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Entropy-Based Metrics For Predicting Choice Behavior Based On Local Response To Reward, Ethan Trepka, Mehran Spitmaan, Bilal A. Bari, Vincent D. Costa, Jeremiah Y. Cohen, Alireza Soltani Dec 2021

Entropy-Based Metrics For Predicting Choice Behavior Based On Local Response To Reward, Ethan Trepka, Mehran Spitmaan, Bilal A. Bari, Vincent D. Costa, Jeremiah Y. Cohen, Alireza Soltani

Dartmouth Scholarship

For decades, behavioral scientists have used the matching law to quantify how animals distribute their choices between multiple options in response to reinforcement they receive. More recently, many reinforcement learning (RL) models have been developed to explain choice by integrating reward feedback over time. Despite reasonable success of RL models in capturing choice on a trial-by-trial basis, these models cannot capture variability in matching behavior. To address this, we developed metrics based on information theory and applied them to choice data from dynamic learning tasks in mice and monkeys. We found that a single entropy-based metric can explain 50% and …

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Location Of Studies And Evidence Of Effects Of Herbivory On Arctic Vegetation: A Systematic Map, E. M. Soininen, I. C. Barrio, R. Bjørkås, K. Björnsdóttir, D. Ehrich, K. A. Hopping, E. Kaarlejärvi, A. L. Kolstad, S. Abdulmanova, R. G. Björk, C. G. Bueno, I. Eischeid, R. Finger-Higgens, J. S. Forbey, C. Gignac, O. Gilg, M. Den Herder, H. S. Holm, B. C. Hwang, J. U. Jepsen Dec 2021

Location Of Studies And Evidence Of Effects Of Herbivory On Arctic Vegetation: A Systematic Map, E. M. Soininen, I. C. Barrio, R. Bjørkås, K. Björnsdóttir, D. Ehrich, K. A. Hopping, E. Kaarlejärvi, A. L. Kolstad, S. Abdulmanova, R. G. Björk, C. G. Bueno, I. Eischeid, R. Finger-Higgens, J. S. Forbey, C. Gignac, O. Gilg, M. Den Herder, H. S. Holm, B. C. Hwang, J. U. Jepsen

Dartmouth Scholarship

Background: Herbivores modify the structure and function of tundra ecosystems. Understanding their impacts is necessary to assess the responses of these ecosystems to ongoing environmental changes. However, the effects of herbivores on plants and ecosystem structure and function vary across the Arctic. Strong spatial variation in herbivore effects implies that the results of individual studies on herbivory depend on local conditions, i.e., their ecological context. An important first step in assessing whether generalizable conclusions can be produced is to identify the existing studies and assess how well they cover the underlying environmental conditions across the Arctic. This systematic map aims …

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A Complex Of Brca2 And Pp2a-B56 Is Required For Dna Repair By Homologous Recombination, Sara M. Ambjørn, Julien P. Duxin, Emil P.T. Hertz, Isha Nasa, Joana Duro, Thomas Kruse, Blanca Lopez-Mendez, Beata Rymarczyk, Lauren E. Cressey, Thomas Van Overeem Hansen, Arminja N. Kettenbach, Vibe H. Oestergaard, Michael Lisby, Jakob Nilsson Dec 2021

A Complex Of Brca2 And Pp2a-B56 Is Required For Dna Repair By Homologous Recombination, Sara M. Ambjørn, Julien P. Duxin, Emil P.T. Hertz, Isha Nasa, Joana Duro, Thomas Kruse, Blanca Lopez-Mendez, Beata Rymarczyk, Lauren E. Cressey, Thomas Van Overeem Hansen, Arminja N. Kettenbach, Vibe H. Oestergaard, Michael Lisby, Jakob Nilsson

Dartmouth Scholarship

Mutations in the tumour suppressor gene BRCA2 are associated with predisposition to breast and ovarian cancers. BRCA2 has a central role in maintaining genome integrity by facilitating the repair of toxic DNA double-strand breaks (DSBs) by homologous recombination (HR). BRCA2 acts by controlling RAD51 nucleoprotein filament formation on resected single-stranded DNA, but how BRCA2 activity is regulated during HR is not fully understood. Here, we delineate a pathway where ATM and ATR kinases phosphorylate a highly conserved region in BRCA2 in response to DSBs. These phosphorylations stimulate the binding of the protein phosphatase PP2A-B56 to BRCA2 through a conserved binding …

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High-Level Cognition During Story Listening Is Reflected In High-Order Dynamic Correlations In Neural Activity Patterns, Lucy L.W. Owen, Thomas H. Chang, Jeremy R. Manning Dec 2021

High-Level Cognition During Story Listening Is Reflected In High-Order Dynamic Correlations In Neural Activity Patterns, Lucy L.W. Owen, Thomas H. Chang, Jeremy R. Manning

Dartmouth Scholarship

Our thoughts arise from coordinated patterns of interactions between brain structures that change with our ongoing experiences. High-order dynamic correlations in neural activity patterns reflect different subgraphs of the brain’s functional connectome that display homologous lower-level dynamic correlations. Here we test the hypothesis that high-level cognition is reflected in high-order dynamic correlations in brain activity patterns. We develop an approach to estimating high-order dynamic correlations in timeseries data, and we apply the approach to neuroimaging data collected as human participants either listen to a ten-minute story or listen to a temporally scrambled version of the story. We train across-participant pattern …

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Small Cell Carcinoma Presenting As A Biatrial Mass With Obstructive Physiology: A Case Report, Sara Ratican, Soomin Shin, John Moretto Dec 2021

Small Cell Carcinoma Presenting As A Biatrial Mass With Obstructive Physiology: A Case Report, Sara Ratican, Soomin Shin, John Moretto

Dartmouth Scholarship

Background: Small cell carcinoma is a highly aggressive and often fatal cancer that most commonly arises in the lung, although it can occasionally arise from other sites, such as the gastrointestinal tract, prostate or cervix. Cardiac involvement, however, is extremely uncommon and therefore has been poorly documented in the literature. Case presentation: We describe a rare case of a 31-year-old male with small cell carcinoma presenting as a massive, 15-cm cardiac tumor invading the bilateral atria, interatrial septum, and pericardium without an apparent primary malignancy on PET CT and cardiac MRI. With extensive tissue necrosis, traditional methods of obtaining a …

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Visualizing Temperature-Dependent Phase Stability In High Entropy Alloys, Daniel Evans, Jiadong Chen, George Bokas, Wei Chen, Geoffroy Hautier, Wenhao Sun Dec 2021

Visualizing Temperature-Dependent Phase Stability In High Entropy Alloys, Daniel Evans, Jiadong Chen, George Bokas, Wei Chen, Geoffroy Hautier, Wenhao Sun

Dartmouth Scholarship

High entropy alloys (HEAs) contain near equimolar amounts of five or more elements and are a compelling space for materials design. In the design of HEAs, great emphasis is placed on identifying thermodynamic conditions for single-phase and multi-phase stability regions, but this process is hindered by the difficulty of navigating stability relationships in high-component spaces. Traditional phase diagrams use barycentric coordinates to represent composition axes, which require (N – 1) spatial dimensions to represent an N-component system, meaning that HEA systems with N > 4 components cannot be readily visualized. Here, we propose forgoing barycentric composition axes in favor of two …

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Pan-Cancer Evaluation Of Gene Expression And Somatic Alteration Data For Cancer Prognosis Prediction, Xingyu Zheng, Christopher I. Amos, H. Robert Frost Dec 2021

Pan-Cancer Evaluation Of Gene Expression And Somatic Alteration Data For Cancer Prognosis Prediction, Xingyu Zheng, Christopher I. Amos, H. Robert Frost

Dartmouth Scholarship

Background: Over the past decades, approaches for diagnosing and treating cancer have seen significant improvement. However, the variability of patient and tumor characteristics has limited progress on methods for prognosis prediction. The development of high-throughput omics technologies now provides multiple approaches for characterizing tumors. Although a large number of published studies have focused on integration of multi-omics data and use of pathway-level models for cancer prognosis prediction, there still exists a gap of knowledge regarding the prognostic landscape across multi-omics data for multiple cancer types using both gene-level and pathway-level predictors. Methods: In this study, we systematically evaluated three often …

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Musical Components Important For The Mozart K448 Effect In Epilepsy, Robert J. Quon, Michael A. Casey, Edward J. Camp, Stephen Meisenhelter, Sarah A. Steimel, Yinchen Song, Markus E. Testorf, Grace A. Leslie, Krzysztof A. Bujarski, Alan B. Ettinger, Barbara C. Jobst Dec 2021

Musical Components Important For The Mozart K448 Effect In Epilepsy, Robert J. Quon, Michael A. Casey, Edward J. Camp, Stephen Meisenhelter, Sarah A. Steimel, Yinchen Song, Markus E. Testorf, Grace A. Leslie, Krzysztof A. Bujarski, Alan B. Ettinger, Barbara C. Jobst

Dartmouth Scholarship

There is growing evidence for the efficacy of music, specifically Mozart’s Sonata for Two Pianos in D Major (K448), at reducing ictal and interictal epileptiform activity. Nonetheless, little is known about the mechanism underlying this beneficial “Mozart K448 effect” for persons with epilepsy. Here, we measured the influence that K448 had on intracranial interictal epileptiform discharges (IEDs) in sixteen subjects undergoing intracranial monitoring for refractory focal epilepsy. We found reduced IEDs during the original version of K448 after at least 30-s of exposure. Nonsignificant IED rate reductions were witnessed in all brain regions apart from the bilateral frontal cortices, where …

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Dna 5-Hydroxymethylcytosine In Pediatric Central Nervous System Tumors May Impact Tumor Classification And Is A Positive Prognostic Marker, Nasim Azizgolshani, Curtis L. Petersen, Youdinghuan Chen, Joshua J. Levy, Lucas A. Salas, Laurent Perreard, Lananh N. Nguyen, Brock C. Christensen Dec 2021

Dna 5-Hydroxymethylcytosine In Pediatric Central Nervous System Tumors May Impact Tumor Classification And Is A Positive Prognostic Marker, Nasim Azizgolshani, Curtis L. Petersen, Youdinghuan Chen, Joshua J. Levy, Lucas A. Salas, Laurent Perreard, Lananh N. Nguyen, Brock C. Christensen

Dartmouth Scholarship

Background: Nucleotide-specific 5-hydroxymethylcytosine (5hmC) remains understudied in pediatric central nervous system (CNS) tumors. 5hmC is abundant in the brain, and alterations to 5hmC in adult CNS tumors have been reported. However, traditional approaches to measure DNA methylation do not distinguish between 5-methylcytosine (5mC) and its oxidized counterpart 5hmC, including those used to build CNS tumor DNA methylation classification systems. We measured 5hmC and 5mC epigenome-wide at nucleotide resolution in glioma, ependymoma, and embryonal tumors from children, as well as control pediatric brain tissues using tandem bisulfite and oxidative bisulfite treatments followed by hybridization to the Illumina Methylation EPIC Array that …

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Cis-Platin Increases Immune Activity Of Monocytes And Cytotoxic T-Cells In A Murine Model Of Epithelial Ovarian Cancer, Daniel Hopkins, Hector Sanchez, Brent Berwin Phd, Ivy Wilkinson Ryan Md Dec 2021

Cis-Platin Increases Immune Activity Of Monocytes And Cytotoxic T-Cells In A Murine Model Of Epithelial Ovarian Cancer, Daniel Hopkins, Hector Sanchez, Brent Berwin Phd, Ivy Wilkinson Ryan Md

Dartmouth Scholarship

Epithelial ovarian cancer (EOC) is an immunologically active malignancy, but thus far immune therapy has had limited success in clinical trials. One barrier to implementation of efficacious immune therapies is a lack of knowledge of the effect of chemotherapy on the monocyte-derived component of the immune infiltrate within the tumor. We utilized the ID8 murine EOC model to investigate alterations within tumor ascites that occur following administration of platinum chemotherapy. Cisplatin treatment resulted in a significant increase in monocytes within the ascites of tumor bearing mice. We identified that CD11b+ cells from the ascites of mice that have been treated …

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The E3 Ubiquitin Ligase Component, Cereblon, Is An Evolutionarily Conserved Regulator Of Wnt Signaling, Chen Shen, Anmada Nayak, Leif R. Neitzel, Amber A. Adams, Maya Silver-Isenstadt, Leah M. Sawyer, Hassina Benchabane, Huilan Wang, Nawat Bunnag, Bin Li, Daniel T. Wynn, Fan Yang, Marta Garcia-Contreras, Charles H. Williams, Sivanesan Dakshanamurthy, Charles C. Hong, Nagi G. Ayad, Anthony J. Capobianco, Yashi Ahmed, Ethan Lee Dec 2021

The E3 Ubiquitin Ligase Component, Cereblon, Is An Evolutionarily Conserved Regulator Of Wnt Signaling, Chen Shen, Anmada Nayak, Leif R. Neitzel, Amber A. Adams, Maya Silver-Isenstadt, Leah M. Sawyer, Hassina Benchabane, Huilan Wang, Nawat Bunnag, Bin Li, Daniel T. Wynn, Fan Yang, Marta Garcia-Contreras, Charles H. Williams, Sivanesan Dakshanamurthy, Charles C. Hong, Nagi G. Ayad, Anthony J. Capobianco, Yashi Ahmed, Ethan Lee

Dartmouth Scholarship

Immunomodulatory drugs (IMiDs) are important for the treatment of multiple myeloma and myelodysplastic syndrome. Binding of IMiDs to Cereblon (CRBN), the substrate receptor of the CRL4CRBN E3 ubiquitin ligase, induces cancer cell death by targeting key neo-substrates for degradation. Despite this clinical significance, the physiological regulation of CRBN remains largely unknown. Herein we demonstrate that Wnt, the extracellular ligand of an essential signal transduction pathway, promotes the CRBN-dependent degradation of a subset of proteins. These substrates include Casein kinase 1α (CK1α), a negative regulator of Wnt signaling that functions as a key component of the β-Catenin destruction complex. Wnt stimulation …

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Associations Between The Gut Microbiome And Metabolome In Early Life, Quang P. Nguyen, Margaret R. Karagas, Juliette C. Madan, Erika Dade, Thomas J. Palys, Hilary G. Morrison, Wimal W. Pathmasiri, Susan Mcritche, Susan J. Sumner, H. Robert Frost, Anne G. Hoen Dec 2021

Associations Between The Gut Microbiome And Metabolome In Early Life, Quang P. Nguyen, Margaret R. Karagas, Juliette C. Madan, Erika Dade, Thomas J. Palys, Hilary G. Morrison, Wimal W. Pathmasiri, Susan Mcritche, Susan J. Sumner, H. Robert Frost, Anne G. Hoen

Dartmouth Scholarship

Background: The infant intestinal microbiome plays an important role in metabolism and immune development with impacts on lifelong health. The linkage between the taxonomic composition of the microbiome and its metabolic phenotype is undefined and complicated by redundancies in the taxon-function relationship within microbial communities. To inform a more mechanistic understanding of the relationship between the microbiome and health, we performed an integrative statistical and machine learning-based analysis of microbe taxonomic structure and metabolic function in order to characterize the taxa-function relationship in early life. Results: Stool samples collected from infants enrolled in the New Hampshire Birth Cohort Study (NHBCS) …

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Optimade, An Api For Exchanging Materials Data, Casper W. Andersen, Rickard Armiento, Evgeny Blokhin, Gareth J. Conduit, Shyam Dwaraknath, Matthew L. Evans, Ádám Fekete, Abhijith Gopakumar, Saulius Gražulis, Andrius Merkys, Fawzi Mohamed, Corey Oses, Giovanni Pizzi, Gian Marco Rignanese, Markus Scheidgen, Leopold Talirz, Cormac Toher, Donald Winston, Rossella Aversa, Kamal Choudhary Dec 2021

Optimade, An Api For Exchanging Materials Data, Casper W. Andersen, Rickard Armiento, Evgeny Blokhin, Gareth J. Conduit, Shyam Dwaraknath, Matthew L. Evans, Ádám Fekete, Abhijith Gopakumar, Saulius Gražulis, Andrius Merkys, Fawzi Mohamed, Corey Oses, Giovanni Pizzi, Gian Marco Rignanese, Markus Scheidgen, Leopold Talirz, Cormac Toher, Donald Winston, Rossella Aversa, Kamal Choudhary

Dartmouth Scholarship

The Open Databases Integration for Materials Design (OPTIMADE) consortium has designed a universal application programming interface (API) to make materials databases accessible and interoperable. We outline the first stable release of the specification, v1.0, which is already supported by many leading databases and several software packages. We illustrate the advantages of the OPTIMADE API through worked examples on each of the public materials databases that support the full API specification.

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Plasma-Borne Indicators Of Inflammasome Activity In Parkinson’S Disease Patients, Faith L. Anderson, Katharine M. Von Herrmann, Angeline S. Andrew, Yuliya I. Kuras, Alison L. Young, Clemens R. Scherzer, William F. Hickey, Stephen L. Lee, Matthew C. Havrda Dec 2021

Plasma-Borne Indicators Of Inflammasome Activity In Parkinson’S Disease Patients, Faith L. Anderson, Katharine M. Von Herrmann, Angeline S. Andrew, Yuliya I. Kuras, Alison L. Young, Clemens R. Scherzer, William F. Hickey, Stephen L. Lee, Matthew C. Havrda

Dartmouth Scholarship

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms and loss of dopaminergic neurons of the substantia nigra. Inflammation and cell death are recognized aspects of PD suggesting that strategies to monitor and modify these processes may improve the management of the disease. Inflammasomes are pro-inflammatory intracellular pattern recognition complexes that couple these processes. The NLRP3 inflammasome responds to sterile triggers to initiate pro-inflammatory processes characterized by maturation of inflammatory cytokines, cytoplasmic membrane pore formation, vesicular shedding, and if unresolved, pyroptotic cell death. Histologic analysis of tissues from PD patients and individuals with nigral cell loss …

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Coculture With Hemicellulose-Fermenting Microbes Reverses Inhibition Of Corn Fiber Solubilization By Clostridium Thermocellum At Elevated Solids Loadings, Dhananjay Beri, Christopher D. Herring, Sofie Blahova, Suresh Poudel, Richard J. Giannone, Robert L. Hettich, Lee R. Lynd Dec 2021

Coculture With Hemicellulose-Fermenting Microbes Reverses Inhibition Of Corn Fiber Solubilization By Clostridium Thermocellum At Elevated Solids Loadings, Dhananjay Beri, Christopher D. Herring, Sofie Blahova, Suresh Poudel, Richard J. Giannone, Robert L. Hettich, Lee R. Lynd

Dartmouth Scholarship

Background: The cellulolytic thermophile Clostridium thermocellum is an important biocatalyst due to its ability to solubilize lignocellulosic feedstocks without the need for pretreatment or exogenous enzyme addition. At low concentrations of substrate, C. thermocellum can solubilize corn fiber > 95% in 5 days, but solubilization declines markedly at substrate concentrations higher than 20 g/L. This differs for model cellulose like Avicel, on which the maximum solubilization rate increases in proportion to substrate concentration. The goal of this study was to examine fermentation at increasing corn fiber concentrations and investigate possible reasons for declining performance. Results: The rate of growth of C. …

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Breath Can Discriminate Tuberculosis From Other Lower Respiratory Illness In Children, Carly A. Bobak, Lili Kang, Lesley Workman, Lindy Bateman, Mohammad S. Khan, Margaretha Prins, Lloyd May, Flavio A. Franchina, Cynthia Baard, Mark P. Nicol, Heather J. Zar, Jane E. Hill Dec 2021

Breath Can Discriminate Tuberculosis From Other Lower Respiratory Illness In Children, Carly A. Bobak, Lili Kang, Lesley Workman, Lindy Bateman, Mohammad S. Khan, Margaretha Prins, Lloyd May, Flavio A. Franchina, Cynthia Baard, Mark P. Nicol, Heather J. Zar, Jane E. Hill

Dartmouth Scholarship

Pediatric tuberculosis (TB) remains a global health crisis. Despite progress, pediatric patients remain difficult to diagnose, with approximately half of all childhood TB patients lacking bacterial confirmation. In this pilot study (n = 31), we identify a 4-compound breathprint and subsequent machine learning model that accurately classifies children with confirmed TB (n = 10) from children with another lower respiratory tract infection (LRTI) (n = 10) with a sensitivity of 80% and specificity of 100% observed across cross validation folds. Importantly, we demonstrate that the breathprint identified an additional nine of eleven patients who had unconfirmed clinical TB and whose …

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Healing Through History: A Qualitative Evaluation Of A Social Medicine Consultation Curriculum For Internal Medicine Residents, Joel Bradley, David Styren, Abigail Laplante, John Howe, Sienna R. Craig, Emily Cohen Dec 2021

Healing Through History: A Qualitative Evaluation Of A Social Medicine Consultation Curriculum For Internal Medicine Residents, Joel Bradley, David Styren, Abigail Laplante, John Howe, Sienna R. Craig, Emily Cohen

Dartmouth Scholarship

Background: Social context guides care; stories sustain meaning; neither is routinely prioritized in residency training. Healing Through History (HTH) is a social medicine consultation curriculum integrating social determinants of health narrative into clinical care for medically and socially complex patients. The curriculum is part of an internal medicine (IM) residency outpatient clinical rotation at a Veterans Health Administration hospital. Our aim was to explore how in-depth social medicine consultations may impact resident clinical practice and foster meaning in work. Methods: From 2017 to 2019, 49 categorical and preliminary residents in their first year of IM training were given two half-day …

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Elitism In Mathematics And Inequality, Ho-Chun Herbert Chang, Feng Fu Dec 2021

Elitism In Mathematics And Inequality, Ho-Chun Herbert Chang, Feng Fu

Dartmouth Scholarship

The Fields Medal, often referred as the Nobel Prize of mathematics, is awarded to no more than four mathematicians under the age of 40, every 4 years. In recent years, its conferral has come under scrutiny of math historians, for rewarding the existing elite rather than its original goal of elevating under-represented mathematicians. Prior studies of elitism focus on citational practices while a characterization of the structural forces that prevent access remain unclear. Here we show the flow of elite mathematicians between countries and lingo-ethnic identity, using network analysis and natural language processing on 240,000 mathematicians and their advisor–advisee relationships. …

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Materials Property Prediction For Limited Datasets Enabled By Feature Selection And Joint Learning With Modnet, Pierre-Paul De Breuck, Geoffroy Hautier, Gian Marco Rignanese Dec 2021

Materials Property Prediction For Limited Datasets Enabled By Feature Selection And Joint Learning With Modnet, Pierre-Paul De Breuck, Geoffroy Hautier, Gian Marco Rignanese

Dartmouth Scholarship

In order to make accurate predictions of material properties, current machine-learning approaches generally require large amounts of data, which are often not available in practice. In this work, MODNet, an all-round framework, is presented which relies on a feedforward neural network, the selection of physically meaningful features, and when applicable, joint-learning. Next to being faster in terms of training time, this approach is shown to outperform current graph-network models on small datasets. In particular, the vibrational entropy at 305 K of crystals is predicted with a mean absolute test error of 0.009 meV/K/atom (four times lower than previous studies). Furthermore, …

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Measuring And Modeling Energy And Power Consumption In Living Microbial Cells With A Synthetic Atp Reporter, Yijie Deng, Douglas Raymond Beahm, Steven Ionov, Rahul Sarpeshkar Dec 2021

Measuring And Modeling Energy And Power Consumption In Living Microbial Cells With A Synthetic Atp Reporter, Yijie Deng, Douglas Raymond Beahm, Steven Ionov, Rahul Sarpeshkar

Dartmouth Scholarship

Background: Adenosine triphosphate (ATP) is the main energy carrier in living organisms, critical for metabolism and essential physiological processes. In humans, abnormal regulation of energy levels (ATP concentration) and power consumption (ATP consumption flux) in cells is associated with numerous diseases from cancer, to viral infection and immune dysfunction, while in microbes it influences their responses to drugs and other stresses. The measurement and modeling of ATP dynamics in cells is therefore a critical component in understanding fundamental physiology and its role in pathology. Despite the importance of ATP, our current understanding of energy dynamics and homeostasis in living cells …

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A Bioimpedance-Based Monitor For Real-Time Detection And Identification Of Secondary Brain Injury, Alicia Everitt, Brandon Root, Daniel Calnan, Preston Manwaring, David Bauer, Ryan Halter Dec 2021

A Bioimpedance-Based Monitor For Real-Time Detection And Identification Of Secondary Brain Injury, Alicia Everitt, Brandon Root, Daniel Calnan, Preston Manwaring, David Bauer, Ryan Halter

Dartmouth Scholarship

Secondary brain injury impacts patient prognosis and can lead to long-term morbidity and mortality in cases of trauma. Continuous monitoring of secondary injury in acute clinical settings is primarily limited to intracranial pressure (ICP); however, ICP is unable to identify essential underlying etiologies of injury needed to guide treatment (e.g. immediate surgical intervention vs medical management). Here we show that a novel intracranial bioimpedance monitor (BIM) can detect onset of secondary injury, differentiate focal (e.g. hemorrhage) from global (e.g. edema) events, identify underlying etiology and provide localization of an intracranial mass effect. We found in an in vivo porcine model …

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Exercise Routine Change Is Associated With Prenatal Depression Scores During The Covid-19 Pandemic Among Pregnant Women Across The United States, Theresa E. Gildner, Elise J. Laugier, Zaneta M. Thayer Dec 2021

Exercise Routine Change Is Associated With Prenatal Depression Scores During The Covid-19 Pandemic Among Pregnant Women Across The United States, Theresa E. Gildner, Elise J. Laugier, Zaneta M. Thayer

Dartmouth Scholarship

Background The COVID-19 pandemic has negatively affected physical and mental health worldwide. Pregnant women already exhibit an elevated risk for depression compared to the general public, a pattern expected to be exacerbated by the pandemic. Certain lifestyle factors, including moderate exercise, may help support mental health during pregnancy, but it is unclear how the pandemic may impact these associations across different locations. Here, we test whether: (i) reported exercise routine alterations during the pandemic are associated with depression scores; and, (ii) the likelihood of reporting pandemic-related exercise changes varies between women living in metro areas and those in non-metro areas. …

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Mitochondrial Atp Fuels Abc Transporter-Mediated Drug Efflux In Cancer Chemoresistance, Emily L. Giddings, Devin P. Champagne, Meng Han Wu, Joshua M. Laffin, Tina M. Thornton, Felipe Valenca-Pereira, Rachel Culp-Hill, Karen A. Fortner, Natalia Romero, James East, Phoebe Cao, Hugo Arias-Pulido, Karatatiwant S. Sidhu, Brian Silverstrim, Yoonseok Kam, Shana Kelley, Mark Pereira, Susan E. Bates, Janice Y. Bunn, Steven N. Fiering Dec 2021

Mitochondrial Atp Fuels Abc Transporter-Mediated Drug Efflux In Cancer Chemoresistance, Emily L. Giddings, Devin P. Champagne, Meng Han Wu, Joshua M. Laffin, Tina M. Thornton, Felipe Valenca-Pereira, Rachel Culp-Hill, Karen A. Fortner, Natalia Romero, James East, Phoebe Cao, Hugo Arias-Pulido, Karatatiwant S. Sidhu, Brian Silverstrim, Yoonseok Kam, Shana Kelley, Mark Pereira, Susan E. Bates, Janice Y. Bunn, Steven N. Fiering

Dartmouth Scholarship

Chemotherapy remains the standard of care for most cancers worldwide, however development of chemoresistance due to the presence of the drug-effluxing ATP binding cassette (ABC) transporters remains a significant problem. The development of safe and effective means to overcome chemoresistance is critical for achieving durable remissions in many cancer patients. We have investigated the energetic demands of ABC transporters in the context of the metabolic adaptations of chemoresistant cancer cells. Here we show that ABC transporters use mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer cells. We further demonstrate that the loss of methylation-controlled J …

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Clinically Relevant Dual Probe Difference Specimen Imaging (Ddsi) Protocol For Freshly Resected Breast Cancer Specimen Staining, Broderick J. House, Marcus J. Kwon, Jasmin M. Schaefer, Connor W. Barth, Allison Solanki, Scott C. Davis, Summer L. Gibbs Dec 2021

Clinically Relevant Dual Probe Difference Specimen Imaging (Ddsi) Protocol For Freshly Resected Breast Cancer Specimen Staining, Broderick J. House, Marcus J. Kwon, Jasmin M. Schaefer, Connor W. Barth, Allison Solanki, Scott C. Davis, Summer L. Gibbs

Dartmouth Scholarship

Background: Re-excision rates following breast conserving surgery (BCS) remain as high as ~ 35%, with positive margins detected during follow-up histopathology. Additional breast cancer resection surgery is not only taxing on the patient and health care system, but also delays adjuvant therapies, increasing morbidity and reducing the likelihood of a positive outcome. The ability to precisely resect and visualize tumor margins in real time within the surgical theater would greatly benefit patients, surgeons and the health care system. Current tumor margin assessment technologies utilized during BCS involve relatively lengthy and labor-intensive protocols, which impede the surgical work flow. Methods: In …

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Prenatal Metal Mixtures And Child Blood Pressure In The Rhea Mother-Child Cohort In Greece, Caitlin G. Howe, Katerina Margetaki, Marina Vafeiadi, Theano Roumeliotaki, Marianna Karachaliou, Manolis Kogevinas, Rob Mcconnell, Sandrah P. Eckel, David V. Conti, Maria Kippler, Shohreh F. Farzan, Leda Chatzi Dec 2021

Prenatal Metal Mixtures And Child Blood Pressure In The Rhea Mother-Child Cohort In Greece, Caitlin G. Howe, Katerina Margetaki, Marina Vafeiadi, Theano Roumeliotaki, Marianna Karachaliou, Manolis Kogevinas, Rob Mcconnell, Sandrah P. Eckel, David V. Conti, Maria Kippler, Shohreh F. Farzan, Leda Chatzi

Dartmouth Scholarship

Background: Child blood pressure (BP) is predictive of future cardiovascular risk. Prenatal exposure to metals has been associated with higher BP in childhood, but most studies have evaluated elements individually and measured BP at a single time point. We investigated impacts of prenatal metal mixture exposures on longitudinal changes in BP during childhood and elevated BP at 11 years of age. Methods: The current study included 176 mother-child pairs from the Rhea Study in Heraklion, Greece and focused on eight elements (antimony, arsenic, cadmium, cobalt, lead, magnesium, molybdenum, selenium) measured in maternal urine samples collected during pregnancy (median gestational age …

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Is Telemedicine The Answer To Rural Expansion Of Medication Treatment For Opioid Use Disorder? Early Experiences In The Feasibility Study Phase Of A National Drug Abuse Treatment Clinical Trials Network Trial, Yih Ing Hser, Allison J. Ober, Alex R. Dopp, Chunqing Lin, Katie P. Osterhage, Sarah E. Clingan, Larissa J. Mooney, Megan E. Curtis, Lisa A. Marsch, Bethany Mcleman, Emily Hichborn, Laurie S. Lester, Laura Mae Baldwin, Yanping Liu, Petra Jacobs, Andrew J. Saxon Dec 2021

Is Telemedicine The Answer To Rural Expansion Of Medication Treatment For Opioid Use Disorder? Early Experiences In The Feasibility Study Phase Of A National Drug Abuse Treatment Clinical Trials Network Trial, Yih Ing Hser, Allison J. Ober, Alex R. Dopp, Chunqing Lin, Katie P. Osterhage, Sarah E. Clingan, Larissa J. Mooney, Megan E. Curtis, Lisa A. Marsch, Bethany Mcleman, Emily Hichborn, Laurie S. Lester, Laura Mae Baldwin, Yanping Liu, Petra Jacobs, Andrew J. Saxon

Dartmouth Scholarship

Telemedicine (TM) enabled by digital health technologies to provide medical services has been considered a key solution to increasing health care access in rural communities. With the immediate need for remote care due to the COVID-19 pandemic, many health care systems have rapidly incorporated digital technologies to support the delivery of remote care options, including medication treatment for individuals with opioid use disorder (OUD). In responding to the opioid crisis and the COVID-19 pandemic, public health officials and scientific communities strongly support and advocate for greater use of TM-based medication treatment for opioid use disorder (MOUD) to improve access to …

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Activity Of Immunoproteasome Inhibitor Onx-0914 In Acute Lymphoblastic Leukemia Expressing Mll–Af4 Fusion Protein, Tyler W. Jenkins, Sondra L. Downey-Kopyscinski, Jennifer L. Fields, Gilbert J. Rahme, William C. Colley, Mark A. Israel, Andrey V. Maksimenko, Steven N. Fiering, Alexei F. Kisselev Dec 2021

Activity Of Immunoproteasome Inhibitor Onx-0914 In Acute Lymphoblastic Leukemia Expressing Mll–Af4 Fusion Protein, Tyler W. Jenkins, Sondra L. Downey-Kopyscinski, Jennifer L. Fields, Gilbert J. Rahme, William C. Colley, Mark A. Israel, Andrey V. Maksimenko, Steven N. Fiering, Alexei F. Kisselev

Dartmouth Scholarship

Proteasome inhibitors bortezomib and carfilzomib are approved for the treatment of multiple myeloma and mantle cell lymphoma and have demonstrated clinical efficacy for the treatment of acute lymphoblastic leukemia (ALL). The t(4;11)(q21;q23) chromosomal translocation that leads to the expression of MLL–AF4 fusion protein and confers a poor prognosis, is the major cause of infant ALL. This translocation sensitizes tumor cells to proteasome inhibitors, but toxicities of bortezomib and carfilzomib may limit their use in pediatric patients. Many of these toxicities are caused by on-target inhibition of proteasomes in non-lymphoid tissues (e.g., heart muscle, gut, testicles). We found that MLL–AF4 cells …

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Rationale And Design Of The Novel Uses Of Adaptive Designs To Guide Provider Engagement In Electronic Health Records (Nudge-Ehr) Pragmatic Adaptive Randomized Trial: A Trial Protocol, Julie C. Lauffenburger, Thomas Isaac, Lorenzo Trippa, Punam Keller, Ted Robertson, Robert J. Glynn, Thomas D. Sequist, Dae H. Kim, Constance P. Fontanet, Edward W.B. Castonguay, Nancy Haff, Renee A. Barlev, Mufaddal Mahesri, Chandrashekar Gopalakrishnan, Niteesh K. Choudhry Dec 2021

Rationale And Design Of The Novel Uses Of Adaptive Designs To Guide Provider Engagement In Electronic Health Records (Nudge-Ehr) Pragmatic Adaptive Randomized Trial: A Trial Protocol, Julie C. Lauffenburger, Thomas Isaac, Lorenzo Trippa, Punam Keller, Ted Robertson, Robert J. Glynn, Thomas D. Sequist, Dae H. Kim, Constance P. Fontanet, Edward W.B. Castonguay, Nancy Haff, Renee A. Barlev, Mufaddal Mahesri, Chandrashekar Gopalakrishnan, Niteesh K. Choudhry

Dartmouth Scholarship

Background: The prescribing of high-risk medications to older adults remains extremely common and results in potentially avoidable health consequences. Efforts to reduce prescribing have had limited success, in part because they have been sub-optimally timed, poorly designed, or not provided actionable information. Electronic health record (EHR)-based tools are commonly used but have had limited application in facilitating deprescribing in older adults. The objective is to determine whether designing EHR tools using behavioral science principles reduces inappropriate prescribing and clinical outcomes in older adults. Methods: The Novel Uses of Designs to Guide provider Engagement in Electronic Health Records (NUDGE-EHR) project uses …

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Using Impression Data To Improve Models Of Online Social Influence, Rui Liu, Kevin T. Greene, Ruibo Liu, Mihovil Mandic, Benjamin A. Valentino, Soroush Vosoughi, V. S. Subrahmanian Dec 2021

Using Impression Data To Improve Models Of Online Social Influence, Rui Liu, Kevin T. Greene, Ruibo Liu, Mihovil Mandic, Benjamin A. Valentino, Soroush Vosoughi, V. S. Subrahmanian

Dartmouth Scholarship

Influence, the ability to change the beliefs and behaviors of others, is the main currency on social media. Extant studies of influence on social media, however, are limited by publicly available data that record expressions (active engagement of users with content, such as likes and comments), but neglect impressions (exposure to content, such as views) and lack “ground truth” measures of influence. To overcome these limitations, we implemented a social media simulation using an original, web-based micro-blogging platform. We propose three influence models, leveraging expressions and impressions to create a more complete picture of social influence. We demonstrate that impressions …

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White Matter Abnormalities In Adults With Bipolar Disorder Type-Ii And Unipolar Depression, Anna Manelis, Adriane Soehner, Yaroslav O. Halchenko, Skye Satz, Rachel Ragozzino, Mora Lucero, Holly A. Swartz, Mary L. Phillips, Amelia Versace Dec 2021

White Matter Abnormalities In Adults With Bipolar Disorder Type-Ii And Unipolar Depression, Anna Manelis, Adriane Soehner, Yaroslav O. Halchenko, Skye Satz, Rachel Ragozzino, Mora Lucero, Holly A. Swartz, Mary L. Phillips, Amelia Versace

Dartmouth Scholarship

Discerning distinct neurobiological characteristics of related mood disorders such as bipolar disorder type-II (BD-II) and unipolar depression (UD) is challenging due to overlapping symptoms and patterns of disruption in brain regions. More than 60% of individuals with UD experience subthreshold hypomanic symptoms such as elevated mood, irritability, and increased activity. Previous studies linked bipolar disorder to widespread white matter abnormalities. However, no published work has compared white matter microstructure in individuals with BD-II vs. UD vs. healthy controls (HC), or examined the relationship between spectrum (dimensional) measures of hypomania and white matter microstructure across those individuals. This study aimed to …

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