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Articles 1891 - 1920 of 20215
Full-Text Articles in Entire DC Network
Barcoded Sars-Cov-2 Viruses Define The Impact Of Duration And Route Of Exposure On The Transmission Bottleneck In A Hamster Model, Reed Trende, Tamarand L Darling, Tianyu Gan, David Wang, Adrianus C M Boon
Barcoded Sars-Cov-2 Viruses Define The Impact Of Duration And Route Of Exposure On The Transmission Bottleneck In A Hamster Model, Reed Trende, Tamarand L Darling, Tianyu Gan, David Wang, Adrianus C M Boon
2020-Current year OA Pubs
The transmission bottleneck, defined as the number of viruses shed from one host to infect another, is an important determinant of the rate of virus evolution and the level of immunity required to protect against virus transmission. Despite its importance, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission bottleneck remains poorly characterized. We adapted a SARS-CoV-2 reverse genetics system to generate a pool of >200 isogenic SARS-CoV-2 viruses harboring specific 6-nucleotide barcodes, infected donor hamsters with this pool, and exposed contact hamsters to paired infected donors, varying the duration and route of exposure. Following exposure, the nasal turbinates, trachea, …
Germline Predisposition In Multiple Myeloma, Fernanda Martins Rodrigues, Yize Li, Erik Storrs, Michael C Wendl, Reyka G Jayasinghe, Mark Fiala, John F Dipersio, Ravi Vij, Li Ding, Et Al.
Germline Predisposition In Multiple Myeloma, Fernanda Martins Rodrigues, Yize Li, Erik Storrs, Michael C Wendl, Reyka G Jayasinghe, Mark Fiala, John F Dipersio, Ravi Vij, Li Ding, Et Al.
2020-Current year OA Pubs
We present a study of rare germline predisposition variants in 954 unrelated individuals with multiple myeloma (MM) and 82 MM families. Using a candidate gene approach, we identified such variants across all age groups in 9.1% of sporadic and 18% of familial cases. Implicated genes included genes suggested in other MM risk studies as potential risk genes (
Recommendations For Interdisciplinary Research Collaboration For Early Career Dissemination And Implementation Researchers: A Multi-Phase Study, Hannah G Lane, Sallie D Allgood, Julie Schexnayder, Hayden B Bosworth, Ana A Baumann, Allison A Lewinski
Recommendations For Interdisciplinary Research Collaboration For Early Career Dissemination And Implementation Researchers: A Multi-Phase Study, Hannah G Lane, Sallie D Allgood, Julie Schexnayder, Hayden B Bosworth, Ana A Baumann, Allison A Lewinski
2020-Current year OA Pubs
INTRODUCTION: Dissemination and implementation (D&I) scientists are key members of collaborative, interdisciplinary clinical and translational research teams. Yet, early career D&I researchers (ECRs) have few guidelines for cultivating productive research collaborations. We developed recommendations for ECRs in D&I when serving as collaborators or co-investigators.
METHODS: We employed a consensus-building approach: (1) group discussions to identify 3 areas of interest: "Marketing yourself" (describing your value to non-D&I collaborators), "Collaboration considerations
RESULTS: Forty-four D&I researchers completed the first survey, 12 of whom attended one of three focus groups. Twenty-nine D&I researchers completed the second survey (
CONCLUSIONS: Research collaborations are essential in …
Comparison Of Sampling And Culture Methods For The Recovery Of Yeast From Hospital Surfaces, Allison R Eberly, Alyssa M Valencia, Kate Peacock, David Mcdonald, Tiffany Hink, Carleigh Samuels, Lucy Vogt, Yao-Peng Xue, Maggie Newberry, Caroline A O'Neil, Gautam Dantas, Jennie H Kwon
Comparison Of Sampling And Culture Methods For The Recovery Of Yeast From Hospital Surfaces, Allison R Eberly, Alyssa M Valencia, Kate Peacock, David Mcdonald, Tiffany Hink, Carleigh Samuels, Lucy Vogt, Yao-Peng Xue, Maggie Newberry, Caroline A O'Neil, Gautam Dantas, Jennie H Kwon
2020-Current year OA Pubs
OBJECTIVE: To compare the recovery of yeast from hospital surfaces from two different collection methods: Eswab moistened with molecular water, and premoistened stick-mounted sponge.
DESIGN: Comparison of collection methods for the recovery of yeast in the hospital environment.
SETTING: This study took place at intensive care units of a large academic medical center.
Molecular Determinants Of Condensate Composition, Alex S Holehouse, Simon Alberti
Molecular Determinants Of Condensate Composition, Alex S Holehouse, Simon Alberti
2020-Current year OA Pubs
Cells use membraneless compartments to organize their interiors, and recent research has begun to uncover the molecular principles underlying their assembly. Here, we explore how site-specific and chemically specific interactions shape the properties and functions of condensates. Site-specific recruitment involves precise interactions at specific sites driven by partially or fully structured interfaces. In contrast, chemically specific recruitment is driven by complementary chemical interactions without the requirement for a persistent bound-state structure. We propose that site-specific and chemically specific interactions work together to determine the composition of condensates, facilitate biochemical reactions, and regulate enzymatic activities linked to metabolism, signaling, and gene …
Rsk1 Is An Exploitable Dependency In Myeloproliferative Neoplasms And Secondary Acute Myeloid Leukemia, Tim Kong, Angelo B A Laranjeira, Christopher T Letson, Layow Yu, Shuyang Lin, Jared S Fowles, Daniel A C Fisher, Sherwin Ng, Wei Yang, Fan He, Jingxian Liu, Alexander B Kim, Maggie J Cox, Mary C Fulbright, Stacey L Rentschler, Li Ding, Grant A Challen, Stephen T Oh, Et Al.
Rsk1 Is An Exploitable Dependency In Myeloproliferative Neoplasms And Secondary Acute Myeloid Leukemia, Tim Kong, Angelo B A Laranjeira, Christopher T Letson, Layow Yu, Shuyang Lin, Jared S Fowles, Daniel A C Fisher, Sherwin Ng, Wei Yang, Fan He, Jingxian Liu, Alexander B Kim, Maggie J Cox, Mary C Fulbright, Stacey L Rentschler, Li Ding, Grant A Challen, Stephen T Oh, Et Al.
2020-Current year OA Pubs
Myeloid malignancies are heterogenous disorders characterized by distinct molecular drivers but share convergence of oncogenic signaling pathways and propagation by ripe pro-inflammatory niches. Here, we establish a comprehensive transcriptional atlas across the spectrum of myeloproliferative neoplasms (MPN) and secondary acute myeloid leukemia (sAML) through RNA-sequencing of 158 primary samples encompassing CD34+ hematopoietic stem/progenitor cells and CD14+ monocytes. Supported by mass cytometry (CyTOF) profiling, we reveal aberrant networks of PI3K/AKT/mTOR signalling and NFκB-mediated hyper-inflammation. Combining ATAC-Seq, CUT&Tag, RNA-seq, and CyTOF, we demonstrate that targeting of ribosomal protein S6 kinase A1 (RSK1) suppresses NFκB activation and diminishes pro-inflammatory mediators including tumor necrosis …
N-Glycosylation In The Serpin Domain Of The C1-Esterase Inhibitor In Hereditary Angioedema, Zhen Ren, John Bao, Shuangxia Zhao, Nicola Pozzi, H. James Wedner, John P. Atkinson
N-Glycosylation In The Serpin Domain Of The C1-Esterase Inhibitor In Hereditary Angioedema, Zhen Ren, John Bao, Shuangxia Zhao, Nicola Pozzi, H. James Wedner, John P. Atkinson
2020-Current year OA Pubs
Hereditary angioedema is an autosomal dominant disorder caused by defects in C1-esterase inhibitor (C1-INH), resulting in poorly controlled activation of the kallikrein-kinin system and bradykinin overproduction. C1-INH is a heavily glycosylated protein in the serine protease inhibitor (SERPIN) family, yet the role of these glycosylation sites remains unclear. To elucidate the functional impact of N-glycosylation in the SERPIN domain of C1-INH, we engineered 4 sets consisting of 26 variants at or near the N-linked sequon (NXS/T). Among these, 6 are reported in patients with hereditary angioedema and 5 are known C1-INH variants without accessible clinical histories. We systematically evaluated their …
A Yeast-Based Oral Therapeutic Delivers Immune Checkpoint Inhibitors To Reduce Intestinal Tumor Burden, Olivia N Rebeck, Miranda J Wallace, Jerome Prusa, Jie Ning, Esse M Evbuomwan, Sunaina Rengarajan, Lemoyne Habimana-Griffin, Suryang Kwak, David Zahrah, Jason Tung, James Liao, Bejan Mahmud, Skye R S Fishbein, Erick S Ramirez Tovar, Rehan Mehta, Bin Wang, Mark G Gorelik, Gautam Dantas, Et Al.
A Yeast-Based Oral Therapeutic Delivers Immune Checkpoint Inhibitors To Reduce Intestinal Tumor Burden, Olivia N Rebeck, Miranda J Wallace, Jerome Prusa, Jie Ning, Esse M Evbuomwan, Sunaina Rengarajan, Lemoyne Habimana-Griffin, Suryang Kwak, David Zahrah, Jason Tung, James Liao, Bejan Mahmud, Skye R S Fishbein, Erick S Ramirez Tovar, Rehan Mehta, Bin Wang, Mark G Gorelik, Gautam Dantas, Et Al.
2020-Current year OA Pubs
Engineered probiotics are an emerging platform for in situ delivery of therapeutics to the gut. Herein, we developed an orally administered, yeast-based therapeutic delivery system to deliver next-generation immune checkpoint inhibitor (ICI) proteins directly to gastrointestinal tumors. We engineered Saccharomyces cerevisiae var. boulardii (Sb), a probiotic yeast with high genetic tractability and innate anticancer activity, to secrete "miniature" antibody variants that target programmed death ligand 1 (Sb_haPD-1). When tested in an ICI-refractory colorectal cancer (CRC) mouse model, Sb_haPD-1 significantly reduced intestinal tumor burden and resulted in significant shifts to the immune cell profile and microbiome composition. This oral therapeutic platform …
A Human Single-Neuron Dataset For Object Recognition, Runnan Cao, Peter Brunner, Nicholas J Brandmeir, Jon T Willie, Shuo Wang
A Human Single-Neuron Dataset For Object Recognition, Runnan Cao, Peter Brunner, Nicholas J Brandmeir, Jon T Willie, Shuo Wang
2020-Current year OA Pubs
Object recognition is fundamental to how we interact with and interpret the world around us. The human amygdala and hippocampus play a key role in object recognition, contributing to both the encoding and retrieval of visual information. Here, we recorded single-neuron activity from the human amygdala and hippocampus when neurosurgical epilepsy patients performed a one-back task using naturalistic object stimuli. We employed two sets of naturalistic object images from leading datasets extensively used in primate neural recordings and computer vision models: we recorded 1204 neurons using the ImageNet stimuli, which included broader object categories (10 different images per category for …
Active Learning Of Enhancers And Silencers In The Developing Neural Retina, Ryan Z Friedman, Avinash Ramu, Sara Lichtarge, Yawei Wu, Lloyd Tripp, Daniel Lyon, Connie A Myers, David M Granas, Maria Gause, Joseph C Corbo, Barak A Cohen, Michael A White
Active Learning Of Enhancers And Silencers In The Developing Neural Retina, Ryan Z Friedman, Avinash Ramu, Sara Lichtarge, Yawei Wu, Lloyd Tripp, Daniel Lyon, Connie A Myers, David M Granas, Maria Gause, Joseph C Corbo, Barak A Cohen, Michael A White
2020-Current year OA Pubs
Deep learning is a promising strategy for modeling cis-regulatory elements. However, models trained on genomic sequences often fail to explain why the same transcription factor can activate or repress transcription in different contexts. To address this limitation, we developed an active learning approach to train models that distinguish between enhancers and silencers composed of binding sites for the photoreceptor transcription factor cone-rod homeobox (CRX). After training the model on nearly all bound CRX sites from the genome, we coupled synthetic biology with uncertainty sampling to generate additional rounds of informative training data. This allowed us to iteratively train models on …
Helminth Infections Affect Host Immune Responses To Viral Infections And Vaccines, Juan García-Bernalt Diego, Pritesh Desai, Stephen T Yeung, Payal Damani-Yokota, Kamal M Khanna, Michael S Diamond, Michael Schotsaert
Helminth Infections Affect Host Immune Responses To Viral Infections And Vaccines, Juan García-Bernalt Diego, Pritesh Desai, Stephen T Yeung, Payal Damani-Yokota, Kamal M Khanna, Michael S Diamond, Michael Schotsaert
2020-Current year OA Pubs
Helminths are highly prevalent in many regions of the world. Due to the chronic nature of most helminth infections, these parasites are proficient immunomodulators of their hosts. This modulation often leads to skewed or even impaired immune responses against unrelated antigens, such as viruses and vaccines, which can be both beneficial and detrimental for the host. The extent of these effects and the impact on the outcomes of viral infection depends on a variety of factors including timing and tropism of both infections, pathological mechanisms, genetic background, and environmental factors. In this review, we dissect these complex interactions between virus …
Engaging Dystonia Networks With Subthalamic Stimulation, Konstantin Butenko, Evan M Gordon, Nico U F Dosenbach, Et Al.
Engaging Dystonia Networks With Subthalamic Stimulation, Konstantin Butenko, Evan M Gordon, Nico U F Dosenbach, Et Al.
2020-Current year OA Pubs
Deep brain stimulation is an efficacious treatment for dystonia. While the internal pallidum serves as the primary target, recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its surroundings have not been studied in depth. Indeed, historical targets that have been used for surgical treatment of dystonia are directly adjacent to the STN. Further, multiple types of dystonia exist, and outcomes are variable, suggesting that not all types would profit maximally from the same target. Therefore, a thorough investigation of neural substrates underlying stimulation effects on dystonia signs and symptoms is warranted. …
Animal Models Of Non-Respiratory, Post-Acute Sequelae Of Covid-19, Abigail Vanderheiden, Michael S Diamond
Animal Models Of Non-Respiratory, Post-Acute Sequelae Of Covid-19, Abigail Vanderheiden, Michael S Diamond
2020-Current year OA Pubs
Post-acute sequelae of COVID-19 (PASC) are a diverse set of symptoms and syndromes driven by dysfunction of multiple organ systems that can persist for years and negatively impact the quality of life for millions of individuals. We currently lack specific therapeutics for patients with PASC, due in part to an incomplete understanding of its pathogenesis, especially for non-pulmonary sequelae. Here, we discuss three animal models that have been utilized to investigate PASC: non-human primates (NHPs), hamsters, and mice. We focus on neurological, gastrointestinal, and cardiovascular PASC and highlight advances in mechanistic insight that have been made using these animal models, …
Sialylated Igg Induces The Transcription Factor Rest In Alveolar Macrophages To Protect Against Lung Inflammation And Severe Influenza Disease, Saborni Chakraborty, Derek E Byers, Philip A Mudd, Michael S Diamond, Et Al.
Sialylated Igg Induces The Transcription Factor Rest In Alveolar Macrophages To Protect Against Lung Inflammation And Severe Influenza Disease, Saborni Chakraborty, Derek E Byers, Philip A Mudd, Michael S Diamond, Et Al.
2020-Current year OA Pubs
While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model. Mechanistic studies show that sialylated IgG mediated this protection by inducing the transcription factor repressor element-1 silencing transcription factor (REST), which repressed nuclear factor κB (NF-κB)-driven responses, preventing severe lung …
Tolerability And Long-Term Disease Control By Ighv Mutation Status Among Patients With Cll On Ibrutinib Arm Of E1912, Tait D Shanafelt, Amanda F Cashen, Et Al.
Tolerability And Long-Term Disease Control By Ighv Mutation Status Among Patients With Cll On Ibrutinib Arm Of E1912, Tait D Shanafelt, Amanda F Cashen, Et Al.
2020-Current year OA Pubs
No abstract provided.
Daily Glucocorticoids Promote Glioblastoma Growth And Circadian Synchrony To The Host, Maria F Gonzalez-Aponte, Anna R Damato, Tatiana Simon, Nigina Aripova, Fabrizio Darby, Myung Sik Jeon, Jingqin Luo, Joshua B Rubin, Erik D Herzog
Daily Glucocorticoids Promote Glioblastoma Growth And Circadian Synchrony To The Host, Maria F Gonzalez-Aponte, Anna R Damato, Tatiana Simon, Nigina Aripova, Fabrizio Darby, Myung Sik Jeon, Jingqin Luo, Joshua B Rubin, Erik D Herzog
2020-Current year OA Pubs
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with a poor prognosis despite aggressive therapy. Here, we hypothesized that daily host signaling regulates tumor growth and synchronizes circadian rhythms in GBM. We find daily glucocorticoids promote or suppress GBM growth through glucocorticoid receptor (GR) signaling depending on time of day and the clock genes, Bmal1 and Cry. Blocking circadian signals, like vasoactive intestinal peptide or glucocorticoids, dramatically slows GBM growth and disease progression. Analysis of human GBM samples from The Cancer Genome Atlas (TCGA) shows that high GR expression significantly increases hazard of mortality. Finally, mouse …
Cannabis Use Characteristics And Associations With Problematic Use Outcomes, Quitting-Related Factors, And Mental Health Among Us Young Adults, Carla J Berg, Cassidy R Loparco, Katelyn F Romm, Yuxian Cui, Darcey M Mccready, Yan Wang, Y Tony Yang, Hannah S Szlyk, Erin Kasson, Rishika Chakraborty, Patricia A Cavazos-Rehg
Cannabis Use Characteristics And Associations With Problematic Use Outcomes, Quitting-Related Factors, And Mental Health Among Us Young Adults, Carla J Berg, Cassidy R Loparco, Katelyn F Romm, Yuxian Cui, Darcey M Mccready, Yan Wang, Y Tony Yang, Hannah S Szlyk, Erin Kasson, Rishika Chakraborty, Patricia A Cavazos-Rehg
2020-Current year OA Pubs
OBJECTIVE: Given the changes in trends of cannabis use (e.g., product types), this study examined latent classes of young adult use and associations with use-related outcomes.
METHODS: We analyzed 2023 survey data among 4,031 US young adults (M
RESULTS: LCA identified 4 classes of cannabis use frequency and types used: 'infrequent-herb/edibles' (41.4%), 'frequent-herb' (16.8%), 'moderate-herb' (28.0%), and 'moderate-oil/other' (13.8%). In multivariable analyses (referent group: 'moderate-herb' class), 'frequent-herb' reported less problematic use (B=-0.18, 95%CI=-0.30, -0.07), while 'moderate-oil/other' reported greater (B = 0.39, 95%CI = 0.27, 0.51). 'Infrequent-herb/edibles' had lower odds of driving post-use of cannabis (aOR = 0.28, 95%CI = 0.22, …
The Effect Of Transcutaneous Auricular Vagus Nerve Stimulation On Cardiovascular Function In Subarachnoid Hemorrhage Patients: A Randomized Trial, Gansheng Tan, Anna L Huguenard, Kara M Donovan, Phillip Demarest, Xiaoxuan Liu, Ziwei Li, Markus Adamek, Kory Lavine, Ananthv K Vellimana, Terrance T Kummer, Joshua W Osbun, Gregory J Zipfel, Peter Brunner, Eric C Leuthardt
The Effect Of Transcutaneous Auricular Vagus Nerve Stimulation On Cardiovascular Function In Subarachnoid Hemorrhage Patients: A Randomized Trial, Gansheng Tan, Anna L Huguenard, Kara M Donovan, Phillip Demarest, Xiaoxuan Liu, Ziwei Li, Markus Adamek, Kory Lavine, Ananthv K Vellimana, Terrance T Kummer, Joshua W Osbun, Gregory J Zipfel, Peter Brunner, Eric C Leuthardt
2020-Current year OA Pubs
BACKGROUND: Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients, like those with SAH, have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this …
Cancer-Related Health Behaviors During The Covid 19 Pandemic In Geographically Diverse Samples Across The Us, Breanna B Greteman, Bettina F Drake, Kia L Davis, Et Al.
Cancer-Related Health Behaviors During The Covid 19 Pandemic In Geographically Diverse Samples Across The Us, Breanna B Greteman, Bettina F Drake, Kia L Davis, Et Al.
2020-Current year OA Pubs
BACKGROUND: The COVID-19 pandemic involved business closures (e.g., gyms), social distancing policies, and prolonged stressful situations that may have impacted engagement in health behaviors. Our study assessed changes in cancer-related health behaviors during the pandemic, specifically physical activity, fruit/vegetable intake, smoking/tobacco use, and alcohol consumption.
METHODS: Eight cancer centers administered mailed/web-based/telephone surveys between June 2020 and March 2021. Surveys assessed demographics, perceptions on social distancing, and self-reported changes of behaviors (less/same/more) associated with cancer prevention or risk, e.g., physical activity, fruit/vegetable intake, tobacco/smoking use, and alcohol consumption. Descriptive analyses and logistic regression models assessed association of variables with behavior change. …
Decreased Lipidated Apoe-Receptor Interactions Confer Protection Against Pathogenicity Of Apoe And Its Lipid Cargoes In Lysosomes, Jing L Guo, Alexandra Litvinchuk, David M Holtzman, Et Al.
Decreased Lipidated Apoe-Receptor Interactions Confer Protection Against Pathogenicity Of Apoe And Its Lipid Cargoes In Lysosomes, Jing L Guo, Alexandra Litvinchuk, David M Holtzman, Et Al.
2020-Current year OA Pubs
While apolipoprotein E (APOE) is the strongest genetic modifier for late-onset Alzheimer's disease (LOAD), the molecular mechanisms underlying isoform-dependent risk and the relevance of ApoE-associated lipids remain elusive. Here, we report that impaired low-density lipoprotein (LDL) receptor (LDLR) binding of lipidated ApoE2 (lipApoE2) avoids LDLR recycling defects observed with lipApoE3/E4 and decreases the uptake of cholesteryl esters (CEs), which are lipids linked to neurodegeneration. In human neurons, the addition of ApoE carrying polyunsaturated fatty acids (PUFAs)-CE revealed an allelic series (ApoE4 > ApoE3 > ApoE2) associated with lipofuscinosis, an age-related lysosomal pathology resulting from lipid peroxidation. Lipofuscin increased lysosomal accumulation of tau …
Biophysical Mapping Of Trem2-Ligand Interactions Reveals Shared Surfaces For Engagement Of Multiple Alzheimer's Disease Ligands, Jessica A Greven, Joshua R Wydra, Rory A Greer, Cynthia Zhi, David A Price, Jordyn D Svoboda, Christopher L M Camitta, Mya Washington, Daisy W Leung, Yuhua Song, Jen Alexander-Brett, Tom J Brett
Biophysical Mapping Of Trem2-Ligand Interactions Reveals Shared Surfaces For Engagement Of Multiple Alzheimer's Disease Ligands, Jessica A Greven, Joshua R Wydra, Rory A Greer, Cynthia Zhi, David A Price, Jordyn D Svoboda, Christopher L M Camitta, Mya Washington, Daisy W Leung, Yuhua Song, Jen Alexander-Brett, Tom J Brett
2020-Current year OA Pubs
TREM2 is a signaling receptor expressed on microglia that has emerged as an important drug target for Alzheimer's disease and other neurodegenerative diseases. While a number of TREM2 ligands have been identified, little is known regarding the structural details of how they engage. To better understand this, we created a protein library of 28 different TREM2 variants that could be used to map interactions with various ligands using biolayer interferometry. The variants are located in previously identified putative binding surfaces on TREM2 called the hydrophobic site, basic site, and site 2. We found that mutations to the hydrophobic site ablated …
A Sequencing Overview Of Malignant Peripheral Nerve Sheath Tumors: Findings And Implications For Treatment, Kangwen Xiao, Kuangying Yang, Angela C Hirbe
A Sequencing Overview Of Malignant Peripheral Nerve Sheath Tumors: Findings And Implications For Treatment, Kangwen Xiao, Kuangying Yang, Angela C Hirbe
2020-Current year OA Pubs
Malignant peripheral nerve sheath tumors (MPNSTs) are rare but aggressive malignancies with a low 5-year survival rate despite current treatments. MPNSTs frequently harbor mutations in key genes such as
Commensal-Pathogen Dynamics Structure Disease Outcomes During Clostridioides Difficile Colonization, Skye R S Fishbein, Anna L Deveaux, Sakshi Khanna, Aura L Ferreiro, James Liao, Wesley Agee, Jie Ning, Bejan Mahmud, Miranda J Wallace, Tiffany Hink, Kimberly A Reske, Candice Cass, Janaki Guruge, Sidh Leekha, Sunaina Rengarajan, Erik R Dubberke, Gautam Dantas
Commensal-Pathogen Dynamics Structure Disease Outcomes During Clostridioides Difficile Colonization, Skye R S Fishbein, Anna L Deveaux, Sakshi Khanna, Aura L Ferreiro, James Liao, Wesley Agee, Jie Ning, Bejan Mahmud, Miranda J Wallace, Tiffany Hink, Kimberly A Reske, Candice Cass, Janaki Guruge, Sidh Leekha, Sunaina Rengarajan, Erik R Dubberke, Gautam Dantas
2020-Current year OA Pubs
Gastrointestinal colonization by Clostridioides difficile is common in healthcare settings and ranges in presentation from asymptomatic carriage to lethal C. difficile infection (CDI). We used a systems biology approach to investigate why patients colonized with C. difficile have a range of clinical outcomes. Microbiota humanization of germ-free mice with fecal samples from toxigenic C. difficile carriers revealed a spectrum of virulence among clinically prevalent clade 1 lineages and identified candidate taxa, including Blautia, as markers of stable colonization. Using gnotobiotic mice engrafted with defined human microbiota, we validated strain-specific CDI severity across clade 1 strains isolated from patients. Mice engrafted …
Development Of A Metabolome-Based Respiratory Infection Prognostic During Covid-19 Arrival, John I Robinson, Laura R Marks, Andrew L Hinton, Jane A O'Halloran, Charles W Goss, Peter J Mucha, Jeffrey P Henderson
Development Of A Metabolome-Based Respiratory Infection Prognostic During Covid-19 Arrival, John I Robinson, Laura R Marks, Andrew L Hinton, Jane A O'Halloran, Charles W Goss, Peter J Mucha, Jeffrey P Henderson
2020-Current year OA Pubs
In a new respiratory virus pandemic, optimizing allocation of scarce medical resources becomes an urgent challenge. Infection prognosis takes on particular importance when allocating scarce antiviral antibodies and drugs, which are most effective when administered before the onset of severe disease. During arrival of the COVID-19 pandemic to the United States in 2020, we conducted a prognostic biomarker discovery and validation effort based upon metabolomic profiling with a liquid-chromatography-mass spectrometer (LC-MS) type used clinically for rapid toxicology. We obtained urine specimens from 163 patients presenting for evaluation. We obtained LC-MS profiles in the initial cohort and used machine learning methods …
Leveraging A New Data Resource To Define The Response Of Cryptococcus Neoformans To Environmental Signals, Yu Sung Kang, Jeffery Jung, Holly L Brown, Chase Mateusiak, Tamara L Doering, Michael R Brent
Leveraging A New Data Resource To Define The Response Of Cryptococcus Neoformans To Environmental Signals, Yu Sung Kang, Jeffery Jung, Holly L Brown, Chase Mateusiak, Tamara L Doering, Michael R Brent
2020-Current year OA Pubs
Cryptococcus neoformans is an opportunistic fungal pathogen with a polysaccharide capsule that becomes greatly enlarged in the mammalian host and during in vitro growth under host-like conditions. To understand how individual environmental signals affect capsule size and gene expression, we grew cells in all combinations of 5 signals implicated in capsule size and systematically measured cell and capsule sizes. We also sampled these cultures over time and performed RNA-seq in quadruplicate, yielding 881 RNA-seq samples. Analysis of the resulting data sets showed that capsule induction in tissue culture medium, typically used to represent host-like conditions, requires the presence of either …
Waste Clearance Shapes Aging Brain Health, Li-Feng Jiang-Xie, Antoine Drieu, Jonathan Kipnis
Waste Clearance Shapes Aging Brain Health, Li-Feng Jiang-Xie, Antoine Drieu, Jonathan Kipnis
2020-Current year OA Pubs
Brain health is intimately connected to fluid flow dynamics that cleanse the brain of potentially harmful waste material. This system is regulated by vascular dynamics, the maintenance of perivascular spaces, neural activity during sleep, and lymphatic drainage in the meningeal layers. However, aging can impinge on each of these layers of regulation, leading to impaired brain cleansing and the emergence of various age-associated neurological disorders, including Alzheimer's and Parkinson's diseases. Understanding the intricacies of fluid flow regulation in the brain and how this becomes altered with age could reveal new targets and therapeutic strategies to tackle age-associated neurological decline.
Ubr5 In Tumor Biology: Exploring Mechanisms Of Immune Regulation And Possible Therapeutic Implications In Mpnst, Diana Akinyi Odhiambo, Selina Fan, Angela C Hirbe
Ubr5 In Tumor Biology: Exploring Mechanisms Of Immune Regulation And Possible Therapeutic Implications In Mpnst, Diana Akinyi Odhiambo, Selina Fan, Angela C Hirbe
2020-Current year OA Pubs
Malignant peripheral nerve sheath tumor (MPNST) is a rare but aggressive soft-tissue sarcoma characterized by poor response to therapy. The primary treatment remains surgical resection with negative margins. Nonetheless, in the setting of neurofibromatosis type 1 (NF1), the five-year survival rate is at 20-50%, with recurrence occurring in up to 50% of individuals. For patients with metastatic and unresectable disease, current treatment options include cytotoxic chemotherapy, which offers minimal benefit, and most patients die within five years of diagnosis. Despite advances in targeted therapy focusing on inhibiting Ras signaling and its downstream effectors, clinical trials report minimal clinical benefit, highlighting …
Analytical Performance Of Oncoprism-Hnscc, An Rna-Based Assay To Inform Immune Checkpoint Inhibitor Treatment Decisions For Recurrent/Metastatic Head And Neck Squamous Cell Carcinoma, Jeffrey Hiken, Jon Earls, Kevin C Flanagan, Rachel L Wellinghoff, Michelle Ponder, David N Messina, Jarret I Glasscock, Eric J Duncavage
Analytical Performance Of Oncoprism-Hnscc, An Rna-Based Assay To Inform Immune Checkpoint Inhibitor Treatment Decisions For Recurrent/Metastatic Head And Neck Squamous Cell Carcinoma, Jeffrey Hiken, Jon Earls, Kevin C Flanagan, Rachel L Wellinghoff, Michelle Ponder, David N Messina, Jarret I Glasscock, Eric J Duncavage
2020-Current year OA Pubs
BACKGROUND: While immune checkpoint inhibitor (ICI) therapies can significantly improve outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC), only about 15-20% benefit from such treatments. Clinical tests that guide the use of ICIs are therefore critically needed. OncoPrism-HNSCC was developed to address this need. The assay combines next generation RNA sequencing-based immunomodulatory gene expression signatures with machine learning algorithms to generate an OncoPrism score that classifies patients as having low, medium, or high likelihood of disease control in response to ICI treatment. Also, OncoPrism-HNSCC leverages the same FFPE patient tumor RNA used for ICI response prediction …
Education Strategies Are The Most Commonly Used In Pediatric Rehabilitation Implementation Research: A Scoping Review, Sahar Ghahramani, Sophia C Larson, Allison J L'Hotta, Kelly M Harris, Kim Lipsey, Elvin H Geng, Lisa A Juckett, Catherine R Hoyt
Education Strategies Are The Most Commonly Used In Pediatric Rehabilitation Implementation Research: A Scoping Review, Sahar Ghahramani, Sophia C Larson, Allison J L'Hotta, Kelly M Harris, Kim Lipsey, Elvin H Geng, Lisa A Juckett, Catherine R Hoyt
2020-Current year OA Pubs
BACKGROUND: Approximately one in six children has a disability, and effective, evidence-based rehabilitation can ameliorate the impact of these conditions over the lifespan. However, implementing interventions in real-world settings remains a challenge. This scoping review aimed to summarize the characteristics, implementation strategies, and outcomes of implementation studies in pediatric rehabilitation.
METHODS: A comprehensive search was conducted in PubMed/MEDLINE, EMBASE, CINAHL, SCOPUS, and Web of Science from the database inception to December 2, 2022. Studies testing implementation strategies in pediatric rehabilitation interventions were included. Data extracted included study characteristics (e.g., country, intervention type, field of rehabilitation), implementation strategies characterized using the …
Functional Performance Of Patients With Stroke During Inpatient Rehabilitation: A Cross-Sectional Study Of Home And Access Visits, Melissa J Krauss, Emily Somerville, Callista Poiter, Rebecca M Bollinger, Brianna M Holden, Gabrielle Blenden, Danielle Kretzer, Susan L Stark
Functional Performance Of Patients With Stroke During Inpatient Rehabilitation: A Cross-Sectional Study Of Home And Access Visits, Melissa J Krauss, Emily Somerville, Callista Poiter, Rebecca M Bollinger, Brianna M Holden, Gabrielle Blenden, Danielle Kretzer, Susan L Stark
2020-Current year OA Pubs
BACKGROUND: Home visits prior to inpatient rehabilitation facility (IRF) discharge allow occupational therapists to observe functional abilities among patients with stroke and address barriers that impact daily activities at home. However, home visits prior to IRF discharge are not standard practice due to barriers of time and cost constraints. We explored whether an access visit (visiting the home without the patient) could serve as an alternative to a home visit (with the patient) to anticipate functional abilities at home.
METHODS: We used baseline data from a randomized controlled trial that occurred before and during the COVID-19 pandemic, which caused predischarge …