bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-1β promotes glutamate excitotoxicity: indications for the link between inflammatory and synaptic vesicle cycle in Ménière’s disease
Authors: Zhang Na , Song Yongdong , Wang Hanyue , Li Xiaofei , Lyu Yafeng , Liu Jiahui , Mu Yurong , Wang Yan , Lu Yao , Li Guorong , Fan Zhaomin , Wang Haibo , Zhang Daogong , Li Na 
Published: November 2024

AbstractMénière’s disease (MD) is a complex inner ear disorder characterized by a range of symptoms, with its pathogenesis linked to immune-related mechanisms. Our previous research demonstrated that IL-1β maturation and release can trigger cell pyroptosis, exacerbating the severity of the endolymphatic hydrops in a mouse model; however, the specific mechanism through which IL-1β influences MD symptoms remains unclear. This study conducted on patients with MD examined changes in protein signatures in the vestibular end organs (VO) and endolymphatic sac (ES) using mass spectrometry. Gene ontology and protein pathway analyses showed that differentially expressed proteins in the ES are closely related to adhesion, whereas those in the VO are related to synapse processes. Additionally, the study found elevated expression of Glutaminase (GLS) in the VO of MD patients compared to controls. Further investigations revealed that IL-1β increased glutamate levels by upregulating GLS expression in HEI-OC1 cells. Treatment with a GLS inhibitor or an IL-1β receptor antagonist alleviated auditory-vestibular dysfunction and reduced glutamate levels in mice with endolymphatic hydrops. These findings collectively suggest that imbalanced neurotransmitter release and immune responses contribute to the pathology of MD, potentially explaining the hearing loss and vertigo associated with the disease and offering new avenues for therapeutic interventions.
Did the COVID-19 pandemic impact antibiotic prescribing patterns among dentists?
Authors: Patel Akshani , Kumar Satish 
Published: November 2024

Abstract
Data sources
Patient records from Wits Oral Health Centre were collected over two years (March 2019–March 2021). The records were divided into two groups: pre-COVID-19 (March 2019–March 2020) and COVID-19 (March 2020–March 2021). The total sample size was 698 systematically selected patient records who received antibiotics.

Study selection
A systematic random sampling method was used to select a sample of patients who received prescriptions for antibiotics. Patients were included based on their treatment time and need for antibiotic prescription. Patients whose records were missing information or treated by independent private practitioners for whom records access was not feasible were excluded.

Data extraction and synthesis
The extracted data contained information regarding the patients’ demographics, medical histories, dental condition, dental procedure, antibiotic type, frequency, dosage, duration of use, and prescribers’ disciplines. The information was categorized and captured in Microsoft Excel to analyze and create figures and tables. Analysis was performed using descriptive statistics, chi-squared, and z-tests to compare pre-COVID-19 and COVID-19 prescription patterns in RStudio.

Results
From an initial pool of 44,067 patient consultations, a systematic random sample of 698 records met the eligibility criteria for inclusion in this study. The sample was divided between pre-COVID-19 (n = 350) and COVID-19 (n = 348). A significant increase in antibiotic prescriptions was found during COVID-19 (1571 prescriptions) compared to pre-COVID-19 (1109 prescriptions). The most commonly prescribed antibiotics were amoxicillin and metronidazole. Specifically, amoxicillin was used in most cases before and during COVID-19. The combination of amoxicillin with metronidazole increased from 16.6% pre-COVID-19 to 24.4% COVID-19. It was found that many of the antibiotics prescribed from both periods were not clinically indicated (53.1% pre-COVID-19 and 54.3% COVID-19).

Conclusions
The authors concluded that the COVID-19 pandemic significantly increased antibiotic prescriptions despite fewer in-person consultations. This was likely due to insufficient surgical intervention and reliance on antibiotics to treat dental conditions. The lack of proper antibiotic use raises concerns regarding dental practitioners’ appropriate use of antibiotics. There is an urgent need for improved antibiotic stewardship to prevent the misuse and growing public health issue of antimicrobial resistance.
A framework for conducting GWAS using repeated measures data with an application to childhood BMI
Authors: Burrows Kimberley , Heiskala Anni , Bradfield Jonathan P. , Balkhiyarova Zhanna , Ning Lijiao , Boissel Mathilde , Chan Yee-Ming , Froguel Philippe , Bonnefond Amelie , Hakonarson Hakon , Alves Alexessander Couto , Lawlor Deborah A. , Kaakinen Marika , Järvelin Marjo-Riitta , Grant Struan F. A. , Tilling Kate , Prokopenko Inga , Sebert Sylvain , Canouil Mickaël , Warrington Nicole M. 
Published: November 2024

AbstractGenetic effects on changes in human traits over time are understudied and may have important pathophysiological impact. We propose a framework that enables data quality control, implements mixed models to evaluate trajectories of change in traits, and estimates phenotypes to identify age-varying genetic effects in GWAS. Using childhood BMI as an example trait, we included 71,336 participants from six cohorts and estimated the slope and area under the BMI curve within four time periods (infancy, early childhood, late childhood and adolescence) for each participant, in addition to the age and BMI at the adiposity peak and the adiposity rebound. GWAS of the 12 estimated phenotypes identified 28 genome-wide significant variants at 13 loci, one of which (in DAOA) has not been previously associated with childhood or adult BMI. Genetic studies of changes in human traits over time could uncover unique biological mechanisms influencing quantitative traits.
A developmental biliary lineage program cooperates with Wnt activation to promote cell proliferation in hepatoblastoma
Authors: Wu Peng V. , Fish Matt , Hazard Florette K. , Zhu Chunfang , Vennam Sujay , Walton Hannah , Wagh Dhananjay , Coller John , Przybyl Joanna , Morri Maurizio , Neff Norma , West Robert B. , Nusse Roel 
Published: November 2024

AbstractCancers evolve not only through the acquisition and clonal transmission of somatic mutations but also by epigenetic mechanisms that modify cell phenotype. Here, we use histology-guided and spatial transcriptomics to characterize hepatoblastoma, a childhood liver cancer that exhibits significant histologic and proliferative heterogeneity despite clonal activating mutations in the Wnt/β-catenin pathway. Highly proliferative regions with embryonal histology show high expression of Wnt target genes, the embryonic biliary transcription factor SOX4, and striking focal expression of the growth factor FGF19. In patient-derived tumoroids with constitutive Wnt activation, FGF19 is a required growth signal for FGF19-negative cells. Indeed, some tumoroids contain subsets of cells that endogenously express FGF19, downstream of Wnt/β-catenin and SOX4. Thus, the embryonic biliary lineage program cooperates with stabilized nuclear β-catenin, inducing FGF19 as a paracrine growth signal that promotes tumor cell proliferation, together with active Wnt signaling. In this pediatric cancer presumed to originate from a multipotent hepatobiliary progenitor, lineage-driven heterogeneity results in a functional growth advantage, a non-genetic mechanism whereby developmental lineage programs influence tumor evolution.
HOX gene expression in the developing human spine
Authors: Lawrence John E. G. , Roberts Kenny , Tuck Elizabeth , Li Tong , Mamanova Lira , Balogh Petra , Usher Inga , Piapi Alice , Mazin Pavel , Anderson Nathaniel D. , Bolt Liam , Richardson Laura , Prigmore Elena , He Xiaoling , Barker Roger A. , Flanagan Adrienne , Young Matthew D. , Teichmann Sarah A. , Bayraktar Omer , Behjati Sam 
Published: November 2024

AbstractPositional coding along the anterior-posterior axis is regulated by HOX genes, whose 3’ to 5’ expression correlates with location along this axis. The precise utilisation of HOX genes in different human cell types is not fully understood. Here, we use single-cell and spatial-transcriptomics, along with in-situ sequencing, to create a developmental atlas of the human fetal spine. We analyse HOX gene expression across cell types during development, finding that neural-crest derivatives unexpectedly retain the anatomical HOX code of their origin while also adopting the code of their destination. This trend is confirmed across multiple organs. In the axial plane of the spinal cord, we find distinct patterns in the ventral and dorsal domains, providing insights into motor pool organisation and loss of collinearity in HOXB genes. Our findings shed new light on HOX gene expression in the developing spine, highlighting a HOX gene ‘source code’ in neural-crest cell derivatives.
Data sharing ethics toolkit: The Human Cell Atlas
Authors: Kirby Emily , Bernier Alexander , Guigó Roderic , Wold Barbara , Arzuaga Fabiana , Kusunose Mayumi , Zawati Ma’n , Knoppers Bartha M. 
Published: November 2024

AbstractStriving to build an exhaustive guidebook of the types and properties of human cells, the Human Cell Atlas’ (HCA) success relies on the sampling of diverse populations, developmental stages, and tissue types. Its open science philosophy preconizes the rapid, seamless sharing of data – as openly as possible. In light of the scope and ambition of such an international initiative, the HCA Ethics Working Group (EWG) has been working to build a solid foundation to address the complexities of data collection and sharing as part of Atlas development. Indeed, a particular challenge of the HCA is the diversity of sampling scenarios (e.g., living participants, deceased donors, pediatric populations, culturally diverse backgrounds, tissues from various developmental stages, etc.), and associated ethical and legal norms, which vary across countries contributing to the effort. Hence, to the extent possible, the EWG set out to provide harmonised, international and interoperable policies and tools, to guide its research community. This paper provides a high-level overview of the types of challenges and approaches proposed by the EWG.
Exploitation of the fibrinolytic system by B-cell acute lymphoblastic leukemia and its therapeutic targeting
Authors: Minciacchi Valentina R. , Bravo Jimena , Karantanou Christina , Pereira Raquel S. , Zanetti Costanza , Kumar Rahul , Thomasberger Nathalie , Llavona Pablo , Krack Theresa , Bankov Katrin , Meister Melanie , Hartmann Sylvia , Maguer-Satta Véronique , Lefort Sylvain , Putyrski Mateusz , Ernst Andreas , Huntly Brian J. P. , Meduri Eshwar , Ruf Wolfram , Krause Daniela S. 
Published: November 2024

AbstractFibrinolysis influences the mobilization of hematopoietic stem cells from their bone marrow microenvironment (BMM). Here we show that activation of plasmin, a key fibrinolytic agent, by annexin A2 (ANXA2) distinctly impacts progression of BCR-ABL1+ B-cell acute lymphoblastic leukemia (B-ALL) via modulation of the extracellular matrix (ECM) in the BMM. The dense ECM in a BMM with decreased plasmin activity entraps insulin-like growth factor (IGF) 1 and reduces mTORC2-dependent signaling and proliferation of B-ALL cells. Conversely, B-ALL conditions the BMM to induce hepatic generation of plasminogen, the plasmin precursor. Treatment with ε-aminocaproic acid (EACA), which inhibits plasmin activation, reduces tumor burden and prolongs survival, including in xenogeneic models via increased fibronectin in the BMM. Human data confirm that IGF1 and fibronectin staining in trephine biopsies are correlated. Our studies suggest that fibrinolysis-mediated ECM remodeling and subsequent growth factor release influence B-ALL progression and inhibition of this process by EACA may be beneficial as adjunct therapy.
Bias and negative values of COVID-19 vaccine effectiveness estimates from a test-negative design without controlling for prior SARS-CoV-2 infection
Authors: Wiegand Ryan E. , Fireman Bruce , Najdowski Morgan , Tenforde Mark W. , Link-Gelles Ruth , Ferdinands Jill M. 
Published: November 2024

AbstractTest-negative designs (TNDs) are used to assess vaccine effectiveness (VE). Protection from infection-induced immunity may confound the association between case and vaccination status, but collecting reliable infection history can be challenging. If vaccinated individuals have less infection-induced protection than unvaccinated individuals, failure to account for infection history could underestimate VE, though the bias is not well understood. We simulated individual-level SARS-CoV-2 infection and COVID-19 vaccination histories and a TND. VE against symptomatic infection and VE against severe disease estimates unadjusted for infection history underestimated VE compared to estimates adjusted for infection history, and unadjusted estimates were more likely to be below 0%, which could lead to an incorrect interpretation that COVID-19 vaccines are harmful. TNDs assessing VE immediately following vaccine rollout introduced the largest bias and potential for negative VE against symptomatic infection. Despite the potential for bias, VE estimates from TNDs without prior infection information are useful because underestimation is rarely more than 8 percentage points.
Enteric bacterial infection stimulates remodelling of bile metabolites to promote intestinal homeostasis
Authors: Zhang Ting , Hasegawa Yuko , Waldor Matthew K. 
Published: November 2024

AbstractThe liver makes bile, an aqueous solution critical for fat absorption, which is secreted into the duodenum. Despite extensive studies on bile salts, other components of bile are less well characterized. Here we used global metabolomic analysis on bile from specific-pathogen-free, germ-free, Citrobacter rodentium-infected or Listeria monocytogenes-infected mice and identified a metabolome of 812 metabolites that were altered by both microbiota and enteric infection. Hepatic transcriptomics identified enteric-infection-triggered pathways that probably underlie bile remodelling. Enteric infection increased levels of four dicarboxylates in bile, including itaconate. Analysis of Acod1−/− mice indicated that increased itaconate also increased tuft cell abundance, altered microbiota composition and function as detected by metagenomic analysis, and modulated host defence, leading to reduced Vibrio cholerae colonization. Our data suggest that enteric-infection-associated signals are relayed between the intestine and liver and induce transcriptional programmes that shape the bile metabolome, modifying the immunomodulatory and host defence functions of bile.
A dataset of venture capitalist types in China (1978–2021): A machine-human hybrid approach
Authors: Chen Jin , Cao Ruining , Song Yifei , Hu Anan , Ding Ying 
Published: November 2024

AbstractDespite escalating interest in distinguishing among various types of venture capitalists (VCs) and their roles in shaping entrepreneurship and innovation, such research remains sparse in the world’s second-largest VC market, i.e., China. To address this important gap, we have devised a machine-human hybrid approach to perform the classification task for VC types. Specifically, we have compiled a list of 49,187 VCs that made investments in China before 2021 from CVSource database, collected VC ownership information from other public sources, developed machine-learning algorithms to predict VC types, and used human coders when machine-learning failed to produce a prediction. Utilizing this hybrid approach, we have classified VCs into one of the following types: GVC (public agency-affiliated, state-owned enterprise-affiliated), CVC (corporate VC), IVC (independent VC), BVC (bank-affiliated VC), FVC (financial/non-bank-affiliated VC), UVC (university-affiliated VC), and PenVC (pension-fund-affiliated VC). We not only provide the most up-to-date database for VC types in the Chinese setting but also demonstrate how to leverage machine-learning algorithms to devise a transparent coding approach for VC-type classifications.
Pathological effects and immune modulation in host during Tilapia Parvovirus (TiPV) outbreak in cage and wetland Tilapia farms
Authors: Das Basanta Kumar , Kumar Vikash , Roy Suvra , Malick Ramesh Chandra , Bisai Kampan , Jana Asim Kumar , Dhar Souvik 
Published: November 2024

AbstractViral diseases arising in farmed fish are an ongoing challenge to the aquaculture industry, causing severe mortality and economic losses. Recently, there has been a spike in the incidence of a viral disease caused by Tilapia Parvovirus (TiPV) inflicts irreparable damage, and large-scale fish kills in the farmed tilapia species. We investigated a case of disease outbreak and severe mortality in cage and wetland farms of tilapia in West Bengal and Odisha, India. The symptomatic fish showed clinical signs, including hemorrhage, discoloration, ulcer, and redness in the body surfaces. Further analysis revealed that Tilapia Parvovirus was associated (validated by PCR, phylogenetic analysis, and cell line assay) with the infection and mortality of tilapia. The virus was detected in gill, heart, spleen, liver, and kidney samples collected from apparently healthy (asymptomatic) and symptomatic tilapia samples from cage and wetland farms. At the same time, negative results were found in the brain and skin tissue samples. The histological analysis revealed that TiPV induces severe damage invariably in almost all studied tissue, including the liver, kidney, spleen, gill, heart, and brain of tilapia samples. The viral quantification analysis showed that the viral genome was higher in the liver, spleen, and heart than in the tilapia samples’ gill, kidney, or brain tissue. Furthermore, the study indicated that TiPV infection has a significant effect on the health of tilapia. The tilapia exhibited an immune reactivity toward TiPV infection (upregulation of chemokine receptors, CRs and interleukin 1β, IL-1β), the majority of the studied immune genes (interleukin 8, IL-8; Toll-like receptors 7, TLR7; tumour necrosis factor α, TNF-α; major histocompatibility complex II, MHC II and nuclear factor kappa B, NF-kB) were significantly downregulated in the kidney, spleen and liver tissue samples of symptomatic tilapia. Further, the in vivo challenge assay confirms that the isolated TiPV is a novel parvovirus pathogen that causes massive mortality in tilapia. The lessons learned from the first cellular and molecular description associated with TiPV epidemiology from wetland and cage farms of tilapia could be critical to developing the current state of the tilapia farming industry. Additionally, a holistic approach is needed to develop management measures to control the virulence and risk factors of TiPV.
Sevoflurane exposure in early life: mitochondrial dysfunction and neurotoxicity in immature rat brains without long-term memory loss
Authors: Qiu Lin , Li Hongwei , Li Bingbing , Ek Joakim , Zhang Xiaoli , Chen Yiwen , Shao Zehua , Zhang Jie , Zhang Jiaqiang , Lin Hongqi , Zhu Changlian , Xu Yiran , Wang Xiaoyang 
Published: November 2024

AbstractNeurotoxic effects of general anesthetics, particularly sevoflurane, on pediatric neurodevelopment are a global concern. This study investigated the molecular and metabolic impacts of repeated short exposures to sevoflurane in neonatal rats. Metabolomics analysis revealed significant changes in fatty acid and mitochondrial energy metabolism. Transcriptomic analysis identified altered gene expression related to neurodevelopment and mitochondrial function. Various analyses emphasized upregulation in oxidative phosphorylation and DNA repair pathways. Weighted gene co-expression network analysis (WGCNA) identified key gene modules associated with sevoflurane exposure. Despite these acute changes, no significant long-term memory impairments were detected. These findings highlight the impact of sevoflurane on mitochondrial energy metabolism, oxidative stress, and neuroinflammation, emphasizing its relevance to pediatric neurodevelopment. The absence of substantial long-term memory impairments provides insights into the safety and implications of sevoflurane use in pediatric anesthesia, calling for further research.
Nonlinear and symptom specific associations between chronotype and depression
Authors: Seizer Lennart , Martínez-Albert Estefanía , Löchner Johanna 
Published: November 2024

AbstractThe chronotype of individuals has been found to be predictive of depression risk and associated with the severity of depression. However, since depression is a phenotypically heterogeneous disease, it seems improbable that chronotype plays a role in every instance of depression. This study investigates the association between the two, while considering possible symptom-specificity and non-linearity of the relationship, utilizing a large sample from the National Health and Nutrition Examination Survey (N = 5217; 54% female; Age: M = 52.65, SD = 18.76). Depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), and chronotype was determined by calculating sleep midpoints. Further, we also explored the potential mediating role of systemic inflammation, measured by C-reactive protein (CRP) levels, in the chronotype-depression link. The findings substantiate previous research indicating late chronotypes to be associated with higher PHQ-9 sum scores, with a minimum in PHQ-9 at a sleep midpoint of 02:49. The study further differentiates between individual depression symptoms, uncovering varying patterns of association with chronotype. No significant effect of chronotype on levels of CRP was found, suggesting that the link between chronotype and depression symptoms may not be directly mediated and appears to be stable and independent from systemic inflammation. The study highlights the non-linear and symptom-specific nature of the chronotype-depression connection and suggests the need for further, longitudinal studies to elucidate causal mechanisms and potential mediators.
Avian raptors are indicator species and victims of high pathogenicity avian influenza virus HPAIV H5N1 (clade 2.3.4.4b) in Germany
Authors: Günther Anne , Krone Oliver , Globig Anja , Pohlmann Anne , King Jacqueline , Fast Christine , Grund Christian , Hennig Christin , Herrmann Christof , Piro Simon , Rubbenstroth Dennis , Schulz Jana , Staubach Christoph , Stacker Lina , Ulrich Lorenz , Ziegler Ute , Harder Timm , Beer Martin 
Published: November 2024

AbstractTransition of highly pathogenic clade 2.3.4.4b H5 avian influenza virus (HPAIV) from epizootic to enzootic status in Northern European countries was associated with severe losses and even mass mortalities among various wild bird species. Both avian and mammalian raptors hunting infected debilitated birds or scavenging on virus-contaminated avian carcasses contracted HPAIV infection. This precarious pathogen-prey-predator relation further worsened when in 2021 and 2022 outbreaks in Germany overlapped with the hatching season of avian raptor species. Retro- and prospective surveillance revealed avian raptors as important indicators of HPAIV and its genetic diversity on the one hand. On the other hand, their role as victims of HPAIV is stipulated. The first case of an HPAIV H5N1-related death of a white-tailed sea eagle (Haliaeetus albicilla; WTSE) hatch in Germany, 2021, followed by several such cases in 2022, and a low overall seropositivity rate of 5.0–7.9% among WTSE nestlings, raised fears of a serious negative impact on reproduction rates of WTSEs and other birds of prey when HPAIV becomes enzootic in an ecosystem. However, comparably stable breeding success of WTSE in the study area in 2022 and a potentially evolving natural immunity raises hope for a less severe long-term impact.