bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Nonsyndromic Bicoronal Synostosis and Syndromic Influences on Orbit and Periorbital Malformation
Authors: Lu Xiaona , Forte Antonio Jorge , Dinis Jacob , Junn Alexandra , Alperovich Michael , Alonso Nivaldo , Persing John A. 
Published: March 2022

Background:
Oculoorbital disproportion in patients with craniosynostosis has similarities and dissimilarities between syndromic and nonsyndromic cases. The authors hypothesized that these two conditions have specific individual influences as they relate to development of the orbital and periorbital skeletons.

Methods:
A total of 133 preoperative computed tomography scans (nonsyndromic bicoronal synostosis, n = 38; Apert syndrome bicoronal synostosis subtype, n = 33; Crouzon syndrome bicoronal synostosis subtype, n = 10; controls, n = 52) were included. Craniometric and volumetric analyses related to the orbit and periorbital anatomy were performed.

Results:
Orbital cavity volume was mildly restricted in nonsyndromic bicoronal synostosis (7 percent, p = 0.147), but more so in Apert and Crouzon syndromes [17 percent (p = 0.002) and 21 percent (p = 0.005), respectively]. The sphenoid side angle in Apert syndrome was wider than when compared to Crouzon syndrome (p = 0.043). The ethmoid side angle in Apert patients, however, was narrower (p = 0.066) than that in Crouzon patients. Maxilla anteroposterior length was more restricted in Apert syndrome than Crouzon syndrome (21 percent, p = 0.003) and nonsyndromic cases (26 percent, p < 0.001). The posterior nasal spine position was retruded in Crouzon syndrome (39 percent, p < 0.001), yet the anterior nasal spine position was similar in Apert and Crouzon syndromes.

Conclusions:
Orbit and periorbital malformation in syndromic craniosynostosis is likely the combined influence of syndromic influences and premature suture fusion. Apert syndrome expanded the anteriorly contoured lateral orbital wall associated with bicoronal synostosis, whereas Crouzon syndrome had more infraorbital rim retrusion, resulting in more severe exorbitism. Apert syndrome developed maxillary hypoplasia, in addition to the maxillary retrusion, observed in Crouzon syndrome and nonsyndromic bicoronal synostosis patients.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, II.
Coronary Computed Tomography Angiography Results in More Computed Tomography Chest Follow-up for Incidental Findings at 1 Year Relative to Stress-perfusion Cardiac Magnetic Resonance Imaging
Authors: Smith Ben C. , Allen Bradley D. 
Published: March 2022

Rationale and Objectives:
The aim of this study is to elucidate the prevalence and factors associated with follow-up chest computed tomography (CT) imaging in patients undergoing stress-perfusion cardiac magnetic resonance imaging (sCMR) and coronary CT angiography (cCTA).

Materials and Methods:
Cardiac imaging encounters between January 1, 2015 and May 16, 2020 were selected for analysis. Follow-up was tracked within 1-year of initial cardiac imaging, up to May 16, 2021. Patient demographics, comorbidities, and cardiopulmonary outcomes were also analyzed.

Results:
Between 2015 and 2020, there were 4024 cCTA and 837 sCMR imaging procedures on unique patients with 1.1% and 0.5% of patients having follow-up CT chest studies within 1 year, respectively. When controlling for patient demographic factors, body mass index, insurance status, smoking history, and comorbid diagnostic codes, there was statistically significant increased odds (adjusted odds ratio [95% confidence interval]: 2.864 [1.129-7.265]) of undergoing follow-up within the cCTA cohort. Pulmonary nodules represented the most common incidental finding, with cCTA associated with higher rates of pulmonary nodules detected on imaging (adjusted odds ratio [95% confidence interval]: 5.947 [4.136-8.552]). sCMR was associated with higher rates of MI, percutaneous coronary intervention, and lung malignancy within 1 year, with no difference in all-cause mortality.

Conclusions:
Patients undergoing either cCTA and sCMR demonstrated a low prevalence of follow-up CT chest imaging; however, follow-up was 2 times greater after cCTA due to greater pulmonary nodule detection. Potential for follow-up should be considered when evaluating the comparative effectiveness of these modalities, including the impact of follow-up imaging on cost and patient outcomes. Strategies to improve lung nodule detection and characterization at the time of sCMR may provide added value in these patients.
Trajectories of gene expression, seasonal influenza, and within-host seasonal immunity: transfer value to covid-19
Authors: Lund Eiliv , Holden Marit , Busund Lill-Tove Rasmussen , Snapkov Igor , Shvetsov Nikita , Holden Lars 
Published: March 2022

AbstractAs a novel approach we will combine trajectories or longitudinal studies of gene expression with information on annual influenza epidemics. Seasonality of gene expression in immune cells from blood could be a consequence of within-host seasonal immunity interacting with the seasonal pandemics of influenza (flu) in temperate regions and, thus, with potential valuable analogy transfer to the proposed seasonal development of covid-19.Here we operationalized within-host immunity as genes with both a significant seasonal term and a significant flu term in the sine-cosine model. Information on gene expression was based on microarray using RNase buffered blood samples collected randomly from a population-based cohort of Norwegian middle-aged women in 2003-2006, The Norwegian Women and Cancer (NOWAC) study. The unique discovery (N=425) and replication (N=432) design were based on identical sampling and preprocessing. Data on proportion of sick leaves due to flu, and the flu intensities per week was obtained from the National Institute of Public Health, giving a semi-ecological analysis.The discovery analysis found 2942 (48.1%) significant genes in a generalized seasonal model over four years. For 1051 within-host genes both the seasonal and the flu term were significant. These genes followed closely the flu intensities. The trajectories showed slightly more genes with a maximum in early winter than in late summer. Moving the flu intensity forward in time indicated a better fit 3-4 weeks before the observed influenza. In the replication analyses, 369 genes (35.1% of 1051) were significant. Exclusion of genes with unknown functions and with more than a season in difference reduced the number of genes in the discovery dataset to 305, illustrating the variability in the measurements and the problem in assessing weak biological relationships. Thus, we found for the first time a clear seasonality in gene expression with marked responses to the annual seasonal influenza in a unique discovery – replication design. Hypothetically, this could support the within-host seasonal immunity concept.
Polygenic risk vectors (PRV) improve genetic risk stratification for cardio-metabolic diseases
Authors: Li Ruowang , Zhang Xinyuan , Li Binglan , Feng Qiping , Kottyan Leah , Luo Yuan , Sawicki Konrad Teodor , Khan Atlas , Limdi Nita , Puckelwartz Megan , Wei Wei-Qi , Weng Chunhua , Chen Yong , Ritchie Marylyn D. , Moore Jason H. 
Published: March 2022

1.AbstractAccurate disease risk stratification can lead to more precise and personalized prevention and treatment of diseases. As an important component to disease risk, genetic risk factors can be utilized as an early and stable predictor for disease onset. Recently, the polygenic risk score (PRS) method has combined the effects from hundreds to millions of single nucleotide polymorphisms (SNPs) into a score that can be used for genetic risk stratification. However, current PRS approaches only utilize the additive associations between SNPs and disease risk in a one-dimensional score. Here, we show that leveraging multiple types of genetic effects in multi-dimensional risk vectors, or a polygenic risk vector (PRV), can improve the stratification of cardio-metabolic diseases risks. Using data from UK Biobank (UKBB) and Electronic Medical Records and Genomics (eMERGE) Network biobank linked electronic health records (EHR) as development and evaluation data, we found that the combined effects between the additive PRS and the dominant PRS outperformed either one in terms of disease risk stratification, especially for the individuals in the high-risk group. Our results demonstrate that disease risks are likely to be influenced by multiple types of genetic effects, and PRV could utilize these effects for better risk stratification while retaining the simplicity of the PRS method.
Hippocampal gamma and sharp wave/ripples mediate bidirectional interactions with cortical networks during sleep
Authors: Pedrosa Rafael , Nazari Mojtaba , Mohajerani Majid H. , Knöpfel Thomas , Stella Federico , Battaglia Francesco 
Published: March 2022

SummaryHippocampus-neocortex interactions during sleep are critical for memory processes: hippocampally-initiated replay contributes to memory consolidation in the neocortex and hippocampal sharp wave/ripples are linked to generalized increases in neocortical cell activity and DOWN-UP state transitions. Yet, the spatial and temporal patterns of this exchange are unknown. With voltage imaging, electrocorticography, and laminarly-resolved hippocampal potentials, we characterized cortico-hippocampal interactions during anesthesia and NREM sleep. We observed neocortical activation transients spanning multiple spatial scales hinting at a quasi-critical regime. Transients were organized in a small number of functional networks matching known anatomical connectivity. A network overlapping with the default mode network and centered on retrosplenial cortex was the most associated with the hippocampus. Interestingly, hippocampal slow gamma was the oscillation that best correlated with this neocortical network, outpacing ripples. In fact, neocortical activity predicted hippocampal slow gamma and followed ripples, suggesting that consolidation processes rely on bi-directional exchanges between hippocampus and neocortex.
Reorganization of F-actin nanostructures is required for the late phases of SARS-CoV-2 replication in pulmonary cells
Authors: Swain Jitendriya , Merida Peggy , Rubio Karla , Bracquemond David , Aguilar-Ordoñez Israel , Günther Stefan , Barreto Guillermo , Muriaux Delphine 
Published: March 2022

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is worldwide the main cause of the COVID-19 pandemic. After infection of human pulmonary cells, intracellular viral replication take place in different cellular compartments resulting in the destruction of the host cells and causing severe respiratory diseases. Although cellular trafficking of SARS-CoV-2 have been explored, little is known about the role of the cytoskeleton during viral replication in pulmonary cells. Here we show that SARS-CoV-2 infection induces dramatic changes of F-actin nanostructures overtime. Ring-like actin nanostructures are surrounding viral intracellular organelles, suggesting a functional interplay between F-actin and viral M clusters during particle assembly. Filopodia-like structures loaded with viruses to neighbour cells suggest these structures as mechanism for cell-to-cell virus transmission. Strikingly, gene expression profile analysis and PKN inhibitor treatments of infected pulmonary cells reveal a major role of alpha-actinins superfamily proteins in SARS-CoV-2 replication. Overall, our results highlight cell actors required for SARS-CoV2 replication that are promises for antiviral targets.TeaserImpairing regulation of actin filaments inhibits SARS-CoV-2 particle production in human pulmonary cells.
Comparative host-pathogen dynamics of Snake Fungal Disease in sympatric species of water snakes (Nerodia)
Authors: Harding Stephen F. , Becker C. Guilherme , Yates Jessica , Crump Paul , Forstner Michael R. J. , Mullin Stephen J. , Rodriguez David 
Published: March 2022

ABSTRACTThe ascomycete fungus Ophidiomyces ophiodiicola (Oo) is the causative agent of ophidiomycosis (Snake Fungal Disease), which has been detected globally. However, surveillance efforts in the central U.S., specifically Texas, have been minimal. The threatened and rare Brazos water snake (Nerodia harteri harteri) is one of the most range restricted snakes in the U.S. and is sympatric with two wide-ranging congeners, N. erythrogaster transversa and N. rhombifer, in north central Texas; thus, providing an opportunity to test comparative host-pathogen dynamics in this system. To accomplish this, we surveyed a portion of the Brazos river drainage (~400 river km) over 29 months and tested 150 Nerodia spp. for the presence of Oo via quantitative PCR and recorded any potential signs of Oo infection. We found Oo was distributed across the entire range of N. h. harteri, Oo prevalence was 46 % overall, and there was a significant association between Oo occurrence and signs of infection in our sample. Models indicated adults had a higher probability of Oo infection than juveniles and subadults, and adult N. h. harteri had a higher probability of infection than adult N. rhombifer but not higher than adult N. e. transversa. High Oo prevalence estimates (94.4%) in adult N. h. harteri has implications for their conservation and management owing to their patchy distribution, comparatively low genetic diversity, and threats from anthropogenic habitat modification.
Lrig3 restricts the size of the colon stem cell compartment
Authors: Stevenson Janelle G. , Sayegh Ryan , Pedicino Natalie , Pellitier Natalie A. , Wheeler Tim , Bechard Matthew E. , Huh Won Jae , Coffey Robert J. , Zemper Anne E. 
Published: March 2022

AbstractThe cellular census of the colonic crypt is tightly regulated, yet the molecular mechanisms that regulate this census are not fully understood. Lrig3, a transmembrane protein, is expressed in colonic crypt epithelial cells, including the stem, progenitor, and differentiated cell types. Mice missing Lrig3 have a disruption in their cellular census: using a novel Lrig3-/- mouse we demonstrate that Lrig3-/- mice have more cells per crypt, a greater mucosal area, and longer colons compared to wildtype mice, suggesting the expression of Lrig3 is required for both the total number of epithelial cells in the mouse colon, as well as colon length. In addition, we show Lrig3-/- mice have significantly more stem, progenitor, and deep crypt secretory cells, yet harbor a normal complement of enteroendocrine, Tuft, and absorptive cells. Lrig3-/- mice also have a concomitant decrease in phosphorylated Extracellular signal-related kinases, indicating the loss of Lrig3 leads to an expansion of the colonic stem cell compartment, in an Erk-dependent manner. Our study describes the expression of Lrig3 within the colon, defines perturbations in mice lacking Lrig3, and supports a role for Lrig3 in the establishment of both colonic crypt structure and cellular census, defined as the epithelial cell type and number in colon crypts.Graphical Abstract
Dynamic Network Curvature Analysis of RNA-Seq Data in Sarcoma
Authors: Elkin Rena , Oh Jung Hun , Cruz Filemon Dela , Deasy Joseph O. , Kung Andrew L. , Tannenbaum Allen R. 
Published: March 2022

AbstractIn this work, we utilized network features of cancer gene interactomes to cluster pediatric sarcoma tumors and identify candidate therapeutic targets in an unsupervised manner. RNA-Seq data were mapped to protein-level interactomes to construct weighted networks for mathematical analysis. We employed a geometric approach centered on a discrete notion of curvature, which provides a measure of the functional association between genes in the context of their connectivity. Specifically, we adopted a recently proposed dynamic extension of graph curvature to extract features of the non-Euclidean, multiscale structure of genomic networks. We propose a hierarchical clustering approach to reveal preferential gene clustering according to their geometric cooperation which captured the characteristicEWSR1-FLI1fusion in Ewing sarcoma. We also performedin silicoedge perturbations to assess systemic response to simulated interventions quantified by changes in curvature. These results demonstrate that geometric network-based features can be useful for identifying non-trivial gene associations in an agnostic manner.
Cross-generational heritability analysis of physiological traits in Porites astreoides across an inshore-offshore gradient in the Lower Florida Keys
Authors: Zhang Yingqi , Barnes Shelby J. , Kenkel Carly D. 
Published: March 2022

AbstractEstimating the heritable genetic variation in fitness-related traits is key to projecting the adaptive evolution of organisms in response to a changing environment. While heritability studies on reef-building corals to date support adaptive capacity, little is known about the dynamics of trait heritability across life stages in which distinct selective pressures can have long-lasting effects both within and across generations. In this study, we obtained heritability estimates for energetic and thermal stress response traits in larval, recruit, and adult Porites astreoides from two populations in the Lower Florida Keys. To induce bleaching phenotypes among individual families, larvae were exposed to a 4-day thermal stress at 32 °C, whereas adults and recruits received the same treatment for 22 days. Origin-dependent tolerance was observed in two life stages where offshore recruits lost more symbiont cells under heat than inshore recruits compared to their respective controls and heat-treated offshore adults suffered a greater loss in total protein content. Surprisingly, larvae appeared to be largely insensitive to heat regardless of origin. Broad sense heritability (H2) estimates varied greatly among traits and life stages, which may reflect changes in the relative importance of genetic and environmental variation throughout development. Notably, more than 80% of the variation in larval chlorophyll a concentration was attributed to genetic factors. The overall moderate to high H2 estimates measured here suggest these corals have considerable potential to adapt to environmental change.
WDR82 mediated H3K4me3 is associated with tumor proliferation and therapeutic efficacy in pediatric high-grade gliomas
Authors: Wadhwani Nitin , Nayak Sonali , Wang Yufen , Hashizume Rintaro , Jie Chunfa , Mania-Farnell Barbara , James Charles David , Xi Guifa , Tomita Tadanori 
Published: March 2022

AbstractPediatric high-grade gliomas (pHGGs) are common malignant brain tumors without effective treatment and poor patient survival. Abnormal posttranslational modification at the histone H3 tail plays critical roles in tumor cell malignancy. We have previously shown that trimethylation of lysine 4 at histone H3 (H3K4me3) plays a significant role in pediatric ependymoma malignancy and is associated with tumor therapeutic sensitivity. Here, we show that H3K4me3 and its methyltransferase WDR82 are elevated in pHGGs. Reduction of H3K4me3 by downregulating WDR82 decreases H3K4me3 promoter occupancy and expression of genes associated with stem cell features, cell proliferation, the cell cycle and DNA damage repair. Reduction of WDR82 mediated H3K4me3 increases the response of pediatric glioma cells to chemotherapy. These findings suggest that WDR82 mediated H3K4me3 is an important determinant of pediatric glioma malignancy and therapeutic response. This highlights the need for a more thorough understanding of the potential of WDR82 as an epigenetic target to increase therapeutic efficacy and improve prognosis for children with malignant gliomas.
HOIL1 regulates group 2 innate lymphoid cell numbers and type 2 inflammation in the small intestine
Authors: Wood Matthew J. , Marshall Jeffrey N. , Hartley Victoria L. , Liu Ta-Chiang , Iwai Kazuhiro , Stappenbeck Thaddeus S. , MacDuff Donna A. 
Published: March 2022

AbstractPatients with mutations in HOIL1 experience a complex immune disorder including intestinal inflammation. To investigate the role of HOIL1 in regulating intestinal inflammation, we employed a mouse model of HOIL1 deficiency. The ileum of Hoil1−/− mice displayed features of type 2 inflammation including tuft cell and goblet cell hyperplasia, and elevated expression of Il13, Il5 and Il25 mRNA. Inflammation persisted in the absence of T and B cells, and bone marrow chimeric mice revealed a requirement for HOIL1 expression in radiation-resistant cells to regulate inflammation. Although disruption of IL-4 receptor alpha (IL4Rα) signaling on intestinal epithelial cells ameliorated tuft and goblet cell hyperplasia, expression of Il5 and Il13 mRNA remained elevated. KLRG1hi CD90lo group 2 innate lymphoid cell (ILC2) were increased independent of IL4Rα signaling, tuft cell hyperplasia and IL-25 induction. Antibiotic treatment dampened intestinal inflammation indicating commensal microbes as a contributing factor. We have identified a key role for HOIL1, a component of the Linear Ubiquitin Chain Assembly Complex, in regulating type 2 inflammation in the small intestine. Understanding the mechanism by which HOIL1 regulates type 2 inflammation will advance our understanding of intestinal homeostasis and inflammatory disorders and may lead to the identification of new targets for treatment.
ID1 and CEBPA Coordinate Epidermal Progenitor Cell Differentiation
Authors: Kantzer Christina Geraldine , Yang Wei , Grommisch David , Patil Kim Vikhe , Mak Kylie Hin-Man , Genander Maria 
Published: March 2022

AbstractThe regulatory circuits that coordinate epidermal differentiation during development are still not fully understood. Here we report that the transcriptional regulator ID1 is enriched in basal epidermal progenitor cells and find ID1 expression to be diminished upon differentiation. In utero silencing of Id1 impairs progenitor cell proliferation, leads to precocious delamination of targeted progenitor cells and enables differentiated keratinocytes to retain progenitor markers and characteristics. Transcriptional profiling suggests ID1 acts by mediating adhesion to the basement membrane while inhibiting spinous layer differentiation. Co-immunoprecipitation reveals ID1 binding to transcriptional regulators of the class I bHLH family. We localize bHLH Tcf3, Tcf4 and Tcf12 to epidermal progenitor cells during epidermal stratification and established TCF3 as a downstream effector of ID1-mediated epidermal proliferation. Finally, we identify crosstalk between CEBPA, a known mediator of epidermal differentiation, and Id1 and demonstrate that CEBPA antagonizes BMP-induced activation of Id1. Our work establishes ID1 as a key coordinator of epidermal development, acting to balance progenitor proliferation with differentiation and unveils how functional crosstalk between CEBPA and Id1 orchestrates epidermal lineage progression.
Genome-wide base editor screen identifies regulators of protein abundance in yeast
Authors: Schubert Olga T. , Bloom Joshua S. , Sadhu Meru J. , Kruglyak Leonid 
Published: March 2022

AbstractAbundance of proteins is extensively regulated both transcriptionally and post-transcriptionally. To systematically characterize how regulation of protein abundance is encoded in the genome and identify protein regulators on a genome-wide scale, we developed a genetic screen that uses a CRISPR base editor. We examined the effects of 16,452 genetic perturbations on the abundance of eleven yeast proteins representing a variety of cellular functions. Thereby, we uncovered hundreds of regulatory relationships, including a novel link between the GAPDH isoenzymes Tdh1/2/3 and the Ras/PKA pathway. Many of the identified regulators are specific to one of the eleven proteins, but we also found genes that, upon perturbation, affected the abundance of most of the tested proteins. While the more specific regulators usually act transcriptionally, broad regulators often have roles in protein translation. Our results provide unprecedented insights into the components, scale and connectedness of the protein regulatory network.