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IntroductionA major goal for conservation planning is the prioritized protection and management of areas that harbor maximal biodiversity. However, such spatial prioritization often suffers from limited data availability, resulting in decisions driven by a handful of iconic or endangered species, with uncertain benefits for co-occurring taxa. We argue that multi-species habitat preferences based on field observations should guide conservation planning to optimize the long-term persistence of as many species as possible.MethodsUsing habitat suitability modeling techniques and data from the community-science platform iNaturalist, we provide a strategy to develop spatially explicit models of habitat suitability that enable better informed, place-based conservation prioritization. Our case study in Greater Los Angeles used Maxent and Random Forests to generate suitability models for 1,200 terrestrial species with at least 25 occurrence records, drawn from plants (45.5%), arthropods (27.45%), vertebrates (22.2%), fungi (3.2%), molluscs (1.3%), and other taxonomic groups (< 0.3%). This modeling strategy further compared spatial thinning and taxonomic bias file corrections to account for the biases inherent to the iNaturalist dataset, modeling species jointly and separately in wildland and urban sub-regions and validated model performance using null models and a “test” dataset of species and occurrences that were not used to train models.ResultsMean models of habitat suitability of all species combined were similar across model settings, but the mean Random Forest model received the highest median AUCROC and AUCPRG scores in model evaluation. Taxonomic groups showed relatively modest differences in their response to the urbanization gradient, while native and non-native species showed contrasting patterns in the most urban and the most wildland habitats and both peaked in mean habitat suitability near the urban-wildland interface.DiscussionOur modeling framework is based entirely on open-source software and our code is provided for further use. Given the increasing availability of urban biodiversity data via platforms such as iNaturalist, this modeling framework can easily be applied to other regions. Quantifying habitat suitability for a large, representative subset of the locally occurring pool of species in this way provides a clear, data-driven basis for further ecological research and conservation decision-making, maximizing the impact of current and future conservation efforts.

Summary: Early erythroid progenitors are transit-amplifying cells with high proliferative capacity committed to undergoing red cell differentiation. CD71/CD24low progenitors are less mature and have greater proliferative capacity than CD71/CD24high. We present protocols for isolation of CD71/CD24low progenitors from mouse fetal liver using both fluorescence-activated cell sorting (FACS) and immunomagnetic enrichment. CD71/CD24low progenitors isolated with both approaches show similar transcriptomes at single-cell resolution and exhibit characteristic proliferative responses to glucocorticoids.For complete details on the use and execution of this protocol, please refer to Li et al. (2019).

A careful reading of Cicero, Pro Plancio 86-90, in conjuction with the known facts of the exile of Metellus Numidicus and the remains of his exilic correspondence, suggest that an important element in his performance of exile was his insistance that his behaviour was devoted to the preservation of law and order in Roman society. Metellus went so far as to claim that that the slaying even of wicked citizens (read: Saturninus and his followers) by Gaius Marius was unacceptable, notwithstanding the very real threat posed by Saturninus. This argument helped to fashion Metellus as respectful of the right political order and aided his supporters in challenging the legitmacy of the position of the chief obstacle to Metellus' restoration to Rome. [ABSTRACT FROM AUTHOR]

Background While many clinical prediction models (CPMs) exist to guide valvular heart disease treatment decisions, the relative performance of these CPMs is largely unknown. We systematically describe the CPMs available for patients with valvular heart disease with specific attention to performance in external validations. Methods and Results A systematic review identified 49 CPMs for patients with valvular heart disease treated with surgery (n=34), percutaneous interventions (n=12), or no intervention (n=3). There were 204 external validations of these CPMs. Only 35 (71%) CPMs have been externally validated. Sixty‐five percent (n=133) of the external validations were performed on distantly related populations. There was substantial heterogeneity in model performance and a median percentage change in discrimination of −27.1% (interquartile range, −49.4%–−5.7%). Nearly two‐thirds of validations (n=129) demonstrate at least a 10% relative decline in discrimination. Discriminatory performance of EuroSCORE II and Society of Thoracic Surgeons (2009) models (accounting for 73% of external validations) varied widely: EuroSCORE II validation c‐statistic range 0.50 to 0.95; Society of Thoracic Surgeons (2009) Models validation c‐statistic range 0.50 to 0.86. These models performed well when tested on related populations (median related validation c‐statistics: EuroSCORE II, 0.82 [0.76, 0.85]; Society of Thoracic Surgeons [2009], 0.72 [0.67, 0.79]). There remain few (n=9) external validations of transcatheter aortic valve replacement CPMs. Conclusions Many CPMs for patients with valvular heart disease have never been externally validated and isolated external validations appear insufficient to assess the trustworthiness of predictions. For surgical valve interventions, there are existing predictive models that perform reasonably well on related populations. For transcatheter aortic valve replacement (CPMs additional external validations are needed to broadly understand the trustworthiness of predictions.

Folate, an essential vitamin, is a one-carbon acceptor and donor in key metabolic reactions. Erythroid cells harbor a unique sensitivity to folate deprivation, as revealed by the primary pathological manifestation of nutritional folate deprivation: megaloblastic anemia. To study this metabolic sensitivity, we applied mild folate depletion to human and mouse erythroid cell lines and primary murine erythroid progenitors. We show that folate depletion induces early blockade of purine synthesis and accumulation of the purine synthesis intermediate and signaling molecule, 5'-phosphoribosyl-5-aminoimidazole-4-carboxamide (AICAR), followed by enhanced heme metabolism, hemoglobin synthesis, and erythroid differentiation. This is phenocopied by inhibition of folate metabolism using the inhibitor SHIN1, and by AICAR supplementation. Mechanistically, the metabolically driven differentiation is independent of mechanistic target of rapamycin complex 1 (mTORC1) and adenosine 5'-monophosphate-activated protein kinase (AMPK) and is instead mediated by protein kinase C. Our findings suggest that folate deprivation-induced premature differentiation of erythroid progenitor cells is a molecular etiology to folate deficiency-induced anemia. [ABSTRACT FROM AUTHOR]

Objective: We published a list of "must-know" routine EEG (rEEG) findings for trainees based on expert opinion. Here, we studied the accuracy and inter-rater agreement (IRA) of these "must-know" rEEG findings among international experts., Methods: A previously validated online rEEG examination was disseminated to EEG experts. It consisted of a survey and 30 multiple-choice questions predicated on the previously published "must-know" rEEG findings divided into four domains: normal, abnormal, normal variants, and artifacts. Questions contained de-identified 10-20-s epochs of EEG that were considered unequivocal examples by five EEG experts., Results: The examination was completed by 258 international EEG experts. Overall mean accuracy and IRA (AC1) were 81% and substantial (0.632), respectively. The domain-specific mean accuracies and IRA were: 76%, moderate (0.558) (normal); 78%, moderate (0.575) (abnormal); 85%, substantial (0.678) (normal variants); 85%, substantial (0.740) (artifacts). Academic experts had a higher accuracy than private practice experts (82% vs. 77%; p = .035). Country-specific overall mean accuracies and IRA were: 92%, almost perfect (0.836) (U.S.); 86%, substantial (0.762) (Brazil); 79%, substantial (0.646) (Italy); and 72%, moderate (0.496) (India). In conclusion, collective expert accuracy and IRA of "must-know" rEEG findings are suboptimal and heterogeneous., Significance: We recommend the development and implementation of pragmatic, accessible, country-specific ways to measure and improve the expert accuracy and IRA., (© 2023 International League Against Epilepsy.)

Background and Objectives: Epilepsy is considered one of the most prevalent and severe chronic neurological disorders worldwide. Our study aims to analyze the national trends in different treatment modalities for individuals with drug-resistant epilepsy and investigate the outcomes associated with these procedural trends in the United States., Methods: Using the National Inpatient Sample database from 2010 to 2020, patients with drug-resistant focal epilepsy who underwent laser interstitial thermal therapy (LITT), open surgical resection, vagus nerve stimulation (VNS), or responsive neurostimulation (RNS) were identified. Trend analysis was performed using piecewise joinpoint regression. Propensity score matching was used to compare outcomes between 10 years prepandemic before 2020 and the first peak of the COVID-19 pandemic., Results: This study analyzed a total of 33 969 patients with a diagnosis of drug-resistant epilepsy, with 3343 patients receiving surgical resection (78%), VNS (8.21%), RNS (8%), and LITT (6%). Between 2010 and 2020, there was an increase in the use of invasive electroencephalography monitoring for seizure zone localization (P = .003). There was an increase in the use of LITT and RNS (P < .001), while the use of surgical resection and VNS decreased over time (P < .001). Most of these patients (89%) were treated during the pre-COVID pandemic era (2010-2019), while a minority (11%) underwent treatment during the COVID pandemic (2020). After propensity score matching, the rate of pulmonary complications, postprocedural hematoma formation, and mortality were slightly higher during the pandemic compared with the prepandemic period (P = .045, P = .033, and P = .026, respectively)., Conclusion: This study indicates a relative decrease in the use of surgical resections, as a treatment for drug-resistant focal epilepsy. By contrast, newer, minimally invasive surgical approaches including LITT and RNS showed gradual increases in usage., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Drug-resistant epilepsy is associated with reduced quality of life (QoL) due to a myriad of disease-related and psychosocial factors. Although consciousness during seizures is a core feature of seizure classification, its impact on QoL in people with epilepsy (PWE) is not well understood. This study aimed to address this gap by comparing QoL between PWE with focal aware (FA) versus impaired awareness (FIA) seizures. Sixty-nine adults with epilepsy completed the Quality of Life in Epilepsy-31 (QoLIE-31) inventory as part of their pre-surgical neuropsychological evaluation (FA: n = 26, FIA: n = 43). There was no group difference in seizure burden as defined by the proportion of comorbid focal to bilateral tonic-clonic seizures (FA:65.4 %; FIA: 79.1 %). People with FA seizures reported lower overall QoL than people with FIA seizures; sub-scale analyses revealed that seizure worry drives this effect. There was no difference in QoL between people with motor and non-motor FA seizures. Results suggest that FA seizures are burdensome on the QoL of PWE. FA seizures may contribute to seizure worry due to preserved awareness of aversive peri-ictal phenomenon. Findings suggest that clinical efforts should continue to be made to optimize seizure control in people with breakthrough FA seizures. Prospective longitudinal monitoring of QoL in trials of consciousness-targeting neurostimulation therapy is needed to determine if QoL changes as a function of improved peri-ictal consciousness following treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Seizure emergencies and potential emergencies, ranging from seizure clusters to prolonged seizure and status epilepticus, may affect adults with epilepsy despite stable antiseizure therapy. Seizure action plans (SAPs) are designed for patients and their caregivers/care partners to provide guidance on the individualized treatment plan, including response to potential seizure emergencies and appropriate use of rescue therapy. The use of pediatric SAPs is common (typically required by schools), however, most adults with epilepsy do not have a plan. Patient-centered action plans are integral to care for other chronic conditions and may offer insights applicable to the care of adults with epilepsy. This review analyzes the potential benefits of action plans for medical conditions by exploring their utility in conditions such as asthma, diabetes, chronic obstructive pulmonary disease, heart disease, and opioid overdose. Evidence across these conditions substantiates the value of action plans for patients, and the benefits of adult SAPs in epilepsy are emerging. Because wide implementation of SAPs has faced barriers, other conditions may provide insights that are relevant to implementing SAPs in epilepsy. Based on these analyses, we propose concrete steps to improve the use of SAPs among adults. A recent consensus statement promoting the use of formal SAPs in epilepsy and advances in rescue therapy delivery methods provides support to engage patients around the value of SAPs. The precedent for use of SAPs for pediatric epilepsy patients serves as the foundation to support increased usage in adults. Seizure action plans in the context of improved clinical outcomes are expected to reduce healthcare utilization, improve patient quality of life, and optimize epilepsy management., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Herman is a consultant for BioSerenity, and has received grant funding from Cerebral Therapeutics; CREmedical; Equilibre; Marinus Pharmaceuticals; Medtronic; Neuroelectrics, and the Epilepsy Foundation. She is President of the National Association of Epilepsy Centers and is a co-leader of the Epilepsy Learning Healthcare System. Dr Detyniecki is a consultant for Aquestive; Neurelis, Inc.; UCB; and Greenwich Biosciences. Ms O’Hara is on the Advisory Board of Greenwich Biosciences. Dr Penovich has served on speakers bureaus for GW Pharmaceuticals; Neurelis, Inc.; SK Life Science; and UCB, and is an advisor to Engage Therapeutics; LVIS Corporation; Neurelis, Inc.; and SK Life Science. Dr Rao has served as a consultant for NeuroPace, Inc., manufacturer of the RNS System. Dr Tatum receives a stipend from Elsevier as Editor-in-Chief of Epilepsy & Behavior Reports and is on the Editorial Board of Journal of Clinical Neurophysiology. He has received grant funding from Esai; Mayo Clinic; McElvey Fund; and Martin Family Foundation and industry research support from Cerevel; Engage; Liva Nova; and Xenon. He serves as a consultant for BioSerenity; Medtronic; Neurelis, Inc.; and Zimmer-Biomet. Royalties from Demos and Springer Publishers. He has patents/patents pending on intraoperative monitoring devices (#62527896; #62770362). Ms Long is a consultant for Neurelis, Inc.; SK Life Science; and Supernus Pharmaceuticals, and is a speaker for LivaNova. Dr Stern is a consultant for Eisai; Jazz; Neurelis, Inc.; SK Life Science; and UCB. Dr Carrazana is an employee of and has received stock and stock options from Neurelis, Inc. Dr Rabinowicz is an employee of and has received stock options from Neurelis, Inc., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The 3D edge-enhancing gradient-echo (EDGE) MR imaging sequence offers superior contrast-to-noise ratio in the detection of focal cortical dysplasia. EDGE could benefit from 7T MR imaging but also faces challenges such as image inhomogeneity and low acquisition efficiency. We propose an EDGE-MP2RAGE sequence that can provide both EDGE and T1-weighted contrast, simultaneously, improving data-acquisition efficiency. We demonstrate that with sequence optimization, EDGE images with sufficient uniformity and T1-weighted images with high gray-to-white matter contrast can be achieved., (© 2023 by American Journal of Neuroradiology.)

Correctly diagnosing and classifying seizures and epilepsies is paramount to ensure the delivery of optimal care to patients with epilepsy. Focal seizures, defined as those that originate within networks limited to one hemisphere, are primarily subdivided into focal aware, focal impaired awareness, and focal to bilateral tonic-clonic seizures. Focal epilepsies account for most epilepsy cases both in children and adults. In children, focal epilepsies are typically subdivided in three groups: self-limited focal epilepsy syndromes (e.g., self-limited epilepsy with centrotemporal spikes), focal epilepsy of unknown cause but which do not meet criteria for a self-limited focal epilepsy syndrome, and focal epilepsy of known cause (e.g., structural lesions-developmental or acquired). In adults, focal epilepsies are often acquired and may be caused by a structural lesion such as stroke, infection and traumatic brain injury, or brain tumors, vascular malformations, metabolic disorders, autoimmune, and/or genetic causes. In addition to seizure semiology, neuroimaging, neurophysiology, and neuropathology constitute the cornerstones of a diagnostic evaluation. Patients with focal epilepsy who become drug-resistant should promptly undergo assessment in an epilepsy center. After excluding pseudo-resistance, these patients should be considered for presurgical evaluation as a means to identify the location and extent of the epileptogenic zone and assess their candidacy for a surgical procedure. The goal of this seminar in epileptology is to summarize clinically relevant information concerning focal epilepsies. This contributes to the ILAE's mission to ensure that worldwide healthcare professionals, patients, and caregivers continue to have access to high-quality educational resources concerning epilepsy., (© 2023 International League Against Epilepsy.)

Nasal administration of treatments for neurologic conditions, including rescue therapies to treat seizure clusters among people with epilepsy, represents a meaningful advance in patient care. Nasal anatomy and physiology underpin the multiple advantages of nasal administration but also present challenges that must be addressed in any successful nasal formulation. Nasal cavity anatomy is complex, with a modest surface area for absorption that limits the dose volume of an intranasal formulation. The mucociliary clearance mechanism and natural barriers of the nasal epithelia must be overcome for adequate absorption. An extensive vasculature and the presence of olfactory nerves in the nasal cavity enable both systemic and direct-to-brain delivery of drugs targeting the central nervous system. Two intranasal benzodiazepine rescue therapies have been approved by the US Food and Drug Administration for seizure-cluster treatment, in addition to the traditional rectal formulation. Nasal sprays are easy to use and offer the potential for quick and consistent bioavailability. This review aims to increase the clinician's understanding of nasal anatomy and physiology and of the formulation of intranasal rescue therapies and to facilitate patient education and incorporate intranasal rescue therapies for seizure clusters (also known as acute repetitive seizures) into their seizure action plans., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Chung is a consultant for Neurelis, Inc.; SK Life Science; Sunovion; and UCB and is a speaker for Eisai, Jazz Pharma, SK Life Science, Sunovion, and UCB. Dr Peters has served as a speaker and consultant for Greenwich Biosciences; Neurelis, Inc.; and Novartis. Dr Detyniecki is a consultant for Aquestive; Greenwich Biosciences; Neurelis, Inc.; and UCB. Dr Tatum receives a stipend from Elsevier as Editor-in-Chief of Epilepsy & Behavior Reports and is on the editorial board of the Journal of Clinical Neurophysiology. He has received grant funding from Esai, Martin Family Foundation, Mayo Clinic, and McElvey Fund and industry research support from Cerevel, Engage, Liva Nova, and Xenon. He serves as a consultant for Bioserenity; Medtronics; Neurelis, Inc.; and Zimmer-Biomet. He receives royalties from Demos, Springer, and Wiley publishers. He has patents/patents pending on intraoperative monitoring devices (#62527896; #62770362). Dr Rabinowicz is an employee of and has received stock options from Neurelis, Inc. Dr Carrazana is an employee of and has received stock and stock options from Neurelis, Inc., (© 2022 The Authors.)

Permanently implanted devices that deliver electrical stimulation are increasingly used to treat patients with drug-resistant epilepsy. Primary care physicians, neurologists, and epilepsy clinicians may encounter patients with a variety of implanted neuromodulation devices in the course of clinical care. Due to the rapidly changing landscape of available epilepsy-related neurostimulators, there may be uncertainty related to how these devices should be handled during imaging procedures and perioperative care. We review the safety and management of epilepsy-related implanted neurostimulators that may be encountered during imaging and surgery. We provide a summary of approved device labeling and recommendations for the practical management of these devices to help guide clinicians as they care for patients treated with bioelectronic medicine., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)