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Modulation Of Hedgehog Signaling By Kappa Opioids To Attenuate Osteoarthritis, Alexander E Weber, Omid Jalali, Sean Limfat, Ruzanna Shkhyan, Robert Van Der Horst, Siyoung Lee, Yucheng Lin, Liangliang Li, Erik N Mayer, Liming Wang, Nancy Q Liu, Frank A Petrigliano, Jay R Lieberman, Denis Evseenko Aug 2020

Modulation Of Hedgehog Signaling By Kappa Opioids To Attenuate Osteoarthritis, Alexander E Weber, Omid Jalali, Sean Limfat, Ruzanna Shkhyan, Robert Van Der Horst, Siyoung Lee, Yucheng Lin, Liangliang Li, Erik N Mayer, Liming Wang, Nancy Q Liu, Frank A Petrigliano, Jay R Lieberman, Denis Evseenko

Faculty, Staff and Students Publications

OBJECTIVE: Inhibition of hedgehog (HH) signaling prevents cartilage degeneration and promotes repair in animal models of osteoarthritis (OA). This study, undertaken in OA models and in human OA articular cartilage, was designed to explore whether kappa opioid receptor (KOR) modulation via the inhibition of HH signaling may have therapeutic potential for achieving disease-modifying activity in OA.

METHODS: Primary human articular cartilage and synovial tissue samples from patients with knee OA undergoing total joint replacement and from healthy human subjects were obtained from the National Disease Research Interchange. For in vivo animal studies, a partial medial meniscectomy (PMM) model of knee …


Low-Dose Versus High-Dose Carfilzomib With Dexamethasone (S1304) In Patients With Relapsed-Refractory Multiple Myeloma, Sikander Ailawadhi, Rachael Sexton, Suzanne Lentzsch, Muneer H Abidi, Peter M Voorhees, Adam D Cohen, Eric M Rohren, Stephen Heitner, Kevin Kelly, Niklas J Mackler, David M Baer, Antje Hoering, Brian Durie, Robert Z Orlowski Aug 2020

Low-Dose Versus High-Dose Carfilzomib With Dexamethasone (S1304) In Patients With Relapsed-Refractory Multiple Myeloma, Sikander Ailawadhi, Rachael Sexton, Suzanne Lentzsch, Muneer H Abidi, Peter M Voorhees, Adam D Cohen, Eric M Rohren, Stephen Heitner, Kevin Kelly, Niklas J Mackler, David M Baer, Antje Hoering, Brian Durie, Robert Z Orlowski

Faculty, Staff and Students Publications

PURPOSE: Treatment of multiple myeloma has evolved tremendously and optimal utilization of available therapies will ensure maximal patient benefits.

PATIENTS AND METHODS: We report the Southwest Oncology Group randomized phase II trial (S1304) comparing twice weekly low-dose (27 mg/m

RESULTS: Among 143 enrolled patients, of whom 121 were eligible and analyzable, the overall response rate was 42.8%, with no significant difference between the arms (

CONCLUSIONS: This randomized trial did not support a benefit of fixed duration, twice weekly 56 mg/m


Prevalence Of Helicobacter Pylori Positive Non-Cardia Gastric Adenocarcinoma Is Low And Decreasing In A Us Population, Theresa H Nguyen, Niharika Mallepally, Tariq Hammad, Yan Liu, Aaron P Thrift, Hashem B El-Serag, Mimi C Tan Aug 2020

Prevalence Of Helicobacter Pylori Positive Non-Cardia Gastric Adenocarcinoma Is Low And Decreasing In A Us Population, Theresa H Nguyen, Niharika Mallepally, Tariq Hammad, Yan Liu, Aaron P Thrift, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

BACKGROUND: Helicobacter pylori infection is an established causal factor for non-cardia gastric cancer. H. pylori negative gastric cancer prevalence among US patients is unclear.

METHODS: This retrospective cohort study examined H. pylori prevalence among consecutive patients with incident non-cardia gastric adenocarcinoma at the Houston VA Hospital (11/2007-10/2018). H. pylori positivity was defined by H. pylori on histopathology, positive antibody serology, stool antigen, or urea breath testing. We examined for trends in H. pylori negative gastric cancer based on year of diagnosis. Associations between histopathologic and cancer-related outcomes with H. pylori positivity were determined using regression models.

RESULTS: Of 91 patients …


Post-Registration Experience Of Nivolumab In Advanced Hepatocellular Carcinoma: An International Study, Petros Fessas, Ahmed Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Uqba Khan, Chiehju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Francesca Benevento, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Marron, David J Pinato Aug 2020

Post-Registration Experience Of Nivolumab In Advanced Hepatocellular Carcinoma: An International Study, Petros Fessas, Ahmed Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Uqba Khan, Chiehju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Francesca Benevento, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Marron, David J Pinato

Faculty, Staff and Students Publications

BACKGROUND: Nivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking.

PATIENTS AND METHODS: We performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia.

RESULTS: Patients received nivolumab for Barcelona Clinic Liver Cancer stage C (n=191, 92.0%) and Child-Pugh (CP) A (n=158, 67.8%) or B (n=75, 32.2%) HCC as first (n=85, 36.5%) or second to fourth systemic therapy line …


Platypnea-Orthodeoxia Syndrome Caused By An Intracardiac Shunt, Sanket P Borgaonkar, Wilson W Lam, Mehdi Razavi, Dhaval R Parekh Aug 2020

Platypnea-Orthodeoxia Syndrome Caused By An Intracardiac Shunt, Sanket P Borgaonkar, Wilson W Lam, Mehdi Razavi, Dhaval R Parekh

Faculty, Staff and Students Publications

Platypnea-orthodeoxia syndrome, a rare condition characterized by posture-related dyspnea, is usually caused by an intracardiac shunt, hepatopulmonary syndrome, or shunting resulting from severe pulmonary disease. We report the case of a 33-year-old woman who presented with increasing dyspnea and oxygen desaturation when she sat up or arose. Our diagnosis was platypnea-orthodeoxia syndrome. A lead of a previously implanted pacemaker exacerbated a severe tricuspid regurgitant jet that was directed toward the patient's intra-atrial septum. Percutaneous closure of a small secundum atrial septal defect eliminated right-to-left shunting and substantially improved the patient's functional status. In addition to this case, we discuss this …


Transcriptional Profiling Reveals Altered Biological Characteristics Of Chorionic Stem Cells From Women With Gestational Diabetes, Liyun Chen, Chung-Teng Wang, Nicholas R Forsyth, Pensee Wu Jul 2020

Transcriptional Profiling Reveals Altered Biological Characteristics Of Chorionic Stem Cells From Women With Gestational Diabetes, Liyun Chen, Chung-Teng Wang, Nicholas R Forsyth, Pensee Wu

Open Access Publications

BACKGROUND: Gestational diabetes (GDM) is a common complication of pregnancy. The impact of pregnancy complications on placental function suggests that extraembryonic stem cells in the placenta may also be affected during pregnancy. Neonatal tissue-derived stem cells, with the advantages of their differentiation capacity and non-invasive isolation processes, have been proposed as a promising therapeutic avenue for GDM management through potential cell therapy approaches. However, the influence of GDM on autologous stem cells remains unclear. Thus, studies that provide comprehensive understanding of stem cells isolated from women with GDM are essential to guide future clinical applications.

METHODS: Human chorionic membrane-derived stem …


Duodenal Microbiota In Stunted Undernourished Children With Enteropathy, Robert Y Chen, Vanderlene L Kung, Matthew C Hibberd, Janaki Guruge, Blanda Di Luccia, Kazi Ahsan, Elizabeth Kennedy, Jesus Santiago-Borges, Michael J Barratt, Jeffrey I Gordon, Et Al Jul 2020

Duodenal Microbiota In Stunted Undernourished Children With Enteropathy, Robert Y Chen, Vanderlene L Kung, Matthew C Hibberd, Janaki Guruge, Blanda Di Luccia, Kazi Ahsan, Elizabeth Kennedy, Jesus Santiago-Borges, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

BACKGROUND: Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota).

METHODS: In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy …


Sars-Cov-2 Reverse Genetics Reveals A Variable Infection Gradient In The Respiratory Tract, Yixuan J. Hou, Kenichi Okuda, Caitlin E. Edwards, David R. Martinez, Takanori Asakura, Kenneth H. Dinnon, Takafumi Kato, Rhianna E. Lee, Boyd L. Yount, Teresa M. Mascenik, Gang Chen, Kenneth N. Olivier, Andrew Ghio, Longping V. Tse, Sarah R. Leist, Lisa E. Gralinski, Alexandra Schäfer, Hong Dang, Rodney Gilmore, Satoko Nakano, Ling Sun, M Leslie Fulcher, Alessandra Livraghi-Butrico, Nathan I. Nicely, Mark Cameron, Cheryl Cameron, David J. Kelvin, Aravinda De Silva, David M. Margolis, Alena Markmann, Luther Bartelt, Ross Zumwalt, Fernando J. Martinez, Steven P. Salvatore, Alain Borczuk, Purushothama R. Tata, Vishwaraj Sontake, Adam Kimple, Ilona Jaspers, Wanda K. O'Neal, Scott H. Randell, Richard C. Boucher, Ralph S. Baric Jul 2020

Sars-Cov-2 Reverse Genetics Reveals A Variable Infection Gradient In The Respiratory Tract, Yixuan J. Hou, Kenichi Okuda, Caitlin E. Edwards, David R. Martinez, Takanori Asakura, Kenneth H. Dinnon, Takafumi Kato, Rhianna E. Lee, Boyd L. Yount, Teresa M. Mascenik, Gang Chen, Kenneth N. Olivier, Andrew Ghio, Longping V. Tse, Sarah R. Leist, Lisa E. Gralinski, Alexandra Schäfer, Hong Dang, Rodney Gilmore, Satoko Nakano, Ling Sun, M Leslie Fulcher, Alessandra Livraghi-Butrico, Nathan I. Nicely, Mark Cameron, Cheryl Cameron, David J. Kelvin, Aravinda De Silva, David M. Margolis, Alena Markmann, Luther Bartelt, Ross Zumwalt, Fernando J. Martinez, Steven P. Salvatore, Alain Borczuk, Purushothama R. Tata, Vishwaraj Sontake, Adam Kimple, Ilona Jaspers, Wanda K. O'Neal, Scott H. Randell, Richard C. Boucher, Ralph S. Baric

Pathology Research and Scholarship

The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 …


Characterization Of A Multicenter Pediatric-Hydrocephalus Shunt Biobank, Jacob Gluski, Paul Zajciw, Prashant Hariharan, Amanda Morgan, Diego M Morales, Andrew Jea, William Whitehead, Neena Marupudi, Steven Ham, Sandeep Sood, James P Mcallister Ii, David D Limbrick Jr, Carolyn A Harris Jul 2020

Characterization Of A Multicenter Pediatric-Hydrocephalus Shunt Biobank, Jacob Gluski, Paul Zajciw, Prashant Hariharan, Amanda Morgan, Diego M Morales, Andrew Jea, William Whitehead, Neena Marupudi, Steven Ham, Sandeep Sood, James P Mcallister Ii, David D Limbrick Jr, Carolyn A Harris

Open Access Publications

BACKGROUND: Pediatric hydrocephalus is a devastating and costly disease. The mainstay of treatment is still surgical shunting of cerebrospinal fluid (CSF). These shunts fail at a high rate and impose a significant burden on patients, their families and society. The relationship between clinical decision making and shunt failure is poorly understood and multifaceted, but catheter occlusion remains the most frequent cause of shunt complications. In order to investigate factors that affect shunt failure, we have established the Wayne State University (WSU) shunt biobank.

METHODS: To date, four hospital centers have contributed various components of failed shunts and CSF from patients …


Trial Of Roflumilast Cream For Chronic Plaque Psoriasis, Mark G. Lebwohl, Kim A. Papp, Linda F. Stein Gold, Melinda J. Gooderham, Leon H. Kircik, Zoe D. Draelos, Steven E. Kempers, Mathew Zirwas, Kathleen Smith, David W. Osborne, Marie-Louise Trotman, Lynn Navale, Charlotte Merritt, David R. Berk, Howard Welgus Jul 2020

Trial Of Roflumilast Cream For Chronic Plaque Psoriasis, Mark G. Lebwohl, Kim A. Papp, Linda F. Stein Gold, Melinda J. Gooderham, Leon H. Kircik, Zoe D. Draelos, Steven E. Kempers, Mathew Zirwas, Kathleen Smith, David W. Osborne, Marie-Louise Trotman, Lynn Navale, Charlotte Merritt, David R. Berk, Howard Welgus

Dermatology Articles

BACKGROUND: Systemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis.

METHODS: In this phase 2b, double-blind trial, we randomly assigned adults with plaque psoriasis in a 1:1:1 ratio to use roflumilast 0.3% cream, roflumilast 0.15% cream, or vehicle (placebo) cream once daily for 12 weeks. The primary efficacy outcome was the investigator's global assessment (IGA) of a status of clear or almost clear at week 6 (assessed on a 5-point scale of plaque thickening, scaling, and erythema; a …


The Influence Of Telehealth For Better Health Across Communities., Jane A. Mcelroy, Tamara M. Day, Mirna Becevic Jul 2020

The Influence Of Telehealth For Better Health Across Communities., Jane A. Mcelroy, Tamara M. Day, Mirna Becevic

Project ECHO Bibliography

Rapid spread of coronavirus disease 2019 (COVID-19) forced an abrupt shift in the traditional US health care delivery model to meet the needs of patients, staff, and communities. Through federal policy changes on telehealth, patient care shifted from in-person to telephone or video visits, and health care providers reached out to patients most at risk for exacerbation of chronic disease symptoms. ECHO (Extension for Community Healthcare Outcomes), a videoconferencing peer learning application, engaged health care providers across Missouri in the treatment and management of complex COVID-19-positive patients. Re-envisioning health care in the digital age includes robust utilization of telehealth to …


Portable, Field-Based Neuroimaging Using High-Density Diffuse Optical Tomography, Andrew K. Fishell, Ana María Arbeláez, Claudia P. Valdés, Tracy N. Burns-Yocum, Arefeh Sherafati, Edward J. Richter, Margarita Torres, Adam T. Eggebrecht, Christopher D. Smyser, Joseph P. Culver Jul 2020

Portable, Field-Based Neuroimaging Using High-Density Diffuse Optical Tomography, Andrew K. Fishell, Ana María Arbeláez, Claudia P. Valdés, Tracy N. Burns-Yocum, Arefeh Sherafati, Edward J. Richter, Margarita Torres, Adam T. Eggebrecht, Christopher D. Smyser, Joseph P. Culver

2020-Current year OA Pubs

Behavioral and cognitive tests in individuals who were malnourished as children have revealed malnutrition-related deficits that persist throughout the lifespan. These findings have motivated recent neuroimaging investigations that use highly portable functional near-infrared spectroscopy (fNIRS) instruments to meet the demands of brain imaging experiments in low-resource environments and enable longitudinal investigations of brain function in the context of long-term malnutrition. However, recent studies in healthy subjects have demonstrated that high-density diffuse optical tomography (HD-DOT) can significantly improve image quality over that obtained with sparse fNIRS imaging arrays. In studies of both task activations and resting state functional connectivity, HD-DOT is …


Electrically Coupled Inhibitory Interneurons Constrain Long-Range Connectivity Of Cortical Networks, Andrew W Kraft, Anish Mitra, Zachary P Rosenthal, Nico U F Dosenbach, Adam Q Bauer, Abraham Z Snyder, Marcus E Raichle, Joseph P Culver, Jin-Moo Lee Jul 2020

Electrically Coupled Inhibitory Interneurons Constrain Long-Range Connectivity Of Cortical Networks, Andrew W Kraft, Anish Mitra, Zachary P Rosenthal, Nico U F Dosenbach, Adam Q Bauer, Abraham Z Snyder, Marcus E Raichle, Joseph P Culver, Jin-Moo Lee

2020-Current year OA Pubs

Spontaneous infra-slow brain activity (ISA) exhibits a high degree of temporal synchrony, or correlation, between distant brain regions. The spatial organization of ISA synchrony is not explained by anatomical connections alone, suggesting that active neural processes coordinate spontaneous activity. Inhibitory interneurons (IINs) form electrically coupled connections via the gap junction protein connexin 36 (Cx36) and networks of interconnected IINs are known to influence neural synchrony over short distances. However, the role of electrically coupled IIN networks in regulating spontaneous correlation over the entire brain is unknown. In this study, we performed OIS imaging on Cx36-/- mice to examine the role …


Cross-Serotype Protection Against Group A Streptococcal Infections Induced By Immunization With Spy_2191, Pooja Sanduja, Manish Gupta, Vikas Kumar Somani, Vikas Yadav, Meenakshi Dua, Emanuel Hanski, Abhinay Sharma, Rakesh Bhatnagar, Atul Kumar Johri Jul 2020

Cross-Serotype Protection Against Group A Streptococcal Infections Induced By Immunization With Spy_2191, Pooja Sanduja, Manish Gupta, Vikas Kumar Somani, Vikas Yadav, Meenakshi Dua, Emanuel Hanski, Abhinay Sharma, Rakesh Bhatnagar, Atul Kumar Johri

Open Access Publications

Group A Streptococcus (GAS) infection causes a range of diseases, but vaccine development is hampered by the high number of serotypes. Here, using reverse vaccinology the authors identify SPy_2191 as a cross-protective vaccine candidate. From 18 initially identified surface proteins, only SPy_2191 is conserved, surface-exposed and inhibits both GAS adhesion and invasion. SPy_2191 immunization in mice generates bactericidal antibodies resulting in opsonophagocytic killing of prevalent and invasive GAS serotypes of different geographical regions, including M1 and M49 (India), M3.1 (Israel), M1 (UK) and M1 (USA). Resident splenocytes show higher interferon-γ and tumor necrosis factor-α secretion upon antigen re-stimulation, suggesting activation …


Molecular And Clinicopathologic Features Of Gliomas Harboring Ntrk Fusions, Matthew Torre, Sonika Dahiya, Et Al Jul 2020

Molecular And Clinicopathologic Features Of Gliomas Harboring Ntrk Fusions, Matthew Torre, Sonika Dahiya, Et Al

Open Access Publications

Fusions involving neurotrophic tyrosine receptor kinase (NTRK) genes are detected in ≤2% of gliomas and can promote gliomagenesis. The remarkable therapeutic efficacy of TRK inhibitors, which are among the first Food and Drug Administration-approved targeted therapies for NTRK-fused gliomas, has generated significant clinical interest in characterizing these tumors. In this multi-institutional retrospective study of 42 gliomas with NTRK fusions, next generation DNA sequencing (n = 41), next generation RNA sequencing (n = 1), RNA-sequencing fusion panel (n = 16), methylation profile analysis (n = 18), and histologic evaluation (n = 42) were performed. All infantile NTRK-fused gliomas (n = 7) …


Clinicopathologic Implications Of Myb And Beta-Catenin Expression In Adenoid Cystic Carcinoma, Susan Park, Manali Vora, Annemieke Van Zante, Joseph Humtsoe, Hyun-Su Kim, Sue Yom, Shweta Agarwal, Patrick Ha Jul 2020

Clinicopathologic Implications Of Myb And Beta-Catenin Expression In Adenoid Cystic Carcinoma, Susan Park, Manali Vora, Annemieke Van Zante, Joseph Humtsoe, Hyun-Su Kim, Sue Yom, Shweta Agarwal, Patrick Ha

Pathology Research and Scholarship

BACKGROUND: Adenoid cystic carcinoma (ACC) is the second most common malignancy of the salivary glands, accounting for ~ 1% of malignant tumors of the head and neck region and 10% of salivary gland neoplasms. Predicting the long-term outcomes of patients with ACC is still challenging, as reliable prognostic biomarkers are not available. Among salivary gland tumors, Myb overexpression is highly specific for ACC. In addition, the MYB-NF1B fusion translocation is a hallmark of ACC, and although the detection of this translocation does not appear to impact prognosis, the MYB-NF1B fusion is also implicated in MYB upregulation. Myb has recently been …


Proteogenomic Characterization Reveals Therapeutic Vulnerabilities In Lung Adenocarcinoma, Michael A. Gillette, Song Cao, Yize Li, Wen-Wei Liang, Michael C Wendl, Ramaswamy Govindan, Et Al. Jul 2020

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities In Lung Adenocarcinoma, Michael A. Gillette, Song Cao, Yize Li, Wen-Wei Liang, Michael C Wendl, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. …


Comparison Of Tissue Molecular Biomarker Testing Turnaround Times And Concordance Between Standard Of Care And The Biocartis Idylla Platform In Patients With Colorectal Cancer, Gregory J. Tsongalis, M Rabie Al Turkmani, Michael Suriawinata, Michael J. Babcock, Kristi Mitchell, Yi Ding, Lisa Scicchitano, Adrian Tira, Lela Buckingham, Sara Atkinson, Amy Lax, Dara L. Aisner, Kurtis D. Davies, Holly N. Wood, Stacey S. O'Neill, Edward A. Levine, Judy Sequeira, Shuko Harada, Gina Defrank, Ravikumar Paluri, Bradford A. Tan, Heather Colabella, Christopher Snead, Marcia Cruz-Correa, Virginia Ramirez, Arnaldo Rojas, Huiya Huang, Alexander C. Mackinnon, Fernando U. Garcia, Sharon M. Cavone, Mutasim Elfahal, Gyorgy Abel, Mohammad A. Vasef, Andrew Judd, Mark W. Linder, Khaled Alkhateeb, William L. Skinner, Ralph Boccia, Kashyap Patel Jul 2020

Comparison Of Tissue Molecular Biomarker Testing Turnaround Times And Concordance Between Standard Of Care And The Biocartis Idylla Platform In Patients With Colorectal Cancer, Gregory J. Tsongalis, M Rabie Al Turkmani, Michael Suriawinata, Michael J. Babcock, Kristi Mitchell, Yi Ding, Lisa Scicchitano, Adrian Tira, Lela Buckingham, Sara Atkinson, Amy Lax, Dara L. Aisner, Kurtis D. Davies, Holly N. Wood, Stacey S. O'Neill, Edward A. Levine, Judy Sequeira, Shuko Harada, Gina Defrank, Ravikumar Paluri, Bradford A. Tan, Heather Colabella, Christopher Snead, Marcia Cruz-Correa, Virginia Ramirez, Arnaldo Rojas, Huiya Huang, Alexander C. Mackinnon, Fernando U. Garcia, Sharon M. Cavone, Mutasim Elfahal, Gyorgy Abel, Mohammad A. Vasef, Andrew Judd, Mark W. Linder, Khaled Alkhateeb, William L. Skinner, Ralph Boccia, Kashyap Patel

Pathology Research and Scholarship

OBJECTIVES: Management of colorectal cancer warrants mutational analysis of KRAS/NRAS when considering anti-epidermal growth factor receptor therapy and BRAF testing for prognostic stratification. In this multicenter study, we compared a fully integrated, cartridge-based system to standard-of-care assays used by participating laboratories.

METHODS: Twenty laboratories enrolled 874 colorectal cancer cases between November 2017 and December 2018. Testing was performed on the Idylla automated system (Biocartis) using the KRAS and NRAS-BRAF cartridges (research use only) and results compared with in-house standard-of-care testing methods.

RESULTS: There were sufficient data on 780 cases to measure turnaround time compared with standard assays. In-house polymerase chain …


Understanding Type 2 Diabetes Mellitus Among Haitian American Women: A Cultural Perspective, Balkys L. Bivins, Indra R Hershorin, Lonar M. Umadhay Jul 2020

Understanding Type 2 Diabetes Mellitus Among Haitian American Women: A Cultural Perspective, Balkys L. Bivins, Indra R Hershorin, Lonar M. Umadhay

Faculty Articles

The prevalence of type 2 diabetes mellitus (T2DM) is 19.7% in Haiti (DeGennaro et al., 2018). Haitian American women (HAW) experience difficulties with adherence to T2DM treatment and management (Bivins, 2016; Magny-Normilus et al., 2019; Vimalananda et al., 2011; Huffman et al., 2013); however, no previous study was found that focused exclusively on Haitian American women with T2DM. Van Manen's six research activities guided this phenomenological qualitative inquiry. Recruitment included 25 Haitian American women (N = 25) with T2DM from three South Florida counties. Data were collected using a vignette and audio-recorded semi-structured interviews with open-ended questions. Recordings were then …


Screening And Treatment Outcomes In Adults And Children With Type 1 Diabetes And Asymptomatic Celiac Disease: The Cd-Diet Study., Farid H Mahmud, Antoine B M Clarke, Kariym C Joachim, Esther Assor, Charlotte Mcdonald, Fred Saibil, Heather A Lochnan, Zubin Punthakee, Amish Parikh, Andrew Advani, Baiju R Shah, Bruce A Perkins, Caroline S Zuijdwijk, David R Mack, Dror Koltin, Emilia N De Melo, Eugene Hsieh, Geetha Mukerji, Jeremy Gilbert, Kevin Bax, Margaret L Lawson, Maria Cino, Melanie D Beaton, Navaaz A Saloojee, Olivia Lou, Patricia H Gallego, Premysl Bercik, Robyn L Houlden, Ronnie Aronson, Susan E Kirsch, William G Paterson, Margaret A Marcon Jul 2020

Screening And Treatment Outcomes In Adults And Children With Type 1 Diabetes And Asymptomatic Celiac Disease: The Cd-Diet Study., Farid H Mahmud, Antoine B M Clarke, Kariym C Joachim, Esther Assor, Charlotte Mcdonald, Fred Saibil, Heather A Lochnan, Zubin Punthakee, Amish Parikh, Andrew Advani, Baiju R Shah, Bruce A Perkins, Caroline S Zuijdwijk, David R Mack, Dror Koltin, Emilia N De Melo, Eugene Hsieh, Geetha Mukerji, Jeremy Gilbert, Kevin Bax, Margaret L Lawson, Maria Cino, Melanie D Beaton, Navaaz A Saloojee, Olivia Lou, Patricia H Gallego, Premysl Bercik, Robyn L Houlden, Ronnie Aronson, Susan E Kirsch, William G Paterson, Margaret A Marcon

Paediatrics Publications

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD.

RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA

RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%,

CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.


Can Children Catch Up From The Consequences Of Undernourishment? Evidence From Child Linear Growth, Developmental Epigenetics, And Brain And Neurocognitive Development, Jef L. Leroy, Edward A. Frongillo Jr., Pragya Dewan, Maureen M. Black, Robert A. Waterland Jul 2020

Can Children Catch Up From The Consequences Of Undernourishment? Evidence From Child Linear Growth, Developmental Epigenetics, And Brain And Neurocognitive Development, Jef L. Leroy, Edward A. Frongillo Jr., Pragya Dewan, Maureen M. Black, Robert A. Waterland

Faculty Publications

Recovery from nutritionally induced height deficits continues to garner attention. The current literature on catch-up growth, however, has 2 important limitations: wide-ranging definitions of catch-up growth are used, and it remains unclear whether children can recover from the broader consequences of undernutrition. We addressed these shortcomings by reviewing the literature on the criteria for catch-up in linear growth and on the potential to recover from undernutrition early in life in 3 domains: linear growth, developmental epigenetics, and child brain and neurocognitive development. Four criteria must be met to demonstrate catch-up growth in height: after a period in which a growth-inhibiting …


Respiratory Viral Panels And Pediatric Airway Evaluation: The Role Of Testing For Upper Respiratory Infections To Stratify Perioperative Risk., Weston L Niermeyer, Jessica Ball, Noah Worobetz, Tran Bourgeois, Amanda Onwuka, Candice Burrier, Tendy Chiang Jul 2020

Respiratory Viral Panels And Pediatric Airway Evaluation: The Role Of Testing For Upper Respiratory Infections To Stratify Perioperative Risk., Weston L Niermeyer, Jessica Ball, Noah Worobetz, Tran Bourgeois, Amanda Onwuka, Candice Burrier, Tendy Chiang

Ambulatory and Primary Care Articles

OBJECTIVES: Children admitted with stridor and respiratory distress comprise a complex patient group that requires the otolaryngologist to decide when to assess and intervene with direct laryngoscopy and bronchoscopy (DLB). Historically, the diagnosis of viral upper respiratory tract infection (URTI) can lead to postponement of surgery due to concerns of perioperative complications related to acute illness. Respiratory viral panels (RVP) are often used to confirm the presence of recent or active viral infection and can affect the differential diagnosis of upper airway obstruction. This study examined whether positive RVP testing is associated with perioperative complications and operative findings in pediatric …


Development Of The Uncertainty Communication Checklist: A Patient-Centered Approach To Patient Discharge From The Emergency Department, Kristin L. Rising, Rhea E. Powell, Kenzie A Cameron, David H Salzman, Dimitrios Papanagnou, Amanda Doty, Lori Latimer, Katherine Piserchia, William C Mcgaghie, Danielle M Mccarthy Jul 2020

Development Of The Uncertainty Communication Checklist: A Patient-Centered Approach To Patient Discharge From The Emergency Department, Kristin L. Rising, Rhea E. Powell, Kenzie A Cameron, David H Salzman, Dimitrios Papanagnou, Amanda Doty, Lori Latimer, Katherine Piserchia, William C Mcgaghie, Danielle M Mccarthy

Department of Emergency Medicine Faculty Papers

Clear communication with patients upon emergency department (ED) discharge is important for patient safety during the transition to outpatient care. Over one-third of patients are discharged from the ED with diagnostic uncertainty, yet there is no established approach for effective discharge communication in this scenario. From 2017 to 2019, the authors developed the Uncertainty Communication Checklist for use in simulation-based training and assessment of emergency physician communication skills when discharging patients with diagnostic uncertainty. This development process followed the established 12-step Checklist Development Checklist framework and integrated patient feedback into 6 of the 12 steps. Patient input was included as …


The Socioeconomic Impact Of Employing Female Deminers In Sri Lanka, Gichd Jul 2020

The Socioeconomic Impact Of Employing Female Deminers In Sri Lanka, Gichd

Global CWD Repository

This report outlines the key findings of the study looking at the socioeconomic impact of employing female deminers in Sri Lanka. 10 years after the first clearance operations in Sri Lanka, hundreds of Sri Lankan women and men are now employed in the Northern and Eastern parts of the country. The key findings highlight how employment has transformed female and male deminers’ capacity to access and own resources and services, as well as changes in female deminers’ decision-making capacities, how they perceive themselves, and shifts in their families’ and community members’ attitudes towards gender norms.


Physiological Factors Of Female Runners With And Without Stress Fracture Histories: A Pilot Study., Therese E Johnston, Colleen Dempsey, Frances Gilman, Ryan Tomlinson, Ann-Katrin Jacketti, Jeremy Close Jul 2020

Physiological Factors Of Female Runners With And Without Stress Fracture Histories: A Pilot Study., Therese E Johnston, Colleen Dempsey, Frances Gilman, Ryan Tomlinson, Ann-Katrin Jacketti, Jeremy Close

Department of Physical Therapy Faculty Papers

BACKGROUND: Female runners are at increased risk of stress fractures (SFs) compared with men. Literature is lacking with regard to best practice for preventing and treating SFs in women. The purpose of the study was to compare physiological measures and running-related factors between women of various ages and running abilities with and without a history of running-related SFs.

HYPOTHESIS: Women with and without SF histories will differ with regard to medical and menstrual history, bone health, body composition, nutrition, and running history.

STUDY DESIGN: Prospective cohort study.

LEVEL OF EVIDENCE: Level 2.

METHODS: A total of 20 female runners with …


Test-Retest Reliability Of Fmri-Measured Brain Activity During Decision Making Under Risk, Ozlem Korucuoglu, Michael P. Harms, Serguei V. Astafiev, James T. Kennedy, Semyon Golosheykin, Deanna M. Barch, Andrey P. Anokhin Jul 2020

Test-Retest Reliability Of Fmri-Measured Brain Activity During Decision Making Under Risk, Ozlem Korucuoglu, Michael P. Harms, Serguei V. Astafiev, James T. Kennedy, Semyon Golosheykin, Deanna M. Barch, Andrey P. Anokhin

2020-Current year OA Pubs

Neural correlates of decision making under risk are being increasingly utilized as biomarkers of risk for substance abuse and other psychiatric disorders, treatment outcomes, and brain development. This research relies on the basic assumption that fMRI measures of decision making represent stable, trait-like individual differences. However, reliability needs to be established for each individual construct. Here we assessed long-term test-retest reliability (TRR) of regional brain activations related to decision making under risk using the Balloon Analogue Risk Taking task (BART) and identified regions with good TRRs and familial influences, an important prerequisite for the use of fMRI measures in genetic …


On The Nature Of Monozygotic Twin Concordance And Discordance For Autistic Trait Severity: A Quantitative Analysis, Lauren Castelbaum, Chad M Sylvester, Yi Zhang, Qiongru Yu, John N Constantino Jul 2020

On The Nature Of Monozygotic Twin Concordance And Discordance For Autistic Trait Severity: A Quantitative Analysis, Lauren Castelbaum, Chad M Sylvester, Yi Zhang, Qiongru Yu, John N Constantino

2020-Current year OA Pubs

The characterizing features of autism spectrum disorder (ASD) are continuously distributed in nature; however, prior twin studies have not systematically incorporated this knowledge into estimations of concordance and discordance. We conducted a quantitative analysis of twin-twin similarity for autistic trait severity in three existing data sets involving 366 pairs of uniformly-phenotyped monozygotic (MZ) twins with and without ASD. Probandwise concordance for ASD was 96%; however, MZ trait correlations differed markedly for pairs with ASD trait burden below versus above the threshold for clinical diagnosis, with R


A Phenomenological Study Examining The Experiences Of Female High School Career And Technical Education Completers Who Participated In A Technology-Based Program Of Study, Stephen Christopher Tate Jul 2020

A Phenomenological Study Examining The Experiences Of Female High School Career And Technical Education Completers Who Participated In A Technology-Based Program Of Study, Stephen Christopher Tate

Doctoral Dissertations and Projects

The purpose of this phenomenological study was to investigate how female high school students who earned Career and Technical Education (CTE) completer status in a technology-based program of study (POS) in Virginia describe their experiences. CTE completer status is defined as having met the Virginia Department of Education’s CTE completer requirements in a technology-based POS. This study was guided by three theories: Self-efficacy theory was applied as it relates to the participants’ status as completers in a technology-based CTE POS; Role-congruity theory suggests that men and women occupy social roles with attendant stereotypes which contributed to how participants described their …


Association Of Interleukin 7 Immunotherapy With Lymphocyte Counts Among Patients With Severe Coronavirus Disease 2019 (Covid-19), Pierre Francois Laterre, Bruno François, Christine Collienne, Philippe Hantson, Robin Jeannet, Kenneth E. Remy, Richard S. Hotchkiss Jul 2020

Association Of Interleukin 7 Immunotherapy With Lymphocyte Counts Among Patients With Severe Coronavirus Disease 2019 (Covid-19), Pierre Francois Laterre, Bruno François, Christine Collienne, Philippe Hantson, Robin Jeannet, Kenneth E. Remy, Richard S. Hotchkiss

Open Access Publications

No abstract provided.


A Simplified, Combined Protocol Versus Standard Treatment For Acute Malnutrition In Children 6-59 Months (Compas Trial): A Cluster-Randomized Controlled Non-Inferiority Trial In Kenya And South Sudan, Jeanette Bailey, Charles Opondo, Natasha Lelijveld, Bethany Marron, Pamela Onyo, Eunice N. Musyoki, Susan W. Adongo, Mark Manary, André Briend, Marko Kerac Jul 2020

A Simplified, Combined Protocol Versus Standard Treatment For Acute Malnutrition In Children 6-59 Months (Compas Trial): A Cluster-Randomized Controlled Non-Inferiority Trial In Kenya And South Sudan, Jeanette Bailey, Charles Opondo, Natasha Lelijveld, Bethany Marron, Pamela Onyo, Eunice N. Musyoki, Susan W. Adongo, Mark Manary, André Briend, Marko Kerac

Open Access Publications

BACKGROUND: Malnutrition underlies 3 million child deaths worldwide. Current treatments differentiate severe acute malnutrition (SAM) from moderate acute malnutrition (MAM) with different products and programs. This differentiation is complex and costly. The Combined Protocol for Acute Malnutrition Study (ComPAS) assessed the effectiveness of a simplified, unified SAM/MAM protocol for children aged 6-59 months. Eliminating the need for separate products and protocols could improve the impact of programs by treating children more easily and cost-effectively, reaching more children globally.

METHODS AND FINDINGS: A cluster-randomized non-inferiority trial compared a combined protocol against standard care in Kenya and South Sudan. Randomization was stratified …