59 Works

Data from: Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials

Leonard H Van Den Berg, Eric Sorenson, Gary Gronseth, Eric A. Macklin, Jinsy Andrews, Robert H. Baloh, Michael Benatar, James D. Berry, Adriano Chio, Philippe Corcia, Angela Genge, Amelie K. Gubitz, Catherine Lomen-Hoerth, Christopher J. McDermott, Erik P. Pioro, Jeffrey Rosenfeld, Vincenzo Silani, Martin R. Turner, Markus Weber, Benjamin Rix Brooks, Robert G. Miller & Hiroshi Mitsumoto
Objective: To revise the 1999 Airlie House consensus guidelines for the design and implementation of preclinical therapeutic studies and clinical trials in amyotrophic lateral sclerosis (ALS). Methods: A consensus committee comprising 140 key members of the international ALS community (ALS researchers, clinicians, patient representatives, research funding representatives, industry and regulatory agencies) addressed nine areas of need within ALS research: 1. Pre-clinical studies; 2. Biological and phenotypic heterogeneity; 3. Outcome measures; 4. Disease-modifying and symptomatic interventions;...

Data from: The neuropathic diabetic foot ulcer microbiome is associated with clinical factors.

Sue E. Gardner, Stephen L. Hillis, Kris Heilmann, Julia A. Segre & Elizabeth A. Grice
Nonhealing diabetic foot ulcers (DFUs) are a common and costly complication of diabetes. Microbial burden, or "bioburden," is believed to underlie delayed healing, although little is known of those clinical factors that may influence microbial load, diversity, and/or pathogenicity. We profiled the microbiomes of neuropathic nonischemic DFUs without clinical evidence of infection in 52 individuals using high-throughput sequencing of the bacterial 16S ribosomal RNA gene. Comparatively, wound cultures, the standard diagnostic in the clinic, vastly...

Data from: Detecting signals of chronic shedding to explain pathogen persistence: Leptospira interrogans in California sea lions

Michael G. Buhnerkempe, Katherine C. Prager, Christopher C. Strelioff, Denise J. Greig, Jeff L. Laake, Sharon R. Melin, Robert L. DeLong, Frances M. D. Gulland & James O. Lloyd-Smith
Identifying mechanisms driving pathogen persistence is a vital component of wildlife disease ecology and control. Asymptomatic, chronically infected individuals are an oft-cited potential reservoir of infection but demonstrations of the importance of chronic shedding to pathogen persistence at the population level remain scarce. Studying chronic shedding using commonly collected disease data is hampered by numerous challenges, including short-term surveillance that focuses on single epidemics and acutely ill individuals, the subtle dynamical influence of chronic shedding...

Data from: Multiple sequence alignment averaging improves phylogeny reconstruction

Haim Ashkenazy, Itamar Sela, Eli Levy Karin, Giddy Landan & Tal Pupko
The classic methodology of inferring a phylogenetic tree from sequence data is composed of two steps. First, a multiple sequence alignment (MSA) is computed. Then, a tree is reconstructed assuming the MSA is correct. Yet, inferred MSAs were shown to be inaccurate and alignment errors reduce tree inference accuracy. It was previously proposed that filtering unreliable alignment regions can increase the accuracy of tree inference. However, it was also demonstrated that the benefit of this...

Data from: High-throughput synapse-resolving two-photon fluorescence microendoscopy for deep-brain volumetric imaging in vivo

Guanghan Meng, Yajie Liang, Sarah Sarsfield, Wan-Chen Jiang, Rongwen Lu, Joshua Tate Dudman, Yeka Aponte & Na Ji
Optical imaging has become a powerful tool for studying brains in vivo. The opacity of adult brains makes microendoscopy, with an optical probe such as a gradient index (GRIN) lens embedded into brain tissue to provide optical relay, the method of choice for imaging neurons and neural activity in deeply buried brain structures. Incorporating a Bessel focus scanning module into two-photon fluorescence microendoscopy, we extended the excitation focus axially and improved its lateral resolution. Scanning...

Data from: Identification of migratory bird flyways in North America using community detection on biological networks

Michael G. Buhnerkempe, Colleen T. Webb, Andrew A. Merton, John E. Buhnerkempe, Geof H. Givens, Ryan S. Miller & Jennifer A. Hoeting
Migratory behavior of waterfowl populations in North America has traditionally been broadly characterized by four north-south flyways, and these flyways have been central to the management of waterfowl populations for more than 80 years. However, previous flyway characterizations are not easily updated with current bird movement data and fail to provide assessments of the importance of specific geographical regions to the identification of flyways. Here, we developed a network model of migratory movement for four...

Time course and diagnostic utility of NfL, tau, GFAp, and UCH-L1 in subacute and chronic TBI

Pashtun Shahim, Adam Politis, Andre Van Der Merwe, Brian Moore, Vindhya Ekanayake, Sara Lippa, Yi-Yu Chou, Dzung Pham, John Butman, Ramon Diaz-Arrastia, Henrik Zetterberg, Kaj Blennow, Jessica Gill, David Brody & Leighton Chan
Objective: To determine whether neurofilament light (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) measured in serum relate to traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) measures of traumatic axonal injury (TAI) in patients with TBI. Methods: Patients with TBI (n = 162) and controls (n = 68) were prospectively enrolled between 2011 and 2019. Patients with TBI also underwent serum, functional outcome, and...

An animal without a mitochondrial genome: the salmon parasite Henneguya salminicola (Cnidaria: Myxozoa)

Dorothée Huchon, Dayana Yahalomi, Stephen D. Atkinson, Moran Neuhof, E. Sally Chang, Hervé Philippe, Paulyn Cartwright & Jerri L. Bartholomew
Although aerobic respiration is a hallmark of eukaryotes, a few unicellular lineages, growing in hypoxic environments, have secondarily lost this ability. In the absence of oxygen, the mitochondria of these organisms have lost all or parts of their genomes and evolved into mitochondria related organelles (MROs). There has been debate regarding the presence of MROs in animals. Using deep sequencing approaches, we discovered that a member of the Cnidaria, the myxozoan Henneguya salminicola, has no...

Data from: Para-aminosalicylic acid acts as an alternative substrate of folate metabolism in Mycobacterium tuberculosis

Sumit Chakraborty, Todd Gruber, , Helena I. Boshoff & Kyu Y. Rhee
Folate biosynthesis is an established anti-infective target, and the antifolate para-aminosalicylic acid (PAS) was one of the first anti-infectives introduced into clinical practice on the basis of target-based drug discovery. Fifty years later, PAS continues to be used to treat tuberculosis. PAS is assumed to inhibit dihydropteroate synthase (DHPS) in Mycobacterium tuberculosis by mimicking the substrate p-aminobenzoate (PABA). However, we found that sulfonamide inhibitors of DHPS inhibited growth of M. tuberculosis only weakly because of...

Data from: An antibody screen of a Plasmodium vivax antigen library identifies novel merozoite proteins associated with clinical protection

Camila T. França, Jessica B. Hostetler, Sumana Sharma, Michael T. White, Enmoore Lin, Benson Kiniboro, Andreea Waltmann, Andrew W. Darcy, Connie S. Li Wai Suen, Peter Siba, Christopher L. King, Julian C. Rayner, Rick M. Fairhurst, Ivo Mueller & Connie S. N. Li Wai Suen
Background. Elimination of Plasmodium vivax malaria would be greatly facilitated by the development of an effective vaccine. A comprehensive and systematic characterization of antibodies to P. vivax antigens in exposed populations is useful in guiding rational vaccine design. Methodology/Principal Findings. In this study, we investigated antibodies to a large library of P. vivax entire ectodomain merozoite proteins in 2 Asia-Pacific populations, analysing the relationship of antibody levels with markers of current and cumulative malaria exposure,...

Data from: Terminated trials in the ClinicalTrials.gov results database: evaluation of availability of primary outcome data and reasons for termination

Rebecca J. Williams, Tony Tse, Katelyn DiPiazza & Deborah A. Zarin
Background: Clinical trials that end prematurely (or “terminate”) raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized. Methods and Findings: A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the...

Data from: Calling in sick: impacts of fever on intra-urban human mobility

T. Alex Perkins, Valerie A. Paz-Soldan, Steven T. Stoddard, Amy C. Morrison, Brett M. Forshey, Kanya C. Long, Eric S. Halsey, Tadeusz J. Kochel, John P. Elder, Uriel Kitron, Thomas W. Scott & Gonzalo M. Vazquez-Prokopec
Pathogens inflict a wide variety of disease manifestations on their hosts, yet the impacts of disease on the behaviour of infected hosts are rarely studied empirically and are seldom accounted for in mathematical models of transmission dynamics. We explored the potential impacts of one of the most common disease manifestations, fever, on a key determinant of pathogen transmission, host mobility, in residents of the Amazonian city of Iquitos, Peru. We did so by comparing two...

Data from: The impact of within-host ecology on the fitness of a drug-resistant parasite

Silvie Huijben, Brian H K Chan, William A Nelson & Andrew F Read
Background and objectives: The rate of evolution of drug resistance depends on the fitness of resistant pathogens. The fitness of resistant pathogens is reduced by competition with sensitive pathogens in untreated hosts and so enhanced by competitive release in drug-treated hosts. We set out to estimate the magnitude of those effects on a variety of fitness measures, hypothesizing that competitive suppression and competitive release would have larger impacts when resistance was rarer to begin with....

Data from: Does high-dose antimicrobial chemotherapy prevent the evolution of resistance?

Troy Day & Andrew F. Read
High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the...

Data from: Cough frequency during treatment associated with baseline cavitary volume and proximity to the airway in pulmonary TB

Alvaro Proaño, David P. Bui, José W. López, Nancy M. Vu, Marjory A. Bravard, Gwenyth O. Lee, Brian H. Tracey, Ziyue Xu, Germán Comina, Eduardo Ticona, Daniel J. Mollura, Jon S. Friedland, David A. J. Moore, Carlton A. Evans, Philip Caligiuri, Robert H. Gilman & Tuberculosis Working Group In Peru
Background: Cough frequency, and its duration, is a lab-free biomarker that can be used in low-resource settings and has been associated with transmission and treatment response. Radiological characteristics associated with increased cough frequency may be important in understanding transmission. The relationship between cough frequency and cavitary lung disease has never been studied. Methods: We analyzed 41 human immunodeficiency virus-negative adults with culture-confirmed, drug-susceptible pulmonary tuberculosis throughout treatment. Cough recordings were based on the Cayetano Cough...

Data from: Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa

Lin Li, Xiaodong Jiao, Ilaria D’Atri, Fumihito Ono, Ralph Nelson, Chi-Chao Chan, Naoki Nakaya, Zhiwei Ma, Yan Ma, Xiaoying Cai, Longhua Zhang, Siying Lin, Abdul Hameed, Barry A. Chioza, Holly Hardy, Gavin Arno, Sarah Hull, Muhammad Imran Khan, James Fasham, V. Gaurav Harlalka, Michel Michaelides, Anthony T. Moore, Zeynep Hande Coban Akdemir, Shalini Jhangiani, James R. Lupski … & Frans P. M. Cremers
We identified a homozygous missense alteration (c.75C>A, p.D25E) in CLCC1, encoding a presumptive intracellular chloride channel highly expressed in the retina, associated with autosomal recessive retinitis pigmentosa (arRP) in eight consanguineous families of Pakistani descent. The p.D25E alteration decreased CLCC1 channel function accompanied by accumulation of mutant protein in granules within the ER lumen, while siRNA knockdown of CLCC1 mRNA induced apoptosis in cultured ARPE-19 cells. TALEN KO in zebrafish was lethal 11 days post...

Data from: Inferring heterogeneous evolutionary processes through time: from sequence substitution to phylogeography

Filip Bielejec, Philippe Lemey, Guy Baele, Andrew Rambaut & Marc A. Suchard
Molecular phylogenetic and phylogeographic reconstructions generally assume time-homogeneous substitution processes. Motivated by computational convenience, this assumption sacrifices biological realism and offers little opportunity to uncover the temporal dynamics in evolutionary histories. Here, we propose an evolutionary approach that explicitly relaxes the time-homogeneity assumption by allowing the specification of different infinitesimal substitution rate matrices across different time intervals, called epochs, along the evolutionary history. We focus on an epoch model implementation in a Bayesian inference framework...

A cross-sectional study of nemaline myopathy supplementary figures

Kimberly Amburgey, Meryl Acker, Samia Saeed, Reshma Amin, Alan H. Beggs, Carsten G. Bönneman, Michael Brudno, Andrei Constantinescu, Johannaz Dastgir, Mamadou Diallo, Casie A. Genetti, Michael Glueck, Stacy Hewson, Courtney Hum, Minal S. Jain, Michael W. Lawlor, Oscar H. Mayer, Leslie Nelson, Nicole Sultanum, Faiza Syed, Tuyen Tran, Ching H. Wang & James J. Dowling
Objective: Nemaline myopathy (NM) is a rare neuromuscular condition with clinical and genetic heterogeneity. To establish disease natural history, we performed a cross-sectional study of NM, complemented by longitudinal assessment and exploration of pilot outcome measures. Methods: Fifty-seven individuals with NM were recruited at two family workshops, including 16 examined at both time points. Subjects were evaluated by clinical history and physical examination. Functional outcome measures included the Motor Function Measure (MFM), pulmonary function tests...

Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells

Clint Allen
Failed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. This approach may still be limited by the presence of immunosuppressive myeloid populations. Here we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. Treatment of syngeneic tumors...

Data from: Genome-wide evolutionary dynamics of influenza B viruses on a global scale

Pinky Langat, Jayna Raghwani, Gytis Dudas, Thomas A. Bowden, Stephanie Edwards, Astrid Gall, Trevor Bedford, Andrew Rambaut, Rodney S. Daniels, Colin A. Russell, Oliver G. Pybus, John McCauley, Paul Kellam & Simon J. Watson
The global-scale epidemiology and genome-wide evolutionary dynamics of influenza B remain poorly understood compared with influenza A viruses. We compiled a spatio-temporally comprehensive dataset of influenza B viruses, comprising over 2,500 genomes sampled worldwide between 1987 and 2015, including 382 newly-sequenced genomes that fill substantial gaps in previous molecular surveillance studies. Our contributed data increase the number of available influenza B virus genomes in Europe, Africa and Central Asia, improving the global context to study...

Data from: Marking mosquitoes in their natural larval sites using 2H-enriched water: a promising approach for tracking over extended temporal and spatial scales

Roy Faiman, Adama Dao, Alpha Yaro, Moussa Diallo, Samake Djibril, Zana L. Sonogo, Yossi Ousmane, Margerie Sullivan, Laura Veru, Benjamin Krajacich, Asha Krishna, Joy Matthews, Christine France, Gabriel Hamer, Keith Hobson & Tovi Lehmann
1. Background. Tracking mosquitoes using current methods of mark-release-recapture are limited to small spatial and temporal scales exposing major gaps in understanding long-range movements and extended survival. Novel approaches to track mosquitoes may yield fresh insights into their biology which improves intervention activities to reduce disease transmission. Stable isotope enrichment of natural mosquito breeding sites allows large-scale marking of wild mosquitoes absent human handling. Mosquito larvae that develop in 2H-enriched water are expected to be...

Data from: A new versatile primer set targeting a short fragment of the mitochondrial COI region for metabarcoding metazoan diversity: application for characterizing coral reef fish gut contents

Matthieu Leray, Joy Y. Yang, Christopher P. Meyer, Suzanne C. Mills, Natalia Agudelo, Ranwez Vincent, Joel T. Boehm & Ryuji J. Machida
Introduction: The PCR-based analysis of homologous genes has become one of the most powerful approaches for species detection and identification, particularly with the recent availability of Next Generation Sequencing platforms (NGS) making it possible to identify species composition from a broad range of environmental samples. Identifying species from these samples relies on the ability to match sequences with reference barcodes for taxonomic identification. Unfortunately, most studies of environmental samples have targeted ribosomal markers, despite the...

Data from: Quantifying hummingbird preference for floral trait combinations: the role of selection on trait interactions in the evolution of pollination syndromes

Charles B. Fenster, Richard J. Reynolds, Christopher W. Williams, Robert Makowsky & Michele R. Dudash
Darwin recognized the flower's importance for the study of adaptation and emphasized that the flower's functionality reflects the coordinated action of multiple traits. Here we use a multi-trait manipulative approach to quantify the potential role of selection acting on floral trait combinations underlying the divergence and maintenance of three related North American species of Silene (Caryophyllaceae). We artificially generated 48 plant phenotypes corresponding to all combinations of key attractive traits differing among the three Silene...

Harnessing clinical annotations to improve deep learning performance in prostate segmentation

Karthik V. Sarma, Alex G. Raman, Nikhil J. Dhinagar, Alan M. Priester, Stephanie Harmon, Thomas Sanford, Sherif Mehralivand, Baris Turkbey, Leonard S. Marks, Steven S. Raman, William Speier & Corey W. Arnold
Purpose Developing large-scale datasets with research-quality annotations is challenging due to the high cost of refining clinically generated markup into high precision annotations. We evaluated the direct use of a large dataset with only clinically generated annotations in development of high-performance segmentation models for small research-quality challenge datasets. Materials and methods We used a large retrospective dataset from our institution comprised of 1,620 clinically generated segmentations, and two challenge datasets (PROMISE12: 50 patients, ProstateX-2: 99...

Neurofilament light as a biomarker in traumatic brain injury

Pashtun Shahim, Adam Politis, Andre Van Der Merwe, Brian Moore, Yi-Yu Chou, Dzung Pham, John Butman, Ramon Diaz-Arrastia, Jessica Gill, David Brody, Henrik Zetterberg, Kaj Blennow & Leighton Chan
Objective: To determine whether serum neurofilament light (NfL) correlates with CSF NfL, traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) estimates of traumatic axonal injury (TAI). Methods: Participants were prospectively enrolled in Sweden and the United States between 2011 and 2019. The Swedish cohort included 45 hockey players with acute concussion sampled at 6 days, 31 with repetitive concussion with persistent postconcussive symptoms (PCS) assessed with paired CSF and...

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