Medical Specialties Commons^™

Psychiatric Medications: Does Education Affect Medication Prescriptions?, Surina M. Narine, Mary D. Ramos, Sarah Chu

Symposium of Student Scholars

Background: There is a lack of research on racial challenges among underrepresented adolescents regarding prescription drug use for mental illnesses. Purpose: This study addressed the following question: In adolescent minorities, how does education about racial disparity and culture affect the stigma and number of prescriptions written for psychiatric medications? This evidence-based practice project aimed to identify if racial awareness directly impacts the amount of psychiatric medication prescribed for adolescent minorities. Methods: Literature reviews analyzed qualitative and quantitative data to provide correlating information on racial disparities and psychotropic medications. This study examined the following possible factors for decreased prescribed drugs within …

Operations, Compliance, & Leadership In Dme At Dasco, Andrew Caddas

Masters Theses/Capstone Projects

The practicum experience was completed with DASCO H.M.E., LLC primarily in their corporate office from August through November 2022. I worked with Ann Cornelius, VP of Operations, to learn more about the industry and the role of home medical equipment in patient care. The areas of focus included Sales & Business Development, Compliance, Branch Operations, and Supply Chain.

A Common Mechanism Links Epstein‐Barr Virus Infections And Autoimmune Diseases, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Epstein‐Barr virus (EBV) infection is associated with a variety of the autoimmune diseases. There is apparently no unified model for the role of EBV in autoimmune diseases. In this article, the development of autoimmune diseases is proposed as a simple two‐step process: specific autoimmune initiators may cause irreversible changes to genetic materials that increase autoimmune risks, and autoimmune promoters promote autoimmune disease formation once cells are susceptible to autoimmunity. EBV has several types of latencies including type III latency with higher proliferation potential. EBV could serve as autoimmune initiators for some autoimmune diseases. At the same time, EBV may play …

Characterizing Pulmonary Function Test Changes For Patients With Lung Cancer Treated On A 2-Institution, 4-Dimensional Computed Tomography-Ventilation Functional Avoidance Prospective Clinical Trial, Ryan C. Miller, Richard Castillo, Edward Castillo, Bernard L Jones, Moyed Miften, Brian Kavanagh, Bo Lu, Maria Werner-Wasik, Nader Ghassemi, Joseph Lombardo, Julie Barta, Inga Grills, Chad G Rusthoven, Thomas Guerrero, Yevgeniy Vinogradskiy

Department of Radiation Oncology Faculty Papers

Purpose: Four-dimensional computed tomography (4DCT)-ventilation-based functional avoidance uses 4DCT images to generate plans that avoid functional regions of the lung with the goal of reducing pulmonary toxic effects. A phase 2, multicenter, prospective study was completed to evaluate 4DCT-ventilation functional avoidance radiation therapy. The purpose of this study was to report the results for pretreatment to posttreatment pulmonary function test (PFT) changes for patients treated with functional avoidance radiation therapy.

Methods and materials: Patients with locally advanced lung cancer receiving chemoradiation were accrued. Functional avoidance plans based on 4DCT-ventilation images were generated. PFTs were obtained at baseline and 3 months …

Knowledge, Attitudes, And Practices (Kap) Towards Covid-19 Pandemic Among Pregnant Women In A Tertiary Hospital In Karachi, Pakistan, Sumaira Naz, Syeda Dur E Shawar, Shamila Saleem, Ayesha Malik, Amir Raza

Department of Obstetrics & Gynaecology

Background: The aim of this study was to evaluate the knowledge, attitude, and practices (KAP) of the pregnant population during the COVID-19 pandemic in a tertiary care hospital.
Methods: This cross-sectional study was conducted at Aga Khan University Hospital, Karachi, Pakistan. KAP towards COVID-19 was assessed using 21-item questionnaires. A score for each category was calculated and points were summed. The outcome variables of KAP were compared with demographic characteristics. Data were analyzed by using SPSS 19.
Results: A total of 377 patients participated in the study. The majority of the patients were multiparous (36.8%) in the age group of …

Indirect Comparison Of Lenadogene Nolparvovec Gene Therapy Versus Natural History In Patients With Leber Hereditary Optic Neuropathy Carrying The M.11778g>A Mt-Nd4 Mutation, Valerio Carelli, Nancy J. Newman, Patrick Yu-Wai-Man, Valerie Biousse, Mark L. Moster, Prem S. Subramanian, Catherine Vignal-Clermont, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Robert C. Sergott, Thomas Klopstock, Alfredo A. Sadun, Gema Rebolleda Fernández, Bart K. Chwalisz, Rudrani Banik, Jean François Girmens, Chiara La Morgia, Adam A. Debusk, Neringa Jurkute, Claudia Priglinger, Rustum Karanjia, Constant Josse, Julie Salzmann, François Montestruc, Michel Roux, Magali Taiel, José-Alain Sahel

Wills Eye Hospital Papers

INTRODUCTION: Lenadogene nolparvovec is a promising novel gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G>A ND4 mutation (MT-ND4). A previous pooled analysis of phase 3 studies showed an improvement in visual acuity of patients injected with lenadogene nolparvovec compared to natural history. Here, we report updated results by incorporating data from the latest phase 3 trial REFLECT in the pool, increasing the number of treated patients from 76 to 174.

METHODS: The visual acuity of 174 MT-ND4-carrying patients with LHON injected in one or both eyes with lenadogene nolparvovec from four pooled phase 3 …

Avpcancerfree: Impact Of A Digital Behavior Change Intervention On Parental Hpv Vaccine –Related Perceptions And Behaviors, Sharon P Coan, Stanley W Spinner, Mathew Wilbur, Elisabeth Becker, Travis Teague, Sally W Vernon

Faculty, Staff and Student Publications

Parent hesitancy contributes to reduced HPV vaccination rates. The HPVcancerfree app (HPVCF) was designed to assist parents in making evidence-based decisions regarding HPV vaccination. This study examined if parents of vaccine-eligible youth (11-12 yrs.) who use HPVCF in addition to usual care demonstrate significantly more positive intentions and attitudes toward HPV vaccination and greater HPV vaccination rates compared to those not using HPVCF. Clinics (n = 51) within a large urban pediatric network were randomly assigned to treatment (HPVCF + usual care) or comparison (usual care only) conditions in a RCT conducted between September 2017 and February 2019. Parents completed …

Biomarkers In The Development Of Individualized Treatment Regimens For Colorectal Cancer, Madison Crutcher, Scott A Waldman

Department of Surgery Faculty Papers

Introduction: Colorectal cancer (CRC) is the third most common and second most deadly malignancy in the world with an estimated 1. 9 million cases and 0.9 million deaths in 2020. The 5-year overall survival for stage I disease is 92% compared to a dismal 11% in stage IV disease. At initial presentation, up to 35% of patients have metastatic colorectal cancer (mCRC), and 20-50% of stage II and III patients eventually progress to mCRC. These statistics imply both that there is a proportion of early stage patients who are not receiving adequate treatment and that we are not adequately treating …

Expansion Of The Detrusor Muscular Ring Surrounding The Bladder Neck On Mri: Moving Beyond The Prostate As An Etiology Of Lower Urinary Tract Symptoms Due To Benign Prostatic Hyperplasia, Kiran Nandalur, David Walker, Hong Ye, Sayf A. Al-Katib, Brian Seifman, David Gangwish, Abhay Dhaliwal, Connor Ervin, Kayla Dobies, Channing Sesoko, Sirisha Nandalur, Bernadette Zwaans, Jennifer Nguyen, Jason Hafron

Conference Presentation Abstracts

Purpose: The etiology of lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH) remains uncertain. The purpose of our study was to quantitatively analyze pelvic anatomic characteristics on magnetic resonance imaging (MRI) to assess for independent factors for symptoms.
*Methods and Materials: This retrospective single-institution study evaluated treatment-naïve men who underwent prostate MRI within 3 months of International Prostate Symptom Score (IPSS) from June 2021 to February 2022. Factors measured on MRI included: detrusor muscular ring surrounding the bladder neck measured as area and alternatively diameter, central gland (CG) mean apparent diffusion coefficient (ADC), levator hiatus (LH) volume, intrapelvic …

Hdac2 In Primary Sensory Neurons Constitutively Restrains Chronic Pain By Repressing Α2Δ-1 Expression And Associated Nmda Receptor Activity, Jixiang Zhang, Shao-Rui Chen, Meng-Hua Zhou, Daozhong Jin, Hong Chen, Ronald A Depinho

Faculty, Staff and Student Publications

α2δ-1 (encoded by the Cacna2d1 gene) is a newly discovered NMDA receptor-interacting protein and is the therapeutic target of gabapentinoids (e.g., gabapentin and pregabalin) frequently used for treating patients with neuropathic pain. Nerve injury causes sustained α2δ-1 upregulation in the dorsal root ganglion (DRG), which promotes NMDA receptor synaptic trafficking and activation in the spinal dorsal horn, a hallmark of chronic neuropathic pain. However, little is known about how nerve injury initiates and maintains the high expression level of α2δ-1 to sustain chronic pain. Here, we show that nerve injury caused histone hyperacetylation and diminished enrichment of histone deacetylase-2 (HDAC2), …

Genome Protection By Dna Polymerase Θ, Richard D Wood, Sylvie Doublié

Faculty, Staff and Student Publications

DNA polymerase θ (Pol θ) is a DNA repair enzyme widely conserved in animals and plants. Pol θ uses short DNA sequence homologies to initiate repair of double-strand breaks by theta-mediated end joining. The DNA polymerase domain of Pol θ is at the C terminus and is connected to an N-terminal DNA helicase-like domain by a central linker. Pol θ is crucial for maintenance of damaged genomes during development, protects DNA against extensive deletions, and limits loss of heterozygosity. The cost of using Pol θ for genome protection is that a few nucleotides are usually deleted or added at the …

An Ai-Driven Clinical Care Pathway To Reduce 30-Day Readmission For Chronic Obstructive Pulmonary Disease (Copd) Patients, Mamta Puppala, Zheng Yin, Aaron W Roberts, Aryan Nezamabadi, Pingyi Xu, Adaani Frost, Robert E Jackson, Stephen T C Wong

Faculty, Staff and Student Publications

Healthcare regulatory agencies have mandated a reduction in 30-day hospital readmission rates and have targeted COPD as a major contributor to 30-day readmissions. We aimed to develop and validate a simple tool deploying an artificial neural network (ANN) for early identification of COPD patients with high readmission risk. Using COPD patient data from eight hospitals within a large urban hospital system, four variables were identified, weighted and validated. These included the number of in-patient admissions in the previous 6 months, the number of medications administered on the first day, insurance status, and the Rothman Index on hospital day one. An …

Tip-Over Injuries Among Children: Data From An Urban Emergency Department Of Karachi, Pakistan, Rubaba Naeem, Asrar Ali, Ahmed Raheem Buksh, Ayesha Quddusi, Uzma Rahim Khan

Department of Emergency Medicine

Introduction: Most unintentional injuries among children occur in the home environment. Tip-overs, defined as incidents where heavy objects fall on children due to some type of interaction, are one of the reasons for injuries inside the home. This study aims to determine injury patterns and outcomes for child injuries resulting from tip-overs in the home environment as reported in the emergency department.
Methods: We performed a retrospective chart review of pediatric (under 18 years) tip-overs injuries occurred in years 2010 to 2015 at the Aga Khan University Hospital. Furthermore, parents of injured children participated in phone interviews to provide information …

Covid-19 Newsletter (Vol. 147), Center For Disaster Medicine, New York Medical College

COVID-19 Newsletter

No abstract provided.

Digital Biomarkers Of Gait And Balance In Diabetic Foot, Measurable By Wearable Inertial Measurement Units: A Mini Review, Gu E. Kang, Angeloh Stout, Ke’Vaughn Waldon, Amanda L. Killeen, Peter A. Crisologo, Michael C. Siah, Daniel C. Jupiter, Bijan Najafi, Ashkan Vaziri, Lawrence A. Lavery

School of Podiatric Medicine Publications

People with diabetic foot frequently exhibit gait and balance dysfunction. Recent advances in wearable inertial measurement units (IMUs) enable to assess some of the gait and balance dysfunction associated with diabetic foot (i.e., digital biomarkers of gait and balance). However, there is no review to inform digital biomarkers of gait and balance dysfunction related to diabetic foot, measurable by wearable IMUs (e.g., what gait and balance parameters can wearable IMUs collect? Are the measurements repeatable?). Accordingly, we conducted a web-based, mini review using PubMed. Our search was limited to human subjects and English-written papers published in peer-reviewed journals. We identified …

Routine Immunization Coverage And Immunization Card Retention In Pakistan: Results From A Cross-Sectional National Survey, Imtiaz Hussain, Ahmad Khan, Dale A. Rhoda, Imran Ahmed, Muhammad Umer, Uzair Ansari, Muhammad Akram Shah, Soofia Yunus, Sajid Bashir Soofi, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Background: Immunization is one of the most successful public health interventions available, saving millions of lives from death and disability each year. Therefore, improving immunization coverage is a high priority for the Government of Pakistan and essential to progress toward universal health coverage. This survey reports the national and provincial/regional coverage and determinants of fully, partially, and not-vaccinated children aged 12–23 months, antigen-wise coverage, percentage of home-based vaccination records (HBR) retention, and reasons for nonretention; dropout, timeliness, and prevalence of missed opportunities for simultaneous vaccination (MOSV).
Methods: The survey was a descriptive cross-sectional national household survey carried out across Pakistan. …

Immunity To Poliovirus In Afghanistan: A Household Sampling Method For Serological Assessment Based On Geographical Information Systems, Amalia Mendes, Ari Whiteman, Benjamin Nygren, Brian Kaplan, Imtiaz Hussain, Sajid Bashir Soofi, Maureen Martinez, Noha H. Farag

Department of Paediatrics and Child Health

Afghanistan continues to experience challenges affecting polio eradication. Mass polio vaccination campaigns, which aim to protect children under the age of 5, are a key eradication strategy. To date, the polio program in Afghanistan has only employed facility-based seroprevalence surveys, which can be subject to sampling bias. We describe the feasibility in implementing a cross-sectional household poliovirus seroprevalence survey based on geographical information systems (GIS) in three districts. Digital maps with randomly selected predetermined starting points were provided to teams, with a total target of 1,632 households. Teams were instructed to navigate to predetermined starting points and enrol the closest …

Digital Biomarkers Of Gait And Balance In Diabetic Foot, Measurable By Wearable Inertial Measurement Units: A Mini Review, Gu Eon Kang, Angeloh Stout, Ke'vaughn Waldon, Seungmin Kang, Amanda L Killeen, Peter A Crisologo, Michael Siah, Daniel Jupiter, Bijan Najafi, Ashkan Vaziri, Lawrence A Lavery

Center on Aging Staff Publications

People with diabetic foot frequently exhibit gait and balance dysfunction. Recent advances in wearable inertial measurement units (IMUs) enable to assess some of the gait and balance dysfunction associated with diabetic foot (i.e., digital biomarkers of gait and balance). However, there is no review to inform digital biomarkers of gait and balance dysfunction related to diabetic foot, measurable by wearable IMUs (e.g., what gait and balance parameters can wearable IMUs collect? Are the measurements repeatable?). Accordingly, we conducted a web-based, mini review using PubMed. Our search was limited to human subjects and English-written papers published in peer-reviewed journals. We identified …

Hippo-Yap Signaling Maintains Sinoatrial Node Homeostasis, Mingjie Zheng, Rich G Li, Jia Song, Xiaolei Zhao, Li Tang, Wen Chen, Xiao Li, Min Li, Jianxin Wang, Sylvia M Evans, Vincent M Christoffels, Na Li, Jun Wang

Faculty, Staff and Student Publications

BACKGROUND: The sinoatrial node (SAN) functions as the pacemaker of the heart, initiating rhythmic heartbeats. Despite its importance, the SAN is one of the most poorly understood cardiac entities because of its small size and complex composition and function. The Hippo signaling pathway is a molecular signaling pathway fundamental to heart development and regeneration. Although abnormalities of the Hippo pathway are associated with cardiac arrhythmias in human patients, the role of this pathway in the SAN is unknown.

METHODS: We investigated key regulators of the Hippo pathway in SAN pacemaker cells by conditionally inactivating the Hippo signaling kinases

RESULTS: We …

Professional Perspectives On Bilingualism In Persons With Autism Spectrum Disorder: A Pilot Study, Rosa N. Benavidez Saldivar, Jessica R. Stewart, Ruth Crutchfield, Roy K. Chen, Lily Puente

Internet Journal of Allied Health Sciences and Practice

Purpose: The present study examined the perspectives of professionals regarding bilingualism and ASD. Methods: A total of 27 professionals participated in this study. Data was collected via an online survey. The survey was designed based on a literature review and consultation with a team of experts in the field of ASD. Information relating to demographic information, professional practice information, and perspectives of bilingualism and ASD was collected. Results: Professionals participating in the present study were most likely to agree with the statement, “A child with ASD from a bilingual household is able to understand both languages” and least likely to …

Patterns Of Suicide And Self-Harm In Pakistan: A Retrospective Descriptive Study Protocol, Nargis Asad, Shahina Pirani, Summaiya Tariq, Asra Qureshi, Mohammad Zaman, Mustafa Aslam, Farhat Mirza, Murad M. Khan

Department of Psychiatry

Introduction: Suicide is a major global public health problem. Low-income and middle-income countries contribute 78% of all suicidal deaths. Pakistan, a South Asian country, lacks official statistics on suicides at national level. Statistics on suicide are neither collected nationally nor published in the annual national morbidity and mortality surveys. Medicolegal reports on suicides and self-harm are extremely rich and important source of information but greatly underused in Pakistan. We aim to examine the patterns of suicides and self-harm retrospectively in patients who were registered with medicolegal centres (MLCs) in Karachi, during the period January 2017 to December 2021.
Methods and …

The Diagnosis Of Severe Combined Immunodeficiency: Implementation Of The Pidtc 2022 Definitions, Christopher C. Dvorak, Elie Haddad, Jennifer Heimall, Elizabeth Dunn, Morton J. Cowan, Sung-Yun Pai, Neena Kapoor, Lisa Forbes Satter, Rebecca H. Buckley, Richard J. O'Reilly, Sharat Chandra, Jeffrey J. Bednarski, Olatundun Williams, Ahmad Rayes, Theodore B. Moore, Christen L. Ebens, Blachy J. Davila Saldana, Aleksandra Petrovic, Deepak Chellapandian, Geoffrey D. E. Cuvelier, Mark T. Vander Lugt, Emi H. Caywood, Shanmuganathan Chandrakasan, Hesham Eissa, Frederick D. Goldman, Evan Shereck, Victor M. Aquino, Kenneth B. Desantes, Lolie Yu, Et Al

School of Medicine Faculty Publications

Background: Shearer et al in 2014 articulated well-defined criteria for the diagnosis and classification of severe combined immunodeficiency (SCID) as part of the Primary Immune Deficiency Treatment Consortium's (PIDTC's) prospective and retrospective studies of SCID. Objective: Because of the advent of newborn screening for SCID and expanded availability of genetic sequencing, revision of the PIDTC 2014 Criteria was needed. Methods: We developed and tested updated PIDTC 2022 SCID Definitions by analyzing 379 patients proposed for prospective enrollment into Protocol 6901, focusing on the ability to distinguish patients with various SCID subtypes. Results: According to PIDTC 2022 Definitions, 18 of 353 …

The Associations Between Central Serous Chorioretinopathy And Muscle Relaxants: A Case-Control Study, Manish Jain, Sunir J. Garg, Mohammad Khan, Varun Chaudhary, Dena Zeraatkar, Dhanya Kurian, Sarath Lal

Wills Eye Hospital Papers

PURPOSE: To evaluate the role of muscle-relaxants as risk factors for the development of central serous chorioretinopathy (CSC) - the second most common retinopathy in our settings; despite multiple risk factors seen in our patients, 21% were initially labelled as idiopathic.

MATERIALS AND METHODS: Retrospective case-control study at a tertiary hospital in the United Arab Emirates, where we reviewed the medical records of 273 patients with CSC examined between 2010 and 2019 for use of muscle-relaxants including tolperisone/eperisone, carisoprodol and gabapentin/pregabalin within a year of onset/recurrence of the disease. Intake of drugs with known association with CSC (including corticosteroids/sympathomimetics) was …

A Systematic Review And Meta-Analysis: Assessment Of Hospital Walking Programs Among Older Patients, Christine Loyd, Yue Zhang, Tara Weisberg, James Boyett, Elizabeth R. Huckaby, Jeri Grundhoefer, Steve Otero, Lisa Roberts, Samantha Giordano-Mooga, Carmen Capo-Lugo, Catherine H. Smith, Richard E. Kennedy, Barbara J. King, Cynthia J. Brown

School of Medicine Faculty Publications

Aim: The aim of this study is to assess effect of hospital walking programs on outcomes for older inpatients and to characterize hospital walking dose reported across studies. Design: A systematic review and meta-analysis examining impact of hospital walking and/or reported walking dose among medical-surgical inpatients. For inclusion, studies were observational or experimental, published in English, enrolled inpatients aged ≥ 65 yrs hospitalized for medical or surgical reasons. Methods: Searches of PubMed, CINAHL, Embase, Scopus, NICHSR, OneSearch, ClinicalTrials.gov, and PsycINFO were completed in December 2020. Two reviewers screened sources, extracted data, and performed quality bias appraisal. Results: Hospital walking dose …

Metabolic Targeting Of Nrf2 Potentiates The Efficacy Of The Trap1 Inhibitor G-Tpp Through Reduction Of Ros Detoxification In Colorectal Cancer, John F Valentine, Noah F Shroyer, Lisa A Lai, Teresa A Brentnall, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial homolog of HSP90 chaperones. It plays an important role in protection against oxidative stress and apoptosis by regulating reactive oxidative species (ROS). To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer. Inhibition of TRAP1 by G-TPP disrupted redox homeostasis and induced cell death. However, colon cancers show a wide range of responses to G-TPP treatment through the induction of variable ER stress responses and ROS accumulation. Interestingly, a strong inverse correlation was observed between …

Genetic And Small-Molecule Modulation Of Stat3 In A Mouse Model Of Crohn's Disease, Prema Robinson, Emily Magness, Kelsey Montoya, Nikita Engineer, Thomas K Eckols, David J Tweardy

Faculty, Staff and Student Publications

Crohn's disease (CD), is an inflammatory bowel disease that can affect any part of the gastro-intestinal tract (GI) and is associated with an increased risk of gastro-intestinal cancer. In the current study, we determined the role of genetic and small-molecule modulation of STAT3 in a mouse model of CD. STAT3 has 2 isoforms (α, β) which are expressed in most cells in a 4:1 ratio (α: β). STAT3α has pro-inflammatory and anti-apoptotic functions, while STAT3β has contrasting roles. We used an animal model of CD consisting of intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid and examined the severity of CD in …

The Fate Of Early Perichondrial Cells In Developing Bones, Yuki Matsushita, Angel Ka Yan Chu, Chiaki Tsutsumi-Arai, Shion Orikasa, Mizuki Nagata, Joshua D Welch, Noriaki Ono

Faculty, Staff and Student Publications

In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. However, how early perichondrial cells distinctively contribute to developing bones remain unidentified. Here we show using in vivo cell-lineage analyses that Dlx5+ fetal perichondrial cells marked by Dlx5-creER do not generate cartilage but sustainably contribute to cortical bone and marrow stromal compartments in a manner complementary to fetal chondrocyte derivatives under the regulation of Hedgehog signaling. Postnatally, Dlx5+ fetal perichondrial cell derivatives preferentially populate the diaphyseal marrow stroma with a dormant adipocyte-biased state and are refractory to parathyroid …

Inactivation Of Lats1/2 Drives Luminal-Basal Plasticity To Initiate Basal-Like Mammary Carcinomas, Joseph G Kern, Andrew M Tilston-Lunel, Anthony Federico, Boting Ning, Amy Mueller, Eleni Stampouloglou, Randy L Johnson, Marc E Lenburg, Jennifer E Beane, Stefano Monti, Xaralabos Varelas

Faculty, Staff and Student Publications

Basal-like breast cancers, an aggressive breast cancer subtype that has poor treatment options, are thought to arise from luminal mammary epithelial cells that undergo basal plasticity through poorly understood mechanisms. Using genetic mouse models and ex vivo primary organoid cultures, we show that conditional co-deletion of the LATS1 and LATS2 kinases, key effectors of Hippo pathway signaling, in mature mammary luminal epithelial cells promotes the development of Krt14 and Sox9-expressing basal-like carcinomas that metastasize over time. Genetic co-deletion experiments revealed that phenotypes resulting from the loss of LATS1/2 activity are dependent on the transcriptional regulators YAP/TAZ. Gene expression analyses of …

Optimal Construction Of A Functional Interaction Network From Pooled Library Crispr Fitness Screens, Veronica Gheorghe, Traver Hart

Faculty, Staff and Student Publications

BACKGROUND: Functional interaction networks, where edges connect genes likely to operate in the same biological process or pathway, can be inferred from CRISPR knockout screens in cancer cell lines. Genes with similar knockout fitness profiles across a sufficiently diverse set of cell line screens are likely to be co-functional, and these "coessentiality" networks are increasingly powerful predictors of gene function and biological modularity. While several such networks have been published, most use different algorithms for each step of the network construction process.

RESULTS: In this study, we identify an optimal measure of functional interaction and test all combinations of options …

Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin

Department of Pathology and Laboratory Medicine

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal …