bluuebunny/crossref_metadata_2025_split huggingface dataset:
An International, Cross-Sectional Survey of Cardiology Researchers and Clinicians: Perceptions of Complementary, Alternative, and Integrative Medicine
Authors: Ng Jeremy Y. , Masood Mehvish , Kathir Sivany , Cramer Holger 
Published: July 2024

AbstractBackgroundComplementary, alternative, and integrative medicine (CAIM) has been increasing in popularity for patients with cardiovascular illnesses. However, little is known about perceptions of CAIM among cardiology researchers and clinicians. In response, this study aimed to assess the practices, perceptions, and attitudes towards CAIM among cardiology researchers and clinicians.MethodsAn anonymous, digital cross-sectional survey was administered to researchers and clinicians who have published articles in cardiology journals indexed in OVID MEDLINE. The survey was sent to 37,915 researchers and clinicians and included 5-point Likert scales, multiple-choice questions, and open-ended questions. Basic descriptive statistics were drawn from quantitative data, and a thematic content analysis was conducted to analyze open-ended responses.ResultsAmong the 309 respondents, the majority (n=173, 55.99%) identified themselves as both researchers and clinicians in the field of cardiology. While 45.78% (n=114) of participants expressed agreement regarding the safety of CAIM therapies, 44.40% (n=111) disagreed on their efficacy. Most respondents believed in the value of conducting research on CAIM therapies (79.2%, n=198). Respondents perceived mind-body therapies (57.61%, n=159) and biologically based practices (47.46%, n=131) as the most promising interventions for the prevention and treatment of cardiovascular conditions. Biofield therapies were the least favoured for integration into mainstream medical practices (11.93%, n=29).ConclusionsWhile cardiology researchers and clinicians perceive CAIM therapies to have potential, many are hesitant about integrating such interventions into the current medical system due to a perceived lack of scientific evidence and standardized products. Insights from this study may help establish educational resources for healthcare practitioners.Clinical PerspectiveWhat is New?While complementary, alternative, and integrative medicine (CAIM) therapies are generally perceived by cardiology professionals as being safe and as having multiple potential benefits, there remains a strong need for additional research and training on CAIM interventions.In this study, support for CAIM therapies varied by modality, with mind-body therapies and biologically based practices garnering the most favor and biofield therapies garnering the least.What Are the Clinical Implications?Given the rising demand for CAIM interventions and the significance of lifestyle factors for cardiac conditions, there is a critical need for cardiology professionals to access CAIM-based research and education to meet patients’ needs.
Impaired Experience-Dependent Theta Oscillation Synchronization and Inter-Areal Synaptic Connectivity in the Visual Cortex of Fmr1 KO Mice
Authors: Cheng Xi , Nareddula Sanghamitra , Gao Hao-Cheng , Chen Yueyi , Xiao Tiange , Nadew Yididiya Y. , Xu Fan , Edens Paige Alyssa , Quinn Christopher J. , Kimbrough Adam , Huang Fang , Chubykin Alexander A. 
Published: July 2024

AbstractFragile X syndrome (FX) is the most prevalent inheritable form of autism spectrum disorder (ASD), characterized by hypersensitivity, difficulty in habituating to new sensory stimuli, and intellectual disability. Individuals with FX often experience visual perception and learning deficits. Visual experience leads to the emergence of the familiarity-evoked theta band oscillations in the primary visual cortex (V1) and the lateromedial area (LM) of mice. These theta oscillations in V1 and LM are synchronized with each other, providing a mechanism of sensory multi-areal binding. However, how this multi-areal binding and the corresponding theta oscillations are altered in FX is not known. Using iDISCO whole brain clearing with light-sheet microscopy, we quantified immediate early gene Fos expression in V1 and LM, identifying deficits in experience-dependent neural activity in FX mice. We performed simultaneous in vivo recordings with silicon probes in V1 and LM of awake mice and channelrhodopsin-2-assisted circuit mapping (CRACM) in acute brain slices to examine the neural activity and strength of long-range synaptic connections between V1 and LM in both wildtype (WT) and Fmr1 knockout (KO) mice, the model of FX, before and after visual experience. Our findings reveal synchronized familiarity-evoked theta oscillations in V1 and LM, the increased strength of V1→LM functional and synaptic connections, which correlated with the corresponding changes of presynaptic short-term plasticity in WT mice. The LM oscillations were attenuated in FX mice and correlated with impaired functional and synaptic connectivity and short-term plasticity in the feedforward (FF) V1→LM and feedback (FB) LM→V1 pathways. Finally, using 4Pi single-molecule localization microscopy (SMLM) in thick brain tissue, we identified experience-dependent changes in the density and shape of dendritic spines in layer 5 pyramidal cells of WT mice, which correlated with the functional synaptic measurements. Interestingly, there was an increased dendritic spine density and length in naïve FX mice that failed to respond to experience. Our study provides the first comprehensive characterization of the role of visual experience in triggering inter-areal neural synchrony and shaping synaptic connectivity in WT and FX mice.
Designer DNA Strand Displacement Reaction toward Controlled Release of Cargos
Authors: Hu Chih-Hsiang , Veneziano Remi 
Published: July 2024

ABSTRACTDynamic DNA nanotechnology systems are used to design DNA logic circuits, signal amplification mechanisms for biosensing, and smart release system that could potentially be used in several biomedical applications. The toehold-mediated strand displacement reaction (TMSDR) is one of the main methods for designing DNA-based biomolecular logic circuits. However, the reaction behaviour such as the displacement rate and the quantity of strand released are difficult to control and often requires chemically modified strands or addition of enzymes. This makes the TMSDR versatility and specificity limited, and not always adapted for biomedical applications. Therefore, further understanding the sequence design parameters enabling fine tuning of the TMSDR behaviour without the need for complex modification, would enable its broader application. In this study, using a DNA motif developed for multiplexed release, we examine how mismatched base(s) in the trigger strand is affecting the release rate and quantity released and found that both location and type of mismatched base(s) significantly impact the displacement parameters of the TMSDR. This allows for a finer control of the cargo release for the multiplexed release system that could be used for varying biomedical applications and help developing release system mimicking the natural distribution of biomolecules.
ATG9A and ARFIP2 cooperate to regulate PI4P levels for lysosomal repair
Authors: De Tito Stefano , Almacellas Eugenia , Yu Daniel Dai , Zhang Wenxin , Millard Emily , Hervás Javier H. , Pellegrino Enrica , Panagi Ioanna , Fodge Ditte , Thurston Theresa L.M , Gutierrez Maximiliano , Tooze Sharon A. 
Published: July 2024

ABSTRACTLysosome damage activates multiple pathways to prevent lysosome-dependent cell death, including a repair mechanism involving ER-lysosome membrane contact sites, phosphatidylinositol 4-kinase- 2a (PI4K2A), phosphatidylinositol-4 phosphate (PI4P) and oxysterol-binding protein-related proteins (ORPs), lipid transfer proteins. PI4K2A localizes to trans-Golgi network and endosomes yet how it is delivered to damaged lysosomes remains unknown. During acute sterile damage, and damage caused by intracellular bacteria, we show that ATG9A-containing vesicles perform a critical role in delivering PI4K2A to damaged lysosomes. ADP ribosylation factor interacting protein 2 (ARFIP2), a component of ATG9A vesicles, binds and sequesters PI4P on lysosomes, balancing ORP- dependent lipid transfer and promoting retrieval of ATG9A vesicles through recruitment of the adaptor protein complex-3 (AP-3). Our results reveal a role for mobilized ATG9A vesicles and ARFIP2 in lysosome homeostasis after damage and bacterial infection.
Cell cycle-driven transcriptome maturation confers multilineage competence to cardiopharyngeal progenitors
Authors: Bernadskaya Yelena Y. , Kuan Ariel , Tjärnberg Andreas , Brandenburg Jonas , Zheng Ping , Wiechecki Keira , Kaplan Nicole , Failla Margaux , Bikou Maria , Madilian Oliver , Wang Wei , Christiaen Lionel 
Published: July 2024

AbstractDuring development, stem and progenitor cells divide and transition through germ layer- and lineage-specific multipotent states to generate the diverse cell types that compose an animal. Defined changes in biomolecular composition underlie the progressive loss of potency and acquisition of lineage-specific characteristics. For example, multipotent cardiopharyngeal progenitors display multilineage transcriptional priming, whereby both the cardiac and pharyngeal muscle programs are partially active and coexist in the same progenitor cells, while their daughter cells engage in a cardiac or pharyngeal muscle differentiation path only after cell division. Here, using the tunicate Ciona, we studied the acquisition of multilineage competence and the coupling between fate decisions and cell cycle progression. We showed that multipotent cardiopharyngeal progenitors acquire the competence to produce distinctTbx1/10(+) and (−) daughter cells shortly before mitosis, which is necessary forTbx1/10activation. By combining transgene-based sample barcoding with single cell RNA-seq (scRNA-seq), we uncovered transcriptome-wide dynamics in migrating cardiopharyngeal progenitors as cells progress through G1, S and G2 phases. We termed this process “transcriptome maturation”, and identified candidate “mature genes”, including the Rho GAP-coding geneDepdc1, which peak in late G2. Functional assays indicated that transcriptome maturation fosters cardiopharyngeal competence, in part through multilineage priming and proper oriented and asymmetric division that influences subsequent fate decisions, illustrating the concept of “behavioral competence”. Both classic feedforward circuits and coupling with cell cycle progression drive transcriptome maturation, uncovering distinct levels of coupling between cell cycle progression and fateful molecular transitions. We propose that coupling competence and fate decision with the G2 and G1 phases, respectively, ensures the timely deployment of lineage-specific programs.
Sleep Fragmentation Modulates the Neurophysiological Correlates of Cognitive Fatigue
Authors: Benkirane Oumaïma , Simor Peter , Mairesse Olivier , Peigneux Philippe 
Published: July 2024

AbstractCognitive fatigue (CF) is a critical factor affecting performance and well-being. It can be altered in suboptimal sleep quality conditions, e.g., in patients suffering from obstructive sleep apnea who experience both intermittent hypoxia and sleep fragmentation (SF). Understanding the neurophysiological basis of SF in healthy individuals can provide insights to improve cognitive functioning in disrupted sleep conditions. In this electroencephalographical (EEG) study, we investigated in 16 healthy young participants the impact of experimentally induced SF on the neurophysiological correlates of CF measured before, during, and after practice on the TloadDback, a working memory task tailored to each individual’s maximal cognitive resources. Participants spent two times three consecutive nights in the laboratory, once in an undisrupted sleep (UdS) condition and once in a SF condition induced by non-awakening auditory stimulations, counterbalanced, and performed the TloadDback task both in a high (HCL) and a low (LCL) cognitive load condition. EEG activity was recorded during wakefulness in the 5-minutes resting state immediately before and after, as well as during the 16-minutes of the TloadDback task practice. In the high cognitive load under sleep fragmentation (HCL/SF) condition, high beta power increased during the TloadDback indicating heightened cognitive effort, and beta and alpha power increased in the post- vs. pre task resting state, suggesting a relaxation rebound. In the low cognitive load/undisturbed sleep (LCL/UdS) condition, low beta activity increased suggesting a relaxed focus, as well as mid beta activity associated with active thinking. These findings highlight the dynamic impact of SF on the neurophysiological correlates of CF and underscore the importance of sleep quality and continuity to maintain optimal cognitive functioning.
Solvatochromic reporter to image plasma membrane order leaflet by leaflet reveals a highly asymmetric bilayer locally modulated by transbilayer interactions
Authors: Patra Chandrima , Samad Muzamil , van Zanten Thomas , Singh Maninder , Vishwakarma Ram A , Singh Parvinder Pal , Mayor Satyajit 
Published: July 2024

ABSTRACTThe plasma membrane (PM) of cells is an asymmetric bilayer composed of a complex mixture of lipids and proteins. The emergent biophysical properties of its leaflets and their consequence on cellular function remain unexplored owing to the limitation in available probes. In this manuscript, we report on the design and characterisation of a PM-localised solvatochromic probe, C3L, based on the established reporter Laurdan. C3L is retained at the inner-leaflet due to flippase and scramblase activity, as determined by Bovine Serum Albumin-based back exchange experiments. By measuring the Generalized Polarization of C3L we are able to determine membrane order, leaflet-by-leaflet at the PM. Our results reveal that the PM is made of a tightly-packed outer/exofacial-leaflet in contrast to a disordered inner/cytoplasmic-leaflet. This differential packing is established by the maintenance of lipid asymmetry, the presence of specific lipids, Sphingomyelin in the outer-leaflet and Phosphatidylserine at the inner-leaflet, and exaggerated during mesenchymal to epithelial transition. We find spatial signatures of local modulation of the inner leaflet by protein scaffolds which promote trans-bilayer coupling of lipids. C3L thus informs on steady state lipid organisation at the asymmetric membrane while allowing further exploration of spatial regulation of lateral heterogeneity at each leaflet.
Parabrachial CGRP neurons modulates conditioned active defensive behavior under a naturalistic threat
Authors: Pyeon Gyeong Hee , Cho Hyewon , Chung Byung Min , Choi June-Seek , Jo Yong Sang 
Published: July 2024

AbstractRecent studies suggest that calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) represent aversive information and signal a general alarm to the forebrain. If CGRP neurons serve as a true general alarm, activation of CGRP neurons can trigger either freezing or fleeing defensive behavior, depending on the circumstances. However, the majority of previous findings have reported that CGRP neurons modulate only freezing behavior. Thus, the present study examined the role of CGRP neurons in active defensive behavior, using a predator-like robot programmed to chase mice in fear conditioning. Our electrophysiological results showed that CGRP neurons encoded the intensity of various unconditioned stimuli (US) through different firing durations and amplitudes. Optogenetic and behavioral results revealed that activation of CGRP neurons in the presence of the chasing robot intensified fear memory and significantly elevated conditioned fleeing behavior during recall of an aversive memory. Animals with inactivated CGRP neurons exhibited significantly low levels of fleeing behavior even when the robot was set to be more threatening during conditioning. Our findings expand the known role of CGRP neurons in the PBN as a crucial part of the brain’s alarm system, showing they can regulate not only passive but also active defensive behaviors.
Rapid and memory-efficient analysis and quality control of large spatial transcriptomics datasets
Authors: Kӧvér Bence , Vigilante Alessandra 
Published: July 2024

AbstractThe 10x Visium spatial transcriptomics platform has been widely adopted due to its established analysis pipelines, robust community support, and manageable data output. However, technologies like 10x Visium have the limitation of being low-resolution, and recently spatial transcriptomics platforms with subcellular resolution have proliferated. Such high-resolution datasets pose significant computational challenges for data analysis, with regards to memory requirement and processing speed. Here, we introduce Pseudovisium, a Python-based framework designed to facilitate the rapid and memory-efficient analysis, quality control and interoperability of high-resolution spatial transcriptomics data. This is achieved by mimicking the structure of 10x Visium through hexagonal binning of transcripts. Analysis of 47 publicly available datasets concluded that Pseudovisium increased data processing speed and reduced dataset size by more than an order of magnitude. At the same time, it preserved key biological signatures, such as spatially variable genes, enriched gene sets, cell populations, and gene-gene correlations. The Pseudovisium framework allows accurate simulation of Visium experiments, facilitating comparisons between technologies and guiding experimental design. Specifically, we found high concordance between Pseudovisium (derived from Xenium or CosMx) and Visium data from consecutive tissue slices. We further demonstrate Pseudovisium’s utility by performing rapid quality control on large-scale datasets from Xenium, CosMx, and MERSCOPE platforms, identifying similar replicates, as well as potentially low-quality samples and probes. The common data format provided by Pseudovisium also enabled direct comparison of metrics across 6 spatial transcriptomics platforms and 59 datasets, revealing differences in transcript capture efficiency and quality. Lastly, Pseudovisium allows merging of datasets for joint analysis, as demonstrated by the identification of shared cell clusters and enriched gene sets in the mouse brain using data from multiple spatial platforms. By lowering the computational requirements and enhancing interoperability and reusability of spatial transcriptomics data, Pseudovisium democratizes analysis for wet-lab scientists and enables novel biological insights.
Virus-induced paraspeckle-like condensates are essential hubs for gene expression and their formation drives genomic instability
Authors: Harper Katherine L. , Harrington Elena , Hayward Connor , Wongwiwat Wiyada , White Robert E , Whitehouse Adrian 
Published: July 2024

SummaryThe nucleus is a highly structured environment containing multiple membrane-less bodies formed through liquid-liquid phase separation. These provide spatial separation and concentration of specific biomolecules enabling efficient and discrete processes to occur which regulate gene expression. One such nuclear body, paraspeckles, are comprised of multiple paraspeckle proteins (PSPs) built around the architectural RNA,NEAT1_2. Paraspeckle function is yet to be fully elucidated but has been implicated in a variety of developmental and disease scenarios. We demonstrate that Kaposi’s sarcoma-associated herpesvirus (KSHV) drives formation of structurally distinct paraspeckles with a dramatically increased size and altered protein composition that are essential for productive lytic replication. We highlight these virus-induced paraspeckle-like structures form adjacent to virus replication centres, functioning as RNA processing hubs for both viral and cellular transcripts during infection. Notably, we reveal that PSP sequestration into virus-induced paraspeckle-like structures results in increased genome instability during both KSHV and Epstein Barr virus (EBV) infection, implicating their formation in virus-mediated tumorigenesis.
What scRNA sequencing taught us about MGMT expression in glioblastoma
Authors: Alnahhas Iyad , Khan Mehak , Shi Wenyin 
Published: July 2024

AbstractIntroductionThe promoter methylation status of O-6-methylguanine-DNA methyltransferase (MGMTp) is an established predictive and prognostic marker in GBM. Previous studies showed that the expression of MGMT based on immunohistochemistry was variable and lacked association with survival. This in part is because non-tumor cells including endothelial cells and macrophages express MGMT. Advanced technologies such as single-cell RNA (scRNA) sequencing have helped to elucidate the cellular composition of cancer and its microenvironment. scRNA sequencing allows to assess gene expression level in tumor cells specifically.MethodsWe used publicly available data from two recent GBM scRNA studies that included MGMTp methylation status data for patients to explore and uncover details about MGMT expression at the single-cell level: CPTAC (13 primary samples) and Neftel (20 primary samples).ResultsIn the CPTAC study, MGMT expression ranged from 0.19%-1.43% in the MGMTp methylated group (median 0.82%), and from 2.17%-28.36% in the MGMTp unmethylated group (median 5.7%). It therefore appears that 2% is a reasonable expression cutoff to predict the MGMTp methylation status based on scRNA data. In the Neftel study, MGMT expression ranged from 0-1.26% in the MGMTp methylated group (median 0.59%), and from 0.3-27.67% in the MGMTp unmethylated group (median 12.44%). Three unmethylated samples (out of 16) did not follow the 2% rule. It remains unclear if this is due to technical inaccuracies as the Neftel paper did not specify the method used to detect MGMTp methylation or even mere typos. Alternatively, could it be that truly MGMTp unmethylated samples can have low MGMT expression? Could this explain why some unmethylated MGMTp GBM patients surpass the expected survival? Interestingly, gene set enrichment analysis shows that MGMT expressing cells are enriched with mesenchymal genes, whereas MGMT negative cells are enriched with proneural genes.ConclusionFewer than 2% of GBM cells express MGMT when MGMTp is methylated.
RORγt-dependent antigen-presenting cells direct regulatory T cell-mediated tolerance to food antigen
Authors: Fu Liuhui , Upadhyay Rabi , Pokrovskii Maria , Romero-Meza Gabriela , Griesemer Adam , Littman Dan R. 
Published: July 2024

AbstractThe gastrointestinal tract is continuously exposed to foreign antigens in food and commensal microbes with potential to induce adaptive immune responses. Peripherally induced T regulatory (pTreg) cells are essential for mitigating inflammatory responses to these agents1–4. While RORγt+antigen-presenting cells (RORγt-APCs) were shown to program gut microbiota-specific pTregs5–7, understanding of their characteristics remains incomplete, and the APC subset responsible for food tolerance has remained elusive. Here, we demonstrate that RORγt-APCs are similarly required for differentiation of food antigen-specific pTregs and establishment of oral tolerance. The ability of these cells to direct both food and microbiota-specific pTreg cell differentiation is contingent on expression of RORγt and on a unique cis-regulatory element within theRorcgene locus (Rorc(t)+7kb). Absent this +7kb element, there was a notable increase in food antigen-specific T helper 2 (Th2) cells in lieu of pTregs, leading to compromised tolerance in a mouse asthma model. By employing single-cell analyses across these models, as well as freshly resected mesenteric lymph nodes from a human organ donor, we identified a rare subset of evolutionarily conserved APCs that are dependent on RORγt, uniquely express the Prdm16 transcription factor, and are endowed with essential mediators for inducing pTreg cell differentiation. Our findings suggest that a better understanding of how RORγt-APCs develop and how they regulate T cell responses to food and microbial antigens could offer new insights into developing therapeutic strategies for autoimmune and allergic diseases as well as organ transplant tolerance.