Medicine and Health Sciences Commons^™

Do Hospital Closures Affect Patient Time In An Ambulance?, Suzanne Troske, Alison Davis

Rural & Underserved Health Research Center Publications

When a hospital closes in a community, patients needing emergency care may spend more time in an ambulance to receive care in an emergency department (ED). We explore how hospital closures affect the time a patient travels from an incident location where 9-1-1 was called to the ED in an ambulance.

• Rural patients average an estimated 11 additional minutes in an ambulance the year after a hospital closure in their zip code, a 76% increase compared to before the closure.
• Urban and suburban patients have no change in transportation time in zip codes where a hospital closes.
• Patients over 64 …

Results Of A Feasibility Randomized Controlled Trial (Rct) Of The Toolkit For Optimal Recovery (Tor): A Live Video Program To Prevent Chronic Pain In At-Risk Adults With Orthopedic Injuries, Ana-Maria Vranceanu, Cale A. Jacobs, Ann Lin, Jonathan Greenberg, Christopher J. Funes, Mitchel B. Harris, Marilyn M. Heng, Eric A. Macklin, David Ring

Orthopaedic Surgery and Sports Medicine Faculty Publications

Background: Orthopedic injuries are the leading cause of hospital admissions in the USA, and many of these patients transition into chronic pain. Currently, there are no evidence-based interventions targeting prevention of chronic pain in patients with orthopedic injuries. We iteratively developed a four-session intervention “The Toolkit for Optimal Recovery” (TOR) which we plan to subsequently test for efficacy in a phase III hybrid efficacy-effectiveness multi-site clinical trial. In order to prevent methodological weaknesses in the subsequent trial, we conducted a feasibility pilot to evaluate the TOR delivered via secure live video versus usual care (UC) in patients with orthopedic injuries …

Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism And Lipid Droplet Formation, Brandon C. Farmer, Jude Kluemper, Lance A. Johnson

Physiology Faculty Publications

Lipid droplets (LDs) serve as energy rich reservoirs and have been associated with apolipoprotein E (APOE) and neurodegeneration. The E4 allele of APOE (E4) is the strongest genetic risk factor for the development of late onset Alzheimer’s disease (AD). Since both E4 carriers and individuals with AD exhibit a state of cerebral lipid dyshomeostasis, we hypothesized that APOE may play a role in regulating LD metabolism. We found that astrocytes expressing E4 accumulate significantly more and smaller LDs compared to E3 astrocytes. Accordingly, expression of perilipin-2, an essential LD protein component, was higher in E4 astrocytes. We then …

Eis Inhibitors, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov, James E. Posey

Pharmaceutical Sciences Faculty Patents

Provided herein are novel small-molecules that have use in the inhibition of Eis, which mediates kanamycin resistance in Mycobacterium tuberculosis. The presently-disclosed subject matter further includes a pharmaceutical composition including a small molecule inhibitor, as described herein, and a suitable pharmaceutical carrier. Methods of treating tuberculosis comprising administering to an individual an effective amount of the disclosed small molecule inhibitors to mediate kanamycin A resistance and treat tuberculosis are also provided.

A Parent-Led Intervention To Promote Recovery Following Pediatric Injury: Study Protocol For A Randomized Controlled Trial, Meghan L. Marsac, Ginny Sprang, Leila Guller, Kristen L. Kohser, John M. Draus Jr., Nancy Kassam-Adams

Pediatrics Faculty Publications

Background: Injury is one of the most prevalent potentially emotionally traumatic events that children experience and can lead to persistent impaired physical and emotional health. There is a need for interventions that promote full physical and emotional recovery and that can be easily accessed by all injured children. Based on research evidence regarding post-injury recovery, we created the Cellie Coping Kit for Children with Injury intervention to target key mechanisms of action and refined the intervention based on feedback from children, families, and experts in the field. The Cellie Coping Kit intervention is parent-guided and includes a toy (for engagement), …

Clinical Features, Survival And Prognostic Factors Of Glycogen-Rich Clear Cell Carcinoma (Grcc) Of The Breast In The U.S. Population, Zhengqiu Zhou, Connor J. Kinslow, Hanina Hibshoosh, Hua Guo, Simon K. Cheng, Chunyan He, Matthew S. Gentry, Ramon C. Sun

Molecular and Cellular Biochemistry Faculty Publications

The World Health Organization (WHO) defines glycogen-rich clear cell carcinoma (GRCC) of the breast as a carcinoma with glycogen accumulation in more than 90% of its tumor cells. Due to the rarity of this disease, its reported survival and clinical associations have been inconsistent due to reliance on case reports and limited case series. As a result, the prognostic implication of this cancer subtype remains unclear. Using the U.S. Surveillance, Epidemiology, and End Results (SEER) program database, we compared the incidence, demographics and prognostic factors of 155 cases of GRCC of the breast to 1,251,584 cases of other (non-GRCC) breast …

Diagnostic Dilemma Of Disseminated Histoplasmosis Mimicking Hemophagocytosis Lymphohistiocytosis In Patient With Rheumatoid Arthritis On Anti-Tnf Therapy: Case Report And Review Of The Literature, Saurav Suman, Aleksander Lenert

Internal Medicine Faculty Publications

Tumor necrosis factor inhibitors (TNFi) have become the cornerstone for the treatment of rheumatoid arthritis and other systemic autoimmune conditions. However, these biologic DMARDs can lead to various opportunistic infections such as viral infection, tuberculosis, and histoplasmosis. Furthermore, these biologics can also cause severe systemic inflammatory reactions known as hemophagocytosis lymphohistiocytosis (HLH) that can lead to multiorgan failure and high mortality. Due to overlapping clinical features and time-intensive microbiological culture methods, distinguishing between HLH and opportunistic infections can be challenging early in the disease course. We present a similar situation with our patient where the patient met the diagnostic criteria …

Timely Linkage Of Individuals To Substance Use Disorder Treatment: Development, Implementation, And Evaluation Of Findhelpnowky.Org, Terry Lee Bunn, Dana Quesinberry, Tyler Jennings, Amber Kizewski, Heather Jackson, Sarah Mckee, Sarah Eustice

Kentucky Injury Prevention and Research Center Faculty Publications

Background: Substance use disorders (SUD) have steadily increased over the last two decades. Seeking SUD treatment involves searching SUD treatment facility types (inpatient, outpatient and intensive outpatient, residential and family residential, and detoxification facilities) that offer specialized SUD treatment depending on individual needs and preferences. Referrals to SUD treatment require innovative strategies that rapidly link individuals to SUD treatment when they are at the critical stage of readiness. The aim of this study was to develop, implement, and evaluate a user-friendly SUD treatment facility opening availability website called FindHelpNowKY.org. The objectives of the study were to 1) recruit SUD treatment …

Blood Volume Analysis As A Guide For Dry Weight Determination In Chronic Hemodialysis Patients: A Crossover Study, Line Malha, Hasan Fattah, Frank Modersitzki, David S. Goldfarb

Internal Medicine Faculty Publications

Background: Volume overload and depletion both lead to high morbidity and mortality. Achieving euvolemia is a challenge in patients with end stage kidney disease on hemodialysis (HD). Blood volume analysis (BVA) uses radiolabeled albumin to determine intravascular blood volume (BV). The measured BV is compared to an ideal BV (validated in healthy controls). We hypothesized that BVA could be used in HD to evaluate the adequacy of the current clinically prescribed “estimated dry weight” (EDW) and to titrate EDW in order to improve overall volume status. We were also interested in the reproducibility of BVA results in end stage kidney …

Adipose-Derived Autotaxin Regulates Inflammation And Steatosis Associated With Diet-Induced Obesity, J. Anthony Brandon, Maria Kraemer, Julia Vandra, Suchismita Halder, Margo F. Ubele, Andrew J. Morris, Susan S. Smyth

Gill Heart & Vascular Institute Faculty Publications

Autotaxin (ATX) is a secreted enzyme that generates the bioactive lipid lysophosphatidic acid (LPA). We generated mice with global inducible post-natal inactivation or adipose-specific loss of the Enpp2 gene encoding ATX. The animals are phenotypically unremarkable and exhibit differences in adipocyte size and adipose tissue expression of inflammatory genes after high fat feeding without gross differences in fat distribution or body mass. Surprisingly, both models of Enpp2- deficiency exhibited marked protection from high fat diet-induced hepatic steatosis. This phenotype was not associated with differences in dietary fat absorption but may be accounted for by differences in hepatic expression of …

A Guide For Using Nih Image J For Single Slice Cross-Sectional Area And Composition Analysis Of The Thigh From Computed Tomography, Douglas E. Long, Alejandro G. Villasante Tezanos, James N. Wise, Phillip A. Kern, Marcas M. Bamman, Charlotte A. Peterson, Richard A. Dennis

Clinical and Translational Science Faculty Publications

Reports using computed tomography (CT) to estimate thigh skeletal muscle cross-sectional area and mean muscle attenuation are often difficult to evaluate due to inconsistent methods of quantification and/or poorly described analysis methods. This CT tutorial provides step-by-step instructions in using free, NIH Image J software to quantify both muscle size and composition in the mid-thigh, which was validated against a robust commercially available software, SliceOmatic. CT scans of the mid-thigh were analyzed from 101 healthy individuals aged 65 and older. Mean cross-sectional area and mean attenuation values are presented across seven defined Hounsfield unit (HU) ranges along with the percent …

A Guide For Using Nih Image J For Single Slice Cross-Sectional Area And Composition Analysis Of The Thigh From Computed Tomography, Douglas E. Long, Alejandro G. Villasante Tezanos, James N. Wise, Philip A. Kern, Marcas M. Bamman, Charlotte A. Peterson, Richard A. Dennis

Center for Muscle Biology Faculty Publications

Reports using computed tomography (CT) to estimate thigh skeletal muscle cross-sectional area and mean muscle attenuation are often difficult to evaluate due to inconsistent methods of quantification and/or poorly described analysis methods. This CT tutorial provides step-by-step instructions in using free, NIH Image J software to quantify both muscle size and composition in the mid-thigh, which was validated against a robust commercially available software, SliceOmatic. CT scans of the mid-thigh were analyzed from 101 healthy individuals aged 65 and older. Mean cross-sectional area and mean attenuation values are presented across seven defined Hounsfield unit (HU) ranges along with the percent …

Carboxylic Acids Accelerate Acidic Environment-Mediated Nanoceria Dissolution, Robert A. Yokel, Matthew L. Hancock, Eric A. Grulke, Jason M. Unrine, Alan K. Dozier, Uschi M. Graham

Pharmaceutical Sciences Faculty Publications

Ligands that accelerate nanoceria dissolution may greatly affect its fate and effects. This project assessed the carboxylic acid contribution to nanoceria dissolution in aqueous, acidic environments. Nanoceria has commercial and potential therapeutic and energy storage applications. It biotransforms in vivo. Citric acid stabilizes nanoceria during synthesis and in aqueous dispersions. In this study, citrate-stabilized nanoceria dispersions (∼4 nm average primary particle size) were loaded into dialysis cassettes whose membranes passed cerium salts but not nanoceria particles. The cassettes were immersed in iso-osmotic baths containing carboxylic acids at pH 4.5 and 37 °C, or other select agents. Cerium atom material …

Teach Students, Empower Patients, Act Collaboratively And Meet Health Goals: An Early Interprofessional Clinical Experience In Transformed Care, Maria Gabriela Castro, Melanie Dicks, Keisa Bennett, Carol Hustedde, David Sacks, Lynn Joyce Hunter, William Elder

Family and Community Medicine Faculty Publications

Purpose: Transformation of care teaching is often didactic and conceptual instead of practical and operational. Clinical environments, slow to transform, limit student exposure to key experiences that characterize transformed care. We describe the design and implementation of TEAM Clinic (Teach students, Empower patients, Act collaboratively, Meet health goals) – an early clinical learning experience to address this gap.

Methods: The TEAM Clinic curriculum was based on a review of existing curricula and best practice recommendations for the transformation of care. Three key elements were selected as the focus for a low-volume, high-service clinic: patient centeredness, interprofessional collaboration and team-based care. …

Li-Rads: A Conceptual And Historical Review From Its Beginning To Its Recent Integration Into Aasld Clinical Practice Guidance, Khaled M. Elsayes, Ania Z. Kielar, Victoria Chernyak, Ali Morshid, Alessandro Furlan, William R. Masch, Robert M. Marks, Aya Kamaya, Richard K. G. Do, Yuko Kono, Kathryn J. Fowler, An Tang, Mustafa R. Bashir, Elizabeth M. Hecht, Kedar Jambhekar, Andrej Lyshchik, Shuchi K. Rodgers, Jay P. Heiken, Marc Kohli, David T. Fetzer, Stephanie R. Wilson, Zahra Kassam, Mishal Mendiratta-Lala, Amit G. Singal, Christopher S. Lim, Irene Cruite, James Lee, Ryan Ash, Donald G. Mitchell, Matthew D. F. Mcinnes

Radiology Faculty Publications

The Liver Imaging Reporting and Data System (LI-RADS^®) is a comprehensive system for standardizing the terminology, technique, interpretation, reporting, and data collection of liver observations in individuals at high risk for hepatocellular carcinoma (HCC). LI-RADS is supported and endorsed by the American College of Radiology (ACR). Upon its initial release in 2011, LI-RADS applied only to liver observations identified at CT or MRI. It has since been refined and expanded over multiple updates to now also address ultrasound-based surveillance, contrast-enhanced ultrasound for HCC diagnosis, and CT/MRI for assessing treatment response after locoregional therapy. The LI-RADS 2018 version was …

Decoding Attentional State To Faces And Scenes Using Eeg Brainwaves, Reza Abiri, Soheil Borhani, Yang Jiang, Xiaopeng Zhao

Behavioral Science Faculty Publications

Attention is the ability to facilitate processing perceptually salient information while blocking the irrelevant information to an ongoing task. For example, visual attention is a complex phenomenon of searching for a target while filtering out competing stimuli. In the present study, we developed a new Brain-Computer Interface (BCI) platform to decode brainwave patterns during sustained attention in a participant. Scalp electroencephalography (EEG) signals using a wireless headset were collected in real time during a visual attention task. In our experimental protocol, we primed participants to discriminate a sequence of composite images. Each image was a fair superimposition of a scene …

What Did We Learn About Vads In 2018?, Maya Guglin

The VAD Journal

No abstract provided.

Volleyball Overhead Swing Volume And Injury Frequency Over The Course Of A Season, Heather Wolfe, Katherine Poole, Alejandro G. Villasante Tezanos, Robert A. English, Timothy L. Uhl

Statistics Faculty Publications

Background: Overuse injuries are common in volleyball; however, few studies exist that quantify the workload of a volleyball athlete in a season. The relationship between workload and shoulder injury has not been extensively studied in women's collegiate volleyball athletes.

Hypothesis/Purpose: This study aims to quantify shoulder workloads by counting overhead swings during practice and matches. The purpose of the current study is to provide a complete depiction of typical overhead swings, serves, and hits, which occur in both practices and matches. The primary hypothesis was that significantly more swings will occur in practices compared to matches. The secondary hypothesis was …

The Relationship Between Pitching Volume And Arm Soreness In Collegiate Baseball Pitchers, Angel L. Lazu, Shawn D. Love, Timothy A. Butterfield, Robert A. English, Timothy L. Uhl

Physical Therapy Faculty Publications

Background: Excessive baseball pitch volume has been associated with increased risk of injury in adolescents. However, many collegiate athletes report non-time loss injuries over the course of the season. It is unknown how pitch volume throughout a collegiate baseball season affects arm soreness.

Purpose: The primary purpose of this study was to determine the relationship between pitch volume and self-reported arm soreness. A secondary purpose was to determine the relationship between change in pitch volume and change in arm soreness over the course of the season for collegiate baseball pitchers.

Study Design: Prospective Cohort.

Methods: Seven collegiate baseball …

Neuromuscular Adaptions Following A Daily Strengthening Exercise In Individuals With Rotator Cuff Related Shoulder Pain: A Pilot Case-Control Study, Amee L. Seitz, Lisa A. Podlecki, Emily R. Melton, Timothy L. Uhl

Physical Therapy Faculty Publications

Background: The goal of therapeutic exercise is to facilitate a neuromuscular response by increasing or decreasing muscular activity in order to reduce pain and improve function. It is not clear what dosage of exercise will create a neuromuscular response.

Purpose: The purpose of this study was to assess the effects following a three-week home program of a daily single exercise, the prone horizontal abduction exercise (PHA), on neuromuscular impairments of motor control as measured by scapular muscle EMG amplitudes, strength, and secondarily outcomes of self-reported pain and function between individuals with and without subacromial pain syndrome.

Study Design: Prospective Case-Control, …

Acute Treadmill Exercise Discriminately Improves The Skeletal Muscle Insulin-Stimulated Growth Signaling Responses In Mice Lacking Redd1, Cory M. Dungan, Bradley S. Gordon, David L Williamson

Physical Therapy Faculty Publications

A loss of the regulated in development and DNA damage 1 (REDD1) hyperactivates mechanistic Target of Rapamycin Complex 1 (mTORC1) reducing insulin‐stimulated insulin signaling, which could provide insight into mechanisms of insulin resistance. Although aerobic exercise acutely inhibits mTORC1 signaling, improvements in insulin‐stimulated signaling are exhibited. The goal of this study was to determine if a single bout of treadmill exercise was sufficient to improve insulin signaling in mice lacking REDD1. REDD1 wildtype (WT) and REDD1 knockout (KO) mice were acutely exercised on a treadmill (30 min, 20 m/min, 5% grade). A within animal noninsulin‐to‐insulin‐stimulated percent change in skeletal muscle …

Rapid 5 Lb Weight Gain Is Not Associated With Readmission In Patients With Heart Failure, Jill Howie-Esquivel, Kathleen Dracup, Mary A. Whooley, Charles Mcculloch, Chengshi Jin, Debra K. Moser, Robyn A. Clark, Michele M. Pelter, Martha J. Biddle, Linda G. Park

Nursing Faculty Publications

Aims Heart failure (HF) patients are taught to identify a rapid 5 lb body‐weight gain for early detection of cardiac decompensation. Few data support this common advice. The study aim was to determine whether a 5 lb weight gain in 1 week and signs and symptoms of HF increased risk for unplanned physician or emergency department (ED) visits or hospital admission in rural HF patients.

Methods and results This was a secondary analysis of a randomized trial. Patients tracked body weight and HF symptoms using diaries. We included patients adherent to daily diaries > 50% over 24 months (N = …

A Phewas Study Of A Large Observational Epidemiological Cohort Of African Americans From The Regards Study, Xueyan Zhao, Xin Geng, Vinodh Srinivasasainagendra, Ninad Chaudhary, Suzanne Judd, Virginia Wadley, Orlando M. Gutiérrez, Henry Wang, Ethan M. Lange, Leslie A. Lange, Daniel Woo, Frederick W. Unverzagt, Monika Safford, Mary Cushman, Nita Limdi, Rakale Quarells, Donna K. Arnett, Marguerite R. Irvin, Degui Zhi

Epidemiology and Environmental Health Faculty Publications

Background: Cardiovascular disease, diabetes, and kidney disease are among the leading causes of death and disability worldwide. However, knowledge of genetic determinants of those diseases in African Americans remains limited.

Results: In our study, associations between 4956 GWAS catalog reported SNPs and 67 traits were examined among 7726 African Americans from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, which is focused on identifying factors that increase stroke risk. The prevalent and incident phenotypes studied included inflammation, kidney traits, cardiovascular traits and cognition. Our results validated 29 known associations, of which eight associations were reported for the …

Human Skeletal Muscle Macrophages Increase Following Cycle Training And Are Associated With Adaptations That May Facilitate Growth, R. Grace Walton, Kate Kosmac, Jyothi Mula, Christopher S. Fry, Bailey D. Peck, Jason S. Groshong, Brian S. Finlin, Beibei Zhu, Philip A. Kern, Charlotte A. Peterson

Center for Muscle Biology Faculty Publications

Skeletal muscle macrophages participate in repair and regeneration following injury. However, their role in physiological adaptations to exercise is unexplored. We determined whether endurance exercise training (EET) alters macrophage content and characteristics in response to resistance exercise (RE), and whether macrophages are associated with other exercise adaptations. Subjects provided vastus lateralis biopsies before and after one bout of RE, after 12 weeks of EET (cycling), and after a final bout of RE. M2 macrophages (CD11b+/CD206+) did not increase with RE, but increased in response to EET (P < 0.01). Increases in M2 macrophages were positively correlated with fiber hypertrophy (r = 0.49) and satellite cells (r = 0.47). M2c macrophages (CD206+/CD163+) also increased following EET (P < 0.001), and were associated with fiber hypertrophy (r = 0.64). Gene expression was quantified using NanoString. Following EET, the change in M2 macrophages was positively associated with changes in HGF, IGF1, and extracellular matrix genes. EET decreased expression of IL6 (P < 0.05), C/EBPβ (P < 0.01), and MuRF (P < 0.05), and increased expression of IL-4 (P < 0.01), TNFα (P < 0.01) and the TWEAK receptor FN14 (P < 0.05). The change in FN14 gene expression was inversely associated with changes in C/EBPβ (r = −0.58) and MuRF (r = −0.46) following EET. In cultured human myotubes, siRNA inhibition of FN14 increased expression of C/EBPβ (P < 0.05) and MuRF (P < 0.05). Our data suggest that macrophages contribute to the muscle response to EET, potentially including modulation of TWEAK-FN14 signaling.

Candidemia Following Ureteric Stent Placement In A Patient With Type 2 Diabetes Treated With Canagliflozin, Rishi Raj, Jon Hendrie, Aasems Jacob, Derick Adams

Internal Medicine Faculty Publications

A 38-year-old female patient with well-controlled type 2 diabetes mellitus treated with canagliflozin underwent ureteral stent placement for obstructive renal calculi. Ten days following ureteroscopy and ureteral stenting, she developed fevers and blood cultures grew Candida glabrata (C. glabrata). The patient was successfully treated with an extended course of broad-spectrum antibiotics and antifungal agents. The clinical presentation of candidemia is indistinguishable from bacteremia resulting in delay in diagnosis and treatment. Candiduria is commonly seen in patients with type 2 diabetes, however it rarely leads to candidemia in an otherwise healthy person following a relatively simple urologic procedure. Sodium-glucose …

Associations Between Slc16a11 Variants And Diabetes In The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Bertha A. Hidalgo, Tamar Sofer, Qibin Qi, Neil Schneiderman, Y. -D. Ida Chen, Robert C. Kaplan, M. Larissa Avilés-Santa, Kari E. North, Donna K. Arnett, Adam Szpiro, Jianwen Cai, Bing Yu, Eric Boerwinkle, George Papanicolaou, Cathy C. Laurie, Jerome I. Rotter, Adrienne M. Stilp

Epidemiology and Environmental Health Faculty Publications

Five sequence variants in SLC16A11 (rs117767867, rs13342692, rs13342232, rs75418188, and rs75493593), which occur in two non-reference haplotypes, were recently shown to be associated with diabetes in Mexicans from the SIGMA consortium. We aimed to determine whether these previous findings would replicate in the HCHS/SOL Mexican origin group and whether genotypic effects were similar in other HCHS/SOL groups. We analyzed these five variants in 2492 diabetes cases and 5236 controls from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), which includes U.S. participants from six diverse background groups (Mainland groups: Mexican, Central American, and South American; and Caribbean groups: Puerto Rican, …

Adgrl3 (Lphn3) Variants Predict Substance Use Disorder, Mauricio Arcos-Burgos, Jorge I. Vélez, Ariel F. Martinez, Marta Ribasés, Josep A. Ramos-Quiroga, Cristina Sánchez-Mora, Vanesa Richarte, Carlos Roncero, Bru Cormand, Noelia Fernández-Castillo, Miguel Casas, Francisco Lopera, David A. Pineda, Juan D. Palacio, Johan E. Acosta-López, Martha L. Cervantes-Henriquez, Manuel G. Sánchez-Rojas, Pedro J. Puentes-Rozo, Brooke S. G. Molina, Mta Cooperative Group, Margaret T. Boden, Deeann Wallis, Brett Lidbury, Saul Newman, Simon Easteal, James Swanson, Hardip Patel, Nora Volkow, Maria T. Acosta, Francisco X. Castellanos, Jose De Leon

Psychiatry Faculty Publications

Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal samples from disparate regions of the world (n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we …

Cytisine-Linked Isoflavonoid Antineoplastic Agents For The Treatment Of Cancer, Chunming Liu, David S. Watt, Mykhaylo S. Frasinyuk, Vitaliy M. Sviripa, Wen Zhang, Svitlana P. Bondarenko

Markey Cancer Center Faculty Patents

Cytisine-linked isoflavonoids, or pharmaceutically acceptable salts thereof or pharmaceutically acceptable compositions thereof, are useful for the treatment of conditions in which cells have a reliance on peroxisomal HSD17B4 to degrade very long chain fatty acids and provide necessary energy for cell proliferation, such as is seen in colorectal cancer and prostate cancer, for example.

Overview Of The Biocreative Vi Precision Medicine Track: Mining Protein Interactions And Mutations For Precision Medicine, Rezarta Islamaj Doğan, Sun Kim, Andrew Chatr-Aryamontri, Chih-Hsuan Wei, Donald C. Comeau, Rui Antunes, Sérgio Matos, Qingyu Chen, Aparna Elangovan, Nagesh C. Panyam, Karin Verspoor, Hongfang Liu, Yanshan Wang, Zhuang Liu, Berna Altınel, Zehra Melce Hüsünbeyi, Arzucan Özgür, Aris Fergadis, Chen-Kai Wang, Hong-Jie Dai, Tung Tran, Ramakanth Kavuluru, Ling Luo, Albert Steppi, Jinfeng Zhang, Jinchan Qu, Zhiyong Lu

Computer Science Faculty Publications

The Precision Medicine Initiative is a multicenter effort aiming at formulating personalized treatments leveraging on individual patient data (clinical, genome sequence and functional genomic data) together with the information in large knowledge bases (KBs) that integrate genome annotation, disease association studies, electronic health records and other data types. The biomedical literature provides a rich foundation for populating these KBs, reporting genetic and molecular interactions that provide the scaffold for the cellular regulatory systems and detailing the influence of genetic variants in these interactions. The goal of BioCreative VI Precision Medicine Track was to extract this particular type of information and …

Itch Nuclear Translocation And H1.2 Polyubiquitination Negatively Regulate The Dna Damage Response, Lufen Chang, Lei Shen, Hu Zhou, Jing Gao, Hangyi Pan, Li Zheng, Brian Armstrong, Yang Peng, Guang Peng, Binhua P. Zhou, Steven T. Rosen, Binghui Shen

Molecular and Cellular Biochemistry Faculty Publications

The downregulation of the DNA damage response (DDR) enables aggressive tumors to achieve uncontrolled proliferation against replication stress, but the mechanisms underlying this process in tumors are relatively complex. Here, we demonstrate a mechanism through which a distinct E3 ubiquitin ligase, ITCH, modulates DDR machinery in triple-negative breast cancer (TNBC). We found that expression of a nuclear form of ITCH was significantly increased in human TNBC cell lines and tumor specimens. Phosphorylation of ITCH at Ser257 by AKT led to the nuclear localization of ITCH and ubiquitination of H1.2. The ITCH-mediated polyubiquitination of H1.2 suppressed RNF8/RNF168-dependent formation of 53BP1 foci, …