Digital Commons Network^™

Loss Of Ptdss1 In Tumor Cells Improves Anti-Pd-1 Therapy, Jielin Liu

Dissertations and Theses (Open Access)

PTDSS1 (Phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of PTDSS1 in tumor cells increased expression of IFNγ-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1. Loss of PTDSS1 in tumor cells also led to increased expression of MHC-I, which was associated with increased expression of cytolytic function related genes in CD8⁺ T cells and increased frequency of an iNOS⁺ myeloid subset. A gene signature derived from the iNOS⁺ myeloid …

Exploring The Role Of Il-1Β/Il-1r In The Pathogenesis Of K-Ras Mutant Lung Cancer, Avantika Krishna

Dissertations and Theses (Open Access)

As the leading cause of cancer-related deaths worldwide, the development of targeted therapeutics to treat lung cancer remains crucial. Non-small cell lung cancer (NSCLC), the most common histological subtype predominantly comprises lung adenocarcinoma with driver mutations in the K-ras oncogene (KM-LUAD). KM-LUAD progression partly occurs through activation of the NF-κB pathway initiating an inflammatory response and creating a pro-tumor microenvironment. Notably, the pro-inflammatory cytokine IL-1β a potent activator and product of the NF-κB pathway is elevated in the lungs and sera of KM-LUAD patients. We have shown that IL-1β blockade promotes an anti-tumor immune phenotype in a mouse model of …

Rna Knockdown Of The Immune Checkpoint Vista Promotes Tumor Regression, Brittany Morrow, Brittany A. Morrow

Dissertations and Theses (Open Access)

Blockade of negative immune regulators for example CTLA-4, and PD-1/PD-L1 has proven to be a clinically effective strategy to enhance tumor specific immune responses. Recently discovered novel immunoglobulin superfamily ligand V-domain Ig suppressor of T-cell Activation (VISTA) is a new target for immunotherapy. VISTA expression is specifically upregulated on tumor infiltrating myeloid cells such as dendritic cells (DCs), tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs). In addition, VISTA expression is increased on tumor-infiltrating regulatory T cells (Tregs) compared to those in the periphery. VISTA has been shown to suppress effector T cells through multiple mechanisms, primarily by …

Importance Of Specific Nk Cell Subsets For Antitumor Immunity In Hpv+ Cancers, Madison O'Hara

Dissertations and Theses (Open Access)

High-risk type human papillomaviruses (HPV) are associated with genital and oral cancers, and the incidence of HPV+ head and neck squamous cell cancers is fast increasing worldwide. Survival rates for patients with locally advanced disease are poor and variable after standard of care (SOC) treatment. Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential for improving clinical outcome. The natural killer (NK) cells are a critical component for antitumor innate effector immunity. Among the multitude of activation and inhibitory receptors on immune cells, HLA-DR is recognized as an important activation marker …

Molecular Basis Of Cell Membrane Adaption Against Daptomycin In Enterococcus Faecalis, April Nguyen

Dissertations and Theses (Open Access)

Daptomycin is a last-resort lipopeptide antibiotic that disrupts cell membrane (CM) and peptidoglycan homeostasis (Grein et al., 2020a; Müller et al., 2016a). Enterococcus faecalis has developed a sophisticated mechanism to avoid daptomycin killing by redistributing CM anionic phospholipids away from the septum. The CM changes are orchestrated by a three-component regulatory system, designated LiaFSR, with a possible contribution of cardiolipin synthase (Cls) (Cesar A Arias et al., 2011a; Khan et al., 2019b; Palmer et al., 2011a; Panesso et al., 2015a; Reyes et al., 2015a). However, the mechanism by which LiaFSR controls the cell membrane response and the role of Cls …

Regulation Of Cd4 T Cell Functions By Ncrna-Mediated Signaling Pathways During Chronic Viral Infections, Lam Nguyen

Electronic Theses and Dissertations

CD4 T cell homeostasis and competency are critical for the effectiveness of antiviral immunity. However, CD4 T cells derived from people living with HIV (PLWH) and individuals with chronic HCV infection often exhibit an inflammaging phenotype, evidenced by persistent inflammation, immune activation, exhaustion, senescence, and cellular apoptosis. Despite intensive investigations, the molecular mechanisms underlying CD4 T cell dysfunction in antiretroviral therapy (ART)-controlled PLWH and HCV-infected patients remain poorly understood. By investigating the roles of non-coding (nc)RNA transcripts in regulating the functions of CD4 T cells derived from PLWH and HCV-infected patients, we demonstrated that long non-coding (lnc)RNA - growth arrest-specific …

Navigating School Restructuring In The Post-Covid Era: A Principal’S Perspective In Sustaining Organizational Health While Bridging The Academic Achievement Gap, Alma Alicia Perez-Campos

Theses and Dissertations

In 2019, the COVID-19 pandemic led to nationwide school closures, followed by a mandate for schools to reopen in 2020, posing challenges for ensuring both educational continuity and student safety. This paper presents findings from a mixed-method study involving ten campus principals in District A, South Texas, post-pandemic. Qualitatively, the study explored the principals' perspectives on restructuring their campuses to address achievement gaps while maintaining organizational health. Quantitatively, it examined the relationship between achievement and organizational health scores and any differences in organizational health pre- and post-COVID-19. The study aimed to offer insights for future …

Targeting Coenzyme A Biosynthesis For Antifungal Development., Jessica Regan

Theses and Dissertations (ETD)

An estimated 1.5 million people die each year from invasive fungal infections (IFIs) involving dissemination to the deeper organs via the bloodstream, with estimated healthcare costs of over $7 billion in the U.S. alone. Collectively, several Candida species account for more than 75% of disseminated fungal infections in the U.S., with attributable mortality rates ranging 35-75%. Unfortunately, the prospect of curing these infections is limited by the modest efficacy of the available antifungal drugs: the azoles, echinocandins, and amphotericin B. Approximately one-third of patients with disseminated Candida infections are non-responsive to treatment with the azoles, and favorable response rates are …

Understanding Infectious Disease Consultation Role For Septic Patients In The Medical Intensive Care Unit, Marisa Stratelak, Cloe Nazeer, Bhavinkumar Dalal

Posters

• Sepsis is a medical emergency requiring immediate recognition and prompt treatment.
• 1 in every 3 hospitalized patients who die have sepsis1.
• The mortality rate for patients with severe sepsis in the intensive care unit (ICU) is 32.2%2.
• Early intervention with fluid resuscitation and intravenous antibiotics can reduce mortality rates by 7-9%3.
• Infectious disease (ID) consultation on antimicrobial therapy in the ICU is associated with reduced ICU mortality and ICU length of stay (LOS)4.
• Gaps in literature exist regarding frequency of ID consultation for septic patients in the ICU, including comparing outcomes of patients with and without ID consultation.
• It is …

Selective Transfection Of A Transferrin Receptor-Expressing Cell Line With Dna-Lipid Nanoparticles And Synthesis Of Parasite-Derived Glycans As Biomarkers For Leishmaniasis, Irodiel Vinales Lozano

Open Access Theses & Dissertations

Despite notable progress in lipid nanoparticle (LNP)-mediated gene delivery, achieving selective transfection of specific cell types, such as cancer cells, remains a significant hurdle, hindering the advancement of innovative gene therapies. In this study, we engineered an LNP formulation encapsulating plasmid DNA (pDNA) encoding the monomeric Green Lantern (mGL) fluorescent reporter protein. The DT7 peptide ligand targeting human transferrin receptor 1 (hTfR1) was also conjugated to the LNP surface for targeted delivery to hTfR1-expressing cells. Optimization of LNP composition yielded favorable particle diameter, ζ-potential, yield, and pDNA encapsulation efficiency. Evaluation of transfection selectivity using a panel of two engineered cell …

Synthesis Of Neoglycoproteins As Potential Biomarkers For Chagas Disease And Cutaneous Leishmaniasis Caused By Leishmania (Viannia) Braziliensis, Eileni Rodriguez Gil

Open Access Theses & Dissertations

Protozoan parasites are responsible for causing numerous diseases in humans and mammals worldwide. Among them are Chagas disease (CD), caused by the parasite Trypanosoma cruzi (T. cruzi), and tegumentary leishmaniasis (TL), caused by the parasite Leishmania (Viannia). Both diseases coexist in many regions of Latin America, and current hurdles to differentially diagnose them and determine chemotherapy success need to be overcome. CD can be diagnosed by traditional serological tests and polymerase chain reaction (PCR), but disadvantages of these methods are that they may produce false negatives because the antigens used in commercial CD kits are not conserved across all T.cruzi …

Developing Anisotropic Soft Matter As Functional Materials To Interface With Biological Systems, Homa Ghaiedi

Graduate Theses and Dissertations

Liquid crystals (LCs) constitute a subset of soft matter possessing hybrid characteristics from both liquid and crystalline phases. In this state, the center of masses remains uncorrelated similar to an isotropic phase, while the long axis of molecules aligns in parallel, resulting in molecules exhibiting orientational and positional order, either individually or concurrently. The directional alignment inherent in LCs arises from the asymmetrical shape and structure of the constituent molecules, causing a spontaneous self-assembly into ordered phases. This cooperative molecular behavior manifests distinctive optical features when subjected to cross polarizers. The remarkable sensitivity of LCs to external stimuli, including temperature, …

Adding Parasite Resistance To A Hair Sheep Breeding Objective, Robert M. Forbes

Department of Animal Science: Dissertations, Theses, and Student Research

The United States Hair Sheep Index was designed to increase total weight of lamb weaned per ewe lambing (TW) using estimated breeding values (EBV) for direct (DWWT) and maternal (MWWT) weaning weight, and number of lambs born (NLB) and weaned (NLW), as selection criteria. Producers are interested in adding post-weaning fecal egg count EBV (PFEC), an indicator of parasite resistance, to the index to achieve genetic change in both TW and PFEC.

First, the effects of adding PFEC alongside TW to the breeding objective of indexes that used either phenotypes or EBV as selection criteria were studied. Since MWWT …

Identifying Temporomandibular Disorder Morphological Risk Factors Via Explainable Deep Learning And Multiscale Biomechanical Modeling, Shuchun Sun

All Dissertations

Clarifying multifactorial musculoskeletal disorder etiologies supports risk analysis and development of targeted prevention and treatment modalities. Deep learning enables comprehensive risk factor identification through systematic analysis of disease datasets but does not provide sufficient context for mechanistic understanding, limiting clinical applicability for etiological investigations. Conversely, multiscale biomechanical modeling can evaluate mechanistic etiology within the relevant biomechanical and physiological context. We propose a hybrid approach combining 3D explainable deep learning and multiscale biomechanical modeling; we applied this approach to investigate temporomandibular joint (TMJ) disorder etiology by systematically identifying risk factors and elucidating mechanistic relationships between risk factors and TMJ biomechanics and …

Use Of Advanced Diagnostics For Timely Identification Of Travel-Associated Leptospira Santarosai Infection In Four Adolescents Through Plasma Microbial Cell-Free Dna Sequencing With The Karius Test, Hai Nguyen-Tran, Guliz Erdem, P Marcelo Laufer, Lori Patterson, Asim A Ahmed, William A Bower, Renee Galloway, Sara Saporta-Keating

Faculty, Staff and Student Publications

Background: Leptospirosis is an important zoonotic infection worldwide. Diagnosis of leptospirosis is challenging given its nonspecific clinical symptoms that overlap with other acute febrile illnesses and limitations with conventional diagnostic testing. Alternative advanced diagnostics, such as microbial cell-free DNA (mcfDNA), are increasingly being used to aid in the diagnosis of infections and can be applied to pathogens with public health importance such as Leptospira , a nationally notifiable disease.

Methods: The Karius Test uses plasma mcfDNA sequencing to detect and quantify DNA-based pathogens. This test offered through the Karius lab detected 4 cases of Leptospira santarosai during a 5-month period …

Practical Approaches For Supporting Informed Consent In Neonatal Clinical Trials, Susan H Wootton, Matthew Rysavy, Peter Davis, Marta Thio, Mar Romero-Lopez, Lindsay F Holzapfel, Tamara Thrasher, Jaleesa D Wade, Louise S Owen

Faculty, Staff and Student Publications

The survival and health of preterm and critically ill infants have markedly improved over the past 50  years, supported by well-conducted neonatal research. However, newborn research is difficult to undertake for many reasons, and obtaining informed consent for research in this population presents several unique ethical and logistical challenges. In this article, we explore methods to facilitate the consent process, including the role of checklists to support meaningful informed consent for neonatal clinical trials. CONCLUSION: The authors provide practical guidance on the design and implementation of an effective consent checklist tailored for use in neonatal clinical research.

Sars-Cov-2 Viral Load In The Nasopharynx At Time Of First Infection Among Unvaccinated Individuals, Leigh H Fisher, Jia Jin Kee, Albert Liu, Claudia M Espinosa, April K Randhawa, James Ludwig, Craig A Magaret, Samuel T Robinson, Peter B Gilbert, Ollivier Hyrien, James G Kublin, Nadine Rouphael, Ann R Falsey, Magdalena E Sobieszczyk, Hana M El Sahly, Beatriz Grinsztejn, Glenda E Gray, Karen L Kotloff, Cynthia L Gay, Brett Leav, Ian Hirsch, Frank Struyf, Lisa M Dunkle, Kathleen M Neuzil, Lawrence Corey, Yunda Huang, Paul A Goepfert, Stephen R Walsh, Lindsey R Baden, Holly Janes, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Student Publications

Importance: SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity.

Objective: To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease.

Design, setting, and participants: This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline …

Experiences In Vocal Psychotherapy Of A Music Therapy Intern With Post-Covid Symptoms, Kyungwon Matilda Choi

Theses & Dissertations

The purpose of this study was to explore my experiences in vocal psychotherapy as a music therapy intern with Long COVID symptoms. This study employed a first-person qualitative research design by assessing two personal therapy sessions with heuristic inquiry. I analyzed my experience as a client receiving 60-minute individual vocal psychotherapy sessions. The music therapist was a trained (certified) vocal psychotherapist with at least five years of clinical practice. Data were collected from recorded session audio/video and personal journals. The recorded session audio/video were transcribed so the data could be analyzed. I asked and answered the research questions as this …

The Role Of Cosmopolitan Orientation In Covid-19-Related Attitudes: Perceived Threats And Opportunities, Vaccination Willingness, And Support For Collective Containment Efforts, Angela K. Y. Leung, Brandon Koh, Verity Yu Qing Lua, James H. Liu, Sarah Y. Choi, I-Ching Lee, Michelle Lee, Mei-Hua Lin, Darrin Hodgetts, Sylvia X. Chen

Research Collection School of Social Sciences

Cosmopolitan individuals identify themselves as "citizens of the world." In the present research, we tested the idea that endorsing a cosmopolitan orientation (CO) is adaptive in the COVID-19 crisis. Cosmopolitan individuals more readily transcend national parochialism, show greater concern for all humanity, and prioritize collective interests. In a two-wave multi-region investigation with six samples from China, Hong Kong, Taiwan, Malaysia, Singapore, and the U.S., we first established longitudinal and cross-cultural measurement invariance of the CO scale. Next, we found that people with a higher CO tended to perceive over time a greater threat posed by COVID-19, take more safety measures, …

Factors Associated With The Ability Of Us Nursing Homes To Accept Residents With Severe Obesity, Cynthia Mcmahan, Bianca Shieu, Alison Trinkoff, Nicholas Castle, David G Wolf, Steven Handler, John A Harris

Faculty, Staff and Student Publications

Objectives: Severe obesity in nursing home (NH) residents is associated with specialized care needs, limited mobility, and challenges in daily living. The COVID-19 pandemic strained NH resources and exacerbated staffing shortages. This study aimed to assess the ability of US NHs to accept and care for residents with severe obesity post-COVID, as well as associated NH factors.

Design: Cross-sectional nationwide survey of NH administrators (2021-2022).

Setting and participants: 290 NHs from a national sample (n = 224) and a targeted sample in Massachusetts and New Jersey (n = 66).

Methods: A survey designed to assess how NHs approach admitting and …

Silver Nanoparticle Biosynthesis Utilizing Ocimum Kilimandscharicum Leaf Extract And Assessment Of Its Antibacterial Activity Against Certain Chosen Bacteria, Horyomba Siaka Ouandaogo, Souleymane Diallo, Eddy Odari, Johnson Kinyu

All Peer-Reviewed Publications

The use of plants in the biological production of silver nanoparticles for antibacterial applications is a growing field of research. In the current work, we formulated Ocimum kilimandscharicum extracts using silver nanoparticles, and evaluated its potential antibacterial activity. Aqueous and methanol plant extracts were used to reduce silver nitrate at different time intervals (30 to 150 minutes) and pH (2 to 11). The UV-visible absorption spectrum recorded for methanol and aqueous extracts revealed a successful synthesis of AgNPs for methanol and aqueous extracts. The antimicrobial activity of the AgNPs was evaluated against Escherichia coli ATCC 25922, Salmonella choleraesuius ATCC 10708, …

Age-Related Differences In The Mouse Corneal Epithelial Transcriptome And Their Impact On Corneal Wound Healing, Anmar Abu-Romman, Kaitlin K Scholand, Gowthaman Govindarajan, Zhiyuan Yu, Sonali Pal-Ghosh, Mary A Stepp, Cintia S De Paiva

Faculty, Staff and Students Publications

PURPOSE: Aging is a risk factor for dry eye. We sought to identify changes in the aged mouse corneal epithelial transcriptome and determine how age affects corneal sensitivity, re-epithelialization, and barrier reformation after corneal debridement.

METHODS: Corneal epithelium of female C57BL/6J (B6) mice of different ages (2, 12, 18, and 24 months) was collected, RNA extracted, and bulk RNA sequencing performed. Cornea sensitivity was measured with an esthesiometer in 2- to 3-month-old, 12- to 13-month-old, 18- to 19-month-old, and 22- to 25-month-old female and male mice. The 2-month-old and 18-month-old female and male mice underwent unilateral corneal debridement using a …

Clinical Outcomes After Acute Coronary Syndromes Or Revascularization Among People Living With Hiv: A Systematic Review And Meta-Analysis, Mohammed Haji, Michael Capilupi, Michael Kwok, Nouran Ibrahim, Gerald S Bloomfield, Christopher T Longenecker, Maria C Rodriguez-Barradas, Chester N Ashong, Eric Jutkowitz, Tracey H Taveira, Michelle Richard, Jennifer L Sullivan, James L Rudolph, Wen-Chih Wu, Sebhat Erqou

Faculty, Staff and Students Publications

IMPORTANCE: Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately.

OBJECTIVE: To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group.

DATA SOURCES: Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023.

STUDY SELECTION: Included studies met the following criteria: patients living with …

Performance Of A Stool-Based Quantitative Pcr Assay For The Diagnosis Of Tuberculosis In Adolescents And Adults: A Multinational, Prospective Diagnostic Accuracy Study, Alexander Kay, Anca Vasiliu, Lucia Carratala-Castro, Bariki Mtafya, Jose Euberto Mendez Reyes, Nontobeko Maphalala, Shilzia Munguambe, Durbbin Mulengwa, Tara Ness, Belen Saavedra, Jason Bacha, Gugu Maphalala, Rojelio Mejia, Godwin Mtetwa, Sozinho Acacio, Patricia Manjate, Edson Mambuque, Nosisa Shiba, Nokwanda Kota, Mangaliso Ziyane, Nyanda Elias Ntinginya, Christoph Lange, H Lester Kirchner, Andrew R Dinardo, Alberto L Garcia-Basteiro, Anna Maria Mandalakas, Stool4tb Global Partnership

Faculty, Staff and Students Publications

BACKGROUND: Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens.

METHODS: We undertook a prospective diagnostic accuracy study in Eswatini, Mozambique, and Tanzania from Sept 21, 2020, to Feb 2, 2023, to compare the diagnostic accuracy for tuberculosis of a novel stool qPCR …

Gut Microbiome Correlates Of Recurrent Urinary Tract Infection: A Longitudinal, Multi-Center Study, Joohee Choi, Robert Thänert, Kimberly A Reske, Katelin B Nickel, Margaret A Olsen, Tiffany Hink, Anna Thänert, Meghan A Wallace, Bin Wang, Candice Cass, Margaret H Barlet, Emily L Struttmann, Zainab Hassan Iqbal, Steven R Sax, Victoria J Fraser, Carey-Ann D Burnham, Erik R Dubberke, Gautam Dantas, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI (rUTI) that is thought to be facilitated by a gut reservoir of uropathogenic

METHODS: 125 patients with UTI caused by an antibiotic-resistant organism (ARO) were enrolled from July 2016 to May 2019 in a longitudinal, multi-center cohort study. Multivariate statistical models were used to assess the relationship between uropathogen colonization and recurrent UTI (rUTI), controlling for clinical characteristics. 644 stool samples and 895 UPEC isolates were interrogated for taxonomic composition, antimicrobial resistance genes, and phenotypic resistance. Cohort …

Assessment Of Illness Severity In Adults Hospitalized With Acute Respiratory Tract Infection Due To Influenza, Respiratory Syncytial Virus, Or Human Metapneumovirus, Ann R Falsey, Edward E Walsh, Stacey L House, Yannick Vandendijck, Marita Stevens, Eric K H Chan, Gabriela Ispas

2020-Current year OA Pubs

BACKGROUND: Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician-rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient-reported outcomes (PROs).

METHODS: HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection …

Patient Engagement In Designing, Conducting, And Disseminating Clinical Pain Research: Immpact Recommended Considerations, Simon Haroutounian, Katherine J. Holzer, Et Al.

2020-Current year OA Pubs

In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are …

Interferons And Tuft Cell Numbers Are Bottlenecks For Persistent Murine Norovirus Infection, Somya Aggarwal, Forrest C. Walker, James S. Weagley, Broc T. Mccune, Xiaofen Wu, Lawrence A. Schriefer, Heyde Makimaa, Dylan Lawrence, Pratyush Sridhar, Megan T. Baldridge

2020-Current year OA Pubs

Noroviruses (NoVs) are a leading cause of viral gastroenteritis. Despite global clinical relevance, our understanding of how host factors, such as antiviral cytokines interferons (IFNs), modulate NoV population dynamics is limited. Murine NoV (MNoV) is a tractable in vivo model for the study of host regulation of NoV. A persistent strain of MNoV, CR6, establishes a reservoir in intestinal tuft cells for chronic viral shedding in stool. However, the influence of host innate immunity and permissive cell numbers on viral population dynamics is an open question. We generated a pool of 20 different barcoded viruses (CR6BC) by inserting 6-nucleotide barcodes …

Impact Of Gram-Negative Bacilli Resistance Rates On Risk Of Death In Septic Shock And Pneumonia, Alison M Hixon, Scott Micek, Victoria J Fraser, Marin Kollef, M Cristina Vazquez Guillamet

2020-Current year OA Pubs

BACKGROUND: Sepsis is a major cause of morbidity and mortality worldwide. When selecting empiric antibiotics for sepsis, clinicians are encouraged to use local resistance rates, but their impact on individual outcomes is unknown. Improved methods to predict outcomes are needed to optimize treatment selection and improve antibiotic stewardship.

METHODS: We expanded on a previously developed theoretical model to estimate the excess risk of death in gram-negative bacilli (GNB) sepsis due to discordant antibiotics using 3 factors: the prevalence of GNB in sepsis, the rate of antibiotic resistance in GNB, and the mortality difference between discordant and concordant antibiotic treatments. We …

National Hiv And Hcv Screening Rates For Hospitalized People Who Use Drugs Are Suboptimal And Heterogeneous Across 11 Us Hospitals, Leo Knudsen Westgard, Laura R Marks, Et Al.

2020-Current year OA Pubs

BACKGROUND: To end the HIV and hepatitis C virus (HCV) epidemics, people who use drugs (PWUD) need more opportunities for testing. While inpatient hospitalizations are an essential opportunity to test people who use drugs (PWUD) for HIV and HCV, there is limited research on rates of inpatient testing for HIV and HCV among PWUD.

METHODS: Eleven hospital sites were included in the study. Each site created a cohort of inpatient encounters associated with injection drug use. From these cohorts, we collected data on HCV and HIV testing rates and HIV testing consent policies from 65 276 PWUD hospitalizations.

RESULTS: Hospitals …