Medicine and Health Sciences Commons^™

Perilous Consequences Of Chemotherapy Induced Alopecia In Afflicted Cancer Survivors: A Comprehensive State Of The Art Review, Salma A. Fereig, Mona Gamal Arafa, Ghada Mamdouh Elzaafarany, Mona Mohamed Ahmed Abdelmottaleb, John Youshia

Pharmacy

Due to researchers’ great efforts during previous and current centuries to cure cancer, a remarkable increase in the number of cancer survivors has been observed. However, side effects of chemotherapeutic agents greatly affect the quality of life of cancer cases, usually referred to as cancer stigma, the most psychologically traumatizing of which is chemotherapy-induced alopecia (anagen effluvium). Unfortunately, there is no preventive protocol for chemotherapy-induced alopecia to date. The only suggested technique is vasoconstriction by scalp cooling during and after chemotherapy sessions to minimize the absorption of cytotoxic agents within the hair follicle area; a technique that is not very …

Emotional Design Of Lecture Slides During Anatomy Lectures: Effect On Mood, Cognitive, Load And Memory Retention, Joshua Raj Narayanan

Student Works (2020-2029)

This study investigates the efficacy of emotional design in Anatomy and Medical education, a subject hitherto unexamined in emotional design studies. Further, unlike previous studies, this study utilised a natural learning environment rather than computer-based lessons. We investigated how the emotional design of lecture slides impacts mood, cognitive load and memory retention in first-year anatomy students studying medicine and dentistry in Universiti Malaya across three separate lectures. The control group (medical students) were exposed to emotionally neutral slides, while the experiment group (dental students) were exposed to emotionally positive slides. Questionnaires were used to assess changes in participants' mood, as …

Association Between Unmet Needs And Happiness In Women Living With Breast Cancer In A Multiethnic, Middle-Income Setting, Nithiya Sinarajoo

Student Works (2020-2029)

While improved breast cancer survival rates are commendable, healthcare professionals and stakeholders must acknowledge potential strains on the healthcare system and society if optimal support and survivorship programs are not established. A global shift towards personalized, holistic patient care is crucial. However, implementing such care in a low- and middle-income country like Malaysia faces significant barriers. Positive psychology, which focuses on fostering positive emotions, has shown promise in promoting better health and longevity in healthy populations. However, research on the concept of happiness, both as a predictor of health outcomes and as a patient-reported outcome in cancer settings, remains limited. …

Small Gtp-Binding Protein Gdp Dissociation Stimulator Influences Cisplatin-Induced Acute Kidney Injury Via Perk-Dependent Er Stress, Yuxue Yang, Ting Xiong, Ti Wang, Xiwei Chen, Ziwei Ma, Bangyun Zuo, Dong Ning, Ruilong Song, Xuesong Liu, Daxin Wang

Children’s Nutrition Research Center Staff Publications

Cisplatin is a common anticancer drug, but its frequent nephrotoxicity limits its clinical use. Small GTP-binding protein GDP dissociation stimulator (smgGDS), a small GTPase chaperone protein, was considerably downregulated during cisplatin-induced acute kidney injury (CDDP-AKI), especially in renal tubular epithelial cells. SmgGDS-knockdown mice was established and found that smgGDS knockdown promoted CDDP-AKI, as demonstrated by an increase in serum creatine, blood urea nitrogen levels and the appearance of tubular patterns. RNA sequencing suggested that protein kinase RNA-like ER kinase (PERK), which bridges mitochondria-associated ER membranes, was involved in smgGDS knockdown following CDDP-AKI, and then identified that smgGDS knockdown increased phosphorylated-PERK …

Assessing Nurse Educators' Competencies For Adopting Blended Learning In The Skills Labs In Uganda's Public Nursing Schools, Eva Kakonge Nampiima, Mathias M Bwanika Ulumba, Musisi Badru, Grace Nakate

School of Nursing & Midwifery, East Africa

Blended learning has become an integral part of nursing education, offering a blend of online and face-to-face instruction that enhances learning experiences, particularly within skills labs. However, the effectiveness of blended learning largely depends on the competencies of nurse educators in utilizing digital tools and methodologies. This study assessed the competencies of nurse educators in Uganda's public nursing schools concerning blended learning adoption. Data was collected from 40 randomly selected nursing educators in 4 public nursing schools in Uganda. The findings indicate significant inadequacies: only 25% are proficient with Learning Management Systems (LMS) like Moodle, 20% can effectively use platforms …

An International Consensus Panel On The Potential Value Of Digital Surgery, Jamie Erskine, Payam Abrishami, Jean Christophe Bernhard, Richard Charter, Richard Culbertson, Jo Carol Hiatt, Ataru Igarashi, Gretchen Purcell Jackson, Matthew Lien, Guy Maddern, Joseph Soon Yau Ng, Anita Patel, Koon Ho Rha, Prasanna Sooriakumaran, Scott Tackett, Giuseppe Turchetti, Anastasia Chalkidou

School of Public Health Faculty Publications

OBJECTIVES: The use of digital technology in surgery is increasing rapidly, with a wide array of new applications from presurgical planning to postsurgical performance assessment. Understanding the clinical and economic value of these technologies is vital for making appropriate health policy and purchasing decisions. We explore the potential value of digital technologies in surgery and produce expert consensus on how to assess this value. DESIGN: A modified Delphi and consensus conference approach was adopted. Delphi rounds were used to generate priority topics and consensus statements for discussion. SETTING AND PARTICIPANTS: An international panel of 14 experts was assembled, representing relevant …

Substitution Of A Single Non-Coding Nucleotide Upstream Of Tmem216 Causes Non-Syndromic Retinitis Pigmentosa And Is Associated With Reduced Tmem216 Expression, Samantha Malka, Pooja Biswas, Anne-Marie Berry, Riccardo Sangermano, Mukhtar Ullah, Siying Lin, Matteo D'Antonio, Aleksandr Jestin, Xiaodong Jiao, Mathieu Quinodoz, Lori Sullivan, Jessica C Gardner, Emily M Place, Michel Michaelides, Karolina Kaminska, Omar A Mahroo, Elena Schiff, Genevieve Wright, Francesca Cancellieri, Veronika Vaclavik, Cristina Santos, Atta Ur Rehman, Sudeep Mehrotra, Hafiz Muhammad Azhar Baig, Muhammad Iqbal, Muhammad Ansar, Luisa Coutinho Santos, Ana Berta Sousa, Viet H Tran, Hiroko Matsui, Anjana Bhatia, Muhammad Asif Naeem, Shehla J Akram, Javed Akram, Sheikh Riazuddin, Carmen Ayuso, Eric A Pierce, Alison J Hardcastle, S Amer Riazuddin, Kelly A Frazer, J Fielding Hejtmancik, Carlo Rivolta, Kinga M Bujakowska, Gavin Arno, Andrew R Webster, Radha Ayyagari

Faculty, Staff and Student Publications

Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in individuals of South Asian and African ancestry, respectively. Genotypes included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations. Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation …

Improving Ligand Pharmacokinetics Via Bioisosteric Substitution Of Amides With 1, 2, 3-Triazoles While Maintaining Dopamine D4 Receptor Selectivity And Potency, Mohammad Alkhatib

Theses and Dissertations

Several neurophysiological functions, such as attention, cognition, and emotional regulation, are regulated by the binding of dopamine on G-Protein coupled receptors. D4Rs are mainly located in the prefrontal cortex and the hippocampus and are known to have a key role in decision-making, memory formation, cognition, and attention. Administration of D4Rs- selective ligands during the preclinical studies enhance the outcomes and the results in animal models suffering from neuropsychiatric disorders, including ADHD, substance use disorders (SUD), and Alzheimer's disease. Recently, we reported a group of D4R-selective ligands with different efficacies depending on their phenylpiperazine ring scaffold to illustrate D4R function during …

Current Diagnostic And Quantitative Techniques In The Field Of Lymphedema Management: A Critical Review, Mary Vargo, Melissa Aldrich, Paula Donahue, Emily Iker, Louise Koelmeyer, Rachelle Crescenzi, Andrea Cheville

The Brown Foundation: Institute of Molecular Medicine

Lymphedema evaluation entails multifaceted considerations for which options continue to evolve and emerge. This paper provides a critical review of the current status of diagnostic and quantitative measures for lymphedema, from traditional and novel bedside assessment tools for volumetric and fluid assessment, to advanced imaging modalities. Modalities are contrasted with regard to empirical support and feasibility of clinical implementation. The manuscript proposes a grid framework for comparing the ability of each modality to quantify specific lymphedema characteristics, including distribution, dysmorphism, tissue composition and fluid content, lymphatic anatomy and function, metaplasia, clinical symptoms, and quality of life and function. This review …

Interoception In Pregnancy: Implications For Peripartum Depression, Paul W. Savoca, Laura M. Glynn, Molly M. Fox, Misty C. Richards, Bridget L. Callaghan

Psychology Faculty Articles and Research

"In this perspective piece, we propose a novel mechanistic framework for peripartum depression in which improved interoceptive functioning in pregnancy and postpartum typically protects against depressive symptoms, but when there is a failure to improve interoception, the result is an inability to maintain metabolic efficiency, which ultimately poses risk for depression. First, we will review an emerging theory that links the modeling and predictive regulation of metabolic resources as central to the expression of many depressive symptoms. Then, focusing on the period of pregnancy to articulate the framework, we will discuss the physiological changes induced by pregnancy that place an …

90y Sir-Spheres Activity Measurement With New Siros D-Vial Delivery Kit, Benjamin P Lopez, S Cheenu Kappadath

Faculty, Staff and Student Publications

A new 90Y SIR-Spheres delivery kit (SIROS D-vial and shield) has been introduced with a different physical form from the legacy V-Vial kit. Here, we establish the dose calibrator settings and exposure-rate-to-activity conversion factor to assay 90Y SIR-Spheres activity in the new SIROS kit.

Methods: Eight D-vials with initial 90Y activities from 1.2 to 6.6 GBq within acrylic shields were assayed with dose calibrators and exposure-rate meters until activities decayed to approximately 0.1 GBq. The dose calibrator settings resulting in the lowest median activity errors and the best-fit slope of exposure rate versus activity were identified.

Results: SIROS D-vial 90Y …

The Scaffolding Function Of Lsd1 Controls Dna Methylation In Mouse Escs, Sandhya Malla, Kanchan Kumari, Carlos A García-Prieto, Jonatan Caroli, Anna Nordin, Trinh T T Phan, Devi Prasad Bhattarai, Carlos Martinez-Gamero, Eshagh Dorafshan, Stephanie Stransky, Damiana Álvarez-Errico, Paulina Avovome Saiki, Weiyi Lai, Cong Lyu, Ludvig Lizana, Jonathan D Gilthorpe, Hailin Wang, Simone Sidoli, Andre Mateus, Dung-Fang Lee, Claudio Cantù, Manel Esteller, Andrea Mattevi, Angel-Carlos Roman, Francesca Aguilo

Faculty, Staff and Student Publications

Lysine-specific histone demethylase 1 (LSD1), which demethylates mono- or di- methylated histone H3 on lysine 4 (H3K4me1/2), is essential for early embryogenesis and development. Here we show that LSD1 is dispensable for mouse embryonic stem cell (ESC) self-renewal but is required for mouse ESC growth and differentiation. Reintroduction of a catalytically-impaired LSD1 (LSD1MUT) recovers the proliferation capability of mouse ESCs, yet the enzymatic activity of LSD1 is essential to ensure proper differentiation. Indeed, increased H3K4me1 in Lsd1 knockout (KO) mouse ESCs does not lead to major changes in global gene expression programs related to stemness. However, ablation of LSD1 but …

Targeting Igf2 To Reprogram The Tumor Microenvironment For Enhanced Viro-Immunotherapy, Min Hye Noh, Jin Muk Kang, Alexandra A Miller, Grace Nguyen, Minxin Huang, Ji Seon Shim, Alberto J Bueso-Perez, Sara A Murphy, Kimberly A Rivera-Caraballo, Yoshihiro Otani, Eunju Kim, Seung-Hee Yoo, Yuanqing Yan, Yeshavanth Banasavadi-Siddegowda, Hiroshi Nakashima, E Antonio Chiocca, Balveen Kaur, Zhongming Zhao, Tae Jin Lee, Ji Young Yoo

Faculty, Staff and Student Publications

BACKGROUND: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME).

METHODS: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance.

RESULTS: Transcriptome analysis identified IGF2 as one of the top-secreted proteins following oHSV treatment. …

Transcatheter Closure Of Complex Multifenestrated Atrial Septal Defect Using Three Septal Occluders: Is Three Too Many?, Hussam Al Hennawi, Appa Bandi, Ahmad Abulshamat, Shaurya Srivastava, Mohammed Qintar

Abington Jefferson Health Papers

Atrial septal defects (ASDs) are a common form of adult congenital heart disease, with surgical or transcatheter closure being the mainstay of treatment in patients with hemodynamic or clinical complications. Transcatheter repair of secundum ASD is safe and effective. Complex secundum ASDs with multifenestrated defects pose a unique challenge to transcatheter repair. We report a successful but complex transcatheter closure of an ASD using three overlapping Amplazter devices.

Racial Attitudes And Perceptions Of Government Response During The Covid-19 Pandemic: Implications For Public Health Strategies., Man Hung, Jeremy D. Franklin, William A. Smith, Carlos J. Crespo, Evelyn U. Ezikwelu, Jerry Bounsanga, Martin S. Lipsky

Institute on Aging Publications

This study explored whether opinions about the government's role in addressing the COVID-19 pandemic vary based on demographic characteristics and racial beliefs. We hypothesized that opinions about the United States (U.S.) government's response to COVID-19 would differ based on an individual's characteristics such as age, race, and racial beliefs.

How Does Your Garden Grow? Development Of A Calculator To Evaluate The Economic And Dietary Impact Of Edible Gardens, Sofia O. Sanchez, Katie Funderburk, Erin Reznicek, Sondra M. Parmer

Journal of Extension

Edible gardens can increase fruit and vegetable availability and access. Weighing produce is a method to evaluate gardens, however there are limited methods that translate garden yields to dietary yields and that document Supplemental Nutrition Assistance Program – Education (SNAP-Ed) garden yields. We developed a Garden Harvest Calculator to evaluate edible garden economic and dietary impact. Over three spring-to-summer growing seasons, 12 – 18 gardens produced 6,499 pounds of produce worth $11,606.95. This equates to 24,922 cups, enough for 4,984 adults to meet dietary recommendations. SNAP-Ed supported gardens may positively contribute to dietary needs while reducing barriers to food access.

Clinical Practice Guideline-Inconsistent Chemotherapy-Induced Vomiting Prophylaxis In Pediatric Cancer Patients In Community Settings: A Children's Oncology Group Study, Aaron J. Sugalski, Allison C. Grimes, Michelle M. Nuño, Subhash Ramakrishnan, Melissa P. Beauchemin, Paula D. Robinson, Nancy Santesso, Alexandra M. Walsh, Andrea R. Wrightson, Lolie C. Yu, Susan K. Parsons, Lillian Sung, L. Lee Dupuis

School of Medicine Faculty Publications

Background: This study aimed to determine the proportion of patients receiving clinical practice guideline (CPG)-inconsistent care related to chemotherapy-induced vomiting (CIV) prophylaxis, and to describe the association between CPG-inconsistent care and site size. The association between delivery of CPG-inconsistent care and patient outcomes (CIV control, admission prolongation, and unplanned healthcare visits) was also described. Methods: This was a retrospective study conducted at Children's Oncology Group (COG) National Cancer Institute Community Oncology Research Program (NCORP) sites. Eligible patients received highly (HEC) or moderately emetogenic chemotherapy (MEC) as inpatients from January 2014 through December 2015, and were previously enrolled in a COG …

Tulips Decorate The Three-Dimensional Genome Of Pfa Ependymoma, Michael J Johnston, John J Y Lee, Bo Hu, Ana Nikolic, Elham Hasheminasabgorji, Audrey Baguette, Seungil Paik, Haifen Chen, Sachin Kumar, Carol C L Chen, Selin Jessa, Polina Balin, Vernon Fong, Melissa Zwaig, Kulandaimanuvel Antony Michealraj, Xun Chen, Yanlin Zhang, Srinidhi Varadharajan, Pierre Billon, Nikoleta Juretic, Craig Daniels, Amulya Nageswara Rao, Caterina Giannini, Eric M Thompson, Miklos Garami, Peter Hauser, Timea Pocza, Young Shin Ra, Byung-Kyu Cho, Seung-Ki Kim, Kyu-Chang Wang, Ji Yeoun Lee, Wieslawa Grajkowska, Marta Perek-Polnik, Sameer Agnihotri, Stephen Mack, Benjamin Ellezam, Alex Weil, Jeremy Rich, Guillaume Bourque, Jennifer A Chan, V Wee Yong, Mathieu Lupien, Jiannis Ragoussis, Claudia Kleinman, Jacek Majewski, Mathieu Blanchette, Nada Jabado, Michael D Taylor, Marco Gallo

Faculty, Staff and Students Publications

Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues. A remarkable feature exclusively present in PFA are type B ultra long-range interactions in PFAs (TULIPs), regions separated by great distances along the linear genome that interact with each other in …

Asymmetric Distribution Of Color-Opponent Response Types Across Mouse Visual Cortex Supports Superior Color Vision In The Sky, Katrin Franke, Chenchen Cai, Kayla Ponder, Jiakun Fu, Sacha Sokoloski, Philipp Berens, Andreas Savas Tolias

Faculty, Staff and Students Publications

Color is an important visual feature that informs behavior, and the retinal basis for color vision has been studied across various vertebrate species. While many studies have investigated how color information is processed in visual brain areas of primate species, we have limited understanding of how it is organized beyond the retina in other species, including most dichromatic mammals. In this study, we systematically characterized how color is represented in the primary visual cortex (V1) of mice. Using large-scale neuronal recordings and a luminance and color noise stimulus, we found that more than a third of neurons in mouse V1 …

Stat3-Mediated Atg7 Expression Regulates Anti-Tumor Immunity In Mouse Melanoma, Sarah M Zimmerman, Erin Suh, Sofia R Smith, George P Souroullas

2020-Current year OA Pubs

Epigenetic modifications to DNA and chromatin control oncogenic and tumor-suppressive mechanisms in melanoma. Ezh2, the catalytic component of the Polycomb Repressive Complex 2 (PRC2), which mediates methylation of lysine 27 on histone 3 (H3K27me3), can regulate both melanoma initiation and progression. We previously found that mutant Ezh2

Cyp3a-Mediated Carbon-Carbon Bond Cleavages In Drug Metabolism, Junhui Zhou, Xuan Qin, Shenzhi Zhou, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

Cytochrome P450 enzymes (P450s) play a critical role in drug metabolism, with the CYP3A subfamily being responsible for the biotransformation of over 50% of marked drugs. While CYP3A enzymes are known for their extensive catalytic versatility, one intriguing and less understood function is the ability to mediate carbon-carbon (C-C) bond cleavage. These uncommon reactions can lead to unusual metabolites and potentially influence drug safety and efficacy. This review focuses on examining examples of C-C bond cleavage catalyzed by CYP3A, exploring the mechanisms, physiological significance, and implications for drug metabolism. Additionally, examples of CYP3A-mediated ring expansion via C-C bond cleavages are …

Adjunctive Intravenous Argatroban Or Eptifibatide For Ischemic Stroke, Opeolu Adeoye, Peter Panagos, Stephanie Pizzella, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear.

METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with …

Prospective Exploratory Evaluation Of Cepheid Xpert Mycobacterium Tuberculosis Host Response Cartridge: A Focus On Adolescents And Young Adults, Marva Seifert, Donald G. Catanzaro, Michael Gracia, Naomi Hillery, Sabira Tahseen, Faisal Masood, Uzma Majeed, Rebecca E. Colman, Rehan Syed, Antonino Catanzaro, Timothy Rodwell

Biological Sciences Faculty Publications and Presentations

Background. An accurate, rapid, non-sputum-based triage test for diagnosing tuberculosis (TB) is needed. Methods. A prospective evaluation of the Cepheid GeneXpert Mycobacterium tuberculosis Host Response cartridge (Xpert- MTB-HR), a prototype blood-based host response mRNA signature assay, among individuals presenting with TB-like symptoms was performed in Pakistan and results were compared to 3 reference standards: Xpert MTB/RIF Ultra, bacteriological confirmation (Xpert MTB/RIF Ultra and/or culture positivity), and composite clinical diagnosis (clinician diagnosis, treatment initiation, Xpert MTB/RIF Ultra, and/or culture positivity). Analyses were conducted both for the entire study cohort and separately in the adolescent and young adult cohort (aged 10–24 years). …

Rna Interacts With Topoisomerase I To Adjust Dna Topology, Mannan Bhola, Kouki Abe, Paola Orozco, Homa Rahnamoun, Pedro Avila-Lopez, Elijah Taylor, Nefertiti Muhammad, Bei Liu, Prachi Patel, John F Marko, Anne C Starner, Chuan He, Eric L Van Nostrand, Alfonso Mondragón, Shannon M Lauberth

Faculty, Staff and Students Publications

Topoisomerase I (TOP1) is an essential enzyme that relaxes DNA to prevent and dissipate torsional stress during transcription. However, the mechanisms underlying the regulation of TOP1 activity remain elusive. Using enhanced cross-linking and immunoprecipitation (eCLIP) and ultraviolet-cross-linked RNA immunoprecipitation followed by total RNA sequencing (UV-RIP-seq) in human colon cancer cells along with RNA electrophoretic mobility shift assays (EMSAs), biolayer interferometry (BLI), and in vitro RNA-binding assays, we identify TOP1 as an RNA-binding protein (RBP). We show that TOP1 directly binds RNA in vitro and in cells and that most RNAs bound by TOP1 are mRNAs. Using a TOP1 RNA-binding mutant …

Neoadjuvant Parpi Or Chemotherapy In Ovarian Cancer Informs Targeting Effector Treg Cells For Homologous-Recombination-Deficient Tumors, Yikai Luo, Yu Xia, Dan Liu, Xiong Li, Huayi Li, Jiahao Liu, Dongchen Zhou, Yu Dong, Xin Li, Yiyu Qian, Cheng Xu, Kangjia Tao, Guannan Li, Wen Pan, Qing Zhong, Xingzhe Liu, Sen Xu, Zhi Wang, Ronghua Liu, Wei Zhang, Wanying Shan, Tian Fang, Siyuan Wang, Zikun Peng, Ping Jin, Ning Jin, Shennan Shi, Yuxin Chen, Mengjie Wang, Xiaofei Jiao, Mengshi Luo, Wenjian Gong, Ya Wang, Yue Yao, Yi Zhao, Xinlin Huang, Xuwo Ji, Zhaoren He, Guangnian Zhao, Rong Liu, Mingfu Wu, Gang Chen, Li Hong, Cocpo Consortium, Ding Ma, Yong Fang, Han Liang, Qinglei Gao

Faculty, Staff and Student Publications

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD …

Implementation Of A Dyadic Nomenclature For Monogenic Diseases, Courtney Thaxton, Leslie G Biesecker, Marina Distefano, Melissa Haendel, Ada Hamosh, Emma Owens, Sharon E Plon, Heidi L Rehm, Jonathan S Berg

Center for Medical Ethics and Health Policy Staff Publications

A core task when establishing the strength of evidence for a gene's role in a monogenic disorder is determining the appropriate disease entity to curate. Establishing this concept determines which evidence can be applied and quantified toward the final gene-disease validity, variant pathogenicity, or actionability classification. Genes with implications in more than one phenotype can necessitate a process of lumping and splitting, disease reorganization, and updates to disease nomenclature. Reappraisal of the names that are used as labels for disease entities is therefore a necessary and perpetual process. The Clinical Genome Resource (ClinGen), in collaboration with representatives from Monarch Disease …

Efficacy Of Parp Inhibitor Therapy After Targeted Braf/Mek Failure In Advanced Melanoma, Jordan Phillipps, George Nassief, Renee Morecroft, Tolulope Adeyelu, Andrew Elliott, Farah Abdulla, Ari Vanderwalde, Soo Park, Omar Butt, Alice Zhou, George Ansstas

2020-Current year OA Pubs

Modern advancements in targeted therapy and immunotherapy have significantly improved survival outcomes for advanced melanoma; however, there remains a need for novel approaches to overcome disease progression and treatment resistance. In recent years, PARPi therapy has shown great promise both as a single regimen and in combination with other therapeutics in melanoma. Here, we describe three unique cases of advanced BRAF V600 mutated melanoma that progressed on targeted BRAF/MEK agents that subsequently exhibited partial to near-complete responses to combinatory PARPi and BRAF/MEK inhibitors. This highlights both a potential synergy underlying this combinatory approach and its efficacy as a treatment option …

Regional Desynchronization Of Microglial Activity Is Associated With Cognitive Decline In Alzheimer's Disease, Artem Zatcepin, Samira Parhizkar, Et Al.

2020-Current year OA Pubs

BACKGROUND: Microglial activation is one hallmark of Alzheimer disease (AD) neuropathology but the impact of the regional interplay of microglia cells in the brain is poorly understood. We hypothesized that microglial activation is regionally synchronized in the healthy brain but experiences regional desynchronization with ongoing neurodegenerative disease. We addressed the existence of a microglia connectome and investigated microglial desynchronization as an AD biomarker.

METHODS: To validate the concept, we performed microglia depletion in mice to test whether interregional correlation coefficients (ICCs) of 18 kDa translocator protein (TSPO)-PET change when microglia are cleared. Next, we evaluated the influence of dysfunctional microglia …

Taste Masked Of Eplerenone Using Egg Box Method, Asmaa Mohammed Rashid

Maaen Journal for Medical Sciences

Eplerenone is a selective mineralocorticoid receptor antagonist employed to manage hypertension, central serous retinopathy, and chronic heart failure. It has a highly bitter taste, which reduces patient compliance with the drug.

The aim of this study was masking the very bitter taste of the eplerenone to improve patient compliance especially for geriatric patient.

The medication was encapsulated utilizing the ionic gelation process, in which a 1% w/w sodium alginate solution was utilized to form egg box structures.Two different concentrations of CaCl2 (0.5.1%w/v) were used as cross-linkers, and different drug: polymer ratios were tested. The formulas were evaluated based on their …

Developing A Stand-Alone Children’S Hospital In Southern Nevada: Improving Pediatric Care And Diversifying The Regional Economy, The Lincy Institute

Lincy Institute Events

Southern Nevada is the largest metropolitan region in the country without a stand-alone children's hospital. The absence of such a facility results in poor health outcomes for children, fragmented and inadequate specialized care, and a shortage of pediatric medical professionals. Currently ranked last in clinical care nationwide, Nevada urgently needs a centralized, academic-based children's hospital to improve health services.

The Lincy Institute hosted a community forum to release the findings of a new report conducted by Tripp Umbach detailing why Southern Nevada needs a stand-alone children’s hospital. Tripp Umbach is a recognized industry leader, with 30 years of successful partnerships …