bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visual Outcomes in Surgically Treated Intracranial Meningiomas
Authors: Zhang Yibing , Kim John , Andrews Chris , Archer Erica , Bursztyn Lulu , Grabe Hilary , Margolin Edward , Sullivan Stephen , Trobe Jonathan 
Published: April 2021

Background:
Intracranial meningiomas that arise from the medial sphenoid ridge, anterior clinoid process, tuberculum sellae, or planum sphenoidale often impair vision by compressing the optic nerves and optic chiasm. Although many studies have reported visual outcome following surgery for these tumors, documentation has often been incomplete and not validated by patient self-report.

Methods:
Retrospective study of 40 patients drawn from a single, academic, medical center. We used a unique method of assessing visual outcome based on whether the change in visual function affected the preoperatively better-sighted or worse-sighted eye in the belief that this method would correlate with effects on activities of daily living (ADL). To elicit patient self-reports of those effects, we conducted telephone interviews of 25 patients with a standard questionnaire. We also assessed putative ophthalmic, imaging, and surgical predictors of visual outcome.

Results:
Visual improvement occurred in 61% of patients with preoperative monocular visual dysfunction, but only 22% of patients reported improvement in their ability to conduct ADL, and 17% lost vision. Visual outcomes were better in patients with preoperative binocular visual dysfunction, where visual improvement occurred in 73% and no patient lost vision in the preoperatively better-sighted eye. However, only 27% of patients with preoperative binocular visual dysfunction reported improvement in their ability to conduct ADL. Long duration of vision impairment, presence of optic disc pallor, large tumor size, and imaging-based preoperative optic canal involvement did not preclude a favorable visual outcome. Aggressive surgical reduction in displacement of the optic nerves was not necessary to obtain a favorable visual outcome and sometimes led to an unfavorable visual outcome.

Conclusions:
In this study, surgery often improved vision, especially in patients with preoperative binocular visual dysfunction. But patients indicated that the effect on their ability to perform ADL was more modest. Moreover, 17% of patients with preoperative monocular visual dysfunction lost vision in the only affected eye, often to a considerable degree. In those patients, surgery would be justified primarily to relieve the concern of having a large brain tumor and to prevent tumor growth. Preoperative ophthalmic and imaging features poorly predicted visual outcomes. Favorable visual outcomes occurred without aggressive surgical debulking of the tumors.
The Effect of Optic Nerve Sheath Fenestration on Intraocular Pressure in Patients With Idiopathic Intracranial Hypertension
Authors: Mullen Martin , Scofield-Kaplan Stacy M. , Ford William C. , Mancini Ronald 
Published: April 2021

Background:
To evaluate the change in intraocular pressure (IOP) in patients with idiopathic intracranial hypertension (IIH) who underwent optic nerve sheath fenestration (ONSF) and to determine if radiographic evidence of posterior scleral or globe indentation influenced IOP.

Methods:
This is a retrospective analysis of IOP in IIH patients who underwent ONSF. The study included all patients from September 2010 to March 2018 operated on by a single surgeon (R.M.). IOPs preoperatively and postoperatively were recorded along with the acetazolamide dosage and whether there was evidence of posterior scleral or globe indentation on preoperative MRI.

Results:
A total of 29 patients (35 eyes) with IIH underwent ONSF. The average reduction in IOP among all patients was 1.24 mm Hg (P = 0.0218), but this increased to 2.69 mm Hg (P = 0.004) in patients who were maintained on the same dosage of acetazolamide in the preoperative and postoperative period. Furthermore, the reduction in IOP in those with posterior scleral or globe indentation was 2.5 mm Hg (P = 0.0095). When the perioperative period was evaluated, the mean decrease in IOP was 1.83 mm Hg (P = 0.0217).

Conclusions:
Reducing the cerebral spinal fluid pressure (CSFP) at the level of the intraorbital optic nerve through an ONSF can slightly reduce the IOP. In those with evidence of posterior globe or scleral indentation/flattening, the reduction in IOP was higher, which supports the theory that CSF pressure indents the globe and leads to an increase in IOP. Although these changes in IOP are small, this study provides further evidence for a connection between IOP and CSFP.
Utility of Ultrasound and Optical Coherence Tomography in Differentiating Between Papilledema and Pseudopapilledema in Children
Authors: Farazdaghi Marybeth K. , Trimboli-Heidler Carmelina , Liu Grant T. , Garcia Arielle , Ying Gui-Shuang , Avery Robert A. 
Published: April 2021

Background:
Differentiating between papilledema and pseudopapilledema in children presenting with mild-to-moderate optic nerve head elevation is challenging. This study sought to determine which B-scan ultrasonography (BSUS) and optical coherence tomography (OCT) features, individually or in combination, are best able to differentiate between papilledema and pseudopapilledema in children.

Methods:
Children presenting with optic nerve head elevation of unknown etiology were eligible if they underwent BSUS and OCT performed by the same investigator. The absolute optic nerve sheath diameter (in millimeter) along with the presence/absence of a hyperreflective nodule(s) at the optic nerve head (indicative of druse) from BSUS was determined. The average circumpapillary retinal nerve fiber layer (cpRNFL), diameter of Bruch membrane opening, maximum papillary height, and the presence/absence of hyper-/hyporeflective lesions at the optic nerve head were calculated. Sensitivity and specificity were calculated to evaluate which BSUS and OCT imaging features, individually and in combination, accurately classified children as having papilledema vs pseudopapilledema.

Results:
One hundred eighty-one eyes from 94 children (mean age, 11.0 years; range, 3.2–17.9) were included; 36 eyes with papilledema and 145 eyes with pseudopapilledema. Among BSUS features, optic nerve sheath widening (>4.5 mm) demonstrated the best sensitivity (86%; 95% confidence interval [CI], 64%–96%) and specificity (88%; 95% CI, 79%–94%) for papilledema. Among OCT measures, cpRNFL thickness of ≥140 µm demonstrated the best sensitivity (83%; 95% CI, 66%–93%) and specificity (76%; 95% CI, 66%–84%) to identify papilledema. The presence of both optic nerve sheath widening (>4.5 mm) and cpRNFL thickness of ≥140 µm reduced the sensitivity (72%; 95% CI, 52%–86%) but increased specificity (95%; 95% CI, 88%–98%).

Conclusion:
BSUS (optic nerve sheath widening [>4.5 mm]) and OCT (cpRNFL thickness ≥140 µm), individually and collectively, have good diagnostic accuracy for differentiating between papilledema and pseudopapilledema. The presence of druse does not exclude the diagnosis of papilledema.
Protective effect of acute splenic irradiation in rats with traumatic brain injury
Authors: Huang Xiaofei , Lu Yuanlan , Li Lie , Sun Tianjing , Jiang Xuheng , Li Mo , Zhang Tianxi , Yu Anyong 
Published: April 2021

Objective
To explore the protective effect of acute splenic irradiation against traumatic brain injury (TBI) in rats.

Methods
A rat model of TBI was established according to Feeney’s method. Splenic irradiation was performed by the reverse intensity-modulated radiation therapy (IMRT) source-axis distance (SAD) irradiation technique. Rat brain tissue samples were collected, the water content of the rat brain tissue was determined and the abundance of microglia was detected by immunofluorescence. Spleens were collected to measure the spleen index. Lung, liver, small intestine and kidney tissues were taken for hematoxylin and eosin staining to observe whether there was radiation-induced pathological damage. Peripheral blood was collected to detect tuftsin and the inflammatory factors IL-6 and IL-10.

Results
Compared with the nonirradiated TBI rat group, the 4-h spleen irradiation TBI rat group showed (1) increased behavioral scores at 3 days after TBI (P
< 0.05), (2) reduced water content of the ipsilateral hemisphere at 3 days after TBI, (3) reduced spleen index at 3 and 7 days after TBI, (4) reduced number of microglia cells infiltrating around the lesion at 7 days after TBI, (5) reduced IL-6 levels at 3 days after TBI, (6) increased IL-10 levels at 3 and 5days after TBI and (7) Compared with the nonirradiated TBI rat group, the 8-h spleen irradiation TBI rat group showed reduced tuftsin levels at 3 and 7days after TBI.

Conclusions
Acute splenic irradiation had a protective effect in rats with TBI.
A functional topography within the cholinergic basal forebrain for encoding sensory cues and behavioral reinforcement outcomes
Authors: Robert Blaise , Kimchi Eyal Y. , Watanabe Yurika , Chakoma Tatenda , Jing Miao , Li Yulong , Polley Daniel B. 
Published: April 2021

AbstractBasal forebrain cholinergic neurons (BFCNs) project throughout the cortex to regulate arousal, stimulus salience, plasticity, and learning. Although often treated as a monolithic structure, the basal forebrain features distinct connectivity along its anteroposterior axis that could impart regional differences in BFCN processing. Here, we performed simultaneous bulk calcium imaging from anterior and posterior BFCNs over a one-month period of variable reinforcement learning in mice. BFCNs in both regions showed equivalently weak responses to unconditioned visual stimuli and anticipated rewards. Anterior BFCNs in the horizontal limb of the diagonal band were more responsive to reward omission, more accurately classified behavioral outcomes, and more closely tracked fluctuations in pupil-indexed global brain state. Posterior BFCNs in globus pallidus and substantia innominata were more responsive to unconditioned auditory stimuli, orofacial movements, aversive reinforcement, and showed robust associative plasticity for punishment-predicting cues. These results identify a functional topography that diversifies cholinergic modulatory signals broadcast to downstream brain regions.
Integrating unmatched scRNA-seq and scATAC-seq data and learning cross-modality relationship simultaneously
Authors: Zhang Ziqi , Yang Chengkai , Zhang Xiuwei 
Published: April 2021

AbstractIt is a challenging task to integrate scRNA-seq and scATAC-seq data obtained from different batches. Existing methods tend to use a pre-defined gene activity matrix (GAM) to convert the scATAC-seq data into scRNA-seq data. The pre-defined GAM is often of low quality and does not reflect the dataset-specific relationship between the two data modalities. We propose scDART (singlecellDeep learning model forATAC-seq andRNA-seqTrajectory), a deep learning framework that integrates scRNA-seq and scATAC-seq data and learns cross-modalities relationships simultaneously. Specifically, the design of scDART allows it to preserve cell trajectories in continuous cell populations and can be applied to trajectory inference on integrated data.
The physiological basis for the computation of direction selectivity in theDrosophilaOFF pathway
Authors: Ramos-Traslosheros Giordano , Silies Marion 
Published: April 2021

AbstractInDrosophila, direction-selective neurons implement a mechanism of motion computation similar to cortical neurons, using contrast-opponent receptive fields with ON and OFF subunits. It is not clear how the presynaptic circuitry of direction-selective neurons in the OFF pathway supports this computation, because all major inputs are OFF-rectified neurons. Here, we reveal the biological substrate for motion computation in the OFF pathway. Three interneurons, Tm2, Tm9 and CT1, also provide information about ON stimuli to the OFF direction-selective neuron T5 across its receptive field, supporting a contrast-opponent receptive field organization. Consistent with its prominent role in motion detection, variability in Tm9 receptive field properties is passed on to T5, and calcium decrements in Tm9 in response to ON stimuli are maintained across behavioral states, while spatial tuning is sharpened by active behavior. Together, our work shows how a key neuronal computation is implemented by its constituent neuronal circuit elements to ensure direction selectivity.
Adipose gene expression profiles reveal novel insights into the adaptation of northern Eurasian semi-domestic reindeer (Rangifer tarandus)
Authors: Weldenegodguad Melak , Pokharel Kisun , Niiranen Laura , Soppela Päivi , Ammosov Innokentyi , Honkatukia Mervi , Lindeberg Heli , Peippo Jaana , Reilas Tiina , Mazzullo Nuccio , Mäkelä Kari A. , Nyman Tommi , Tervahauta Arja , Herzig Karl-Heinz , Stammler Florian , Kantanen Juha 
Published: April 2021

AbstractReindeer (Rangifer tarandus) are semi-domesticated animals adapted to the challenging arctic conditions of northern Eurasia. Adipose tissues play a crucial role in animals living in northern environments by altering gene expression in their tissues to regulate energy homeostasis and thermogenic activity. Here, we performed transcriptome profiling by RNA sequencing of adipose tissues from three different anatomical depots: metacarpal (bone marrow), perirenal, and prescapular fat in Finnish and Even reindeer (in Sakha) during two seasonal time points (spring and winter). On average 36.5 million pair-ended clean reads were obtained for each sample, and a total of 16,362 genes were expressed in our data. Gene expression profiles in metacarpal tissue were distinct and clustered separately from perirenal and prescapular adipose tissues. Notably, metacarpal adipose tissue appeared to have a significant role in the regulation of the energy metabolism of reindeer in spring when their nutritional condition is poor after winter. During spring, when the animals are in less optimal condition, genes associated with the immune system (e.g.,CCL2,CCL11,CXCL14,IGSF3,IGHM,IGLC7,IGKC,JCHAIN,andIGSF10) were upregulated in the perirenal and prescapular adipose tissue, while genes involved in energy metabolism (e.g.,ACOT2,APOA1,ANGPTL1,ANGPTL8,ELOVL7,MSMO1,PFKFB1, andST3GAL6) were upregulated in metacarpal tissue. Even reindeer harboured relatively fewer significantly differentially expressed genes than Finnish reindeer, irrespective of the season, possibly owing to climatic and management differences. Moreover, blood and tissue parameters reflecting general physiological and metabolic status showed less seasonal variation in Even reindeer than in Finnish reindeer. This study identified adipose candidate genes potentially involved in immune response, fat deposition, energy metabolism, development, cell growth, and organogenesis. Taken together, this study provides new information on the mechanisms by which reindeer adapt to less optimal arctic conditions.
Ultra-rare constrained missense variants in the epilepsies: Shared and specific enrichment patterns in neuronal gene-sets
Authors: Koko Mahmoud , Krause Roland , Sander Thomas , Bobbili Dheeraj Reddy , Nothnagel Michael , May Patrick , Lerche Holger ,   Epi25 Collaborative
Published: April 2021

AbstractBackgroundBurden analysis in epilepsy has shown an excess of deleterious ultra-rare variants (URVs) in few gene-sets, such as known epilepsy genes, constrained genes, ion channel or GABAAreceptor genes. We set out to investigate the burden of URVs in a comprehensive range of gene-sets presumed to be implicated in epileptogenesis.MethodsWe investigated several constraint and conservation-based strategies to study whole exome sequencing data from European individuals with developmental and epileptic encephalopathies (DEE,n= 1,003), genetic generalized epilepsy (GGE,n= 3,064), and non-acquired focal epilepsy (NAFE,n= 3,522), collected by the Epi25 Collaborative, compared to 3,962 ancestry-matched controls. The burden of 12 non-synonymous URVs types in 92 gene-sets was compared between epilepsy cases (DDE, GGE, NAFE) and controls using logistic regression analysis.ResultsBurden analysis of brain-expressed genes revealed an excess of different URVs types in all three epilepsy categories which was largest for missense variants in highly constrained sites (constrained missense variants). The URVs burden was prominent in neuron-specific, synaptic and developmental genes as well as genes encoding ion channels and receptors, and it was generally higher for DEE and GGE compared to NAFE. The patterns of URVs burden in gene-sets expressed in inhibitory vs. excitatory neurons or receptors suggested a high burden in both groups in DEE but a differential involvement of inhibitory genes in GGE, while excitatory genes were predominantly affected in NAFE. Top ranking susceptibility genes from a recent genome-wide association study (GWAS) of generalized and focal epilepsies displayed a higher URVs burden in constrained coding regions in GGE and NAFE, respectively.ConclusionsUsing exome-based gene-set burden analysis, we demonstrate that missense URVs affecting mainly constrained sites are enriched in neuronal genes in both common and rare severe epilepsy syndromes. Our results indicate a differential impact of these URVs in genes expressed in inhibitory vs. excitatory neurons and receptors in generalized vs. focal epilepsies. The excess of URVs in top-ranking GWAS risk-genes suggests a convergence of rare deleterious and common risk-variants in the pathogenesis of generalized and focal epilepsies.
Food web aggregation: effects on key positions
Authors: Giacomuzzo Emanuele , Jordán Ferenc 
Published: April 2021

AbstractProviding standard definitions of what should be considered as a node in food webs is still an unsolved problem. Especially for comparative and predictive food web modelling, a more systematic understanding is needed for the effects of trophic aggregation procedures. Aggregation is unavoidable during data management. Therefore, it is crucial to know whether food web properties are conserved during this process.Here, we study how different aggregation methods change the positional importance of species in food webs. In particular, we investigated the effects of various aggregation algorithms on 24 indices of importance. Our work was carried out on 76 aquatic food webs coming from the Ecopath with Ecosim database (EcoBase). We considered six main types of aggregation, according to the way that the nodes were clustered. These were (i) hierarchical clustering based on the Jaccard index, (ii) hierarchical clustering based on the regular equivalence index (REGE), (iii) maximisation of directed modularity, (iv) maximisation of modularity according to modules in which species fed on the same preys, (v) maximisation of modularity according to modules in which species are fed upon by the same predators, and (vi) clustering through the group model.Hierarchical clustering based on the Jaccard index and REGE index outperformed the other four methods on maintaining the relative importance of species for all the indices of importance (except for the contrastatus index (s′) and betweenness centrality (BC)). The choice between these two methods should follow our research question and the importance index we are interested in studying. The other four aggregation methods change more the centrality of species, especially the one based on maximising directed modularity. When using these aggregation algorithms, one has to keep in mind that the network will not only be smaller but also provides different information.
Single-molecule imaging of IQGAP1 regulating actin filament dynamics in real time
Authors: Hoeprich Gregory J. , Shekhar Shashank , Goode Bruce L. 
Published: April 2021

ABSTRACTIQGAP is a conserved family of actin-binding proteins with essential roles in cell motility, cytokinesis, and cell adhesion, yet it has remained poorly understood how IQGAP proteins directly regulate actin filament dynamics. To close this gap, we used single-molecule and single-filament TIRF microscopy to directly visualize IQGAP regulating actin dynamics in real time. To our knowledge, this is the first study to do so. Our results show that full-length human IQGAP1 forms dimers that stably bind to filament sides and transiently cap barbed ends. These interactions organize actin filaments into thin bundles, suppress barbed end growth, and inhibit filament disassembly. Surprisingly, each activity depends on distinct combinations of IQGAP1 domains and/or dimerization, suggesting that different mechanisms underlie each functional effect on actin. These observations have important implications for how IQGAP functions as a direct actin regulator in vivo, and how it is deployed and regulated in different biological settings.
Network controllability enrichment analysis reveals that SARS-CoV-2 infection tends to target indispensable nodes of a directed human protein-protein interaction network
Authors: Lee Ho-Joon 
Published: April 2021

ABSTRACTThe COVID-19 disease has been a global threat caused by the new coronavirus species, SARS-CoV-2, since early 2020 with an urgent need for therapeutic interventions. In order to provide insight into human proteins targeted by SARS-CoV-2, here we study a directed human protein-protein interaction network (dhPPIN) based on our previous work on network controllability of virus targets. We previously showed that human proteins targeted by viruses tend to be those whose removal in a dhPPIN requires more control of the network dynamics, which were classified as indispensable nodes. In this study we introduce a more comprehensive rank-based enrichment analysis of our previous dhPPIN for SARS-CoV-2 infection and show that SARS-CoV-2 also tends to target indispensable nodes in the dhPPIN using multiple proteomics datasets, supporting validity and generality of controllability analysis of viral infection in humans. Also, we find differential controllability among SARS-CoV-2, SARS-CoV-1, and MERS-CoV from a comparative proteomics study. Moreover, we show functional significance of indispensable nodes by analyzing heterogeneous datasets from a genome-wide CRISPR screening study, a time-course phosphoproteomics study, and a genome-wide association study. Specifically, we identify SARS-CoV-2 ORF3A as most frequently interacting with indispensable proteins in the dhPPIN, which are enriched in TGF-beta signaling and tend to be sources nodes and interact with each other. Finally, we built an integrated network model of ORF3A-interacting indispensable proteins with multiple functional supports to provide hypotheses for experimental validation as well as therapeutic opportunities. Therefore, a sub-network of indispensable proteins targeted by SARS-CoV-2 could serve as a prioritized network of drug targets and a basis for further functional and mechanistic studies from a network controllability perspective.