bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of cell isolation magnetic particles on DNA quantification by UV absorbance spectrophotometry
Authors: Bajwa Izza Usman , Sigaud Samuel 
Published: April 2023

AbstractMagnetic particles are commonly used to isolate specific cell types from blood samples. Residual particles present in the genomic DNA extracted from these cells can interfere with concentration measurements by UV absorbance spectrophotometry. In this study, we determined the degree of inaccuracy of DNA quantification by UV spectrophotometry, in the context of the lineage-specific chimerism analysis workflow. We showed that the presence of residual magnetic particles and RNA leads to an overestimation of the DNA concentration.
Acute dorsal genital nerve stimulation increases subjective arousal in women with and without spinal cord injury: a preliminary investigation
Authors: Bottorff Elizabeth C. , Gupta Priyanka , Ippolito Giulia M. , Moore Mackenzie B. , Rodriguez Gianna M. , Bruns Tim M. 
Published: April 2023

AbstractIntroductionFemale sexual dysfunction (FSD) impacts an estimated 40% of women. Unfortunately, female sexual function is understudied, leading to limited treatment options for FSD. Neuromodulation has demonstrated some success in improving FSD symptoms. We developed a pilot study to investigate the short-term effect of electrical stimulation of the dorsal genital nerve and tibial nerve on sexual arousal in healthy women, women with FSD, and women with spinal cord injury (SCI) and FSD.MethodsThis study consists of a randomized crossover design in three groups: women with SCI, women with non-neurogenic FSD, and women without FSD or SCI. The primary outcome measure was change in vaginal pulse amplitude (VPA) from baseline. Secondary outcome measures were changes in subjective arousal, heart rate, and mean arterial pressure from baseline. Participants attended one or two study sessions where they received either transcutaneous dorsal genital nerve stimulation (DGNS) or tibial nerve stimulation (TNS). At each session, a vaginal photoplethysmography sensor was used to measure VPA. Participants also rated their level of subjective arousal and were asked to report any pelvic sensations.ResultsWe found that subjective arousal increased significantly from before to after stimulation in DGNS study sessions across all women. TNS had no effect on subjective arousal. There were significant differences in VPA between baseline and stimulation, baseline and recovery, and stimulation and recovery periods among participants, but there were no trends across groups or stimulation type. Two participants with complete SCIs experienced genital sensations.DiscussionThis is the first study to measure sexual arousal in response to acute neuromodulation in women. This study demonstrates that acute DGNS, but not TNS, can increase subjective arousal, but the effect of stimulation on genital arousal is inconclusive. This study provides further support for DGNS as a treatment for female sexual dysfunction.
Can an online battery match in-person cognitive testing in predicting age-related cortical changes?
Authors: Thienel R. , Borne L. , Faucher C. , Robinson G.A. , Fripp J. , Giorgio J. , Ceslis A. , McAloney K. , Adsett J. , Galligan D. , Martin N.G. , Breakspear M. , Lupton M. K. 
Published: April 2023

AbstractUnderstanding how cognition and brain structure change across the lifespan is crucial for gaining insight into the healthy ageing process, as well as identifying early signs of neurodegenerative changes. In our recent prospective study of healthy ageing in midlife and older adults1, we compared the association of two cognitive batteries with age-related variability in brain morphology. Our findings revealed that online cognitive testing, which is more cost-effective, demonstrated comparable association to sulcal width as comprehensive in person assessment. Both cognitive assays show similarly strong correlations with sulcal width. In addition, it was found that both cognitive assessment assays showed a more pronounced age-related decline in individuals with Aβ burden. These findings suggest that online assessment is able to detect accelerated cognitive ageing comparably to the in-person assay in our preclinical sample, even in the early stages of Aβ accumulation before significant structural brain changes occur. Taken together with their greater cost effectiveness, online cognitive testing could lead to more equitable early detection and intervention for neurodegenerative diseases.
What would other emergency stroke teams do? Using explainable machine learning to understand variation in thrombolysis practice
Authors: Pearn Kerry , Allen Michael , Laws Anna , Monks Thomas , Everson Richard , James Martin 
Published: April 2023

AbstractObjectivesTo understand between-hospital variation in thrombolysis use among patients in England and Wales who arrive at hospital within 4 hours of stroke onset.DesignMachine learning was applied to the Sentinel Stroke National Audit Programme (SSNAP) data set, to learn which patients in each hospital would likely receive thrombolysis.SettingAll hospitals (n=132) providing emergency stroke care in England and Wales. Thrombolysis use in patients arriving within 4 hours of known or estimated stroke onset ranged from 7% to 49% between hospitals.Participants88,928 stroke patients recorded in the national stroke audit who arrived at hospital within 4 hours of stroke onset, from 2016 to 2018.InterventionExtreme Gradient Boosting (XGBoost) machine learning models, coupled with a SHAP model for explainability.Main Outcome MeasuresShapley (SHAP) values, providing estimates of how patient features, and hospital identity, influence the odds of receiving thrombolysis.ResultsThe XGBoost/SHAP model revealed that the odds of receiving thrombolysis reduced 9 fold over the first 120 minutes of arrival-to-scan time, varied 30 fold depending on stroke severity, reduced 3 fold with estimated rather than precise stroke onset time, fell 6 fold with increasing pre-stroke disability, fell 4 fold with onset during sleep, fell 5 fold with use of anticoagulants, fell 2 fold between 80 and 110 years of age, reduced 3 fold between 120 and 240 minutes of onset-to-arrival time, and varied 13 fold between hospitals. The hospital attended explained 56% of the variance in between-hospital thrombolysis use, adding in other hospital processes explained 74%, the patient population alone explained 36%, and the combined information from both patient population and hospital processes explained 95% of the variance in between-hospital thrombolysis use. Patient SHAP values expose how suitable a patient is considered for thrombolysis. Hospital SHAP values expose the threshold at which patients are likely to receive thrombolysis.ConclusionsUsing explainable machine learning, we have identified that the majority of the between-hospital variation in thrombolysis use in England and Wales, for patients arriving with time to thrombolyse, may be explained by differences in in-hospital processes and differences in attitudes to judging suitability for thrombolysis.
Reservoir Computing in Epidemiological Forecasting: Predicting Chicken Pox incidence
Authors: Kumar Kaushal 
Published: April 2023

AbstractWe examine the applicability of time-series forecasting techniques to model and predict chickenpox incidence rates using publicly available epidemiological data from Rozemberczki et al. [1]. Analyzing data across both time and location is crucial in understanding disease dynamics, allowing for the identification of patterns such as temporal clustering, detection of high-incidence areas, characterization of disease spread, measurement of temporal synchrony, and forecasting future incidence rates. The primary objective of this study is to evaluate the effectiveness of neural networks in addressing this problem. Reservoir Computing, ARIMA, and various types of Recurrent Neural Networks (RNNs) have demonstrated success in tackling complex time-series issues. We assess several models based on different RNN architectures, including Long Short-Term Memory (LSTM), Bidirectional LSTM (BLSTM), Gated Recurrent Unit (GRU), Bidirectional GRU (BGRU), and compare their performance. We use a deep learning approach based on Reservoir Computing to predict chickenpox counts based on past incidence rates. We implement all the aforementioned neural network architectures for fore-casting chickenpox incidence rates and compare their prediction accuracy. Our results indicate that Reservoir Computing prediction models outperform all other models trained on the same data. Furthermore, we demonstrate that Reservoir Computing prediction models are more efficient and quicker to train and deploy in epidemiology.
Noise-induced damage in the zebrafish inner ear endorgans: evidence for higher acoustic sensitivity of saccular and lagenar hair cells
Authors: Lau Ieng Hou , Vasconcelos Raquel O. 
Published: April 2023

AbstractThe three otolithic endorgans of the inner ear are known to be involved in sound detection in different teleost fishes, yet their relative roles for auditory-vestibular functions within the same species remain unclear. In zebrafish (Danio rerio), saccule and utricle are thought to play key functions in encoding auditory and vestibular information, respectively, but the biological function of lagena is not clear. We hypothesized that the saccule is the main auditory endorgan and lagena might serve an auditory function given its connectivity to the saccule and dominant vestibular function of the utricle in this species.We investigated the acoustic sensitivity of the three otolithic endorgans in adult zebrafish by comparing the impact of acoustic trauma (continuous white noise at 168 dB for 24 h) on their sensory epithelia.Noise treatment caused hair cell loss in both the saccule and lagena, but not in the utricle. This effect was identified immediately after acoustic treatment and did not increase 24h post trauma. Furthermore, hair cell loss was accompanied by a reduction in presynaptic activity measured based on Ribeye b expression but mainly in the saccule, supporting its main contribution for noise-induced hearing loss.Our findings support the hypothesis that the saccule plays a major role in hearing and that lagena is also acoustically affected but with less sensitivity most likely extending the species hearing dynamic range.Summary statementNoise-treated zebrafish showed higher hair cell loss and synaptopathy in the inner ear saccule and, to some extent, in the lagena, confirming their higher sensitivity and contribution for hearing loss compared to utricle.
Can Single Cell Respiration be Measured by Scanning Electrochemical Microscopy (SECM)?
Authors: Cremin Kelsey , Meloni Gabriel N. , Valavanis Dimitrios , Soyer Orkun S. , Unwin Patrick R. 
Published: April 2023

AbstractUltramicroelectrode (UME), or - equivalently - microelectrode, probes are increasingly used for single-cell measurements of cellular properties and processes, including physiological activity, such as metabolic fluxes and respiration rates. Major challenges for the sensitivity of such measurements include: (i) the relative magnitude of cellular and UME fluxes (manifested in the current); and (ii) issues around the stability of the UME response over time. To explore the extent to which these factors impact the precision of electrochemical cellular measurements, we undertake a systematic analysis of measurement conditions and experimental parameters for determining single cell respiration rates, via the oxygen consumption rate (OCR) at single HeLa cells. Using scanning electrochemical microscopy (SECM), with a platinum UME as the probe, we employ a self-referencing measurement protocol, rarely employed in SECM, whereby the UME is repeatedly approached from bulk solution to a cell, and a short pulse to oxygen reduction reaction (ORR) potentials is performed near the cell and in bulk solution. This approach enables the periodic tracking of the bulk UME response to which the near-cell response is repeatedly compared (referenced), and also ensures that the ORR near the cell is performed only briefly, minimizing the effect of the electrochemical process on the cell. SECM experiments are combined with a finite element method (FEM) modeling framework, to simulate oxygen diffusion and the UME response. Taking a realistic range of single cell OCR to be 1×10−18to 1×10−16mol s-1, results from the combination of FEM simulations and self-referencing SECM measurements show that these OCR values are at - or below - the present detection sensitivity of the technique. We provide a set of model-based suggestions for improving these measurements in the future, but highlight that extraordinary improvements in the stability and precision of SECM measurements will be required if single cell OCR measurements are to be realized.TOC
Genomic Correlates of Tailocin Sensitivity inPseudomonas syringae
Authors: Baltrus David A. , Weaver Savannah , Krings Laura , Nguyen Anh Evy 
Published: April 2023

AbstractPhage derived bacteriocins, also referred to as tailocins, are structures encoded by bacterial genomes and deployed into the extracellular environment to target and kill sensitive cells. Tailocins display great potential as agricultural antimicrobials due to their durability, efficiency, and specificity of killing with prophylactic application of these molecules having been shown to prevent infection by multiple phytopathogens. Although previous reports have strongly suggested that tailocins ofPseudomonas syringaebind sugar moieties in the LipoPolySaccharide (LPS) of target cells, the molecular mechanisms and binding interactions that enable tailocins fromP. syringaeto kill sensitive targets remain unclear. We therefore carried out a genome-wide association study investigating tailocin sensitivity across a diverse set ofP. syringaegenomes. Our results demonstrate that genes strongly correlated with tailocin sensitivity are localized to one contiguous region on theP. syringaechromosome encoding LPS structures similar to the Common Polysaccharide Antigen ofP. aeruginosa. We further find that enzymes involved in the biosynthesis and transport of D-rhamnose and L-rhamnose are associated with tailocin sensitivity classes A and B, respectively, with large-scale recombination of the O-antigen biosynthesis region likely underlying rapid and fundamental changes in LPS structure between strains. We identify therfbDgene as an additional genomic indicator to predict tailocin sensitivity and use this information to test tailocin interactions with unscreened strains from across phylogroups, including some in which LPS chains have been previously characterized. Overall, our results strongly support that tailocin sensitivity acrossP. syringaestrains is largely determined by recombination events across strains that lead to differential production of either D or L-rhamnose moieties in the main LPS chain.
Quantitative prediction of right ventricular and size and function from the electrocardiogram
Authors: Duong Son Q. , Vaid Akhil , Vy Ha My Thi , Butler Liam R. , Lampert Joshua , Pass Robert H. , Charney Alexander W. , Narula Jagat , Khera Rohan , Greenspan Hayit , Gelb Bruce D. , Do Ron , Nadkarni Girish 
Published: April 2023

ABSTRACTBackgroundRight ventricular ejection fraction (RVEF) and end-diastolic volume (RVEDV) are not readily assessed through traditional modalities. Deep-learning enabled 12-lead electrocardiogram analysis (DL-ECG) for estimation of RV size or function is unexplored.MethodsWe trained a DL-ECG model to predict RV dilation (RVEDV>120 mL/m2), RV dysfunction (RVEF<40%), and numerical RVEDV/RVEF from 12-lead ECG paired with reference-standard cardiac MRI (cMRI) volumetric measurements in UK biobank (UKBB; n=42,938). We fine-tuned in a multi-center health system (MSHoriginal; n=3,019) with prospective validation over 4 months (MSHvalidation; n=115). We evaluated performance using area under the receiver operating curve (AUROC) for categorical and mean absolute error (MAE) for continuous measures overall and in key subgroups. We assessed association of RVEF prediction with transplant-free survival with Cox proportional hazards models.ResultsPrevalence of RV dysfunction for UKBB/MSHoriginal/MSHvalidationcohorts was 1.0%/18.0%/15.7%, respectively. RV dysfunction model AUROC for UKBB/MSHoriginal/MSHvalidationcohorts was 0.86/0.81/0.77, respectively. Prevalence of RV dilation for UKBB/MSHoriginal/MSHvalidationcohorts was 1.6%/10.6%/4.3%. RV dilation model AUROC for UKBB/MSHoriginal/MSHvalidationcohorts 0.91/0.81/0.92, respectively. MSHoriginalMAE was RVEF=7.8% and RVEDV=17.6 ml/m2. Performance was similar in key subgroups including with and without left ventricular dysfunction. Over median follow-up of 2.3 years, predicted RVEF was independently associated with composite outcome (HR 1.37 for each 10% decrease, p=0.046).ConclusionsDL-ECG analysis can accurately identify significant RV dysfunction and dilation both overall and in key subgroups. Predicted RVEF is independently associated with clinical outcome.
Characterization of Pro-Fibrotic Signaling Pathways using Human Hepatic Organoids
Authors: Guan Yuan , Fang Zhuoqing , Hu Angelina , Roberts Sarah , Wang Meiyue , Ren Wenlong , Johansson Patrik K. , Heilshorn Sarah C. , Enejder Annika , Peltz Gary 
Published: April 2023

AbstractDue to the limitations of availablein vitrosystems and animal models, we lack a detailed understanding of the pathogenetic mechanisms and have minimal treatment options for liver fibrosis. To overcome this barrier, we engineered a live cell imaging system that identifies collagen producing cells in a human multi-lineage hepatic organoid. This system was adapted for use as a microwell-based platform (i.e., microHOs) where exposure to PDGF or TGFβ1 induced the formation of thick collagen fibers. Transcriptomic analysis revealed that TGFβ1 exposure converted mesenchymal cells into myofibroblast-like cells that contribute to the development of liver fibrosis. When pro-fibrotic intracellular signaling pathways were examined using pharmacological probes, the anti-fibrotic effect of receptor-specific tyrosine kinase inhibitors was limited to the fibrosis induced by the corresponding growth factor, which indicates that their anti-fibrotic efficacy would be limited to fibrotic diseases that were solely mediated by that growth factor. Transcriptomic and transcription factor activation analyses were used to identify pathways that were jointly activated by PDGF and TGFβ1. GSK3β or p38 MAPK inhibitors could prevent TGFβ1- or PDGF-induced fibrosis in microHOs because they block intracellular signaling pathways that are commonly utilized by the TGFβ1 and PDGF receptors. Hence, these studies identified GSK3β and p38 MAPK inhibitors as potential new broad-spectrum therapies for liver fibrosis, and it is likely that other new therapies could subsequently be identified using this microHO system.
Emotional information facilitates or disrupts memory integration through distinct hippocampal processes of reactivation and connectivity
Authors: Zhu Yannan , Liu Wei , Kohn Nils , Fernández Guillén 
Published: April 2023

AbstractEmotion has a significant impact on how related experiences are organized into integrated memories. However, the neurobiological mechanisms of how emotion modulates memory integration for related information with different valences remain unclear. In this between-subject functional magnetic resonance imaging (fMRI) study, we investigated different emotional modulations of memory integration by manipulating the valence of stimuli used in an associative memory paradigm. Three groups of participants were tested: one group integrated emotional (i.e., negative) information with neutral information, one group integrated two emotional pieces of information, and one control group integrated two neutral pieces of information. Behaviorally, emotional information facilitated its integration with neutral information but interfered with the other emotional information. Neurally, the emotion-induced facilitation effect, occurring on memory integration of neutral and emotional information, was associated with increased trial-specific reactivation in the hippocampus during both encoding and retrieval. This facilitated integration was also supported by strengthened hippocampal connectivity with the amygdala, as well as a set of neocortical areas related to emotion regulation and the default mode network (DMN). In contrast, the emotion-induced interference effect, occurring on memory integration of two emotional pieces of information, was associated with impaired hippocampal trial-specific reactivation during retrieval that appeared to offset the facilitating effect of increased reactivation during encoding. Similar but relatively weak hippocampal connectivity was found underlying this interfered integration. Taken together, emotional information facilitates memory integration with neutral information, while disrupting the integration with other emotional information, through distinct dynamical processes of hippocampal trial-specific reactivation and connectivity.
Biochemical and genetic dissection of the RNA-binding surface of the FinO domain ofEscherichia coliProQ
Authors: Stein Ewa M. , Wang Suxuan , Dailey Katherine , Gravel Chandra M , Wang Shiying , Olejniczak Mikołaj , Berry Katherine E 
Published: April 2023

ABSTRACTRNA-binding proteins play important roles in bacterial gene regulation through interactions with both coding and non-coding RNAs. ProQ is a FinO-domain protein that binds a large set of RNAs inEscherichia coli, though the details of how ProQ binds these RNAs remain unclear. In this study, we used a combination ofin vivoandin vitrobinding assays to confirm key structural features ofE. coliProQ’s FinO domain and explore its mechanism of RNA interactions. Using a bacterial three-hybrid assay, we performed forward genetic screens to confirm the importance of the concave face of ProQ in RNA binding. Using gel shift assays, we directly probed the contributions of ten amino acids on ProQ binding to seven RNA targets. Certain residues (R58, Y70, and R80) were found to be essential for binding of all seven RNAs, while substitutions of other residues (K54 and R62) caused more moderate binding defects. Interestingly, substitutions of two amino acids (K35, R69), which are evolutionarily variable but adjacent to conserved residues, showed varied effects on the binding of different RNAs; these may arise from the differing sequence context around each RNA’s terminator hairpin. Together, this work confirms many of the essential RNA-binding residues in ProQ initially identifiedin vivoand supports a model in which residues on the conserved concave face of the FinO domain such as R58, Y70 and R80 form the main RNA-binding site ofE. coliProQ, while additional contacts contribute to the binding of certain RNAs.