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The prevalence of carotid artery atherosclerosis and stroke is increasing. Carotid artery stenting (CAS), which treats carotid artery stenosis and prevents strokes, has benefited from advances in techniques and technology. In this study, we aimed to identify significant risk factors for major complications following contemporary CAS.Utilizing the National Surgical Quality Improvement Program registry, we investigated individuals who underwent CAS between the years 2015-2018. Multivariable logistic regression was performed to identify risk factors associated with stroke, myocardial infarction (MI), and death within 30 days of CAS.Of the 770 patients within the National Surgical Quality Improvement Program registry who met study criteria, 3.2% experienced strokes, 1.6% experienced MIs, and 2.2% died within 30 days of CAS. A total of 6.1% of patients experienced any of these major complications. Of the 395 asymptomatic patients, 3.5% suffered a stroke, 1.5% experienced an MI, and 1.0% died for a total of 5.6% patients suffering from any event. Of the 375 symptomatic patients, there were 2.9% strokes, 1.6% MIs, and 3.5% deaths with 6.7% suffering any event. Age, race, and hyponatremia were significantly associated with stroke, and hyponatremia was associated with MI. Age, anemia, hypoalbuminemia, international normalized ratio, and emergency case were associated with death.These results suggest that preoperative risk stratification of CAS patients may not be straightforward as each adverse event has its own risk factors, precluding a generalized CAS risk stratification scoring system from being created. This paper can aid in patient selection for CAS by highlighting risk factors in modern CAS.

Flow cytometry estimates of genome sizes among species ofDrosophilashow a 3-fold variation, ranging from ∼127 Mb inDrosophila mercatorumto ∼400 Mb inDrosophila cyrtoloma. However, the assembled portion of the Muller F Element (orthologous to the fourth chromosome inDrosophila melanogaster) shows a nearly 14-fold variation in size, ranging from ∼1.3 Mb to > 18 Mb. Here, we present chromosome-level long read genome assemblies for fourDrosophilaspecies with expanded F Elements ranging in size from 2.3 Mb to 20.5 Mb. Each Muller Element is present as a single scaffold in each assembly. These assemblies will enable new insights into the evolutionary causes and consequences of chromosome size expansion.

Introduction Intracranial hemorrhage (ICH) causes often devastating brain injury. Predicting long-term motor prognosis and identifying neurosurgical candidates in cases of ICH has been an imprecise practice. Diffusion tensor tractography (DTT) is an imaging modality that may aid in this challenge. This literature review aimed to investigate DTT applications in patients with spontaneous ICH for either motor function prognosis or surgical intervention. Materials and methods A PubMed and Ovid literature review was performed to select and evaluate studies utilizing DTT for motor prognostication or analysis/optimization of surgical outcomes in patients with spontaneous hypertensive ICH. Studies investigating ICH due to suspected vascular anomalies were excluded. Results Forty-two studies met criteria. Six studies addressed surgical application. Surgery was not associated with increased mortality but was associated with decreased hematoma volume and CST compression and improved motor outcomes. Prognostic studies demonstrated that DTT correlates with motor function at multiple timepoints. Conclusion DTT is a relatively new imaging technique that may help predict prognosis of patients’ motor function after spontaneous ICH. Additionally, it could possibly serve as an adjunct for determining which patients would benefit from surgical decompression or even help guide surgical approach to hematomas that displace the CST.

Patients with cerebrovascular syndromes are at risk for additional concerns associated with their syndrome. A wide variety of syndromes are associated with cerebrovascular diseases. Multidisciplinary care is helpful to ensure comprehensive evaluation and management. Precise diagnosis and appreciation for the underlying syndrome is critical for effective cerebrovascular and broader care. This text focuses on these conditions with a focus on underlying pathophysiology and associated genetics, presentation, diagnosis, and management of each disease.

The novel coronavirus disease (COVID-19) pandemic poses a substantial threat to the health of healthcare personnel on the front line of caring for COVID-19 patients. The Centers for Medicare and Medicaid Services previously announced that all non-essential planned surgeries and procedures should be postponed until further notice and only urgent procedures should proceed.We share our experiences with safely performing neurosurgical procedures on confirmed and suspected COVID-19 patients, to aide other neurosurgical teams in preparing for these high-risk cases, especially for neurosurgical interventions which are essential at saving a life or preserving functioning of the central nervous system that cannot be delayed. Perioperative and intraoperative strategies, considerations, as well as challenges arisen under the specific circumstance have been discussed: the hospital should be equipped with negative pressure areas and multiple areas to quarantine positive patients; the operating rooms should be negative pressure or have HEPA-filtration systems in place; all healthcare personnel who immediately participate in neurosurgical interventions for confirmed and suspected COVID-19 patients should take airborne precautions and wear enhanced personal protective equipment.Successful management of neurosurgical emergencies without healthcare personnel infection has been achieved during this pandemic crisis.Following the proposed guidance, urgent neurosurgical surgeries and procedures can be safely performed for the benefit of critical patients with or suspected for COVID-19.

Understanding plant‐insect interactions is an active area of research in both ecology and evolution. Much attention has been focused on the impact of secondary metabolites in the host plant or fungi on these interactions. Plants and fungi contain a variety of biologically active compounds, and the secondary metabolite profile can vary significantly between individual samples. However, many experiments characterize the biological effects of only a single secondary metabolite or a subset of these compounds.Here, we develop an exhaustive extraction protocol using an accelerated solvent extraction protocol to recover the complete suite of cyclopeptides and other secondary metabolites found in Amanita phalloides (death cap mushrooms) and compare its efficacy to the “Classic” extraction method used in earlier works.We demonstrate that our extraction protocol recovers the full suite of cyclopeptides and other secondary metabolites in A. phalloides unlike the “Classic” method that favors polar cyclopeptides.Based on these findings, we provide recommendations for how to optimize protocols to ensure exhaustive extracts and also the best practices when using natural extracts in ecological experiments., While host plants and fungi contain a complex suite of metabolites, many studies examining plant‐insect interactions focus on the biological effect of a single compound. We developed a new protocol to exhaustively extract secondary metabolites from Amanita phalloides mushrooms. Based on our findings, we present recommendations of best practices for studies using secondary metabolite extracts.

Gene Model for the ortholog of Tsc1 in the Drosophila yakuba DyakCAF1 assembly (GCA_000005975.1).

Gene Model for

There are multiple risk factors associated with spontaneous subdural hematoma (SDH), including substance abuse, hypertension, vascular abnormalities, and neoplasms. The illicit drugs typically cited as risk factors for spontaneous SDH are alcohol and cocaine. We report a rare case of spontaneous, significant SDH associated exclusively with methamphetamine. Although it is unclear whether the underlying pathophysiology involves vasculitis, sympathomimetic-induced hypertension, or a combination of both, this case further illustrates the risks of methamphetamine abuse.

Obesity is an increasing pandemic and is caused by multiple factors including genotype, psychological stress, and gut microbiota. Our project investigated the effects produced by high fat and high sugar dietary modifications on microbiota and metabolic phenotype of Drosophila melanogaster. Larvae raised on the high fat and high sugar diets exhibited bacterial communities that were compositionally and phylogenetically different from bacterial communities of the larvae raised on normal diets, especially if parental microbiota were removed. Several of the dominant bacteria taxa that are commonly associated with high fat and high sugar diets across model organisms and even human populations showed similar pattern in our results. Corynebacteriaceae and Erysipelotrichaceae were connected with high fat food, while Enterobacteriaceae and Lactobacillaceae were associated with high sugar diets. In addition, we observed that presence of symbiotic microbiota often mitigated the effect that harmful dietary modifications produced on larvae, including elevated triglyceride concentrations and was crucial for Drosophila survival, especially on high sugar peach diets.

The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits. While the GEP CURE produces positive outcomes overall, the students with more positive attitudes toward science, particularly with respect to epistemic beliefs, showed greater gains. The findings indicate the importance of a student's epistemic beliefs to achieving positive learning outcomes.

Summary Intractable epilepsy is commonly associated with developmental cortical malformations. Using the rodent freeze lesion model, we have sought the underlying circuit abnormalities contributing to the epileptiform activity that occurs in association with the structural pathology of four‐layered microgyria. We showed previously that within the epileptogenic paramicrogyral region (PMR) surrounding the malformation, non–fast‐spiking neurons commonly containing somatostatin (SSt) exhibit alterations, including having a greater maximum firing rate. Here we examined the output of SSt interneurons with optogenetics, using SSt‐Cre mice mated to mice with floxed channelrhodopsin‐2. Voltage clamp recordings from layer V pyramidal neurons in ex vivo slices had significantly enhanced SSt‐evoked inhibitory postsynaptic currents in PMR cortex compared to control. In addition, under conditions of low‐Mg2+ artificial cerebral spinal fluid (aCSF), light activation of the SSt neurons evoked field potential epileptiform activity in the PMR cortex, but not in control. These data suggest that within the PMR cortex, SSts have a significantly larger effect on excitatory neurons. Surprisingly, the network effect of this enhanced inhibition is hyperexcitability with propagating epileptiform activity, perhaps due to disinhibition of other interneuron cell types or to enhanced synchrony of excitatory cortical elements. This identification creates a new locus for potential modulation of epileptiform activity associated with cortical malformation.

Annotating the genomes of multiple organisms allows us to study their genes as well as the evolution of those genes. While many eukaryotic genome assemblies already include computational gene predictions, these predictions can benefit from review and refinement through manual gene annotation. The Genomics Education Partnership (GEP; thegep.org) has developed an annotation protocol for protein-coding genes that enables undergraduate students and other researchers to create high-quality gene annotations that can be utilized in subsequent scientific investigations. For example, this protocol has been utilized by the GEP faculty to engage undergraduate students in the comparative annotation of genes involved in the insulin signaling pathway in 28 Drosophila species, using D. melanogaster as the informant genome. Students construct gene models using multiple lines of computational and experimental evidence including expression data (e.g., RNA-Seq), sequence similarity (e.g., BLAST, multiple sequence alignments), and computational gene predictions. For quality control, each gene is annotated by at least two students working independently, followed by reconciliation of the submitted gene models by a more experienced student. This article provides an overview of the annotation protocol and describes how discrepancies in student submitted gene models are resolved to produce a final, high-quality gene set suitable for subsequent analyses. This annotation protocol can be adapted to other scientific questions (e.g., expansion of the Drosophila Muller F element) and other species (e.g., parasitoid wasps) to provide additional opportunities for undergraduate students to participate in genomics research. These student annotation efforts can substantially improve the quality of gene annotations in publicly available genomic databases.

Symbiotic microbiota can help its host to overcome nutritional challenges, which is consistent with a holobiont theory of evolution. Our project investigated the effects produced by the microbiota community, acquired from the environment and horizontal transfer, on metabolic traits related to obesity. The study applied a novel approach of raising Drosophila melanogaster, from ten wild-derived genetic lines on naturally fermented peaches, preserving genuine microbial conditions. Larvae raised on the natural and standard lab diets were significantly different in every tested phenotype. Frozen peach food provided nutritional conditions similar to the natural ones and preserved key microbial taxa necessary for survival and development. On the peach diet, the presence of parental microbiota increased the weight and development rate. Larvae raised on each tested diet formed microbial communities distinct from each other. The effect that individual microbial taxa produced on the host varied significantly with changing environmental and genetic conditions, occasionally to the degree of opposite correlations.

Most head and neck cancers require aggressive surgical resection followed by external beam radiation therapy. The carotid artery can be injured by surgery or radiation resulting in a delayed "blowout." A patient who had undergone orbital exenteration for a lacrimal adenoid cystic carcinoma (ACC) followed by external beam radiation presented 16 years later with arterial bleeding from the orbit caused by "blowout" of the cavernous internal carotid artery (ICA). We review the literature on carotid blowout syndrome (CBS) and treatment. The patient was emergently transferred to a hybrid operating room and underwent a balloon occlusion test (BOT) and endovascular sacrifice of the ICA with no neurological deficits postoperatively. Emergent endovascular embolization is an effective treatment for an intracranial ICA blowout in this first reported case of a blowout through the orbit. Elevated radiation dose and lack of tissue coverage may put the cavernous ICA at risk for this delayed complication.

Obesity is an increasing worldwide epidemic and contributes to physical and mental health losses. The development of obesity is caused by multiple factors including genotype, hormonal misregulation, psychological stress, and gut microbiota. Our project investigated the effects produced by microbiota community, acquired from the environment and horizontal transfer, on traits related to obesity. The study applied a novel approach of raising Drosophila melanogaster from ten, wild-derived genetic lines (DGRP) on naturally fermented peaches, thereby preserving genuine microbial conditions. Our results indicated that larvae raised on the natural and standard lab diets were significantly different from each other in every tested phenotype. In addition, sterilized larvae raised on the autoclaved peach diet, therefore exposed to natural nutritional stress but lacking natural microbiota community, were associated with adverse phenotypes such as low survival rate, longer developmental time, smaller weight, and elevated triglyceride and glucose levels. Our findings suggested that frozen peach food provided nutritional conditions similar to the natural ones and preserved key microbial taxa necessary for survival and development of Drosophila larvae. The presence of parental microbiota did not produce a significant effect on any of the tested phenotypes when larvae were raised on the lab diet. Contrarily, on the peach diet, the presence of parental microbiota increased the weight and development rate, even if the original peach microbiota were still present. In addition, we found that larvae raised on the peach diet formed a microbial community distinctive from larvae raised on the lab or peach autoclaved diets. The effect that individual microbial taxa produced on the host varied significantly with changing environmental and genetic conditions, occasionally to the degree of opposite correlations.

A 57-year-old woman with metastatic chondroblastic osteosarcoma developed sudden-onset right-sided weakness and aphasia. She was found to have an occluded left middle cerebral artery (M1 segment) and underwent endovascular stroke intervention with return to a normal neurological exam within 24 h. Histologic analysis of the embolus was consistent with chondroblastic osteosarcoma.

Primary central nervous system (CNS) tumors are a leading cause of death worldwide, with an incidence of 7.08 per 100,000 and an average of 15,944 deaths per year in the United States alone. The 5-year survival rate is 35.8% for all malignant CNS tumors, and only 6.8% for glioblastomas (1); thus, determining a method of monitoring effectiveness of treatment and recurrence is of utmost importance.

A hallmark of the research experience is encountering experimental difficulty and working through that challenge to reach success. The ability to overcome scientific challenges is essential to being a successful scientist, but replicating these challenges can be difficult in a teaching setting. The Genomics Education Partnership (GEP) is a consortium of faculty who engage their students in a genomics Course-based Undergraduate Research Experience (CURE). Students participate in genome annotation, generating gene models using multiple lines of experimental evidence. Our observations suggested that the students’ learning experience in this research is continuous and recursive, frequently beginning with frustration but eventually leading to success. In order to explore our “formative frustration” hypothesis, we gathered data about this research experience from faculty via a survey, and from students both via a general survey and a small set of focus groups administered at the end of the GEP CURE. All three datasets contained comments mentioning frustration and struggle, as well as learning and better understanding of the scientific process. Bioinformatics projects are particularly well suited to the process of iteration and refinement because iterations can be performed quickly and are inexpensive in both time and money. Based on these findings, we suggest that a dynamic of what we have deemed “formative frustration” is an important aspect for a successful CURE.

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae. Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5′ ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains.

Following similar global efforts to exchange genomic and other biomedical data, global databases in metabolomics have now been established. MetaboLights, the first general purpose, publically available, cross-species, cross-application database in metabolomics, has become the fastest growing data repository at the European Bioinformatics Institute in terms of data volume. Here we present the automated assembly of species metabolomes in MetaboLights, a crucial reference for chemical biology, which is growing through user submissions.

Model organisms are important in many areas of chemical biology. In metabolomics, model organisms can provide excellent samples for methods development as well as the foundation of comparative phylometabolomics, which will become possible as metabolomics applications expand. Comparative studies of conserved and unique metabolic pathways will help in the annotation of metabolites as well as provide important new targets of investigation in biology and biomedicine. However, most chemical biologists are not familiar with genetics, which needs to be considered when choosing a model organism. In this review we summarize the strengths and weaknesses of several genetic systems, including natural isolates, recombinant inbred lines, and genetic mutations. We also discuss methods to detect targets of selection on the metabolome.

The bacterial gut microbiota of many animals is known to be important for many physiological functions including detoxification. The selective pressures imposed on insects by exposure to toxins may also be selective pressures on their symbiotic bacteria, who thus may contribute to the mechanism of toxin tolerance for the insect. Amatoxins are a class of cyclopeptide mushroom toxins that primarily act by binding to RNA polymerase II and inhibiting transcription. Several species of mycophagous Drosophila are tolerant to amatoxins found in mushrooms of the genus Amanita, despite these toxins being lethal to most other known eukaryotes. These species can tolerate amatoxins in natural concentrations to utilize toxic mushrooms as larval hosts, but the mechanism by which these species are tolerant remains unknown. Previous data have shown that a local population of D. tripunctata exhibits significant genetic variation in toxin tolerance. This study assesses the potential role of the microbiome in α‐amanitin tolerance in six wild‐derived strains of Drosophila tripunctata. Normal and antibiotic‐treated samples of six strains were reared on diets with and without α‐amanitin, and then scored for survival from the larval stage to adulthood and for development time to pupation. Our results show that a substantial reduction in bacterial load does not influence toxin tolerance in this system, while confirming genotype and toxin‐specific effects on survival are independent of the microbiome composition. Thus, we conclude that this adaptation to exploit toxic mushrooms as a host is likely intrinsic to the fly's genome and not a property of their microbiome., Several species of mycophagous Drosophila are tolerant to amatoxins found in mushrooms of the genus Amanita, despite these toxins being lethal to most other known eukaryotes. This study assesses the potential role of the microbiome in α‐amanitin tolerance in six wild‐derived strains of Drosophila tripunctata. Our results show that the microbiome does not contribute to toxin tolerance in this system, while confirming genotype and toxin‐specific effects on survival independent of the microbiome.

Obesity is a complex disease, shaped by both genetic and environmental factors such as diet. In this study, we use untargeted metabolomics and Drosophila melanogaster to model how diet and genotype shape the metabolome of obese phenotypes. We used 16 distinct outbred genotypes of Drosophila larvae raised on normal (ND) and high-fat (HFD) diets, to produce three distinct phenotypic classes, genotypes that stored more triglycerides on a ND relative to the HFD, genotypes that stored more triglycerides on a HFD relative to ND, and genotypes that showed no change in triglyceride storage on either of the two diets. Using untargeted metabolomics we characterized 350 metabolites: 270 with definitive chemical IDs and 80 that were chemically unidentified. Using random forests, we determined metabolites that were important in discriminating between the HFD and ND larvae as well as between the triglyceride phenotypic classes. We found that flies fed on a HFD showed evidence of an increased use of omega fatty acid oxidation pathway, an alternative to the more commonly used beta fatty acid oxidation pathway. Additionally, we observed no correlation between the triglyceride storage phenotype and free fatty acid levels (laurate, caprate, caprylate, caproate), indicating that the distinct metabolic profile of fatty acids in high-fat diet fed Drosophila larvae does not propagate into triglyceride storage differences. However, dipeptides did show moderate differences between the phenotypic classes. We fit Gaussian graphical models (GGMs) of the metabolic profiles for HFD and ND flies to characterize changes in metabolic network structure between the two diets, finding the HFD to have a greater number of edges indicating that metabolome varies more across samples on a HFD. Taken together, these results show that, in the context of obesity, metabolomic profiles under distinct dietary conditions may not be reliable predictors of phenotypic outcomes in a genetically diverse population.

Adaptive radiations provide an opportunity to examine complex evolutionary processes such as ecological specialization and speciation. While a well-resolved phylogenetic hypothesis is critical to completing such studies, the rapid rates of evolution in these groups can impede phylogenetic studies. Here we study the quinaria and testacea species groups of the immigrans-tripunctata radiation of Drosophila, which represent a recent adaptive radiation and are a developing model system for ecological genetics. We were especially interested in understanding host use evolution in these species. In order to infer a phylogenetic hypothesis for this group we sampled loci from both the nuclear genome and the mitochondrial DNA to develop a dataset of 43 protein-coding loci for these two groups along with their close relatives in the immigrans-tripunctata radiation. We used this dataset to examine their evolutionary relationships along with the evolution of feeding behavior. Our analysis recovers strong support for the monophyly of the testacea but not the quinaria group. Results from our ancestral state reconstruction analysis suggests that the ancestor of the testacea and quinaria groups exhibited mushroom-feeding. Within the quinaria group, we infer that transition to vegetative feeding occurred twice, and that this transition did not coincide with a genome-wide change in the rate of protein evolution.

The incidence of complex metabolic diseases has increased as a result of a widespread transition towards lifestyles of increased caloric intake and lowered activity levels. These multifactorial diseases arise from a combination of genetic, environmental, and behavioral factors. One such complex disease is Metabolic Syndrome (MetS), which is a cluster of metabolic disorders, including hypertension, hyperglycemia, and abdominal obesity. Exercise and dietary intervention are the primary treatments recommended by doctors to mitigate obesity and its subsequent metabolic diseases. Exercise intervention, in particular aerobic interval training, stimulates favorable changes in the common risk factors for Type 2 Diabetes Mellitus (T2DM), Cardiovascular Disease (CVD), and other conditions. With the influx of evidence describing the therapeutic effect exercise has on metabolic health, establishing a system that models exercise in a controlled setting provides a valuable tool for assessing the effects of exercise in an experimental context. Drosophila melanogaster is a great tool for investigating the physiological and molecular changes that result from exercise intervention. The flies have short lifespans and similar mechanisms of metabolizing nutrients when compared to humans. To induce exercise in Drosophila, we developed a machine called the TreadWheel, which utilizes the fly's innate, negative geotaxis tendency to gently induce climbing. This enables researchers to perform experiments on large cohorts of genetically diverse flies to better understand the genotype-by-environment interactions underlying the effects of exercise on metabolic health.