bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-Specific Haemodynamic Analysis of Virtual Grafting Strategies in Type-B Aortic Dissection: Impact of Compliance Mismatch
Authors: Girardin Louis , Stokes Catriona , Thet Myat Soe , Oo Aung Ye , Balabani Stavroula , Díaz-Zuccarini Vanessa 
Published: June 2023

AbstractIntroductionCompliance mismatch between the aortic wall and Dacron Grafts is a clinical problem concerning aortic haemodynamics and morphological degeneration. The aortic stiffness introduced by grafts can lead to an increased left ventricular (LV) afterload. This study quantifies the impact of compliance mismatch by virtually testing different Type-B aortic dissection (TBAD) surgical grafting strategies in patient-specific, compliant computational fluid dynamics (CFD) simulations.Materials and MethodsA post-operative case of TBAD was segmented from computed tomography angiography data. Three virtual surgeries were generated using different grafts; two additional cases with compliant grafts were assessed. Compliant CFD simulations were performed using a patient-specific inlet flow rate and three-element Windkessel outlet boundary conditions informed by 2D-Flow Magnetic Resonance Imaging (2DMRI) data. The wall compliance was calibrated using Cine-MRI images. Pressure, wall shear stress (WSS) indices and energy loss (EL) were computed.ResultsIncreased aortic stiffness and longer grafts increased aortic pressure and EL. Implementing a compliant graft matching the aortic compliance of the patient reduced the pulse pressure by 11% and EL by 4%. The endothelial cell activation potential (ECAP) differed the most within the aneurysm, where the maximum percentage difference between the reference case and the mid (MDA) and complete (CDA) descending aorta replacements increased by 16% and 20%, respectively.ConclusionThis study highlights the negative impact of increased graft length on LV condition after surgical aortic replacement in TBAD. To mitigate the associated risks to the patient, graft manufacturers should allocate more resources toward developing compliant biomimetic grafts.
Fungal infections in Sudan: an underestimated health problem
Authors: Ahmed Sarah A. , Ismail Mawahib , Albirair Mohamed , Nail Abdelsalam Mohamed Ahmed , Denning David W. 
Published: June 2023

AbstractFungal diseases are associated with high morbidity and mortality, yet their epidemiology and burden are not well addressed. While deaths probably exceed 1.5 million per year, many cases remain undiagnosed and underreported. Estimating the burden of these diseases is needed for prioritization and implementation of effective control programs. Here we used a model based on population at risk to estimate the burden of serious fungal infections in Sudan. The prevalence of the susceptible population including HIV, TB, cancer, asthma, and COPD was obtained from the literature. Incidence and prevalence of fungal infections were calculated using local data when applicable and if not available then regional or international figures were used. In total, the estimated number of Sudanese suffering from fungal disease is 5 M (10% of the total population). Tinea capitis, recurrent vulvovaginitis and keratitis are estimated to affect 4,127,760, 631,261, and 6,552 patients, respectively. HIV-related mycosis is estimated to affect 5,945 oral candidiasis, 1,921 esophageal candidiasis, 571Pneumocystispneumonia, and 462 cryptococcal meningitis cases.Aspergillusinfections are estimated as follow: 3,438 invasive aspergillosis, 14,950 chronic pulmonary aspergillosis, 67,860 allergic bronchopulmonary aspergillosis cases, while the prevalence of severe asthma with fungal sensitization and fungal rhinosinusitis was 86,860 and 93,600 cases, respectively. The neglected tropical disease eumycetoma was estimated to affect 16,837 cases with a rate of 36/100,000. Serious fungal infections are quite common in Sudan and require urgent attention to improve diagnosis, promote treatment, and develop surveillance programs.Author SummaryFungal infections are present globally, but the burden is higher in sub-Saharan Africa. Many of these infections occur because of underline clinical conditions such as HIV, TB, cancer, asthma, and chronic obstructive pulmonary disease (COPD), while some may occur without underline conditions. We used the prevalence of susceptible populations to estimate the burden of fungal diseases in Sudan. Based on that, we found a total of 5 million Sudanese suffering from fungal infection. The most common disease was scalp infection (tinea capitis), followed by recurrent vulvovaginitis. Fungal eye infection was estimated to affect 6,552 patients, and the subcutaneous neglected tropical disease eumycetoma affects 16,837 individuals. We also reported a high burden for HIV- and TB-related mycoses. The study highlighted the need to develop surveillance programs for fungal infections in Sudan.
Childhood growth trajectory patterns are associated with the pubertal gut microbiota
Authors: López-Domínguez Lorena , Bourdon Celine , Hamilton Jill , Taibi Amel , Bassani Diego G , dos Santos Vaz Juliana , Buffarini Romina , Tovo Rodrigues Luciana , Santos Iná S , Matijasevich Alicia , Borges M Carolina , Hanley Anthony J , Barros Aluísio JD , Bandsma Robert HJ , Comelli Elena M 
Published: June 2023

ABSTRACTThe relationship between growth and gut microbiota establishment is critical but under-investigated during late childhood. This is an important knowledge gap since the adult microbiota connects with other organs to influence health. We studied gut microbial communities composition and dietary patterns in 13 years old males and females from the 2004 Pelotas birth cohort (Brazil). We had previously shown that three BMIZ and HAZ patterns of growth since birth are present in this cohort, reflecting the nutritional status of these children. Here, we show that there is an association between growth patterns and gut microbiota, which encompasses the five pubertal stages, and which is affected by sex. Using Partial Least Square Path Modelling, we also show that there is a strong relationship between dietary patterns and gut microbiota, in males but not females. These data provide the microbiota and dietary profiles of highly phenotyped children and highlight the importance of childhood growth and sex for the maturation of the gut microbiota and long-term healthy growth. The role of pubertal diet in the relationships identified, further underlies the importance of dietary patterns establishment during adolescence while providing an opportunity for late modification of growth-microbiota relationships.
Quantifying Associations Between Child Health and Neighborhood Social Vulnerability: Does the Choice of Index Matter?
Authors: Zolotor Anna , Huang Ro W. , Bhavsar Nrupen A. , Cholera Rushina 
Published: June 2023

AbstractImportancePolicymakers have increasingly utilized place-based social disadvantage indices to quantify the impacts of place on health and inform equitable resource allocation. Indices vary in design, content, and purpose but are often used interchangeably, potentially resulting in differential assignments of relative disadvantage depending on index choice.ObjectiveTo compare associations between three commonly used disadvantage indices (Social Vulnerability Index (SVI), Area Deprivation Index (ADI), and Child Opportunity Index (COI)) and two epidemiologically distinct child health outcomes—infant well-child check (WCC) attendance and adolescent obesity.DesignCross-sectional analysis of Duke University Health System electronic health record (EHR) data from January 2014 to December 2019.ParticipantsChildren ≤18 years of age with outpatient encounters between January 2014 and December 2019, and who were Durham County residents were eligible. WCC attendance was assessed for infants ages 0-15 months; obesity was assessed for children ages 11-17 years.Exposures2014 Social Vulnerability Index (SVI), 2015 Area Deprivation Index (ADI), and 2015 Child Opportunity Index (COI) 2.0.Main Outcomes1) Infant WCC attendance: attending less than the minimum recommended six WCCs in the first 15 months of life, and 2) Adolescent obesity: BMI ≥ the 95th percentile at both the most recent encounter and an encounter within the prior 9-36 months.ResultsOf 10175 patients in the WCC cohort, 20% (n = 2073) had less than six WCCs. Of 14961 patients in the obesity cohort, 20% (n = 2933) had obesity. All three indices were associated with both WCCs (OR for SVI 1.10, 95% CI 1.08-1.12; OR for ADI 1.10, 95% CI 1.08-1.12; OR for COI 1.12, 95% CI 1.10-1.14) and obesity (OR for SVI 1.05, 95% CI 1.04-1.08; OR for ADI 1.08, 95% CI 1.06-1.10; OR for COI 1.07, 95% CI 1.05-1.08).Conclusions and relevanceHigher social disadvantage as defined by all three indices was similarly associated with both adolescent obesity and decreased infant WCC attendance. While the COI incorporates a broader set of child-specific variables, the SVI and ADI may often be just as suitable for pediatric research. Users should consider population and outcome characteristics when selecting an index.
Prothrombin Knockdown Protects Podocytes and Reduces Proteinuria in Glomerular Disease
Authors: Waller Amanda P. , Wolfgang Katelyn J. , Pruner Iva , Stevenson Zachary S. , Abdelghani Eman , Muralidharan Kaushik , Wilkie Tasha K. , Blissett Angela R. , Calomeni Edward P. , Vetter Tatyana A. , Brodsky Sergey V. , Smoyer William E. , Nieman Marvin T. , Kerlin Bryce A. 
Published: June 2023

ABSTRACTChronic kidney disease (CKD) is a leading cause of death, and its progression is driven by glomerular podocyte injury and loss, manifesting as proteinuria. Proteinuria includes urinary loss of coagulation zymogens, cofactors, and inhibitors. Importantly, both CKD and proteinuria significantly increase the risk of thromboembolic disease. Prior studies demonstrated that anticoagulants reduced proteinuria in rats and that thrombin injured cultured podocytes. Herein we aimed to directly determine the influence of circulating prothrombin on glomerular pathobiology. We hypothesized that (pro)thrombin drives podocytopathy, podocytopenia, and proteinuria. Glomerular proteinuria was induced with puromycin aminonucleoside (PAN) in Wistar rats. Circulating prothrombin was either knocked down using a rat-specific antisense oligonucleotide or elevated by serial intravenous infusions of prothrombin protein, which are previously established methods to model hypo- (LoPT) and hyper-prothrombinemia (HiPT), respectively. After 10 days (peak proteinuria in this model) plasma prothrombin levels were determined, kidneys were examined for (pro)thrombin co-localization to podocytes, histology, and electron microscopy. Podocytopathy and podocytopenia were determined and proteinuria, and plasma albumin were measured. LoPT significantly reduced prothrombin colocalization to podocytes, podocytopathy, and proteinuria with improved plasma albumin. In contrast, HiPT significantly increased podocytopathy and proteinuria. Podocytopenia was significantly reduced in LoPT vs. HiPT rats. In summary, prothrombin knockdown ameliorated PAN-induced glomerular disease whereas hyper-prothrombinemia exacerbated disease. Thus, (pro)thrombin antagonism may be a viable strategy to simultaneously provide thromboprophylaxis and prevent podocytopathy-mediated CKD progression.
Sperm production and allocation in response to risk of sperm competition in the black soldier flyHermetia illucens
Authors: Manas Frédéric , Labrousse Carole , Bressac Christophe 
Published: June 2023

AbstractIn polyandrous species, competition between males for offspring paternity goes on after copulation through the competition of their ejaculates for the fertilisation of female’s oocytes. Given that males allocating more spermatozoa are favored, different models of sperm competition predict adaptive plasticity in male sperm production and allocation. These predictions were tested experimentally in the black soldier fly (BSF)Hermetia illucens. In this farmed insect, adult biology is little known despite the economic interest of larvae for bioconversion and as an animal feedstuff. Two sets of experiments were carried out to modify the risk of sperm competition perceived by males. The first consisted of placing adult males alone or in groups of 10 – modifying mean risk of sperm competition – and then measuring their sperm production. The second took place at the beginning of copulation; pairs with males from the two mean risk of sperm competition treatments were transferred to different contexts of immediate risk of sperm competition (empty cages, cages containing 10 males, or cages containing 10 females) and the number of spermatozoa stored by the females was counted. Males reared in groups of 10 showed more spermatozoa in their seminal vesicles than males reared alone. Regarding sperm allocation, females that mated in the presence of conspecifics – either 10 males or 10 females – stored more spermatozoa than those that mated alone. This study shows that sperm production and allocation are dependent on sperm competition risk in BSF, revealing a plasticity of reproduction under socio-sexual situations.
Deep learning, data ramping, and uncertainty estimation for detecting artifacts in large, imbalanced databases of MRI images
Authors: Pizarro Ricardo , Assemlal Haz-Edine , Boopathy Jegathambal Sethu K. , Jubault Thomas , Antel Samson , Arnold Douglas , Shmuel Amir 
Published: June 2023

ABSTRACTMagnetic resonance imaging (MRI) is increasingly being used to delineate morphological changes underlying neurological disorders. Successfully detecting these changes depends on the MRI data quality. Unfortunately, image artifacts frequently compromise the MRI utility, making it critical to screen the data. Currently, quality assessment requires visual inspection, a time-consuming process that suffers from inter-rater variability. Automated methods to detect MRI artifacts could improve the efficiency of the process. Such automated methods have achieved high accuracy using small datasets, with balanced proportions of MRI data with and without artifacts. With the current trend towards big data in neuroimaging, there is a need for automated methods that achieve accurate detection in large and imbalanced datasets. Deep learning (DL) is the ideal MRI artifact detection algorithm for large neuroimaging databases. However, the inference generated by DL does not commonly include a measure of uncertainty. Here, we present the first stochastic DL algorithm to generate automated, high-performing MRI artifact detection implemented on a large and imbalanced neuroimaging database. We implemented Monte Carlo dropout in a 3D AlexNet to generate probabilities and epistemic uncertainties. We then developed a method to handle class imbalance, namely data-ramping to transfer the learning by extending the dataset size and the proportion of the artifact-free data instances. We used a 34,800 scans (98% clean) dataset. At baseline, we obtained 89.3% testing accuracy (F1 = 0.230). Following the transfer learning (with data-ramping), we obtained 94.9% testing accuracy (F1 = 0.357) outperforming focal cross-entropy (92.9% testing accuracy, F1 = 0.304) incorporated for comparison at handling class imbalance. By implementing epistemic uncertainties, we improved the testing accuracy to 99.5% (F1 = 0.834), outperforming the results obtained in previous comparable studies. In addition, we estimated aleatoric uncertainties by incorporating random flips to the MRI volumes, and demonstrated that aleatoric uncertainty can be implemented as part of the pipeline. The methods we introduce enhance the efficiency of managing large databases and the exclusion of artifact images from big data analyses.HighlightsWe address the difficulty in automatically detecting artifacts in a large, imbalanced image database.We reproduced high accuracy in detecting artifacts in small balanced datasets.We implemented Monte Carlo (MC) dropout in 3D AlexNet to generate uncertainty metrics.We transfer the learning from a small balanced dataset to a large imbalanced dataset, outperforming focal loss.We outperformed artifact detection in previous studies using comparable large imbalanced datasetsThe user can select an operating point to consider manual inspection vs. artifact detection error.
p97/VCP targetsToxoplasma gondiivacuoles for parasite restriction in interferon-stimulated human cells
Authors: Clough Barbara , Fisch Daniel , Mize Todd H , Encheva Vesela , Snijders Ambrosius , Frickel Eva-Maria 
Published: June 2023

AbstractInfection with the parasiteToxoplasma gondiileads to production of interferon gamma (IFNγ) that stimulates cells to upregulate defence proteins targeting the parasite for cell intrinsic elimination or growth restriction. Various host defence mechanisms operate at the parasitophorous vacuole (PV) in different human cell types leading to PV disruption, acidification, or membrane envelopment. Ubiquitin and p62 are players in all human host control mechanisms ofToxoplasma, but other unifying proteins have not been identified. Here, we show that p97/valosin-containing protein (VCP), as well as its associated proteins ANKRD13A and UBXD1 controlToxoplasmainfection while recruited to the PV in IFNγ-stimulated endothelial cells. Convergent deposition of ANKRD13A, p97/VCP and UBXD1 onto the same vacuole is dependent on vacuolar ubiquitination and observed within 2h post-infection. ANKRD13A, p97/VCP and UBXD1 all drive the acidification mechanism of the vacuole, which is the IFNγ-dependent control pathway ofToxoplasmain endothelial cells. We assessed p97/VCP inToxoplasmacontrol in various human cells and demonstrate that p97/VCP is a universal IFNγ-dependent host restriction factor targeting theToxoplasmaPV in epithelial (HeLa) and endothelial cells (HUVEC), fibroblasts (HFF) and macrophages (THP1).
RAS G-domains fine-tune the sorting of phosphatidylserine acyl chains in the plasma membrane
Authors: Arora Neha , Liang Hong , Zhou Yong 
Published: June 2023

AbstractMutant RAS are major contributors to cancer and signal from nanoclusters on the plasma membrane (PM), via isoform-specific membrane anchors. However, the same RAS isoform bound to different guanine nucleotides are segregated on the PM. Paradoxically, various segregated RAS nanoclusters all enrich a type of anionic phospholipid, phosphatidylserine (PS). These findings suggest intricate participation of RAS G-domains in their PM distribution, which have not been explored. We now show that wild-types, oncogenic G12V mutants and membrane anchors of isoforms HRAS, KRAS4A and KRAS4B sort distinct PS species. Mechanistically, shifting orientation states of KRAS4B G-domain exposes residues, such as Arg 73, Arg 102 and Arg 135, to the PM, and contributes to PS acyl chain sorting. Oncogenic mutations may shift orientation states of G-domains. We show that G12V, G12D, G12C, G13D and Q61H mutants of KRAS4B sort distinct PS species. Thus, RAS G-domains fine-tune their lateral distribution on the PM.
Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes
Authors: Meijer Marieke , Öttl Miriam , Yang Jie , Subkhangulova Aygul , Kumar Avinash , Groffen Alexander J. , van Weering Jan R.T. , Zhang Yongli , Verhage Matthijs 
Published: June 2023

SummaryTomosyns are soluble SNARE proteins proposed to attenuate membrane fusion by competing with synaptobrevin-2/VAMP2 for SNARE-complex assembly. Here, we present evidence against this scenario using a novel mouse model, energy barrier recordings, and single-molecule force measurements. Tomosyn-1/2 deficiency drastically enhanced the probability that synaptic vesicles fuse at synapses, resulting in stronger synapses with faster depression and slower recovery. While wildtype tomosyn-1m rescued these phenotypes, substitution of its SNARE motif with that of synaptobrevin-2/VAMP2 did not. Force measurements revealed that tomosyn’s SNARE motif cannot substitute synaptobrevin-2/VAMP2 to form template complexes with Munc18-1 and syntaxin-1, an essential intermediate for SNARE assembly. Instead, tomosyns bind synaptobrevin-2/VAMP2-containing template complexes and prevent SNAP-25 association. Structure-function analyses indicate that regions outside the SNARE motif contribute to tomosyn’s inhibitory function. These results reveal that tomosyns regulate synaptic transmission by preventing SNAP-25 binding to template complexes, increasing the energy barrier for synaptic vesicle fusion, and limiting synaptic depression.
Extended correlation functions for spatial analysis of multiplex imaging data
Authors: Bull Joshua A. , Mulholland Eoghan J. , Leedham Simon J. , Byrne Helen M. 
Published: June 2023

AbstractImaging platforms for generating highly multiplexed histological images are being continually developed and improved. Significant improvements have also been made in the accuracy of methods for automated cell segmentation and classification. However, less attention has focussed on the quantification and analysis of the resulting point clouds which describe the spatial coordinates of individual cells. We focus here on a particular spatial statistical method, the cross-pair correlation function (cross-PCF), which can identify positive and negative spatial correlation between cells across a range of length scales. However, limitations of the cross-PCF hinder its widespread application to multiplexed histology. For example, it can only consider relations between pairs of cells, and cells must be classified using discrete categorical labels (rather than labelling continuous labels such as stain intensity).In this paper, we present three extensions to the cross-PCF which address these limitations and permit more detailed analysis of multiplex images: Topographical Correlation Maps (TCMs) can visualise local clustering and exclusion between cells; Neighbourhood Correlation Functions (NCFs) can identify colocalisation of two or more cell types; and weighted-PCFs (wPCFs) describe spatial correlation between points with continuous (rather than discrete) labels. We apply the extended PCFs to synthetic and biological datasets in order to demonstrate the insight that they can generate.Impact statementThis paper introduces three methods for performing spatial analysis on multiplex digital pathology images. We apply the methods to synthetic datasets and regions of interest from a murine colorectal carcinoma, in order to illustrate their relative strengths and weaknesses. We note that these methods have wider application to marked point pattern data from other sources.
Walking entrains unique oscillations in performance on a visual detection task
Authors: Davidson Matthew J. , Verstraten Frans A.J. , Alais David 
Published: June 2023

AbstractWalking is among our most frequent and natural of voluntary behaviours, yet the consequences of locomotion upon perceptual and cognitive function remain largely unknown. Recent work has highlighted that although walking feels smooth and continuous, critical phases exist within each step-cycle for the successful coordination of perceptual and motor function. Here, we tested whether these phasic demands impact upon visual perception, by assessing performance in a visual detection task during natural unencumbered walking. We finely sampled visual performance over the stride cycle as participants walked along a smooth linear path at a comfortable speed in a wireless virtual reality environment. At the group-level, accuracy, reaction times, and response likelihood showed strong oscillations, modulating at approximately 2 cycles-per-stride (∼2 Hz) with a marked phase of optimal performance aligned with the swing phase of each step. At the participant level, Bayesian inference of population prevalence revealed highly prevalent oscillations that clustered in two idiosyncratic frequency ranges (2 or 4 cycles per stride), with a strong phase alignment across participants.