Digital Commons Network^™

Clarification Of Adverse Drug Reactions By A Pharmacovigilance Team Results In Increased Antibiotic Re-Prescribing At A Freestanding United States Children's Hospital., Keith Feldman, Sarah Suppes, Jennifer Goldman

Manuscripts, Articles, Book Chapters and Other Papers

Documentation of adverse drug reactions (ADRs) is a key factor in guiding future prescribing. However, incomplete documentation is common and often fails to distinguish implicated drugs as true allergies. This in turn leads to unnecessary avoidance of implicated drug classes and may result in sub-optimal prescribing. Pharmacovigilance (PV) programs utilize a systematic approach to clarify ADR documentation and are known to improve patient safety. Yet it remains unclear if PV alters prescribing. Or, if the existence of the ADR documentation itself continues to prompt avoidance of implicated drugs. To address this, our work presents a retrospective cohort study assessing if …

Sepsis Epidemiology In Australian And New Zealand Children (Sentinel): Protocol For A Multicountry Prospective Observational Study, Elliot Long, Meredith L. Borland, Shane George, Shefali Jani, Eunicia Tan, Jocelyn Neutze, Natalie Phillips, Amit Kochar, Simon Craig, Anna Lithgow, Arjun Rao, Stuart Dalziel, Ed Oakley, Stephen Hearps, Sonia Singh, Ben Gelbart, Sarah Mcnab, Fran Balamuth, Scott Weiss, Nathan Kuppermann, Amanda Williams, Franz E. Babl

Department of Pediatrics Faculty Papers

INTRODUCTION: Sepsis affects 25.2 million children per year globally and causes 3.4 million deaths, with an annual cost of hospitalisation in the USA of US$7.3 billion. Despite being common, severe and expensive, therapies and outcomes from sepsis have not substantially changed in decades. Variable case definitions, lack of a reference standard for diagnosis and broad spectrum of disease hamper efforts to evaluate therapies that may improve sepsis outcomes. This landscape analysis of community-acquired childhood sepsis in Australia and New Zealand will characterise the burden of disease, including incidence, severity, outcomes and cost. Sepsis diagnostic criteria and risk stratification tools will …

Fecal Pharmacokinetics And Gut Microbiome Effects Of Oral Omadacycline Versus Vancomycin In Healthy Volunteers, Jinhee Jo, Chenlin Hu, Khurshida Begum, Weiqun Wang, Thanh M Le, Samantha Agyapong, Blake M Hanson, Hossaena Ayele, Chris Lancaster, M Jahangir Alam, Anne J Gonzales-Luna, Kevin W Garey

Faculty, Staff and Student Publications

BACKGROUND: Clostridioides difficile infection (CDI) is a common healthcare-associated infection with limited treatment options. Omadacycline, an aminomethylcycline tetracycline, has potent in vitro activity against C difficile and a low propensity to cause CDI in clinical trials. We aimed to assess fecal pharmacokinetics and gut microbiome effects of oral omadacycline compared to oral vancomycin in healthy adults.

METHODS: This was a phase 1, nonblinded, randomized clinical trial conducted in healthy volunteers aged 18-40 years. Subjects received a 10-day course of omadacycline or vancomycin. Stool samples were collected at baseline, daily during therapy, and at follow-up visits. Omadacycline and vancomycin stool concentrations …

Targeting Innate Immunity In Glioma Therapy, Andrew G Gillard, Dong Ho Shin, Lethan A Hampton, Andres Lopez-Rivas, Akhila Parthasarathy, Juan Fueyo, Candelaria Gomez-Manzano

Faculty, Staff and Student Publications

Currently, there is a lack of effective therapies for the majority of glioblastomas (GBMs), the most common and malignant primary brain tumor. While immunotherapies have shown promise in treating various types of cancers, they have had limited success in improving the overall survival of GBM patients. Therefore, advancing GBM treatment requires a deeper understanding of the molecular and cellular mechanisms that cause resistance to immunotherapy. Further insights into the innate immune response are crucial for developing more potent treatments for brain tumors. Our review provides a brief overview of innate immunity. In addition, we provide a discussion of current therapies …

Chagas Disease Diagnostic Practices At Four Major Hospital Systems In California And Texas, Emily A Kelly, Jose I Echeverri Alegre, Katherine Promer, Jesica Hayon, Roumen Iordanov, Khuzaima Rangwalla, Jerry J Zhang, Zian Fang, Cindy Huang, Cassiana E Bittencourt, Sharon Reed, Rosa M Andrade, Caryn Bern, Eva H Clark, Jeffrey D Whitman

Faculty, Staff and Students Publications

BACKGROUND: Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early diagnosis and antiparasitic therapy.

METHODS: We reviewed electronic health records of patients who underwent testing for CD at four hospital systems in California and Texas between 2016 and 2020. Descriptive analyses were performed as a needs assessment for improving CD diagnosis.

RESULTS: In total, 470 patients were tested for CD. Cardiac indications made up more than half (60%) of all …

Covid-19 Convalescent Plasma Therapy Decreases Inflammatory Cytokines: A Randomized Controlled Trial, Feben Habtehyimer, Xianming Zhu, Andrew D Redd, Kelly A Gebo, Alison G Abraham, Eshan U Patel, Oliver Laeyendecker, Thomas J Gniadek, Reinaldo E Fernandez, Owen R Baker, Malathi Ram, Edward R Cachay, Judith S Currier, Yuriko Fukuta, Jonathan M Gerber, Sonya L Heath, Barry Meisenberg, Moises A Huaman, Adam C Levine, Aarthi Shenoy, Shweta Anjan, Janis E Blair, Daniel Cruser, Donald N Forthal, Laura L Hammitt, Seble Kassaye, Giselle S Mosnaim, Bela Patel, James H Paxton, Jay S Raval, Catherine G Sutcliffe, Matthew Abinante, Kevin S Oei, Valerie Cluzet, Marie Elena Cordisco, Benjamin Greenblatt, William Rausch, David Shade, Amy L Gawad, Sabra L Klein, Andrew Pekosz, Shmuel Shoham, Arturo Casadevall, Evan M Bloch, Daniel Hanley, Aaron A R Tobian, David J Sullivan

Faculty, Staff and Student Publications

This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.

Assessing Covid-Related Concerns And Their Impact On Antenatal And Delivery Care Among Pregnant Women Living With Hiv In Kenya: A Brief Report., Catherine Wexler, May Maloba, Sharon Mokua, Shadrack Babu, Nicodemus Maosa, Vincent Staggs, Kathy Goggin, Harshdeep Acharya, Emily A. Hurley, Sarah Finocchario-Kessler

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Some studies indicate that pregnant Kenyan women were concerned about Coronavirus disease 2019 (COVID-19) exposure during maternity care. We assessed concern regarding COVID-19 exposure and any impact on antenatal care (ANC) enrollment and/or hospital delivery among pregnant women living with human immunodeficiency virus (HIV) in Kenya.

METHODS: Data were collected from 1,478 pregnant women living with HIV enrolled in prevention of mother to child transmission of HIV (PMTCT) care at 12 Kenyan hospitals from October 2020 to July 2022. Surveys were conducted when women first presented for PMTCT services at the study hospital and asked demographic questions as well …

Identifying Opportunities For Prevention Of Adverse Outcomes Following Female Genital Fistula Repair: Protocol For A Mixed-Methods Study In Uganda, Alison El Ayadi, Susan Obore, Fred Kirya, Suellen Miller, Abner Korn, Hadija Nalubwama, John Neuhaus, Monica Getahun, Patrick Eyul, Robert Twine, Erin Andrew, Justus Barageine

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Female genital fistula is a traumatic debilitating injury, frequently caused by prolonged obstructed labor, affecting between 500,000-2 million women in lower-resource settings. Vesicovaginal fistula causes urinary incontinence, and other morbidity may occur during fistula development. Women with fistula are stigmatized, limit social and economic engagement, and experience psychiatric morbidity. Improved surgical access has reduced fistula consequences yet post-repair risks impacting quality of life and well-being include fistula repair breakdown or recurrence and ongoing or changing urine leakage or incontinence. Limited evidence on risk factors contributing to adverse outcomes hinders interventions to mitigate adverse events. This study aims to quantify …

Heterozygous Mutations In The C-Terminal Domain Of Copa Underlie A Complex Autoinflammatory Syndrome, Selket Delafontaine, Tarin M. Bigley, Megan A. Cooper, Et Al.

2020-Current year OA Pubs

Mutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C, and p.R1142X) in 6 children from 3 unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD COPA mutations disrupt the integrity and the function of coat protein complex I (COPI). In COPAR1142X and COPAR1058C fibroblasts, we demonstrated that COPI dysfunction causes both an anterograde ER-to-Golgi and a retrograde Golgi-to-ER trafficking defect. The disturbed intracellular …

An Evolutionary Perspective On Complex Neuropsychiatric Disease, Jon M Mcclellan, Anthony W Zoghbi, Joseph D Buxbaum, Carolina Cappi, James J Crowley, Jonathan Flint, Dorothy E Grice, Suleyman Gulsuner, Conrad Iyegbe, Sanjeev Jain, Po-Hsiu Kuo, Maria Claudia Lattig, Maria Rita Passos-Bueno, Meera Purushottam, Dan J Stein, Anna B Sunshine, Ezra S Susser, Christopher A Walsh, Olivia Wootton, Mary-Claire King

Faculty, Staff and Students Publications

The forces of evolution-mutation, selection, migration, and genetic drift-shape the genetic architecture of human traits, including the genetic architecture of complex neuropsychiatric illnesses. Studying these illnesses in populations that are diverse in genetic ancestry, historical demography, and cultural history can reveal how evolutionary forces have guided adaptation over time and place. A fundamental truth of shared human biology is that an allele responsible for a disease in anyone, anywhere, reveals a gene critical to the normal biology underlying that condition in everyone, everywhere. Understanding the genetic causes of neuropsychiatric disease in the widest possible range of human populations thus yields …

Implementation And Outcomes Of A Pilot Collaborative Surgical Hydrocele Training In Côte D'Ivoire, Kevin Montes, Georgina Angoa, Catherine M Bjerum, Adama Guira, Olivier K Kouadio, Allassane F Ouattara, Gary J Weil, Peter U Fischer, Aboulaye Meite, Benjamin G Koudou, Philip J Budge

2020-Current year OA Pubs

Lymphatic filariasis (LF) is a neglected tropical disease that can cause hydrocele and its associated stigma, loss of economic productivity, and depression. Hydrocele surgery is an essential part of LF morbidity management but can be difficult for national programs to implement. To improve access to hydrocele surgeries in Côte d'Ivoire, we provided a WHO-certified surgical training for six surgical teams from five health districts in Côte d'Ivoire. We then evaluated the surgical outcomes and assessed the impact of hydrocele surgery on quality of life of hydrocelectomy patients. Preoperative and operative records were reviewed to describe baseline hydrocele characteristics and operative …

Surveillance And Selective Treatment Of Brugia Malayi Filariasis Eleven Years After Stopping Mass Drug Administration In Belitung District, Indonesia, Taniawati Supali, Yenny Djuardi, Santoso, Lita Renata Sianipar, Nungki Hapsari Suryaningtyas, Rahmat Alfian, Yossi Destani, Elisa Iskandar, Hendri Astuty, Noviani Sugianto, Peter U Fischer

2020-Current year OA Pubs

A key component to achieving the global goal of elimination of lymphatic filariasis (LF) is the availability of appropriate tools for disease mapping, monitoring, and surveillance. However, the development of these tools for a neglected disease such as LF can be a challenge. The lack of a commercial market and low familiarity with these diseases leave little incentive for diagnostic manufacturers to invest in this space. The Filarial Test Strip (FTS) development story provides a case study on how a multi-stakeholder, public-private partnership model facilitated the development, evaluation, and introduction of a new monitoring and surveillance tool for LF. This …

Microbial Co-Occurrences On Catheters From Long-Term Catheterized Patients, Taylor M Nye, Zongsen Zou, Chloe L P Obernuefemann, Jerome S Pinkner, Erin Lowry, Kent Kleinschmidt, Karla Bergeron, Aleksandra Klim, Karen W Dodson, Ana L Flores-Mireles, Jennifer N Walker, Daniel Garrett Wong, Alana Desai, Michael G Caparon, Scott J Hultgren

Faculty, Staff and Student Publications

Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in catheter and urine samples from 55 human long-term catheterized patients collected over one year. Although most of these patients were prescribed antibiotics over several collection periods, their catheter samples remain colonized by one or more bacterial species. Examination of a total of 366 catheter and urine samples identify 13 positive and 13 negative genus co-occurrences over 12 collection periods, representing associations that occur more or less frequently than expected …

Pediatric Medical Subspecialist Use In Outpatient Settings, Christopher B Forrest, Candice P Chen, Eliana M Perrin, Christopher J Stille, Ruth Cooper, Katherine Harris, Qian Luo, Mitchell G Maltenfort, Lauren E Parlett

Faculty, Staff and Student Publications

Importance

A first step toward understanding whether pediatric medical subspecialists are meeting the needs of the nation’s children is describing rates of use and trends over time.

Objectives

To quantify rates of outpatient pediatric medical subspecialty use.

Design, Setting, and Participants

This repeated cross-sectional study of annual subspecialist use examined 3 complementary data sources: electronic health records from PEDSnet (8 large academic medical centers [January 1, 2010, to December 31, 2021]); administrative data from the Healthcare Integrated Research Database (HIRD) (14 commercial health plans [January 1, 2011, to December 31, 2021]); and administrative data from the Transformed Medicaid Statistical Information …

Microbial Co-Occurrences On Catheters From Long-Term Catheterized Patients, Taylor M Nye, Zongsen Zou, Chloe L P Obernuefemann, Jerome S Pinkner, Erin Lowry, Kent Kleinschmidt, Karla Bergeron, Aleksandra Klim, Karen W Dodson, Ana L Flores-Mireles, Jennifer N Walker, Daniel Garrett Wong, Alana Desai, Michael G Caparon, Scott J Hultgren

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in catheter and urine samples from 55 human long-term catheterized patients collected over one year. Although most of these patients were prescribed antibiotics over several collection periods, their catheter samples remain colonized by one or more bacterial species. Examination of a total of 366 catheter and urine samples identify 13 positive and 13 negative genus co-occurrences over 12 collection periods, representing associations that occur more or less frequently than expected …

Genome-Wide And Targeted Crispr Screens Identify Rnf213 As A Mediator Of Interferon Gamma-Dependent Pathogen Restriction In Human Cells, Sumit K Matta, Hinissan P Kohio, Pallavi Chandra, Adam Brown, John G Doench, Jennifer A Philips, Siyuan Ding, L David Sibley

2020-Current year OA Pubs

To define cellular immunity to the intracellular pathogen

Combinatorial Effects Of Ion Channel Mis-Splicing As A Cause Of Myopathy In Myotonic Dystrophy, Larissa Nitschke, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder caused by an unstable expanded CTG repeat located in the 3'-UTR of the DM1 protein kinase (DMPK) gene. The pathogenic mechanism results in misregulated alternative splicing of hundreds of genes, creating the dilemma of establishing which genes contribute to the mechanism of DM1 skeletal muscle pathology. In this issue of the JCI, Cisco and colleagues systematically tested the combinatorial effects of DM1-relevant mis-splicing patterns in vivo and identified the synergistic effects of mis-spliced calcium and chloride channels as a major contributor to DM1 skeletal muscle impairment. The authors further demonstrated …

Choclo Virus (Chov) Recovered From Deep Metatranscriptomics Of Archived Frozen Tissues In Natural History Biorepositories, Paris S Salazar-Hamm, William L Johnson, Robert A Nofchissey, Jacqueline R Salazar, Publio Gonzalez, Samuel M Goodfellow, Jonathan L Dunnum, Steven B Bradfute, Blas Armién, Joseph A Cook, Daryl B Domman, Darrell L Dinwiddie

Pediatrics Research and Scholarship

BACKGROUND: Hantaviruses are negative-stranded RNA viruses that can sometimes cause severe disease in humans; however, they are maintained in mammalian host populations without causing harm. In Panama, sigmodontine rodents serve as hosts to transmissible hantaviruses. Due to natural and anthropogenic forces, these rodent populations are having increased contact with humans.

METHODS: We extracted RNA and performed Illumina deep metatranscriptomic sequencing on Orthohantavirus seropositive museum tissues from rodents. We acquired sequence reads mapping to Choclo virus (CHOV, Orthohantavirus chocloense) from heart and kidney tissue of a two-decade old frozen museum sample from a Costa Rican pygmy rice rat (Oligoryzomys costaricensis) collected …

Pharmacokinetic-Pharmacodynamic Evidence From A Phase 3 Trial To Support Flat-Dosing Of Rifampicin For Tuberculosis, Huy X. Ngo, Ava Y. Xu, Gustavo E. Velásquez, Nan Zhang, Vincent K. Chang, Ekaterina V. Kurbatova, William C. Whitworth, Erin Sizemore, Kia Bryant, Wendy Carr, Marc Weiner, Kelly E. Dooley, Melissa Engle, Susan E. Dorman, Payam Nahid, Susan Swindells, Richard E. Chaisson, Pheona Nsubuga, Madeleine Lourens, Rodney Dawson, Radojka M. Savic

Journal Articles: Infectious Diseases

BACKGROUND: The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes.

METHODS: We analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months; TB-related unfavorable outcomes at 9, 12, and 18 months using …

Artificial Intelligence, Big Data, And Regulation Of Immunity: Challenges And Opportunities, Bhagirath Singh, Anthony M Jevnikar, Eric Desjardins

Microbiology & Immunology Publications

The immune system is regulated by a complex set of genetic, molecular, and cellular interactions. Rapid advances in the study of immunity and its network of interactions have been boosted by a spectrum of "omics" technologies that have generated huge amounts of data that have reached the status of big data (BD). With recent developments in artificial intelligence (AI), theoretical and clinical breakthroughs could emerge. Analyses of large data sets with AI tools will allow the formulation of new testable hypotheses open new research avenues and provide innovative strategies for regulating immunity and treating immunological diseases. This includes diagnosis and …

Resilience Of Mental Health Services Amidst Ebola Disease Outbreaks In Africa, Frankline Sevidzem Wirsiy, Nancy B. Tahmo, Lambed Tatah, David Brett-Major

Journal Articles: Epidemiology

INTRODUCTION: Health systems including mental health (MH) systems are resilient if they protect human life and produce better health outcomes for all during disease outbreaks or epidemics like Ebola disease and their aftermaths. We explored the resilience of MH services amidst Ebola disease outbreaks in Africa; specifically, to (i) describe the pre-, during-, and post-Ebola disease outbreak MH systems in African countries that have experienced Ebola disease outbreaks, (ii) determine the prevalence of three high burden MH disorders and how those prevalences interact with Ebola disease outbreaks, and, (iii) describe the resilience of MH systems in the context of these …

Teaching Procedural Skills: Integrating Educational Theory Into Practice, Christopher J. Smith, Cory Rohlfsen, Jana L. Wardian, Khalid Sahak

Journal Articles: Hospital Medicine

Introduction: Teaching procedural skills is an essential part of health professions education, yet formal training is often lacking from traditional curricula.

Methods: A workshop on teaching procedural skills was developed as part of a clinician educator track at a large health professions university. Participants included medical residents and fellows (postgraduate years 2-6) from various training programs. The 90-minute, interactive training integrated Gagne's model of instructional design with evidence-based teaching practices. Workshop outcomes were evaluated with pre- and postworkshop surveys. Learner reactions (Kirkpatrick level 1) were assessed via course evaluation. Learning and behavior (Kirkpatrick level 2) were evaluated via attitudinal and …

Unified Resource Browser: An Interactive And Reconfigurable Web Framework For Biomedical Metadata Exploration, Visualization, And Management, Shiwei Lin, Ling Tong, Kimberly A Smith, Lydia Ng, Tyler Mollenkopf, Yan Huang, Rashmie Abeysinghe, Wei-Chun Chou, Antarr T Byrd, Licong Cui, Guo-Qiang Zhang, Xiaojin Li, Shiqiang Tao

Faculty, Staff and Student Publications

We present Unified Resource Browser, a web-based framework designed to optimize the configuration, exploration, visualization, and dissemination of complex biomedical metadata. As a core component of Neuroanatomy-Anchored Information Management Platform (NIMP), Unified Resource Browser enables researchers to efficiently access donor information, brain tissue samples, and sequencing data through structured resource tables and advanced search and filtering capabilities. The platform allows users to customize data views, share configurations via direct links, and seamlessly export data for further analysis. Integrated visualization tools offer immediate insights through customizable charts, enhancing data interpretation. By improving the accessibility and usability of biomedical data resources, Unified …

Design Of A Targeted Blood Transcriptional Panel For Monitoring Immunological Changes Accompanying Pregnancy., Tobias Brummaier, Darawan Rinchai, Mohammed Toufiq, Mohammed Y Karim, Tanwir Habib, Jürg Utzinger, Daniel H Paris, Rose Mcgready, Alexandra K Marr, Tomoshige Kino, Annalisa Terranegra, Souhaila Al Khodor, Damien Chaussabel, Basirudeen Syed Ahamed Kabeer

Faculty Research 2024

BACKGROUND: Immunomodulatory processes exert steering functions throughout pregnancy. Detecting diversions from this physiologic immune clock may help identify pregnant women at risk for pregnancy-associated complications. We present results from a data-driven selection process to develop a targeted panel of mRNAs that may prove effective in detecting pregnancies diverting from the norm.

METHODS: Based on a

RESULTS: We identified 176 transcripts that were complemented with eight housekeeping genes. Changes in transcript abundance were seen in the early stages of pregnancy and similar patterns were observed in both datasets. Functional gene annotation suggested significant changes in the lymphoid, prostaglandin and inflammation-associated compartments, …

Mucosal-Associated Invariant T Cells In Cancer: Dual Roles, Complex Interactions And Therapeutic Potential., Mesut Yigit, Omer Faruk Basoglu, Derya Unutmaz

Faculty Research 2024

Mucosal-associated invariant T (MAIT) cells play diverse roles in cancer, infectious diseases, and immunotherapy. This review explores their intricate involvement in cancer, from early detection to their dual functions in promoting inflammation and mediating anti-tumor responses. Within the solid tumor microenvironment (TME), MAIT cells can acquire an 'exhausted' state and secrete tumor-promoting cytokines. On the other hand, MAIT cells are highly cytotoxic, and there is evidence that they may have an anti-tumor immune response. The frequency of MAIT cells and their subsets has also been shown to have prognostic value in several cancer types. Recent innovative approaches, such as programming …

Spop Downregulation Promotes Bladder Cancer Progression Based On Cancer Cell-Macrophage Crosstalk Via Stat3/Ccl2/Il-6 Axis And Is Regulated By Vezf1., Meiqian Li, Yangyan Cui, Qi Qi, Jiakuan Liu, Jiaxuan Li, Guifang Huang, Jiale Yang, Jingya Sun, Zhihui Ma, Shengjie Liang, Dianzheng Zhang, Jun Jiang, Rujian Zhu, Qiuli Liu, Ruimin Huang, Jun Yan

PCOM Scholarly Works

Background: Cancer cells are intimately intertwined with tumor microenvironment (TME), fostering a symbiotic relationship propelling cancer progression. However, the interaction between cancer cells and tumor-associated macrophages (TAMs) in urothelial bladder cancer (UBC) remains poorly understood. Methods: UBC cell lines (5637, T24 and SW780), along with a monocytic cell line (U937) capable of differentiating into macrophage, were used in a co-culture system for cell proliferation and stemness by MTT, sphere formation assays. VEZF1/SPOP/STAT3/CCL2/ IL-6 axis was determined by luciferase reporter, ChIP, RNA-seq, co-IP, in vitro ubiquitination, RT-qPCR array and ELISA analyses. Results: We observed the frequent downregulation of SPOP, an E3 …

Hpv Vaccination In Africa In The Covid-19 Era: A Cross-Sectional Survey Of Healthcare Providers' Knowledge, Training, And Recommendation Practices, Joel Fokom Domgue, Issimouha Dille, Sharon Kapambwe, Robert Yu, Freddy Gnangnon, Lameck Chinula, Gad Murenzi, Nomonde Mbatani, Mala Pande, Fatoumata Sidibe, Joseph Kamgno, Bangaly Traore, Hicham El Fazazi, Mamadou Diop, Pierre-Marie Tebeu, Mohenou Isidore Diomande, Fabrice Lecuru, Isaac Adewole, Marie Plante, Partha Basu, Jean-Marie Dangou, Sanjay Shete

Faculty, Staff and Student Publications

INTRODUCTION: Although the burden of cervical cancer in Africa is highest, HPV vaccination coverage remains alarmingly low in this region. Providers' knowledge and recommendation are key drivers of HPV vaccination uptake. Yet, evidence about providers' knowledge and recommendation practices about the HPV vaccine against a backdrop of emerging vaccine hesitancy fueled by the COVID-19 pandemic is lacking in Africa.

METHODS: A cross-sectional study was conducted in 2021-2022 among healthcare providers involved in cervical cancer prevention activities in Africa. They were invited to report prior training, the availability of the HPV vaccine in their practice, whether they recommended the HPV vaccine, …

Phospholipid Metabolic Adaptation Promotes Survival Of Idh2 Mutant Acute Myeloid Leukemia Cells, Tatsuya Morishima, Koichi Takahashi, Desmond Wai Loon Chin, Yuxin Wang, Kenji Tokunaga, Yuichiro Arima, Masao Matsuoka, Toshio Suda, Hitoshi Takizawa

Faculty, Staff and Student Publications

Genetic mutations in the isocitrate dehydrogenase (IDH) gene that result in a pathological enzymatic activity to produce oncometabolite have been detected in acute myeloid leukemia (AML) patients. While specific inhibitors that target mutant IDH enzymes and normalize intracellular oncometabolite level have been developed, refractoriness and resistance has been reported. Since acquisition of pathological enzymatic activity is accompanied by the abrogation of the crucial WT IDH enzymatic activity in IDH mutant cells, aberrant metabolism in IDH mutant cells can potentially persist even after the normalization of intracellular oncometabolite level. Comparisons of isogenic AML cell lines with and without IDH2 gene mutations …

The Immunobiology Of Myelodysplastic Neoplasms: A Mini-Review, Shruthi Kannan, Rolando A Vedia, Jeffrey J Molldrem

Faculty, Staff and Student Publications

This mini review summarizes the immunobiology of myelodysplastic syndromes, specifically focusing on the interactions between immune cells, cytokines, and dysplastic cells within the tumor microenvironment in the bone marrow. We elucidate in detail how immune dysregulation and evasion influence the initiation and progression of myelodysplastic syndromes, as well as resistance to therapy and progression to AML. In addition, we highlight a range of therapeutic strategies, including the most recent breakthroughs and experimental therapies for treating MDS. Finally, we address the existing knowledge gaps in the understanding of the immunobiology of MDS and propose future research directions, promising advancements toward enhancing …

Pcv15, A Pneumococcal Conjugate Vaccine, For The Prevention Of Invasive Pneumococcal Disease In Infants And Children., Timothy J. Chapman, Liset Olarte, Ghassan Dbaibo, Avril Melissa Houston, Gretchen Tamms, Robert Lupinacci, Kristen Feemster, Ulrike K. Buchwald, Natalie Banniettis

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION:

Streptococcus pneumoniae is a causative agent of pneumonia and acute otitis media (AOM), as well as invasive diseases such as meningitis and bacteremia. PCV15 (V114) is a new 15-valent pneumococcal conjugate vaccine (PCV) approved for use in individuals ≥6 weeks of age for the prevention of pneumonia, AOM, and invasive pneumococcal disease.

AREAS COVERED: This review summarizes the V114 Phase 3 development program leading to approval in infants and children, including pivotal studies, interchangeability and catch-up vaccination studies, and studies in at-risk populations. An integrated safety summary is presented in addition to immunogenicity and concomitant use of V114 with …