bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data Visualization for Surgical Informed Consent to Communicate Personalized Risks and Patient Preferences
Authors: Gisladottir Undina , Nakikj Drashko , Jhunjhunwala Rashi , Brat Gabriel , Gehlenborg Nils 
Published: March 2020

STRUCTURED ABSTRACTObjectiveIdentify key elements of an effective visualization method for communicating personalized surgical risks to patients.BackgroundCurrently, there is no consensus on which risks should be communicated during the informed consent process and how. Furthermore, patient preferences are often not considered during the consent process. These inefficiencies can lead to non-beneficial outcomes and raise the potential for legal implications. To address the limitations of the informed consent process, we propose a visual consent tool (VCT) that incorporates patient preferences and communicates personalized risks to patients using data visualization.MethodsTo understand how patients perceive risk visualizations and their role in the informed consent discussion, we gathered feedback on visualizations by conducting semi-structured interviews during postoperative visits. Thematic analysis was performed to identify major themes. Iterative evaluation and consolidation of the major themes were performed with domain experts.ResultsA total of 20 patients were interviewed for this study with a median age of 59 (sd = 14). The thematic analysis revealed factors that influence the perception of risk, of risk visualizations, and the usefulness of the proposed VCT. We found that patients preferred VCT over the current methods and had different preferences for risk visualization. Further, our findings suggest that surgical concerns of patients were not in line with existing risk calculators.ConclusionWe were able to identify key elements that influence effective risk communication in the perioperative setting. We found that patient preference is variable and should influence choices for risk presentation and visualization.
The effects of containment measures in the Italian outbreak of COVID-19
Authors: Supino M. , d’Onofrio A. , Luongo F. , Occhipinti G. , Co A. Dal 
Published: March 2020

AbstractBackgroundThe COVID-19 pandemic is spreading worldwide. Italy emerged early on as the country with the largest outbreak outside Asia. The outbreak in Northern Italy demonstrates that it is fundamental to contain the virus’ spread at a very early stage of diffusion. At later stages, no containment measure, even if strict, can prevent the saturation of the hospitals and of the intensive care units in any country.Methods and ResultsHere we show that it is possible to predict when the intensive care units will saturate, within a few days from the first cases of COVID-19 intensive care patients. Using early counts of intensive care patients, we predict the saturation for Lombardy, Italy.ConclusionsGovernments should use the Italian outbreak as a precedent and implement appropriate containment measures to prevent the saturation of their intensive care units and protect their population, also, and above all, in anticipation of a possible second rapid spread of infections.
Pathophysiological subtypes of Alzheimer’s disease based on cerebrospinal fluid proteomics
Authors: Tijms Betty M. , Gobom Johan , Reus Lianne , Jansen Iris , Hong Shengjun , Dobricic Valerija , Kilpert Fabian , Kate Mara ten , Barkhof Frederik , Tsolaki Magda , Verhey Frans RJ , Popp Julius , Alvarez Pablo Martinez-Lage , Vandenberghe Rik , Lleó Alberto , Molinuevo José Luís , Engelborghs Sebastiaan , Bertram Lars , Lovestone Simon , Streffer Johannes , Vos Stephanie , Bos Isabelle ,   ADNI, Blennow Kaj , Scheltens Philip , Teunissen Charlotte E. , Zetterberg Henrik , Visser Pieter Jelle 
Published: March 2020

AbstractAlzheimer’s disease (AD) is biologically heterogeneous, and detailed understanding of the processes involved in patients is critical for development of treatments. Cerebrospinal fluid (CSF) contains hundreds of proteins, with concentrations reflecting ongoing (patho)physiological processes. This provides the opportunity to study many biological processes at the same time in patients. We studied whether AD biological subtypes can be detected in cerebrospinal fluid (CSF) proteomics using the dual clustering technique non-negative matrix factorization. In two independent cohorts (EMIF-AD MBD and ADNI) we found that 705 (77% of 913 tested) proteins differed between AD (defined as having abnormal amyloid, n=425) and controls (defined as having normal CSF amyloid and tau and intact cognition, n=127). Using these proteins for data-driven clustering, we identified within each cohorts three robust pathophysiological AD subtypes showing 1) hyperplasticity and increased BACE1 levels; 2) innate immune activation; and 3) blood-brain barrier dysfunction with low BACE1 levels. In both cohorts, the majority of individuals was labelled as having subtype 1 (80, 36% in EMIF-AD MBD; 117, 59% in ADNI), 71 (32%) in EMIF-AD MBD and 41 (21%) in ADNI were labelled as subtype 2, 72 (32%) in EMIF-AD MBD and 39 (20%) individuals in ADNI were labelled as subtype 3. Genetic analyses showed that all subtypes had an excess of genetic risk for AD (all p>0.01). Additional pathological comparisons that were available for a subset in ADNI only further showed that subtypes showed similar severity of AD pathology, and did not differ in the frequencies of co-pathologies, providing further support that these differences truly reflect AD heterogeneity. Compared to controls all non-demented AD individuals had increased risk to show clinical progression, and compared to subtype 1, subtype 2 showed faster progression to after correcting for age, sex, level of education and tau levels (HR (95%CI) subtype 2 vs 1 = 2.5 (1.2, 5.1), p = 0.01), and subtype 3 at trend level (HR (95%CI) = 2.1 (1.0, 4.4)). Together, these results demonstrate the value of CSF proteomics to study biological heterogeneity in AD patients, and suggest that subtypes may require tailored therapy.
On the assessment of more reliable COVID-19 infected number: the italian case
Authors: Tradigo Giuseppe , Guzzi Pietro Hiram , Veltri Pierangelo 
Published: March 2020

AbstractCOVID-19 (SARS-CoV-2) is the most recent pandemic disease the world is currently managing. It started in China at the end of 2019, and it is diffusing throughout Italy, one of the most affected countries, and it is currently spreading through European countries and USA. Patients affected by COVID-19 are identified employing medical swabs applied mainly to (i) citizens with COVID-19 symptoms such as flu or high temperature, or (ii) citizens that had contacts with COVID-19 patients. A percentage of COVID-19 affected patients needs hospitalisation, whereas a portion needs to be treated in Intensive Care Units (ICUs).Nevertheless, it is a matter of current intuition that COVID-19 infected citizens are more than those detected, and sometime the infection is detected too late. Thus there are many efforts in both tracking people activities as well as diffusing low cost reliable COVID-19 tests for early detection.Starting from mortality rates of diseases caused by viruses in the same family (e.g. MERS, SARS, H1N1), we study the relations between the number of COVID-19 infections and the number of deaths, through Italian regions. We thus assess several infections being higher than the ones currently measured. We thus focus on the characterisation of the pandemic diffusion by estimating the infected number of patients versus the number of death. We use such an estimated number of infections, to foresee the effects of restriction actions adopted by governments to constrain virus diffusion. We finally think that our model can support the healthcare system to react when COVID-19 is increasing.
A Simple Mathematical Model for Estimating the Inflection Points of COVID-19 Outbreaks
Authors: Ma Zhanshan Sam 
Published: March 2020

AbstractBackgroundExponential-like infection growths leading to peaks (which could be the inflection points or turning points) are usually the hallmarks of infectious disease outbreaks including coronaviruses. To predict the inflection points, i.e., inflection time (Tmax) & maximal infection number (Imax) of the novel coronavirus (COVID-19), we adopted a trial and error strategy and explored a series of approaches from simple logistic modeling (that has an asymptomatic line) to sophisticated tipping point detection techniques for detecting phase transitions but failed to obtain satisfactory results.MethodInspired by its success in diversity-time relationship (DTR), we apply the PLEC (power law with exponential cutoff) model for detecting the inflection points of COVID-19 outbreaks. The model was previously used to extend the classic species-time relationship (STR) for general DTR (Ma 2018), and it has two “secondary” parameters (computed from its 3 parameters including power law scaling parameter w, taper-off parameter d to overwhelm virtually exponential growth ultimately, and a parameter c related to initial infections): one that was originally used for estimating the potential or ‘dark’ biodiversity is proposed to estimate the maximal infection number (Imax) and another is proposed to determine the corresponding inflection time point (Tmax).ResultsWe successfully estimated the inflection points [Imax, Tmax] for most provinces (≈85%) in China with error rates <5% in both Imax and Tmax. We also discussed the constraints and limitations of the proposed approach, including (i) sensitive to disruptive jumps, (ii) requiring sufficiently long datasets, and (iii) limited to unimodal outbreaks.
Non-Parametric Analysis of Inter-Individual Relations Using an Attention-Based Neural Network
Authors: Morita Takashi , Toyoda Aru , Aisu Seitaro , Kaneko Akihisa , Suda-Hashimoto Naoko , Adachi Ikuma , Matsuda Ikki , Koda Hiroki 
Published: March 2020

AbstractSocial network analysis, which has been widely adopted in animal studies over the past decade, enables the revelation of global characteristic patterns of animal social systems from pairwise inter-individual relations. Animal social networks are typically drawn based on geometric proximity and/or frequency of social behaviors (e.g., grooming), but the appropriate metric for inter-individual relationship is not clear, especially when prior knowledge on the species/data is limited.In this study, researchers explored a non-parametric analysis of inter-individual relations using a neural network with the attention mechanism, which plays a central role in natural language processing. The high interpretability of the attention mechanism and flexibility of the entire neural network allow for automatic detection of inter-individual relations included in the raw data, without requiring prior knowledge/assumptions about what modes/types of relations are included in the data. For these case studies, three-dimensional location data collected from simulated agents and real Japanese macaques were analyzed.The proposed method successfully recovered the latent relations behind the simulated data and discovered female-oriented relations in the real data, which are in accordance with previous generalizations about the macaque social structure.The proposed method does not exploit any behavioral patterns that are particular to Japanese macaques, and researchers can use it for location data of other animals. The exibility of the neural network would also allow for its application to a wide variety of data with interacting components, such as vocal communication.
Iron acquisition system ofSphingobiumsp. strain SYK-6, a degrader of lignin-derived aromatic compounds
Authors: Fujita Masaya , Sakumoto Taichi , Tanatani Kenta , Yu Hong Yang , Mori Kosuke , Kamimura Naofumi , Masai Eiji 
Published: March 2020

AbstractIron, an essential element for all organisms, acts as a cofactor of enzymes in bacterial degradation of recalcitrant aromatic compounds. The bacterial family, Sphingomonadaceae comprises various degraders of recalcitrant aromatic compounds; however, little is known about their iron acquisition system. Here, we investigated the iron acquisition system in a model bacterium capable of degrading lignin-derived aromatics,Sphingobiumsp. strain SYK-6. Analyses of SYK-6 mutants revealed that FiuA (SLG_34550), a TonB-dependent receptor (TBDR), was the major outer membrane iron transporter. Three other TBDRs encoded by SLG_04340, SLG_04380, and SLG_10860 also participated in iron uptake, andtonB2(SLG_34550), one of the sixtonBcomprising the Ton complex which enables TBDR-mediated transport was critical for iron uptake. The ferrous iron transporter FeoB (SLG_36840) played an important role in iron uptake across the inner membrane. The promoter activities of most of the iron uptake genes were induced under iron-limited conditions, and their regulation is controlled by SLG_29410 encoding the ferric uptake regulator, Fur. AlthoughfeoB, among all the iron uptake genes identified is highly conserved in Sphingomonad strains, the outer membrane transporters seem to be diversified. Elucidation of the iron acquisition system promises better understanding of the bacterial degradation mechanisms of aromatic compounds.
panRGP: a pangenome-based method to predict genomic islands and explore their diversity
Authors: Bazin Adelme , Gautreau Guillaume , Médigue Claudine , Vallenet David , Calteau Alexandra 
Published: March 2020

AbstractMotivationHorizontal gene transfer (HGT) is a major source of variability in prokaryotic genomes. Regions of Genome Plasticity (RGPs) are clusters of genes located in highly variable genomic regions. Most of them arise from HGT and correspond to Genomic Islands (GIs). The study of those regions at the species level has become increasingly difficult with the data deluge of genomes. To date no methods are available to identify GIs using hundreds of genomes to explore their diversity.ResultsWe present here the panRGP method that predicts RGPs using pangenome graphs made of all available genomes for a given species. It allows the study of thousands of genomes in order to access the diversity of RGPs and to predict spots of insertions. It gave the best predictions when benchmarked along other GI detection tools against a reference dataset. In addition, we illustrated its use on Metagenome Assembled Genomes (MAGs) by redefining the borders of theleuXtRNA hotspot, a well studied spot of insertion inEscherichia coli. panRPG is a scalable and reliable tool to predict GIs and spots making it an ideal approach for large comparative studies.AvailabilityThe methods presented in the current work are available through the following software:https://github.com/labgem/PPanGGOLiN. Detailed results and scripts to compute the benchmark metrics are available athttps://github.com/axbazin/panrgp_supdata.Contactvallenet@genoscope.cns.frandacalteau@genoscope.cns.frSupplementary informationNone.
Action enhances predicted touch
Authors: Thomas Emily R. , Yon Daniel , de Lange Floris P. , Press Clare 
Published: March 2020

AbstractIt is widely believed that predicted tactile action outcomes are perceptually attenuated. The present experiments determined whether predictive mechanisms always generate attenuation, or instead can enhance perception – as typically observed in sensory cognition domains outside of action. We manipulated probabilistic expectations in a paradigm often used to demonstrate tactile attenuation. Participants produced actions and subsequently rated the intensity of forces on a passive finger. Experiment 1 confirmed previous findings that action outcomes are perceived less intensely than passive stimulation, but demonstrated more intense perception when active finger stimulation was removed. Experiments 2 and 3 manipulated prediction explicitly and found that expected touch during action is perceivedmoreintensely than unexpected touch. Computational modelling suggested that expectations increase the gain afforded to expected tactile signals. These findings challenge a central tenet of prominent motor control theories and demonstrate that sensorimotor predictions do not exhibit a qualitatively distinct influence on tactile perception.Statement of RelevancePerception of expected action outcomes is thought to be attenuated. Such a mechanism may be adaptive because surprising inputs are more useful - e.g., signalling the need to take new courses of action - and is thought to explain why we cannot tickle ourselves and unusual aspects of action and awareness in clinical populations. However, theories outside of action purport that predicted events are perceptually facilitated, allowing us to generate largely accurate representations of our noisy sensory world. We do not know whether action predictions really alter perception differently from other predictions because different manipulations have been performed. Here we perform similar manipulations and demonstrate that action predictions can enhance, rather than attenuate, touch. We thereby demonstrate that action predictions may not have a qualitatively distinct influence on perception, such that we must re-examine theories concerning how predictions influence perception across domains and clinical theories based upon their assumptions.
Localized inhibition in theDrosophilamushroom body
Authors: Amin Hoger , Suárez-Grimalt Raquel , Vrontou Eleftheria , Lin Andrew C. 
Published: March 2020

AbstractMany neurons show compartmentalized activity, in which activity does not spread readily across the cell, allowing input and output to occur locally. However, the functional implications of compartmentalized activity for the wider neural circuit are often unclear. We addressed this problem in theDrosophilamushroom body, whose principal neurons, Kenyon cells, receive feedback inhibition from a large, non-spiking interneuron called APL. We used local stimulation and volumetric calcium imaging to show that APL inhibits Kenyon cells in both their dendrites and axons, and that both activity in APL and APL’s inhibitory effect on Kenyon cells are spatially localized, allowing APL to differentially inhibit different mushroom body compartments. Applying these results to theDrosophilahemibrain connectome predicts that individual Kenyon cells inhibit themselves via APL more strongly than they inhibit other individual Kenyon cells. These findings reveal how cellular physiology and detailed network anatomy can combine to influence circuit function.
SPEARS: Standard Performance Evaluation of Ancestral Reconstruction through Simulation
Authors: Manching H. , Wisser R. J. 
Published: March 2020

MotivationAncestral haplotype maps provide useful information about genomic variation and biological processes. Reconstructing the descendent haplotype structure of homologous chromosomes, particularly for large numbers of individuals, can help with characterizing the recombination landscape, elucidating genotype-to-phenotype relationships, improving genomic predictions and more. Inferring haplotype maps from sparse genotype data is an efficient approach to whole-genome haplotyping, but this is a non-trivial problem. A standardized approach is needed to validate whether haplotype reconstruction software, conceived population designs and existing data for a given population provides accurate haplotype information for further inference.ResultsWe introduce SPEARS, a pipeline for whole simulation-based appraisal of genome-wide ancestral haplotype inference. The pipeline generates virtual genotypes (truth data) with real-world missing data structure. It then proceeds to mimic analysis in practice, capturing sources of error due to imputation and reconstruction of ancestral haplotypes. Standard metrics allow researchers to assess which features of haplotype structure or regions of the genome are sufficiently accurate for analysis and reporting. Haplotype maps for 1,000 outcross progeny from a multi-parent population of maize is used to demonstrate SPEARS.Availabilityhttps://github.com/maizeatlas/spears
Loss ofdmrt1restores female fates in the absence ofcyp19a1abut notrbpms2
Authors: Romano Shannon , Kaufman Odelya H. , Marlow Florence L. 
Published: March 2020

AbstractSex determination and differentiation is a complex process regulated by multiple factors, including factors from the germline or surrounding somatic tissue. In zebrafish, sex-determination begins with establishment of a bipotential gonad that undergoes sex-specific differentiation and maintenance to form the functional adult gonad. However, the relationships among these factors are not fully understood. Here we identify potential Rbpms2 targets and apply genetic epistasis experiments to decipher the genetic hierarchy of regulators of sex-specific differentiation. We provide evidence that the critical female factor,rbpms2is epistatic to the male factordmrt1in terms of adult sex. Moreover, Rbpms2’s role in promoting female fates extends beyond repression of Dmrt1, as Rbpms2 is essential for female differentiation even in the absence of Dmrt1. In contrast, female fates can be restored in mutants lackingcyp19a1ain the absence ofdmrt1.Taken together this work indicates that Cyp19a1a-mediated suppression of Dmrt1 is key to establish a bipotential gonad and initiate female fate acquisition, possibly by promotingrbpms2. Then, after female fate specification, Cyp19a1a regulates subsequent oocyte maturation and sustains female fates independent of Dmrt1 repression.Author SummaryWe show thatcyp19a1a-mediated suppression ofdmrt1establishes a bipotential gonad and female fate acquisition, possibly throughrbpms2which is required for female fates, even in the absence of Dmrt1.
Immortalised hippocampal astrocytes from 3xTG-AD mice fail to support BBB integrityin vitro: Role of extracellular vesicles in glial-endothelial communication
Authors: Kriaučiūnaitė Karolina , Kaušylė Aida , Pajarskienė Justina , Tunaitis Virginijus , Lim Dmitry , Verkhratsky Alexei , Pivoriūnas Augustas 
Published: March 2020

AbstractImpairments of the blood brain barrier (BBB) and vascular dysfunction contribute to Alzheimer’s disease (AD) from the earliest stages. However, the effects of AD-affected astrocytes on the BBB remain largely unexplored. In the present study we created an in vitro BBB using human immortalised endothelial cells in combination with immortalised astroglial cell lines from the hippocampus of 3xTG-AD and wild-type mice (3Tg-iAstro and WT-iAstro, respectively). We found that co-culturing endothelial monolayers with WT-iAstro up-regulates expression of endothelial tight junction proteins (claudin-5, occludin, ZO-1) and increases the trans-endothelial electrical resistance (TEER). In contrast, co-culturing with 3Tg-iAstro does not affect expression of tight junction proteins and does not change the TEER of endothelial monolayers. The same in vitro model has been used to evaluate the effects of extracellular vesicles (EVs) derived from the WT-iAstro and 3Tg-iAstro. The EVs derived from WT-iAstro increased TEER and up-regulated expression of tight junction proteins, whereas EVs from 3Tg-iAstro were ineffective. In conclusion, we show for the first time that immortalised hippocampal astrocytes from 3xTG-AD mice exhibit impaired capacity to support BBB integrity in vitro through paracrine mechanisms and may represent an important factor underlying vascular abnormalities during development of AD.