bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative immuno-biology at clinical recognition of early multiple organ dysfunction syndrome in pediatric and adult patients using single-cell transcriptomics
Authors: Shankar Rama , Goodyke Austin W. , Koirala Shubham , Paithankar Shreya , Chen Ruoqiao , Hartog Nicholas L. , Chesla Dave , Rajasekaran Surender , Chen Bin 
Published: January 2025

AbstractGlobally, sepsis remains a major health issue, with Multiple Organ Dysfunction Syndrome (MODS) being a leading cause of mortality. MODS, a severe condition often seen in intensive care units, typically results from infections or trauma and involves complex pathophysiological processes requiring various clinical interventions. Although infections are the main triggers, the mechanisms driving MODS remain unclear. To investigate the transition of sepsis to MODS, we generated a single cell RNA sequencing dataset comprising 86,839 immune cells from pediatric sepsis patients at the clinical onset of MODS patients and age-matched controls, identifying 22 distinct cell types. A cluster ofS100genes, located in the same genomic region, was highly expressed in neutrophils in MODS patients, demonstrating strong diagnostic potential across cohorts (AUC=0.94– 0.99) and potential as therapeutic targets. We found that many B and T cells showed heightened inflammation and increased apoptotic activity during early MODS. Additionally, specific transcription regulators and surface proteins associated with inflammation andS100regulations were uniquely expressed in MODS. Pseudotime analysis revealed distinctS100gene expression patterns between controls and MODS. Cell-cell interaction analysis highlighted dendritic cells as key mediators, enhancing communication between plasma cells and Vδ T cells while activating inflammatory and immunosuppressive pathways. We also analyzed 116,803 immune cells from adult MODS patients, revealing stronger immune dysregulation compared to pediatric MODS, including alteredS100gene expression, and enhanced cell-cell interactions. These findings suggest thatS100genes may serve as a marker for MODS. Furthermore, insights gained from adult MODS could improve our understanding of rare pediatric MODS and contribute to the development of better therapeutics for all MODS patients.
CD38 expression by neonatal human naïve CD4+T cells shapes their distinct metabolic state and high regulatory T cell potential
Authors: Dwyer Laura R. , Clancy Sean , Gouirand Victoire , Chien Charles , Rogers Elizabeth E. , Oltman Scott P. , Jelliffe-Pawlowski Laura L. , Lynch Susan V. , Wagner Allon , Combes Alexis J. , Scharschmidt Tiffany C. 
Published: January 2025

AbstractNeonatal life is marked by rapid antigen exposure, necessitating establishment of peripheral immune tolerance via conversion of naïve CD4+T cells into regulatory T cells (Tregs). Here, we demonstrate that increased Treg differentiation by naive CD4+T cells from human cord blood versus adult blood is integrally linked to their unique metabolic profile and their elevated expression of the NADase, CD38. Early life naïve CD4+T cells demonstrate a metabolic preference for glycolysis, which directly facilitates their Treg generation. We reveal an age-dependent gradient in CD38 levels on naïve CD4+T cells and show that high CD38 expression contributes to both the glycolytic state and high Treg potential of neonatal CD4+T cells, effects that are mediated at least in part via the NAD-dependent deacetylase SIRT1. Thus, the early life window for peripheral tolerance in humans is critically enabled by the immunometabolic state of the naïve CD4+compartment.
Real-time fMRI neurofeedback reduces default mode network and auditory cortex functional connectivity in schizophrenia
Authors: Zhang Jiahe , Bauer Clemens C.C. , Morfini Francesca , Lee Yoonji , Stone Lena , Awad Angelina , Okano Kana , Hwang Melissa , Shinn Ann K. , Niznikiewicz Margaret A. , Whitfield-Gabrieli Susan 
Published: January 2025

ABSTRACTBackground and HypothesisAuditory verbal hallucinations (AHs) are a cardinal symptom of schizophrenia that can cause distress but are not always responsive to antipsychotic medications. There is a critical need to develop novel interventions that target neural mechanisms underlying AHs. We developed a real-time fMRI neurofeedback (NFB) paradigm for AHs that aims at modulating default mode network (DMN) functional connectivity.Study DesignPatients with schizophrenia or schizoaffective disorders who were experiencing AHs (N= 25) attempted to decrease brain activation while listening to sentences recorded in another person’s voice and increase brain activation while listening to sentences recorded in their own voice. Participants randomly assigned to the ‘real’ group (n= 12) received neurofeedback based on signals from their auditory cortex in the superior temporal gyrus (STG) and those assigned to the ‘sham’ group (n= 13) received neurofeedback based on motor cortex signals.Study ResultsAnalyzing resting state fMRI data collected pre- and post-NFB, we found that: (1) at baseline, stronger within-DMN connectivity between the medial prefrontal cortex (MPFC) and posterior cingulate cortex was associated with higher AHs severity; (2) after NFB, participants in the real group, compared to those in the sham group, showed greater reduction in functional connectivity between the MPFC and auditory cortices in the STG and middle temporal gyrus (MTG). Notably, the reduction in MPFC-STG/MTG connectivity was found in all participants in the real group.ConclusionsThese findings suggest that NFB can effectively and non-invasively modulate functional connectivity in regions associated with AHs in psychosis.
Separation measurement of two freely rotating dipole emitters at near optimal precision
Authors: Liu Sheng , Pani Sujeet , Khan Sajjad A. , Becerra Francisco E. , Lidke Keith A. 
Published: January 2025

AbstractAccording to Rayleigh’s criterion, two incoherent emitters with a separation below the diffraction limit are not resolvable with a conventional fluorescence microscope. One method of Super-Resolution Microscopy (SRM) breaks the diffraction-limited resolution by precisely estimating the centroid position of spatiotemporally independent emitters. However, conventional detection methods of SRM techniques are not optimal for estimating the separation of two simultaneously excited emitters. Recently, a number of detection methods based on modal imaging were developed to achieve the quantum Cramér-Rao lower bound (QCRB) for estimating separations between two nearby emitters. The QCRB determines the minimum achievable precision across all possible detection methods. Current modal imaging techniques assume a scalar field generated from a point source, such as an optical fiber or a pinhole. However, for fluorescently labeled samples, point emitters are single fluorophores that can be modeled as dipole emitters, and in practice are often freely rotating. Dipole radiation must be expressed in vectorial theory and the assumption of a scalar field no longer holds. Here we propose a detection scheme based on one of the modal imaging techniques, super-localization by image inversion interferometry (SLIVER), for separation estimation of two freely rotating dipoles. We introduce a vortex wave plate before the SLIVER detection to separate the radial and azimuthal components of the dipole radiation. We demonstrated that our method achieves near constant precision independent of the separation between two dipole emitters. We also quantified the effect of numerical aperture, detection bandwidth, number of estimation parameters, background and misalignment on separation estimation. Our method provides a near optimal detection scheme for measuring the separation of two freely-rotating dipole emitters such as fluorescently tagged molecules.
A NovelXACTlncRNA Transcript with Functions Transcending X-Chromosome Inactivation
Authors: Zhang Peifen , Angles Paula Haro , Zhang Hong , Li Tingyue , Mulet-Lazaro Roger , van IJcken Wilfred F.J. , Philipsen Sjaak , Delwel Ruud , Gribnau Joost , Huylebroeck Danny , Grosveld Frank , Rougeulle Claire , Mulugeta Eskeatnaf 
Published: January 2025

AbstractX-chromosome inactivation (XCI) is initiated during early mammalian embryogenesis by a long non-coding RNA (lncRNA)XIST, which coats one of the two X-chromosomes and facilitates epigenetic transcriptional silencing. A second, evolutionarily recent primate-specific lncRNAXACTwas proposed to antagonizeXIST’s ability to induce XCI.XACTexpression is restricted to pluripotent states and early embryonic stages and coats the active X-chromosome in both females and males. Here, we report a novelXACTtranscript expressed in normal and cancerous somatic cells from both the inactive (Xi) and active (Xa) X chromosomes. It coexists withXISTon the Xi without affectingXISTexpression or (re)activating X-linked genes inactivated by XCI. During hematopoietic stem cell (HSC) differentiation,XACTis primarily expressed in myeloid progenitors in both sexes.XACTexpression is activated in HSCs and peaks in megakaryocyte-erythrocyte progenitor cells (MEPs) before rapidly declining as the MEPs differentiate into megakaryocytes or erythrocytes. By combining CRISPR-basedXACTperturbation with epigenomic and transcriptional studies, we revealed the key role ofXACTin the self-renewal and differentiation of erythroid progenitors into erythrocytes, by recruiting cis-regulatory proteins and regulating transcription through ETS and AP-1 transcription factors. Furthermore,XACTis expressed in a subset of acute myeloid leukemia (AML) patients, with high levels found in erythroid-megakaryocytic blast cells; suggestingXACT’s potential as a marker for AML subtypes. Thus, we identified a novelXACTtranscript with a unique expression profile and important roles in normal and cancer cells, revealingXACTlncRNA functions beyond its previously proposed role in XCI during embryogenesis.
Is increasing the effective leg length of a human runner metabolically beneficial?
Authors: Bertschy Montgomery , Lino Herlandt , Healey Laura , Hoogkamer Wouter 
Published: January 2025

AbstractThe purpose of this study was to understand if footwear midsole thickness can decrease the metabolic cost of running by increasing the effective leg length of a runner. We also sought to understand the role of midsole compliance on these measures.Participants (n = 16) ran on a treadmill at 14 km h-1in four mass-matched shoe conditions: 30, 40, and 60 mm thickness of a firm midsole foam and 60 mm thickness of a compliant midsole foam. Over two testing sessions, we measured metabolic cost (two 5-minute trials in each condition) and biomechanical measures (one 2-minute trial in each condition).Increasing thickness in the firm midsole conditions increased effective leg length during early, mid, and late stance (all p < 0.001). However, metabolic cost increased (p = 0.031). Changing material from firm to compliant decreased effective leg length during midstance (p < 0.001), but not during early or late stance, and decreased metabolic cost (p < 0.001).Results suggest that increasing midsole thickness can increase the effective leg length of a runner, but this isolated effect leads to increasing in metabolic cost. On the other hand, increasing midsole compliance leads to reductions in metabolic cost, agreeing with previous literature.We suggest that the performance benefits seen in advanced footwear technology with increased midsole thickness are likely due to increased capacity to return mechanical energy, not due increases in effective leg length.Summary StatementIncreased midsole compliance, not increased effective leg length, is responsible for decreased metabolic cost in running.
Highly efficient organ-targeting transport through the ventral midline interstitial channels injection: a new development of interstitium
Authors: Song Xiaojing , Gu Xin , Xiong Feng , Jia Shuyong , Wang Shuyou , Wang Guangjun , Wang Yanpin , Zhang Weibo 
Published: January 2025

AbstractHow to improve the drugs bioavailability has always been a hot and difficult topic. Conventional drug delivery methods, such as oral administration and the blood circulation system, suffer from issues such as low targeting efficiency, low bioavailability, and high side effects. Recently, interstitium has gradually been recognized as an important new organ. Interstitial injection allows small molecules to move through interstitial channels with interstitial fluid flow and be transported to organs, providing new possibilities for drug delivery. In this study, using fluorescein sodium as a drug model, we systematically investigated the distribution of the fluorescein sodium in organs and body surface of the rats after ventral midline interstitial channels injection. In addition, we observed the microstructure of the ventral midline interstitial channels of abdominal wall and the effects of channels ligation on fluorescein sodium delivery and target organs, to explore the mechanism of interstitial injection. We found that fluorescein sodium can be efficiently transported to the uterus and ovaries along the ventral midline interstitial channels, and the parallel fibers and interconnected interstitial spaces of the channels facilitate long-distance transport of solutes. Additionally, the blockage of the transmission through those channels had results in a significant decrease in targeted transport efficiency over long distances, a decrease in oestrogen levels, organ coefficients, and body weights in female rats. Therefore, the ventral midline interstitial channels with free fluid flow may be a potential communication pathway between body surface and organs. These findings have significant value in the development of drug delivery.
Small Hands, Big Ideas: Exploring Nurturing Care Through Beatrice Alemagna’s “What is a Child?”
Authors: Ravaldi Claudia , Vannacci Alfredo 
Published: January 2025

AbstractThis study examines the use of Beatrice Alemagna’s picture book "What is a Child?" as a tool for understanding and implementing nurturing care principles in perinatal healthcare settings. Through mixed-methods analysis of forum discussions among 42 perinatal professionals, including psychologists, midwives, physicians, nurses, pharmacists and early childhood educators, we explored how engagement with the book’s metaphorical and visual elements facilitated professional reflection and development. Qualitative analysis revealed four primary themes: the power of metaphors in conveying complex caregiving concepts, the importance of collective care and community support, understanding the temporality of care, and fostering transformative dialogue. Quantitative analysis demonstrated significant differences in thematic engagement across professional groups, with medical professionals emphasizing physical health (20.8%) and nutrition (32.1%), while psychologists focused more on early learning opportunities (28.3%) and responsive caregiving (21.0%). However, the picture book’s narrative framework encouraged professionals to transcend their domain-specific perspectives, fostering a more holistic appreciation of nurturing care principles. These findings suggest that carefully selected picture books can serve as sophisticated tools for professional development in perinatal care, particularly in translating abstract theoretical concepts into actionable insights while honoring different professional perspectives and expertise.
Understanding the United States Black-White Life Expectancy Gap, 2007-2018
Authors: Wetzler Harry 
Published: January 2025

ABSTRACTBackgroundLife expectancy is a critical measure of population health. In the U.S., Black Americans have historically experienced lower life expectancy than White Americans due to factors such as health insurance inequities, socioeconomic disparities, and systemic barriers. Though the Black-White life expectancy gap narrowed after 1990, it has fluctuated in recent years, influenced by socioeconomic changes and the COVID-19 pandemic.ObjectiveThis study examines how national-level differences in education and income contributed to the Black-White life expectancy gap in the United States from 2007 to 2018.MethodsData were analyzed from the National Health and Nutrition Examination Survey (2007–2018) and its Linked Mortality File. Using 3 survival models, this study assessed life expectancy at age 20 for Non-Hispanic Black (NHB) and Non-Hispanic White (NHW) populations. Covariates included education and income.ResultsThe unadjusted life expectancy gap at age 20 between NHB and NHW individuals averaged 3 years. Adjusting for education using a flexible parametric survival model reduced the gap by 50%, while adjusting for income reduced the gap by 75%. When both factors were adjusted simultaneously, two survival models indicated that NHB life expectancy slightly exceeded NHW life expectancy. Income disparities persisted across educational levels, signifying unequal economic returns to education.ConclusionsAddressing income disparities is essential for reducing racial inequities in life expectancy. Policies promoting both equitable education access and income equivalence are critical for achieving health equity and improving population health.
Transcriptional responses to prolonged oxidative stress require cholinergic activation of G-protein-coupled receptor signaling
Authors: Biswas Kasturi , Moore Caroline , Rogers Hannah , Wani Khursheed A , Pukkila-Worley Read , Higgins Daniel P , Walker Amy K , Rand James B , Francis Michael M 
Published: January 2025

ABSTRACTOrganisms have evolved protective strategies that are geared toward limiting cellular damage and enhancing organismal survival in the face of environmental stresses, but how these protective mechanisms are coordinated remains unclear. Here, we define a requirement for neural activity in mobilizing the antioxidant defenses of the nematodeCaenorhabditis elegansboth during prolonged oxidative stress and prior to its onset. We show that acetylcholine-deficient mutants are particularly vulnerable to prolonged oxidative stress. We find that prolonged oxidative stress mobilizes a broad transcriptional response which is strongly dependent on both cholinergic signaling and activation of the muscarinic G-protein acetylcholine coupled receptor (mAChR) GAR-3. Gene enrichment analysis revealed a lack of upregulation of proteasomal proteolysis machinery in both cholinergic-deficient andgar-3mAChR mutants, suggesting that muscarinic activation is critical for stress-responsive upregulation of protein degradation pathways. Further, we find that GAR-3 overexpression in cholinergic motor neurons prolongs survival during prolonged oxidative stress. Our studies demonstrate neuronal modulation of antioxidant defenses through cholinergic activation of G protein-coupled receptor signaling pathways, defining new potential links between cholinergic signaling, oxidative damage, and neurodegenerative disease.
FAXC and Metaxin Proteins of Fungi and Bacteria: Distinct Categories of Proteins with Shared Structural Features
Authors: Adolph Kenneth W. 
Published: January 2025

ABSTRACTFAXC (failed axon connections) proteins are shown to be present in fungi and bacteria and to have structural homology to metaxin proteins of vertebrates and invertebrates. Fungal and bacterial FAXC proteins also share structural features with the metaxin-like proteins of plants and protists. But the FAXC and metaxin proteins are different categories of proteins, as seen in the low percentages of identical amino acids in pairwise sequence alignments. The metaxin-like structural features include the conserved protein domains that are characteristic of metaxin proteins. These are the GST_N_Metaxin, GST_C_Metaxin, and Tom37 domains. Another metaxin-like structural feature is a conserved pattern of α-helical and β-strand secondary structure. The FAXC proteins of both fungi and bacteria share this pattern of secondary structure with vertebrate and invertebrate metaxin proteins. The predicted 3D structures of fungal and bacterial FAXC proteins revealed a characteristic 4-stranded, β-sheet motif that was also found to characterize metaxin proteins. Phylogenetic analysis demonstrated that fungal and bacterial FAXC proteins are related by evolution to vertebrate metaxin proteins, though more closely related to vertebrate FAXC proteins. The neighboring genes of the FAXC genes of fungi are different than the neighboring genes of vertebrate FAXC and metaxin genes. A high level of protein sequence homology was found for the multiple predicted FAXC proteins of fungi that have multiple FAXC genes, and in comparing the FAXC proteins of different species of bacteria of the same genus.
Rhythms of Early Life: Gut Microbiota Rhythmicity and Circadian Maturation in infants
Authors: Mühlematter Christophe , Nielsen Dennis S. , Castro-Mejía Josue L. , Walser Jean-Claude , Schoch Sarah F. , Kurth Salome 
Published: January 2025

AbstractBackgroundThe human gut microbiota undergoes daily fluctuations, yet its interaction with sleep-wake patterns during infancy remains largely uncharted. This study aims to elucidate the relationship between gut microbiota rhythmicity and the development of sleep patterns in infants over the first year of life. We continuously monitored 162 healthy infants across multiple days at 3, 6, and 12 months of age using ankle actigraphy and 24-hour diaries. The Circadian Function Index (CFI) was computed as a proxy for sleep-wake rhythm maturation. Stool samples were collected to profile gut microbiota composition via 16S rRNA gene amplicon sequencing, and microbial oscillations were assessed through sine and cosine fitting to detect 24-hour patterns.ResultsOur findings revealed that the abundance of bacterial taxa exhibited rhythmic patterns, with 26 zOTUs (1.74%) following a sine pattern and 100 zOTUs (6.69%) displaying cosine rhythmicity. Cosine rhythmicity became more pronounced with age, showing strong maturation: 7 zOTUs at 3 months, 2 zOTUs at 6 months, and 86 zOTUs at 12 months. Notably, 105 zOTUs (7.02%) were associated with CFI, demonstrating a significant relationship between gut microbiota rhythms and sleep development. Among these, 27 zOTUs with sine dynamics and 96 zOTUs with cosine dynamics were linked to CFI, with this association strengthening as infants aged.ConclusionsThese results highlight the increasing synchronization between gut microbiota rhythmicity and sleep-wake cycles during infancy, pointing to a critical window for potential health interventions. This novel observation, previously reported in rodents and adults, underscores the role of gut microbiota in early human development, offering new avenues for enhancing developmental outcomes through targeted interventions.