QuICSeedR: an R package for analyzing fluorophore-assisted seed amplification assay data.

Motivation: Fluorophore-assisted seed amplification assays (F-SAAs), such as real-time quaking-induced conversion (RT-QuIC) and fluorophore-assisted protein misfolding cyclic amplification (F-PMCA), have become indispensable tools for studying protein misfolding in neurodegenerative diseases. However, analyzing data generated by these techniques often requires complex and time-consuming manual processes. In addition, the lack of standardization in F-SAA data analysis presents a significant challenge to the interpretation and reproducibility of F-SAA results across different laboratories and studies.

A new mouse model for PRPH2 pattern dystrophy exhibits functional compensation prior and subsequent to retinal degeneration.

Mutations in PRPH2 are a relatively common cause of sight-robbing inherited retinal degenerations (IRDs). Peripherin-2 (PRPH2) is a photoreceptor-specific tetraspanin protein that structures the disk rim membranes of rod and cone outer segment (OS) organelles, and is required for OS morphogenesis. PRPH2 is noteworthy for its broad spectrum of disease phenotypes; both inter- and intra-familial heterogeneity have been widely observed and this variability in disease expression and penetrance confounds efforts to understand genotype-phenotype correlations and pathophysiology.

The establishment of a collaborative surveillance program with indigenous hunters to characterize primate health in Southern Guyana.

The consumption of primates is integral to the traditional subsistence strategies of many Indigenous communities throughout Amazonia. Understanding the overall health of primates harvested for food in the region is critical to Indigenous food security and thus, these communities are highly invested in long-term primate population health. Here, we describe the establishment of a surveillance comanagement program among the Waiwai, an Indigenous community in the Konashen Amerindian Protected Area (KAPA).

Nanopore adaptive sampling for targeted mitochondrial genome sequencing and bloodmeal identification in hematophagous insects.

Background: Blood-feeding insects are important vectors for an array of zoonotic pathogens. While previous efforts toward generating molecular resources have largely focused on major vectors of global medical and veterinary importance, molecular data across a large number of hematophagous insect taxa remain limited. Advancements in long-read sequencing technologies and associated bioinformatic pipelines provide new opportunities for targeted sequencing of insect mitochondrial (mt) genomes.

A mixed-methods approach to understanding domestic dog health and disease transmission risk in an indigenous reserve in Guyana, South America.

Domestic dogs (Canis lupus familiaris) can transmit a variety of pathogens due to their ubiquitousness in urban, rural and natural environments, and their close interactions with wildlife and humans. In this study, we used a mixed-methods approach to assess the role of domestic dogs as potential intermediaries of disease transmission from wildlife to humans among indigenous Waiwai in the Konashen Community Owned Conservation Area, Guyana. To address these objectives we 1) performed physical examinations and collected biological samples to assess Waiwai domestic dog health, and 2) administered questionnaires to characterize the role of dogs in the community and identify potential transmission pathways between wildlife, dogs, and humans.

Creating a health equity and inclusion office in an academic pediatric medical center: priorities addressed and lessons learned.

Background: Over the last two decades, medical schools and academic health centers have acknowledged the persistence of health disparities in their patients and the lack of diversity in their faculty, leaders and extended workforce. We established an Office of Health Equity and Inclusion (OHEI) at our pediatric academic medical center after a thorough evaluation of prior diversity initiatives and review of faculty development data.

Objective: To describe the lessons learned at a pediatric academic medical center in prioritizing and implementing health equity, diversity and inclusion (EDI) initiatives in creating the OHEI.

Altered mental status in COVID-19.

Background: Altered mental status (AMS) is a common neurological manifestation of COVID-19 infection in hospitalized patients. The principal causes of AMS have yet to be determined. We aimed to identify the common causes of AMS in patients with COVID-19 presenting to the emergency department with AMS on arrival.

An Ethnographic Approach to Characterizing Potential Pathways of Zoonotic Disease Transmission from Wild Meat in Guyana.

The hunting, butchery, and consumption of wild meat is an important interface for zoonotic disease transmission. Despite this, few researchers have used ethnography to understand the sociocultural factors that may increase zoonotic disease transmission from hunting, particularly in Amazonia. Here, we use ethnographic methods consisting of structured, semi-structured and unstructured interviews, and participant observation to address questions pertaining to wild meat consumption, pathways of zoonotic disease transmission, food security, and the cultural identity of indigenous Waiwai in the Konashen Community Owned Conservation Area, Guyana.

Phase II Clinical Trial of Everolimus in a Pan-Cancer Cohort of Patients with mTOR Pathway Alterations.

Purpose: This was a multicenter, histology-agnostic, single-arm prospective phase II trial of therapeutic activity of everolimus, an oral mTORC1 inhibitor, in patients with advanced solid tumors that harbored / or mutations.

Patients And Methods: Patients with tumors with inactivating / or activating mutations identified in any Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory were eligible. Patients were treated with everolimus 10 mg once daily until disease progression or unacceptable toxicity.

Neurologic Syndromes Predict Higher In-Hospital Mortality in COVID-19.

Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is protean in its manifestations, affecting nearly every organ system. However, nervous system involvement and its effect on disease outcome are poorly characterized. The objective of this study was to determine whether neurologic syndromes are associated with increased risk of inpatient mortality.

Rooting carbon dioxide removal research in the social sciences.

Reports from a variety of bodies have highlighted the role that carbon dioxide removal (CDR) technologies and practices must play in order to try to avoid the worst effects of anthropogenic climate change. Research into the feasibility of these technologies is primarily undertaken by scholars in the natural sciences, yet, as we argue in this commentary, there is great value in collaboration between these scholars and their colleagues in the social sciences. Spurred by this belief, in 2019, a university and a non-profit organization organized and hosted a workshop in Washington, DC, intended to bring natural and physical scientists, technology developers, policy professionals and social scientists together to explore how to better integrate social science knowledge into the field of CDR research.

Folding a neuroscience center into streamlined COVID-19 response teams: Lessons in origami.

In response to the COVID-19 pandemic epicenter in Bronx, NY, the Montefiore Neuroscience Center required rapid and drastic changes when considering the delivery of neurologic care, health and safety of staff, and continued education and safety for house staff. Health care leaders rely on principles that can be in conflict during a disaster response such as this pandemic, with equal commitments to ensure the best care for those stricken with COVID-19, provide high-quality care and advocacy for patients and families coping with neurologic disease, and advocate for the health and safety of health care teams, particularly house staff and colleagues who are most vulnerable. In our attempt to balance these principles, over 3 weeks, we reformatted our inpatient neuroscience services by reducing from 4 wards to just 1, in the following weeks delivering care to over 600 hospitalized patients with neuro-COVID and over 1,742 total neuroscience hospital bed days.

Multistep peripherin-2/rds self-assembly drives membrane curvature for outer segment disk architecture and photoreceptor viability.

Rod and cone photoreceptor outer segment (OS) structural integrity is essential for normal vision; disruptions contribute to a broad variety of retinal ciliopathies. OSs possess many hundreds of stacked membranous disks, which capture photons and scaffold the phototransduction cascade. Although the molecular basis of OS structure remains unresolved, recent studies suggest that the photoreceptor-specific tetraspanin, peripherin-2/rds (P/rds), may contribute to the highly curved rim domains at disk edges.

Measurement of resident fatigue using rapid number naming.

Objective: Sleep deprivation has a negative effect on neurocognitive performance. The King-Devick test (KDT), which tests speed and accuracy of number-reading, requires integrity of saccades, visual processing, and cognition. This study investigated effects of sleep deprivation in on-call residents using KDT.

Pharmacokinetic Evidence from the HIRIF Trial To Support Increased Doses of Rifampin for Tuberculosis.

Rifamycins exhibit concentration-dependent killing of ; higher exposures potentially induce better outcomes. We randomized 180 tuberculosis patients in Peru to receive rifampin at 10, 15, or 20 mg/kg/day. A total of 168 had noncompartmental pharmacokinetic analyses; 67% were sampled twice, and 33% were sampled six times.

Establishing Effective Mentoring Networks: Rationale and Strategies.

Introduction: Mentoring networks constitute an effective mentoring model in academic medicine and significantly add to the traditional dyadic mentor-mentee relationship. There is an unmet educational need for medical faculty to recognize the importance and characteristics of effective mentoring networks and to develop tools and strategies to appraise and construct strong, individualized mentoring networks.

Methods: An interactive educational session on developmental mentoring networks for physicians and scientists in an academic environment was designed.

An inducible amphipathic helix within the intrinsically disordered C terminus can participate in membrane curvature generation by peripherin-2/rds.

Peripherin-2/rds is required for biogenesis of vertebrate photoreceptor outer segment organelles. Its localization at the high-curvature rim domains of outer segment disk membranes suggests that it may act to shape these structures; however, the molecular function of this protein is not yet resolved. Here, we apply biochemical, biophysical, and imaging techniques to elucidate the role(s) played by the protein's intrinsically disordered C-terminal domain and an incipient amphipathic α-helix contained within it.

(Re)moving the needle: prospects for all-oral treatment for multidrug-resistant tuberculosis.

Background: Currently recommended regimens for multidrug-resistant tuberculosis (MDR-TB) contain painful daily injections and are unsuccessful in approximately half of patients. Removal of the injectable agent to fashion all-oral regimens could transform MDR-TB treatment and access to care.

Objective: To explore evidence for all-oral treatment regimens.

Bayesian adaptive randomization in a clinical trial to identify new regimens for MDR-TB: the endTB trial.

Background: Evidence-based optimization of treatment for multidrug-resistant tuberculosis (MDR-TB), including integration of new drugs, is urgent. Such optimization would benefit from efficient trial designs requiring fewer patients. Implementation of such innovative designs could accelerate improvements in and access to MDR-TB treatment.

A dedicated scholarly research program in an adult and pediatric neurology residency program.

Objective: To describe and assess the effectiveness of a formal scholarly activity program for a highly integrated adult and pediatric neurology residency program.

Methods: Starting in 2011, all graduating residents were required to complete at least one form of scholarly activity broadly defined to include peer-reviewed publications or presentations at scientific meetings of formally mentored projects. The scholarly activity program was administered by the associate residency training director and included an expanded journal club, guided mentorship, a required grand rounds platform presentation, and annual awards for the most scholarly and seminal research findings.