Digital Commons Network^™

K27m In Canonical And Noncanonical H3 Variants Occurs In Distinct Oligodendroglial Cell Lineages In Brain Midline Gliomas, Selin Jessa, Abdulshakour Mohammadnia, Ashot S Harutyunyan, Maud Hulswit, Srinidhi Varadharajan, Hussein Lakkis, Nisha Kabir, Zahedeh Bashardanesh, Steven Hébert, Damien Faury, Maria C Vladoiu, Samantha Worme, Marie Coutelier, Brian Krug, Augusto Faria Andrade, Manav Pathania, Andrea Bajic, Alexander G Weil, Benjamin Ellezam, Jeffrey Atkinson, Roy W R Dudley, Jean-Pierre Farmer, Sebastien Perreault, Benjamin A Garcia, Valérie Larouche, Mathieu Blanchette, Livia Garzia, Aparna Bhaduri, Keith L Ligon, Pratiti Bandopadhayay, Michael D Taylor, Stephen C Mack, Nada Jabado, Claudia L Kleinman

Faculty, Staff and Students Publications

Canonical (H3.1/H3.2) and noncanonical (H3.3) histone 3 K27M-mutant gliomas have unique spatiotemporal distributions, partner alterations and molecular profiles. The contribution of the cell of origin to these differences has been challenging to uncouple from the oncogenic reprogramming induced by the mutation. Here, we perform an integrated analysis of 116 tumors, including single-cell transcriptome and chromatin accessibility, 3D chromatin architecture and epigenomic profiles, and show that K27M-mutant gliomas faithfully maintain chromatin configuration at developmental genes consistent with anatomically distinct oligodendrocyte precursor cells (OPCs). H3.3K27M thalamic gliomas map to prosomere 2-derived lineages. In turn, H3.1K27M ACVR1-mutant pontine gliomas uniformly mirror early ventral …

Statin Use And Risk Of Diabetes By Subclinical Atherosclerosis Burden (From A Multi-Ethnic Study Of Atherosclerosis Report), Mahmoud Al Rifai, Moyses Szklo, Jaideep Patel, Michael J Blaha, Christie M Ballantyne, Vera Bittner, Pamela Morris, John W Mcevoy, Michael D Shapiro, Mouaz H Al-Mallah, Philip Greenland, Salim S Virani

Faculty, Staff and Students Publications

Although there is a significant reduction in atherosclerotic cardiovascular disease risk with statins, a higher risk of diabetes mellitus has been demonstrated in randomized clinical trials. The risk of incident diabetes with statins may be heterogeneous by presence of coronary artery calcium (CAC). We evaluated participants without prevalent diabetes at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of subjects free of clinical cardiovascular disease at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between statin use and incident diabetes, adjusting for sociodemographic and cardiovascular risk factors, including time-varying statin use and …

Highlights Of Cardiovascular Disease Prevention Studies Presented At The 2022 European Society Of Cardiology Congress, Melody Hermel, Megan Pelter, Timothy Jordan, Azka Latif, Mohamed M Gad, Leandro Slipczuk, Dinesh Kalra, Salim S Virani

Faculty, Staff and Students Publications

Purpose of review: Focused review of select studies presented at the 2022 European Society of Cardiology Congress.

Recent findings: Included studies assessed the effects of aspirin and omega-3 fatty acid supplements on heart failure (ASCEND study); the impact of icosapent ethyl on ST-elevation MI incidence (REDUCE-IT); air temperature's effect on cardiovascular mortality (EXHAUSTION project); LVEF outcomes after troponin-guided neurohormonal blockade for the prevention of anthracycline toxicity; efficacy of routine stress testing after high-risk PCI (POST-PCI trial); influenza vaccine among patients with acute coronary syndromes (VIP-ACS trial); empagliflozin in patients with acute myocardial infarction (EMMY); effects of comprehensive imaging-based cardiovascular screening …

Lipid-Lowering Therapy Use And Intensification Among United States Veterans Following Myocardial Infarction Or Coronary Revascularization Between 2015 And 2019, Alexander R Zheutlin, Catherine G Derington, Jennifer S Herrick, Robert S Rosenson, Bharat Poudel, Monika M Safford, Todd M Brown, Elizabeth A Jackson, Mark Woodward, Stephanie Reading, Kate Orroth, Jason Exter, Salim S Virani, Paul Muntner, Adam P Bress

Faculty, Staff and Students Publications

Background: Understanding how statins, ezetimibe, and PCSK9i (proprotein convertase subtilisin/kexin type 9 serine protease inhibitors) are prescribed after a myocardial infarction (MI) or elective coronary revascularization may improve lipid-lowering therapy (LLT) intensification and reduce recurrent atherosclerotic cardiovascular disease events. We described the use and intensification of LLT among US veterans who had a MI or elective coronary revascularization between July 24, 2015, and December 9, 2019, within 12 months of hospital discharge.

Methods: LLT intensification was defined as increasing statin dose, or initiating a statin, ezetimibe, or a PCSK9i, overall and among those with an LDL-C (low-density lipoprotein cholesterol) ≥ …

Outcomes In Participants With Failure Of Initial Antibacterial Therapy For Hospital-Acquired/Ventilator-Associated Bacterial Pneumonia Prior To Enrollment In The Randomized, Controlled Phase 3 Aspect-Np Trial Of Ceftolozane/Tazobactam Versus Meropenem, Marin H Kollef, Jean-François Timsit, Ignacio Martin-Loeches, Richard G Wunderink, Jennifer A Huntington, Erin H Jensen, Brian Yu, Christopher J Bruno

2020-Current year OA Pubs

BACKGROUND: Ceftolozane/tazobactam, a combination antibacterial agent comprising an anti-pseudomonal cephalosporin and β-lactamase inhibitor, is approved for the treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in adults. Participants in the ASPECT-NP trial received ceftolozane/tazobactam (3 g [2 g ceftolozane/1 g tazobactam] every 8 h) or meropenem (1 g every 8 h). Participants failing prior antibacterial therapy for the current HABP/VABP episode at study entry had lower 28-day all-cause mortality (ACM) rates with ceftolozane/tazobactam versus meropenem treatment. Here, we report a post hoc analysis examining this result.

METHODS: The phase 3, randomized, controlled, double-blind, multicenter, noninferiority trial compared ceftolozane/tazobactam versus meropenem for treatment …

Association Between Cause Of Kidney Failure And Fracture Incidence In A National Us Dialysis Population Cohort Study, Susan Ziolkowski, Sai Liu, Maria E Montez-Rath, Michelle Denburg, Wolfgang C Winkelmayer, Glenn M Chertow, Michelle M O'Shaughnessy

Faculty, Staff and Students Publications

Background: Whether fracture rates, overall and by fracture site, vary by cause of kidney failure in patients receiving dialysis is unknown.

Methods: Using the US Renal Data System, we compared fracture rates across seven causes of kidney failure in patients who started dialysis between 1997 and 2014. We computed unadjusted and multivariable adjusted proportional sub-distribution hazard models, with fracture events (overall, and by site) as the outcome and immunoglobulin A nephropathy as the reference group. Kidney transplantation and death were competing events.

Results: Among 491 496 individuals, with a median follow-up of 2.0 (25%, 75% range 0.9-3.9) years, 62 954 …

Understanding Post-Covid-19 Interstitial Lung Disease (Ild): A New Fibroinflammatory Disease Entity, Puja Mehta, Ivan O Rosas, Mervyn Singer

Faculty, Staff and Students Publications

Immunomodulation and immunity from vaccination and natural infection have reduced mortality from coronavirus disease 2019 (COVID-19). However, there are ongoing concerns regarding emerging variants and residual pulmonary sequelae in survivors, given that the lungs are the principal site for the triumvirate of infection, inflammation and injury. The initial waves of acute, severe COVID-19 were profoundly inflammatory, usually manifest as organising pneumonia ± acute respiratory distress syndrome (ARDS). The extent of the fibrogenic potential of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the modifiability of the pathogenic processes and disease course are unclear. Interestingly patients can develop ‘post-COVID interstitial lung disease’ …

Long-Term Relugolix Combination Therapy For Symptomatic Uterine Leiomyomas, Ayman Al-Hendy, Andrea S Lukes, Alfred N Poindexter, Roberta Venturella, Claudio Villarroel, Laura Mckain, Yulan Li, Rachel B Wagman, Elizabeth A Stewart

Faculty, Staff and Students Publications

OBJECTIVE: In the LIBERTY 1 and LIBERTY 2 placebo-controlled trials, once-daily relugolix combination therapy reduced menstrual blood loss volume and pain in women with heavy menstrual bleeding associated with uterine leiomyomas and was well tolerated, with preservation of bone mineral density (BMD) through 24 weeks. Here we report the long-term efficacy and safety of relugolix combination therapy treatment for up to 52 weeks.

METHODS: Women with uterine leiomyoma-associated heavy menstrual bleeding who completed any treatment arm in either the LIBERTY 1 or LIBERTY 2 trial were eligible to enroll in a 28-week long-term extension study. All participants received once-daily relugolix …

Outcomes Of Audio-Instructed And Video-Instructed Dispatcher-Assisted Cardiopulmonary Resuscitation: A Systematic Review And Meta-Analysis, Karol Bielski, Bernd W Böttiger, Michal Pruc, Aleksandra Gasecka, Mariusz Sieminski, Milosz J Jaguszewski, Jacek Smereka, Natasza Gilis-Malinowska, Frank W Peacock, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: The present meta-analysis of clinical and simulation trials aimed to compare video-instructed dispatcher-assisted bystander cardiopulmonary resuscitation (V-DACPR) with conventional audio-instructed dispatcher-assisted bystander cardiopulmonary resuscitation (C-DACPR).

METHODS: We searched PubMed, Embase, Web of Science, Cochrane Collaboration databases and Scopus from inception until June 10, 2021. The primary outcomes were the prehospital return of spontaneous circulation (ROSC), survival to hospital discharge, and survival to hospital discharge with a good neurological outcome for clinical trials, and chest compression quality for simulation trials. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) indicated the pooled effect. The analyses were performed …

Factors Affecting Rates Of Neurodevelopmental Follow-Up In Infants With Congenital Heart Disease, Sonia Monteiro, Faridis Serrano, Danielle Guffey, Keila N Lopez, Estrella Mazarico De Thomas, Robert G Voigt, Lara Shekerdemian, Shaine A Morris

Faculty, Staff and Students Publications

BACKGROUND: Neurodevelopmental outcomes programs for children with congenital heart disease (CHD) support early identification and intervention for developmental impairments; however, not all eligible children attend such programs. The purpose of our study was to examine factors, including sociodemographic, associated with cardiac neurodevelopmental outcomes program attendance.

METHODS: Children with CHD born April 2013-April 2018 who underwent cardiac surgery before age 6 months were included. The primary outcome was at least one neurodevelopmental clinic visit, and secondary outcome was number of visits attended during the first two years of life. Predictor variables included maternal and infant characteristics, surgical data, geographic location of …

The Genetic Risk Factor Cel-Hyb1 Causes Proteotoxicity And Chronic Pancreatitis In Mice, Karianne Fjeld, Steven J Wilhelm, Jianguo Lin, Xunjun Xiao, Mark E Lowe, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: The CEL gene encodes the digestive enzyme carboxyl ester lipase. CEL-HYB1, a hybrid allele of CEL and its adjacent pseudogene CELP, is a genetic variant suggested to increase the risk of chronic pancreatitis (CP). Our aim was to develop a mouse model for CEL-HYB1 that enables studies of pancreatic disease mechanisms.

METHODS: We established a knock-in mouse strain where the variable number of tandem repeat (VNTR) region of the endogenous mouse Cel gene was substituted with the mutated VNTR of the human CEL-HYB1 allele. Heterozygous and homozygous Cel-HYB1 mice and littermate wildtype controls were characterized with respect …

Vascular Endothelial-Cadherin As A Marker Of Endothelial Injury In Preclinical Alzheimer Disease, Rawan Tarawneh, Rachel S Kasper, Jessie Sanford, Chia-Ling Phuah, Jason Hassenstab, Carlos Cruchaga

2020-Current year OA Pubs

OBJECTIVE: Endothelial dysfunction is an early and prevalent pathology in Alzheimer disease (AD). We here investigate the value of vascular endothelial-cadherin (VEC) as a cerebrospinal fluid (CSF) marker of endothelial injury in preclinical AD.

METHODS: Cognitively normal participants (Clinical Dementia Rating [CDR] 0) from the Knight Washington University-ADRC were included in this study (n = 700). Preclinical Alzheimer's Cognitive Composite (PACC) scores, CSF VEC, tau, p-tau181, Aβ42/Aβ40, neurofilament light-chain (NFL) levels, and magnetic resonance imaging (MRI) assessments of white matter injury (WMI) were obtained from all participants. A subset of participants underwent brain amyloid imaging using positron emission tomography (amyloid-PET) …

The Clinical Landscape Of Cell-Free Dna Alterations In 1671 Patients With Advanced Biliary Tract Cancer, J E Berchuck, B Tan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for cancer genomic profiling that overcomes many limitations of traditional tissue-based analysis. We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology.

PATIENTS AND METHODS: We analyzed next-generation sequencing data of 2068 cfDNA samples from 1671 patients with advanced BTC generated with Guardant360. We carried out clinical annotation on a multi-institutional subset (n = 225) to assess intra-patient cfDNA-tumor concordance and the association of cfDNA variant …

Cortical Bone Relationships Are Maintained Regardless Of Sex And Diet In A Large Population Of Lgxsm Advanced Intercross Mice, Nicole Migotsky, Michael D Brodt, James M Cheverud, Matthew J Silva

2020-Current year OA Pubs

INTRODUCTION: Knowledge of bone structure-function relationships in mice has been based on relatively small sample sets that limit generalizability. We sought to investigate structure-function relationships of long bones from a large population of genetically diverse mice. Therefore, we analyzed previously published data from the femur and radius of male and female mice from the F34 generation of the Large-by-Small advanced intercross line (LGXSM AI), which have over a two-fold continuous spread of bone and body sizes (Silva et al. 2019 JBMR).

METHODS: Morphological traits, mechanical properties, and estimated material properties were collected from the femur and radius from 1113 LGXSM …

Community Access To Primary Care Is An Important Geographic Disparity Among Ovarian Cancer Patients Undergoing Cytoreductive Surgery, Abigail S Zamorano, Angela L Mazul, Christine Marx, Mary M Mullen, Molly Greenwade, L Stewart Massad, Carolyn K Mccourt, Andrea R Hagemann, Premal H Thaker, Katherine C Fuh, Matthew A Powell, David G Mutch, Dineo Khabele, Lindsay M Kuroki

2020-Current year OA Pubs

OBJECTIVE: Given the importance of understanding neighborhood context and geographic access to care on individual health outcomes, we sought to investigate the association of community primary care (PC) access on postoperative outcomes and survival in ovarian cancer patients.

METHODS: This was a retrospective cohort study of Stage III-IV ovarian cancer patients who underwent surgery at a single academic, tertiary care hospital between 2012 and 2015. PC access was determined using a Health Resources and Services Administration designation. Outcomes included 30-day surgical and medical complications, extended hospital stay, ICU admission, hospital readmission, progression-free and overall survival. Descriptive statistics and chi-squared analyses …

Leflunomide-Induced And Paraneoplastic Ulcers In A Rheumatoid Arthritis Patient, Michael R Vittori, Jonathan Z Tang, William H Mccoy Iv

2020-Current year OA Pubs

No abstract provided.

Dawn-To-Dusk Dry Fasting Induces Anti-Atherosclerotic, Anti-Inflammatory, And Anti-Tumorigenic Proteome In Peripheral Blood Mononuclear Cells In Subjects With Metabolic Syndrome, Ayse L Mindikoglu, Jihwan Park, Antone R Opekun, Mustafa M Abdulsada, Zoe R Wilhelm, Prasun K Jalal, Sridevi Devaraj, Sung Yun Jung

Faculty, Staff and Students Publications

BACKGROUND: Metabolic syndrome characterized by abdominal obesity, high blood pressure, elevated fasting glucose and triglyceride levels and low high-density lipoprotein cholesterol level is associated with pro-inflammatory state, increased risk for atherosclerosis, and multiple cancers. Our previous results on subjects with metabolic syndrome showed that 4-week dawn-to-dusk (sunset) dry fasting resulted in significant changes in the serum proteome and improvement in several metabolic risk factors. Peripheral blood mononuclear cells (PBMC) proteomics is a powerful tool that can provide mechanistic insights into how dawn-to-dusk dry fasting affects protein expression in metabolic pathways at cellular level. In this study, we determined whether dawn-to-dusk …

Stellate Ganglion Block For Long Covid Symptom Management: A Case Report, Mashfee H Khan, Kennedy P Kirkpatrick, Yi Deng, Krishna B Shah

Faculty, Staff and Students Publications

Stellate ganglion block (SGB) is gaining increasing acceptance as a treatment modality for various medical conditions. It works by blocking neuronal transmissions which in turn alleviates sympathetically-driven disease processes. Many of the prolonged sequelae of long COVID are thought to be mediated by dysregulation of the autonomic nervous system, and SGB is being investigated as a potential option for symptomatic management of long COVID. This case report demonstrates the efficacy of SGB in a previously healthy patient for the management of long COVID symptoms including fatigue, post-exertional malaise, shortness of breath, and gastrointestinal symptoms.

Factors Affecting Need For Blood Transfusion In Paediatric Patients Undergoing Open Surgery For Hip Dysplasia, Adam C Adler, Lisa A H Hensch, Brittany E Bryant, Arvind Chandrakantan, Hai-Yen Nguyen, Brian H Nathanson, Scott B Rosenfeld

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: The management of intraoperative blood loss in the surgical treatment of paediatric hip dysplasia is resource intensive. There are numerous clinical factors that impact the need for intraoperative transfusion. Identification of patient and surgical factors associated with increased blood loss may reduce the unnecessary use of resources. This study aimed to identify factors predictive of intraoperative transfusion in children undergoing hip dysplasia surgery.

MATERIALS AND METHODS: This is a single-centre retrospective review of patients undergoing surgery for hip dysplasia from 1 January 2012 to 15 April 2021. Patient demographic factors, anaesthetic, surgical and transfusion histories were reviewed. …

A Consensus List Of Ultrasound Competencies For Graduating Emergency Medicine Residents, David A Haidar, William J Peterson, Patrick G Minges, Jennifer Carnell, Jason T Nomura, John Bailitz, Jeremy S Boyd, Megan M Leo, E Liang Liu, Youyou Duanmu, Josie Acuña, Ross Kessler, Marco F Elegante, Mathew Nelson, Rachel B Liu, Resa E Lewiss, Arun Nagdev, Rob D Huang

Faculty, Staff and Students Publications

OBJECTIVES: Emergency ultrasound (EUS) is a critical component of emergency medicine (EM) resident education. Currently, there is no consensus list of competencies for EUS training, and graduating residents have varying levels of skill and comfort. The objective of this study was to define a widely accepted comprehensive list of EUS competencies for graduating EM residents through a modified Delphi method.

METHODS: We developed a list of EUS applications through a comprehensive literature search, the American College of Emergency Physicians list of core EUS benchmarks, and the Council of Emergency Medicine Residency-Academy of Emergency Ultrasound consensus document. We assembled a multi-institutional …

Proteasome Inhibitors Silence Oncogenes In Multiple Myeloma Through Localized Histone Deacetylase 3 (Hdac3) Stabilization And Chromatin Condensation, Laure Maneix, Polina Iakova, Shannon E Moree, Joanne I Hsu, Ragini M Mistry, Fabio Stossi, Premal Lulla, Zheng Sun, Ergun Sahin, Sarvari V Yellapragada, André Catic

Faculty, Staff and Students Publications

Proteasome inhibitors have become the standard of care for multiple myeloma (MM). Blocking protein degradation particularly perturbs the homeostasis of short-lived polypeptides such as transcription factors and epigenetic regulators. To determine how proteasome inhibitors directly impact gene regulation, we performed an integrative genomics study in MM cells. We discovered that proteasome inhibitors reduce the turnover of DNA-associated proteins and repress genes necessary for proliferation through epigenetic silencing. Specifically, proteasome inhibition results in the localized accumulation of histone deacetylase 3 (HDAC3) at defined genomic sites, which reduces H3K27 acetylation and increases chromatin condensation. The loss of active chromatin at super-enhancers critical …

Multicenter Randomized Clinical Trial Of A Mailed Outreach Strategy For Hepatocellular Carcinoma Surveillance, Amit G Singal, Sarah Reddy, Himani Radadiya Aka Patel, Deyaun Villarreal, Aisha Khan, Yan Liu, Vanessa Cerda, Nicole E Rich, Caitlin C Murphy, Jasmin A Tiro, Jennifer R Kramer, Ruben Hernaez

Faculty, Staff and Students Publications

BACKGROUND: The effectiveness of hepatocellular carcinoma (HCC) surveillance is mitigated by underuse in clinical practice, highlighting a need for interventions. We evaluated the effectiveness of mailed HCC surveillance outreach to promote HCC surveillance in patients with cirrhosis.

METHODS: We conducted a multicenter pragmatic randomized clinical trial comparing mailed outreach for surveillance ultrasound (n = 1436) and usual care with visit-based surveillance (n = 1436) among patients with cirrhosis at 3 health systems (tertiary care referral center, safety net health system, and Veterans Affairs medical center) from April 2018 to December 2019. The primary outcome of this interim analysis was guideline …

Distinctive Kidney Function Trajectories Following Left Ventricular Assist Device Implantation, Carl P Walther, Julia S Benoit, Harveen K Lamba, Andrew B Civitello, Kevin F Erickson, Nandan K Mondal, Kenneth K Liao, Sankar D Navaneethan

Faculty, Staff and Students Publications

BACKGROUND: The aim of this study was to assess for distinct kidney function trajectories following left ventricular assist device (LVAD) placement. Cohort studies of LVAD recipients demonstrate that kidney function tends to increase early after LVAD placement, followed by decline and limited sustained improvement. Inter-individual differences in kidney function response may be obscured.

METHODS: We identified continuous flow LVAD implantations in US adults (2016-2017) from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). Primary outcomes were estimated glomerular filtration rate (eGFR) trajectories pre-implantation to ∼12 months. Latent class mixed models were applied to primary and validation samples. Clinical differences among …

Pediatric Lung Transplantation For Covid-19: Unique Clinical And Psychosocial Barriers, Anupam Kumar, Gloria W Li, Justin M Segraves, Aladdein Mattar, Maheshwari Ramineni, Gabriel Loor, Puneet S Garcha

Faculty, Staff and Students Publications

BACKGROUND: SARS-CoV-2 infection in the age group of 0-17 years contributes to approximately 22% of all laboratory-confirmed SARS-CoV-2 infections. Fortunately, this age group has a lower death rate (0.5 per 100 000) that accounts for only 4% of the total deaths due to COVID-19. Despite the low mortality rate in the pediatric population, children of minority groups represented 78% of the deaths highlighting the existing disparities in access to health care.

METHODS: With the emergence of the more contagious COVID-19 variants and the relatively slow pace of vaccination among the pediatric population, it is possible to see more cases of …

Patient And Clinician Perceptions Of Precision Cardiology Care: Findings From The Heartcare Study, Hadley Stevens Smith, Clarissa E Sanchez, Ronald Maag, Alexandria Buentello, David R Murdock, Ginger A Metcalf, Trevor D Hadley, Daniel L Riconda, Eric Boerwinkle, Xander H T Wehrens, Christie M Ballantyne, Richard A Gibbs, Amy L Mcguire, Stacey Pereira

Faculty, Staff and Students Publications

BACKGROUND: Routine genome-wide screening for cardiovascular disease risk may inform clinical decision-making. However, little is known about whether clinicians and patients would find such testing useful or acceptable within the context of a genomics-enabled learning health system.

METHODS: We conducted surveys with patients and their clinicians who were participating in the HeartCare Study, a precision cardiology care project that returned results from a next-generation sequencing panel of 158 genes associated with cardiovascular disease risk. Six weeks after return of results, we assessed patients' and clinicians' perceived utility and disutility of HeartCare, the effect of the test on clinical recommendations, and …

Analysis Of Genome-Wide Knockout Mouse Database Identifies Candidate Ciliopathy Genes, Kendall Higgins, Bret A Moore, Zorana Berberovic, Hibret A Adissu, Mohammad Eskandarian, Ann M Flenniken, Andy Shao, Denise M Imai, Dave Clary, Louise Lanoue, Susan Newbigging, Lauryl M J Nutter, David J Adams, Fatima Bosch, Robert E Braun, Steve D M Brown, Mary E Dickinson, Michael Dobbie, Paul Flicek, Xiang Gao, Sanjeev Galande, Anne Grobler, Jason D Heaney, Yann Herault, Martin Hrabe De Angelis, Hsian-Jean Genie Chin, Fabio Mammano, Chuan Qin, Toshihiko Shiroishi, Radislav Sedlacek, J-K Seong, Ying Xu, Impc Consortium, K C Kent Lloyd, Colin Mckerlie, Ala Moshiri

Faculty, Staff and Students Publications

We searched a database of single-gene knockout (KO) mice produced by the International Mouse Phenotyping Consortium (IMPC) to identify candidate ciliopathy genes. We first screened for phenotypes in mouse lines with both ocular and renal or reproductive trait abnormalities. The STRING protein interaction tool was used to identify interactions between known cilia gene products and those encoded by the genes in individual knockout mouse strains in order to generate a list of "candidate ciliopathy genes." From this list, 32 genes encoded proteins predicted to interact with known ciliopathy proteins. Of these, 25 had no previously described roles in ciliary pathobiology. …

A Phase I/Ii Trial Of Nivolumab Plus Ipilimumab In Children And Young Adults With Relapsed/Refractory Solid Tumors: A Children's Oncology Group Study Advl1412, Kara L Davis, Elizabeth Fox, Emasenyie Isikwei, Joel M Reid, Xiaowei Liu, Charles G Minard, Stephan Voss, Stacey L Berg, Brenda J Weigel, Crystal L Mackall

Faculty, Staff and Students Publications

PURPOSE: In many cancers, nivolumab in combination with ipilimumab improves response rates compared with either agent alone, but the combination has not been evaluated in childhood cancer. We conducted a phase I/II trial of nivolumab plus ipilimumab in children and young adults with recurrent/refractory solid tumors.

PATIENTS AND METHODS: ADVL1412, Part C assessed safety of nivolumab plus ipilimumab at two dose levels (DL): DL1 1 mg/kg of each drug and DL2 3 mg/kg nivolumab plus 1 mg/kg ipilimumab. Part D evaluated response at the recommended phase II dose (RP2D) in Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma. Part E tested DL3 (1 …

Cognition And The Single Neuron: How Cell Types Construct The Dynamic Computations Of Frontal Cortex, Amelia J Christensen, Torben Ott, Adam Kepecs

2020-Current year OA Pubs

Frontal cortex is thought to underlie many advanced cognitive capacities, from self-control to long term planning. Reflecting these diverse demands, frontal neural activity is notoriously idiosyncratic, with tuning properties that are correlated with endless numbers of behavioral and task features. This menagerie of tuning has made it difficult to extract organizing principles that govern frontal neural activity. Here, we contrast two successful yet seemingly incompatible approaches that have begun to address this challenge. Inspired by the indecipherability of single-neuron tuning, the first approach casts frontal computations as dynamical trajectories traversed by arbitrary mixtures of neurons. The second approach, by contrast, …

Effects Of A Non-Uniform Magnetic Field On The Current Flow Of Silicon Photodiodes And Solar Cells, Jason J. Buranich

Theses and Dissertations

This research investigates an approach to improve efficiency of low-cost devices by applying an external arched magnetic field to p-n junction devices to observe the effect such a magnetic field would have on the flow of charge carriers. Electro-optic p-n junction devices of photodiodes and solar cells were designed and fabricated to incorporate the dimensions of commercially available neodymium magnets. The devices were placed in the magnetic fields created by the magnets then current and voltage characteristics were measured via a 4-point probe setup. These measurements were compared to measurements taken from the same devices when not in the magnetics …

Clinician’S Recommendations In Treating Victims And Survivors Of Narcissistic Abuse, Sadaf Shalchian

Loma Linda University Electronic Theses, Dissertations & Projects

Although marriage and family therapists are one of the main providers in treating mental and relational health issues, there is not a significant emphasis on the identification, assessment, and treatment of victims and survivors of narcissistic abuse in COAMFTE-accredited Masters level Marriage and Family Therapy programs (COAMFTE, 2017). This needs assessment aimed to identify the knowledge and clinical skills recommended by clinicians who treat victims and survivors of narcissistic abuse to identify some needs, assessments, and treatment practices that can guide LMFTs in treating this population. This needs assessment explored current literature, research, and academic and clinical resources focused on …