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The Structure And Diversity Of Strain-Level Variation In Vaginal Bacteria, Brett A Tortelli, Amanda L Lewis, Justin C Fay Mar 2021

The Structure And Diversity Of Strain-Level Variation In Vaginal Bacteria, Brett A Tortelli, Amanda L Lewis, Justin C Fay

2020-Current year OA Pubs

The vaginal microbiome plays an important role in human health and species of vaginal bacteria have been associated with reproductive disease. Strain-level variation is also thought to be important, but the diversity, structure and evolutionary history of vaginal strains is not as well characterized. We developed and validated an approach to measure strain variation from metagenomic data based on SNPs within the core genomes for six species of vaginal bacteria:


Impact Of Obesity On Day-Night Differences In Cardiac Metabolism, Sobuj Mia, Ravi Sonkar, Lamario Williams, Mary N Latimer, Isabelle Frayne Robillard, Abhinav Diwan, Stuart J Frank, Christine Des Rosiers, Martin E Young Mar 2021

Impact Of Obesity On Day-Night Differences In Cardiac Metabolism, Sobuj Mia, Ravi Sonkar, Lamario Williams, Mary N Latimer, Isabelle Frayne Robillard, Abhinav Diwan, Stuart J Frank, Christine Des Rosiers, Martin E Young

2020-Current year OA Pubs

An intrinsic property of the heart is an ability to rapidly and coordinately adjust flux through metabolic pathways in response to physiologic stimuli (termed metabolic flexibility). Cardiac metabolism also fluctuates across the 24-hours day, in association with diurnal sleep-wake and fasting-feeding cycles. Although loss of metabolic flexibility has been proposed to play a causal role in the pathogenesis of cardiac disease, it is currently unknown whether day-night variations in cardiac metabolism are altered during disease states. Here, we tested the hypothesis that diet-induced obesity disrupts cardiac "diurnal metabolic flexibility", which is normalized by time-of-day-restricted feeding. Chronic high fat feeding (20-wk)-induced …


Abaloparatide Real-World Patient Experience Study, Deborah T Gold, Richard Weiss, Tammy Beckett, Chad Deal, Robert S Epstein, Andrew L James, Jacqueline M Kernaghan, Mahshid Mohseni, Michael Spiegel, Tamara Vokes, Jenna Roberts, Tom Bailey, Yamei Wang, Setareh A Williams Mar 2021

Abaloparatide Real-World Patient Experience Study, Deborah T Gold, Richard Weiss, Tammy Beckett, Chad Deal, Robert S Epstein, Andrew L James, Jacqueline M Kernaghan, Mahshid Mohseni, Michael Spiegel, Tamara Vokes, Jenna Roberts, Tom Bailey, Yamei Wang, Setareh A Williams

2020-Current year OA Pubs

Despite the availability of various osteoporosis treatments, adherence remains suboptimal. One contributing factor may be patient experience with therapy. This US, multicenter, combined retrospective chart review and patient questionnaire study included postmenopausal women at high risk for fracture and is the first study to describe real-world patient experience with abaloparatide (ABL) injection. Eight geographically diverse secondary care sites in the United States participated (


Genome-Wide Association Study Of Phenotypes Measuring Progression From First Cocaine Or Opioid Use To Dependence Reveals Novel Risk Genes, Richard Sherva, Congcong Zhu, Leah Wetherill, Howard J Edenberg, Emma Johnson, Louisa Degenhardt, Arpana Agrawal, Nicholas G Martin, Elliot Nelson, Henry R Kranzler, Joel Gelernter, Lindsay A Farrer Feb 2021

Genome-Wide Association Study Of Phenotypes Measuring Progression From First Cocaine Or Opioid Use To Dependence Reveals Novel Risk Genes, Richard Sherva, Congcong Zhu, Leah Wetherill, Howard J Edenberg, Emma Johnson, Louisa Degenhardt, Arpana Agrawal, Nicholas G Martin, Elliot Nelson, Henry R Kranzler, Joel Gelernter, Lindsay A Farrer

2020-Current year OA Pubs

AIM: Substance use disorders (SUD) result in substantial morbidity and mortality worldwide. Opioids, and to a lesser extent cocaine, contribute to a large percentage of this health burden. Despite their high heritability, few genetic risk loci have been identified for either opioid or cocaine dependence (OD or CD, respectively). A genome-wide association study of OD and CD related phenotypes reflecting the time between first self-reported use of these substances and a first DSM-IV dependence diagnosis was conducted.

METHODS: Cox proportional hazards regression in a discovery sample of 6,188 African-Americans (AAs) and 6,835 European-Americans (EAs) participants in a genetic study of …


Medalt: Single-Cell Copy Number Lineage Tracing Enabling Gene Discovery, Fang Wang, Qihan Wang, Vakul Mohanty, Shaoheng Liang, Jinzhuang Dou, Jincheng Han, Darlan Conterno Minussi, Ruli Gao, Li Ding, Nicholas Navin, Ken Chen Feb 2021

Medalt: Single-Cell Copy Number Lineage Tracing Enabling Gene Discovery, Fang Wang, Qihan Wang, Vakul Mohanty, Shaoheng Liang, Jinzhuang Dou, Jincheng Han, Darlan Conterno Minussi, Ruli Gao, Li Ding, Nicholas Navin, Ken Chen

2020-Current year OA Pubs

We present a Minimal Event Distance Aneuploidy Lineage Tree (MEDALT) algorithm that infers the evolution history of a cell population based on single-cell copy number (SCCN) profiles, and a statistical routine named lineage speciation analysis (LSA), whichty facilitates discovery of fitness-associated alterations and genes from SCCN lineage trees. MEDALT appears more accurate than phylogenetics approaches in reconstructing copy number lineage. From data from 20 triple-negative breast cancer patients, our approaches effectively prioritize genes that are essential for breast cancer cell fitness and predict patient survival, including those implicating convergent evolution.The source code of our study is available at https://github.com/KChen-lab/MEDALT .


The Second Ninds/Nibib Consensus Meeting To Define Neuropathological Criteria For The Diagnosis Of Chronic Traumatic Encephalopathy, Kevin F Bieniek, Nigel J Cairns, Et Al. Feb 2021

The Second Ninds/Nibib Consensus Meeting To Define Neuropathological Criteria For The Diagnosis Of Chronic Traumatic Encephalopathy, Kevin F Bieniek, Nigel J Cairns, Et Al.

2020-Current year OA Pubs

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder associated with exposure to head trauma. In 2015, a panel of neuropathologists funded by the NINDS/NIBIB defined preliminary consensus neuropathological criteria for CTE, including the pathognomonic lesion of CTE as "an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern," based on review of 25 tauopathy cases. In 2016, the consensus panel met again to review and refine the preliminary criteria, with consideration around the minimum threshold for diagnosis and the reproducibility of a proposed …


Removal Of Epididymal Visceral Adipose Tissue Prevents Obesity-Induced Multi-Organ Insulin Resistance In Male Mice, Michael P Franczyk, Mai He, Jun Yoshino Feb 2021

Removal Of Epididymal Visceral Adipose Tissue Prevents Obesity-Induced Multi-Organ Insulin Resistance In Male Mice, Michael P Franczyk, Mai He, Jun Yoshino

2020-Current year OA Pubs

Obesity is associated with insulin resistance, an important risk factor of type 2 diabetes, atherogenic dyslipidemia, and nonalcoholic fatty liver disease. The major purpose of this study was to test hypothesize that prophylactic removal of epididymal visceral adipose tissue (VAT) prevents obesity-induced multi-organ (liver, skeletal muscle, adipose tissue) insulin resistance. Accordingly, we surgically removed epididymal VAT pads from adult C57BL/6J mice and evaluated in vivo and cellular metabolic pathways involved in glucose and lipid metabolism following chronic high-fat diet (HFD) feeding. We found that VAT removal decreases HFD-induced body weight gain while increasing subcutaneous adipose tissue (SAT) mass. Strikingly, VAT …


The State Of Neuro-Oncology During The Covid-19 Pandemic: A Worldwide Assessment, Maciej M. Mrugala, Milan G. Chheda, Et Al Feb 2021

The State Of Neuro-Oncology During The Covid-19 Pandemic: A Worldwide Assessment, Maciej M. Mrugala, Milan G. Chheda, Et Al

2020-Current year OA Pubs

No abstract provided.


Photosensitivity Reaction From Operating Room Lights After Oral Administration Of 5-Aminolevulinic Acid For Fluorescence-Guided Resection Of A Malignant Glioma, Alexander T. Yahanda, Gavin P. Dunn, Michael R. Chicoine Feb 2021

Photosensitivity Reaction From Operating Room Lights After Oral Administration Of 5-Aminolevulinic Acid For Fluorescence-Guided Resection Of A Malignant Glioma, Alexander T. Yahanda, Gavin P. Dunn, Michael R. Chicoine

2020-Current year OA Pubs

Orally administered 5-aminolevulinic acid (5-ALA), which was approved in the United States in 2017, is preferentially metabolized by malignant glioma cells into protoporphyrin IX and enhances tumor visualization when using a blue light filter on an operating microscope. Photosensitivity after 5-ALA administration is a known side effect, but a photosensitivity reaction from operating room lights has not yet been documented. We report the case of a 56-year-old man with a history of previous resection of a grade II astrocytoma who presented with imaging concerning for tumor recurrence and possible malignant transformation. Repeat surgical resection utilized 5-ALA. Soon after the surgery, …


Limited Effects Of Long-Term Daily Cranberry Consumption On The Gut Microbiome In A Placebo-Controlled Study Of Women With Recurrent Urinary Tract Infections, Timothy J Straub, Wen-Chi Chou, Abigail L Manson, Henry L Schreiber 4th, Bruce J Walker, Christopher A Desjardins, Sinéad B Chapman, Kerrie L Kaspar, Orsalem J Kahsai, Elizabeth Traylor, Karen W Dodson, Meredith A J Hullar, Scott J Hultgren, Christina Khoo, Ashlee M Earl Feb 2021

Limited Effects Of Long-Term Daily Cranberry Consumption On The Gut Microbiome In A Placebo-Controlled Study Of Women With Recurrent Urinary Tract Infections, Timothy J Straub, Wen-Chi Chou, Abigail L Manson, Henry L Schreiber 4th, Bruce J Walker, Christopher A Desjardins, Sinéad B Chapman, Kerrie L Kaspar, Orsalem J Kahsai, Elizabeth Traylor, Karen W Dodson, Meredith A J Hullar, Scott J Hultgren, Christina Khoo, Ashlee M Earl

2020-Current year OA Pubs

BACKGROUND: Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes > 80% of UTIs.

RESULTS: The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances …


Microbiota Restoration Reduces Antibiotic-Resistant Bacteria Gut Colonization In Patients With Recurrent Clostridioides Difficile Infection From The Open-Label Punch Cd Study, Amy Langdon, Drew J Schwartz, Christopher Bulow, Xiaoqing Sun, Tiffany Hink, Kimberly A Reske, Courtney Jones, Carey-Ann D Burnham, Erik R Dubberke, Gautam Dantas, Cdc Prevention Epicenter Program Feb 2021

Microbiota Restoration Reduces Antibiotic-Resistant Bacteria Gut Colonization In Patients With Recurrent Clostridioides Difficile Infection From The Open-Label Punch Cd Study, Amy Langdon, Drew J Schwartz, Christopher Bulow, Xiaoqing Sun, Tiffany Hink, Kimberly A Reske, Courtney Jones, Carey-Ann D Burnham, Erik R Dubberke, Gautam Dantas, Cdc Prevention Epicenter Program

2020-Current year OA Pubs

BACKGROUND: Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and …


Areas Of Metabolomic Exploration For Helminth Infections, Jeffrey D Whitman, Judy A Sakanari, Makedonka Mitreva Feb 2021

Areas Of Metabolomic Exploration For Helminth Infections, Jeffrey D Whitman, Judy A Sakanari, Makedonka Mitreva

2020-Current year OA Pubs

Helminths represent a diverse category of parasitic organisms that can thrive within a host for years, if not decades, in the absence of treatment. As such, they must establish mechanisms to subsist off their hosts, evade the immune system, and develop a niche among the other cohabiting microbial communities. The complex interplay of biologically small molecules (collectively known as the metabolome) derived from, utilized by, or in response to the presence of helminths within a host is an emerging field of study. In this Perspective, we briefly summarize the current existing literature, categorize key host-pathogen-microbiome interfaces that could be studied …


Sense Of Coherence In Adults With Congenital Heart Disease In 15 Countries: Patient Characteristics, Cultural Dimensions And Quality Of Life, Philip Moons, Kamila White, Et Al. Feb 2021

Sense Of Coherence In Adults With Congenital Heart Disease In 15 Countries: Patient Characteristics, Cultural Dimensions And Quality Of Life, Philip Moons, Kamila White, Et Al.

2020-Current year OA Pubs

BACKGROUND: Previous studies have found that sense of coherence (SOC) is positively related to quality of life (QoL) in persons with chronic conditions. In congenital heart disease (CHD), the evidence is scant.

AIMS: We investigated (i) intercountry variation in SOC in a large international sample of adults with CHD; (ii) the relationship between demographic and clinical characteristics and SOC; (iii) the relationship between cultural dimensions of countries and SOC; and (iv) variation in relative importance of SOC in explaining QoL across the countries.

METHODS: APPROACH-IS was a cross-sectional, observational study, with 4028 patients from 15 countries enrolled. SOC was measured …


Focused Ultrasound-Mediated Intranasal Brain Drug Delivery Technique (Fusin), Dezhuang Ye, Hong Chen Feb 2021

Focused Ultrasound-Mediated Intranasal Brain Drug Delivery Technique (Fusin), Dezhuang Ye, Hong Chen

2020-Current year OA Pubs

The blood-brain barrier (BBB) is the major obstacle for brain drug delivery and limits the treatment options for central nervous system diseases. To circumvent the BBB, we introduce focused ultrasound-mediated intranasal brain drug delivery (FUSIN). FUSIN utilizes the nasal route for direct nose-to-brain drug administration, bypassing the BBB and minimizing systemic exposure to the major organs, such as heart, lung, liver, and kidney [1]. It also uses transcranial ultrasound energy focused at a targeted brain region to induce microbubble cavitation, enhancing the transport of intranasally administered agents at the FUS-targeted brain location. FUSIN is unique because it can achieve noninvasive …


Investigating The Relevance Of Major Signaling Pathways In Cancer Survival Using A Biologically Meaningful Deep Learning Model, Jiarui Feng, Heming Zhang, Fuhai Li Feb 2021

Investigating The Relevance Of Major Signaling Pathways In Cancer Survival Using A Biologically Meaningful Deep Learning Model, Jiarui Feng, Heming Zhang, Fuhai Li

2020-Current year OA Pubs

BACKGROUND: Survival analysis is an important part of cancer studies. In addition to the existing Cox proportional hazards model, deep learning models have recently been proposed in survival prediction, which directly integrates multi-omics data of a large number of genes using the fully connected dense deep neural network layers, which are hard to interpret. On the other hand, cancer signaling pathways are important and interpretable concepts that define the signaling cascades regulating cancer development and drug resistance. Thus, it is important to investigate potential associations between patient survival and individual signaling pathways, which can help domain experts to understand deep …


Robotic Bronchoscopy For Peripheral Pulmonary Lesions: A Multicenter Pilot And Feasibility Study (Benefit), Alexander C Chen, Nicholas J Pastis Jr, Amit K Mahajan, Sandeep J Khandhar, Michael J Simoff, Michael S Machuzak, Joseph Cicenia, Thomas R Gildea, Gerard A Silvestri Feb 2021

Robotic Bronchoscopy For Peripheral Pulmonary Lesions: A Multicenter Pilot And Feasibility Study (Benefit), Alexander C Chen, Nicholas J Pastis Jr, Amit K Mahajan, Sandeep J Khandhar, Michael J Simoff, Michael S Machuzak, Joseph Cicenia, Thomas R Gildea, Gerard A Silvestri

2020-Current year OA Pubs

BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPL) continues to present clinical challenges. Despite extensive experience with guided bronchoscopy, the diagnostic yield has not improved significantly. Robotic-assisted bronchoscopic platforms have been developed potentially to improve the diagnostic yield for PPL. Presently, limited data exist that evaluate the performance of robotic systems in live human subjects.

RESEARCH QUESTION: What is the safety and feasibility of robotic-assisted bronchoscopy in patients with PPLs?

STUDY DESIGN AND METHODS: This was a prospective, multicenter pilot and feasibility study that used a robotic bronchoscopic system with a mother-daughter configuration in patients with PPL 1 to 5 …


A Timely Call To Arms: Covid-19, The Circadian Clock, And Critical Care, Jeffrey Haspel, Minjee Kim, Phyllis Zee, Tanja Schwarzmeier, Sara Montagnese, Satchidananda Panda, Adriana Albani, Martha Merrow Feb 2021

A Timely Call To Arms: Covid-19, The Circadian Clock, And Critical Care, Jeffrey Haspel, Minjee Kim, Phyllis Zee, Tanja Schwarzmeier, Sara Montagnese, Satchidananda Panda, Adriana Albani, Martha Merrow

2020-Current year OA Pubs

We currently find ourselves in the midst of a global coronavirus disease 2019 (COVID-19) pandemic, caused by the highly infectious novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we discuss aspects of SARS-CoV-2 biology and pathology and how these might interact with the circadian clock of the host. We further focus on the severe manifestation of the illness, leading to hospitalization in an intensive care unit. The most common severe complications of COVID-19 relate to clock-regulated human physiology. We speculate on how the pandemic might be used to gain insights on the circadian clock but, more importantly, on …


Nf-Κb-Mediated Effects On Behavior And Cartilage Pathology In A Non-Invasive Loading Model Of Post-Traumatic Osteoarthritis, I M Berke, E Jain, B Yavuz, T Mcgrath, L Chen, M J Silva, G Mbalaviele, F Guilak, D L Kaplan, L A Setton Feb 2021

Nf-Κb-Mediated Effects On Behavior And Cartilage Pathology In A Non-Invasive Loading Model Of Post-Traumatic Osteoarthritis, I M Berke, E Jain, B Yavuz, T Mcgrath, L Chen, M J Silva, G Mbalaviele, F Guilak, D L Kaplan, L A Setton

2020-Current year OA Pubs

OBJECTIVE: This study aimed to examine the temporal activation of NF-κB and its relationship to the development of pain-related sensitivity and behavioral changes in a non-invasive murine knee loading model of PTOA.

METHOD: Following knee injury NF-κB activity was assessed longitudinally via in vivo imaging in FVB. Cg-Tg (HIV-EGFP,luc)8Tsb/J mice. Measures of pain-related sensitivity and behavior were also assessed longitudinally for 16 weeks. Additionally, we antagonized NF-κB signaling via intra-articular delivery of an IκB kinase two antagonist to understand how local NF-κB inhibition might alter disease progression.

RESULTS: Following joint injury NF-κB signaling within the knee joint was transiently increased …


Characterization And Localization Of Antigens For Serodiagnosis Of Human Paragonimiasis, Kurt C Curtis, Kerstin Fischer, Young-Jun Choi, Makedonka Mitreva, Gary J Weil, Peter U Fischer Feb 2021

Characterization And Localization Of Antigens For Serodiagnosis Of Human Paragonimiasis, Kurt C Curtis, Kerstin Fischer, Young-Jun Choi, Makedonka Mitreva, Gary J Weil, Peter U Fischer

2020-Current year OA Pubs

Paragonimiasis is a foodborne trematode infection that affects 23 million people, mainly in Asia. Lung fluke infections lead frequently to chronic cough with fever and hemoptysis, and are often confused with lung cancer or tuberculosis. Paragonimiasis can be efficiently treated with praziquantel, but diagnosis is often delayed, and patients are frequently treated for other conditions. To improve diagnosis, we selected five Paragonimus kellicotti proteins based on transcriptional abundance, recognition by patient sera, and conservation among trematodes and expressed them as His-fusion proteins in Escherichia coli. Sequences for these proteins have 76-99% identity with amino acid sequences for orthologs in the …


Fronto-Cerebellar Connectivity Mediating Cognitive Processing Speed, Clive H Y Wong, Jiao Liu, Tatia M C Lee, Jing Tao, Alex W K Wong, Bolton K H Chau, Lidian Chen, Chetwyn C H Chan Feb 2021

Fronto-Cerebellar Connectivity Mediating Cognitive Processing Speed, Clive H Y Wong, Jiao Liu, Tatia M C Lee, Jing Tao, Alex W K Wong, Bolton K H Chau, Lidian Chen, Chetwyn C H Chan

2020-Current year OA Pubs

Processing speed is an important construct in understanding cognition. This study was aimed to control task specificity for understanding the neural mechanisms underlying cognitive processing speed. Forty young adult subjects performed attention tasks of two modalities (auditory and visual) and two levels of task rules (compatible and incompatible). Block-design fMRI captured BOLD signals during the tasks. Thirteen regions of interest were defined with reference to publicly available activation maps for processing speed tasks. Cognitive speed was derived from task reaction times, which yielded six sets of connectivity measures. Mixed-effect LASSO regression revealed six significant paths suggestive of a cerebello-frontal network …


Decoding Visual Information From High-Density Diffuse Optical Tomography Neuroimaging Data, Kalyan Tripathy, Zachary E Markow, Andrew K Fishell, Arefeh Sherafati, Tracy M Burns-Yocum, Mariel L Schroeder, Alexandra M Svoboda, Adam T Eggebrecht, Mark A Anastasio, Bradley L Schlaggar, Joseph P Culver Feb 2021

Decoding Visual Information From High-Density Diffuse Optical Tomography Neuroimaging Data, Kalyan Tripathy, Zachary E Markow, Andrew K Fishell, Arefeh Sherafati, Tracy M Burns-Yocum, Mariel L Schroeder, Alexandra M Svoboda, Adam T Eggebrecht, Mark A Anastasio, Bradley L Schlaggar, Joseph P Culver

2020-Current year OA Pubs

BACKGROUND: Neural decoding could be useful in many ways, from serving as a neuroscience research tool to providing a means of augmented communication for patients with neurological conditions. However, applications of decoding are currently constrained by the limitations of traditional neuroimaging modalities. Electrocorticography requires invasive neurosurgery, magnetic resonance imaging (MRI) is too cumbersome for uses like daily communication, and alternatives like functional near-infrared spectroscopy (fNIRS) offer poor image quality. High-density diffuse optical tomography (HD-DOT) is an emerging modality that uses denser optode arrays than fNIRS to combine logistical advantages of optical neuroimaging with enhanced image quality. Despite the resulting promise …


Clinical Validation Of Combinatorial Pharmacogenomic Testing And Single-Gene Guidelines In Predicting Psychotropic Medication Blood Levels And Clinical Outcomes In Patients With Depression, Anthony J Rothschild, Charles R Conway, Et Al. Feb 2021

Clinical Validation Of Combinatorial Pharmacogenomic Testing And Single-Gene Guidelines In Predicting Psychotropic Medication Blood Levels And Clinical Outcomes In Patients With Depression, Anthony J Rothschild, Charles R Conway, Et Al.

2020-Current year OA Pubs

We evaluated the clinical validity of a combinatorial pharmacogenomic test and single-gene Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines against patient outcomes and medication blood levels to assess their ability to inform prescribing in major depressive disorder (MDD). This is a secondary analysis of the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial, which included patients with a diagnosis of MDD, and ≥1 prior medication failure. The ability to predict increased/decreased medication metabolism was validated against blood levels at screening (adjusted for age, sex, smoking status). The ability of predicted gene-drug interactions (pharmacogenomic test) or therapeutic recommendations (single-gene guidelines) to …


Implications Of Oligomeric Amyloid-Beta (Oaβ42) Signaling Through Α7Β2-Nicotinic Acetylcholine Receptors (Nachrs) On Basal Forebrain Cholinergic Neuronal Intrinsic Excitability And Cognitive Decline, Andrew A George, Jaime M Vieira, Cameron Xavier-Jackson, Michael T Gee, John R Cirrito, Heather A Bimonte-Nelson, Marina R Picciotto, Ronald J Lukas, Paul Whiteaker Jan 2021

Implications Of Oligomeric Amyloid-Beta (Oaβ42) Signaling Through Α7Β2-Nicotinic Acetylcholine Receptors (Nachrs) On Basal Forebrain Cholinergic Neuronal Intrinsic Excitability And Cognitive Decline, Andrew A George, Jaime M Vieira, Cameron Xavier-Jackson, Michael T Gee, John R Cirrito, Heather A Bimonte-Nelson, Marina R Picciotto, Ronald J Lukas, Paul Whiteaker

2020-Current year OA Pubs

Neuronal and network-level hyperexcitability is commonly associated with increased levels of amyloid-β (Aβ) and contribute to cognitive deficits associated with Alzheimer's disease (AD). However, the mechanistic complexity underlying the selective loss of basal forebrain cholinergic neurons (BFCNs), a well-recognized characteristic of AD, remains poorly understood. In this study, we tested the hypothesis that the oligomeric form of amyloid-β (oAβ


Complete Mapping Of Mutations To The Sars-Cov-2 Spike Receptor-Binding Domain That Escape Antibody Recognition, Allison J. Greaney, Paul W. Rothlauf, Zhuoming Liu, Sean P. J. Whelan, Et Al. Jan 2021

Complete Mapping Of Mutations To The Sars-Cov-2 Spike Receptor-Binding Domain That Escape Antibody Recognition, Allison J. Greaney, Paul W. Rothlauf, Zhuoming Liu, Sean P. J. Whelan, Et Al.

2020-Current year OA Pubs

Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of …


Relationship Between Clinicopathologic Factors And Fdg Avidity In Radioiodine-Negative Recurrent Or Metastatic Differentiated Thyroid Carcinoma, Le Ngoc Ha, Amir Iravani, Nguyen Thi Nhung, Ngo Thi Minh Hanh, Febby Hutomo, Mai Hong Son Jan 2021

Relationship Between Clinicopathologic Factors And Fdg Avidity In Radioiodine-Negative Recurrent Or Metastatic Differentiated Thyroid Carcinoma, Le Ngoc Ha, Amir Iravani, Nguyen Thi Nhung, Ngo Thi Minh Hanh, Febby Hutomo, Mai Hong Son

2020-Current year OA Pubs

BACKGROUND: In this study, we investigated the relationship between clinicopathologic factors, BRAF

METHODS: From 2015 to 2018 all patients with suspected recurrent or metastatic radioiodine-negative DTC patients who underwent FDG positron emission tomography/computed tomography (PET/CT) were retrospectively reviewed. Suspected lesions on FDG PET/CT were biopsied and underwent BRAF

RESULTS: Sixty-three consecutive patients, 55 (87.3%) female, with median age of 48 (range 17-81) were included. The majority of patients had BRAF

CONCLUSION: The majority of recurrent or metastatic RAI-negative DTC have BRAF


Application Of Systems Dynamics And Group Model Building To Identify Barriers And Facilitators To Acute Care Delivery In A Resource Limited Setting, Fiona Muttalib, Ellis Ballard, Josephine Langton, Sara Malone, Yudy Fonseca, Andreas Hansmann, Kenneth Remy, Peter Hovmand, Allan Doctor Jan 2021

Application Of Systems Dynamics And Group Model Building To Identify Barriers And Facilitators To Acute Care Delivery In A Resource Limited Setting, Fiona Muttalib, Ellis Ballard, Josephine Langton, Sara Malone, Yudy Fonseca, Andreas Hansmann, Kenneth Remy, Peter Hovmand, Allan Doctor

2020-Current year OA Pubs

BACKGROUND: Group model building (GMB) is a method to facilitate shared understanding of structures and relationships that determine system behaviors. This project aimed to determine the feasibility of GMB in a resource-limited setting and to use GMB to describe key barriers and facilitators to effective acute care delivery at a tertiary care hospital in Malawi.

METHODS: Over 1 week, trained facilitators led three GMB sessions with two groups of healthcare providers to facilitate shared understanding of structures and relationships that determine system behaviors. One group aimed to identify factors that impact patient flow in the paediatric special care ward. The …


Going Remote: Implementing Digital Research Methods At An Academic Medical Center During Covid-19, Katie E Keenoy, Eric J Lenze, Ginger E Nicol Jan 2021

Going Remote: Implementing Digital Research Methods At An Academic Medical Center During Covid-19, Katie E Keenoy, Eric J Lenze, Ginger E Nicol

2020-Current year OA Pubs

COVID-19 has forced medical research institutions to conduct clinical research remotely. Here, we describe how a university's mHealth Research Core helped facilitate the shift to remote research during the COVID-19 pandemic. In 2019 (pre-pandemic), we conducted stakeholder interviews and leadership group sessions to identify, create, and implement resources and core functions to support investigator-initiated mHealth research. Between April 2019 and February 2020, we identified four investigator needs: 1) a


Inhibition Of Nox1 Mitigates Blood Pressure Increases In Elastin Insufficiency, Angela Troia, Russell H Knutsen, Carmen M Halabi, Daniela Malide, Zu Xi Yu, Amanda Wardlaw-Pickett, Elise K Kronquist, Kit Man Tsang, Attila Kovacs, Robert P Mecham, Beth A Kozel Jan 2021

Inhibition Of Nox1 Mitigates Blood Pressure Increases In Elastin Insufficiency, Angela Troia, Russell H Knutsen, Carmen M Halabi, Daniela Malide, Zu Xi Yu, Amanda Wardlaw-Pickett, Elise K Kronquist, Kit Man Tsang, Attila Kovacs, Robert P Mecham, Beth A Kozel

2020-Current year OA Pubs

Elastin (ELN) insufficiency leads to the cardiovascular hallmarks of the contiguous gene deletion disorder, Williams-Beuren syndrome, including hypertension and vascular stiffness. Previous studies showed that Williams-Beuren syndrome deletions, which extended to include the


Salvage Therapies For Radiation-Relapsed Isocitrate Dehydrogenase-Mutant Astrocytoma And 1p/19q Codeleted Oligodendroglioma, Sirui Ma, Soumon Rudra, Jian L Campian, Milan G Chheda, Tanner M Johanns, George Ansstas, Christopher D Abraham, Michael R Chicoine, Eric C Leuthardt, Joshua L Dowling, Gavin P Dunn, Albert H Kim, Jiayi Huang Jan 2021

Salvage Therapies For Radiation-Relapsed Isocitrate Dehydrogenase-Mutant Astrocytoma And 1p/19q Codeleted Oligodendroglioma, Sirui Ma, Soumon Rudra, Jian L Campian, Milan G Chheda, Tanner M Johanns, George Ansstas, Christopher D Abraham, Michael R Chicoine, Eric C Leuthardt, Joshua L Dowling, Gavin P Dunn, Albert H Kim, Jiayi Huang

2020-Current year OA Pubs

BACKGROUND: Optimal management for recurrent IDH-mutant glioma after radiation therapy (RT) is not well-defined. This study assesses practice patterns for managing recurrent IDH-mutant astrocytoma (Astro) and 1p/19q codeleted oligodendroglioma (Oligo) after RT and surveys their clinical outcomes after different salvage approaches.

METHODS: Ninety-four recurrent Astro or Oligo patients after RT who received salvage systemic therapy (SST) between 2001 and 2019 at a tertiary cancer center were retrospectively analyzed. SST was defined as either alkylating chemotherapy (AC) or nonalkylating therapy (non-AC). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method from the start of SST. Multivariable analysis …


Development Of A Digital Toolkit To Improve Quality Of Life Of Patients With Systemic Lupus Erythematosus, Jerik Leung, Laura Kloos, Alfred H Kim, Elizabeth A Baker Jan 2021

Development Of A Digital Toolkit To Improve Quality Of Life Of Patients With Systemic Lupus Erythematosus, Jerik Leung, Laura Kloos, Alfred H Kim, Elizabeth A Baker

2020-Current year OA Pubs

OBJECTIVE: The purpose of this manuscript is to detail development and initial usability testing of an e-toolkit designed to provide skills and knowledge around self-management behaviors for individuals living with systemic lupus erythematosus.

METHODS: Researchers worked with a steering committee of patients and providers to (1) develop a clickable prototype of an e-toolkit and (2) conduct alpha (individuals not affiliated with an academic clinic as patient or provider) and beta (individual patients with systemic lupus erythematosus as well as members of the clinic healthcare team and individuals who work in patient advocacy organizations) usability testing through semistructured interviews.

RESULTS: During …