bluuebunny/crossref_metadata_2025_split huggingface dataset:
An acoustic platform for single-cell, high-throughput measurements of the viscoelastic properties of cells
Authors: Romanov Valentin , Silvani Giulia , Zhu Huiyu , Cox Charles D , Martinac Boris 
Published: September 2020

ABSTRACTCellular processes including adhesion, migration and differentiation are governed by the distinct mechanical properties of each cell. Importantly, the mechanical properties of individual cells can vary depending on local physical and biochemical cues in a time-dependent manner resulting in significant inter-cell heterogeneity. While several different methods have been developed to interrogate the mechanical properties of single cells, throughput to capture this heterogeneity remains an issue. While new high-throughput techniques are slowly emerging, they are primarily aimed at characterizing cells in suspension, whereas high-throughput measurements of adherent cells have proven to be more challenging. Here, we demonstrate single-cell, high-throughput characterization of adherent cells using acoustic force spectroscopy. We demonstrate that cells undergo marked changes in viscoelasticity as a function of temperature, the measurements of which are facilitated by a closed microfluidic culturing environment that can rapidly change temperature between 21 °C and 37 °C. In addition, we show quantitative differences in cells exposed to different pharmacological treatments specifically targeting the membrane-cytoskeleton interface. Further, we utilize the high-throughput format of the AFS to rapidly probe, in excess of 1000 cells, three different cell-lines expressing different levels of a mechanosensitive protein, Piezo1, demonstrating the ability to differentiate between cells based on protein expression levels.
Unique prediction of developmental psychopathology from genetic and familial risk
Authors: Loughnan Robert , Palmer Clare E. , Makowski Carolina , Thompson Wesley K. , Barch Deanna M. , Jernigan Terry L. , Dale Anders M. , Fan Chun Chieh 
Published: September 2020

ABSTRACTBackgroundEarly detection is critical for easing the rising burden of psychiatric disorders. However, the specificity of psychopathological measurements and genetic predictors is unclear among youth.MethodsWe measured associations between genetic risk for psychopathology (polygenic risk scores (PRS) and family history (FH) measures) and a wide range of behavioral measures in a large sample (n=5204) of early adolescent participants (9-11 years) from the Adolescent Brain and Cognitive Development (ABCD) StudySM. Associations were measured both with and without taking into consideration shared variance across measures of genetic risk.ResultsPolygenic risk for Attention Deficit Hyperactivity Disorder (ADHD) and depression (DEP) shared many significant associations with externalizing, internalizing and psychosis-related behaviors. However, when accounting for all measures of genetic and familial risk these two PRS also showed clear, unique patterns of association: the DEP PRS showed significantly stronger associations with somatic complaints and depression symptoms; whereas the ADHD PRS showed stronger associations with ADHD symptoms, impulsivity and prodromal psychosis. The Schizophrenia PRS showed a unique negative association with performance on cognitive tasks measuring fluid abilities, such as working memory and executive function, that was not accounted for by other measures of genetic risk. FH accounted for unique variability in behavior above and beyond PRS and vice versa with FH measures explaining a greater proportion of unique variability compared to the PRS.ConclusionOur results indicate that, among youth, many behaviors show shared genetic influences; however, there is also specificity in the profile of emerging psychopathologies for individuals with high genetic risk for particular disorders. This may be useful for quantifying early, differential risk for psychopathology in development.FundingThe ABCD Study is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, U24DA041147, U01DA041093, and U01DA041025. A full list of supporters is available at https://abcdstudy.org/federal-partners.html. R.L was supported by Kavli Innovative Research Grant under award number 2019-1624. C.F. was supported by grant R01MH122688 and RF1MH120025 funded by the National Institute for Mental Health (NIMH).
Small-form-factor LED-based light application surface for indocyanine green-mediated antibacterial photothermal therapy
Authors: Nikinmaa Sakari , Moilanen Niina , Sorsa Timo , Rantala Juha , Alapulli Heikki , Kotiranta Anja , Auvinen Petri , Kankuri Esko , Meurman Jukka , Pätilä Tommi 
Published: September 2020

ABSTRACTWe present here a small-form-factor LED-based antimicrobial photothermal therapy (aPTT) applicator surface, and its clinical feasibility as well as efficacy for administration of indocyanine green (ICG)-assisted aPTT to the dental plaque.Fifteen healthy adults were assigned to this four-day randomized study. After rinsing with ICG, 100J/cm2 of 810 nm light was applied to the aPTT-treatment area. Plaque area and gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) were measured, and plaque bacteriomes before and after the study were analyzed using 16S rRNA sequencing.aPTT administration was preformed successfully and plaque-specifically with the applicator surface. Total plaque area and endpoint MMP-8 levels were reduced on the aPTT-treatment side. aPTT reduced Streptococcus, Acinetobacteria, Capnocytophaga, and Rothia bacteria species in plaques. The applicator surface is feasible for aPTT self-administration, targets therapy to dental plaque, reduces plaque forming bacteria and exerts anti-inflammatory and –proteolytic effects.
Why women choose abortion through telemedicine outside the formal health sector in Germany? A mixed-methods study
Authors: Killinger Kristina , Günther Sophie , Atay Hazal , Gomperts Rebecca , Endler Margit 
Published: September 2020

AbstractIntroductionIn April 2019 the abortion telemedicine service Women on Web (WoW) opened their helpdesk to Germany and saw a progressive rise in consultations. Our aim was to understand the motivations, and perceived barriers to access, for women who choose telemedicine abortion outside the formal health sector in Germany.MethodsWe conducted a parallel convergent mixed-methods study among 1090 women in Germany, who requested medical abortion through WoW between January 1st and December 31st, 2019. We performed a cross-sectional study of data contained in online consultations and a content analysis of 108 email texts. Analysis was done until saturation; results were merged, and triangulation was used to validate results.ResultsFrequent reported reasons for choosing telemedicine abortion in the consultation forms were “I need to keep the abortion a secret from my partner or family” (48%) and “I would rather keep my abortion private” (48%). The content analysis developed two main themes and seven subsidiary categories: 1) internal motivations for seeking telemedicine abortion encompassing i) autonomy, ii) perception of external threat, iii) shame and stigma, and 2) external barriers to formal abortion care, encompassing: (iv) financial stress, v) logistic barriers to access vi) provider attitudes, and vii) vulnerability of foreigners). The findings in the quantitative and qualitative analysis were consistent.ConclusionWomen in Germany who choose telemedicine abortion outside the formal health sector do so both from a place of empowerment and a place of disempowerment. Numerous barriers to abortion access exist in the formal sector which are of special relevance to vulnerable groups such as adolescents and undocumented immigrants.Key message pointsWhen Women on Web, an abortion telemedicine service operating outside the formal health care sector, opened in Germany in April 2019, 1205 women consulted the service in the first nine months.Women who choose telemedicine abortion do so both from a position of empowerment, for reasons of autonomy, and from a position of disempowerment and lack of autonomy.Numerous barriers to abortion access, as permitted by German law exist in the formal health sector, which may most impact vulnerable groups such as adolescents, women with low financial means, and undocumented immigrants.
The impact of COVID-19 restriction measures on loneliness among older adults in Austria
Authors: Stolz Erwin , Mayerl Hannes , Freidl Wolfgang 
Published: September 2020

AbstractBackgroundTo halt the spread of COVID-19, Austria implemented a 7-week ‘shut-down’ of public life in March/April 2020 which was followed by a gradual withdrawal of these restriction measures in May/June 2020. We expect that the ensuing reduction in social contacts led to increased loneliness among older adults (60+).MethodsWe conducted three analyses to assess the association between COVID-19 public health restriction measures and loneliness: (1) A comparison between pre-pandemic (SHARE: 2013–2017) and pandemic (May 2020) levels of loneliness (UCLA-3 scale), (2) an analysis of the correlation between being affected by COVID-19 restriction measures and loneliness based on cross-sectional survey data from early May 2020, and (3) a longitudinal analysis of weekly changes in loneliness (Corona panel data) from late March to early June 2020.ResultsWe found (1) loneliness levels to have increased in 2020 in comparison with previous years, (2) an association between the number of restriction measures older adults reported to be affected from and loneliness, and (3) that loneliness was higher during ‘shut-down’ compared to the subsequent re-opening phase, particularly among those who live alone.DiscussionOur results provide evidence that COVID-19 restriction measures in Austria have indeed resulted in increased levels of loneliness among older adults. However, these effects seem to be short-lived, and thus we do not expect strong negative consequences for older adults’ mental health downstream. Nonetheless, effects of longer and/or repeated future restriction measures aiming at social distancing should be closely monitored.
Prevention of EAE by PEGylated Antigenic Peptides
Authors: Pfeil Jennifer , Simonetti Mario , Lauer Uta , von Thülen Bianca , Durek Pawel , Poulsen Christina , Pawlowska Justyna , Kröger Matthias , Krähmer Ralf , Leenders Frank , Hoffmann Ute , Hamann Alf 
Published: September 2020

AbstractThe treatment of autoimmune disorders such as multiple sclerosis (MS) so far relies largely on the use of non-specific immunosuppressive drugs, which are not able to cure the disease. Presently, approaches to induce antigen-specific tolerance e.g. by peptide-based tolerogenic “inverse” vaccines regain interest. We previously have shown that coupling of peptides to carriers can enhance their capacity to induce regulatory T cellsin vivo. We here investigated in an experimental autoimmune encephalomyelitis (EAE) model for chronic MS (MOG C57BL/6) whether the tolerogenic potential of immunodominant myelin T cell epitopes can be improved by conjugation to the synthetic carrier polyethylene glycol (PEG). Indeed, preventive administration of the PEGylated antigenic peptide could almost completely protect mice from EAE development, which was accompanied by reduced immune cell infiltration in the central nervous system (CNS). Depletion of Tregs abrogated the protective effect indicating that Tregs play a crucial role in induction of antigen-specific tolerance in EAE. Treatment during the acute phase was safe and did not induce immune activation. However, treatment at the peak of disease was not affecting the disease course, suggesting that either induction of Tregs is not occurring in the highly inflamed situation, or that the immune system is refractory to regulation in this condition. Thus, PEGylation of antigenic peptides is an effective and feasible strategy to improve tolerogenic (Treg-inducing) peptide-based vaccines, but application in overt disease might require modifications or combination therapies that simultaneously suppress effector mechanisms.
MorphOT: Transport-based interpolation between EM maps with UCSF ChimeraX
Authors: Ecoffet Arthur , Poitevin Frédéric , Dao Duc Khanh 
Published: September 2020

AbstractMotivationCryogenic Electron-Microscopy offers the unique potential to capture conformational heterogeneity, by solving multiple 3D classes that co-exist within a single cryo-EM image dataset. To investigate the extent and implications of such heterogeneity, we propose to use an optimal-transport based metric to interpolate barycenters between EM maps and produce morphing trajectories. While standard linear interpolation mostly fails to produce realistic transitions, our method yields continuous trajectories that displace densities to morph one map into the other, instead of blending them.ImplementationOur method is implemented as a plug-in forChimeraXcalledMorphOT, which allows the use of both CPU or GPU resources. The code is publicly available on GitHub (https://github.com/kdd-ubc/MorphOT.git), with documentation containing tutorial and datasets.Contactkdd@math.ubc.ca
Leaf form diversification in an heirloom tomato results from alterations in two differentHOMEOBOXgenes
Authors: Nakayama Hokuto , Rowland Steven D. , Cheng Zizhang , Zumstein Kristina , Kang Julie , Kondo Yohei , Sinha Neelima R. 
Published: September 2020

AbstractDomesticated plants and animals display tremendous diversity in various phenotypic traits and often this diversity is seen within the same species. Tomato (Solanum lycopersicum; Solanaceae) cultivars show wide variation in leaf morphology, but the influence of breeding efforts in sculpting this diversity is not known. Here, we demonstrate that a single nucleotide deletion in the homeobox motif ofBIPINNATA, which is aBEL-LIKE HOMEODOMAINgene, led to a highly complex leaf phenotype in an heirloom tomato, Silvery Fir Tree (SiFT). Additionally, a comparative gene network analysis revealed that reduced expression of the ortholog ofWUSCHEL RELATED HOMEOBOX 1is also important for the narrow leaflet phenotype seen in SiFT. Phylogenetic and comparative genome analysis using whole-genome sequencing data suggests that thebipmutation in SiFT is likely ade novomutation, instead of standing genetic variation. These results provide new insights into natural variation in phenotypic traits introduced into crops during improvement processes after domestication.
Direct contribution of skeletal muscle mesenchymal progenitors to bone repair
Authors: Anais Julien , Anuya Kanagalingam , Jérome Megret , Marine Luka , Mickaël Ménager , Frédéric Relaix , Céline Colnot 
Published: September 2020

AbstractTissue regeneration relies on the activation of tissue resident stem cells concomitant with a transient fibrous tissue deposition to allow functional tissue recovery. Bone regeneration involves skeletal stem/progenitors from periosteum and bone marrow, the formation of a fibrous callus followed by the deposition of cartilage and bone to consolidate the fracture. Here, we show that mesenchymal progenitors residing in skeletal muscle adjacent to the bone fracture play a crucial role in mediating the initial fibrotic response to bone injury and also participate in cartilage and bone formation in the fracture callus. Combined lineage and scRNAseq analyses reveal that skeletal muscle mesenchymal progenitors adopt a fibrogenic fate before they engage in a chondrogenic fate after fracture. In polytrauma, where bone and skeletal muscle are injured, skeletal muscle mesenchymal progenitors fail to undergo fibrogenesis and chondrogenesis. This leads to impaired healing and persistent callus fibrosis originating from skeletal muscle. Thus, essential bone-muscle interactions govern bone regeneration through the direct contribution of skeletal muscle as a source of mesenchymal progenitors driving the fibrotic response and fibrotic remodeling, and supporting cartilage and bone formation.
Sensitivity to Envelope Interaural Time Difference: Models of Diverse LSO Neurons
Authors: Brughera Andrew , Ballestero Jimena A. , McAlpine David 
Published: September 2020

AbstractA potential auditory spatial cue, the envelope interaural time difference (ITDENV) is encoded in the lateral superior olive (LSO) of the brainstem. Here, we explore computationally modeled LSO neurons, in reflecting behavioral sensitivity to ITDENV. Transposed tones (half-wave rectified low-frequency tones, frequency-limited, then multiplying a high-frequency carrier) stimulate a bilateral auditory-periphery model driving each model LSO neuron, where electrical membrane impedance low-pass filters the inputs driven by amplitude-modulated sound, limiting the upper modulation rate for ITDENVsensitivity. Just-noticeable differences in ITDENVfor model LSO neuronal populations, each distinct to reflect the LSO range in membrane frequency response, collectively reproduce the largest variation in ITDENVsensitivity across human listeners. At each stimulus carrier frequency (4-10 kHz) and modulation rate (32-800 Hz), the top-performing model population generally reflects top-range human performance. Model neurons of each speed are the top performers for a particular range of modulation rate. Off-frequency listening extends model ITDENVsensitivity above 500-Hz modulation, as sensitivity decreases with increasing modulation rate. With increasing carrier frequency, the combination of decreased top membrane speed and decreased number of model neurons capture decreasing human sensitivity to ITDENV.
Integrative approaches to improve the informativeness of deep learning models for human complex diseases
Authors: Dey Kushal K. , Kim Samuel S. , Gazal Steven , Nasser Joseph , Engreitz Jesse M. , Price Alkes L. 
Published: September 2020

AbstractDeep learning models have achieved great success in predicting genome-wide regulatory effects from DNA sequence, but recent work has reported that SNP annotations derived from these predictions contribute limited unique information for human complex disease. Here, we explore three integrative approaches to improve the disease informativeness of allelic-effect annotations (predicted difference between reference and variant alleles) constructed using several previously trained deep learning models: DeepSEA, Basenji and DeepBind (and a related machine learning model, deltaSVM). First, we employ gradient boosting to learn optimal combinations of deep learning annotations, using fine-mapped SNPs and matched control SNPs (on held-out chromosomes) for training. Second, we improve the specificity of these annotations by restricting them to SNPs implicated by (proximal and distal) SNP-to-gene (S2G) linking strategies, e.g. prioritizing SNPs involved in gene regulation. Third, we predict gene expression (and derive allelic-effect annotations) from deep learning annotations at SNPs implicated by S2G linking strategies — generalizing the previously proposed ExPecto approach, which incorporates deep learning annotations based on distance to TSS. We evaluated these approaches using stratified LD score regression, using functional data in blood and focusing on 11 autoimmune diseases and blood-related traits (averageN=306K). We determined that the three approaches produced SNP annotations that were uniquely informative for these diseases/traits, despite the fact that linear combinations of the underlying DeepSEA, Basenji, DeepBind and deltaSVM blood annotations were not uniquely informative for these diseases/traits. Our results highlight the benefits of integrating SNP annotations produced by deep learning models with other types of data, including data linking SNPs to genes.
Diversity and Function of the Eastern Oyster (Crassostrea virginica) Microbiome
Authors: Pimentel Zachary T. , Dufault-Thompson Keith , Russo Kayla T. , Scro Abigail K. , Smolowitz Roxanna M. , Gomez-Chiarri Marta , Zhang Ying 
Published: September 2020

ABSTRACTMarine invertebrate microbiomes play important roles in various host and ecological processes. However, a mechanistic understanding of host-microbe interactions is so far only available for a handful of model organisms. Here, an integrated taxonomic and functional analysis of the microbiome of the eastern oyster,Crassostrea virginica, was performed using 16S rRNA gene amplicon profiling, shotgun metagenomics, and genome-scale metabolic reconstruction. A relatively low number of amplicon sequence variants (ASVs) were observed in oyster tissues compared to water samples, while high variability was observed across individual oysters and among different tissue types. Targeted metagenomic sequencing of the gut microbiota led to further characterization of a dominant bacterial taxon, the classMollicutes, which was captured by the reconstruction of a metagenome-assembled genome (MAG). Genome-scale metabolic reconstruction of the oysterMollicutesMAG revealed a reduced set of metabolic functions and a high reliance on the uptake of host-derived nutrients. A chitin degradation and an arginine deiminase pathway were unique to the MAG as compared to other closely relatedMycoplasmagenomes, indicating a distinct mechanism of carbon and energy acquisition by the oyster- associatedMollicutes. A systematic reanalysis of public eastern oyster-derived microbiome data revealed theMollicutesas a ubiquitous taxon among adult oysters despite their general absence in larvae and biodeposit samples, suggesting potential horizontal transmission via an unknown mechanism.IMPORTANCEDespite well-documented biological significance of invertebrate microbiomes, a detailed taxonomic and functional characterization is frequently missing from many non-model marine invertebrates. By using 16S rRNA gene-based community profiling, shotgun metagenomics, and genome-scale metabolic reconstruction, this study provides an integrated taxonomic and functional analysis of the microbiome of the eastern oyster,Crassostrea virginica. Community profiling revealed a surprisingly low richness, as compared to surrounding seawater, and high variability among different tissue types and individuals. Reconstruction of aMollicutesMAG enabled the phylogenomic positioning and functional characterization of the oyster-associatedMollicutes. Comparative analysis of the adult oyster gut, biodeposits, and oyster larvae samples indicated the potentially ubiquitous associations of theMollicutestaxon with adult oysters. To the best of our knowledge, this study represented the first metagenomics derived functional inference of the eastern oyster microbiome. An integrated analytical procedure was developed for the functional characterization of microbiomes in other non-model host species.