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Intrinsic And Innate Defenses Of Neurons: Détente With The Herpesviruses, Lynn Enquist, David A. Leib
Intrinsic And Innate Defenses Of Neurons: Détente With The Herpesviruses, Lynn Enquist, David A. Leib
Dartmouth Scholarship
Neuroinvasive herpesviruses have evolved to efficiently infect and establish latency in neurons. The nervous system has limited capability to regenerate, so immune responses therein are carefully regulated to be nondestructive, with dependence on atypical intrinsic and innate defenses. In this article we review studies of some of these noncanonical defense pathways and how herpesvirus gene products counter them, highlighting the contributions that primary neuronal in vitro models have made to our understanding of this field.
Levels Of Infants’ Urinary Arsenic Metabolites Related To Formula Feeding And Weaning With Rice Products Exceeding The Eu Inorganic Arsenic Standard, Antonio J. Signes-Pastor, Jayne V. Woodside, Paul Mcmullan, Karen Mullan, Manus Carey, Margaret R. Karagas, Andrew A. Meharg
Levels Of Infants’ Urinary Arsenic Metabolites Related To Formula Feeding And Weaning With Rice Products Exceeding The Eu Inorganic Arsenic Standard, Antonio J. Signes-Pastor, Jayne V. Woodside, Paul Mcmullan, Karen Mullan, Manus Carey, Margaret R. Karagas, Andrew A. Meharg
Dartmouth Scholarship
Early childhood inorganic arsenic (i-As) exposure is of particular concern since it may adversely impact on lifetime health outcomes. Infants’ urinary arsenic (As) metabolites were analysed in 79 infants by inductively coupled plasma—mass spectrometric detection (IC-ICP-MS) to evaluate i-As exposure pre- and post-weaning. Levels of i-As in rice-based weaning and infants’ foods were also determined to relate to urinary As levels. Higher As levels, especially of monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), were found in urine from formula fed infants compared to those breastfed. Urine from infants post-weaning consuming rice-products resulted in higher urinary MMA and DMA compared to …
A Longitudinal Cline Characterizes The Genetic Structure Of Human Populations In The Tibetan Plateau, Choongwon Jeong, Benjamin M. Peter, Buddha Basnyat, Maniraj Neupane, Geoff Childs, Sienna Craig, John Novembre, Anna Di Rienzo
A Longitudinal Cline Characterizes The Genetic Structure Of Human Populations In The Tibetan Plateau, Choongwon Jeong, Benjamin M. Peter, Buddha Basnyat, Maniraj Neupane, Geoff Childs, Sienna Craig, John Novembre, Anna Di Rienzo
Dartmouth Scholarship
Indigenous populations of the Tibetan plateau have attracted much attention for their good performance at extreme high altitude. Most genetic studies of Tibetan adaptations have used genetic variation data at the genome scale, while genetic inferences about their de- mography and population structure are largely based on uniparental markers. To provide genome-wide information on population structure, we analyzed new and published data of 338 individuals from indigenous populations across the plateau in conjunction with world- wide genetic variation data. We found a clear signal of genetic stratification across the east- west axis within Tibetan samples. Samples from more eastern locations …
Population Effect Model Identifies Gene Expression Predictors Of Survival Outcomes In Lung Adenocarcinoma For Both Caucasian And Asian Patients, Guoshuai Cai, Feifei Xiao, Chao Cheng, Yafang Li, Christopher I. I. Amos, Michael L. Whitfield
Population Effect Model Identifies Gene Expression Predictors Of Survival Outcomes In Lung Adenocarcinoma For Both Caucasian And Asian Patients, Guoshuai Cai, Feifei Xiao, Chao Cheng, Yafang Li, Christopher I. I. Amos, Michael L. Whitfield
Dartmouth Scholarship
Background: We analyzed and integrated transcriptome data from two large studies of lung adenocarcinomas on distinct populations. Our goal was to investigate the variable gene expression alterations between paired tumor-normal tissues and prospectively identify those alterations that can reliably predict lung disease related outcomes across populations. Methods: We developed a mixed model that combined the paired tumor-normal RNA-seq from two populations. Alterations in gene expression common to both populations were detected and validated in two independent DNA microarray datasets. A 10-gene prognosis signature was developed through a l1 penalized regression approach and its prognostic value was evaluated in a third …
Pseudomonas Aeruginosa Alginate Overproduction Promotes Coexistence With Staphylococcus Aureus In A Model Of Cystic Fibrosis Respiratory Infection, Dominique H. Limoli, Gregory B. Whitfield, Tomoe Kitao, Melissa L. Ivey, Michael R. Davis, Nora Grahl, Deborah A. Hogan, Laurence G. Rahme, P. Lynne Howell, George A. O'Toole, Joanna B. Goldberg
Pseudomonas Aeruginosa Alginate Overproduction Promotes Coexistence With Staphylococcus Aureus In A Model Of Cystic Fibrosis Respiratory Infection, Dominique H. Limoli, Gregory B. Whitfield, Tomoe Kitao, Melissa L. Ivey, Michael R. Davis, Nora Grahl, Deborah A. Hogan, Laurence G. Rahme, P. Lynne Howell, George A. O'Toole, Joanna B. Goldberg
Dartmouth Scholarship
While complex intra- and interspecies microbial community dynamics are apparent during chronic infections and likely alter patient health outcomes, our understanding of these interactions is currently limited. For example, Pseudomonas aeruginosa and Staphylococcus aureus are often found to coinfect the lungs of patients with cystic fibrosis (CF), yet these organisms compete under laboratory conditions. Recent observations that coinfection correlates with decreased health outcomes necessitate we develop a greater understanding of these interbacterial interactions. In this study, we tested the hypothesis that P. aeruginosa and/or S. aureus adopts phenotypes that allow coexistence during infection. We compared competitive interactions of P. aeruginosa …
Lactate Dehydrogenase In Toxoplasma Gondii Controls Virulence, Bradyzoite Differentiation, And Chronic Infection, Abdelbaset E. Abdelbaset, Barbara A. Fox, Mohamed H. Karram, Mahmoud R. Abd Ellah, David J. Bzik, Makoto Igarashi
Lactate Dehydrogenase In Toxoplasma Gondii Controls Virulence, Bradyzoite Differentiation, And Chronic Infection, Abdelbaset E. Abdelbaset, Barbara A. Fox, Mohamed H. Karram, Mahmoud R. Abd Ellah, David J. Bzik, Makoto Igarashi
Dartmouth Scholarship
In the asexual stages, Toxoplasma gondii stage converts between acute phase rapidly replicating tachyzoites and chronic phase slowly dividing bradyzoites. Correspondingly, T. gondii differentially expresses two distinct genes and isoforms of the lactate dehydrogenase enzyme, expressing LDH1 exclusively in the tachyzoite stage and LDH2 preferentially in the bradyzoite stage. LDH catalyzes the interconversion of pyruvate and lactate in anaerobic growth conditions and is utilized for energy supply, however, the precise role of LDH1 and LDH2 in parasite biology in the asexual stages is still unclear. Here, we investigated the biological role of LDH1 and LDH2 in the asexual stages, …
Neighborhood Environment And Falls Among Community-Dwelling Older Adults, Emily Nicklett, Matthew Lohman, Matthew Smith
Neighborhood Environment And Falls Among Community-Dwelling Older Adults, Emily Nicklett, Matthew Lohman, Matthew Smith
Dartmouth Scholarship
Falls present a major challenge to active aging, but the relationship between neighborhood factors and falls is poorly understood. This study examined the relationship between fall events and neighborhood factors, including neighborhood social cohesion (sense of belonging, trust, friendliness, and helpfulness) and physical environment (vandalism/graffiti, rubbish, vacant/deserted houses, and perceived safety walking home at night).
Re-Thinking Anxiety: Using Inoculation Messages To Reduce And Reinterpret Public Speaking Fears, Ben Jackson, Josh Compton, Ashleigh L. Thornton, James A. Dimmock
Re-Thinking Anxiety: Using Inoculation Messages To Reduce And Reinterpret Public Speaking Fears, Ben Jackson, Josh Compton, Ashleigh L. Thornton, James A. Dimmock
Dartmouth Scholarship
Inoculation theory offers a framework for protecting individuals against challenges to an existing attitude, belief, or state. Despite the prevalence and damaging effects of public speaking anxiety, inoculation strategies have yet to be used to help individuals remain calm before and during public speaking. We aimed to test the effectiveness of an inoculation message for reducing the onset of public speaking anxiety, and helping presenters interpret their speech-related anxiety more positively. Participants (Mage = 20.14, SD = 2.72) received either an inoculation (n = 102) or control (n = 128) message prior to engaging a public …
Caesarean Sections And For-Profit Status Of Hospitals: Systematic Review And Meta-Analysis, Ilir Hoxha, Lamprini Syrogiannouli, Xhyljeta Luta, Kali Tal, David C. Goodman
Caesarean Sections And For-Profit Status Of Hospitals: Systematic Review And Meta-Analysis, Ilir Hoxha, Lamprini Syrogiannouli, Xhyljeta Luta, Kali Tal, David C. Goodman
Dartmouth Scholarship
Objective: Financial incentives may encourage private for-profit providers to perform more caesarean section (CS) than non-profit hospitals. We therefore sought to determine the association of for-profit status of hospital and odds of CS.
Design: Systematic review and meta-analysis. Data sources: MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews from the first year of records through February 2016. Eligibility criteria: To be eligible, studies had to report data to allow the calculation of ORs of CS comparing private for-profit hospitals with public or private non-profit hospitals in a specific geographic area. Outcomes: The prespecified primary outcome was the adjusted OR …
Neutralization Of Diverse Human Cytomegalovirus Strains Conferred By Antibodies Targeting Viral Gh/Gl/Pul128-131 Pentameric Complex, Sha Ha, Fengsheng Li, Matthew C. Troutman, Daniel C. Freed, Aimin Tang, John W. Loughney, Dai Wang, I-Ming Wang, Josef Vlasak, David C. Nickle, Richard R. Rustandi, Melissa Hamm, Pete A. Dephillips, Ningyan Zhang, Jason S. Mclellan, Stuart P. Adler, Michael A. Mcvoy, Zhiqiang An, Tong-Ming Fu
Neutralization Of Diverse Human Cytomegalovirus Strains Conferred By Antibodies Targeting Viral Gh/Gl/Pul128-131 Pentameric Complex, Sha Ha, Fengsheng Li, Matthew C. Troutman, Daniel C. Freed, Aimin Tang, John W. Loughney, Dai Wang, I-Ming Wang, Josef Vlasak, David C. Nickle, Richard R. Rustandi, Melissa Hamm, Pete A. Dephillips, Ningyan Zhang, Jason S. Mclellan, Stuart P. Adler, Michael A. Mcvoy, Zhiqiang An, Tong-Ming Fu
Dartmouth Scholarship
Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross-neutralize the field strains of HCMV, remains a challenge. In this study, with a panel of neutralizing antibodies from three healthy human donors with natural HCMV infection or a …
Supporting Shared Decision-Making For Older People With Multiple Health And Social Care Needs: A Protocol For A Realist Synthesis To Inform Integrated Care Models, Frances Bunn, Claire Goodman, Jill Manthorpe, Marie-Anne Durand, Isabel Hodkinson, Greta Rait, Paul Millac, Sue L. Davies, Bridget Russell, Patricia Wilson
Supporting Shared Decision-Making For Older People With Multiple Health And Social Care Needs: A Protocol For A Realist Synthesis To Inform Integrated Care Models, Frances Bunn, Claire Goodman, Jill Manthorpe, Marie-Anne Durand, Isabel Hodkinson, Greta Rait, Paul Millac, Sue L. Davies, Bridget Russell, Patricia Wilson
Dartmouth Scholarship
Introduction: Including the patient or user perspective is a central organising principle of integrated care. Moreover, there is increasing recognition of the importance of strengthening relationships among patients, carers and practitioners, particularly for individuals receiving substantial health and care support, such as those with long-term or multiple conditions. The overall aims of this synthesis are to provide a context-relevant understanding of how models to facilitate shared decision-making (SDM) might work for older people with multiple health and care needs, and how they might be applied to integrated care models.
Methods and analysis: The synthesis draws on the principles of realist …
Inferring Condition-Specific Targets Of Human Tf-Tf Complexes Using Chip-Seq Data, Chia-Chun Yang, Min-Hsuan Chen, Sheng-Yi Lin, Erik H. Andrews, Chao Cheng, Jeremy J.W Chen
Inferring Condition-Specific Targets Of Human Tf-Tf Complexes Using Chip-Seq Data, Chia-Chun Yang, Min-Hsuan Chen, Sheng-Yi Lin, Erik H. Andrews, Chao Cheng, Jeremy J.W Chen
Dartmouth Scholarship
Background:
Transcription factors (TFs) often interact with one another to form TF complexes that bind DNA and regulate gene expression. Many databases are created to describe known TF complexes identified by either mammalian two-hybrid experiments or data mining. Lately, a wealth of ChIP-seq data on human TFs under different experiment conditions are available, making it possible to investigate condition-specific (cell type and/or physiologic state) TF complexes and their target genes.
Results:
Here, we developed a systematic pipeline to infer Condition-Specific Targets of human TF-TF complexes (called the CST pipeline) by integrating ChIP-seq data and TF motifs. In total, we predicted …
The Annual Burden Of Seasonal Influenza In The Us Veterans Affairs Population, Yinong Young-Xu, Robertus Van Aalst, Ellyn Russo, Jason K. H. Lee, Ayman Chit
The Annual Burden Of Seasonal Influenza In The Us Veterans Affairs Population, Yinong Young-Xu, Robertus Van Aalst, Ellyn Russo, Jason K. H. Lee, Ayman Chit
Dartmouth Scholarship
Seasonal influenza epidemics have a substantial public health and economic burden in the United States (US). On average, over 200,000 people are hospitalized and an estimated 23,000 people die from respiratory and circulatory complications associated with seasonal influenza virus infections each year. Annual direct medical costs and indirect productivity costs across the US have been found to average respectively at $10.4 billion and $16.3 billion. The objective of this study was to estimate the economic impact of severe influenza-induced illness on the US Veterans Affairs population. The five-year study period included 2010 through 2014. Influenza-attributed outcomes were estimated with a …
Your Teaching Strategy Matters: How Engagement Impacts Application In Health Information Literacy Instruction, Heather A. Johnson, Laura C. Barrett
Your Teaching Strategy Matters: How Engagement Impacts Application In Health Information Literacy Instruction, Heather A. Johnson, Laura C. Barrett
Dartmouth Scholarship
The purpose of this study was to compare two pedagogical methods, active learning and passive instruction, to determine which is more useful in helping students to achieve the learning outcomes in a one-hour research skills instructional session.
Calcium-Mediated Actin Reset (Caar) Mediates Acute Cell Adaptations, Pauline Wales, Christian Schuberth, Roland Aufschnaiter, Johannes Fels, Ireth Garcia-Aguilar, Annette Janning, Christopher D. Dlugos, Marco Schaefer-Herte, Christoph Klingner, Mike Waelte, Julian Kuhlmann, Ekaterina Menis, Hockaday Kang Hockaday Kang, Kerstin C. Maier, Wenya Hou, Antonella Russo, Henry N. Higgs
Calcium-Mediated Actin Reset (Caar) Mediates Acute Cell Adaptations, Pauline Wales, Christian Schuberth, Roland Aufschnaiter, Johannes Fels, Ireth Garcia-Aguilar, Annette Janning, Christopher D. Dlugos, Marco Schaefer-Herte, Christoph Klingner, Mike Waelte, Julian Kuhlmann, Ekaterina Menis, Hockaday Kang Hockaday Kang, Kerstin C. Maier, Wenya Hou, Antonella Russo, Henry N. Higgs
Dartmouth Scholarship
Actin has well established functions in cellular morphogenesis. However, it is not well understood how the various actin assemblies in a cell are kept in a dynamic equilibrium, in particular when cells have to respond to acute signals. Here, we characterize a rapid and transient actin reset in response to increased intracellular calcium levels. Within seconds of calcium influx, the formin INF2 stimulates filament polymerization at the endoplasmic reticulum (ER), while cortical actin is disassembled. The reaction is then reversed within a few minutes. This Calcium-mediated actin reset (CaAR) occurs in a wide range of mammalian cell types and in …
Development Of A Measure Of Model Fidelity For Mental Health Crisis Resolution Teams, Brynmor Lloyd-Evans, Gary R. Bond, Torleif Ruud, Ada Ivanecka
Development Of A Measure Of Model Fidelity For Mental Health Crisis Resolution Teams, Brynmor Lloyd-Evans, Gary R. Bond, Torleif Ruud, Ada Ivanecka
Dartmouth Scholarship
Crisis Resolution Teams (CRTs) provide short-term intensive home treatment to people experiencing mental health crisis. Trial evidence suggests CRTs can be effective at reducing hospital admissions and increasing satisfaction with acute care. When scaled up to national level however, CRT implementation and outcomes have been variable. We aimed to develop and test a fidelity scale to assess adherence to a model of best practice for CRTs, based on best available evidence.
Impact Of Conflict On Medical Education: A Cross-Sectional Survey Of Students And Institutions In Iraq, Ashton Barnett-Vanes, Sondus Hassounah, Marwan Shawki, Omar Abdulkadir Ismail, Chi Fung, Tara Kedia, Salman Rawaf, Azeem Majeed
Impact Of Conflict On Medical Education: A Cross-Sectional Survey Of Students And Institutions In Iraq, Ashton Barnett-Vanes, Sondus Hassounah, Marwan Shawki, Omar Abdulkadir Ismail, Chi Fung, Tara Kedia, Salman Rawaf, Azeem Majeed
Dartmouth Scholarship
Objective: This study surveyed all Iraqi medical schools and a cross-section of Iraqi medical students regarding their institutional and student experiences of medical education amidst ongoing conflict. The objective was to better understand the current resources and challenges facing medical schools, and the impacts of conflict on the training landscape and student experience, to provide evidence for further research and policy development. Setting: Deans of all Iraqi medical schools registered in the World Directory of Medical Schools were invited to participate in a survey electronically. Medical students from three Iraqi medical schools were invited to participate in a survey electronically. …
Signaling Through Lrg1, Rho1 And Pkc1 Governs Candida Albicans Morphogenesis In Response To Diverse Cues, Jinglin L. Xie, Nora Grahl, Trevor Sless, Michelle Leach, Sang Hu Kim, Deborah Hogan
Signaling Through Lrg1, Rho1 And Pkc1 Governs Candida Albicans Morphogenesis In Response To Diverse Cues, Jinglin L. Xie, Nora Grahl, Trevor Sless, Michelle Leach, Sang Hu Kim, Deborah Hogan
Dartmouth Scholarship
The capacity to transition between distinct morphological forms is a key virulence trait for diverse fungal pathogens. A poignant example of a leading opportunistic fungal pathogen of humans for which an environmentally responsive developmental program underpins virulence is Candida albicans. C. albicans mutants that are defective in the transition between yeast and filamentous forms typically have reduced virulence. Although many positive regulators of C. albicans filamentation have been defined, there are fewer negative regulators that have been implicated in repression of filamentation in the absence of inducing cues. To discover novel negative regulators of filamentation, we screened …
Circnet: A Database Of Circular Rnas Derived From Transcriptome Sequencing Data, Yu-Chen Liu, Jian-Rong Li, Chuan-Hu Sun, Erik Andrews, Rou-Fang Chao, Feng-Mao Lin, Shun-Long Weng, Sheng-Da Hsu, Chieh-Chen Huang, Chao Cheng, Chun-Chi Liu, Hsien-Da Huang
Circnet: A Database Of Circular Rnas Derived From Transcriptome Sequencing Data, Yu-Chen Liu, Jian-Rong Li, Chuan-Hu Sun, Erik Andrews, Rou-Fang Chao, Feng-Mao Lin, Shun-Long Weng, Sheng-Da Hsu, Chieh-Chen Huang, Chao Cheng, Chun-Chi Liu, Hsien-Da Huang
Dartmouth Scholarship
Circular RNAs (circRNAs) represent a new type of regulatory noncoding RNA that only recently has been identified and cataloged. Emerging evidence indicates that circRNAs exert a new layer of post-transcriptional regulation of gene expression. In this study, we utilized transcriptome sequencing datasets to systematically identify the expression of circRNAs (including known and newly identified ones by our pipeline) in 464 RNA-seq samples, and then constructed the CircNet database (http://circnet.mbc.nctu.edu.tw/) that provides the following resources: (i) novel circRNAs, (ii) integrated miRNA-target networks, (iii) expression profiles of circRNA isoforms, (iv) genomic annotations of circRNA isoforms (e.g. 282 948 exon positions), …
Throat Swabs And Sputum Culture As Predictors Of P. Aeruginosa Or S. Aureus Lung Colonization In Adult Cystic Fibrosis Patients, Darius Seidler, Mary Griffin, Amanda Nymon, Katja Koeppen, Alix Ashare
Throat Swabs And Sputum Culture As Predictors Of P. Aeruginosa Or S. Aureus Lung Colonization In Adult Cystic Fibrosis Patients, Darius Seidler, Mary Griffin, Amanda Nymon, Katja Koeppen, Alix Ashare
Dartmouth Scholarship
Background:
Due to frequent infections in cystic fibrosis (CF) patients, repeated respiratory cultures are obtained to inform treatment. When patients are unable to expectorate sputum, clinicians obtain throat swabs as a surrogate for lower respiratory cultures. There is no clear data in adult subjects demonstrating the adequacy of throat swabs as a surrogate for sputum or BAL. Our study was designed to determine the utility of throat swabs in identifying lung colonization with common organisms in adults with CF.
Methods:
Adult CF subjects (n = 20) underwent bronchoscopy with BAL. Prior to bronchoscopy, a throat swab was obtained. A sputum …
Incidence And Duration Of Type-Specific Human Papillomavirus Infection In High-Risk Hpv-Naïve Women: Results From The Control Arm Of A Phase Ii Hpv-16/18 Vaccine Trial, Agnihotram V. Ramanakumar, Paulo Naud, Cecilia M. Roteli-Martins, Newton S. De Carvalho, Paola C. De Borba, Julio C. Teixeira, Mark Blatter, Anna-Barbara Moscicki, Diane M. Harper, Barbara Romanowski, Stephen K. Tyring, Brian Ramjattan, Anne Schuind, Gary Dubin, Eduardo L. Franco
Incidence And Duration Of Type-Specific Human Papillomavirus Infection In High-Risk Hpv-Naïve Women: Results From The Control Arm Of A Phase Ii Hpv-16/18 Vaccine Trial, Agnihotram V. Ramanakumar, Paulo Naud, Cecilia M. Roteli-Martins, Newton S. De Carvalho, Paola C. De Borba, Julio C. Teixeira, Mark Blatter, Anna-Barbara Moscicki, Diane M. Harper, Barbara Romanowski, Stephen K. Tyring, Brian Ramjattan, Anne Schuind, Gary Dubin, Eduardo L. Franco
Dartmouth Scholarship
OBJECTIVES:
Persistence of human papillomaviruses (HPVs) is necessary for cervical carcinogenesis. We evaluated incidence and duration of type-specific HPV infections and the influence of age and number of sexual partners.
METHODS:
Data were obtained from 553 women (15-25 years), who were seronegative and DNA-negative for high-risk HPV (HR-HPV) types and were enrolled in the placebo arm of a randomised trial of the HPV-16/18 vaccine (NCT00689741/NCT00120848). They were followed for 6.3 years. Cervicovaginal samples were self-collected at 3-month intervals for up to 27 months, and cervical samples were collected by clinicians at 6-month intervals until study end. …
Secretion Of Rhoptry And Dense Granule Effector Proteins By Nonreplicating Toxoplasma Gondii Uracil Auxotrophs Controls The Development Of Antitumor Immunity, Barbara A. Fox, Kiah L. Sanders, Leah M. Rommereim, Rebekah B. Guevara, David J. Bzik
Secretion Of Rhoptry And Dense Granule Effector Proteins By Nonreplicating Toxoplasma Gondii Uracil Auxotrophs Controls The Development Of Antitumor Immunity, Barbara A. Fox, Kiah L. Sanders, Leah M. Rommereim, Rebekah B. Guevara, David J. Bzik
Dartmouth Scholarship
Nonreplicating type I uracil auxotrophic mutants of Toxoplasma gondii possess a potent ability to activate therapeutic immunity to established solid tumors by reversing immune suppression in the tumor microenvironment. Here we engineered targeted deletions of parasite secreted effector proteins using a genetically tractable Δku80 vaccine strain to show that the secretion of specific rhoptry (ROP) and dense granule (GRA) proteins by uracil auxotrophic mutants of T. gondii in conjunction with host cell invasion activates antitumor immunity through host responses involving CD8α+ dendritic cells, the IL-12/interferon-gamma (IFN-γ) TH1 axis, as well as CD4+ and CD8 …
The Brain Imaging Data Structure, A Format For Organizing And Describing Outputs Of Neuroimaging Experiments, Krzysztof Gorgolewski, Tibor Auer, Vince Calhoun, R Cameron Craddock, Samir Das, Eugene Duff, Guillaume Flandin, Tristan Glatard, Yaroslav Halchenko
The Brain Imaging Data Structure, A Format For Organizing And Describing Outputs Of Neuroimaging Experiments, Krzysztof Gorgolewski, Tibor Auer, Vince Calhoun, R Cameron Craddock, Samir Das, Eugene Duff, Guillaume Flandin, Tristan Glatard, Yaroslav Halchenko
Dartmouth Scholarship
The development of magnetic resonance imaging (MRI) techniques has defined modern neuroimaging. Since its inception, tens of thousands of studies using techniques such as functional MRI and diffusion weighted imaging have allowed for the non-invasive study of the brain. Despite the fact that MRI is routinely used to obtain data for neuroscience research, there has been no widely adopted standard for organizing and describing the data collected in an imaging experiment. This renders sharing and reusing data (within or between labs) difficult if not impossible and unnecessarily complicates the application of automatic pipelines and quality assurance protocols. To solve this …
Consistency Of Hemoglobin A1c Testing And Cardiovascular Outcomes In Medicare Patients With Diabetes, Philip P. Goodney, Karina A. Newhall, Kimon Bekelis, Daniel Gottlieb, Richard Comi, Sushela Chaudrain, Adrienne E. Faerber, Todd A. Mackenzie, Jonathan S. Skinner
Consistency Of Hemoglobin A1c Testing And Cardiovascular Outcomes In Medicare Patients With Diabetes, Philip P. Goodney, Karina A. Newhall, Kimon Bekelis, Daniel Gottlieb, Richard Comi, Sushela Chaudrain, Adrienne E. Faerber, Todd A. Mackenzie, Jonathan S. Skinner
Dartmouth Scholarship
Background:
Annual hemoglobin A1c testing is recommended for patients with diabetes mellitus. However, it is unknown how consistently patients with diabetes mellitus receive hemoglobin A1c testing over time, or whether testing consistency is associated with adverse cardiovascular outcomes.
Methods and Results:
We identified 1 574 415 Medicare patients (2002–2012) with diabetes mellitus over the age of 65. We followed each patient for a minimum of 3 years to determine their consistency in hemoglobin A1C testing, using 3 categories: low (testing in 0 or 1 of 3 years), medium (testing in 2 of 3 years), and high (testing in all 3 …
Micron-Scale Plasma Membrane Curvature Is Recognized By The Septin Cytoskeleton, Andrew A. Bridges, Maximilian S. Jentzsch, Patrick W. Oakes, Patricia Occhipinti, Amy S. Gladfelter
Micron-Scale Plasma Membrane Curvature Is Recognized By The Septin Cytoskeleton, Andrew A. Bridges, Maximilian S. Jentzsch, Patrick W. Oakes, Patricia Occhipinti, Amy S. Gladfelter
Dartmouth Scholarship
Cells change shape in response to diverse environmental and developmental conditions, creating topologies with micron-scale features. Although individual proteins can sense nanometer-scale membrane curvature, it is unclear if a cell could also use nanometer-scale components to sense micron-scale contours, such as the cytokinetic furrow and base of neuronal branches. Septins are filament-forming proteins that serve as signaling platforms and are frequently associated with areas of the plasma membrane where there is micron-scale curvature, including the cytokinetic furrow and the base of cell protrusions. We report here that fungal and human septins are able to distinguish between different degrees of micron-scale …
Where Are You Looking? Pseudogaze In Afterimages, Daw-An Wu, Patrick Cavanagh
Where Are You Looking? Pseudogaze In Afterimages, Daw-An Wu, Patrick Cavanagh
Dartmouth Scholarship
How do we know where we are looking? A frequent assumption is that the subjective experience of our direction of gaze is assigned to the location in the world that falls on our fovea. However, we find that observers can shift their subjective direction of gaze among different nonfoveal points in an afterimage. Observers were asked to look directly at different corners of a diamond-shaped afterimage. When the requested corner was 3.5° in the periphery, the observer often reported that the image moved away in the direction of the attempted gaze shift. However, when the corner was at 1.75° eccentricity, …
Smn Protein Can Be Reliably Measured In Whole Blood With An Electrochemiluminescence (Ecl) Immunoassay: Implications For Clinical Trials, Phillip Zaworski, Katharine M. Von Herrmann, Shannon Taylor, Sara S. Sunshine, Kathleen Mccarthy, Nicole Risher, Tara Newcomb, Marla Weetall, Thomas W. Prior, Kathryn J. Swoboda, Karen S. Chen, Sergey Paushkin
Smn Protein Can Be Reliably Measured In Whole Blood With An Electrochemiluminescence (Ecl) Immunoassay: Implications For Clinical Trials, Phillip Zaworski, Katharine M. Von Herrmann, Shannon Taylor, Sara S. Sunshine, Kathleen Mccarthy, Nicole Risher, Tara Newcomb, Marla Weetall, Thomas W. Prior, Kathryn J. Swoboda, Karen S. Chen, Sergey Paushkin
Dartmouth Scholarship
Spinal muscular atrophy (SMA) is caused by defects in the survival motor neuron 1 (SMN1) gene that encodes survival motor neuron (SMN) protein. The majority of therapeutic approaches currently in clinical development for SMA aim to increase SMN protein expression and there is a need for sensitive methods able to quantify increases in SMN protein levels in accessible tissues. We have developed a sensitive electrochemiluminescence (ECL)-based immunoassay for measuring SMN protein in whole blood with a minimum volume requirement of 5μL. The SMN-ECL immunoassay enables accurate measurement of SMN in whole blood and other tissues. Using the assay, …
Costs Of Diagnostic And Preoperative Workup With And Without Breast Mri In Older Women With A Breast Cancer Diagnosis, Tracy Onega, Anna N.A Tosteson, Julie Weiss, Jennifer Alford-Teaster, Rebecca A. Hubbard, Louise M. Henderson, Karla Kerlikowske, Martha E. Goodrich, Cristina O'Donoghue, Karen J. Wernli, Wendy B. Demartini, Beth A. Virnig
Costs Of Diagnostic And Preoperative Workup With And Without Breast Mri In Older Women With A Breast Cancer Diagnosis, Tracy Onega, Anna N.A Tosteson, Julie Weiss, Jennifer Alford-Teaster, Rebecca A. Hubbard, Louise M. Henderson, Karla Kerlikowske, Martha E. Goodrich, Cristina O'Donoghue, Karen J. Wernli, Wendy B. Demartini, Beth A. Virnig
Dartmouth Scholarship
Background: Breast cancer in the U.S. - estimated at 232,670 incident cases in 2014 - has the highest aggregate economic burden of care relative to other female cancers. Yet, the amount of cost attributed to diagnostic/ preoperative work up has not been characterized. We examined the costs of imaging and biopsy among women enrolled in Medicare who did and did not receive diagnostic/preoperative Magnetic Resonance Imaging (MRI). Methods: Using Surveillance, Epidemiology and End Results (SEER)- Medicare data, we compared the per capita costs (PCC) based on amount paid, between diagnosis date and primary surgical treatment for a breast cancer diagnosis …
Comprehensive Genetic Testing Identifies Targetable Genomic Alterations In Most Patients With Non-Small Cell Lung Cancer, Specifically Adenocarcinoma, Single Institute Investigation, Janani Vigneswaran, Yi-Hung Carol Tan, Septimiu D. Murgu, Brian M. Won, Kathryn Alexa Patton, Victoria M. Villaflor, Philip C. Hoffman, Thomas Hensing, D. Kyle Hogarth, Renuka Malik
Comprehensive Genetic Testing Identifies Targetable Genomic Alterations In Most Patients With Non-Small Cell Lung Cancer, Specifically Adenocarcinoma, Single Institute Investigation, Janani Vigneswaran, Yi-Hung Carol Tan, Septimiu D. Murgu, Brian M. Won, Kathryn Alexa Patton, Victoria M. Villaflor, Philip C. Hoffman, Thomas Hensing, D. Kyle Hogarth, Renuka Malik
Dartmouth Scholarship
This study reviews extensive genetic analysis in advanced non-small cell lung cancer (NSCLC) patients in order to: describe how targetable mutation genes interrelate with the genes identified as variants of unknown significance; assess the percentage of patients with a potentially targetable genetic alterations; evaluate the percentage of patients who had concurrent alterations, previously considered to be mutually exclusive; and characterize the molecular subset of KRAS. Thoracic Oncology Research Program Databases at the University of Chicago provided patient demographics, pathology, and results of genetic testing. 364 patients including 289 adenocarcinoma underwent genotype testing by various platforms such as FoundationOne, Caris Molecular …
Cddo-Me Redirects Activation Of Breast Tumor Associated Macrophages, Michael S. Ball, Emilie P. Shipman, Hyunjung Kim, Karen T. Liby, Patricia A. Pioli
Cddo-Me Redirects Activation Of Breast Tumor Associated Macrophages, Michael S. Ball, Emilie P. Shipman, Hyunjung Kim, Karen T. Liby, Patricia A. Pioli
Dartmouth Scholarship
Tumor-associated macrophages can account for up to 50% of the tumor mass in breast cancer patients and high TAM density is associated with poor clinical prognosis. Because TAMs enhance tumor growth, development, and metastatic potential, redirection of TAM activation may have significant therapeutic benefit. Our studies in primary human macrophages and murine breast TAMs suggest that the synthetic oleanane triterpenoid CDDO-methyl ester (CDDO-Me) reprograms the activation profile of TAMs from tumor-promoting to tumor-inhibiting. We show that CDDO-Me treatment inhibits expression of IL-10 and VEGF in stimulated human M2 macrophages and TAMs but increases expression of TNF-α and IL-6. Surface expression …