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Marijuana And Its Cardiovascular Implications, Albert Bui, Daniel Powell, Victoria Cho, Kelsey Lindsley, Lindsey Peters Dec 2019

Marijuana And Its Cardiovascular Implications, Albert Bui, Daniel Powell, Victoria Cho, Kelsey Lindsley, Lindsey Peters

Pharmacy and Wellness Review

As marijuana becomes legalized for medical use, it is important for prescribers and pharmacists to be knowledgeable about the important aspects of marijuana such as mechanism of action, indications and abuse potential. Although marijuana's medicinal benefits are frequently reported, the risks, namely cardiovascular risks, associated with its utilization are often overlooked. Use of marijuana has been reported to increase the risk of myocardial infarction, tachycardia and hypotension, among others. Health care providers must determine if marijuana's benefits outweigh such risks when marijuana therapy is an option. It is also important for pharmacists to understand how to successfully counsel patients using …


Fda Approves New Inhaled Insulin: Afrezza® (Technosphere® Insulin), Benjamin Finley, Christina Ciccone, Kimberly Loughlin, Michelle Musser Dec 2019

Fda Approves New Inhaled Insulin: Afrezza® (Technosphere® Insulin), Benjamin Finley, Christina Ciccone, Kimberly Loughlin, Michelle Musser

Pharmacy and Wellness Review

Diabetes is an endocrine disease caused by deficiency or malfunction of insulin that results in high blood glucose levels and places patients at higher risk for a number of complications. This chronic disease is difficult to manage and affects millions of people in the United States, costing the health care system billions of dollars a year. Of a variety of antidiabetic agents used to control blood glucose, insulin is perhaps the most effective, but until recently it was only available in injectable form. As of June 27, 2014, a new inhaled insulin called Afrezza® (Technosphere® insulin) was approved by the …


Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 3.0., Eric W Deutsch, Lydie Lane, Christopher M Overall, Nuno Bandeira, Mark S Baker, Charles Pineau, Robert L Moritz, Fernando Corrales, Sandra Orchard, Jennifer E Van Eyk, Young-Ki Paik, Susan T Weintraub, Yves Vandenbrouck, Gilbert S Omenn Dec 2019

Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 3.0., Eric W Deutsch, Lydie Lane, Christopher M Overall, Nuno Bandeira, Mark S Baker, Charles Pineau, Robert L Moritz, Fernando Corrales, Sandra Orchard, Jennifer E Van Eyk, Young-Ki Paik, Susan T Weintraub, Yves Vandenbrouck, Gilbert S Omenn

Articles, Abstracts, and Reports

The Human Proteome Organization's (HUPO) Human Proteome Project (HPP) developed Mass Spectrometry (MS) Data Interpretation Guidelines that have been applied since 2016. These guidelines have helped ensure that the emerging draft of the complete human proteome is highly accurate and with low numbers of false-positive protein identifications. Here, we describe an update to these guidelines based on consensus-reaching discussions with the wider HPP community over the past year. The revised 3.0 guidelines address several major and minor identified gaps. We have added guidelines for emerging data independent acquisition (DIA) MS workflows and for use of the new Universal Spectrum Identifier …


Snord94 Expression Level Alters Methylation At C62 In Snrna U6., Allison Ogren, Nataliya Kibiryeva, Jennifer A. Marshall, James O'Brien, Douglas C. Bittel Dec 2019

Snord94 Expression Level Alters Methylation At C62 In Snrna U6., Allison Ogren, Nataliya Kibiryeva, Jennifer A. Marshall, James O'Brien, Douglas C. Bittel

Manuscripts, Articles, Book Chapters and Other Papers

Understanding the regulation of development can help elucidate the pathogenesis behind many developmental defects found in humans and other vertebrates. Evidence has shown that alternative splicing of messenger RNA (mRNA) plays a role in developmental regulation, but our knowledge of the underlying mechanisms that regulate alternative splicing are incomplete. Notably, a subset of small noncoding RNAs known as scaRNAs (small cajal body associated RNAs) contribute to spliceosome maturation and function through guiding covalent modification of spliceosomal RNAs with either methylation or pseudouridylation on specific nucleotides, but the developmental significance of these modifications is not well understood. Our focus is on …


Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito Dec 2019

Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

Physiology Faculty Publications

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …


Text-Mining Clinically Relevant Cancer Biomarkers For Curation Into The Civic Database, Jake Lever, Martin R Jones, Arpad M Danos, Kilannin Krysiak, Melika Bonakdar, Jasleen K Grewal, Luka Culibrk, Obi L Griffith, Malachi Griffith, Steven J M Jones Dec 2019

Text-Mining Clinically Relevant Cancer Biomarkers For Curation Into The Civic Database, Jake Lever, Martin R Jones, Arpad M Danos, Kilannin Krysiak, Melika Bonakdar, Jasleen K Grewal, Luka Culibrk, Obi L Griffith, Malachi Griffith, Steven J M Jones

Open Access Publications

BACKGROUND: Precision oncology involves analysis of individual cancer samples to understand the genes and pathways involved in the development and progression of a cancer. To improve patient care, knowledge of diagnostic, prognostic, predisposing, and drug response markers is essential. Several knowledgebases have been created by different groups to collate evidence for these associations. These include the open-access Clinical Interpretation of Variants in Cancer (CIViC) knowledgebase. These databases rely on time-consuming manual curation from skilled experts who read and interpret the relevant biomedical literature.

METHODS: To aid in this curation and provide the greatest coverage for these databases, particularly CIViC, we …


Hccs And Hcas In Non-Cirrhotic Patients: What You See May Not Be Enough, Christina Ling, Sameen Khalid, David Martin, Joshua Hanson, Daniel Castresana, Denis Mccarthy Dec 2019

Hccs And Hcas In Non-Cirrhotic Patients: What You See May Not Be Enough, Christina Ling, Sameen Khalid, David Martin, Joshua Hanson, Daniel Castresana, Denis Mccarthy

Pathology Research and Scholarship

Case 1 A previously healthy 16-year-old man was initially evaluated in the emergency department for traumatic injuries following a high-impact motor vehicle accident. He was a bodybuilder who used anabolic steroids. He denied abdominal or back pain. His physical examination was signifcant for a palpable liver edge. Routine laboratory tests including liver function tests were unremarkable. A computed tomographic (CT) scan showed an unsuspected mass in the right lobe of the liver. A subsequent triple-phase magnetic resonance imaging (MRI) scan of the abdomen showed a 15.1 × 15.0 × 10.8 cm mass in the right hepatic lobe that exhibited heterogeneous …


Impact Of Project Echo Models Of Medical Tele-Education: A Systematic Review, Ryan K. Mcbain, Jessica L. Sousa, Adam J. Rose, Sangita M. Baxi, Laura J. Faherty, Caroline Taplin, Andre Chappel, Shira H. Fischer Dec 2019

Impact Of Project Echo Models Of Medical Tele-Education: A Systematic Review, Ryan K. Mcbain, Jessica L. Sousa, Adam J. Rose, Sangita M. Baxi, Laura J. Faherty, Caroline Taplin, Andre Chappel, Shira H. Fischer

Project ECHO Bibliography

BACKGROUND: Extension for Community Healthcare Outcomes (ECHO) and related models of medical tele-education are rapidly expanding; however, their effectiveness remains unclear. This systematic review examines the effectiveness of ECHO and ECHO-like medical tele-education models of healthcare delivery in terms of improved provider- and patient-related outcomes.

METHODS: We searched English-language studies in PubMed, Embase, and PsycINFO databases from 1 January 2007 to 1 December 2018 as well as bibliography review. Two reviewers independently screened citations for peer-reviewed publications reporting provider- and/or patient-related outcomes of technology-enabled collaborative learning models that satisfied six criteria of the ECHO framework. Reviewers then independently abstracted data, …


Results Of A Phase 1 Multicentre Investigation Of Dexmedetomidine Bolus And Infusion In Corrective Infant Cardiac Surgery, Athena F Zuppa, Susan C Nicolson, Nicole S Wilder, Juan C Ibla, Erin A Gottlieb, Kristin M Burns, Mario Stylianou, Felicia Trachtenberg, Hua Ni, Tera H Skeen, Dean B Andropoulos Dec 2019

Results Of A Phase 1 Multicentre Investigation Of Dexmedetomidine Bolus And Infusion In Corrective Infant Cardiac Surgery, Athena F Zuppa, Susan C Nicolson, Nicole S Wilder, Juan C Ibla, Erin A Gottlieb, Kristin M Burns, Mario Stylianou, Felicia Trachtenberg, Hua Ni, Tera H Skeen, Dean B Andropoulos

Faculty, Staff and Students Publications

BACKGROUND: Dexmedetomidine (DEX) is increasingly used intraoperatively in infants undergoing cardiac surgery. This phase 1 multicentre study sought to: (i) determine the safety of DEX for cardiac surgery with cardiopulmonary bypass; (ii) determine the pharmacokinetics (PK) of DEX; (iii) create a PK model and dosing for steady-state DEX plasma levels; and (iv) validate the PK model and dosing.

METHODS: We included 122 neonates and infants (0-180 days) with D-transposition of the great arteries, ventricular septal defect, or tetralogy of Fallot. Dose escalation was used to generate NONMEM® PK modelling, and then validation was performed to achieve low (200-300 pg ml …


Mutations In Lamb2 Are Associated With Albuminuria And Optic Nerve Hypoplasia With Hypopituitarism, Mona Tahoun, Jennifer C Chandler, Emma Ashton, Scott Haston, Athia Hannan, Ji Soo Kim, Felipe D'Arco, D Bockenhauer, G Anderson, Meei-Hua Lin, Salah Marzouk, Marwa H Saied, Jeffrey H Miner, Mehul T Dattani, Aoife M Waters Nov 2019

Mutations In Lamb2 Are Associated With Albuminuria And Optic Nerve Hypoplasia With Hypopituitarism, Mona Tahoun, Jennifer C Chandler, Emma Ashton, Scott Haston, Athia Hannan, Ji Soo Kim, Felipe D'Arco, D Bockenhauer, G Anderson, Meei-Hua Lin, Salah Marzouk, Marwa H Saied, Jeffrey H Miner, Mehul T Dattani, Aoife M Waters

Open Access Publications

CONTEXT: Mutations in LAMB2, encoding the basement membrane protein, laminin β2, are associated with an autosomal recessive disorder characterized by congenital nephrotic syndrome, ocular abnormalities, and neurodevelopmental delay (Pierson syndrome).

CASE DESCRIPTION: This report describes a 12-year-old boy with short stature, visual impairment, and developmental delay who presented with macroscopic hematuria and albuminuria. He had isolated growth hormone deficiency, optic nerve hypoplasia, and a small anterior pituitary with corpus callosum dysgenesis on his cranial magnetic resonance imaging, thereby supporting a diagnosis of optic nerve hypoplasia syndrome. Renal histopathology revealed focal segmental glomerulosclerosis. Using next-generation sequencing on a targeted gene panel …


Three Genetic-Environmental Networks For Human Personality, Igor Zwir, Coral Del-Val, Dragan M Svrakic, Nigel Lester, Sandor Rozsa, Maribel Martinez, Daniel Mamah, C Charles Gu, C Robert Cloninger, Et Al Nov 2019

Three Genetic-Environmental Networks For Human Personality, Igor Zwir, Coral Del-Val, Dragan M Svrakic, Nigel Lester, Sandor Rozsa, Maribel Martinez, Daniel Mamah, C Charles Gu, C Robert Cloninger, Et Al

Open Access Publications

Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are …


Six Month Abstinence Heterogeneity In The Best Quit Study., Harold S Javitz, Terry M Bush, Jennifer C Lovejoy, Alula J Torres, Tallie Wetzel, Ken P Wassum, Marcia M Tan, Nabil Alshurafa, Bonnie Spring Nov 2019

Six Month Abstinence Heterogeneity In The Best Quit Study., Harold S Javitz, Terry M Bush, Jennifer C Lovejoy, Alula J Torres, Tallie Wetzel, Ken P Wassum, Marcia M Tan, Nabil Alshurafa, Bonnie Spring

Articles, Abstracts, and Reports

BACKGROUND: Understanding the characteristics of smokers who are successful in quitting may help to increase smoking cessation rates.

PURPOSE: To examine heterogeneity in cessation outcome at 6 months following smoking cessation behavioral counseling with or without weight management counseling.

METHODS: 2,540 smokers were recruited from a large quitline provider and then randomized to receive proactive smoking cessation behavioral counseling without or with two versions of weight management counseling. A Classification and Regression Tree (CART) analysis was conducted to identify the individual pretreatment and treatment characteristics of groups of smokers with different quitting success (as measured by point prevalence of self-reported …


Validation Of A 5-Item Tool To Measure Patient Assessment Of Clinician Compassion In The Emergency Department, Praveen Sabapathi, Michael B Roberts, Brian M Fuller, Michael A Puskarich, Christopher W Jones, J Hope Kilgannon, Valerie Braz, Christina Creel-Bulos, Nathaniel Scott, Kristina L Tester, Anthony Mazzarelli, Stephen Trzeciak, Brian W Roberts Nov 2019

Validation Of A 5-Item Tool To Measure Patient Assessment Of Clinician Compassion In The Emergency Department, Praveen Sabapathi, Michael B Roberts, Brian M Fuller, Michael A Puskarich, Christopher W Jones, J Hope Kilgannon, Valerie Braz, Christina Creel-Bulos, Nathaniel Scott, Kristina L Tester, Anthony Mazzarelli, Stephen Trzeciak, Brian W Roberts

Open Access Publications

BACKGROUND: To test if the 5-item compassion measure (a tool previously validated in the outpatient setting to measure patient assessment of clinician compassion) is a valid and reliable tool to quantify a distinct construct (i.e. clinical compassion) among patients evaluated in the emergency department (ED).

METHODS: Cross-sectional study conducted in three academic emergency departments in the U.S. between November 2018 and April 2019. We enrolled adult patients who were evaluated in the EDs of the participating institutions and administered the 5-item compassion measure after completion of care in the ED. Validity testing was performed using confirmatory factor analysis. Cronbach's alpha …


Gene Expression Analysis To Detect Disseminated Tumor Cells In The Bone Marrow Of Triple-Negative Breast Cancer Patients Predicts Metastatic Relapse, Chidananda M Siddappa, Sreeraj G Pillai, Jackie Snider, Patsy Alldredge, Kathyrn Trinkaus, Mark A Watson, Rebecca Aft Nov 2019

Gene Expression Analysis To Detect Disseminated Tumor Cells In The Bone Marrow Of Triple-Negative Breast Cancer Patients Predicts Metastatic Relapse, Chidananda M Siddappa, Sreeraj G Pillai, Jackie Snider, Patsy Alldredge, Kathyrn Trinkaus, Mark A Watson, Rebecca Aft

Open Access Publications

PURPOSE: Disseminated tumor cells (DTCs) in the BM of breast cancer patients predict early disease relapse, but the molecular heterogeneity of these cells is less well characterized. Expression of a 46-gene panel was used to detect DTCs and classify patient BM samples to determine whether a composite set of biomarkers could better predict metastatic relapse.

METHODS: Using a high-throughput qRT-PCR assay platform, BM specimens collected from 70 breast cancer patients prior to neoadjuvant therapy were analyzed for the expression of 46 gene transcripts. Gene expression was scored positive (detectable) relative to a reference pool of 16 healthy female control BM …


Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha Nov 2019

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …


Development And Psychometric Properties Of A Prostate Cancer Knowledge Scale For African American Men, Otis L. Owens, Abbas Tavakoli Drph, Theda Rose, Nikki R. Wooten Nov 2019

Development And Psychometric Properties Of A Prostate Cancer Knowledge Scale For African American Men, Otis L. Owens, Abbas Tavakoli Drph, Theda Rose, Nikki R. Wooten

Faculty Publications

African American men have the highest prostate cancer-related mortality nationally. In response to this disparity, targeted interventions are emerging to enhance African American men's prostate cancer (PrCA) knowledge to ensure they are equipped to make informed decisions about PrCA screening with health-care providers. African American men's PrCA knowledge has been measured inconsistently over time with limited psychometric evidence. The factor structure of this construct in African American men is relatively unknown. This study describes the development and psychometric evaluation of an 18-item Prostate Cancer Knowledge Scale among 352 African American men. Exploratory factor analysis (EFA) was conducted using weighted least …


Las Dos Cosas Versus Exclusive Breastfeeding: A Culturally And Linguistically Exploratory Intervention Study In Hispanic Mothers Living In Kentucky, Ana Maria Linares, Diana Cartagena, Mary Kay Rayens Nov 2019

Las Dos Cosas Versus Exclusive Breastfeeding: A Culturally And Linguistically Exploratory Intervention Study In Hispanic Mothers Living In Kentucky, Ana Maria Linares, Diana Cartagena, Mary Kay Rayens

Nursing Faculty Publications

INTRODUCTION: Formula supplementation among infants of breastfeeding Hispanic immigrants is common practice known as las dos cosas. The purpose of this study was to assess the feasibility, effectiveness, and acceptability of a culturally and linguistically diverse intervention to promote exclusive breastfeeding (EBF) for the first 6 months.

METHODS: A sample of 39 Hispanic pregnant women was recruited and randomly assigned to intervention (n = 20) and control groups (n = 19). The intervention included a peer counselor and professional support, and mothers were followed from pregnancy to 6 months after birth.

RESULTS: After the study, women assigned to …


The Nonsteroidal Anti-Inflammatory Drug Indomethacin Induces Heterogeneity In Lipid Membranes: Potential Implication For Its Diverse Biological Action, Mihnea P Dragomir, Stefan Tudor, Keishi Okubo, Masayoshi Shimizu, Meng Chen, Dana Elena Giza, William Ruixian He, Cristina Ivan, George A Calin, Catalin Vasilescu Nov 2019

The Nonsteroidal Anti-Inflammatory Drug Indomethacin Induces Heterogeneity In Lipid Membranes: Potential Implication For Its Diverse Biological Action, Mihnea P Dragomir, Stefan Tudor, Keishi Okubo, Masayoshi Shimizu, Meng Chen, Dana Elena Giza, William Ruixian He, Cristina Ivan, George A Calin, Catalin Vasilescu

Faculty, Staff and Student Publications

Splenectomy is a common surgical procedure performed in millions of people worldwide. Epidemiologic data show that splenectomy is followed by infectious (sepsis) and non-infectious complications, with unknown mechanisms. In order to explore the role of the non-coding transcripts involved in these complications, we analysed a panel of circulating microRNAs (miRNAs), which were previously reported to be deregulated in sepsis, in the plasma of splenectomized patients. MiR-223 was overexpressed immediately and late after splenectomy, while miR-146a was overexpressed immediately after splenectomy, returning latter to basal levels; and miR-16, miR-93, miR-26a and miR-26b were overexpressed only late after splenectomy, suggesting similarities with …


Outcomes Of Hematopoietic Cell Transplantation In Patients With Germline Samd9/Samd9l Mutations., Ibrahim A. Ahmed, Midhat S. Farooqi, Mark T. Vander Lugt, Jessica Boklan, Melissa Rose, Erika D. Friehling, Brandon Triplett, Kenneth Lieuw, Blachy Davila Saldana, Christine M. Smith, Jason R. Schwartz, Rakesh K. Goyal Nov 2019

Outcomes Of Hematopoietic Cell Transplantation In Patients With Germline Samd9/Samd9l Mutations., Ibrahim A. Ahmed, Midhat S. Farooqi, Mark T. Vander Lugt, Jessica Boklan, Melissa Rose, Erika D. Friehling, Brandon Triplett, Kenneth Lieuw, Blachy Davila Saldana, Christine M. Smith, Jason R. Schwartz, Rakesh K. Goyal

Manuscripts, Articles, Book Chapters and Other Papers

Germline mutations in SAMD9 and SAMD9L genes cause MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) (OMIM: *610456) and ataxia-pancytopenia (OMIM: *611170) syndromes, respectively, and are associated with chromosome 7 deletions, myelodysplastic syndrome (MDS), and bone marrow failure. In this retrospective series, we report outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with hematologic disorders associated with SAMD9/SAMD9L mutations. Twelve patients underwent allogeneic HCT for MDS (n = 10), congenital amegakaryocytic thrombocytopenia (n = 1), and dyskeratosis congenita (n = 1). Exome sequencing revealed heterozygous mutations in SAMD9 (n = 6) or SAMD9L (n = …


Gilteritinib Or Chemotherapy For Relapsed Or Refractory Flt3-Mutated Aml, Alexander E. Perl, Giovanni Martinelli, Jorge E. Cortes, Andreas Neubauer, Ellin Berman, Stefania Paolini, Pau Montesinos, Maria R. Baer, Richard A. Larson, Celalettin Ustun, Francesco Fabbiano, Harry P. Erba, Antonio Di Stasi, Robert Stuart, Rebecca Olin, Margaret Kasner, Fabio Ciceri, Wen-Chien Chou, Nikolai Podoltsev, Christian Recher, Hisayuki Yokoyama, Naoko Hosono, Sung-Soo Yoon, Je-Hwan Lee, Timothy Pardee, Amir T. Fathi, Chaofeng Liu, Nahla Hasabou, Xuan Liu, Erkut Bahceci, Mark J. Levis Oct 2019

Gilteritinib Or Chemotherapy For Relapsed Or Refractory Flt3-Mutated Aml, Alexander E. Perl, Giovanni Martinelli, Jorge E. Cortes, Andreas Neubauer, Ellin Berman, Stefania Paolini, Pau Montesinos, Maria R. Baer, Richard A. Larson, Celalettin Ustun, Francesco Fabbiano, Harry P. Erba, Antonio Di Stasi, Robert Stuart, Rebecca Olin, Margaret Kasner, Fabio Ciceri, Wen-Chien Chou, Nikolai Podoltsev, Christian Recher, Hisayuki Yokoyama, Naoko Hosono, Sung-Soo Yoon, Je-Hwan Lee, Timothy Pardee, Amir T. Fathi, Chaofeng Liu, Nahla Hasabou, Xuan Liu, Erkut Bahceci, Mark J. Levis

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemotherapy. Gilteritinib is an oral, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML.

METHODS: In a phase 3 trial, we randomly assigned adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy. The two primary end points were overall survival and the percentage of patients who had complete remission …


Integrated Proteogenomic Characterization Of Clear Cell Renal Cell Carcinoma, David J Clark, Yize Li, Yige Wu, Matthew A Wyczalkowski, Sunantha Sethuraman, Song Cao, Feng Chen, James J Hsieh, Li Ding, Et Al Oct 2019

Integrated Proteogenomic Characterization Of Clear Cell Renal Cell Carcinoma, David J Clark, Yize Li, Yige Wu, Matthew A Wyczalkowski, Sunantha Sethuraman, Song Cao, Feng Chen, James J Hsieh, Li Ding, Et Al

Open Access Publications

To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale …


Burden Of Relapsing-Remitting Multiple Sclerosis On Workers In The Us: A Cross-Sectional Analysis Of Survey Data., Jacqueline A Nicholas, Batul Electricwala, Lulu K Lee, Kristen M Johnson Oct 2019

Burden Of Relapsing-Remitting Multiple Sclerosis On Workers In The Us: A Cross-Sectional Analysis Of Survey Data., Jacqueline A Nicholas, Batul Electricwala, Lulu K Lee, Kristen M Johnson

Neuroscience Articles

BACKGROUND: Multiple sclerosis (MS) is prevalent among working age individuals (20-60 years), leading to high burden on work productivity. Few data are available about the absenteeism and presenteeism in employed individuals with MS in comparison to non-MS personnel. This study aimed to quantify the burden of illness of employed US adults with relapsing-remitting multiple sclerosis (RRMS) and examine burden by levels of work impairment.

METHODS: A retrospective cross-sectional analysis was conducted using patient-reported responses from the US National Health and Wellness Survey (NHWS). Data from NHWS 2015-2016 were analyzed from 196 employed RRMS respondents who were matched 1:4 to employed …


Safety Climate, Safety Climate Strength, And Length Of Stay In The Nicu, Daniel S Tawfik, Eric J Thomas, Timothy J Vogus, Jessica B Liu, Paul J Sharek, Courtney C Nisbet, Henry C Lee, J Bryan Sexton, Jochen Profit Oct 2019

Safety Climate, Safety Climate Strength, And Length Of Stay In The Nicu, Daniel S Tawfik, Eric J Thomas, Timothy J Vogus, Jessica B Liu, Paul J Sharek, Courtney C Nisbet, Henry C Lee, J Bryan Sexton, Jochen Profit

Faculty, Staff and Student Publications

BACKGROUND: Safety climate is an important marker of patient safety attitudes within health care units, but the significance of intra-unit variation of safety climate perceptions (safety climate strength) is poorly understood. This study sought to examine the standard safety climate measure (percent positive response (PPR)) and safety climate strength in relation to length of stay (LOS) of very low birth weight (VLBW) infants within California neonatal intensive care units (NICUs).

METHODS: Observational study of safety climate from 2073 health care providers in 44 NICUs. Consistent perceptions among a NICU's respondents, i.e., safety climate strength, was determined via intra-unit standard deviation …


Choice Of Conditioning Regimens For Bone Marrow Transplantation In Severe Aplastic Anemia., Nelli Bejanyan, Soyoung Kim, Kyle M. Hebert, Natasha Kekre, Hisham Abdel-Azim, Ibrahim A. Ahmed, Mahmoud Aljurf, Sherif M. Badawy, Amer Beitinjaneh, Jaap Jan Boelens, Miguel Angel Diaz, Christopher C. Dvorak, Shahinaz Gadalla, James Gajewski, Robert Peter Gale, Siddhartha Ganguly, Andrew R. Gennery, Biju George, Usama Gergis, David Gómez-Almaguer, Marta Gonzalez Vicent, Hasan Hashem, Rammurti T. Kamble, Kimberly A. Kasow, Hillard M. Lazarus, Vikram Mathews, Paul J. Orchard, Michael Pulsipher, Olle Ringden, Kirk Schultz, Pierre Teira, Ann E. Woolfrey, Blachy Dávila Saldaña, Bipin Savani, Jacek Winiarski, Jean Yared, Daniel J. Weisdorf, Joseph H. Antin, Mary Eapen Oct 2019

Choice Of Conditioning Regimens For Bone Marrow Transplantation In Severe Aplastic Anemia., Nelli Bejanyan, Soyoung Kim, Kyle M. Hebert, Natasha Kekre, Hisham Abdel-Azim, Ibrahim A. Ahmed, Mahmoud Aljurf, Sherif M. Badawy, Amer Beitinjaneh, Jaap Jan Boelens, Miguel Angel Diaz, Christopher C. Dvorak, Shahinaz Gadalla, James Gajewski, Robert Peter Gale, Siddhartha Ganguly, Andrew R. Gennery, Biju George, Usama Gergis, David Gómez-Almaguer, Marta Gonzalez Vicent, Hasan Hashem, Rammurti T. Kamble, Kimberly A. Kasow, Hillard M. Lazarus, Vikram Mathews, Paul J. Orchard, Michael Pulsipher, Olle Ringden, Kirk Schultz, Pierre Teira, Ann E. Woolfrey, Blachy Dávila Saldaña, Bipin Savani, Jacek Winiarski, Jean Yared, Daniel J. Weisdorf, Joseph H. Antin, Mary Eapen

Manuscripts, Articles, Book Chapters and Other Papers

Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n = 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy ± Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P = .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n …


Tinnitus And Self-Perceived Hearing Handicap In Firefighters: A Cross-Sectional Study, Samson Jamesdaniel, Kareem G Elhage, Rita Rosati, Samiran Ghosh, Bengt Arnetz, James Blessman Oct 2019

Tinnitus And Self-Perceived Hearing Handicap In Firefighters: A Cross-Sectional Study, Samson Jamesdaniel, Kareem G Elhage, Rita Rosati, Samiran Ghosh, Bengt Arnetz, James Blessman

Faculty, Staff and Student Publications

Firefighters are susceptible to auditory dysfunction due to long-term exposure to noise from sirens, air horns, equipment, and tools used in forcible entry, ventilation, and extrication. In addition, they are exposed to ototoxic chemicals, particularly, during overhaul operations. Studies indicate that 40% of firefighters have hearing loss in the noise-sensitive frequencies of 4 and 6 kHz. Noise-induced hearing loss (NIHL) is often accompanied by tinnitus, which is characterized by ringing noise in the ears. The presence of phantom sounds can adversely affect the performance of firefighters. However, there has been limited research conducted on the prevalence of tinnitus in firefighters. …


The Gut-Microbiome In Gulf War Veterans: A Preliminary Report, Patricia A. Janulewicz, Ratanesh K. Seth, Jeffrey M. Carlson, Joy Ajama, Emily Quinn, Timothy Heeren, Nancy Klimas, Steven M. Lasley, Ronnie Horner, Kimberly Sullivan, Saurabh Chatterjee Oct 2019

The Gut-Microbiome In Gulf War Veterans: A Preliminary Report, Patricia A. Janulewicz, Ratanesh K. Seth, Jeffrey M. Carlson, Joy Ajama, Emily Quinn, Timothy Heeren, Nancy Klimas, Steven M. Lasley, Ronnie Horner, Kimberly Sullivan, Saurabh Chatterjee

Faculty Publications

Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting the central nervous system (CNS), immune and gastrointestinal (GI) systems of Gulf War veterans (GWV). We assessed the relationships between GWI, GI symptoms, gut microbiome and inflammatory markers in GWV from the Boston Gulf War Illness Consortium (GWIC). Three groups of GWIC veterans were recruited in this pilot study; GWV without GWI and no gastrointestinal symptoms (controls), GWV with GWI and no gastrointestinal symptoms (GWI-GI), GWV with GWI who reported gastrointestinal symptoms (GW+GI). Here we report on a subset of the first thirteen stool samples analyzed. Results showed significantly different …


Differences In Duration Of Untreated Psychosis For Racial And Ethnic Minority Groups With First-Episode Psychosis: An Updated Systematic Review And Meta-Analysis., Nicole Schoer, Chen Wei Huang, Kelly K. Anderson Oct 2019

Differences In Duration Of Untreated Psychosis For Racial And Ethnic Minority Groups With First-Episode Psychosis: An Updated Systematic Review And Meta-Analysis., Nicole Schoer, Chen Wei Huang, Kelly K. Anderson

Epidemiology and Biostatistics Publications

PURPOSE: Ethnic minority groups with early psychosis may have longer treatment delays, potentially leading to poorer outcomes. We updated a previous systematic review of the literature on racial and ethnic differences in duration of untreated psychosis (DUP) among people with first-episode psychosis.

RESULTS: Six of 17 studies described significant differences across aggregated racial groups; however, the pooled estimates did not show differences across groups. Additional data from this update allowed for disaggregated analyses, finding that Black-African groups have a shorter DUP, whereas Black-Caribbean groups have longer DUP, relative to White groups.

CONCLUSIONS: These findings highlight the importance of in-depth research …


Which Components Of Processing Speed Are Affected In Adhd Subtypes?, Michelle Y Kibby, Sarah A Vadnais, Audreyana C Jagger-Rickels Oct 2019

Which Components Of Processing Speed Are Affected In Adhd Subtypes?, Michelle Y Kibby, Sarah A Vadnais, Audreyana C Jagger-Rickels

Publications

The term "processing speed" (PS) encompasses many components including perceptual, cognitive and output speed. Despite evidence for reduced PS in Attention-Deficit/Hyperactivity Disorder (ADHD), little is known about which component(s) is most impacted in ADHD, or how it may vary by subtypes. Participants included 151 children, ages 8-12 years, with ADHD Predominantly Inattentive Type, ADHD Combined Type and typically developing controls using DSM-IV criteria. All children completed four measures of processing speed: Symbol Search, Coding, Decision Speed, and simple reaction time. We found children with ADHD-PI and ADHD-C had slower perceptual and psychomotor/incidental learning speed than controls and that ADHD-PI had …


Salivary Duct Carcinoma: A Case Report Of Oncocytic Variant With Possible Treatment Implications And Review Of Literature, Radhika Sekhri, Ibrahim Ortanca, Christopher Boals, Shweta Agarwal Oct 2019

Salivary Duct Carcinoma: A Case Report Of Oncocytic Variant With Possible Treatment Implications And Review Of Literature, Radhika Sekhri, Ibrahim Ortanca, Christopher Boals, Shweta Agarwal

Pathology Research and Scholarship

Salivary duct carcinoma (SDC) is an aggressive malignancy, resembling high-grade ductal carcinoma of the breast. Histologically, it shows cords and nests with cribriforming, marked nuclear atypia, comedonecrosis, perineural, and lymphovascular invasion. We report a rare case of SDC in a 61-year-old woman presenting with facial asymmetry, dysphagia, and cervical lymphadenopathy. Imaging showed an ill-defined infiltrating mass in parotid gland and multiple enlarged cervical lymph nodes. Histologically, the largest focus of tumor consisted of an intra-parotid lymph node replaced by sheets of bland appearing oncocytic tumor cells with abundant cytoplasm, centrally placed nucleus, and single prominent nucleolus. No mitotic figures were …


Astrovirus Replication In Human Intestinal Enteroids Reveals Multi-Cellular Tropism And An Intricate Host Innate Immune Landscape, Abimbola O. Kolawole, Andrew B Janowski, David Wang, Christiane E. Wobus, Et Al. Oct 2019

Astrovirus Replication In Human Intestinal Enteroids Reveals Multi-Cellular Tropism And An Intricate Host Innate Immune Landscape, Abimbola O. Kolawole, Andrew B Janowski, David Wang, Christiane E. Wobus, Et Al.

Open Access Publications

Human astroviruses (HAstV) are understudied positive-strand RNA viruses that cause gastroenteritis mostly in children and the elderly. Three clades of astroviruses, classic, MLB-type and VA-type have been reported in humans. One limitation towards a better understanding of these viruses has been the lack of a physiologically relevant cell culture model that supports growth of all clades of HAstV. Herein, we demonstrate infection of HAstV strains belonging to all three clades in epithelium-only human intestinal enteroids (HIE) isolated from biopsy-derived intestinal crypts. A detailed investigation of infection of VA1, a member of the non-canonical HAstV-VA/HMO clade, showed robust replication in HIE …