bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential diagnosis of thymic epithelial neoplasms on computed tomography using the diameter of the thymic vein
Authors: Sakamoto Naoya , Kurokawa Ryo , Watadani Takeyuki , Morikawa Teppei , Nakaya Moto , Cho Shinichi , Fujita Nana , Kamio Satoru , Koyama Hiroaki , Suzuki Satoshi , Yamada Haruyasu , Abe Osamu , Gonoi Wataru 
Published: November 2021

Abstract
Although differentiating benign and malignant thymic epithelial lesions is important to avoid unnecessary treatment and predict prognosis, it is challenging because of overlaps in the chest computed tomography (CT) findings. In this study, we investigated whether the diameter of the thymic vein and other CT findings could differentiate between benign (thymoma and thymic cysts) and malignant (thymic carcinoma, [TCa]) lesions.
We conducted a retrospective study across two tertiary referral hospitals in Japan between November 2009 and June 2018. We included 12 patients with TCa, 34 patients with thymomas, and 17 patients with thymic cysts. We analyzed the receiver operating characteristic (ROC) curve to determine the best cut-off values and performed univariate and multivariate analyses of CT findings to distinguish TCa from other benign lesions. Post-hoc analysis was performed for the maximum short axis of the thymic vein using the Mann–Whitney U test, and the number of the maximum short axis of the thymic vein ≥ the cutoff was determined using the Fisher exact test with a family-wise error-correction using Bonferroni's method.
ROC analysis showed that a maximum short axis of the thymic vein ≥2 mm was considerably more frequent in TCa than in the other lesions (P < .001 for both), with 83% sensitivity and 86% specificity. Univariate and multivariate analyses revealed the association with TCa of the number of the maximum short axis of the thymic vein ≥2 mm (P = .005, multivariate generalized linear model analysis), ill-defined margin (P = .001), and mediastinal lymphadenopathy (P < .001). Thymic vein diameter was in descendimg order of TCa > thymoma > thymic cysts with statistically significant differences between the groups (Ps < .05).
Thymic vein diameter was significantly longer in TCa than in thymoma and thymic cysts. Measurement of the maximum short axis of the thymic vein could be a powerful diagnostic tool to differentiate TCa from thymoma and thymic cysts.
A Replicable, Solution-Focused Approach to Cross-Sector Data Sharing for Evaluation of Community Violence Prevention Programming
Authors: Mayfield Carlene A. , Siegal Rachel , Herring Melvin , Campbell Tracie , Clark Catie L. , Langhinrichsen-Rohling Jennifer 
Published: November 2021

Context:
Community violence is a public health problem that erodes social infrastructure. Structural racism contributes to the disparate concentration of violence in communities of color. In Mecklenburg County, North Carolina, increasing trends in community violence show racial and geographic disparities that emphasize the need for cross-sector, data-driven approaches to program and policy change. Cross-sector collaborations are challenged by data sharing barriers that hinder implementation.

Program:
In response to community advocacy, Mecklenburg County Public Health (MCPH) launched a Community Violence Prevention Plan with evidence-based programming. The Cure Violence (CV) model, a public health approach to disrupting violence through equitable resource provision, network building, and changing norms, was implemented at the community level. The Health Alliance for Violence Intervention (HAVI) model, a hospital-based screening and case management intervention for victims of violence, was implemented at Carolinas Medical Center in Charlotte, the region's only level I trauma center.

Methods:
A data collaborative was created to optimize evaluation of CV and HAVI programs including MCPH, the city of Charlotte, Atrium Health, Charlotte-Mecklenburg Schools, Johnson C. Smith University, and the University of North Carolina Charlotte. A comprehensive approach to facilitate data sharing was designed with a focus on engaging stakeholders and generating solutions to commonly reported barriers. Structured interviews were used to inform a solution-focused strategy.

Results:
Stakeholders reported perceptions of their organization's barriers and facilitators to cross-sector data sharing. Common technology, legal, and governance barriers were addressed through partnership with a local integrated data system. Solutions for trust and motivational challenges were built into ongoing collaborative processes.

Discussion:
Data silos inhibit the understanding of complex public health issues such as community violence, along with the design and evaluation of collective impact efforts. This approach can be replicated and scaled to support cross-sector collaborations seeking to influence social and health inequities stemming from structural racism.
The Massachusetts Racial Equity Data Road Map: Data as a Tool Toward Ending Structural Racism
Authors: Manning Susan E. , Blinn Antonia M. , Selk Sabrina C. , Silva Christine F. , Stetler Katie , Stone Sarah L. , Yazdy Mahsa M. , Bharel Monica 
Published: November 2021

Background:
In 2015, the Massachusetts Department of Public Health (MDPH) adopted a Title V maternal and child health priority to “promote health and racial equity by addressing racial justice and reducing disparities.” A survey assessing staff capacity to support this priority identified data collection and use as opportunities for improvement. In response, MDPH initiated a quality improvement project to improve use of data for action to promote racial equity.

Methods:
MDPH conducted value stream mapping to understand existing processes for using data to inform racial equity work. Key informant interviews and a survey of program directors identified challenges to using data to promote racial equity. MDPH used a cause-and-effect diagram to identify and organize challenges to using data to inform racial equity work and better understand opportunities for improvement and potential solutions.

Results:
Key informants highlighted the need to consider structural factors and historical and community contexts when interpreting data. Program directors noted limited staff time, lack of performance metrics, competing priorities, low data quality, and unclear expectations as challenges. To address the identified challenges, the team identified potential solutions and prioritized development and piloting of the MDPH Racial Equity Data Road Map (Road Map).

Conclusions:
The Road Map framework provides strategies for data collection and use that support the direction of actionable data-driven resources to racial inequities. The Road Map is a resource to support programs to authentically engage communities; frame data in the broader contexts that impact health; and design solutions that address root causes. With this starting point, public health systems can work toward creating data-driven programs and policies to improve racial equity.
Early Treatment With a Single Dose of Mesenchymal Stem Cell Derived Extracellular Vesicles Modulates the Brain Transcriptome to Create Neuroprotective Changes in a Porcine Model of Traumatic Brain Injury and Hemorrhagic Shock
Authors: Bambakidis Ted , Dekker Simone E. , Williams Aaron M. , Biesterveld Ben E. , Bhatti Umar F. , Liu Baoling , Li Yongqing , Pickell Zachary , Buller Benjamin , Alam Hasan B. 
Published: November 2021

ABSTRACT

Background:
Cell-based therapies using mesenchymal stem cell derived extracellular vesicles (EVs) improve neurologic outcomes in animal models of traumatic brain injury (TBI), stroke, and hemorrhage. Using a porcine 7-day survival model of TBI and hemorrhagic shock (HS), we previously demonstrated that EV-treatment was associated with reduced brain lesion size, neurologic severity score, and cerebral inflammation. However, the underlying cellular and genomic mechanisms remain poorly defined. We hypothesize that EV treatment modulates the brain transcriptome to enhance neuroprotection and neurorestoration following TBI + HS.

Methods:
Swine were subjected to severe TBI (8-mm cortical impact) and HS (40% blood volume). After 1 h of shock, animals were randomized (n = 4/group) to treatment with either lactated Ringer's (LR) or LR + EV. Both groups received fluid resuscitation after 2 h of shock, and autologous packed red blood cells 5 h later.
After 7-days, brains were harvested and RNA-sequencing was performed. The transcriptomic data were imported into the iPathway pipeline for bioinformatics analyses.

Results:
5,273 genes were differentially expressed in the LR + EV group versus LR alone (total 9,588 measured genes). Genes with the greatest upregulation were involved in synaptic transmission and neuronal development and differentiation, while downregulated genes were involved in inflammation. GO-terms experiencing the greatest modulation were involved in inflammation, brain development, and cell adhesion. Pathway analysis revealed significant modulation in the glutamatergic and GABAergic systems. Network analysis revealed downregulation of inflammation, and upregulation of neurogenesis, and neuron survival and differentiation.

Conclusions:
In a porcine model of TBI + HS, EV treatment was associated with an attenuation of cerebral inflammatory networks and a promotion of neurogenesis and neuroplasticity. These transcriptomic changes could explain the observed neuroprotective and neurorestorative properties associated with EV treatment.
Genetic relationships between efficiency traits and gut microbiota traits in growing pigs fed a conventional or a high fiber diet
Authors: Déru V. , Bouquet A. , Zemb O. , Blanchet B. , De Almeida M.L , Cauquil L. , Carillier-Jacquin C. , Gilbert H. 
Published: November 2021

AbstractIn pigs, the gut microbiota composition plays a major role in the process of digestion, but is influenced by many external factors, especially diet. To be used in breeding applications, genotype by diet interactions on microbiota composition have to be quantified, as well as their impact on genetic covariances with feed efficiency (FE) and digestive efficiency (DE) traits. This study aimed at determining the impact of an alternative diet on variance components of microbiota traits (genera and alpha diversity indices), and estimating genetic correlations between microbiota and efficiency traits for pigs fed a conventional (CO) or a high fiber (HF) diet. Fecal microbes of 812 full-siblings fed a CO diet and 752 pigs fed the HF diet were characterized at 16 weeks of age by sequencing the V3-V4 region of the 16S rRNA gene. A total of 231 genera were identified. Digestibility coefficients of nitrogen, organic matter and energy were predicted analyzing the same fecal samples with near infrared spectrometry. Daily feed intake, feed conversion ratio, residual feed intake and average daily gain (ADG) were also recorded. The 71 genera with less than 20% of zeros were retained for genetic analyses. Heritability (h2) of microbiota traits were similar between diets (from null to 0.38 ± 0.12 in the CO diet and to 0.39 ± 0.12 in the HF diet). Only three out of the 24 genera and two alpha diversity indices with significant h2 in both diets had genetic correlations across diets significantly different from 0.99 (P < 0.05), indicating limited genetic by diet interactions for these traits. When both diets were analyzed jointly, 59 genera had h2 significantly different from zero. Based on the genetic correlations between these genera and ADG, FE and DE traits, three groups of genera could be identified. A group of 29 genera was favorably correlated with DE and FE traits, 14 genera were unfavorably correlated with DE traits, and the last group of 16 genera had correlations close to zero with production traits. However, genera favorably correlated with DE and FE traits were unfavorably correlated with ADG, and vice versa. Alpha diversity indices had correlation patterns similar to the first group. In the end, genetic by diet interactions on gut microbiota composition of growing pigs were limited in this study. Based on this study, microbiota-based traits could be used as proxies to improve FE and DE in growing pigs.
Affinity Scores: An Individual-centric Fingerprinting Framework for Neuropsychiatric Disorders
Authors: Wannan Cassandra M J , Pantelis Christos , Merritt Antonia , Tonge Bruce , Syeda Warda T 
Published: November 2021

AbstractBackgroundPopulation-centric frameworks of biomarker identification for psychiatric disorders focus primarily on comparing averages between groups and assume that diagnostic groups are (1) mutually-exclusive, and (2) homogeneous. There is a paucity of individual-centric approaches capable of identifying individual-specific ‘fingerprints’ across multiple domains. To address this, we propose a novel framework, combining a range of biopsychosocial markers, including brain structure, cognition, and clinical markers, into higher-level ‘fingerprints’, capable of capturing intra-illness heterogeneity and inter-illness overlap.MethodsA multivariate framework was implemented to identify individualised patterns of brain structure, cognition and clinical markers based on affinity to other participants in the database. First, individual-level affinity scores defined each participant’s “neighbourhood” across each measure based on variable-specific hop sizes. Next, diagnostic verification and classification algorithms were implemented based on multivariate affinity score profiles. To perform affinity-based classification, data were divided into training and test samples, and 5-fold nested cross-validation was performed on the training data. Affinity-based classification was compared to weighted K-nearest neighbours (KNN) classification. K-means clustering was used to create clusters based on multivariate affinity score profiles. The framework was applied to the Australian Schizophrenia Research Bank (ASRB) dataset.ResultsIndividualised affinity scores provided a ‘fingerprint’ of brain structure, cognition, and clinical markers, which described the affinity of an individual to the representative groups in the dataset Diagnostic verification capability was moderate to high depending on the choice of multivariate affinity metric. Affinity score-based classification achieved a high degree of accuracy in the training, nested cross-validation and prediction steps, and outperformed KNN classification in the training and test datasets.ConclusionAffinity scores demonstrate utility in two keys ways: (1) Early and accurate diagnosis of neuropsychiatric disorders, whereby an individual can be grouped within a diagnostic category/ies that best matches their fingerprint, and (2) identification of biopsychosocial factors that most strongly characterise individuals/disorders, and which may be most amenable to intervention.
Analysis of MRI-derived spleen iron in the UK Biobank identifies genetic variation linked to iron homeostasis and erythrocyte morphology
Authors: Sorokin Elena P. , Basty Nicolas , Whitcher Brandon , Liu Yi , Bell Jimmy D. , Cohen Robert L. , Cule Madeleine , Thomas E. Louise 
Published: November 2021

AbstractThe spleen plays a key role in iron homeostasis. It is the largest filter of the blood and performs iron reuptake from old or damaged erythrocytes. Despite this role, spleen iron concentration has not been measured in a large, population-based cohort. In this study, we quantify spleen iron in 41,764 participants of the UK Biobank using magnetic resonance imaging, and provide the first reference range for spleen iron in an unselected population. Through genome-wide association study, we identify associations between spleen iron and regulatory variation at two hereditary spherocytosis genes, ANK1 and SPTA1. Spherocytosis-causing coding mutations in these genes are associated with lower reticulocyte volume and increased reticulocyte percentage, while these novel common alleles are associated with increased expression of ANK1 and SPTA1 in blood and with larger reticulocyte volume and reduced reticulocyte percentage. As genetic modifiers, these common alleles may explain mild spherocytosis phenotypes that have been observed clinically. Our genetic study also identifies a signal which co-localizes with a splicing quantitative trait locus for MS4A7, and we show this gene is abundantly expressed in the spleen and in macrophages. The combination of deep learning and efficient image processing enables non-invasive measurement of spleen iron and, in turn, characterization of genetic factors related to iron recycling and erythrocyte morphology.
HSP90 modulates T2R bitter taste receptor nitric oxide production and innate immune responses in human airway epithelial cells and macrophages
Authors: Carey Ryan M. , Hariri Benjamin M. , Adappa Nithin D. , Palmer James N. , Lee Robert J. 
Published: November 2021

ABSTRACTBitter taste receptors (T2Rs) are G protein-coupled receptors (GPCRs) expressed in various cell types including ciliated airway epithelial cells and macrophages. T2Rs in these two airway innate immune cell types are activated by bitter products, including some secreted by Pseudomonas aeruginosa, leading to Ca2+-dependent activation of endothelial nitric oxide (NO) synthase (eNOS). NO enhances mucociliary clearance and has direct antibacterial effects in ciliated epithelial cells and increases phagocytosis by macrophages. Using biochemistry and live cell imaging, we explored the role of heat shock protein 90 (HSP90) in regulating T2R-dependent NO pathways in primary sinonasal epithelial cells, primary monocyte-derived macrophages, and a human bronchiolar cell line (H441). We used immunofluorescence to show that H441 cells express eNOS and certain T2Rs and that the bitterant denatonium benzoate activates NO production in an HSP90-dependent manner in cells grown either as submerged cultures and at air liquid interface. In primary sinonasal epithelial cells, we determined that HSP-90 inhibition reduces T2R-stimulated NO production and ciliary beating which are crucial for pathogen clearance. In primary monocyte-derived macrophages, we found that HSP-90 is integral to T2R-stimulated NO production and phagocytosis of FITC-labeled Escherichia coli and pHrodo-Staphylococcus aureus. Our study demonstrates that HSP90 serves an innate immune role by regulating NO production downstream of T2R signaling by augmenting eNOS activation without impairing upstream calcium signaling. These findings suggest that HSP90 plays an important role in airway antibacterial innate immunity and may be an important target in airway diseases like chronic rhinosinusitis, asthma, or cystic fibrosis.
Characterizing Protein Conformational Spaces using Dimensionality Reduction and Algebraic Topology
Authors: Joshi Arpita , Haspel Nurit , González Eduardo 
Published: November 2021

AbstractDatasets representing the conformational landscapes of protein structures are high dimensional and hence present computational challenges. Efficient and effective dimensionality reduction of these datasets is therefore paramount to our ability to analyze the conformational landscapes of proteins and extract important information regarding protein folding, conformational changes and binding. Representing the structures with fewer attributes that capture the most variance of the data, makes for quicker and precise analysis of these structures. In this work we make use of dimensionality reduction methods for reducing the number of instances and for feature reduction. The reduced dataset that is obtained is then subjected to topological and quantitative analysis. In this step we perform hierarchical clustering to obtain different sets of conformation clusters that may correspond to intermediate structures. The structures represented by these conformations are then analyzed by studying their high dimension topological properties to identify truly distinct conformations and holes in the conformational space that may represent high energy barriers. Our results show that the clusters closely follow known experimental results about intermediate structures, as well as binding and folding events.
Impacts of Taxon-Sampling Schemes on Bayesian Molecular Dating under the Unresolved Fossilized Birth-Death Process
Authors: Luo Arong , Zhang Chi , Zhou Qing-Song , Ho Simon Y.W. , Zhu Chao-Dong 
Published: November 2021

AbstractEvolutionary timescales can be estimated using a combination of genetic data and fossil evidence based on the molecular clock. Bayesian phylogenetic methods such as tip dating and total-evidence dating provide a powerful framework for inferring evolutionary timescales, but the most widely used priors for tree topologies and node times often assume that present-day taxa have been sampled randomly or exhaustively. In practice, taxon sampling is often carried out so as to include representatives of major lineages, such as orders or families. We examined the impacts of these diversified sampling schemes on Bayesian molecular dating under the unresolved fossilized birth-death (FBD) process, in which fossil taxa are topologically constrained but their exact placements are not inferred. We used synthetic data generated by simulation of nucleotide sequence evolution, fossil occurrences, and diversified taxon sampling. Our analyses show that increasing sampling density does not substantially improve divergence-time estimates under benign conditions. However, when the tree topologies were fixed to those used for simulation or when evolutionary rates varied among lineages, the performance of Bayesian tip dating improves with sampling density. By exploring three situations of model mismatches, we find that including all relevant fossils without pruning off those inappropriate for the FBD process can lead to underestimation of divergence times. Our reanalysis of a eutherian mammal data set confirms some of the findings from our simulation study, and reveals the complexity of diversified taxon sampling in phylogenomic data sets. In highlighting the interplay of taxon-sampling density and other factors, the results of our study have useful implications for Bayesian molecular dating in the era of phylogenomics.
Senescent stroma induces nuclear deformations in cancer cells via the inhibition of RhoA/ROCK/myosin II-based cytoskeletal tension
Authors: Aifuwa Ivie , Philip Jude M. , Kim Byoung Choul , Luperchio Teresa R. , Jimenez Angela , Perestrelo Tania , Lee Sang-Hyuk , Longe Nick , Reddy Karen , Ha Taekjip , Wirtz Denis 
Published: November 2021

ABSTRACTThe presence of senescent cells within tissues has been functionally linked to malignant transformations. Here, using tension-gauge tethers technology, particle-tracking microrheology, and quantitative microscopy, we demonstrate that senescent associated secretory phenotype (SASP) derived from senescent fibroblasts impose nuclear lobulations and volume shrinkage on malignant cells, which stems from the loss of RhoA/ROCK/myosin II-based cortical tension. This loss in cytoskeletal tension induces decreased cellular contractility, adhesion, and increased mechanical compliance. These SASP-induced morphological changes are in part mediated by lamin A/C. These findings suggest that SASP induces a defective outside-in mechanotransduction, from actomyosin fibers in the cytoplasm to the nuclear lamina, thereby triggering a cascade of biophysical and biomolecular changes in cells that associate with malignant transformations.