Ultrahigh-resolution 7-Tesla anatomic magnetic resonance imaging and diffusion tensor imaging of formalin-fixed human brainstem-cerebellum complex.

Introduction: Brain cross-sectional images, tractography, and segmentation are valuable resources for neuroanatomical education and research but are also crucial for neurosurgical planning that may improve outcomes in cerebellar and brainstem interventions. Although ultrahigh-resolution 7-Tesla (7T) magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) reveal such structural brain details in living or fresh unpreserved brain tissue, imaging standard formalin-preserved cadaveric brain specimens often used for neurosurgical anatomic studies has proven difficult. This study sought to develop a practical protocol to provide anatomic information and tractography results of an human brainstem-cerebellum specimen.

Capture rates of increase following white-nose syndrome across the eastern US.

Emerging infectious diseases threaten wildlife globally. While the effects of infectious diseases on hosts with severe infections and high mortality rates often receive considerable attention, effects on hosts that persist despite infection are less frequently studied. To understand how persisting host populations change in the face of disease, we quantified changes to the capture rates of (big brown bats), a persisting species susceptible to infection by the invasive fungal pathogen (; causative agent for white-nose syndrome), across the eastern US using a 30-year dataset.

RBM39 degrader invigorates natural killer cells to eradicate neuroblastoma despite cancer cell plasticity.

The cellular plasticity of neuroblastoma is defined by a mixture of two major cell states, adrenergic (ADRN) and mesenchymal (MES), which may contribute to therapy resistance. However, how neuroblastoma cells switch cellular states during therapy remains largely unknown and how to eradicate neuroblastoma regardless of their cell states is a clinical challenge. To better understand the lineage switch of neuroblastoma in chemoresistance, we comprehensively defined the transcriptomic and epigenetic map of ADRN and MES types of neuroblastomas using human and murine models treated with indisulam, a selective RBM39 degrader.

Conditional c-MYC activation in catecholaminergic cells drives distinct neuroendocrine tumors: neuroblastoma vs somatostatinoma.

The MYC proto-oncogenes (c-MYC, , ) are among the most deregulated oncogenic drivers in human malignancies including high-risk neuroblastoma, 50% of which are -amplified. Genetically engineered mouse models (GEMMs) based on the transgene have greatly expanded the understanding of neuroblastoma biology and are powerful tools for testing new therapies. However, a lack of c-MYC-driven GEMMs has hampered the ability to better understand mechanisms of neuroblastoma oncogenesis and therapy development given that c-MYC is also an important driver of many high-risk neuroblastomas.

Management of acute perianal abscess: is surgeon specialization associated with improved outcomes?

Background: Acute surgical units (ASU) are increasingly being adopted and in our system are staffed by colorectal and non-colorectal general surgeons. This study aims to evaluate whether surgeon specialization was associated with improved outcomes in perianal abscess.

Methods: Patients with perianal abscess admitted to the ASU between 2016 and 2020 were identified from a prospective database and their medical records reviewed.

Long-term spring through fall capture data of in the eastern USA before and after white-nose syndrome.

Emerging infectious diseases threaten wildlife populations. Without well monitored wildlife systems, it is challenging to determine accurate population and ecosystem losses following disease emergence. North American temperate bats present a unique opportunity for studying the broad impacts of wildlife disease emergence, as their federal monitoring programs were prioritized in the USA throughout the 20 century and they are currently threatened by the invasive fungal pathogen, (), which causes white-nose syndrome.

Little Brown Bats () Support the Binding of SARS-CoV-2 Spike and Are Likely Susceptible to SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), believed to have originated from a bat species, can infect a wide range of non-human hosts. Bats are known to harbor hundreds of coronaviruses capable of spillover into human populations. Recent studies have shown a significant variation in the susceptibility among bat species to SARS-CoV-2 infection.

Assessment of complementary white matter microstructural changes and grey matter atrophy in a preclinical model of Alzheimer's disease.

Alzheimer's disease (AD) has been associated with amyloid and tau pathology, as well as neurodegeneration. Beyond these hallmark features, white matter microstructural abnormalities have been observed using MRI. The objective of this study was to assess grey matter atrophy and white matter microstructural changes in a preclinical mouse model of AD (3xTg-AD) using voxel-based morphometry (VBM) and free-water (FW) diffusion tensor imaging (FW-DTI).

A novel SNP assay reveals increased genetic variability and abundance following translocations to a remnant Allegheny woodrat population.

Background: Allegheny woodrats (Neotoma magister) are found in metapopulations distributed throughout the Interior Highlands and Appalachia. Historically these metapopulations persisted as relatively fluid networks, enabling gene flow between subpopulations and recolonization of formerly extirpated regions. However, over the past 45 years, the abundance of Allegheny woodrats has declined throughout the species' range due to a combination of habitat destruction, declining hard mast availability, and roundworm parasitism.

Seasonal roost selection and activity of a remnant population of northern myotis in Pennsylvania.

The decline in northern myotis (Myotis septentrionalis) populations due to the disease white-nose syndrome (WNS) has led to the species receiving federal protection in the United States and Canada, requiring conservation of critical habitats. However, considerably more is known about summer habitat preferences of northern myotis compared to late summer through winter. Our goal was to describe the seasonal presence and habitat use of a remnant colony of northern myotis in central Pennsylvania.

Unrecognized diversity of mammalian orthoreoviruses in North American bats.

Bats have recently been identified as potential reservoir hosts for mammalian orthoreoviruses (MRVs) throughout Europe and China. Here we present the first evolutionary and biological characterization of bat-borne MRVs in North America, including phylogenomic analysis, in vitro relative infectivity in bat and other mammalian cell cultures, host cell receptor specificity, and epifluorescence microscopy of viral factory formation. Through genetic and phylogenetic comparisons, we show that two divergent MRV serotype 2 (T2) strains - isolated from a silver-haired bat (Lasionycteris noctivagans) and a big brown bat (Eptesicus fuscus) from Pennsylvania, USA - provide an evolutionary link to an MRV strain (T2W) recovered from an 8-week-old infant who died in Winnipeg, Manitoba, Canada in 1997.

Complement C3a Receptor (C3aR) Mediates Vascular Dysfunction, Hippocampal Pathology, and Cognitive Impairment in a Mouse Model of VCID.

Vascular contributions to cognitive impairment and dementia (VCID) secondary to chronic mild-moderate cerebral ischemia underlie a significant percentage of cases of dementia. We previously reported that either genetic deficiency of the complement C3a receptor (C3aR) or its pharmacological inhibition protects against cerebral ischemia in rodents, while others have implicated C3aR in the pathogenesis seen in rodent transgenic models of Alzheimer's disease. In the present study, we evaluated the role of complement C3a-C3aR signaling in the onset and progression of VCID.

Novel experimental model of brain arteriovenous malformations using conditional Alk1 gene deletion in transgenic mice.

Objective: Hereditary hemorrhagic telangiectasia is the only condition associated with multiple inherited brain arteriovenous malformations (AVMs). Therefore, a mouse model was developed with a genetics-based approach that conditionally deleted the causative activin receptor-like kinase 1 (Acvrl1 or Alk1) gene. Radiographic and histopathological findings were correlated, and AVM stability and hemorrhagic behavior over time were examined.

Strategies for Antibiotic Administration for Bowel Preparation Among Patients Undergoing Elective Colorectal Surgery: A Network Meta-analysis.

Importance: There are discrepancies in guidelines on preparation for colorectal surgery. While intravenous (IV) antibiotics are usually administered, the use of mechanical bowel preparation (MBP), enemas, and/or oral antibiotics (OA) is controversial.

Objective: To summarize all data from randomized clinical trials (RCTs) that met selection criteria using network meta-analysis (NMA) to determine the ranking of different bowel preparation treatment strategies for their associations with postoperative outcomes.

Cooling of bat hibernacula to mitigate white-nose syndrome.

White-nose syndrome (WNS) is a fungal disease that has caused precipitous declines in several North American bat species, creating an urgent need for conservation. We examined how microclimates and other characteristics of hibernacula have affected bat populations following WNS-associated declines and evaluated whether cooling of warm, little-used hibernacula could benefit bats. During the period following mass mortality (2013-2020), we conducted 191 winter surveys of 25 unmanipulated hibernacula and 6 manipulated hibernacula across Pennsylvania (USA).

The scope and severity of white-nose syndrome on hibernating bats in North America.

Assessing the scope and severity of threats is necessary for evaluating impacts on populations to inform conservation planning. Quantitative threat assessment often requires monitoring programs that provide reliable data over relevant spatial and temporal scales, yet such programs can be difficult to justify until there is an apparent stressor. Leveraging efforts of wildlife management agencies to record winter counts of hibernating bats, we collated data for 5 species from over 200 sites across 27 U.

Phylogeographic analysis of Pseudogymnoascus destructans partitivirus-pa explains the spread dynamics of white-nose syndrome in North America.

Understanding the dynamics of white-nose syndrome spread in time and space is an important component for the disease epidemiology and control. We reported earlier that a novel partitivirus, Pseudogymnoascus destructans partitivirus-pa, had infected the North American isolates of Pseudogymnoascus destructans, the fungal pathogen that causes white-nose syndrome in bats. We showed that the diversity of the viral coat protein sequences is correlated to their geographical origin.

Acute diverticulitis: an ongoing economic burden on the health system.

Background: Acute diverticulitis (AD) is an increasingly common cause of acute hospital admissions. An understanding of its economic burden is necessary to plan resource allocation, and for targeting health research funding. The aim of this study is to obtain an accurate estimate of the cost of AD, accounting not only for the initial episode, but all related costs incurred during long-term follow-up.

Statin use and risk of acute diverticulitis: A population-based case-control study.

The goal of the study was to examine the association between statin use and the development of acute diverticulitis requiring hospital admission.Acute diverticulitis is a common and costly gastrointestinal disorder. Although the incidence is increasing its pathophysiology and modifiable risk factors are incompletely understood.

Genome-Wide Changes in Genetic Diversity in a Population of Affected by White-Nose Syndrome.

Novel pathogens can cause massive declines in populations, and even extirpation of hosts. But disease can also act as a selective pressure on survivors, driving the evolution of resistance or tolerance. Bat white-nose syndrome (WNS) is a rapidly spreading wildlife disease in North America.