bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of hybrid hydrogels combining natural polymers
Authors: Taylan Derin , Güneş İlayda , Durukan Emine , Gök Özgül 
Published: September 2023

ABSTRACTHydrogels have emerged as an important field of study in biomedical engineering, biomaterials research and soft tissue modeling due to their versatility and customizable structures. They are three-dimensional networks capable of absorbing significant amounts of water and can be chemically or physically bonded, rendering them insoluble. The unique properties of hydrogels, such as excellent biocompatibility, degradation abilities, and ability to form chemical bonds between macromolecules, make them valuable in a variety of applications. One of the main applications of hydrogels is tissue engineering, where they are used in implantation, surgical procedures, targeted drug delivery and tissue regeneration. Hydrogels can act as scaffolds to mimic the properties of natural tissues, including mechanical strength, degradation properties, gel transformation, and swelling. Crosslinking hydrogels with other polymers, both natural and synthetic, allows their degradation rate to be controlled. Composite hydrogels or biohybrid gels offer advantages such as consistent properties between batches and a high degree of control in the manufacturing process. Using different types of polymers, researchers can fine-tune the chemical and physical properties of the resulting hydrogel, which is crucial for certain biomedical applications such as drug delivery, biocompatibility, and mechanical stability. In this study, our aim is to make hybrid hydrogel scaffolds more suitable for biomedical applications, which can show the healing effect of adding natural polymers to the scaffold structure. Our results revealed that the hybrid hydrogel obtained by chemically linking gelatin polymer chains to PEG polymers during crosslinking via UV light provides more advantageous properties in the final hydrogel structure, such as better durability and pore sizes for future cell placement in tissue engineering applications.
Seeding Activity of Skin Misfolded Tau as a Novel Biomarker for Tauopathies
Authors: Wang Zerui , Wu Ling , Gerasimenko Maria , Gilliland Tricia , Shah Zahid Syed Ali , Gunzler Steven A. , Donadio Vincenzo , Liguori Rocco , Xu Bin , Zou Wen-Quan 
Published: September 2023

AbstractTauopathies are a group of age-related neurodegenerative diseases with a molecular hallmark of the prion-like propagation and accumulation of pathologically phosphorylated tau protein in the brain. They include Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick’s disease (PiD). Currently, in the peripheral tissues and body fluids there are no reliable diagnostic biomarkers available that are able to directly reflect the capability of propagation and spreading of the misfolded tau aggregates. Here, we revealed significantly increased amounts of phosphorylated tau in the skin of AD patients compared to those in other tauopathies and normal controls. Moreover, the seed-amplification assay (SAA) by the ultrasensitive real-time quaking-induced conversion (RT-QuIC) displayed that the prion-like seeding activity of pathological tau in the skin of cadavers with neuropathologically confirmed tauopathies including AD, PSP, CBD, PiD was dramatically higher than that in normal controls, yielding 75-80% sensitivity and 95-100% specificity, respectively, depending on different tau substrates used. The increased tau-seeding activity was also observed in biopsy skin samples from living AD and PSP patients. Moreover, analysis of the end products of skin-tau SAA confirmed that the increased seeding activity is accompanied with formation of tau aggregates that are of different physicochemical properties determined by the different tau-substrates used. Our study provides proof-of-concept that the skin tau-SAA can differentiate tauopathies from normal controls, suggesting that the seeding activity of the skin misfolded tau can serve as an accurate diagnostic biomarker of tauopathies.
Neural representations of concrete concepts enable identification of individuals during naturalistic story listening
Authors: Botch Thomas L. , Finn Emily S. 
Published: September 2023

AbstractDifferent people listening to the same story may converge upon a largely shared interpretation while still developing idiosyncratic experiences atop that shared foundation. What semantic properties support this individualized experience of natural language? Here, we investigate how the “concreteness” of word meanings — i.e., the extent to which a concept is derived from sensory experience — relates to variability in the neural representations of language. Leveraging a large dataset of participants who each listened to four auditory stories while undergoing functional MRI, we demonstrate that an individual’s neural representations of concrete concepts are reliable across stories and unique to the individual. In contrast, we find that neural representations of abstract concepts are variable both within individuals and across the population. Using natural language processing tools, we show that concrete words exhibit similar neural signatures despite spanning larger distances within a high-dimensional semantic space, which potentially reflects an underlying signature of sensory experience — namely, imageability — shared by concrete words but absent from abstract words. Our findings situate the concrete-abstract semantic axis as a core dimension that supports reliable yet individualized representations of natural language.
Adaptation of RiPCA for the Live-Cell Detection of mRNA-Protein Interactions
Authors: Soueid Dalia M. , Garner Amanda L. 
Published: September 2023

ABSTRACTRNA-binding proteins (RBPs) act as essential regulators of cell fate decisions through their ability to bind and regulate the activity of cellular RNAs. For protein-coding messenger RNAs (mRNAs), RBPs control the localization, stability, degradation, and ultimately translation of mRNAs to impact gene expression. Disruption of the vast network of mRNA-protein interactions has been implicated in many human diseases, and accordingly, targeting these interactions has surfaced as a new frontier in RNA-targeted drug discovery. To catalyze this new field, methods are needed to enable the detection and subsequent screening of mRNA-RBP interactions, particularly in live cells. Using our laboratory’s RNA-interaction with Protein-mediated Complementation Assay (RiPCA) technology, herein we describe its application to mRNA-protein interactions and present a guide for the development of future RiPCA assays for structurally diverse classes of mRNA-protein interactions.
The Sensation and Pain Rating Scale: easy to use, clear to interpret, and responsive to clinical change
Authors: Madden Victoria J , Kamerman Peter , Leake Hayley B. , Catley Mark J. , Heathcote Lauren C. , Moseley G Lorimer 
Published: September 2023

AbstractBackgroundThe Sensation and Pain Rating Scale (SPARS) allows rating of non-painful as well as painful percepts. While it performs well in the experimental context, its clinical utility is untested. This prospective, repeated-measures study mixed qualitative and quantitative methods to examine the utility and performance of the SPARS in a clinical context, and to compare it with the widely used 11-point NRS for pain.MethodsPeople presenting for outpatient physiotherapy (n = 121) provided ratings on the SPARS and NRS at first consultation, before and after sham and active clinical interventions, and at follow-up consultation. Clinicians (n = 9) reported each scale’s usability and interpretability using Likert-type scales and free text, and answered additional questions with free text. Each data type was initially analysed separately: quantitative data were visualised and the ES II metric was used to estimate SPARS internal responsiveness; qualitative data were analysed with a reflexive inductive thematic approach. Data types were then integrated for triangulation and complementarity.ResultsThe SPARS was well received and considered easy to use, after initial familiarisation. Clinicians favoured the SPARS over the NRS for clarity of interpretation and inter-rater reliability. SPARS sensitivity to change was good (ESII=0.9; 95%CI: 0.75-1.10). The greater perceptual range of the SPARS was deemed especially relevant in the later phases of recovery, when pain may recede into discomfort that still warrants clinical attention.ConclusionThe SPARS is a promising tool for assessing patient percept, with strong endorsement from clinicians for its clarity and superior perceptual scope.SignificanceClinicians in this mixed-methods study favoured the Sensation and Pain Rating Scale (SPARS) over a 0-10 Numerical Rating Scale for pain because the SPARS provides a clearly labelled range for rating non-painful events, which supports inter-rater reliability and clear interpretation. Clinicians reported rapid adjustment to the SPARS structure. The SPARS had good internal responsiveness to change. The SPARS may be particularly useful as a person recovers from a painful episode, when residual discomfort still requires clinical attention.
Feasibility Study of the CT Clock Tool for Estimating Onset Time of Ischaemic Stroke: Study Protocol
Authors: Mair Grant , Whiteley William , Chappell Francesca , MacRaild Allan , Wardlaw Joanna 
Published: September 2023

ABSTRACTIschaemic stroke is a devastating disease with high rates of death and disability affecting ∼100,000 people annually in the UK. Effective treatments are only offered when the time of stroke onset is known and within specific limits. For the 20% where onset time is unknown or delayed, advanced imaging methods can identify people for safe and effective treatment. However, this advanced imaging is not widely available. We have developed a method for identifying patients who can still be treated even without advanced imaging. The CT Clock Tool uses only the non-enhanced CT brain scan, that most patients with stroke receive upon arrival at hospital, to determine whether patients are eligible for treatment.This project aims to provide the first prospective clinical testing of the CT Clock Tool in a single-centre feasibility analysis. We will recruit patients in the emergency department with ischaemic stroke and obtain consent to use their acute CT brain imaging and other data relating to their care. We will ask treating clinicians to apply our CT Clock Tool method in real time, but we will not alter routine care pathways or otherwise involve patients. We have powered the study to validate previous estimates of the diagnostic accuracy and precision of our method for identifying treatment eligible patients. Results from this project will enable a future definitive randomised-controlled trial, which if successful would allow the routine use of our method anywhere CT brain imaging is available for patients with stroke.
Co-expression in tissue-specific gene networks links genes in cancer-susceptibility loci to known somatic driver genes
Authors: Urzúa-Traslaviña Carlos G. , van Lieshout Tijs , Boulogne Floranne , Domanegg Kevin , Zidan Mahmoud , Bakker Olivier B. , Claringbould Annique , de Ridder Jeroen , Zwart Wilbert , Westra Harm-Jan , Deelen Patrick , Franke Lude 
Published: September 2023

AbstractBackgroundThe genetic background of cancer remains complex and challenging to integrate. Many somatic mutations in genes are known to cause and drive cancer, while genome-wide association studies (GWAS) of cancer have revealed many germline risk factors associated with cancer. However, the overlap between known somatic driver genes and positional candidate genes from GWAS loci is surprisingly small. We hypothesised that genes from multiple independent cancer GWAS loci should show tissue-specific co-regulation patterns that converge on cancer-specific driver genes.ResultsWe studied recent well powered GWAS of breast, prostate, colorectal and skin cancer by estimating co-expression between genes and subsequently prioritising genes that show co- expression with genes mapping within susceptibility loci from cancer GWAS. We observed that the prioritised genes were strongly enriched for cancer drivers defined by COSMIC, intOGen and Dietleinet al. The enrichment of known cancer driver genes was most significant when using co-expression networks derived from non-cancer samples from the relevant tissue of origin.ConclusionWe show how genes in risk loci identified by cancer GWAS can be linked to known cancer driver genes through tissue-specific co-expression networks. This provides an important explanation for why seemingly unrelated sets of genes that harbour either germline risk factors or somatic mutations can eventually cause the same type of disease.
Clinical predictors of severe forms of influenza A H1N1 in adults and children during the 2009 epidemic in Brazil
Authors: Braga Jose Ueleres 
Published: September 2023

AbstractThe World Health Organization (WHO) raised the global alert level for the A(H1N1) influenza pandemic in June 2009. However, since the beginning of the epidemic, the fight against the epidemic lacked foundations for managing cases to reduce the disease lethality. It was urgent to carry out studies that would indicate a model for predicting severe forms of influenza. This study aimed to identify risk factors for severe forms during the 2009 influenza epidemic and develop a prediction model based on clinical epidemiological data. A case-control of cases notified to the health secretariats of the states of Rio de Janeiro, São Paulo, Minas Gerais, Paraná, and Rio Grande do Sul was conducted. Cases had fever, respiratory symptoms, positive confirmatory test for the presence of the virus associated with one of the three conditions: (i) presenting respiratory complications such as pneumonia, ventilatory failure, severe acute respiratory distress syndrome, sepsis, acute cardiovascular complications or death; or respiratory failure requiring invasive or non-invasive ventilatory support, (ii) having been hospitalized or (iii) having been admitted to an Intensive Care Unit. Controls were individuals diagnosed with the disease on the same date (or same week) as the cases. A total of 1653 individuals were included in the study, (858 cases/795 controls). These participants had a mean age of 26 years, a low level of education, and were mostly female. The most important predictors identified were systolic blood pressure in mmHg, respiratory rate in bpm, dehydration, obesity, pregnancy (in women), and vomiting (in children). Three clinical prediction models of severity were developed, for adults, adult women, and for children. The performance evaluation of these models indicated good predictive capacity. The area values under the ROC curve of these models were 0.89; 0.98 and 0.91 respectively for the model of adults, adult women, and children respectively.
Can routine antenatal data be used to assess HIV antiretroviral therapy coverage among pregnant women? Evaluating the validity of different data sources in the Western Cape, South Africa
Authors: Jacob Nisha , Rice Brian , Heekes Alexa , Johnson Leigh F. , Brinkmann Samantha , Kufa Tendesayi , Boulle Andrew 
Published: September 2023

AbstractBackgroundAccurate measurement of antenatal antiretroviral treatment (ART) coverage in pregnancy is imperative in tracking progress towards elimination of vertical HIV transmission. In the Western Cape, South Africa, public-sector individual-level routine data are consolidated from multiple sources, enabling the description of temporal changes in population-wide antenatal antiretroviral coverage. We evaluated the validity of different methods for measuring ART coverage among pregnant women.MethodsWe compared self-reported ART data from a 2014 antenatal survey with laboratory assay data from a sub-sample within the survey population. Thereafter, we conducted a retrospective cohort analysis of all pregnancies consolidated in the Provincial Health Data Centre (PHDC) from January 2011 to December 2020. Evidence of antenatal and HIV care from electronic platforms were linked using a unique patient identifier. ART coverage estimates were triangulated with available antenatal survey estimates, aggregated programmatic data from registers recorded in the District Health Information System (DHIS) and Thembisa modelling estimates.ResultsSelf-reported ART in the 2014 sentinel antenatal survey (n=1434) had high sensitivity (83.5%), specificity (94.5%) and agreement (k=0.8) with the gold standard of laboratory analysis of ART. Based on linked routine data, ART coverage by the time of delivery in mothers of live births increased from 67.4% in 2011 to 94.7% by 2019. This pattern of increasing antenatal ART coverage was also seen in the DHIS data, and estimated by the Thembisa model, but was less consistent in the antenatal survey data.ConclusionThis study is the first in a high-burden HIV setting to compare sentinel ART surveillance data with consolidated individuated administrative data. Although self-report in survey conditions showed high validity, more recent data sources based on self-report and medical records may be uncertain with increasing ART coverage over time. Linked individuated data may offer a promising option for ART coverage estimation with greater granularity and efficiency.
Translational modulation by ISRIB alleviates synaptic and behavioral phenotypes in Fragile X syndrome
Authors: Coulson Rochelle L. , Frattini Valentina , Moyer Caitlin E. , Hodges Jennifer , Walter Peter , Mourrain Philippe , Zuo Yi , Wang Gordon X. 
Published: September 2023

SummaryFragile X syndrome (FXS) is caused by the functional loss of Fragile X messenger ribonucleoprotein (FMRP), a translational regulator that binds the transcripts of many proteins involved in synaptic function and plasticity. Dysregulated protein synthesis is a central effect of FMRP loss and to date direct translational modulation has not been leveraged in the treatment of FXS. Thus, we examined the effect of the small molecule translational modulator, Integrated Stress Response Inhibitor (ISRIB), in treating synaptic and behavioral symptoms of FXS. Using a combination of population-level single synapse analysis,in vivotwo-photon microscopy, and behavioral analysis, we revealed a mechanism for the appearance of dense and immature dendritic spines, which are observed in human FXS patients andFmr1knockout (KO) mice. Our data suggest that FMRP loss at the synapse dysregulates synaptic protein abundance and that spines are disproportionately stabilized through increased PSD-95 expression but prevented from maturing through reduced synaptic accumulation of glutamate receptors. ISRIB rescues these molecular and synaptic deficits in FXS and improves social recognition inFmr1KO mice. These findings highlight the therapeutic potential of targeting core translational mechanisms and the differential impact of FMRP on synaptic and cellular function in FXS and neurodevelopmental disorders more broadly.
Evaluating the Utilities of Foundation Models in Single-cell Data Analysis
Authors: Liu Tianyu , Li Kexing , Wang Yuge , Li Hongyu , Zhao Hongyu 
Published: September 2023

AbstractFoundation Models (FMs) have made significant strides in both industrial and scientific domains. In this paper, we evaluate the performance of FMs for single-cell sequencing data analysis through comprehensive experiments across eight downstream tasks pertinent to single-cell data. Overall, the top FMs include scGPT, Geneformer, and CellPLM by considering model performances and user accessibility among ten single-cell FMs. However, by comparing these FMs with task-specific methods, we found that single-cell FMs may not consistently excel than task-specific methods in all tasks, which challenges the necessity of developing foundation models for single-cell analysis. In addition, we evaluated the effects of hyper-parameters, initial settings, and stability for training single-cell FMs based on a proposedscEvalframework, and provide guidelines for pre-training and fine-tuning, to enhance the performances of single-cell FMs. Our work summarizes the current state of single-cell FMs, points to their constraints and avenues for future development, and offers a freely available evaluation pipeline to benchmark new models and improve method development.
Deep learning-assisted single-molecule detection of protein post-translational modifications with a biological nanopore
Authors: Cao Chan , Magalhães Pedro , Krapp Lucien Fabrice , Bada Juarez Juan F. , Mayer Simon , Rukes Verena , Chiki Anass , Lashuel Hilal A. , Dal Peraro Matteo 
Published: September 2023

AbstractProtein post-translational modifications (PTMs) play a crucial role in countless biological processes, profoundly modulating protein properties on both the spatial and temporal scales. Protein PTMs have also emerged as reliable biomarkers for several diseases. However, only a handful of techniques are available to accurately measure their levels, capture their complexity at a single molecule level and characterize their multifaceted roles in health and disease. Nanopore sensing provides high sensitivity for the detection of low-abundance proteins, holding the potential to impact single-molecule proteomics and PTM detection in particular. Here, we demonstrate the ability of a biological nanopore, the pore-forming toxin aerolysin, to detect and distinguish α-synuclein-derived peptides bearing single or multiple PTMs, namely phosphorylation, nitration and oxidation occurring at different positions and in various combinations. The characteristic current signatures of the α-synuclein peptide and its PTM variants could be confidently identified using a deep learning model for signal processing. We further demonstrate that this framework can quantify α-synuclein peptides at picomolar concentration and detect the C-terminal peptides generated by digestion of full-length α-synuclein. Collectively, our work highlights the unique advantage of using nanopore as a tool for simultaneous detection of multiple PTMs and paves the way for their use in biomarker discovery and diagnostics.