bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large-Scale Validation Study of an Improved Semi-Autonomous Urine Cytology Assessment Tool: AutoParis-X
Authors: Levy Joshua J. , Chan Natt , Marotti Jonathan D. , Kerr Darcy A. , Gutmann Edward J. , Glass Ryan E. , Dodge Caroline P. , Suriawinata Arief A. , Christensen Brock , Liu Xiaoying , Vaickus Louis J. 
Published: March 2023

AbstractAdopting a computational approach for the assessment of urine cytology specimens has the potential to improve the efficiency, accuracy and reliability of bladder cancer screening, which has heretofore relied on semi-subjective manual assessment methods. As rigorous, quantitative criteria and guidelines have been introduced for improving screening practices, e.g., The Paris System for Reporting Urinary Cytology (TPS), algorithms to emulate semi-autonomous diagnostic decision-making have lagged behind, in part due to the complex and nuanced nature of urine cytology reporting. In this study, we report on a deep learning tool, AutoParis-X, which can facilitate rapid semi-autonomous examination of urine cytology specimens. Through a large-scale retrospective validation study, results indicate that AutoParis-X can accurately determine urothelial cell atypia and aggregate a wide-variety of cell and cluster-related information across a slide to yield an Atypia Burden Score (ABS) that correlates closely with overall specimen atypia, predictive of TPS diagnostic categories. Importantly, this approach accounts for challenges associated with assessment of overlapping cell cluster borders, which improved the ability to predict specimen atypia and accurately estimate the nuclear-to-cytoplasm (NC) ratio for cells in these clusters. We developed an interactive web application that is publicly available and open-source, which features a simple, easy-to-use display for examining urine cytology whole-slide images (WSI) and determining the atypia level of specific cells, flagging the most abnormal cells for pathologist review. The accuracy of AutoParis-X (and other semi-automated digital pathology systems) indicates that these technologies are approaching clinical readiness and necessitates full evaluation of these algorithms via head-to-head clinical trials.
Discovering Digital Biomarkers of Panic Attack Risk in Consumer Wearables Data
Authors: McGinnis Ellen W. , Lunna Shania , Berman Isabel , Loftness Bryn C. , Bagdon Skylar , Danforth Christopher M. , Price Matthew , Copeland William E. , McGinnis Ryan S. 
Published: March 2023

AbstractPanic attacks are an impairing mental health problem that impacts more than one out of every 10 adults in the United States (US). Clinical guidelines suggest panic attacks occur without warning and their unexpected nature worsens their impact on quality of life. Individuals who experience panic attacks would benefit from advance warning of when an attack is likely to occur so that appropriate steps could be taken to manage or prevent it. Our recent work suggests that an individual’s likelihood of experiencing a panic attack can be predicted by self-reported mood and community-level Twitter-derived mood the previous day. Prior work also suggests that physiological markers may indicate a pending panic attack. However, the ability of objective physiological, behavioral, and environmental measures to predict next-day panic attacks has not yet been explored. To address this question, we consider data from 38 individuals who regularly experienced panic attacks recruited from across the US. Participants responded to daily questions about their panic attacks for 28 days and provided access to data from their Apple Watches. Results indicate that objective measures of ambient noise (louder) and resting heart rate (higher) are related to the likelihood of experiencing a panic attack the next day. These preliminary results suggest, for the first time, that panic attacks may be predictable from data passively collected by consumer wearable devices, opening the door to improvements in how panic attacks are managed and to the development of new preventative interventions.Clinical RelevanceObjective data from consumer wearables may predict when an individual is at high risk for experiencing a next-day panic attack. This information could guide treatment decisions, help individuals manage their panic, and inform the development of new preventative interventions.
Blood lipid density decreases at the early-stage of stomach adenocarcinoma
Authors: Prakash Om , Khan Feroz 
Published: March 2023

ABSTRACTBackgroundInduction of cancer creates many molecular to physiological changes in the human body. Observation of these variations between normal & diseased conditions become the basis of disease diagnosis. Present study analyzed blood lipid profile, relative to changes in genotype, at the early stage of stomach adenocarcinoma.Materials and MethodPresent study was based on establishment of relationship between genotype to phenotype. Genotypic features were collected through RNAseq analysis, which was further mapped with phenotypic expression in the form of blood lipid profile.ResultsTo observe the significance difference between phenotypic expressions of normal and cancerous condition, gene signatures from multiple sources of studies were mapped with blood lipid profile including: Total Cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides, Non-HDL-C, and TG to HDL ratio. Significance difference found between phenotypic expression of normal and cancerous condition.ConclusionThrough multi-signature-based population observation, it was found that blood-lipid density decreases at the early-stage of stomach adenocarcinoma. Further, blood-lipid profile can be used for early disease prediction of stomach adenocarcinoma as well as other cancer types.
metaGE: Investigating Genotype × Environment interactions through meta-analysis
Authors: De Walsche Annaïg , Vergne Alexis , Rincent Renaud , Roux Fabrice , Nicolas Stephane , Welcker Claude , Mezmouk Sofiane , Charcosset Alain , Mary-Huard Tristan 
Published: March 2023

AbstractDissecting the genetic components of Genotype-by-Environment interactions is of key importance in the context of increasing instability and plant competition due to climate change and phytosanitary treatment limitations. It is widely addressed in plants using Multi-Environment Trials (MET), in which statistical modelling for genome-wide association studies (GWAS) is promising but significantly more complex than for single-environment studies. In this context, we introduce metaGE, a flexible and computationally efficient meta-analysis approach for the joint analysis of any MET GWAS experiment. To cope with the specific requirements of the MET context, metaGE accounts for both the heterogeneity of QTL effects across environments and the correlation between GWAS summary statistics acquired on the same or related set(s) of genotypes. Compared to previous GWAS in 3 plant species and a multi-parent population, metaGE identified known and new QTLs. It provided valuable insight into the genetic architecture of several complex traits and the variation of QTL effects conditional to environmental conditions.
Intermittent Hypoxia in Neonatal Rodents Affects Facial Bone Growth
Authors: Pae Eung-Kwon , Harper Ronald M. 
Published: March 2023

AbstractPreterm human infants often show periodic breathing (PB) or apnea of prematurity (AOP), breathing patterns which are accompanied by intermittent hypoxia (IH). We examined cause-effect relationships between transient IH and reduced facial bone growth using a rat model. Neonatal pups from 14 timed pregnant Sprague-Dawley rats were randomly assigned to an IH condition, with oxygen altering between 10% and 21% every 4 min for 1 h immediately after birth, or to a litter-matched control group. The IH pups were compared with their age- and sex-matched control groups in body weight (WT), size of facial bones and nor-epinephrine (NE) levels in blood at 3, 4, and 5-weeks. Markedly increased activity of osteoclasts in sub-condylar regions of 3-week-old IH-treated animals appeared, as well as increased numbers of sympathetic nerve endings in the same region of tissue sections. Male IH-pups showed significantly higher levels of NE levels in sera at 3, 4 as well as 5-week-old time points. NE levels in 4- and-5-weekold female pups did not differ significantly. Intercondylar Width, Mandible Length and Intermolar Width measures consistently declined after IH insults in 3- and 4-week-old male as well as female animals. Three-week-old male IH-pups only showed a significantly reduced (p < 0.05) body weight compared to those of 3-week controls. However, female IH-pups were heavier than age-matched controls at all 3 time-points. Trabecular bone configuration, size of facial bones, and metabolism are disturbed after an IH challenge 1 h immediately after birth. The findings raise the possibility that IH, introduced by breathing patterns such as PB or AOP, induce significantly impaired bone development and metabolic changes in human newborns. The enhanced NE outflow from IH exposure may serve a major role in deficient bone growth, and may affect bone and other tissue influenced by that elevation.
Development of a novel epigenetic clock resistant to changes in immune cell composition
Authors: Tomusiak Alan , Floro Ariel , Tiwari Ritesh , Riley Rebeccah , Matsui Hiroyuki , Andrews Nicolas , Kasler Herbert G. , Verdin Eric 
Published: March 2023

AbstractEpigenetic clocks are age predictors that use machine-learning models trained on DNA CpG methylation values to predict chronological or biological age. Increases in predicted epigenetic age relative to chronological age (epigenetic age acceleration) are connected to aging-associated pathologies, and changes in epigenetic age are linked to canonical aging hallmarks. However, epigenetic clocks rely on training data from bulk tissues whose cellular composition changes with age. We found that human naive CD8+T cells, which decrease during aging, exhibit an epigenetic age 15–20 years younger than effector memory CD8+T cells from the same individual. Importantly, homogenous naive T cells isolated from individuals of different ages show a progressive increase in epigenetic age, indicating that current epigenetic clocks measure two independent variables, aging and immune cell composition. To isolate the age-associated cell intrinsic changes, we created a new clock, the IntrinClock, that did not change among 10 immune cell types tested. IntrinClock showed a robust predicted epigenetic age increase in a model of replicative senescencein vitroand age reversal during OSKM-mediated reprogramming.
A refined single cell landscape of haematopoiesis in the mouse foetal liver
Authors: Ceccacci Elena , Villa Emanuela , Santoro Fabio , Minucci Saverio , Ruhrberg Christiana , Fantin Alessandro 
Published: March 2023

AbstractDuring prenatal life, the foetal liver is colonised by several waves of haematopoietic stem and progenitor cells (HSPCs) to act as the main haematopoietic organ. Single cell (sc) RNA-seq has been used to identify foetal liver cell types via their transcriptomic signature and to compare gene expression pattern as haematopoietic development proceeds. To obtain a refined single cell landscape of haematopoiesis in the foetal liver, we have generated a novel scRNA-seq dataset from whole mouse E12.5 liver that includes a larger number of cells than prior datasets at this stage and was obtained without cell type preselection to include all liver cell populations. We combined mining of this dataset with that of previously published datasets at other developmental stages to follow transcriptional dynamics as well as cell cycle state of developing haematopoietic lineages. Our findings corroborate several prior reports on the timing of liver colonisation by HSPCs and the emergence of differentiated lineages and provide further molecular characterisation of each cell population. Extending these findings, we demonstrate the existence of a foetal intermediate haemoglobin profile in the mouse, similar to that previously identified in humans, and a previously unidentified population of primitive erythroid cells in the foetal liver.
Classification of Parkinson’s Disease and Delineating Progression Markers from the Sebum Volatilome
Authors: Walton-Doyle Caitlin , Heim Beatrice , Sinclair Eleanor , Lim Sze Hway , Hollywood Katherine A , Milne Joy , Holzknecht Evi , Stefani Ambra , Högl Birgit , Seppi Klaus , Silverdale Monty , Poewe Werner , Barran Perdita , Trivedi Drupad K 
Published: March 2023

AbstractParkinson’s Disease (PD) has been associated with a distinct odour, which emanates from the skin and is strongest in sebum-rich areas. In this study, sebum was sampled from participants using cotton gauze and the volatile components emanating from these swabs were analysed directly with thermal desorption gas chromatography - mass spectrometry (TD GC-MS). We analysed subjects with clinically established PD (n=46) along with healthy controls (n=28) sampled from two sites. The volatilome profiles obtained for PD and control cohorts were compared with the profile of participants (n=9) with isolated REM sleep behaviour disorder (iRBD) to investigate metabolite changes in probable prodromal PD. We also compared PD participants sampled at yearly intervals for a total of three years. Volatile compounds from TD GC-MS analysis were found in different quantities between PD, control and iRBD subjects. We found 55 significant features where abundance in samples from individuals with iRBD was intermediate between that found for PD and control samples. Significant features were found to be alkanes and fatty acid methyl esters (FAMEs), with other metabolites identified as an aldehyde, purine and tropinone. In olfactory analysis of the iRBD samples three out of nine were classified PD, and on clinical follow up two of these showed PD symptoms. Further, when analysing the volatilome from longitudinal PD sampling, almost two-thirds of the significant features showed differential regulation over the three visits. Our findings support the use of sebum as an accessible biofluid rich with measurable volatile compounds which alter in abundance in individuals with PD and iRBD, as the disease progresses.
Regulatory sites in the Mon1-Ccz1 complex control Rab5 to Rab7 transition and endosome maturation
Authors: Borchers Ann-Christin , Janz Maren , Schäfer Jan-Hannes , Moeller Arne , Kümmel Daniel , Paululat Achim , Ungermann Christian , Langemeyer Lars 
Published: March 2023

AbstractMaturation from early to late endosomes depends on the exchange of their marker proteins Rab5 to Rab7. This requires Rab7 activation by its specific guanine nucleotide exchange factor (GEF) Mon1-Ccz1. Efficient GEF activity of this complex on membranes depends on Rab5, thus driving Rab-exchange on endosomes. However, molecular details on the role of Rab5 in Mon1-Ccz1 activation are unclear. Here we identify key features in Mon1 involved in GEF regulation. We show that the intrinsically disordered N-terminal domain of Mon1 autoinhibits Rab5-dependent GEF-activity on membranes. Consequently, Mon1 truncations result in higher GEF activityin vitro, and a shift from Rab5 to more Rab7 positive structures inDrosophilanephrocytes and yeast, suggesting faster endosomal maturation. Using modeling, we further identify a conserved Rab5 binding site in Mon1. Mutations impairing Rab5 interaction result in poor GEF activity on membranes and growth defectsin vivo. Our analysis provides a framework to understand the mechanism of Rab-conversion and organelle maturation along the endomembrane system.SummaryTransport of proteins via the endolysosomal pathway requires Rab5 on early endosomes, which is replaced by Rab7 on late endosomes. Here, we identify distinct regulatory sites in the Rab7 activator, the Mon1-Ccz1 complex, shedding light on the regulation of Rab5 to Rab7 transition.
Plural breeding among unrelated females and other insights on complex social structure in the cooperatively breeding Variegated Fairywren
Authors: Boersma Jordan , Thrasher Derrick J. , Welklin Joseph F. , Baldassarre Daniel T. , Webster Michael S. 
Published: March 2023

AbstractCooperatively breeding species vary widely in degree of social complexity, and disentangling relationships among group members can reveal the costs and benefits of cooperation. Here, we explore the social system of a relatively unstudied cooperatively breeding bird, the Variegated Fairywren (Malurus lamberti), and explore how social complexity and group dynamics may affect cooperation and conflict. We used a combination of field-based population monitoring and detailed social association observations to determine group membership annually across four breeding seasons (2014 – 2017), and used a ddRAD-seq genotyping method to determine genetic relationships within social groups. Social groups ranged in size from 2 – 8 individuals and nearly half of all social groups had multiple adult individuals of both sexes. Approximately two-thirds of those groups exhibited plural breeding, in which multiple females within the same social group nested individually on the same territory. Genetic relationships were diverse across social groups, and many consisted of a combination of relatives and non-relatives of each sex. Notably, although related females often were present within a social group, co-breeding females in the same social group were never closely related to each other. Given extensive variation in relatedness among group members, cooperation in the Variegated Fairywren is likely maintained by a combination of direct and indirect fitness benefits.
Flexible early prospection of potential behavior in working memory
Authors: Nasrawi Rose , Boettcher Sage E.P. , van Ede Freek 
Published: March 2023

ABSTRACTFor visual working memory to serve upcoming behavior, it is crucial that we prepare for the potential use of working-memory contents ahead of time. Recent studies have demonstrated how the prospection and planning for an upcoming manual action starts early after visual encoding, and occurs alongside visual retention. Here, we address whether such ‘output planning’ in visual working memory flexibly adapts to different visual-motor mappings, and occurs even when an upcoming action will only potentially become relevant for behavior. Participants performed a visual-motor working memory task in which they remembered one or two visual items for later (potential) use. We tracked planning of upcoming behavior through contralateral attenuation of beta-band activity – a canonical motor-cortical EEG signature of manual-action planning. This revealed how action encoding and subsequent planning alongside visual working memory (1) reflects anticipated task demands rather than specific visual-motor mappings, (2) occurs even for actions that will only potentially become relevant for behavior, and (3) is associated with better performance for the encoded item, at the expense of performance to other working-memory content. This reveals how the potential prospective use of visual working memory content is flexibly planned early on, with consequences for later performance.
Impulse perturbation reveals cross-modal access to sensory working memory through learned associations
Authors: Kandemir Güven , Akyürek Elkan G. 
Published: March 2023

AbstractWe investigated if learned associations between visual and auditory stimuli can afford full cross-modal access to working memory. Previous research using the impulse perturbation technique has shown that cross-modal access to working memory is one-sided; visual impulses reveal both auditory and visual memoranda, but auditory impulses do not seem to reveal visual memoranda (Wolff et al., 2020b). Our participants first learned to associate six auditory pure tones with six visual orientation gratings. Next, a delayed match-to-sample task for the orientations was completed, while EEG was recorded. Orientation memories were recalled either via their learned auditory counterpart, or were visually presented. We then decoded the orientation memories from the EEG responses to both auditory and visual impulses presented during the memory delay. Working memory content could always be decoded from visual impulses. Importantly, through recall of the learned associations, the auditory impulse also evoked a decodable response from the visual WM network, providing evidence for full cross-modal access. We also observed that after a brief initial dynamic period, the representational codes of the memory items generalized across time, as well as between perceptual maintenance and long-term recall conditions. Our results thus demonstrate that accessing learned associations in long-term memory provides a cross-modal pathway to working memory that seems to be based on a common coding scheme.
Commensal Bacteria Maintain a Qa-1b-restricted Unconventional CD8+T Population in Gut Epithelium
Authors: Guan Jian , Peske J. David , Valerio Michael Manoharan , Park Chansu , Robey Ellen A. , Sadegh-Nasseri Scheherazade 
Published: March 2023

AbstractIntestinal intraepithelial lymphocytes (IELs) are characterized by an unusual phenotype and developmental pathway, yet their specific ligands and functions remain largely unknown. Here by analysis of QFL T cells, a population of CD8+T cells critical for monitoring the MHC I antigen processing pathway, we established that unconventional Qa-1b-restricted CD8+T cells are abundant in intestinal epithelium. We found that QFL T cells showed a Qa-1b-dependent unconventional phenotype in the spleen and small intestine of naïve wild-type mice. The splenic QFL T cells showed innate-like functionality exemplified by rapid response to cytokines or antigen, while the gut population was refractory to stimuli. Microbiota was required for the maintenance, but not the initial gut homing of QFL T cells. Moreover, monocolonization withPediococcus pentosaceus,which expresses a peptide that cross-activated QFL T cells, was sufficient to maintain QFL T cells in the intestine. Thus, microbiota is critical for shaping the Qa-1b-restricted IEL landscape.
A lack of population structure characterizes the invasiveLonicera japonicain West Virginia and across eastern North America
Authors: Barrett Craig F. , Corbett Cameron W. , Thixton-Nolan Hana L. ,   Biology 320 Class
Published: March 2023

ABSTRACTInvasive plant species cause massive ecosystem damage globally, yet represent powerful case studies in population genetics and rapid adaptation to new habitats. The availability of digitized herbarium collections data, and the ubiquity of invasive species across the landscape make them highly accessible for studies of invasion history and population dynamics associated with their introduction, establishment, spread, and ecological interactions. Here we focus onLonicera japonica, one of the most damaging invasive vine species in North America. We leveraged digitized collections data and contemporary field collections to reconstruct the invasion history and characterize patterns of genomic variation in the eastern USA, using a straightforward method for generating nucleotide polymorphism data and a recently published, chromosome-level genome for the species. We found an overall lack of population structure among sites in northern West Virginia, USA, as well as across sites in the central and eastern USA. Heterozygosity and population differentiation were both low based onFst, analysis of molecular variance, principal components analysis, and cluster-based analyses. We also found evidence of high inbreeding coefficients and significant linkage disequilibrium, in line with the ability of this otherwise outcrossing, perennial species to propagate vegetatively. Our findings corroborate earlier studies based on allozyme data, and suggest that intentional, human-assisted spread explains the lack of population structure, as this species was planted for erosion control and as an ornamental, escaping cultivation repeatedly across the USA. Finally, we discuss how plant invasion genomics can be incorporated into experiential undergraduate education as a way to integrate teaching and research.