bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing a new device to measure lung volumes with three traditional methods in individuals with different lung conditions
Authors: Zac Jacob , Zac Salomon , Pérez-Padilla Rogelio , Remigio-Luna Arantxa , Guzmán-Boulloud Nicolas , Gochicoa-Rangel Laura , Guzmán-Valderrábano Carlos , Thirión-Romero Ireri 
Published: March 2021

AbstractBackgroundLung volumes can be measured by body plethysmography (BP), by inert gas dilution during a single-breath or multiple breaths and by radiographic methods based on chest roentgenogram or CT scanning. Our objective was to analyze the concordance between several methods including a new instrument in a variety of pulmonary conditions.MethodsWe recruited four groups of adult volunteers at the COPD and Tobacco Clinic of a respiratory referral hospital: patients with lung bullae, with obstructive lung diseases, with restrictive lung diseases and healthy controls; all subjects underwent lung volume measurements according to ATS/ERS standards in random order with each method and then CT scanning. Differences among groups were estimated by Kruskal-Wallis tests. Concordance correlation coefficients (CCC) and Bland-Altman plots were performed.ResultsSixty-two patients were studied including 15 with lung bullae, 14 with obstructive lung diseases, 12 with restrictive lung disease and 21 healthy subjects. Highest concordance was obtained between BP and CT scanning (CCC 0.95, mean difference −0.35 L) and the lowest, with TLC-DLCOsb (CCC 0.65, difference - 1.05 L). TLC measured by BP had a moderate concordance with Minibox (CCC=0.91, mean difference −0.19 L). Minibox, on the other hand had the lowest intratest repeatibility (2.7%) of all tested methods.ConclusionsLung volumes measured by BP and CT had a substantial concordance in the scenario of varied pulmonary conditions including lung bullae, restrictive and obstructive diseases. The new minibox device, had low intratest variability, and was easy to perform, with a reasonable concordance with BP.
Genetic heterogeneity and subtypes of major depression
Authors: Nguyen Thuy-Dung , Harder Arvid , Xiong Ying , Kowalec Kaarina , Hägg Sara , Cai Na , Kuja-Halkola Ralf , Dalman Christina , Sullivan Patrick F , Lu Yi 
Published: March 2021

ABSTRACTMajor depression (MD) is a heterogeneous disorder; however, the extent to which genetic factors distinguish MD patient subgroups (genetic heterogeneity) remains uncertain. This study sought evidence for genetic heterogeneity in MD. Using UK Biobank cohort, the authors defined 16 MD subtypes within eight comparison groups (vegetative symptoms, symptom severity, comorbid anxiety disorder, age at onset, recurrence, suicidality, impairment and postpartum depression; N∼3 000-47 000). To compare genetic component of these subtypes, subtype-specific genome-wide association studies were performed to estimate SNP-heritability, and genetic correlations within subtype comparison and with other related disorders or traits. The findings indicated that MD subtypes were divergent in their SNP-heritability, and genetic correlations both within subtype comparisons and with other related disorders/traits. Three subtype comparisons (vegetative symptoms, age at onset, and impairment) showed significant differences in SNP-heritability; while genetic correlations within subtype comparisons ranged from 0.55 to 0.86, suggesting genetic profiles are only partially shared among MD subtypes. Furthermore, subtypes that are more clinically challenging, e.g., early-onset, recurrent, suicidal, more severely impaired, had stronger genetic correlations with other psychiatric disorders. MD with atypical-like features showed a positive genetic correlation (+0.40) with BMI while a negative correlation (−0.09) was found in those without atypical-like features. Novel genomic loci with subtype-specific effects were identified. These results provide the most comprehensive evidence to date for genetic heterogeneity within MD, and suggest that the phenotypic complexity of MD can be effectively reduced by studying the subtypes which share partially distinct etiologies.
North Carolina macular dystrophy: phenotypic variability and computational analysis of disease-implicated non-coding variants
Authors: Green David J. , Lenassi Eva , Manning Cerys S. , McGaughey David , Sharma Vinod , Black Graeme C. , Ellingford Jamie M. , Sergouniotis Panagiotis I. 
Published: March 2021

ABSTRACTPurposeNorth Carolina macular dystrophy (NCMD) is an autosomal dominant, congenital disorder affecting the central retina. Here, we report clinical and genetic findings in three families segregating NCMD and use epigenomic datasets from human tissues to gain insights into the effect of NCMD-implicated variants.MethodsClinical assessment and genetic testing were performed. Publicly-available transcriptomic and epigenomic datasets were analyzed and the ‘Activity-by-Contact’ (ABC) method for scoring enhancer elements and linking them to target genes was used.ResultsA previously-described, heterozygous, non-coding variant upstream of thePRDM13gene was detected in all six affected study participants (chr6:100,040,987G>C [GRCh37/hg19]). Inter- and intra-familial variability were observed; the visual acuity ranged from 0.0 to 1.6 LogMAR and fundoscopic findings ranged from visually insignificant, confluent, drusen-like macular deposits to coloboma-like macular lesions. Variable degrees of peripheral retinal spots (which were easily detected on widefield retinal imaging) were observed in all study subjects. Notably, a 6-year-old patient developed choroidal neovascularization and required treatment with intravitreal bevacizumab injections. Computational analysis of the five single nucleotide variants that have been implicated in NCMD revealed that these non-coding changes lie within two putative enhancer elements; these elements are predicted to interact withPRDM13in the developing human retina.PRDM13was found to be expressed in the fetal retina, with highest expression in the amacrine precursor cell population.ConclusionsWe provide further evidence supporting the role ofPRDM13dysregulation in the pathogenesis of NCMD and highlight the utility of widefield retinal imaging in individuals suspected to have this condition.
A Novel Computer-Assisted Drug-Induced Liver Injury Causality Assessment Tool (DILI-CAT)
Authors: Tillmann Hans L. , Suzuki Ayako , Merz Michael , Hermann Richard , Rockey Don C. 
Published: March 2021

AbstractObjectiveWe hypothesized that a drug-characteristic DILI-phenotype could be defined and be used to develop a computer-assisted DILI causality assessment-tool (DILI-CAT).DesignA drug-specific DILI-phenotype was developed for amoxicillin-clavulanate (AMX/CLA), cefazolin, cyproterone, and polygonum multiflorum using data from published case series, and subsequently a DILI-CAT Score (DILI-CAT-S) was created for each drug. The phenotype was made up of the following three parameters: (1) latency, R-value, and (3) AST/ALT ratio (also de Ritis ratio). A point allocation system was developed with points allocated depending on the degree of deviation from the core of published data for the three phenotypic parameters.ResultsThe four drugs had a significantly different phenotype based on the three parameters utilized. For example, the median cyproterone latency was 150 days versus less than 43 days for the other three drugs (median: 26 for AMX/CLA, 20 for cefazolin, and 20 days for polygonum multiflorum; p<0·001). The R-value for the four drugs was also significantly different (median: cyproterone [12.4] and polygonum multiflorum [10.9]) from AMX/CLA (1.44) and cefazolin (1.57; p<0.001). The resulting DILI-CAT-S effectively separated cyproterone and polygonum multiflorum from AMX/CLA and cefazolin, respectively (p<0·001). Notably, because of overlap in phenotype AMX/CLA and cefazolin could not be differentiated by DILI-CAT-S.ConclusionDILI-CAT is a data-driven, diagnostic tool built to define drug-specific phenotypes. Data presented here provide proof of principle that a drug-specific, data-driven causality assessment tool can be developed for different drugs and raise the possibility that such a process could improve and standardize causality assessment methods.FundingDCR was supported by the NIH, grant P30 DK 123704
Inflammatory, but not respiratory symptoms, associated with ongoing upper airway viral replication in outpatients with uncomplicated COVID-19
Authors: Jacobson Karen B. , Purington Natasha , Parsonnet Julie , Andrews Jason , Balasubramanian Vidhya , Bonilla Hector , Edwards Karlie , Desai Manisha , Singh Upinder , Hedlin Haley , Jagannathan Prasanna 
Published: March 2021

AbstractBackgroundThe vast majority of SARS-CoV-2 infections are uncomplicated and do not require hospitalization, but contribute to ongoing transmission. Our understanding of the clinical course of uncomplicated COVID-19 remains limited.MethodsWe detailed the natural history of uncomplicated COVID-19 among 120 outpatients enrolled in a randomized clinical trial of Peginterferon Lambda. We characterized symptom trajectory and clusters using exploratory factor analysis, assessed predictors of symptom resolution and cessation of oropharyngeal viral shedding using Cox proportional hazard models, and evaluated associations between symptoms and viral shedding using mixed effects linear models.ResultsHeadache, myalgias and chills peaked at day 4 after symptom onset; cough peaked on day 9. Two distinct symptom cluster trajectories were identified; one with mild, upper respiratory symptoms, and the other with more severe and prolonged inflammatory symptoms. The median time to symptom resolution from earliest symptom onset was 17 days (95% CI 14-18). Neither enrollment SARS-CoV-2 IgG levels (Hazard ratio [HR] 1.88, 95% CI 0.84-4.20) nor oropharyngeal viral load at enrollment (HR 1.01, 95% CI 0.98-1.05) were significantly associated with the time to symptom resolution. The median time to cessation of viral shedding was 10 days (95% CI 8-12), with higher SARS-CoV-2 IgG levels at enrollment associated with hastened resolution of viral shedding (HR 3.12, 95% CI 1.4-6.9, p=0.005). Myalgia, joint pains, and chills were associated with a significantly greater odds of oropharyngeal SARS-CoV-2 RNA detection.ConclusionsIn this outpatient cohort, inflammatory symptoms peaked early and were associated with ongoing SARS-CoV-2 replication. SARS-CoV-2 antibody levels were associated with more rapid viral shedding cessation, but not with time to symptom resolution. These findings have important implications for COVID-19 screening approaches and clinical trial design.
A Simple Fluorescence Assay for Cystine Uptake via the xCT in Cells using Selenocystine and a Fluorescent Probe
Authors: Shimomura Takashi , Hirakawa Norio , Ohuchi Yuya , Ishiyama Munetaka , Shiga Masanobu , Ueno Yuichiro 
Published: March 2021

ABSTRACTThe cystine/glutamate antiporter (xCT) is a crucial transporter that maintains cellular redox balance by regulating intracellular glutathione synthesis via cystine uptake. However, no robust and simple method to determine the cystine uptake activity of xCT is currently available. We have developed a method to measure the xCT activity via the reaction of selenocysteine and fluoresceinO,O′-diacrylate (FOdA). Selenocystine, a cystine analog, is transported into cells through xCT on the cell membrane. The amount of the transported selenocystine was then determined by a reaction using tris(2-carboxyethyl)phosphine (TCEP) and FOdA in a weak acidic buffer at pH 6. Using this method, the cystine uptake activity of xCT in various cells, and the inhibitory efficiency of xCT inhibitors, were evaluated.
Disentangling effects of climate and land use on biodiversity and ecosystem services – a multi-scale experimental design
Authors: Redlich Sarah , Zhang Jie , Benjamin Caryl , Dhillon Maninder Singh , Englmeier Jana , Ewald Jörg , Fricke Ute , Ganuza Cristina , Haensel Maria , Hovestadt Thomas , Kollmann Johannes , Koellner Thomas , Kübert-Flock Carina , Kunstmann Harald , Menzel Annette , Moning Christoph , Peters Wibke , Riebl Rebekka , Rummler Thomas , Botero Sandra Rojas , Tobisch Cynthia , Uhler Johannes , Uphus Lars , Müller Jörg , Steffan-Dewenter Ingolf 
Published: March 2021

SummaryClimate and land-use change are key drivers of environmental degradation in the Anthropocene, but too little is known about their interactive effects on biodiversity and ecosystem services. Long-term data on biodiversity trends are currently lacking. Furthermore, previous ecological studies have rarely considered climate and land use in a joint design, did not achieve variable independence or lost statistical power by not covering the full range of environmental gradients.Here, we introduce a multi-scale space-for-time study design to disentangle effects of climate and land use on biodiversity and ecosystem services. The site selection approach coupled extensive GIS-based exploration and correlation heatmaps with a crossed and nested design covering regional, landscape and local scales. Its implementation in Bavaria (Germany) resulted in a set of study plots that maximizes the potential range and independence of environmental variables at different spatial scales.Stratifying the state of Bavaria into five climate zones and three prevailing land-use types, i.e. near-natural, agriculture and urban, resulted in 60 study regions covering a mean annual temperature gradient of 5.6–9.8 °C and a spatial extent of 380×360 km. Within these regions, we nested 180 study plots located in contrasting local land-use types, i.e. forests, grasslands, arable land or settlement (local climate gradient 4.5–10 °C). This approach achieved low correlations between climate and land-use (proportional cover) at the regional and landscape scale with |r≤0.33| and |r≤0.29|, respectively. Furthermore, using correlation heatmaps for local plot selection reduced potentially confounding relationships between landscape composition and configuration for plots located in forests, arable land and settlements.The suggested design expands upon previous research in covering a significant range of environmental gradients and including a diversity of dominant land-use types at different scales within different climatic contexts. It allows independent assessment of the relative contribution of multi-scale climate and land use on biodiversity and ecosystem services. Understanding potential interdependencies among global change drivers is essential to develop effective restoration and mitigation strategies against biodiversity decline, especially in expectation of future climatic changes. Importantly, this study also provides a baseline for long-term ecological monitoring programs.
Scarcity of hosts for gregarious parasitoids indicates an increase of individual offspring fertility by reducing their own fertility
Authors: Samková Alena , Raška Jan , Hadrava Jiří , Skuhrovec Jiří 
Published: March 2021

ABSTRACTThe gregarious parasitoid strategy allows multiple larvae to complete development in a single host due to their tolerance and/or lower mobility and thus flexibly adjust their reproductive potential amidst changing environmental conditions. Reproductive success is generally measured as the number of each mother’s offspring. We propose that with scarcity of host, for gregarious parasitoids is important the view on the fertility not only of a mother but also of her offspring (F1 generation). Due to the body size-fitness correlation, each female deliberately adjusts the clutch size, determining the offspring body size and their reproductive potential. In our study, usingAnaphes flavipesas a model species, we showed that under a limited number of hosts, the females reduced their fertility. We propose that the lower fertility of mothers can cause higher fertility in the F2 generation using a larger offspring body while halving fertility. The females increase their individual offspring’s fertility by reducing their own fertility. Moreover, we showed that with a scarcity of hosts, the mothers increased the number of their female offspring, and thus, they obtained more offspring in the F2 generation. Additionally, other costs and benefits of the gregarious strategy in relation to superparasitism were tested and discussed.
Network diffusion for scalable embedding of massive single-cell ATAC-seq data
Authors: Dong Kangning , Zhang Shihua 
Published: March 2021

ABSTRACTWith the rapid development of single-cell ATAC-seq technology, it has become possible to profile the chromatin accessibility of massive individual cells. However, it remains challenging to characterize their regulatory heterogeneity due to the high-dimensional, sparse and near-binary nature of data. Most existing data representation methods were designed based on correlation, which may be ill-defined for sparse data. Moreover, these methods do not well address the issue of excessive zeros. Thus, a simple, fast and scalable approach is needed to analyze single-cell ATAC-seq data with massive cells, address the “missingness” and accurately categorize cell types. To this end, we developed a network diffusion method for scalable embedding of massive single-cell ATAC-seq data (named as scAND). Specifically, we considered the near-binary single-cell ATAC-seq data as a bipartite network that reflects the accessible relationship between cells and accessible regions, and further adopted a simple and scalable network diffusion method to embed it. scAND can take information from similar cells to alleviate the sparsity and improve cell type identification. Extensive tests and comparison with existing methods using synthetic and real data as benchmarks demonstrated its distinct superiorities in terms of clustering accuracy, robustness, scalability and data integration.AvailabilityThe Python-based scAND tool is freely available athttp://page.amss.ac.cn/shihua.zhang/software.html.
Coordination of movement via complementary interactions of leaders and followers in termite mating pairs
Authors: Mizumoto Nobuaki , Lee Sang-Bin , Valentini Gabriele , Chouvenc Thomas , Pratt Stephen C. 
Published: March 2021

AbstractLeadership of animal group movements depends on social feedback, hence leader’s signals and follower’s responses should be attuned to each other. However, leader and follower roles are difficult to disentangle in species with high levels of coordination. To overcome this challenge, we investigated a simple case of movement coordination: termite pairs in which a female leads a male as they search for a nest site. To tease apart leader and follower roles, we created conspecific and heterospecific pairs ofCoptotermes gestroiandC. formosanus, which share a pairing pheromone so that males follow females of either species. Conspecific pairs were stable for both species, even thoughC. gestroifemales produce less pheromone thanC. formosanus. Heterospecific pairs withC. gestroimales were also stable, but not those withC. formosanusmales. We attributed this difference to theC. gestroimale’s unique capacity to follow females that release small amounts of pheromone;C. formosanusmales cannot follow or rejectC. gestroifemales as unsuitable. This conclusion was supported by an information-theoretic analysis that detected information flow fromC. formosanusfemales toC. gestroimales as in conspecific pairs, but not fromC. gestroifemales toC. formosanusmales. Despite their following ability,C. gestroimales lost toC. formosanusmales in competitions to followC. formosanusfemales. Thus, partner selection has shaped the species-specific association of mating pairs. Our results demonstrate that a similar level of coordination can emerge from distinct sets of complementary sender-receiver interactions.
Conserved, divergent and heterochronic gene expression duringBrachypodiumandArabidopsisembryo development
Authors: Hao Zhaodong , Zhang Zhongjuan , Xiang Daoquan , Venglat Prakash , Chen Jinhui , Gao Peng , Datla Raju , Weijers Dolf 
Published: March 2021

AbstractEmbryogenesis, transforming the zygote into the mature embryo, represents a fundamental process for all flowering plants. Current knowledge of cell specification and differentiation during plant embryogenesis is largely based on studies of the dicot model plantArabidopsis thaliana. However, the major crops are monocots and the transcriptional programs associated with the differentiation processes during embryogenesis in this clade were largely unknown. Here, we combined analysis of cell division patterns with development of a temporal transcriptomic resource during embryogenesis of the monocot model plantBrachypodium distachyon. We found that early divisions of theBrachypodiumembryo were highly regular, while later stages were marked by less stereotypic patterns. Comparative transcriptomic analysis betweenBrachypodiumandArabidopsisrevealed that the early and late embryogenesis shared a common transcriptional program, whereas mid-embryogenesis was divergent between species. Analysis of orthology groups revealed widespread heterochronic expression of potential developmental regulators between the species. Interestingly,Brachypodiumgenes tend to be expressed at earlier stages thanArabidopsiscounterparts, which suggests that embryo patterning may occur early duringBrachypodiumembryogenesis. Detailed investigation of auxin-related genes shows that the capacity to synthesize, transport, and respond to auxin is established early in the embryo. However, while early PIN1 polarity could be confirmed, it is unclear if an active response is mounted. This study presents a resource for studyingBrachypodiumand grass embryogenesis, and shows that divergent angiosperms share a conserved genetic program that is marked by heterochronic gene expression.Key messageDevelopmental and transcriptomic analysis ofBrachypodiumembryogenesis, and comparison withArabidopsis, identifies conserved and divergent phases of embryogenesis, and reveals widespread heterochrony of developmental gene expression.
Neurodegeneration in human brain organoids infected with herpes simplex virus type 1
Authors: Rybak-Wolf Agnieszka , Wyler Emanuel , Legnini Ivano , Loewa Anna , Glažar Petar , Kim Seung Joon , Pentimalli Tancredi Massimo , Martinez Anna Oliveras , Beyersdorf Benjamin , Woehler Andrew , Landthaler Markus , Rajewsky Nikolaus 
Published: March 2021

AbstractHerpes simplex virus type 1 (HSV-1) infection of the nervous system may lead to brain damage, including neurodegeneration. However, lack of suitable experimental models hinders understanding molecular mechanisms and cell-type-specific responses triggered by HSV-1. Here, we infected human brain organoids with HSV-1. Known features of HSV-1 infection such as alteration of neuronal electrophysiology and induction of antisense transcription were confirmed. Full-length mRNA-sequencing revealed aberrant 3’ end formation and poly(A)-tail lengthening. Single-cell RNA-seq and spatial transcriptomics uncovered changes in the cellular composition of the infected organoids caused by viral replication and dysregulation of molecular pathways in cell-type specific manner. Furthermore, hallmarks of early neurodegeneration were observed, namely extracellular matrix disruption, STMN2 and TARDBP/TDP43 downregulation, and upregulation of the AD-related non-coding RNA BC200/BCYRN1. These hallmarks were weaker/absent when infecting with a mutant HSV-1 control. Together, our data indicate that brain organoids serve as a powerful model to study mechanisms of HSV-1-driven neurodegeneration.