With the advent of deep sequencing techniques, it is now possible to track the evolution of viruses with ever-increasing detail. Here, we present Flexible Inference from Time-Series (FITS)-a computational tool that allows inference of one of three parameters: the fitness of a specific mutation, the mutation rate or the population size from genomic time-series sequencing data. FITS was designed first and foremost for analysis of either short-term Evolve & Resequence (E&R) experiments or rapidly recombining populations of viruses. We thoroughly explore the performance of FITS on simulated data and highlight its ability to infer the fitness/mutation rate/population size. We further show that FITS can infer meaningful information even when the input parameters are inexact. In particular, FITS is able to successfully categorize a mutation as advantageous or deleterious. We next apply FITS to empirical data from an E&R experiment on poliovirus where parameters were determined experimentally and demonstrate high accuracy in inference.
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http://dx.doi.org/10.1093/ve/vez011 | DOI Listing |
Epilepsia
January 2025
Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps.
View Article and Find Full Text PDFBioData Min
January 2025
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
Background: The mechanistic pathways that give rise to the extreme symptoms exhibited by rare disease patients are complex, heterogeneous, and difficult to discern. Understanding these mechanisms is critical for developing treatments that address the underlying causes of diseases rather than merely the presenting symptoms. Moreover, the same dysfunctional series of interrelated symptoms implicated in rare recessive diseases may also lead to milder and potentially preventable symptoms in carriers in the general population.
View Article and Find Full Text PDFClin Ther
January 2025
Acadia Pharmaceuticals, Inc., San Diego, California. Electronic address:
Purpose: Rett syndrome (RTT) is a rare neurodevelopmental disorder that mainly affects girls and women. Trofinetide is approved for the treatment of RTT in adults and children aged ≥2 years. To gain insight into experiences with RTT and effects of trofinetide treatment at different stages of RTT, interviews with caregivers of individuals with RTT were conducted upon their exit from the open-label trofinetide trials.
View Article and Find Full Text PDFTransplant Proc
January 2025
Neurology Service, Department of Diagnostic and Therapeutic Services, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT) - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Pittsburgh Medical Center (UPMC), Palermo, Italy.
Background: After encephalopathy, epileptic seizures (ES) are the second most common neurologic complication after orthotopic liver transplantation (OLT) and may announce a disabling/fatal neurologic disease.
Methods: In this retrospective study, we collected clinical information from patients who underwent OLT at our institution and analyzed outcomes and potential risk factors for developing ES after OLT.
Results: Fourteen of our 376 patients (3.
J Neurointerv Surg
January 2025
Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
Background: Post-stroke epilepsy (PSE) is a major complication of stroke. However, data about the predictors of PSE in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy are limited.
Objective: To evaluate the relationship between intraoperative angiographic signs and PSE risk in patients with anterior circulation AIS who underwent mechanical thrombectomy.
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