bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccine beliefs, adverse effects, and quality of life in patients with cancer undergoing routine COVID-19 vaccination
Authors: Body Amy , Donoghoe Mark , Lal Luxi , Wakefield Claire , Ahern Elizabeth Stephanie , Anazodo Antoinette , Fuentes Bolanos Noemi Auxiliadora , Padhye Bhavna , Downie Peter , Opat Stephen , Hamad Nada , Leahy Michael Francis , Milch Vivienne , Segelov Eva 
Published: June 2024

AbstractBackgroundConcerns about side effects and treatment interactions and delays may contribute to COVID-19 vaccine hesitancy amongst cancer patients. In the large prospective SerOzNET study of COVID-19 vaccine response in children and adults with cancer, vaccine beliefs, physician- and participant-reported adverse events (AE), treatment interruptions and quality of life (QoL) were studied.MethodsThe Australian experience with COVID-19 gave a unique opportunity to study vaccination response in an infection- and vaccine-naïve cancer population. Patients with current or recent solid or hematological malignancy, aged five and over, had serial assessments prior to and following multiple SARS-CoV-2 vaccinations. Electronic surveys were administered at baseline and after first, second and third doses to collect vaccine beliefs (Oxford Confidence and Complacency Scale), patient-reported toxicity and QoL (QLQC30 or PedsQL). Detailed toxicity data were collected at clinic visits and from medical records.ResultsA total of 1385 vaccination doses were administered (93% BNT162b2), with at least 1 dose received by 499 patients, of whom only seven had known prior COVID-19 infection. Vaccine related beliefs were generally positive. There were no vaccine-related interruptions to cancer therapy. AE occurred in 95% of recipients, with the highest ranked severity being mild in 36% and moderate, severe or serious in 31%, 19% and 6% respectively. QoL showed no significant deterioration post-vaccination.ConclusionThis robust dataset provides evidence regarding safety and tolerance of SARS-CoV-2 vaccination in adults and children with cancer. Patients and families can be reassured that rates of AEs are comparable to the general population and do not impact delivery of cancer therapy or QoL.
A myelinic channel system for motor-driven organelle transport
Authors: Chapple Katie J. , Green Tabitha R.F. , Wirth Sarah , Chen Yi-Hsin , Gerwig Ulrike , Aicher Marie Louise , Kim Yeonsu , Komarek Lina , Brown Angus , Crawford Colin L. , Smith Rebecca Sherrard , Lee Jeff , Pardo-Fernandez Luis , McHugh Rebecca E , Kassmann Celia M. , Werner Hauke B. , Davis Ilan , Kneussel Matthias , Brown Euan R , Goebbels Sandra , Nave Klaus-Armin , Edgar Julia M. 
Published: June 2024

SummaryMyelin sheaths comprise compacted layers of oligodendroglial membrane wrapped spirally around axons. Each sheath, if imagined unwrapped, has a cytoplasm-filled space at its perimeter, linking it to the oligodendrocyte soma via a short process. By electron microscopy (EM), this space, which we term the ‘myelinic channel system’ contains microtubules and membranous organelles, but whether these are remnants of development or serve a function is unknown. Performing live imaging of myelinating oligodendrocytes expressing fluorescent reporters, we found that the myelinic channel system serves microtubule-dependent organelle transport. Further, the intra-myelinic movement of peroxisomes was modulated by neuronal electrical activity in these mixed neural cell cultures. Loss of oligodendroglial Kif21b or CNPin vivoled to apparent stasis of myelin organelles and secondary axon pathology. This suggests that oligodendrocytes require motor transport in myelin to maintain axonal integrity.
AgRP neurons mediate activity-dependent development of oxytocin connectivity and autonomic regulation
Authors: Biddinger Jessica E. , Elson Amanda E.T. , Fathi Payam A. , Sweet Serena R. , Nishimori Katsuhiko , Ayala Julio E. , Simerly Richard B. 
Published: June 2024

AbstractDuring postnatal life, the adipocyte-derived hormone leptin is required for proper targeting of neural inputs to the paraventricular nucleus of the hypothalamus (PVH) and impacts the activity of neurons containing agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus. Activity-dependent developmental mechanisms are known to play a defining role during postnatal organization of neural circuits, but whether leptin-mediated postnatal neuronal activity specifies neural projections to the PVH or impacts downstream connectivity is largely unexplored. Here, we blocked neuronal activity of AgRP neurons during a discrete postnatal period and evaluated development of AgRP inputs to defined regions in the PVH, as well as descending projections from PVH oxytocin neurons to the dorsal vagal complex (DVC) and assessed their dependence on leptin or postnatal AgRP neuronal activity. In leptin-deficient mice, AgRP inputs to PVH neurons were significantly reduced, as well as oxytocin-specific neuronal targeting by AgRP. Moreover, downstream oxytocin projections from the PVH to the DVC were also impaired, despite the lack of leptin receptors found on PVH oxytocin neurons. Blocking AgRP neuron activity specifically during early postnatal life reduced the density of AgRP inputs to the PVH, as well as the density of projections from PVH oxytocin neurons to the DVC, and these innervation deficits were associated with dysregulated autonomic function. These findings suggest that postnatal targeting of descending PVH oxytocin projections to the DVC requires leptin-mediated AgRP neuronal activity, and represents a novel activity-dependent mechanism for hypothalamic specification of metabolic circuitry, with consequences for autonomic regulation.Significance statementHypothalamic neural circuits maintain homeostasis by coordinating endocrine signals with autonomic responses and behavioral outputs to ensure that physiological responses remain in tune with environmental demands. The paraventricular nucleus of the hypothalamus (PVH) plays a central role in metabolic regulation, and the architecture of its neural inputs and axonal projections is a defining feature of how it receives and conveys neuroendocrine information. In adults, leptin regulates multiple aspects of metabolic physiology, but it also functions during development to direct formation of circuits controlling homeostatic functions. Here we demonstrate that leptin acts to specify the input-output architecture of PVH circuits through an activity-dependent, transsynaptic mechanism, which represents a novel means of sculpting neuroendocrine circuitry, with lasting effects on how the brain controls energy balance.
Prophages are Infrequently Associated With Antibiotic Resistance inPseudomonas aeruginosaClinical Isolates
Authors: Chang Tony H. , Pourtois Julie D. , Haddock Naomi L. , Furkuawa Daisuke , Kelly Kate E. , Amanatullah Derek F. , Burgener Elizabeth , Milla Carlos , Banaei Niaz , Bollyky Paul L. 
Published: June 2024

AbstractLysogenic bacteriophages can integrate their genome into the bacterial chromosome in the form of a prophage and can promote genetic transfer between bacterial strainsin vitro. However, the contribution of lysogenic phages to the incidence of antimicrobial resistance (AMR) in clinical settings is poorly understood. Here, in a set of 186 clinical isolates ofPseudomonas aeruginosacollected from respiratory cultures from 82 patients with cystic fibrosis (CF), we evaluate the links between prophage counts and both genomic and phenotypic resistance to six anti-pseudomonal antibiotics: tobramycin, colistin, ciprofloxacin, meropenem, aztreonam, and piperacillin-tazobactam. We identified 239 different prophages in total. We find thatP. aeruginosaisolates contain on average 3.06 +/- 1.84 (SD) predicted prophages. We find no significant association between the number of prophages per isolate and the minimum inhibitory concentration (MIC) for any of these antibiotics. We then investigate the relationship between particular prophages and AMR. We identify a single lysogenic phage associated with phenotypic resistance to the antibiotic tobramycin and, consistent with this association, we observe that AMR genes associated with resistance to tobramycin are more likely to be found when this prophage is present. However we find that they are not encoded directly on prophage sequences. Additionally, we identify a single prophage statistically associated with ciprofloxacin resistance but do not identify any genes associated with ciprofloxacin phenotypic resistance. These findings suggest that prophages are only infrequently associated with the AMR genes in clinical isolates ofP. aeruginosa.ImportanceAntibiotic-resistant infections ofPseudomonas aeruginosa, a leading pathogen in patients with Cystic Fibrosis (CF) are a global health threat. While lysogenic bacteriophages are known to facilitate horizontal gene transfer, their role in promoting antibiotic resistance in clinical settings remains poorly understood. In our analysis of 186 clinical isolates ofP. aeruginosafrom CF patients, we find that prophage abundance does not predict phenotypic resistance to key antibiotics but that specific prophages are infrequently associated with tobramycin resistance genes. In addition, we do not find antimicrobial resistance (AMR) genes encoded directly on prophages. These results highlight that while phages can be associated with AMR, phage-mediated AMR transfer may be rare in clinical isolates and difficult to identify. This work is important for future efforts on mitigating AMR in Cystic Fibrosis and other vulnerable populations affected byPseudomonas aeruginosainfections and advances our understanding of bacterial-phage dynamics in clinical infections.
Inhibition of the HSP90 homodimerization and HSP90-HIF1α interactions by employing small molecules at C-terminal ATP binding site of HSP90
Authors: Poyya Jagadeesha , Joshi Chandrashekhar G 
Published: June 2024

AbstractThe Heat shock protein HSP 90-alpha (HSP90AA1) is a major chaperone that stabilizes the hypoxia-inducible factor 1α under hypoxic stress and develops solid tumors. Recent studies revealed that in addition to N-terminal ATP binding site, HSP90 has an additional ATP binding site at the C-terminal end. So, disruption of HSP90 and HIF 1 α interaction is an innovative method to control cancer progression. This can be achieved by employing small molecules at C-terminal ATP-binding that do not affect the overall functioning of the HSP90. But there is a lack of structural basis for HIF-1α and HSP90AA1 interactions. This study screened natural products and their derivatives against HSP90AA1 and HIF-1α interaction disruption. Virtual screening was carried out using Glide. We found that compounds with indole rings bind to the C-terminal ATP binding site of HSP90 and prevent its interaction with HIF-1α. Tryptamine derivatives with indole rings showed a greater binding affinity than other molecules. Thus, Tryptamine hydrochloride compounds can be used as a drug repurposing approach to treat hypoxic tumors.Abstract Figure
Ecological fNIRS in mobile children: Using short separation channels to correct for systemic contamination during naturalistic neuroimaging
Authors: Pinti P. , Dina L.M , Smith T 
Published: June 2024

AbstractSignificanceThe advances and the miniaturization in functional Near Infrared Spectroscopy (fNIRS) instrumentation offers the potential to move the classical laboratory-based cognitive neuroscience investigations into more naturalistic settings. Wearable and mobile fNIRS devices also provide a novel child-friendly means to image functional brain activity in freely moving toddlers and preschoolers. Measuring brain activity in more ecologically valid settings with fNIRS presents additional challenges, such as the increased impact of physiological interferences. One of the most popular methods to minimize such interferences is to regress out short separation channels from the long separation channels (i.e., superficial signal regression or SSR). Whilst this has been extensively investigated in adults, little is known about the impact of systemic changes on the fNIRS signals recorded in children in either classical or novel naturalistic experiments.AimWe aim to investigate if extracerebral physiological changes occur in toddlers and preschoolers, and whether SSR can help minimize these interferences.ApproachWe collected fNIRS data from 3-to-7 years olds during a conventional computerized static task and in a dynamic naturalistic task in an immersive virtual reality (VR) continuous automatic virtual environment (CAVE).ResultsOur results show that superficial signal contamination data is present in both young children as in adults. Importantly, we find that SSR helps in improving the localization of functional brain activity, both in the computerized task and, to a larger extent, in the dynamic VR task.ConclusionsFollowing from these results, we formulate suggestions to advance the field of developmental neuroimaging with fNIRS, particularly in ecological settings.
Diverse intrinsic properties shape transcript stability and stabilization inMycolicibacterium smegmatis
Authors: Sun Huaming , Vargas-Blanco Diego A. , Zhou Ying , Masiello Catherine S. , Kelly Jessica M. , Moy Justin K. , Korkin Dmitry , Shell Scarlet S. 
Published: June 2024

ABSTRACTIn mycobacteria, regulation of transcript degradation is known to occur in response to environmental stress and to facilitate adaptation. However, the mechanisms underlying this regulation are unknown. Here we sought to gain an understanding of the mechanisms controlling mRNA stability by investigating the transcript properties associated with variance in transcript stability and stress-induced transcript stabilization. We performed transcriptome-wide mRNA degradation profiling ofMycolicibacterium smegmatisin both log phase growth and hypoxia-induced growth arrest. The transcriptome was globally stabilized in response to hypoxia, with all transcripts having longer half-lives, but some having greater degrees of stabilization than others. The transcripts of essential genes were generally stabilized more than those of non-essential genes. We then developed machine learning models that utilized a compendium of transcript properties and enabled us to identify the non-linear collective effect of diverse properties on transcript stability and stabilization. The comparisons of these properties confirmed the association of 5’ UTRs with transcript stability, along with other differences between leadered and leaderless transcripts. Our analysis highlighted the protective effect of translation in log phase but not in hypoxia-induced growth arrest. Steady-state transcript abundance had a weak negative association with transcript half-life that was stronger in hypoxia, while coding sequence length showed an unexpected correlation with half-life in hypoxia only. In summary, we found that transcript properties are differentially associated with transcript stability depending on both the transcript type and the growth condition. Our results reveal the complex interplay between transcript features and microenvironment that shapes transcript stability in mycobacteria.
Diptera-specific Daedalus controls Zucchini endonucleolysis in piRNA biogenesis independent of exonucleases
Authors: Koga Yuica , Hirakata Shigeki , Negishi Mayu , Yamazaki Hiroya , Siomi Mikiko C. 
Published: June 2024

SummarypiRNAs protect germline genomes and maintain fertility by repressing transposons. Daedalus and Gasz act together as a mitochondrial scaffold for Armitage, a necessary factor for Zucchini-dependent piRNA processing. However, the mechanism underlying this function remains unclear. Here, we find that the roles of Daedalus and Gasz in this process are distinct, although both are necessary: Daedalus physically interacts with Armitage, whereas Gasz supports Daedalus to maintain its function. Daedalus binds to Armitage through two distinct regions, an extended coiled-coil identified in this study, and a SAM. The former tethers Armitage to mitochondria, while the latter controls Zucchini endonucleolysis to define the length of piRNAs in an exonuclease-independent manner. piRNAs produced in the absence of Daedalus SAM do not exhibit full transposon silencing functionality. Daedalus is Diptera specific. UnlikeDrosophilaand mosquitoes, evolutionarily more complex species, such as mice, rely on exonucleases after Zucchini processing to specify the length of piRNAs.
A chromosome-level reference-quality genome ofPunica granatumL
Authors: Yan Ming 
Published: June 2024

AbstractPomegranate (Punica granatumL.) is one of the most ancient edible fruit tree species. Here we reported a new chromosome-level genome assembly and annotation of sour pomegranate. We assembled the genome with a size of 331.47 Mb and used BUSCO to estimate the completeness of the assembly as 98.8%. More than 97.40% of sequences in the final assembly were anchored to 8 pseudochromosomes, higher than the corresponding percentages for the existing reference genomes ‘Tunisia’ (92.62%). Using a combination of de novo prediction, protein homology and RNA-seq annotation, 29,326 protein-coding genes were predicted. We re-annotated the protein-coding genes of five other published pomegranate genomes using the same annotation method. We constructed the pan-genome of pomegranate using protein-coding genes, integrating data from our newly assembled genome and five other published genomes. The pan-genome was composed of 28,314 gene families, of which 68.96% were core genes, 30.00% were dispensable genes, and 1.04% were private genes. The chromosome-level reference genome of sour pomegranate would be valuable resource for research and molecular breeding of pomegranate.
Ultrasonic cerebrospinal fluid clearance improves outcomes in hemorrhagic brain injury models
Authors: Azadian Matine M. , Macedo Nicholas , Yu Brenda J. , Fame Ryann M. , Airan Raag D. 
Published: June 2024

Introduction (Abstract)Impaired clearance of the byproducts of aging and neurologic disease from the brain exacerbates disease progression and severity. We have developed a noninvasive, low intensity transcranial focused ultrasound protocol that facilitates the removal of pathogenic substances from the cerebrospinal fluid (CSF) and the brain interstitium. This protocol clears neurofilament light chain (NfL) – an aging byproduct – in aged mice and clears red blood cells (RBCs) from the central nervous system in two mouse models of hemorrhagic brain injury. Cleared RBCs accumulate in the cervical lymph nodes from both the CSF and interstitial compartments, indicating clearance through meningeal lymphatics. Treating these hemorrhagic brain injury models with this ultrasound protocol reduced neuroinflammatory and neurocytotoxic profiles, improved behavioral outcomes, decreased morbidity and, importantly, increased survival. RBC clearance efficacy was blocked by mechanosensitive channel antagonism and was effective when applied in anesthetized subjects, indicating a mechanosensitive channel mediated mechanism that does not depend on sensory stimulation or a specific neural activity pattern. Notably, this protocol qualifies for an FDA non-significant risk designation given its low intensity, making it readily clinically translatable. Overall, our results demonstrate that this low-intensity transcranial focused ultrasound protocol clears hemorrhage and other harmful substances from the brain via the meningeal lymphatic system, potentially offering a novel therapeutic tool for varied neurologic disorders.
BaseNet: A Transformer-Based Toolkit for Nanopore Sequencing Signal Decoding
Authors: Li Qingwen , Sun Chen , Wang Daqian , Lou Jizhong 
Published: June 2024

AbstractNanopore sequencing provides a rapid, convenient and high-throughput solution for nucleic acid sequencing. Accurate basecalling in nanopore sequencing is crucial for downstream analysis. Traditional approaches such as Hidden Markov Models (HMM), Recurrent Neural Networks (RNN), and Convolutional Neural Networks (CNN) have improved basecalling accuracy but there is a continuous need for higher accuracy and reliability. In this study, we introduce BaseNet, an open-source toolkit that utilizes transformer models for advanced signal decoding in nanopore sequencing. BaseNet incorporates both autoregressive and non-autoregressive transformer-based decoding mechanisms, offering state-of-the-art algorithms freely accessible for future improvement. Our research indicates that cross-attention weights effectively map the relationship between current signals and base sequences, joint loss training through adding a pair of forward and reverse decoder facilitate model converge, and large-scale pre-trained models achieve superior decoding accuracy. This study helps to advance the field of nanopore sequencing signal decoding, contributes to technological advancements, and provides novel concepts and tools for researchers and practitioners.
Unveiling the guardians: IL-26-expressing MAIT cells protect epithelial barrier function and are dysregulated in Crohn’s disease
Authors: Bosáková Veronika , Ke Bo-Jun , Kohoutková Marcela Hortová , Papatheodorou Ioanna , Kafka Filip , Zuani Marco De , Santhosh Sneha , Biscu Francesca , Abdurahiman Saeed , Greef Ine De , Verstockt Sare , Verstockt Bram , Vermeire Séverine , Argüello Rafael J , Matteoli Gianluca , Frič Jan 
Published: June 2024

ABSTRACTBACKGROUND & AIMSInflammatory bowel disease (IBD) is characterized by a dysregulated immune response against the host’s microbiome. Mucosal-associated invariant T (MAIT) cells recognize microbiota-derived riboflavin metabolites and play a crucial role in mucosal homeostasis. However, their specific role in IBD remains enigmatic. MAIT cells express IL-26, a novel IL-10 family cytokine with a controversial role in IBD. We investigated the functions of MAIT cells and IL-26 in IBD using a unique combination of state-of-the-art 3D human intestinal tissue models and clinical samples.METHODSWe analyzed MAIT cells from the peripheral blood and intestinal tissue of Crohn’s disease (CD) patients, using immunofluorescence staining and flow cytometry to describe the phenotype and IL-26 expression of MAIT cells. We used 3D iPSC-derived intestinal organoids as a complexin vitromodel of human tissue and RNA sequencing and functional assays such as wound healing assay to study the role of IL-26 in mucosal homeostasis and inflammation.RESULTSWe observed a reduction of MAIT cells in the peripheral blood of CD patients compared to healthy donors (1.5 ± 0.4%; 4.1 ± 1.1%; p < .0065) and a significant decrease of MAIT cells in inflamed compared to non-inflamed ileum of CD patients (0.1 ± 0.03%; 0.17 ± 0.05%; p < .042). MAIT cells were found pathologically activated in inflamed tissue, exhibiting differences in CD8 and CD4 expression and dysregulation of IL-26 expression. Furthermore, we demonstrated a protective role of IL-26 in mucosal homeostasis and inflammation in the iPSC-derived organoid model.CONCLUSIONOur results show a crucial role for IL-26 and MAIT cells in the homeostasis of intestinal tissue and in the pathogenesis of IBD. These cells may therefore represent new therapeutic targets for CD patients.