bluuebunny/crossref_metadata_2025_split huggingface dataset:
VeCell: A Fiji Plugin to unveil differences in spatio-temporal dynamics of macroglial cell development and proximity to blood vessels
Authors: Guille Naomie , Monnet Héloïse , Hourcade Tristan , Mailly Philippe , Cohen-Salmon Martine , Boulay Anne-Cécile 
Published: January 2025

AbstractCortical development results from the proliferation, differentiation, migration and maturation of many cell types. While neuronal development has been extensively studied, the mechanisms regulating the development and maturation of macroglial cells (oligodendrocytes and astrocytes) are still largely to be determined. Here we present VeCell, a Fiji plugin designed to analyse the development of macroglial cells. Using immunolabeling for two transcription factors, Sox9 (specific to macroglial progenitors and astrocytes) and Sox10 (specific to oligodendrocyte lineage), we determined their density, distribution within and across cortical layers and distance to the blood vessels from postnatal day (P) 5 and P60 in the somatosensory cortex. We found that Sox9+ cells are evenly distributed in the cortex with regular intercellular distances and comparable densities between the upper and lower parts of the cortex. In contrast, Sox10+ cells are predominantly concentrated in the lower cortical layers, and exhibited a more random distribution with variable distances between cells. Finally, while confirming the increased density and branching of the vascular network after P5, we also showed that macroglial cells are closer to blood vessels from P15 onward. In summary,VeCellprovides a valuable tool for analyzing the development and spatial organization of macroglial cells. Our findings in the cortex reveal distinct patterns of distribution and proximity to the vasculature for macroglial cells during postnatal development. These insights contribute to a deeper understanding of glial maturation and highlight the dynamic interplay between macroglial cells and the vascular network, offering new avenues for future research into brain development and function.
Technical and biological sources of noise confound multiplexed enhancer AAV screening
Authors: Hunker Avery C. , Mich John K. , Taskin Naz , Torkelson Amy , Pham Trangthanh , Bertagnolli Darren , Chakka Anish Bhaswanth , Chakrabarty Rushil , Donadio Nicholas P. , Ferrer Rebecca , Gasperini Molly , Goldy Jeff , Guzman Junitta B. , Jin Kelly , Khem Shannon , Kutsal Rana , Lalanne Jean-Benoît , Martinez Refugio A. , Newman Dakota , Pena Nick , Shapovalova Nadiya V. , Weed Natalie , Zhou Thomas , Yao Shenqin , Shendure Jay , Smith Kimberly A. , Lein Ed S. , Tasic Bosiljka , Levi Boaz P. , Ting Jonathan T. 
Published: January 2025

AbstractCis-acting regulatory enhancer elements are valuable tools for gaining cell type-specific genetic access. Leveraging large chromatin accessibility atlases, putative enhancer sequences can be identified and deployed in adeno-associated virus (AAV) delivery platforms. However, a significant bottleneck in enhancer AAV discovery is charting their detailed expression patternsin vivo, a process that currently requires gold-standard one-by-one testing. Here we present a barcoded multiplex strategy for screening enhancer AAVs at cell type resolution using single cell RNA sequencing and taxonomy mapping. We executed a proof-of-concept study using a small pool of validated enhancer AAVs expressing in a variety of neuronal and non-neuronal cell types across the mouse brain. Unexpectedly, we encountered substantial technical and biological noise including chimeric packaging products, necessitating development of novel techniques to accurately deconvolve enhancer expression patterns. These results underscore the need for improved methods to mitigate noise and highlight the complexity of enhancer AAV biologyin vivo.
A compound heterozygosity of two haplotypes in the TTN gene contributes to risk for Cleft Lip and Palate in a recessive manner
Authors: Singh Ved Prakash , Singh Subodh Kumar , Ali Akhtar 
Published: January 2025

AbstractCleft lip and palate (CLP) are complex congenital anomalies with multifactorial etiology and significant genetic heterogeneity. This study aimed to elucidate the genetic basis of nonsyndromic CLP in an Indian family, wherein phenotypically normal parents had three affected offspring, including monozygotic twins, all presenting with bilateral complete CLP. Whole exome sequencing (WES) identified a compound heterozygous haplotype in theTTNgene shared by all affected siblings. The paternal haplotype comprised variants c.96140C>T (p.Thr32047Met), c.77412C>G (p.Phe25804Leu), c.2605A>T (p.Thr869Ser), and c.18663A>C (p.Glu6221Asp), while the maternal haplotype included variants c.107779G>A (p.Glu35927Lys), c.103147G>C (p.Glu34383Gln), c.63907G>A (p.Val21303Met), and c.26863A>G (p.Ile8955Val). In silico analyses predicted these variants to have deleterious effects on protein structure and function, consistent with a recessive mode of inheritance. AlthoughTTNis primarily known for its role in muscle structure and function, emerging evidence implicates its involvement in craniofacial development. This study expands the phenotypic spectrum ofTTN-associated disorders and suggests a novel role forTTNin nonsyndromic CLP. These findings underscore the importance of comprehensive genomic analyses in unraveling the molecular mechanisms underlying complex congenital anomalies.
Urban crops demonstrate comparable potential for organic carbon storage as natural ecosystems
Authors: Jiménez-Prieto Beatriz , García-Palacios Pablo , Lorenzo Carmen , Aguilar-Santana Elena , Algora Camelia , Armas Cristina , Bastida Felipe , Calvo Leonor , Casado Coy Nuria , Campos-Castro Axel , Centenaro Giada , Chamizo Sonia , Costa Joana , Martín-Bravo Santiago , Delgado-Baquerizo Manuel , Dashevskaya Svetlana , Carmona-Yáñez María Dolores , Durán Humia Jorge , Fernández-Alonso Maria José , Figueira Daniela , Garcia Eva , Alday Josu G. , de la Riva Enrique G. , Ladrón de Guevara Mónica , López-Velasco Ana , Lucas-Borja Manuel Esteban , Prieto Aguilar Ivan , Pérez-López Jesús , Plaza-Alvárez Pedro Antonio , Rodríguez Pereiras Alexandra , Sanz-Lazaro Carlos , Soliveres Santiago , Terrones Alejandro , Torres Aurora , Leo María 
Published: January 2025

AbstractUrban greenspaces, encompassing parks, golf courses, roundabouts, and urban crops, have potential to offset urban carbon footprints by storing soil organic carbon (SOC). This study analyzed particulate organic carbon (POC) and mineral-associated organic carbon (MAOC) stocks in topsoil across 27 Iberian cities, comparing urban greenspaces with natural ecosystems under varying climatic and edaphic conditions. Results revealed that urban greenspaces store comparable SOC stocks to natural ecosystems, with MAOC stocks being more dominant and stable across land-use types. POC stocks showed variability, particularly lower in roundabouts and parks compared to natural ecosystems, but remained similar in golf courses and urban crops. SOC fractions correlated inversely with mean annual temperature (MAT), emphasizing the need for cooling strategies in urban areas to preserve stable carbon pools. While MAOC exhibited saturation at higher SOC levels, POC showed a linear increase. This study highlights the importance of tailored management practices to enhance carbon storage in urban soils for climate change mitigation.
Remodeling of nucleosome by a DNA translocating bacterial restriction-modification enzyme
Authors: Sharma Sujata S. Gaiwala , Chand Mahesh Kumar , Ahmed Ishtiyaq , Haque Nibrasul , Saikrishnan Kayarat 
Published: January 2025

AbstractA eukaryotic cell has specialized ATP-dependent chromatin remodelers, such as SWI/SNF, to unfurl DNA from nucleosome for functional processing. The ATPase that powers the movement of the chromatin remodeler on the DNA (translocation) is evolutionarily related to those powering the translocation of the functionally distinct bacterial restriction-modification (RM) enzymes. The collision of a SWI/SNF chromatin remodeler and a nucleosome, results in sliding/ejection of the constituent histone octamer, while two converging ATP-dependent RM enzymes catalyze DNA cleavage. Here, we investigate if an ATP-dependent Type ISP RM enzyme, an active and directional translocase, can remodel nucleosomes. Our results reveal that in presence of ATP, a Type ISP RM enzyme can displace the octamers from not just mononucleosomes but also two tandem nucleosomes. However, a Type III RM enzyme, which employs a homologous ATPase as a switch to facilitate bidirectional 1D diffusion along the DNA, fails to remodel the nucleosome. This implies that an actively translocating Type ISP RM enzyme generates sufficient force for chromatin remodeling, and may serve as artificial sequence-specific chromatin remodelers.
Stimulus-driven cerebrospinal fluid dynamics is impaired in glaucoma patients
Authors: Bang Ji Won , Parra Carlos , Yu Kevin , Lee Hyun Seo , Wollstein Gadi , Schuman Joel S. , Chan Kevin C. 
Published: January 2025

AbstractCerebrospinal fluid (CSF) dynamics, driven by sensory stimulation-induced neuronal activity, is crucial for maintaining homeostasis and clearing metabolic waste. However, it remains unclear whether such CSF flow is impaired in age-related neurodegenerative diseases of the visual system. This study addresses this gap by examining CSF flow during visual stimulation in glaucoma patients and healthy older adults using functional magnetic resonance imaging. The findings reveal that in glaucoma, CSF inflow becomes decoupled from visually evoked blood-oxygenation-level-dependent (BOLD) response. Furthermore, stimulus-locked CSF patterns, characterized by decreases following stimulus onset and increases after offset, diminish as glaucoma severity worsens. Mediation analysis suggests that this flattened CSF pattern is driven by a flatter BOLD slope, resulting in a shallower CSF trough and a reduced rebound. These findings unveil a novel pathophysiological mechanism underlying disrupted stimulation-driven CSF dynamics in glaucoma and highlight potentialin vivobiomarkers for monitoring CSF in the glaucomatous brain.
Large language models outperform traditional structured data-based approaches in identifying immunosuppressed patients
Authors: Guggilla Vijeeth , Kang Mengjia , Bak Melissa J , Tran Steven D , Pawlowski Anna , Nannapaneni Prasanth , Rasmussen Luke V , Schneider Daniel , Donnelly Helen , Agrawal Ankit , Liebovitz David , Misharin Alexander V , Budinger GR Scott , Wunderink Richard G , Walunas Theresa L , Gao Catherine A ,   The NU SCRIPT Study Investigators
Published: January 2025

AbstractIdentifying immunosuppressed patients using structured data can be challenging. Large language models effectively extract structured concepts from unstructured clinical text. Here we show that GPT-4o outperforms traditional approaches in identifying immunosuppressive conditions and medication use by processing hospital admission notes. We also demonstrate the extensibility of our approach in an external dataset. Cost-effective models like GPT-4o mini and Llama 3.1 also perform well, but not as well as GPT-4o.
Pay-it-forward strategy reduced HPV vaccine delay and increased uptake among catch-up age girls: A randomized clinical trial
Authors: Li Jing , Li Yifan , Qi Chuanyu , He Yu , Lu Haidong , Xie Yewei , Ong Jason J. , Lu Yajiao , Yang Ying , Yang Fan , Du Heng , Gong Wenfeng , Zou Fei , Larson Heidi J. , Jit Mark , Lin Leesa , Smith Jennifer S. , Geng Elvin H. , Xu Dong , Tang Weiming , Tang Shenglan , Tucker Joseph D. , Wu Dan 
Published: January 2025

AbstractBackgroundCatch-up HPV vaccination is challenging in many low and middle-income countries (LMICs). Pay-it-forward offers an individual a subsidized vaccine, then an opportunity to donate to help others access vaccinations. Our randomized control trial assessed the effectiveness of pay-it-forward in improving HPV vaccination among girls aged 15-18 years in China.Methods and findingsEligible participants were randomly assigned to either the pay-it-forward arm or standard-of-care arm (self-paid vaccination). The primary outcome was the first-dose HPV vaccination rate, verified against clinical records. Among 321 participants enrolled, most caregivers were female (80.1%). In the pay-it-forward arm, 55 of 161 (34.2%) girls received the HPV vaccine, compared with 28 of 160 (17.5%) girls in the standard-of-care arm (adjusted proportion difference = 17.9%, 95% CI: 8.7, 27.0, P<0.001). Among 55 girls in the pay-it-forward arm who received the vaccination, 37 (67.3%) wrote a postcard message, and 39 (70.9%) of their caregivers donated to support future girls. The financial cost per person vaccinated was $294 in the standard-of-care arm and $230 in the pay-it-forward arm.ConclusionsThe pro-social pay-it-forward strategy was effective to increase catch-up HPV vaccination among teenage girls with comparable costs.Trial RegistrationChiCTR2200055542
A novel inhibitor against the bromodomainPfBDP1 of the malaria pathogenPlasmodium falciparum
Authors: Amann Marius , Warstat Robin , Rechten Kay Kristin , Theuer Philip , Schustereder Magdalena , Clavey Sophie , Breit Bernhard , Einsle Oliver , Huegle Martin , Petter Michaela , Guenther Stefan 
Published: January 2025

AbstractThe rise of drug resistances in malaria necessitates the exploration of novel therapeutic strategies. Targeting epigenetic pathways could open new, promising treatment avenues. In this study, we focus onPfBDP1, an essential bromodomain protein inP. falciparum. Utilizing the pan-selective bromodomain inhibitor MPM6, we identified a potent initial hit and subsequently developed it into a nanomolar binder. Through a combination of virtual docking, isothermal titration calorimetry, and X-ray crystallography, we elucidated the molecular interactions of the new inhibitors withPfBD1. Our findings include the first cocrystallized structures ofPfBD1 andPvBD1 with these inhibitors, providing insights into their binding mechanisms. Further validation using conditional knockdown ofPfBDP1 inP. falciparumdemonstrated parasite sensitivity to the inhibitor, underscoring its potential as a targeted therapeutic approach against malaria.
Electro-composting: an emerging technology
Authors: Hozad Ahmad Shabir , Abendroth Christian 
Published: January 2025

AbstractThe present study focuses on electrical stimulation for composting. Using the PSALSAR method, a systematic review resulted in 24 relevant articles. For each system, the review describes key materials, composter design, operating conditions, temperature evolution, compost maturity, microbial community, and outcome. The examined studies fall into four main systems: electric field-assisted aerobic composting (EAAC), electrolytic oxygen aerobic composting (EOAC), microbial fuel cells (MFC), and thermoelectric generators (TEG). Apart from the main systems highlighted above, there is a rare case, which remains hardly studied. This includes bioelectrochemically assisted anaerobic composting (AnCBE, III). EAAC and EOAC systems biologically balance microbial activity and organic matter decomposition, whereas MFC and TEG systems have dual functioning due to energy generated alongside waste degradation. These innovative systems significantly improve composting efficiency by speeding up organic matter breakdown, increasing oxygen supply, and facilitating energy recovery. Together, they overcome the drawbacks of conventional composting systems and promote more environmentally friendly waste management solutions.Research HighlightsThe four most frequently investigated electro-composting systems are EAAC, EOAC, MFC, and TEG.MFCs make it easier to turn organic waste into electricity, which makes decomposition more environmentally friendly.Thermal energy generated during decomposition is utilized by TEGs to produce electricity.The research on AnCBEis highly limited.
Optimizing SARS-CoV-2 RBD Boundaries for EnhancedE. coliExpression
Authors: Biswas Anamika , Sarkar Arighna , Raran-Kurussi Sreejith , Mandal Kalyaneswar 
Published: January 2025

AbstractThe outbreak of Coronavirus Disease 2019 (COVID-19) has posed a significant risk to global health, warranting the formulation of efficient preventive and therapeutic measures to tackle its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein of coronaviruses plays a pivotal role in viral attachment and entry into host cells. The receptor-binding domain (RBD) of the SARS-CoV-2 S protein has demonstrated a robust binding affinity to ACE2 receptors in humans. Consequently, it has become a prime target for therapeutic interventions using antibodies, vaccines, or other designed inhibitors. This paper presents an optimized RBD sequence that can be efficiently expressed inEscherichia coliand refolded to yield a functional protein. Using optimized refolding procedures, we obtained 10-12 mg of active protein from a one-liter LB culture. The biological activity of the refolded RBD was confirmed by monitoring its interaction with the designed LCB1 miniprotein ligand by surface plasmon resonance, wherein they exhibited significant affinity levels as reflected by their dissociation constants (KDs < 10 nM). The resulting RBD could be an ideal target for designing potent COVID-19 antivirals.
The quantitative spatiotemporal relationship of whole brain activity of human brains revealed by fMRI
Authors: Huang Jie 
Published: January 2025

AbstractHuman brain consists of many functional systems from the essential sensory, motor, attention and memory systems to higher order cognitive functions such as reasoning and language. Performing even a simple task may evoke multiple systems and cognitive functions, resulting in a whole brain activity across the entire brain. Despite the importance of studying task-evoked brain activated networks, investigating this whole brain activity may be crucial for understanding the neural bases of individual behavioral and clinical traits. BOLD-fMRI measures the four-dimensional (3 spatial and 1 temporal) neural activity across the entire brain at large-scale systems level. All local activities across the entire brain constitute the whole brain activity and each local activity is a part of that whole brain activity. Unlike a local activity that is characterized by its temporal neural activity, the whole brain activity is characterized by its spatial variation across the entire brain. We present a novel data-driven method to analyze the whole brain activity when performing tasks. The method enabled us to analyze the whole brain activity for each task trial and each individual subject with no requirement of a priori knowledge of task-evoked BOLD response. Our study revealed a quantitative spatiotemporal relationship of the whole brain activity with the local activities. The whole brain activity demonstrated a remarkable dynamic activity that varied from trial to trial when performing the same task repeatedly, showing the importance of analyzing the whole brain activity for investigating the neural bases of personal traits.
Thalamic involvement defines distinct slow-wave subtypes in NREM sleep
Authors: Bergamo Damiana , Handjaras Giacomo , Picchioni Dante , Ricciardi Emiliano , Özbay Pınar S. , de Zwart Jacco A. , Duyn Jeff H. , Bernardi Giulio , Betta Monica 
Published: January 2025

AbstractSlow waves (0.5–4 Hz) are a key feature of non-rapid-eye-movement (NREM) sleep, traditionally believed to arise from neocortical circuits. However, growing evidence suggests that subcortical structures, particularly the thalamus, may play a crucial role in initiating and synchronizing slow waves. We tested the hypothesis that slow waves may arise from distinct cortico-cortical and thalamo-cortical mechanisms using simultaneous EEG-fMRI in healthy adults. Spatial mapping based on thalamic fMRI responses revealed two slow-wave associated clusters. Cluster-1 C1, characterized by an early thalamic fMRI-signal increase, corresponded to large, efficiently synchronized waves associated with sleep spindles and with markers of higher arousal and autonomic activation. Cluster-2 C2, marked by an initial negative fMRI response, corresponded to smaller slow waves potentially resulting from cortico-cortical synchronization. These waves tended to more often occur during low-fragility phases of NREM sleep. These findings highlight distinct slow-wave subtypes with different thalamic involvement and, potentially, synchronization mechanisms.
Isometric handgrip contraction increases tibialis anterior intrinsic motoneuron excitability in a dose-dependent manner
Authors: Ugliara L. , Orssatto L. B. R. , Vieira A. , Trajano G. S. 
Published: January 2025

AbstractPersistent inward currents (PICs) contribution to motoneuron firing in the lower limb typically increase after a remote handgrip contraction, believed to result from diffuse increases of serotonergic input on the spinal cord. We investigated whether handgrip contraction intensity, duration, and/or impulse would affect tibialis anterior estimates of PICs. High-density electromyograms were recorded from the tibialis anterior of 21 participants (18-40 years) during 20% dorsiflexion before and after four handgrip conditions: i)80%15s, 80% of their maximal handgrip strength sustained for 15s; ii)40%15s, 40% sustained for 15s; iii)40%30s, 40% sustained for 30s; and iv)Control(no handgrip). PICs contribution to motoneuron firing was estimated with the delta frequency (ΔF) using the paired motor unit analysis. The ‘brace height’, normalised as a percentage of a right triangle (%rTri), was used to quantify the effects of PICs on the non-linearity of firing patterns, representing the neuromodulatory drive (regulation of neural activity via neurotransmitter actions) onto the motoneurons. ΔF increased by 0.30 peaks per second (pps; 95%CI 0.11–0.49,d=0.37) after40%30sand by 0.20 pps (0.04–0.36,d=0.24) after80%15sbut remained unchanged after40%15sandControl. Similarly, brace height increased by 2.39 %rTri (0.55–4.23,d=0.25) after40%30sand by 2.74 %rTri (1.14–4.34,d=0.28) after80%15s;remaining unchanged after40%15sandControl. The increase in PICs contribution to motoneuron firing induced by a remote handgrip contraction is impulse-dependent rather than intensity or duration. The parallel increases in ΔF and brace height suggest augmented neuromodulatory input onto the spinal cord.