bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating genetically stratified subgroups to better understand the etiology of alcohol misuse
Authors: Thijssen Anaïs B. ,   Spit for Science Working Group,   Director, Chartier Karen ,   Co-Director, Amstadter Ananda ,   Past Founding Director, Dick Danielle M. ,   Registry management, Lilley Emily , Gelzinis Renolda , Morris Anne ,   Data cleaning and management, Bountress Katie , Adkins Amy E. , Thomas Nathaniel , Neale Zoe , Pedersen Kimberly , Bannard Thomas , Cho Seung B. ,   Data collection, Barr Peter , Byers Holly , Berenz Erin C. , Caraway Erin , Clifford James S. , Cooke Megan , Do Elizabeth , Edwards Alexis C. , Goyal Neeru , Hack Laura M. , Halberstadt Lisa J. , Hawn Sage , Kuo Sally , Lasko Emily , Lend Jennifer , Lind Mackenzie , Long Elizabeth , Martelli Alexandra , Meyers Jacquelyn L. , Mitchell Kerry , Moore Ashlee , Moscati Arden , Nasim Aashir , Opalesky Jill , Overstreet Cassie , Pais A. Christian , Raldiris Tarah , Salvatore Jessica , Savage Jeanne , Smith Rebecca , Sosnowski David , Su Jinni , Walker Chloe , Walsh Marcie , Willoughby Teresa , Woodroof Madison , Yan Jia ,   Genotypic data processing and cleaning, Sun Cuie , Wormley Brandon , Riley Brien , Aliev Fazil , Peterson Roseann , Webb Bradley T. , Dick Danielle M. , Posthuma Danielle , Savage Jeanne E. 
Published: July 2023

AbstractAlcohol misuse (AM) is highly prevalent and harmful, with theorized subgroups differing on internalizing and externalizing dimensions. Despite known heterogeneity, genome-wide association studies (GWAS) are usually conducted on unidimensional phenotypes. These approaches have identified important genes related to AM but fail to capture a large part of the heritability, even with recent increases in sample sizes. This study aimed to address phenotypic heterogeneity in GWAS to aid gene finding and to uncover the etiology of different types of AM. Genetic and phenotypic data from 410,414 unrelated individuals of multiple ancestry groups (primarily European) in the UK Biobank were obtained. Mixture modeling was applied to measures of alcohol misuse and internalizing/externalizing psychopathology to uncover phenotypically homogenous subclasses, which were carried forward to GWAS and functional annotation. A four-class model emerged with “low risk”, “internalizing—light/non-drinkers”, “heavy alcohol use—low impairment”, and “broad high risk” classes. SNP heritability ranged from 3 to 18% and both known AM signals and novel signals were captured by genomic risk loci. Class comparisons showed distinct patterns of regional brain tissue enrichment and genetic correlations with internalizing and externalizing phenotypes. Despite some limitations, this study demonstrated the utility of genetic research on homogenous subclasses. Not only were novel genetic signals identified that might be used for follow-up studies, but addressing phenotypic heterogeneity allows for the discovery and investigation of differential genetic vulnerabilities in the development of AM, which is an important step towards the goal of personalized medicine.
Intravenous immunoglobulin G therapy for neonatal hyperbilirubinemia
Authors: Rasiah Saisujani , Jegathesan Thivia , Campbell Douglas M. , Shah Prakeshkumar S. , Sgro Michael D. 
Published: July 2023

Abstract
Background
Neonatal hyperbilirubinemia (NHb) results from increased total serum bilirubin and is a common reason for admission and readmission amongst newborn infants born in North America. The use of intravenous immunoglobulin (IVIG) therapy for treating NHb has been widely debated, and the current incidence of NHb and its therapies remain unknown.

Methods
Using national and provincial databases, a population-based retrospective cohort study of infants born in Ontario from April 2014 to March 2018 was conducted.

Results
Of the 533,084 infants born in Ontario at ≥35 weeks gestation, 29,756 (5.6%) presented with NHb. Among these infants, 80.1–88.2% received phototherapy, 1.1–2.0% received IVIG therapy and 0.1–0.2% received exchange transfusion (ET) over the study period. Although phototherapy was administered (83.0%) for NHb, its use decreased from 2014 to 2018 (88.2–80.1%) (P < 0.01). Similarly, the incidence of IVIG therapy increased from 71 to 156 infants (1.1–2.0%) (P < 0.01) and a small change in the incidence of ET (0.2–0.1%) was noted.

Conclusion
IVIG therapy is increasingly being used in Ontario despite limited studies evaluating its use. The results of this study could inform treatment and management protocols for NHb.

Impacts

Clinically significant neonatal hyperbilirubinemia still occurs in Ontario, with an increasing number of infants receiving Intravenous Immunoglobulin G (IVIG) therapy.

IVIG continues to be used at increasing rates despite inconclusive evidence to recommend its use.

This study highlights the necessity of a future prospective study to better determine the effectiveness of IVIG use in treating neonatal hyperbilirubinemia, especially given the recent shortage in IVIG supply in Ontario.

The results of this study could inform treatment and management protocols for neonatal hyperbilirubinemia.
Heparanase 2 (Hpa2)- a new player essential for pancreatic acinar cell differentiation
Authors: Kayal Yasmin , Barash Uri , Naroditsky Inna , Ilan Neta , Vlodavsky Israel 
Published: July 2023

AbstractHeparanase 2 (Hpa2, HPSE2) is a close homolog of heparanase. Hpa2, however, lacks intrinsic heparan sulfate (HS)-degrading activity, the hallmark of heparanase enzymatic activity. Mutations of HPSE2 were identified in patients diagnosed with urofacial syndrome (UFS), a rare genetic disorder that exhibits abnormal facial expression and bladder voiding dysfunction, leading to renal damage and eventually renal failure. In order to reveal the role of HPSE2 in tissue homeostasis, we established a conditional Hpa2-KO mouse. Interestingly, the lack of Hpa2 was associated with a marked decrease in the expression of key pancreatic transcription factors such as PTF1, GATA6, and Mist1. This was associated with a two-fold decrease in pancreas weight, increased pancreatic inflammation, and profound morphological alterations of the pancreas. These include massive accumulation of fat cells, possibly a result of acinar-to-adipocyte transdifferentiation (AAT), as well as acinar-to-ductal metaplasia (ADM), both considered to be pro-tumorigenic. Furthermore, exposing Hpa2-KO but not wild-type mice to a carcinogen (AOM) and pancreatic inflammation (cerulein) resulted in the formation of pancreatic intraepithelial neoplasia (PanIN), lesions that are considered to be precursors of invasive ductal adenocarcinoma of the pancreas (PDAC). These results strongly support the notion that Hpa2 functions as a tumor suppressor. Moreover, Hpa2 is shown here for the first time to play a critical role in the exocrine aspect of the pancreas.
Single-cell transcriptomics reveals intestinal cell heterogeneity and identifies Ep300 as a potential therapeutic target in mice with acute liver failure
Authors: Yin Jie , Zhao Ziming , Huang Jianzheng , Xiao Yang , Rehmutulla Mewlude , Zhang Biqiong , Zhang Zijun , Xiang Ming , Tong Qingyi , Zhang Yonghui 
Published: July 2023

AbstractAcute liver failure (ALF) is a severe life-threatening disease associated with the disorder of the gut-liver axis. However, the cellular characteristics of ALF in the gut and related therapeutic targets remain unexplored. Here, we utilized the D-GALN/LPS (D/L)-induced ALF model to characterize 33,216 single-cell transcriptomes and define a mouse ALF intestinal cellular atlas. We found that unique, previously uncharacterized intestinal immune cells, including T cells, B cells, macrophages, and neutrophils, are responsive to ALF, and we identified the transcriptional profiles of these subsets during ALF. We also delineated the heterogeneity of intestinal epithelial cells (IECs) and found that ALF-induced cell cycle arrest in intestinal stem cells and activated specific enterocyte and goblet cell clusters. Notably, the most significantly altered IECs, including enterocytes, intestinal stem cells and goblet cells, had similar activation patterns closely associated with inflammation from intestinal immune activation. Furthermore, our results unveiled a common Ep300-dependent transcriptional program that coordinates IEC activation during ALF, which was confirmed to be universal in different ALF models. Pharmacological inhibition of Ep300 with an inhibitor (SGC-CBP30) inhibited this cell-specific program, confirming that Ep300 is an effective target for alleviating ALF. Mechanistically, Ep300 inhibition restrained inflammation and oxidative stress in the dysregulated cluster of IECs through the P38-JNK pathway and corrected intestinal ecology by regulating intestinal microbial composition and metabolism, thereby protecting IECs and attenuating ALF. These findings confirm that Ep300 is a novel therapeutic target in ALF and pave the way for future pathophysiological studies on ALF.
The allotetraploid horseradish genome provides insights into subgenome diversification and formation of critical traits
Authors: Shen Fei , Xu Shixiao , Shen Qi , Bi Changwei , Lysak Martin A. 
Published: July 2023

AbstractPolyploidization can provide a wealth of genetic variation for adaptive evolution and speciation, but understanding the mechanisms of subgenome evolution as well as its dynamics and ultimate consequences remains elusive. Here, we report the telomere-to-telomere (T2T) gap-free reference genome of allotetraploid horseradish (Armoracia rusticana) sequenced using a comprehensive strategy. The (epi)genomic architecture and 3D chromatin structure of the A and B subgenomes differ significantly, suggesting that both the dynamics of the dominant long terminal repeat retrotransposons and DNA methylation have played critical roles in subgenome diversification. Investigation of the genetic basis of biosynthesis of glucosinolates (GSLs) and horseradish peroxidases reveals both the important role of polyploidization and subgenome differentiation in shaping the key traits. Continuous duplication and divergence of essential genes of GSL biosynthesis (e.g., FMOGS-OX, IGMT, and GH1 gene family) contribute to the broad GSL profile in horseradish. Overall, the T2T assembly of the allotetraploid horseradish genome expands our understanding of polyploid genome evolution and provides a fundamental genetic resource for breeding and genetic improvement of horseradish.
Neural network-based Bluetooth synchronization of multiple wearable devices
Authors: Balasubramanian Karthikeyan Kalyanasundaram , Merello Andrea , Zini Giorgio , Foster Nathan Charles , Cavallo Andrea , Becchio Cristina , Crepaldi Marco 
Published: July 2023

AbstractBluetooth-enabled wearables can be linked to form synchronized networks to provide insightful and representative data that is exceptionally beneficial in healthcare applications. However, synchronization can be affected by inevitable variations in the component’s performance from their ideal behavior. Here, we report an application-level solution that embeds a Neural network to analyze and overcome these variations. The neural network examines the timing at each wearable node, recognizes time shifts, and fine-tunes a virtual clock to make them operate in unison and thus achieve synchronization. We demonstrate the integration of multiple Kinematics Detectors to provide synchronized motion capture at a high frequency (200 Hz) that could be used for performing spatial and temporal interpolation in movement assessments. The technique presented in this work is general and independent from the physical layer used, and it can be potentially applied to any wireless communication protocol.
Ezh2 emerges as an epigenetic checkpoint regulator during monocyte differentiation limiting cardiac dysfunction post-MI
Authors: Rondeaux Julie , Groussard Déborah , Renet Sylvanie , Tardif Virginie , Dumesnil Anaïs , Chu Alphonse , Di Maria Léa , Lemarcis Théo , Valet Manon , Henry Jean-Paul , Badji Zina , Vézier Claire , Béziau-Gasnier Delphine , Neele Annette E. , de Winther Menno P. J. , Guerrot Dominique , Brand Marjorie , Richard Vincent , Durand Eric , Brakenhielm Ebba , Fraineau Sylvain 
Published: July 2023

AbstractEpigenetic regulation of histone H3K27 methylation has recently emerged as a key step during alternative immunoregulatory M2-like macrophage polarization; known to impact cardiac repair after Myocardial Infarction (MI). We hypothesized that EZH2, responsible for H3K27 methylation, could act as an epigenetic checkpoint regulator during this process. We demonstrate for the first time an ectopic EZH2, and putative, cytoplasmic inactive localization of the epigenetic enzyme, during monocyte differentiation into M2 macrophages in vitro as well as in immunomodulatory cardiac macrophages in vivo in the post-MI acute inflammatory phase. Moreover, we show that pharmacological EZH2 inhibition, with GSK-343, resolves H3K27 methylation of bivalent gene promoters, thus enhancing their expression to promote human monocyte repair functions. In line with this protective effect, GSK-343 treatment accelerated cardiac inflammatory resolution preventing infarct expansion and subsequent cardiac dysfunction in female mice post-MI in vivo. In conclusion, our study reveals that pharmacological epigenetic modulation of cardiac-infiltrating immune cells may hold promise to limit adverse cardiac remodeling after MI.
Compilation of reported protein changes in the brain in Alzheimer’s disease
Authors: Askenazi Manor , Kavanagh Tomas , Pires Geoffrey , Ueberheide Beatrix , Wisniewski Thomas , Drummond Eleanor 
Published: July 2023

AbstractProteomic studies of human Alzheimer’s disease brain tissue have potential to identify protein changes that drive disease, and to identify new drug targets. Here, we analyse 38 published Alzheimer’s disease proteomic studies, generating a map of protein changes in human brain tissue across thirteen brain regions, three disease stages (preclinical Alzheimer’s disease, mild cognitive impairment, advanced Alzheimer’s disease), and proteins enriched in amyloid plaques, neurofibrillary tangles, and cerebral amyloid angiopathy. Our dataset is compiled into a searchable database (NeuroPro). We found 848 proteins were consistently altered in 5 or more studies. Comparison of protein changes in early-stage and advanced Alzheimer’s disease revealed proteins associated with synapse, vesicle, and lysosomal pathways show change early in disease, but widespread changes in mitochondrial associated protein expression change are only seen in advanced Alzheimer’s disease. Protein changes were similar for brain regions considered vulnerable and regions considered resistant. This resource provides insight into Alzheimer’s disease brain protein changes and highlights proteins of interest for further study.
Circular RNA encoded MET variant promotes glioblastoma tumorigenesis
Authors: Zhong Jian , Wu Xujia , Gao Yixin , Chen Junju , Zhang Maolei , Zhou Huangkai , Yang Jia , Xiao Feizhe , Yang Xuesong , Huang Nunu , Qi Haoyue , Wang Xiuxing , Bai Fan , Shi Yu , Zhang Nu 
Published: July 2023

AbstractActivated by its single ligand, hepatocyte growth factor (HGF), the receptor tyrosine kinase MET is pivotal in promoting glioblastoma (GBM) stem cell self-renewal, invasiveness and tumorigenicity. Nevertheless, HGF/MET-targeted therapy has shown limited clinical benefits in GBM patients, suggesting hidden mechanisms of MET signalling in GBM. Here, we show that circular MET RNA (circMET) encodes a 404-amino-acid MET variant (MET404) facilitated by the N6-methyladenosine (m6A) reader YTHDF2. Genetic ablation of circMET inhibits MET404 expression in mice and attenuates MET signalling. Conversely, MET404 knock-in (KI) plus P53 knock-out (KO) in mouse astrocytes initiates GBM tumorigenesis and shortens the overall survival. MET404 directly interacts with the MET β subunit and forms a constitutively activated MET receptor whose activity does not require HGF stimulation. High MET404 expression predicts poor prognosis in GBM patients, indicating its clinical relevance. Targeting MET404 through a neutralizing antibody or genetic ablation reduces GBM tumorigenicity in vitro and in vivo, and combinatorial benefits are obtained with the addition of a traditional MET inhibitor. Overall, we identify a MET variant that promotes GBM tumorigenicity, offering a potential therapeutic strategy for GBM patients, especially those with MET hyperactivation.
Cytokine and chemokine map of peripheral specific immune cell subsets in Parkinson’s disease
Authors: Jiang Si-Si , Wang Yi-Ling , Xu Qiu-Han , Gu Lu-Yan , Kang Rui-Qing , Yang Wen-Yi , Zhang Bao-Rong , Tian Jun , Pu Jia-Li 
Published: July 2023

AbstractPeripheral immune cells play a vital role in the development of Parkinson’s disease (PD). However, their cytokine and chemokine secretion functions remain unclear. Therefore, we aimed to explore the cytokine and chemokine secretion functions of specific immune cell subtypes in drug-naïve patients with PD at different ages of onset. We included 10 early-onset and 10 late-onset patients with PD and age-matched healthy controls (HCs). We used mass cytometry to select specific immune cell subsets and evaluate intracellular cytokine and chemokine expression. Statistical tests includedt-tests, analysis of variance, bivariate correlation analysis, and linear regression analysis. Compared with HCs, patients with PD exhibited significantly decreased intracellular pro-inflammatory cytokines and chemokines in selected clusters (e.g., tumor necrosis factor (TNF)-α, interleukin (IL)−8, IL-1β, and CC-chemokine ligand (CCL)17). Specific cytokines and cell clusters were associated with clinical symptoms. TNF-α played an important role in cognitive impairment. Intracellular TNF-α levels in the naïve CD8+T-cell cluster C16 (CD57−naïve CD8+T) and natural killer (NK) cell cluster C32 (CD57−CD28−NK) were negatively correlated with Montreal Cognitive Assessment scores. The C16 cluster affected cognitive function and motor symptoms. Increased TNF-α and decreased interferon-γ expression in C16 correlated with increased Unified Parkinson’s Disease Rating Scale III scores in patients with PD. In summary, we developed a more detailed cytokine and chemokine map of peripheral specific CD8+T cell and NK cell subsets, which revealed disrupted secretory function in patients with PD and provided unique clues for further mechanistic exploration.
Dataset of metals and metalloids in food crops and soils sampled across the mining region of Moquegua in Peru
Authors: Bedoya-Perales Noelia S. , Escobedo-Pacheco Elias , Maus Diogo , Neimaier Alisson , Pumi Guilherme 
Published: July 2023

AbstractIn recent years, there has been an increase in interest in the accumulation of heavy metals and metal(loid)s (HMM) in areas where agriculture and mining exist side by side. As a contribution to this body of knowledge, we report the first dataset into HMM concentrations in food crops and agricultural soils in Moquegua, which is a typical mining region and contains one of Peru’s largest copper deposits. Thanks to its geographic diversity, samples were taken in different agroecological regions at altitudes between 9 and 3,934 m. For food crops, 31 elements were measured using inductively coupled plasma mass spectrometry and atomic absorption spectrometry. For soils, 23 elements were measured using inductively coupled plasma optical emission spectrometry. Thus, the dataset includes a total of 13,828 observations from 341 sampling sites. We hope that this dataset will facilitate a wide range of agricultural and food safety studies, as well as serving as a reference for monitoring changes in pollution over time or comparing HMM levels with other farmlands influenced by mining activities.
Soft-robotic green sea turtle (Chelonia mydas) developed to replace animal experimentation provides new insight into their propulsive strategies
Authors: van der Geest Nick , Garcia Lorenzo , Borret Fraser , Nates Roy , Gonzalez Alberto 
Published: July 2023

AbstractGreen sea turtles (Chelonia mydas) can swim up to 50 km per day while only consuming seagrass or microalgae. How the animal accomplishes this vast journey on such low energy intake points to the effectiveness of their swimming technique and is a testament to the power of evolution. Understanding the green sea turtle's ability to accomplish these journeys requires insight into their propulsive strategies. Conducting animal testing to uncover their propulsive strategies brings significant challenges: firstly, the ethical issues of conducting experiments on an endangered animal, and secondly, the animal may not even swim with its regular routine during the experiments. In this work, we develop a new soft-robotic sea turtle that reproduces the real animal's form and function to provide biomechanical insights without the need for invasive experimentation. We found that the green sea turtle may only produce propulsion for approximately 30% of the limb beat cycle, with the remaining 70% exploiting a power-preserving low-drag glide. Due to the animal's large mass and relatively low drag coefficient, losses in swim speed are minimal during the gliding stage. These findings may lead to the creation of a new generation of robotic systems for ocean exploration that use an optimised derivative of the sea turtle propulsive strategy.
Traces of early developmental bias in the adult brain
Authors: Serero Gad , Lev Maria , Sagi Dov , Polat Uri 
Published: July 2023

AbstractDuring the first 2 years of life, there is a high prevalence of optical distortions in the human eye, causing vertical blur on the retina (astigmatism), which is naturally resolved by the age of 5; thus, it is not treated. Here we determined the possible long-term effects on visual grouping resulting from optical distortions during the development of visual perception. Our results show a clear directional bias in shape perception for optically corrected astigmatic adults, compared with non-astigmatic ones, with remarkably slow decision times. These effects can be explained by a mismatch between the developmental timescales of different components in the visual system.
Psychological distance intervention reminders reduce alcohol consumption frequency in daily life
Authors: Jovanova Mia , Cosme Danielle , Doré Bruce , Kang Yoona , Stanoi Ovidia , Cooper Nicole , Helion Chelsea , Lomax Silicia , McGowan Amanda L. , Boyd Zachary M. , Bassett Dani S. , Mucha Peter J. , Ochsner Kevin N. , Lydon-Staley David M. , Falk Emily B. 
Published: July 2023

AbstractModifying behaviors, such as alcohol consumption, is difficult. Creating psychological distance between unhealthy triggers and one’s present experience can encourage change. Using two multisite, randomized experiments, we examine whether theory-driven strategies to create psychological distance—mindfulness and perspective-taking—can change drinking behaviors among young adults without alcohol dependence via a 28-day smartphone intervention (Study 1, N = 108 participants, 5492 observations; Study 2, N = 218 participants, 9994 observations). Study 2 presents a close replication with a fully remote delivery during the COVID-19 pandemic. During weeks when they received twice-a-day intervention reminders, individuals in the distancing interventions reported drinking less frequently than on control weeks—directionally in Study 1, and significantly in Study 2. Intervention reminders reduced drinking frequency but did not impact amount. We find that smartphone-based mindfulness and perspective-taking interventions, aimed to create psychological distance, can change behavior. This approach requires repeated reminders, which can be delivered via smartphones.