from a progressive degeneration of the inner hair cell (IHC) ribbon synapses. The functional changes occurring at these synapses during aging are not fully understood. Here, we characterized this aging process in IHCs of C57BL/6J mice, a strain which is known to carry a cadherin23 mutation and experiences early hearing loss with age. These mice, while displaying a large increase in auditory brainstem thresholds due to 50 % loss of IHC synaptic ribbons at middle age (postnatal day 365), paradoxically showed enhanced acoustic startle reflex suggesting a hyperacusis-like response. The auditory defect was associated with a large shrinkage of the IHCs’ cell body and a drastic enlargement of their remaining presynaptic ribbons which were facing enlarged postsynaptic AMPAR clusters. Presynaptic Ca2+microdomains and the capacity of IHCs to sustain high rates of exocytosis were largely increased, while on the contrary the expression of the fast repolarizing BK channels, known to negatively control transmitter release, was decreased. This age-related synaptic plasticity in IHCs suggested a functional potentiation of synaptic transmission at the surviving synapses, a process that could partially compensate the decrease in synapse number and underlie hyperacusis.
Dopamine influences attentional rate modulation in Macaque posterior parietal cortex
Authors: van Kempen Jochem , Brandt Christian , Distler Claudia , Bellgrove Mark A. , Thiele Alexander 
Published: May 2020

AbstractCognitive neuroscience has made great strides in understanding the neural substrates of attention, but our understanding of its neuropharmacology remains incomplete. Although dopamine has historically been studied in relation to frontal functioning, emerging evidence suggests important dopaminergic influences in parietal cortex. We recorded single- and multi-unit activity whilst iontophoretically administering dopaminergic agonists and antagonists while rhesus macaques performed a spatial attention task. Out of 88 units, 50 revealed activity modulation by drug administration. Dopamine inhibited firing rates according to an inverted-U shaped dose-response curve and increased gain variability. Dopamine modulated attention-related rate changes and Fano Factors in broad and narrow-spiking units, respectively. D1 receptor antagonists diminished firing rates according to a monotonic function and interacted with attention modulating gain variability in broad-spiking units. Finally, both drugs decreased the pupil light reflex. These data show that dopamine shapes neuronal responses and modulates attentional processing in parietal cortex.