Digital Commons Network^™

Short Tandem Repeat Profiling Via Next-Generation Sequencing For Cell Line Authentication, Yi-Hsien Chen, Jon P Connelly, Colin Florian, Xiaoxia Cui, Shondra M Pruett-Miller

2020-Current year OA Pubs

Cell lines are indispensable models for modern biomedical research. A large part of their usefulness derives from the ability of a cell line to proliferate over multiple passages (often indefinitely), allowing multiple experiments to be performed. However, over time, cell line identity and purity can be compromised by human errors. Cross-contamination from other cell lines and complete misidentification are both possible. Routine cell line authentication is a necessary preventive measure and has become a requirement for many funding applications and publications. Short tandem repeat (STR) profiling is the most common method for cell line authentication and is usually carried out …

Clinical And Biological Significance Of Circulating Mirnas In Chronic Pancreatitis Patients Undergoing Total Pancreatectomy With Islet Autotransplantation, Srividya Vasu, Giovanna Saracino, Carly M Darden, Kenjiro Kumano, Yang Liu, Michael C Lawrence, Bashoo Naziruddin

Faculty, Staff and Student Publications

Background: Specific microRNAs (miRNAs) were elevated in chronic pancreatitis (CP) patients during islet infusion after total pancreatectomy (TPIAT). We aimed to identify circulating miRNA signatures of pancreatic damage, predict miRNA-mRNA networks to identify potential links to CP pathogenesis and identify islet isolation and transplantation functional outcomes.

Methods: Small RNA sequencing was performed to identify distinct circulating miRNA signatures in CP. Plasma miRNAs were measured using miRCURY LNA SYBR green quantitative real-time polymerase chain reaction assays. Correlation analyses were performed using R software. The miRNA target and disease interactions were determined using miRNet and the miRNA enrichment and annotation tool.

Results: …

Regression Analysis Of General Mixed Recurrent Event Data, Ryan Sun, Dayu Sun, Liang Zhu, Jianguo Sun

Faculty, Staff and Student Publications

In modern biomedical datasets, it is common for recurrent outcomes data to be collected in an incomplete manner. More specifically, information on recurrent events is routinely recorded as a mixture of recurrent event data, panel count data, and panel binary data; we refer to this structure as general mixed recurrent event data. Although the aforementioned data types are individually well-studied, there does not appear to exist an established approach for regression analysis of the three component combination. Often, ad-hoc measures such as imputation or discarding of data are used to homogenize records prior to the analysis, but such measures lead …

Antibody Response To Sars-Cov-2 Vaccines In Patients With Relapsing Multiple Sclerosis Treated With Evobrutinib: A Bruton's Tyrosine Kinase Inhibitor, Amit Bar-Or, Anne H Cross, Anthony L Cunningham, Yann Hyvert, Andrea Seitzinger, Hans Gühring, Elise E Drouin, Nektaria Alexandri, Davorka Tomic, Xavier Montalban

2020-Current year OA Pubs

BACKGROUND: Evobrutinib is an oral, central nervous system (CNS)-penetrant and highly selective covalent Bruton's tyrosine kinase inhibitor under clinical development for patients with relapsing multiple sclerosis (RMS).

OBJECTIVE: To investigate the effect of evobrutinib on immune responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinated patients with RMS from a Phase II trial (NCT02975349).

METHODS: A

RESULTS: In the vaccinated subgroup, mean/minimum evobrutinib exposure pre-vaccination was 105.2/88.7 weeks. In total, 43 of 45 patients developed/increased S1/S2 IgG antibody levels post-vaccination; one patient's antibody response remained negative post-vaccination and the other had antibody levels above the upper limit of detection, …

Evaluation Of The Natural History Of Disease By Combining Incident And Prevalent Cohorts: Application To The Nun Study, Daewoo Pak, Jing Ning, Richard J Kryscio, Yu Shen

Faculty, Staff and Student Publications

The Nun study is a well-known longitudinal epidemiology study of aging and dementia that recruited elderly nuns who were not yet diagnosed with dementia (i.e., incident cohort) and who had dementia prior to entry (i.e., prevalent cohort). In such a natural history of disease study, multistate modeling of the combined data from both incident and prevalent cohorts is desirable to improve the efficiency of inference. While important, the multistate modeling approaches for the combined data have been scarcely used in practice because prevalent samples do not provide the exact date of disease onset and do not represent the target population …

A Translational Blueprint For Developing Intraoperative Imaging Agents Via Radiopharmaceutical-Guided Drug Design, Teresa E Sullivan, Servando Hernandez Vargas, Sukhen C Ghosh, Solmaz Aghaamiri, Naruhiko Ikoma, Ali Azhdarinia

Faculty, Staff and Student Publications

Cancer imaging is a rapidly evolving field due to the discovery of novel molecular targets and the availability of corresponding techniques to detect them with high precision, accuracy, and sensitivity. Nuclear medicine is the most widely used molecular imaging modality and has a growing toolkit of clinically used radiopharmaceuticals that enable whole-body tumor visualization, staging, and treatment monitoring for a variety of tumors in a non-invasive manner. The need for similar imaging capabilities in the operating room has led to the emergence of fluorescence-guided surgery (FGS) as a powerful technique that gives surgeons unprecedented ability to distinguish tumors from healthy …

Emphasizing Others’ Persistence Can Promote Unwarranted Social Inferences In Children And Adults, Jamie Amemiya, Gail D Heyman, Caren M Walker

Faculty, Staff and Student Publications

People often hear stories about individuals who persist to overcome their constraints. While these stories can be motivating, emphasizing others’ persistence may promote unwarranted judgments about constrained individuals who do not persist. Using a developmental social inference task (Study 1a: n = 124 U.S. children, 5 to 12 years of age; Study 1b [n = 135] and Study 2 [n = 120]: U.S. adults), the present research tested whether persistence stories lead people to infer that a constrained individual who does not persist, and instead accepts the lower-quality option that is available to them, prefers it over a …

Co-Targeting Bcl-Xl And Bcl-2 By Protac 753b Eliminates Leukemia Cells And Enhances Efficacy Of Chemotherapy By Targeting Senescent Cells, Yannan Jia, Lina Han, Cassandra L Ramage, Zhe Wang, Connie C Weng, Lei Yang, Simona Colla, Helen Ma, Weiguo Zhang, Michael Andreeff, Naval Daver, Nitin Jain, Naveen Pemmaraju, Kapil Bhalla, Satu Mustjoki, Peiyi Zhang, Guangrong Zheng, Daohong Zhou, Qi Zhang, Marina Konopleva

Faculty, Staff and Student Publications

BCL-XL and BCL-2 are key anti-apoptotic proteins and validated cancer targets. 753B is a novel BCL-XL/BCL-2 proteolysis targeting chimera (PROTAC) that targets both BCL-XL and BCL-2 to the von Hippel-Lindau (VHL) E3 ligase, leading to BCLX L/BCL-2 ubiquitination and degradation selectively in cells expressing VHL. Because platelets lack VHL expression, 753B spares on-target platelet toxicity caused by the first-generation dual BCL-XL/BCL-2 inhibitor navitoclax (ABT-263). Here, we report pre-clinical single-agent activity of 753B against different leukemia subsets. 753B effectively reduced cell viability and induced dose-dependent degradation of BCL-XL and BCL-2 in a subset of hematopoietic cell lines, acute myeloid leukemia (AML) …

A Novel Pathogenic Mutation Of Mecp2 Impairs Chromatin Association Independent Of Protein Levels, Jian Zhou, Claudia Cattoglio, Yingyao Shao, Harini P Tirumala, Carlo Vetralla, Sameer S Bajikar, Yan Li, Hu Chen, Qi Wang, Zhenyu Wu, Bing Tang, Mahla Zahabiyon, Aleksandar Bajic, Xiangling Meng, Jack J Ferrie, Anel Lagrone, Ping Zhang, Jean J Kim, Jianrong Tang, Zhandong Liu, Xavier Darzacq, Nathaniel Heintz, Robert Tjian, Huda Y Zoghbi

Faculty, Staff and Students Publications

Loss-of-function mutations in MECP2 cause Rett syndrome (RTT), a severe neurological disorder that mainly affects girls. Mutations in MECP2 do occur in males occasionally and typically cause severe encephalopathy and premature lethality. Recently, we identified a missense mutation (c.353G>A, p.Gly118Glu [G118E]), which has never been seen before in MECP2, in a young boy who suffered from progressive motor dysfunction and developmental delay. To determine whether this variant caused the clinical symptoms and study its functional consequences, we established two disease models, including human neurons from patient-derived iPSCs and a knock-in mouse line. G118E mutation partially reduces MeCP2 abundance …

Age-Related Differences In The Contribution Of Systolic Blood Pressure And Biomarkers To Cardiovascular Disease Risk Prediction: The Atherosclerosis Risk In Communities (Aric) Study, Mahmoud Al Rifai, George E Taffet, Kunihiro Matsushita, Salim S Virani, James De Lemos, Amit Khera, Jarrett Berry, Chiadi Ndumele, David Aguilar, Caroline Sun, Ron C Hoogeveen, Elizabeth Selvin, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

We sought to determine how biomarkers known to be associated with hypertension-induced end-organ injury complement the use of systolic blood pressure (SBP) for cardiovascular disease (CVD) risk prediction at different ages. Using data from visits 2 (1990 to 1992) and 5 (2011 to 2013) of the Atherosclerosis Risk in Communities (ARIC) study, 3 models were used to predict CVD (composite of coronary heart disease, stroke, and heart failure). Model A included traditional risk factors (TRFs) except SBP, model B-TRF plus SBP, and model C-TRF plus biomarkers (high-sensitivity troponin T [hsTnT] and N-terminal pro-B-type natriuretic peptide [NT-proBNP]). Harrel's C-statistics were used …

Scalable Nanopore Sequencing Of Human Genomes Provides A Comprehensive View Of Haplotype-Resolved Variation And Methylation, Mikhail Kolmogorov, Kimberley J Billingsley, Mira Mastoras, Melissa Meredith, Jean Monlong, Ryan Lorig-Roach, Mobin Asri, Pilar Alvarez Jerez, Laksh Malik, Ramita Dewan, Xylena Reed, Rylee M Genner, Kensuke Daida, Sairam Behera, Kishwar Shafin, Trevor Pesout, Jeshuwin Prabakaran, Paolo Carnevali, Jianzhi Yang, Arang Rhie, Sonja W Scholz, Bryan J Traynor, Karen H Miga, Miten Jain, Winston Timp, Adam M Phillippy, Mark Chaisson, Fritz J Sedlazeck, Cornelis Blauwendraat, Benedict Paten

Faculty, Staff and Students Publications

Long-read sequencing technologies substantially overcome the limitations of short-reads but have not been considered as a feasible replacement for population-scale projects, being a combination of too expensive, not scalable enough or too error-prone. Here we develop an efficient and scalable wet lab and computational protocol, Napu, for Oxford Nanopore Technologies long-read sequencing that seeks to address those limitations. We applied our protocol to cell lines and brain tissue samples as part of a pilot project for the National Institutes of Health Center for Alzheimer's and Related Dementias. Using a single PromethION flow cell, we can detect single nucleotide polymorphisms with …

Human Intestinal Organoids As Models To Study Enteric Bacteria And Viruses, Grace Adeniyi-Ipadeola, Hephzibah Nwanosike, Sasirekha Ramani

Faculty, Staff and Students Publications

Laboratory studies of host-microbe interactions have historically been carried out using transformed cell lines and animal models. Although much has been learned from these models, recent advances in the development of multicellular, physiologically active, human intestinal organoid (HIO) cultures are allowing unprecedented discoveries of host-microbe interactions. Here, we review recent literature using HIOs as models to investigate the pathogenesis of clinically important enteric bacteria and viruses and study commensal intestinal microbes. We also discuss limitations of current HIO culture systems and how technical advances and innovative engineering approaches are providing new directions to improve the model. The studies discussed here …

Spanish-Language Communication Of Covid-19 Information Across Us Local Health Department Websites, Isabelle S Kusters, Amanda M Gutierrez, Julianna M Dean, Mark Sommer, Anna Klyueva

Center for Medical Ethics and Health Policy Staff Publications

The COVID-19 pandemic has brought new urgency to a longstanding problem: the US health system is not well-equipped to accommodate the country's large limited English proficient (LEP) population in times of national emergency. We examined the landscape of Spanish-language COVID-19 website information compared to information in English provided by health departments of the top 10 cities by population in the USA. For each city, coders evaluated three score measures (amount of information, presentation quality, and ease of navigation) for six content types (general information, symptoms, testing, prevention, vaccines, and live statistics) across six delivery modes (print resources, website text, videos, …

New Jak3-Insl3 Fusion Transcript-An Oncogenic Event In Cutaneous T-Cell Lymphoma, Loka Reddy Velatooru, Cheng Hui Hu, Pedram Bijani, Xiaohong Wang, Pierr Bojaxhi, Hao Chen, Madeleine Duvic, Xiao Ni

Faculty, Staff and Student Publications

Constitutively activated tyrosine kinase JAK3 is implicated in the pathogenesis of cutaneous T-cell lymphomas (CTCL). The mechanisms of constitutive JAK3 activation are unknown although a JAK3 mutation was reported in a small portion of CTCL patients. In this study, we assessed the oncogenic roles of a newly identified JAK3-INSL3 fusion transcript in CTCL. Total RNA from malignant T-cells in 33 patients with Sézary syndrome (SS), a leukemic form of CTCL, was examined for the new JAK3-INSL3 fusion transcript by RT-PCR followed by Sanger sequencing. The expression levels were assessed by qPCR and correlated with patient survivals. Knockdown and/or knockout assays …

Differential Effects Of Pancreatic Cancer-Derived Extracellular Vesicles Driving A Suppressive Environment, Anurag Purushothaman, Jacqueline Oliva-Ramírez, Warapen Treekitkarnmongkol, Deivendran Sankaran, Mark W Hurd, Nagireddy Putluri, Anirban Maitra, Cara Haymaker, Subrata Sen

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) cells display extensive crosstalk with their surrounding environment to regulate tumor growth, immune evasion, and metastasis. Recent advances have attributed many of these interactions to intercellular communication mediated by small extracellular vesicles (sEVs), involving cancer-associated fibroblasts (CAF). To explore the impact of sEVs on monocyte lineage transition as well as the expression of checkpoint receptors and activation markers, peripheral blood monocytes from healthy subjects were exposed to PDAC-derived sEVs. Additionally, to analyze the role of sEV-associated HA in immune regulation and tissue-resident fibroblasts, monocytes and pancreatic stellate cells were cultured in the presence of PDAC sEVs …

A Peptide-Binding Domain Shared With An Antarctic Bacterium Facilitates, Cameron J Lloyd, Shuaiqi Guo, Brett Kinrade, Hossein Zahiri, Robert Eves, Syed Khalid Ali, Fitnat Yildiz, Ilja K Voets, Peter L Davies, Karl E Klose

Faculty, Staff and Student Publications

No abstract provided.

Axl-Initiated Paracrine Activation Of Pstat3 Enhances Mesenchymal And Vasculogenic Supportive Features Of Tumor-Associated Macrophages, Chia-Nung Hung, Meizhen Chen, Daniel T Dearmond, Cheryl H-L Chiu, Catherine A Limboy, Xi Tan, Meena Kusi, Chih-Wei Chou, Li-Ling Lin, Zhao Zhang, Chiou-Miin Wang, Chun-Liang Chen, Kohzoh Mitsuya, Pawel A Osmulski, Maria E Gaczynska, Nameer B Kirma, Ratna K Vadlamudi, Don L Gibbons, Steve Warner, Andrew J Brenner, Daruka Mahadevan, Joel E Michalek, Tim H-M Huang, Josephine A Taverna

Faculty, Staff and Student Publications

Tumor-associated macrophages (TAMs) are integral to the development of complex tumor microenvironments (TMEs) and can execute disparate cellular programs in response to extracellular cues. However, upstream signaling processes underpinning this phenotypic plasticity remain to be elucidated. Here, we report that concordant AXL-STAT3 signaling in TAMs is triggered by lung cancer cells or cancer-associated fibroblasts in the cytokine milieu. This paracrine action drives TAM differentiation toward a tumor-promoting "M2-like" phenotype with upregulation of CD163 and putative mesenchymal markers, contributing to TAM heterogeneity and diverse cellular functions. One of the upregulated markers, CD44, mediated by AXL-IL-11-pSTAT3 signaling cascade, enhances macrophage ability to …

Setd2 Safeguards The Genome Against Isochromosome Formation, Frank M Mason, Emily S Kounlavong, Anteneh T Tebeje, Rashmi Dahiya, Tiffany Guess, Abid Khan, Logan Vlach, Stephen R Norris, Courtney A Lovejoy, Ruhee Dere, Brian D Strahl, Ryoma Ohi, Peter Ly, Cheryl Lyn Walker, W Kimryn Rathmell

Faculty, Staff and Students Publications

Isochromosomes are mirror-imaged chromosomes with simultaneous duplication and deletion of genetic material which may contain two centromeres to create isodicentric chromosomes. Although isochromosomes commonly occur in cancer and developmental disorders and promote genome instability, mechanisms that prevent isochromosomes are not well understood. We show here that the tumor suppressor and methyltransferase SETD2 is essential to prevent these errors. Using cellular and cytogenetic approaches, we demonstrate that loss of SETD2 or its epigenetic mark, histone H3 lysine 36 trimethylation (H3K36me3), results in the formation of isochromosomes as well as isodicentric and acentric chromosomes. These defects arise during DNA replication and are …

Inhibition Of Trap1 Accelerates The Dna Damage Response, Activation Of The Heat Shock Response And Metabolic Reprogramming In Colon Cancer Cells, Nobel Bhasin, Prerna Dabral, Lakmini Senavirathna, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

BACKGROUND: Colorectal cancer (CRC) is one of the major causes of cancer-related mortality worldwide. The tumor microenvironment plays a significant role in CRC development, progression and metastasis. Oxidative stress in the colon is a major etiological factor impacting tumor progression. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial member of the heat shock protein 90 (HSP90) family that is involved in modulating apoptosis in colon cancer cells under oxidative stress. We undertook this study to provide mechanistic insight into the role of TRAP1 under oxidative stress in colon cells.

METHODS: We first assessed the The Cancer Genome Atlas …

The Fda-Approved Compound, Pramipexole And The Clinical-Stage Investigational Drug, Dexpramipexole, Reverse Chronic Allodynia From Sciatic Nerve Damage In Mice, And Alter Il-1Β And Il-10 Expression From Immune Cell Culture, J E Sanchez, S Noor, M S Sun, J Zimmerly, A Pasmay, J J Sanchez, A G Vanderwall, M K Haynes, L A Sklar, P R Escalona, E D Milligan

Pathology Research and Scholarship

During the onset of neuropathic pain from a variety of etiologies, nociceptors become hypersensitized, releasing neurotransmitters and other factors from centrally-projecting nerve terminals within the dorsal spinal cord. Consequently, glial cells (astrocytes and microglia) in the spinal cord are activated and mediate the release of proinflammatory cytokines that act to enhance pain transmission and sensitize mechanical non-nociceptive fibers which ultimately results in light touch hypersensitivity, clinically observed as allodynia. Pramipexole, a D2/D3 preferring agonist, is FDA-approved for the treatment of Parkinson's disease and demonstrates efficacy in animal models of inflammatory pain. The clinical-stage investigational drug, R(+) enantiomer of pramipexole, dexpramipexole, …

Transcriptomic Analysis Of Stem Cells From Chorionic Villi Uncovers The Impact Of Chromosomes 2, 6 And 22 In The Clinical Manifestations Of Down Syndrome, Salvatore Vaiasicca, Gianmarco Melone, David W James, Marcos Quintela, Alessandra Preziuso, Richard H Finnell, Robert Steven Conlan, Lewis W Francis, Bruna Corradetti

Faculty, Staff and Students Publications

BACKGROUND: Down syndrome (DS) clinical multisystem condition is generally considered the result of a genetic imbalance generated by the extra copy of chromosome 21. Recent discoveries, however, demonstrate that the molecular mechanisms activated in DS compared to euploid individuals are more complex than previously thought. Here, we utilize mesenchymal stem cells from chorionic villi (CV) to uncover the role of comprehensive functional genomics-based understanding of DS complexity.

METHODS: Next-generation sequencing coupled with bioinformatic analysis was performed on CV obtained from women carrying fetuses with DS (DS-CV) to reveal specific genome-wide transcriptional changes compared to their euploid counterparts. Functional assays were …

Bap1 Promotes Osteoclast Function By Metabolic Reprogramming, Nidhi Rohatgi, Wei Zou, Yongjia Li, Kevin Cho, Patrick L Collins, Eric Tycksen, Gaurav Pandey, Carl J Deselm, Gary J Patti, Anwesha Dey, Steven L Teitelbaum

2020-Current year OA Pubs

Treatment of osteoporosis commonly diminishes osteoclast number which suppresses bone formation thus compromising fracture prevention. Bone formation is not suppressed, however, when bone degradation is reduced by retarding osteoclast functional resorptive capacity, rather than differentiation. We find deletion of deubiquitinase, BRCA1-associated protein 1 (Bap1), in myeloid cells (Bap1

Prospective Associations Of Neighborhood Healthy Food Access And Walkability With Weight Status In A Regional Pediatric Health System., Qianxia Jiang, Bethany Forseth, Lauren Fitzpatrick, Helena Laroche, Sarah Hampl, Ann M. Davis, Chelsea Steel, Jordan A. Carlson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Most neighborhood food and activity related environment research in children has been cross-sectional. A better understanding of prospective associations between these neighborhood environment factors and children's weight status can provide stronger evidence for informing interventions and policy. This study examined associations of baseline and changes in neighborhood healthy food access and walkability with changes in children's weight status over 5 years.

METHODS: Height, weight, and home address were obtained for 4,493 children (> 75% were Black or Latinx) from primary care visits within a large pediatric health system. Eligible participants were those who had measures collected during two time …

Critical Functions Of Extracellular Matrix In Brain Metastasis Seeding, Arseniy E Yuzhalin, Dihua Yu

Faculty, Staff and Student Publications

Human brain is characterized by extremely sparse extracellular matrix (ECM). Despite its low abundance, the significance of brain ECM in both physiological and pathological conditions should not be underestimated. Brain metastasis is a serious complication of cancer, and recent findings highlighted the contribution of ECM in brain metastasis development. In this review, we provide a comprehensive outlook on how ECM proteins promote brain metastasis seeding. In particular, we discuss (1) disruption of the blood-brain barrier in brain metastasis; (2) role of ECM in modulating brain metastasis dormancy; (3) regulation of brain metastasis seeding by ECM-activated integrin signaling; (4) functions of …

Virtual Blebbistatin: A Robust And Rapid Software Approach To Motion Artifact Removal In Optical Mapping Of Cardiomyocytes, Louis G Woodhams, Jingxuan Guo, David Schuftan, John J Boyle, Kenneth M Pryse, Elliot L Elson, Nathaniel Huebsch, Guy M Genin

2020-Current year OA Pubs

Fluorescent reporters of cardiac electrophysiology provide valuable information on heart cell and tissue function. However, motion artifacts caused by cardiac muscle contraction interfere with accurate measurement of fluorescence signals. Although drugs such as blebbistatin can be applied to stop cardiac tissue from contracting by uncoupling calcium-contraction, their usage prevents the study of excitation-contraction coupling and, as we show, impacts cellular structure. We therefore developed a robust method to remove motion computationally from images of contracting cardiac muscle and to map fluorescent reporters of cardiac electrophysiological activity onto images of undeformed tissue. When validated on cardiomyocytes derived from human induced pluripotent …

Abcc1 And Glutathione Metabolism Limit The Efficacy Of Bcl-2 Inhibitors In Acute Myeloid Leukemia, Jessica Ebner, Johannes Schmoellerl, Martin Piontek, Gabriele Manhart, Selina Troester, Bing Z Carter, Heidi Neubauer, Richard Moriggl, Gergely Szakács, Johannes Zuber, Thomas Köcher, Michael Andreeff, Wolfgang R Sperr, Peter Valent, Florian Grebien

Faculty, Staff and Student Publications

The BCL-2 inhibitor Venetoclax is a promising agent for the treatment of acute myeloid leukemia (AML). However, many patients are refractory to Venetoclax, and resistance develops quickly. ATP-binding cassette (ABC) transporters mediate chemotherapy resistance but their role in modulating the activity of targeted small-molecule inhibitors is unclear. Using CRISPR/Cas9 screening, we find that loss of ABCC1 strongly increases the sensitivity of AML cells to Venetoclax. Genetic and pharmacologic ABCC1 inactivation potentiates the anti-leukemic effects of BCL-2 inhibitors and efficiently re-sensitizes Venetoclax-resistant leukemia cells. Conversely, ABCC1 overexpression induces resistance to BCL-2 inhibitors by reducing intracellular drug levels, and high ABCC1 levels …

A Bibliometric Analysis Of The Rise Of Chatgpt In Medical Research, Nikki M. Barrington, Nithin Gupta, Basel Musmar, David Doyle, Nicholas Panico, Nikhil Godbole, Taylor K. Reardon, Randy S. D'Amico

Neurology Articles

The rapid emergence of publicly accessible artificial intelligence platforms such as large language models (LLMs) has led to an equally rapid increase in articles exploring their potential benefits and risks. We performed a bibliometric analysis of ChatGPT literature in medicine and science to better understand publication trends and knowledge gaps. Following title, abstract, and keyword searches of PubMed, Embase, Scopus, and Web of Science databases for ChatGPT articles published in the medical field, articles were screened for inclusion and exclusion criteria. Data were extracted from included articles, with citation counts obtained from PubMed and journal metrics obtained from Clarivate Journal …

Notes From The Field: Online Weight Loss Supplements Labeled As Tejocote (Crataegus Mexicana) Root, Substituted With Yellow Oleander (Cascabela Thevetia) - United States, 2022, Noah Berland, James Kababick, Cynthia Santos, Diane P Calello

Faculty, Staff and Student Publications

No abstract provided.

The Effectiveness Of Disinfection Protocols In Osteopathic Family Medicine Offices, Riley Phyu, Harrison A Patrizio, Thomas Boyle, Todd Schachter

Rowan-Virtua School of Osteopathic Medicine Departmental Research

CONTEXT: Healthcare-associated infections (HAIs) pose a substantial public health threat. Despite significant strides to curb HAIs in hospital environments, outpatient settings have not received the same degree of attention. Given their emphasis on holistic, patient-centered care, osteopathic family medicine offices are pivotal in both disease prevention and comprehensive patient treatment. The importance of simple yet effective disinfection protocols, such as thorough cleaning between patient appointments, cannot be overstated in these settings because they are integral to minimizing disease transmission.

OBJECTIVES: This study aims to assess the effectiveness of the current disinfection protocols in osteopathic family medicine offices.

METHODS: A cross-sectional …

Pathogen-Driven Crispr Screens Identify Trex1as A Regulator Of Dna Self-Sensing During Influenza Virus Infection, Cason R King, Yiping Liu, Katherine A Amato, Grace A Schaack, Clayton Mickelson, Autumn E Sanders, Tony Hu, Srishti Gupta, Ryan A Langlois, Judith A Smith, Andrew Mehle

Faculty, Staff and Student Publications

Host:pathogen interactions dictate the outcome of infection, yet the limitations of current approaches leave large regions of this interface unexplored. Here, we develop a novel fitness-based screen that queries factors important during the middle to late stages of infection. This is achieved by engineering influenza virus to direct the screen by programming dCas9 to modulate host gene expression. Our genome-wide screen for pro-viral factors identifies the cytoplasmic DNA exonuclease TREX1. TREX1 degrades cytoplasmic DNA to prevent inappropriate innate immune activation by self-DNA. We reveal that this same process aids influenza virus replication. Infection triggers release of mitochondrial DNA into the …