Medicine and Health Sciences Commons^™

Mapk4 Promotes Prostate Cancer By Concerted Activation Of Androgen Receptor And Akt, Tao Shen, Wei Wang, Wolong Zhou, Ilsa Coleman, Qinbo Cai, Bingning Dong, Michael M Ittmann, Chad J Creighton, Yingnan Bian, Yanling Meng, David R Rowley, Peter S Nelson, David D Moore, Feng Yang

Faculty, Staff and Students Publications

Prostate cancer (PCa) is the second leading cause of cancer death in American men. Androgen receptor (AR) signaling is essential for PCa cell growth/survival and remains a key therapeutic target for lethal castration-resistant PCa (CRPC). GATA2 is a pioneer transcription factor crucial for inducing AR expression/activation. We recently reported that MAPK4, an atypical MAPK, promotes tumor progression via noncanonical activation of AKT. Here, we demonstrated that MAPK4 activated AR by enhancing GATA2 transcriptional expression and stabilizing GATA2 protein through repression of GATA2 ubiquitination/degradation. MAPK4 expression correlated with AR activation in human CRPC. Concerted activation of both GATA2/AR and AKT by …

Targeting Nsd2-Mediated Src-3 Liquid-Liquid Phase Separation Sensitizes Bortezomib Treatment In Multiple Myeloma, Jing Liu, Ying Xie, Jing Guo, Xin Li, Jingjing Wang, Hongmei Jiang, Ziyi Peng, Jingya Wang, Sheng Wang, Qian Li, Linquan Ye, Yuping Zhong, Qiguo Zhang, Xiaozhi Liu, David M Lonard, Jin Wang, Bert W O'Malley, Zhiqiang Liu

Faculty, Staff and Students Publications

Development of chemoresistance is the main reason for failure of clinical management of multiple myeloma (MM), but the genetic and epigenetic aberrations that interact to confer such chemoresistance remains unknown. In the present study, we find that high steroid receptor coactivator-3 (SRC-3) expression is correlated with relapse/refractory and poor outcomes in MM patients treated with bortezomib (BTZ)-based regimens. Furthermore, in immortalized cell lines, high SRC-3 enhances resistance to proteasome inhibitor (PI)-induced apoptosis. Overexpressed histone methyltransferase NSD2 in patients bearing a t(4;14) translocation or in BTZ-resistant MM cells coordinates elevated SRC-3 by enhancing its liquid-liquid phase separation to supranormally modify histone …

Lessons Learned From Inadequate Implementation Planning Of Team-Based Chronic Disease Management: Implementation Evaluation., Shannon L Sibbald, Rachelle Van Asseldonk, Peiwen L Cao, Benson Law

Health Studies Publications

BACKGROUND: This study was a retrospective evaluation of an unsuccessfully implemented team-based, chronic disease management program, with an aim to understand more about implementation barriers. The program, the Chronic Disease Management Initiative (CDMI) was a new collaborative model of care for patients with COPD. It utilized customized health information and interactive tools, mainly smartphones, for ongoing disease management. The program's goal was to demonstrate that integrated team-based models of care could improve patient care, as well as reduce readmission rates and emergency department visits. The program planning for CDMI began in 2017, followed by the implementation and evaluation period in …

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 …

Bax 335 Hemophilia B Gene Therapy Clinical Trial Results: Potential Impact Of Cpg Sequences On Gene Expression, Barbara A Konkle, Christopher E Walsh, Miguel A Escobar, Neil C Josephson, Guy Young, Annette Von Drygalski, Scott W J Mcphee, R Jude Samulski, Ivan Bilic, Maurus De La Rosa, Birgit M Reipert, Hanspeter Rottensteiner, Friedrich Scheiflinger, John C Chapin, Bruce Ewenstein, Paul E Monahan

Faculty, Staff and Student Publications

Gene therapy has the potential to maintain therapeutic blood clotting factor IX (FIX) levels in patients with hemophilia B by delivering a functional human F9 gene into liver cells. This phase 1/2, open-label dose-escalation study investigated BAX 335 (AskBio009, AAV8.sc-TTR-FIXR338Lopt), an adeno-associated virus serotype 8 (AAV8)-based FIX Padua gene therapy, in patients with hemophilia B. This report focuses on 12-month interim analyses of safety, pharmacokinetic variables, effects on FIX activity, and immune responses for dosed participants. Eight adult male participants (aged 20-69 years; range FIX activity, 0.5% to 2.0%) received 1 of 3 BAX 335 IV doses: 2.0 × 1011; …

Phenytoin Inhibits Cell Proliferation Through Microrna-196a-5p In Mouse Lip Mesenchymal Cells, Hiroki Yoshioka, Sai Shankar Ramakrishnan, Akiko Suzuki, Junichi Iwata

Faculty, Staff and Student Publications

Cleft lip (CL) is one of the most common birth defects. It is caused by either genetic mutations or environmental factors. Recent studies suggest that environmental factors influence the expression of noncoding RNAs [e.g., microRNA (miRNA)], which can regulate the expression of genes crucial for cellular functions. In this study, we examined which miRNAs are associated with CL. Among 10 candidate miRNAs (miR-98-3p, miR-101a-3p, miR-101b-3p, miR-141-3p, miR-144-3p, miR-181a-5p, miR-196a-5p, miR-196b-5p, miR-200a-3p, and miR-710) identified through our bioinformatic analysis of CL-associated genes, overexpression of miR-181a-5p, miR-196a-5p, miR-196b-5p, and miR-710 inhibited cell proliferation through suppression of genes associated with CL in cultured …

Vertical Sleeve Gastrectomy Confers Metabolic Improvements By Reducing Intestinal Bile Acids And Lipid Absorption In Mice, Lili Ding, Eryun Zhang, Qiaoling Yang, Lihua Jin, Kyle M Sousa, Bingning Dong, Yangmeng Wang, Jui Tu, Xiaoxiao Ma, Jingyan Tian, Hongli Zhang, Zhipeng Fang, Ana Guan, Yixin Zhang, Zhengtao Wang, David D Moore, Li Yang, Wendong Huang

Faculty, Staff and Students Publications

Vertical sleeve gastrectomy (VSG) is a highly effective bariatric surgery that sustainably treats obesity and type 2 diabetes (T2D). However, the underlying mechanisms governing its metabolic benefits remain unclear. In this study, we have used four different genetically modified mouse lines to understand the link between bile acid circulation and metabolic effects of VSG. Instead of directly activating the nuclear bile acid receptor farnesoid X receptor (Fxr) in the liver or intestine, VSG reduces intestinal levels of bile acids, thereby decreasing fat absorption in the intestine. Given the rising popularity of bariatric surgeries to treat obesity and associated T2D, the …

Association Of Nt-Probnp, Blood Pressure, And Cardiovascular Events: The Aric Study, Aliza Hussain, Wensheng Sun, Anita Deswal, James A De Lemos, John W Mcevoy, Ron C Hoogeveen, Kunihiro Matsushita, David Aguilar, Biykem Bozkurt, Salim S Virani, Amil M Shah, Elizabeth Selvin, Chiadi Ndumule, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

BACKGROUND: Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.

OBJECTIVES: This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.

METHODS: Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, …

Common Questions And Misconceptions About Creatine Supplementation: What Does The Scientific Evidence Really Show?, Jose Antonio, Darren G Candow, Scott C Forbes, Bruno Gualano, Andrew R Jagim, Richard B Kreider, Eric S Rawson, Abbie E Smith-Ryan, Trisha A Vandusseldorp, Darryn S Willoughby, Tim N Ziegenfuss

Faculty, Staff and Students Publications

Supplementing with creatine is very popular amongst athletes and exercising individuals for improving muscle mass, performance and recovery. Accumulating evidence also suggests that creatine supplementation produces a variety of beneficial effects in older and patient populations. Furthermore, evidence-based research shows that creatine supplementation is relatively well tolerated, especially at recommended dosages (i.e. 3-5 g/day or 0.1 g/kg of body mass/day). Although there are over 500 peer-refereed publications involving creatine supplementation, it is somewhat surprising that questions regarding the efficacy and safety of creatine still remain. These include, but are not limited to: 1. Does creatine lead to water retention? 2. …

Impaired Eif5a Function Causes A Mendelian Disorder That Is Partially Rescued In Model Systems By Spermidine., Víctor Faundes, Martin D. Jennings, Siobhan Crilly, Sarah Legraie, Sarah E. Withers, Sara Cuvertino, Sally J. Davies, Andrew G L Douglas, Andrew E. Fry, Victoria Harrison, Jeanne Amiel, Daphné Lehalle, William G. Newman, Patricia Newkirk, Judith Ranells, Miranda Splitt, Laura A. Cross, Carol J. Saunders, Bonnie Sullivan, Jorge L. Granadillo, Christopher T. Gordon, Paul R. Kasher, Graham D. Pavitt, Siddharth Banka

Manuscripts, Articles, Book Chapters and Other Papers

The structure of proline prevents it from adopting an optimal position for rapid protein synthesis. Poly-proline-tract (PPT) associated ribosomal stalling is resolved by highly conserved eIF5A, the only protein to contain the amino acid hypusine. We show that de novo heterozygous EIF5A variants cause a disorder characterized by variable combinations of developmental delay, microcephaly, micrognathia and dysmorphism. Yeast growth assays, polysome profiling, total/hypusinated eIF5A levels and PPT-reporters studies reveal that the variants impair eIF5A function, reduce eIF5A-ribosome interactions and impair the synthesis of PPT-containing proteins. Supplementation with 1 mM spermidine partially corrects the yeast growth defects, improves the polysome profiles …

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 …

Safety And Efficacy Of Hypofractionated Stereotactic Radiosurgery For High-Grade Gliomas At First Recurrence: A Single-Center Experience., Yun Guan, Ji Xiong, Mingyuan Pan, Wenyin Shi, Jing Li, Huaguang Zhu, Xiu Gong, Chao Li, Guanghai Mei, Xiaoxia Liu, Li Pan, Jiazhong Dai, Yang Wang, Enmin Wang, Xin Wang

Department of Radiation Oncology Faculty Papers

BACKGROUND: The optimal treatment for recurrent high-grade gliomas (rHGGs) remains uncertain. This study aimed to investigate the efficacy and safety of hypofractionated stereotactic radiosurgery (HSRS) as a first-line salvage treatment for in-field recurrence of high-grade gliomas.

METHODS: Between January 2016 and October 2019, 70 patients with rHGG who underwent HSRS were retrospectively analysed. The primary endpoint was overall survival (OS), and secondary endpoints included both progression-free survival (PFS) and adverse events, which were assessed according to Common Toxicity Criteria Adverse Events (CTCAE) version 5. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of …

Addressing Artificial Intelligence Bias In Retinal Diagnostics, Philippe Burlina, Neil Joshi, William Paul, Katia D Pacheco, Neil M Bressler

Faculty, Staff and Students Publications

PURPOSE: This study evaluated generative methods to potentially mitigate artificial intelligence (AI) bias when diagnosing diabetic retinopathy (DR) resulting from training data imbalance or domain generalization, which occurs when deep learning systems (DLSs) face concepts at test/inference time they were not initially trained on.

METHODS: The public domain Kaggle EyePACS dataset (88,692 fundi and 44,346 individuals, originally diverse for ethnicity) was modified by adding clinician-annotated labels and constructing an artificial scenario of data imbalance and domain generalization by disallowing training (but not testing) exemplars for images of retinas with DR warranting referral (DR-referable) from darker-skin individuals, who presumably have greater …

Efficacy And Safety Of The Mrna-1273 Sars-Cov-2 Vaccine, Lindsey R Baden, Hana M El Sahly, Brandon Essink, Karen Kotloff, Sharon Frey, Rick Novak, David Diemert, Stephen A Spector, Nadine Rouphael, C Buddy Creech, John Mcgettigan, Shishir Khetan, Nathan Segall, Joel Solis, Adam Brosz, Carlos Fierro, Howard Schwartz, Kathleen Neuzil, Larry Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, John Mascola, Laura Polakowski, Julie Ledgerwood, Barney S Graham, Hamilton Bennett, Rolando Pajon, Conor Knightly, Brett Leav, Weiping Deng, Honghong Zhou, Shu Han, Melanie Ivarsson, Jacqueline Miller, Tal Zaks, Cove Study Group

Faculty, Staff and Students Publications

BACKGROUND: Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.

METHODS: This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. …

The Intersection Of Rural Residence And Minority Race/Ethnicity In Cancer Disparities In The United States, Whitney Zahnd, Cathryn Murphy, Marie Knoll, Gabriel A. Benavidez, Kelsey R. Day, Radhika Ranganathan, Parthenia Luke, Anja Zgodic, Kewei Shi, Melinda A. Merrell, Elizabeth L. Crouch, Heather M. Brandt, Jan Eberth

Faculty Publications

One in every twenty-five persons in America is a racial/ethnic minority who lives in a rural area. Our objective was to summarize how racism and, subsequently, the social determinants of health disproportionately affect rural racial/ethnic minority populations, provide a review of the cancer disparities experienced by rural racial/ethnic minority groups, and recommend policy, research, and intervention approaches to reduce these disparities. We found that rural Black and American Indian/Alaska Native populations experience greater poverty and lack of access to care, which expose them to greater risk of developing cancer and experiencing poorer cancer outcomes in treatment and ultimately survival. There …

Eosinophils Attenuate Hepatic Ischemia-Reperfusion Injury In Mice Through St2-Dependent Il-13 Production, Yaochun Wang, Yang Yang, Meng Wang, Shuhong Wang, Jong-Min Jeong, Long Xu, Yankai Wen, Christoph Emontzpohl, Constance Lynn Atkins, Kevin Duong, Nicolas F Moreno, Xiaoyi Yuan, David R Hall, Wasim Dar, Dechun Feng, Bin Gao, Yong Xu, Zoltan Czigany, Sean P Colgan, J Steve Bynon, Shizuo Akira, Jared M Brown, Holger K Eltzschig, Elizabeth A Jacobsen, Cynthia Ju

Faculty, Staff and Students Publications

Eosinophils are a myeloid cell subpopulation that mediates type 2 T helper cell immune responses. Unexpectedly, we identified a rapid accumulation of eosinophils in 22 human liver grafts after hepatic transplantation. In contrast, no eosinophils were detectable in healthy liver tissues before transplantation. Studies with two genetic mouse models of eosinophil deficiency and a mouse model of antibody-mediated eosinophil depletion revealed exacerbated liver injury after hepatic ischemia and reperfusion. Adoptive transfer of bone marrow-derived eosinophils normalized liver injury of eosinophil-deficient mice and reduced hepatic ischemia and reperfusion injury in wild-type mice. Mechanistic studies combining genetic and adoptive transfer approaches identified …

Risk Stratification Among Survivors Of Cardiac Arrest Considered For Coronary Angiography., Ahmed A Harhash, Teresa L May, Chiu-Hsieh Hsu, Sachin Agarwal, David B Seder, Michael R Mooney, Nainesh C. Patel Md, John Mcpherson, Paul Mcmullan, Richard Riker, Eldar Soreide, Karen G Hirsch, Pascal Stammet, Alison Dupont, Sten Rubertsson, Hans Friberg, Niklas Nielsen, Tanveer Rab, Karl B Kern

Cardiology Division

BACKGROUND: The American College of Cardiology Interventional Council published consensus-based recommendations to help identify resuscitated cardiac arrest patients with unfavorable clinical features in whom invasive procedures are unlikely to improve survival.

OBJECTIVES: This study sought to identify how many unfavorable features are required before prognosis is significantly worsened and which features are most impactful in predicting prognosis.

METHODS: Using the INTCAR (International Cardiac Arrest Registry), the impact of each proposed "unfavorable feature" on survival to hospital discharge was individually analyzed. Logistic regression was performed to assess the association of such unfavorable features with poor outcomes.

RESULTS: Seven unfavorable features (of …

Pandemic Makes Chronic Disease Prevention A Priority., Karen S. Kmetik, Alexis Skoufalos, David B. Nash

College of Population Health Faculty Papers

This article is the authors' final version prior to publication in Population Health Management, Volume 24, Issue 1, February 2021, Pages 1-2

Final publication is available from Mary Ann Liebert, Inc., publishers https://doi.org/10.1089/pop.2020.0126

The Association Of "Loss Of Smell" To Covid-19: A Systematic Review And Meta-Analysis., Muhammad Aziz, Hemant Goyal, Hossein Haghbin, Wade M Lee-Smith, Mahesh Gajendran, Abhilash Perisetti Md

Other Specialties

BACKGROUND: The presence of olfactory dysfunction or "loss of smell" has been reported as an atypical symptom in patients with coronavirus disease 2019 (COVID-19). We performed a systematic review and meta-analysis of the available literature to evaluate the prevalence of "loss of smell" in COVID-19 as well as its utility for prognosticating the disease severity.

METHODS: An exhaustive search of the PubMed/Medline, Embase, Web of Science, Cochrane Library, LitCovid NIH, and WHO COVID-19 database was conducted through August 6

RESULTS: A total of 51 studies with 11074 confirmed COVID-19 patients were included. Of these, 21 studies used a control group …

Defining The Genotypic And Phenotypic Spectrum Of X-Linked Msl3-Related Disorder, Theresa Brunet, Kirsty Mcwalter, Katharina Mayerhanser, Grace M Anbouba, Amy Armstrong-Javors, Ingrid Bader, Evan Baugh, Amber Begtrup, Caleb P Bupp, Bert L Callewaert, Anna Cereda, Margot A Cousin, Juan C Del Rey Jimenez, Laurie Demmer, Nikita R Dsouza, Nicole Fleischer, Ralitza H Gavrilova, Sumedha Ghate, Elisabeth Graf, Andrew Green, Sarah R Green, Maria Iascone, Ameni Kdissa, Dirk Klee, Eric W Klee, Emily Lancaster, Kristin Lindstrom, Johannes A Mayr, Meriel Mcentagart, Naomi J L Meeks, Dana Mittag, Harrison Moore, Anne K Olsen, Damara Ortiz, Gretchen Parsons, Loren D M Pena, Richard E Person, Sumit Punj, Gonzalo Alonso Ramos-Rivera, Maria J Guillen Sacoto, G Bradley Schaefer, Rhonda E Schnur, Tiana M Scott, Daryl A Scott, Carolyn R Serbinski, Vandana Shashi, Victoria Mok Siu, Barbro Fossøy Stadheim, Jennifer A Sullivan, Jana Švantnerová, Lea Velsher, David S Wargowski, Ingrid M Wentzensen, Dagmar Wieczorek, Juliane Winkelmann, Patrick Yap, Michael Zech, Michael T Zimmermann, Thomas Meitinger, Felix Distelmaier, Matias Wagner

Paediatrics Publications

PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome).

METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers.

RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of …

Rapid Decline In Telestroke Consults In The Setting Of Covid-19., Syed O. Shah., Robin Dharia, Jaime Stazi, Maureen Deprince, Robert H. Rosenwasswer

Farber Institute for Neuroscience Faculty Papers

Background and Purpose: As coronavirus disease 2019 (COVID-19) continues to be a global pandemic, there is a growing body of evidence suggesting that incidence of diseases that require emergent care, particularly myocardial infarction and ischemic stroke, has declined rapidly. The objective of this study is to quantify our experience of telestroke (TS) consults at a large tertiary comprehensive stroke center during the COVID-19 pandemic.

Methods: We retrospectively reviewed TS consults of patients presenting to our neuroscience network. Those with a confirmed diagnosis of acute ischemic stroke or transient ischemia attack were included. Data were compared from April 1, 2019, to …

Computer Automation For Physics Chart Check Should Be Adopted In Clinic To Replace Manual Chart Checking For Radiotherapy, Edward L. Clouser, Quan Chen, Yi Rong

Radiation Medicine Faculty Publications

No abstract provided.

Prediction Model For Freedom From Tlr From A Multi-Study Analysis Of Long-Term Results With The Zilver Ptx Drug-Eluting Peripheral Stent., Michael D Dake, Fabrizio Fanelli, Aaron E Lottes, Erin E O'Leary, Heidi Reichert, Xiaohui Jiang, Weiguo Fu, Osamu Iida, Kan Zen, Marc Schermerhorn, Thomas Zeller, Gary M Ansel

Heart and Vascular Articles

PURPOSE: Develop a prediction model to determine the impact of patient and lesion factors on freedom from target lesion revascularization (ffTLR) for patients who are candidates for Zilver PTX drug-eluting stent (DES) treatment for femoropopliteal lesions.

METHODS: Patient factors, lesion characteristics, and TLR results from five global studies were utilized for model development. Factors potentially associated with TLR (sex, age, diabetes, hypertension, hypercholesterolemia, renal disease, smoking status, Rutherford classification, lesion length, reference vessel diameter (RVD), popliteal involvement, total occlusion, calcification severity, prior interventions, and number of runoff vessels) were analyzed in a Cox proportional hazards model. Probability of ffTLR was …

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 …

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

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 …

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

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 …

Disparities In Sars-Cov-2 Positivity Rates: Associations With Race And Ethnicity, Harvey W Kaufman, Justin K Niles, David B. Nash

College of Population Health Faculty Papers

Numerous reports indicate that African Americans and Latinos are being affected disproportionately by coronavirus disease 2019 (COVID-19). Positivity rates have not been analyzed on scale because only 4 states report race/ethnicity as part of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Previous studies also have had little ability to control for many known risk factors to better identify the effects of COVID-19 on racial and ethnic communities. Using test results from a large national reference laboratory database that included patients from all 50 states and the District of Columbia, this study compared positivity rates for SARS-CoV-2 nucleic acid amplification …

The Quest For Conquering Covid-19: Updates From The Laboratory, David B. Nash

College of Population Health Faculty Papers

No abstract provided.