Medicine and Health Sciences Commons^™

Increasing Nurses’ Knowledge Regarding Beers Criteria And Polypharmacy In Elderly, Non-Institutionalized Patients, Florence Chinwe Ukenye

Walden Dissertations and Doctoral Studies

The elderly population, comprising individuals ages 65 years and above, accounts for 12% of the total population in the United States. Many elderly individuals residing in noninstitutionalized communities continue to experience the effects of polypharmacy despite efforts to employ evidence-based practices for medication reconciliation. Preventing polypharmacy among people ages 65 and older is crucial to avoid unintended drug abuse and subsequent adverse drug effects in this vulnerable patient group. One significant strategy to prevent drug-related problems and negative effects of medications is using the Beers criteria. The gap in practice in a post-acute care and rehabilitation facility addressed in this …

The Importance Of Blood Pressure Control In The Survival Of Peritoneal Dialysis Patients Using A Multistate Model, Hadis Najafimehr, Abbas Rahimi Foroushani, Mir Saeed Yekaninejad, Mahmoud Yousefifard, Mostafa Hosseini

Kesmas

Since less attention has been paid to the effect of passing blood pressure states on the survival of peritoneal dialysis (PD) patients, this study aimed to inves­tigate the survival of PD patients with and without hypertension, estimate the probability of hypertension and determine the influential factors. In this retro­spective cohort study, the data of 700 patients visiting dialysis centers from all provinces of Iran from 1997-2009 were analyzed. For data analysis, the multistate survival model was used. The median survival time (months) and five-year survival were 75% and 56%, respectively. Males had a higher probability of hypertension (63%) than females …

Depression Among Islamic Boarding Schools Students During The Covid-19 Pandemic In East Java, Indonesia, Yuni Asri, Dian Pitaloka Priasmoro, Muhammad Solihuddin Muhtar, Yankuba B. Manga

Kesmas

The COVID-19 pandemic significantly impacts many aspects of life, including health, economy, society, education, and mental well-being. The pandemic impact on mental health, in particular, leads to increased rates of depression, anxiety, and stress. This study aimed to determine the prevalence of depression among Islamic boarding school students in Indonesia and identify factors associated with depression symptoms. This cross-sectional study employed questionnaires for data collection. Assessment of depression levels used the DASS-21 tool. Descriptive statistics and multivariate logistic regression were applied to analyze relationships between variables. The study findings indicated that 62.4% of the students exhibited factors associated with depression. …

Transitioning Rn Residency Program: Implementing Medication Safety Education In Practice, Francine Lyon

SACAD: Scholarly Activities

Clinical nursing can affect a nurse's physical and mental well-being. The aging population stresses healthcare providers, including nurses, due to the increased comorbidities and medications needed to treat them. New graduate nurses (NGRNs) can enhance their success by completing a Practice Transition Accreditation Program (PTAP). Despite residency programs, new nurses often find it challenging to meet the demands of clinical settings, leading to compromised patient outcomes and medication errors (MEs). Offering comprehensive medication administration education can reduce errors and discrepancies. Equipping new graduate nurses with the necessary knowledge and skills is crucial for improving patient outcomes and ensuring long-lasting nursing …

Use Of Technology In Training Periop 101 Students, John Carroll, Bsn, Rn. Cnor. Tcrn, Rnfa, Annamarie R. Vrobel, Bsn, Rv, Cpt, Sarah Germanovich, Msn, Rn, Cnor, Tcrn

Jefferson Hospital Staff Papers and Presentations

Presented at the 2024 Association of periOperative Registered Nurses (AORN) Global Surgical Conference & Expo.

The Card8 Inflammasome Dictates Hiv/Siv Pathogenesis And Disease Progression, Qiankun Wang, Kolin M Clark, Ritudhwaj Tiwari, Nagarajan Raju, Gregory K Tharp, Jeffrey Rogers, R Alan Harris, Muthuswamy Raveendran, Steven E Bosinger, Tricia H Burdo, Guido Silvestri, Liang Shan

2020-Current year OA Pubs

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Biological Insights From Plasma Proteomics Of Non-Small Cell Lung Cancer Patients Treated With Immunotherapy, Jair Bar, Raya Leibowitz, Niels Reinmuth, Astrid Ammendola, Eyal Jacob, Mor Moskovitz, Adva Levy-Barda, Michal Lotem, Rivka Katsenelson, Abed Agbarya, Mahmoud Abu-Amna, Maya Gottfried, Tatiana Harkovsky, Ido Wolf, Ella Tepper, Gil Loewenthal, Ben Yellin, Yehuda Brody, Nili Dahan, Maya Yanko, Coren Lahav, Michal Harel, Shani Raveh Shoval, Yehonatan Elon, Itamar Sela, Adam Dicker, Yuval Shaked

Department of Radiation Oncology Faculty Papers

INTRODUCTION: Immune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.

METHODS: Pre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using …

The Effects Of Environmental Noise On Annoyance, Stress, And Urine Cortisol Levels Among Residents Living Near Industrial Sites In Bangkok, Thailand, Nutthajit Onmek, Narisa Kengtrong Bordeerat, Supat Wangwongwatana

Kesmas

People are exposed to environmental noise each day. It may be annoying, cause stress, induce hormonal changes, and negatively affect long-term health. This study aimed to determine the effects of environmental noise on annoyance, perceived stress, stress symptoms, and urine cortisol in people living in a selected area. This cross-sectional study was conducted from April to October 2022 on 142 participants. Urine samples were collected to determine cortisol levels, and perceived stress, stress symptoms, and environmental noise annoyance were evaluated using questionnaires. Stress symptoms correlated with traffic, industrial, and community noise, but not aircraft noise. Community noise correlated most strongly …

Daily Income Targets And Passenger Pressure On Safety Risky Riding Behavior Among Online Motorcycle Taxi Riders In Jakarta, Indonesia, Zulkifli Djunaidi, Agra Mohamad Khaliwa, Azka Hafia, Nadya Putri

Kesmas

Online motorcycle taxi riders, a vulnerable group on the road, are more susceptible to serious injury than non-motorcycle riders. This study analyzed a correlation between daily income targets, passenger pressure, risk perception, safety attitudes, and risky riding behavior. This cross-sectional study used a semi-quantitative approach by collecting online-based questionnaires from 500 online motorcycle taxi riders in Jakarta, and 50 of them were obtained through offline interviews. The findings revealed a significant relationship between daily income targets, passenger pressure, risk perception (danger level, stochastic evaluation, and safety priority), safety attitudes (pragmatic attitude to rule violations and dissatisfaction with traffic rules), and …

Road Traffic Noise Annoyance And Cardiovascular Disease Risk In Population: A Case Series Study In Kota Bharu, Malaysia, Faridah Naim, Nurin H M Nasir

Kesmas

Noise pollution can cause annoyance, significantly threatening the population’s health and well-being. This study aimed to find an association between road traffic noise exposure and cardiovascular disease (CVD) risk among residents in Kota Bharu, Malaysia. This descriptive study used a case series approach and surveyed 34 residents in selected residential areas near main roads. An adapted questionnaire was distributed to residents using a purposive sampling method. Questions related to sociodemographic information, self-reporting about CVD, and road traffic noise assessment were asked to investigate the underlying risk factors for CVD. The average score of CVD assessment was classified as moderate risk. …

Interim Estimates Of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States., Aaron M. Frutos, Ashley M. Price, Elizabeth Harker, Emily L. Reeves, Haris M. Ahmad, Vel Murugan, Emily T. Martin, Stacey House, Elie A. Saade, Richard K. Zimmerman, Manjusha Gaglani, Karen J. Wernli, Emmanuel B. Walter, Marian G. Michaels, Mary A. Staat, Geoffrey A. Weinberg, Rangaraj Selvarangan, Julie A. Boom, Eileen J. Klein, Natasha B. Halasa, Adit A. Ginde, Kevin W. Gibbs, Yuwei Zhu, Wesley H. Self, Sara Y. Tartof, Nicola P. Klein, Kristin Dascomb, Malini B. Desilva, Zachary A. Weber, Duck-Hye Yang, Sarah W. Ball, Diya Surie, Jennifer Decuir, Fatimah S. Dawood, Heidi L. Moline, Ariana P. Toepfer, Benjamin R. Clopper, Ruth Link-Gelles, Amanda B. Payne, Jessie R. Chung, Brendan Flannery, Nathaniel M. Lewis, Samantha M. Olson, Katherine Adams, Mark W. Tenforde, Shikha Garg, Lisa A. Grohskopf, Carrie Reed, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators

Manuscripts, Articles, Book Chapters and Other Papers

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE …

Integrin Α9Β1 Deficiency Does Not Impact The Development Of Atherosclerosis In Mice, In-Hyuk Jung, Nathan O Stitziel

2020-Current year OA Pubs

Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes cardiovascular disease in humans and mice. However, the receptor mediating the effect of SVEP1 on the development of disease remains unclear. We previously demonstrated that depleting either vascular smooth muscle cell (VSMC)- or myeloid cell-derived integrin α9β1, the first receptor that was identified to interact with SVEP1, did not phenocopy the disease-abrogating effect of depleting SVEP1. Due to its wide expression in tissues and cell types, here we extend this line of investigation to definitively determine if integrin α9β1 …

Quantification Of Surface-Localized And Total Oxytocin Receptor In Myometrial Smooth Muscle Cells, Yingye Fang, Erin L Reinl, Audrey Liu, Trinidi D Prochaska, Manasi Malik, Antonina I Frolova, Sarah K England, Princess I Imoukhuede

2020-Current year OA Pubs

Oxytocin acts through the oxytocin receptor (OXTR) to modulate uterine contractility. We previously identified OXTR genetic variants and showed that, in HEK293T cells, two of the OXTR protein variants localized to the cell surface less than wild-type OXTR. Here, we sought to measure OXTR in the more native human myometrial smooth muscle cell (HMSMC) line on both the cell-surface and across the whole cell, and used CRISPR editing to add an HA tag to the endogenous OXTR gene for anti-HA measurement. Quantitative flow cytometry revealed that these cells possessed 55,000 ± 3200 total OXTRs and 4900 ± 390 cell-surface OXTRs …

Targeting The Cell Cycle, Rrm2 And Nf-Κb For The Treatment Of Breast Cancers, Nahid Sultana, Howard L. Elford, Jesika S. Faridi

Pacific Faculty Work

A hallmark of cancer is the dysregulation of the cell cycle. The CDK4/6 inhibitor palbociclib is approved for treating advanced estrogen-receptor-positive breast cancer, but its success is limited by the development of acquired resistance owing to long-term therapy despite promising clinical outcomes. This situation necessitates the development of potential combination strategies. Here, we report that didox, an inhibitor of ribonucleotide reductase in combination with palbociclib, can overcome palbociclib resistance in ER-positive and ER-negative breast cancers. This study shows didox downregulates an element of the cell cycle checkpoint, cyclin D1, accompanied by a reduction in NF-κB activity in vitro and tumor …

An Independent Analysis Of A Retrospective Cohort Of 30,423 Covid-19 Patients Treated At Ihu-Mediterranean In Marseille, France: Part 1, Efficacy Of Early Treatment With Hydroxychloroquine And Azithromycin, Valere Lounnas, Eleftherios Gkioulekas, Marc Rendell, Alexis Lacout, Xavier Azalbert, Christian Perronne

School of Mathematical & Statistical Sciences Faculty Publications

A cohort of 30,423 Covid-19 patients treated between March 2020 and December 2021 at the IHU-Méditerranée Infection in Marseille (France) was retrospectively analyzed in terms of treatment attempted and disease worsening factors to quantify efficacy with respect to the composite endpoint of transfer to intensive care unit or death, within a couple of months (56 days) from admission. Within limitations of the data and of the models, after adjustment for sampling biases, multivariate logistic regression analyses were performed to determine unadjusted and adjusted odds ratios (ORs) for the subset of patients having received the combined treatment hydroxychloroquine plus azithromycin (HCQ-AZ) …

Efficient Gene Editing For Heart Disease Via Elip-Based Crispr Delivery System, Xing Yin, Romain Harmancey, Brion Frierson, Jean G Wu, Melanie R Moody, David D Mcpherson, Shao-Ling Huang

Faculty, Staff and Student Publications

Liposomes as carriers for CRISPR/Cas9 complexes represent an attractive approach for cardiovascular gene therapy. A critical barrier to this approach remains the efficient delivery of CRISPR-based genetic materials into cardiomyocytes. Echogenic liposomes (ELIP) containing a fluorescein isothiocyanate-labeled decoy oligodeoxynucleotide against nuclear factor kappa B (ELIP-NF-κB-FITC) were used both in vitro on mouse neonatal ventricular myocytes and in vivo on rat hearts to assess gene delivery efficacy with or without ultrasound. In vitro analysis was then repeated with ELIP containing Cas9-sg-IL1RL1 (interleukin 1 receptor-like 1) RNA to determine the efficiency of gene knockdown. ELIP-NF-κB-FITC without ultrasound showed limited gene delivery in …

A Short-Term, Randomized, Controlled, Feasibility Study Of The Effects Of Different Vegetables On The Gut Microbiota And Microrna Expression In Infants, Lynn E. Ferro, Kyle Bittinger, Sabrina P. Trudo, Kaleigh E. Beane, Shawn W. Polson, Jae Kyeom Kim, Jillian C. Trabulsi

General Human Environmental Sciences Faculty Publications and Presentations

The complementary diet influences the gastrointestinal (gut) microbiota composition and, in turn, host health and, potentially, microRNA (miRNA) expression. This study aimed to assess the feasibility of altering the gut microbial communities with short-term food introduction and to determine the effects of different vegetables on the gut microbiota and miRNA expression in infants. A total of 11 infants were randomized to one of the following intervention arms: control, broccoli, or carrot. The control group maintained the milk diet only, while the other groups consumed either a broccoli puree or a carrot puree on days 1–3 along with their milk diet …

The Effect Of Formal Mentorship Programs On Nurse Faculty Retention: An Integrative Review, Lisa Livingston

Doctoral Dissertations and Projects

The nursing shortage has been a hot topic for decades, and literature supports a need to address this issue. Although faculty are critical to educating the nurses of the future, the shortage has impacted nurse faculty numbers as well. Nursing shortages are predicted to increase over the next decade. Evidenced-based interventions are critical to help sustain the nursing workforce. This integrative review highlights the importance of formal mentorship programs for new nurse faculty as a retention strategy for use by administrators of schools of nursing.

What Are The Facilitators And Barriers To Health Literacy For African American Females In Maryland, Ages 18 Or Older, In The Medicaid Versus Commercial Lines Of Business?, Angel Oluwatumininu Benson

Doctoral Dissertations and Projects

This qualitative case study's goal is to identify patterns in the health disparities experienced by African American women and to identify the factors that help and hinder African American females' ability to become health-literate consumers in the commercial and Medicaid markets. This study focuses on African American women's health outcomes and how they relate to health literacy. The purpose of this study is to increase health literacy for the African American population of women, specifically ages 18 and older. Various trends in health literacy are observed among all demographics. An example of this, specifically with African American women, is the …

Improving Self-Efficacy In Flight Nurse Practitioners In Preparation For The Role Of The Law Enforcement Tactical Nurse Practitioner, Gregory S. Wamack

Doctoral Dissertations and Projects

Current evidence demonstrates that the number of prehospital nurse practitioners working in both civilian and military settings is growing. Additional training beyond the formal nurse practitioner curriculum is necessary to increase the self-efficacy, knowledge, and skills of the nurse practitioner for operational battlefield conditions in far-forward austere and tactical settings. Evidence also demonstrates that the Tactical Combat Casualty Care (TC3) course is the national standard for tactical care and training for all health care providers. The purpose of this evidence-based pilot study was to increase the tactical self-efficacy of the United States based nontactical civilian highly trained and skilled flight …

An Independent Analysis Of A Retrospective Cohort Of 30,423 Covid-19 Patients Treated At Ihu-Mediterranean In Marseille, France: Part 2, A Real-Life Assessment Of Covid-19 Vaccination Efficacy, Valere Lounnas, Eleftherios Gkioulekas, Marc Rendell, Alexis Lacout, Xavier Azalbert, Christian Perronne

School of Mathematical & Statistical Sciences Faculty Publications

A cohort of 30,423 Covid-19 patients treated between March 2020 and December 2021 at the IHU-Méditerranée Infection in Marseille (France) was retrospectively analyzed in terms of treatment attempted and disease worsening factors to quantify vaccination efficacy with respect to the composite endpoint of transfer to intensive care unit or death, within a couple of months (56 days) from admission. Within limitations of the data and of the models, after adequate adjustment for sampling biases, multivariate logistic regression analyses were performed to determine unadjusted and adjusted odds ratios (ORs) for the subset of patients admitted after the Covid-19 vaccination program was …

Integrating Primary Care, Shared Decision Making, And Community Engagement To Facilitate Equitable Access To Multi-Cancer Early Detection Clinical Trials, Cheryl L. Thompson, Adam H. Buchanan, Ronald E. Myers, David S. Weinberg

Department of Medical Oncology Faculty Papers

Effective implementation of cancer screening programs can reduce disease-specific incidence and mortality. Screening is currently recommended for breast, cervical, colorectal and lung cancer. However, initial and repeat adherence to screening tests in accordance with current guidelines is sub-optimal, with the lowest rates observed in historically underserved groups. If used in concert with recommended cancer screening tests, new biospecimen-based multi-cancer early detection (MCED) tests could help to identify more cancers that may be amendable to effective treatment. Clinical trials designed to assess the safety and efficacy of MCED tests to assess their potential for reducing cancer mortality are needed and many …

Indigenous Approaches To Health Assessment: A Scoping Review Protocol, Nabina Sharma, Jennifer D Walker, Elizabeth Wenghofer, Taima Moeke-Pickering, Jeannette Lindenbach

Faculty, Staff and Student Publications

BACKGROUND: Health assessment tools developed using mainstream or Western concepts have been widely used in clinical practice worldwide. However, even culturally adapted or culturally based tools may not be relevant in other social contexts if they are grounded in Western beliefs and perspectives. The application of mainstream assessment tools, when used in Indigenous populations, can lead to the inappropriate application of normative data and inaccurate or biased diagnosis of conditions as Indigenous concepts of health differ from Western biomedical concepts of health. Thus, considering the need for culturally meaningful, sensitive, safe, and unbiased health assessment approaches and instruments over recent …

Mechanisms Of Sleep Disturbances In Long-Term Cancer Survivors: A Childhood Cancer Survivor Study Report, Lauren C Daniel, Huiqi Wang, Tara M Brinkman, Kathy Ruble, Eric S Zhou, Oxana Palesh, Robyn Stremler, Rebecca Howell, Daniel A Mulrooney, Valerie M Crabtree, Sogol Mostoufi-Moab, Kevin Oeffinger, Joseph Neglia, Yutaka Yasui, Gregory T Armstrong, Kevin Krull

Faculty, Staff and Student Publications

Background: Sleep problems following childhood cancer treatment may persist into adulthood, exacerbating cancer-related late effects and putting survivors at risk for poor physical and psychosocial functioning. This study examines sleep in long-term survivors and their siblings to identify risk factors and disease correlates.

Methods: Childhood cancer survivors (≥5 years from diagnosis; n = 12 340; 51.5% female; mean [SD] age = 39.4 [9.6] years) and siblings (n = 2395; 57.1% female; age = 44.6 [10.5] years) participating in the Childhood Cancer Survivor Study completed the Pittsburgh Sleep Quality Index (PSQI). Multivariable Poisson-error generalized estimating equation compared prevalence of binary sleep …

The Emerging Importance Of Skull-Brain Interactions In Traumatic Brain Injury, Peixi Zhao, Rui Jin, Bin Zhao, Le Han, Wenjuan Chen, Nina Hao, Yi Cui, Ankit Madan, Joy Awosika, Shane Lloyd, Yili Zhang

Faculty, Staff and Student Publications

Background and Objective

Immune checkpoint inhibitors (ICIs) have been widely applied and studied in the treatment of gastrointestinal (GI) cancers, and have achieved good results. However, in clinical practice, it has been observed that only some patients respond well to ICIs, and some patients may experience various degrees of adverse reactions during the treatment. Timely evaluation of the potential therapeutic effects and adverse reactions of ICIs for patients has important clinical significance. This review aimed to summarize recent progress regarding efficacy-associated biomarkers for ICIs in GI cancer.

Methods

The literature on ICI treatment in GI cancers was searched in the …

The Global Landscape Of Immune-Derived Lncrna Signature In Colorectal Cancer, Mengying Zhang, Yifei Wu, Jingyi Mou, Yang Yao, Pengbo Wen, Xin Liu, Shipeng Shang, Xingxing Kang, Jiaqi Tian, Yan Liu, Enhui Lv, Liang Wang

Research outputs 2022 to 2026

Background: Colorectal cancer (CRC) is a highly heterogeneous cancer. This heterogeneity has an impact on the efficacy of immunotherapy. Long noncoding RNAs (lncRNAs) have been found to play regulatory functions in cancer immunity. However, the global landscape of immune-derived lncRNA signatures has not yet been explored in colorectal cancer. Methods: In this study, we applied DESeq2 to identify differentially expressed lncRNAs in colon cancer. Next, we performed an integrative analysis to globally identify immune-driven lncRNA markers in CRC, including immune-associated pathways, tumor immunogenomic features, tumor-infiltrating immune cells, immune checkpoints, microsatellite instability (MSI) and tumor mutation burden (TMB). Results: We also …

A Leadership Training Program Improves Nurse Manager Retention, Lisa A. Longley

Doctoral Dissertations and Projects

The need to retain nursing managers is at an all-time high. The turnover rate for a local xxxxxxxxxx (removed to protect privacy) healthcare system is 14% post pandemic compared to 8% pre-pandemic. The nursing management team reported a need for nursing specific management orientation because the current training included all organizational supervisors and covered general concepts, failing to meet the complex needs of frontline nursing managers. Literature confirms that organizations that provide nursing management training develop role competency have higher satisfaction and lower turnover rates. An organizational-specific needs assessment designed within the American Organization of Nursing Leadership competency framework was …

The Combined Immunohistochemical Expression Of Ambra1 And Sqstm1 Identifies Patients With Poorly Differentiated Cutaneous Squamous Cell Carcinoma At Risk Of Metastasis: A Proof Of Concept Study, Michael H. Alexander, William J. Cousins, Tom Ewen, Andrew P. South, Penny Lovat, Niki Stefanos

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) incidence continues to increase globally with, as of yet, an unmet need for reliable prognostic biomarkers to identify patients at increased risk of metastasis. The aim of the present study was to test the prognostic potential of the combined immunohistochemical expression of the autophagy regulatory biomarkers, AMBRA1 and SQSTM1, to identify high-risk patient subsets.

METHODS: A retrospective cohort of 68 formalin-fixed paraffin-embedded primary cSCCs with known 5-year metastatic outcomes were subjected to automated immunohistochemical staining for AMBRA1 and SQSTM1. Digital images of stained slides were annotated to define four regions of interest: the normal …

Pan-Cancer Proteogenomics Characterization Of Tumor Immunity, Francesca Petralia, Weiping Ma, Tomer M Yaron, Francesca Pia Caruso, Nicole Tignor, Joshua M Wang, Daniel Charytonowicz, Jared L Johnson, Emily M Huntsman, Giacomo B Marino, Anna Calinawan, John Erol Evangelista, Myvizhi Esai Selvan, Shrabanti Chowdhury, Dmitry Rykunov, Azra Krek, Xiaoyu Song, Berk Turhan, Karen E Christianson, David A Lewis, Eden Z Deng, Daniel J B Clarke, Jeffrey R Whiteaker, Jacob J Kennedy, Lei Zhao, Rossana Lazcano Segura, Harsh Batra, Maria Gabriela Raso, Edwin Roger Parra, Rama Soundararajan, Ximing Tang, Yize Li, Xinpei Yi, Shankha Satpathy, Ying Wang, Maciej Wiznerowicz, Tania J González-Robles, Antonio Iavarone, Sara J C Gosline, Boris Reva, Ana I Robles, Alexey I Nesvizhskii, D R Mani, Michael A Gillette, Robert J Klein, Marcin Cieslik, Bing Zhang, Amanda G Paulovich, Robert Sebra, Zeynep H Gümüş, Galen Hostetter, David Fenyö, Gilbert S Omenn, Lewis C Cantley, Avi Ma'ayan, Alexander J Lazar, Michele Ceccarelli, Pei Wang, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Student Publications

Despite the successes of immunotherapy in cancer treatment over recent decades, less than <10%-20% cancer cases have demonstrated durable responses from immune checkpoint blockade. To enhance the efficacy of immunotherapies, combination therapies suppressing multiple immune evasion mechanisms are increasingly contemplated. To better understand immune cell surveillance and diverse immune evasion responses in tumor tissues, we comprehensively characterized the immune landscape of more than 1,000 tumors across ten different cancers using CPTAC pan-cancer proteogenomic data. We identified seven distinct immune subtypes based on integrative learning of cell type compositions and pathway activities. We then thoroughly categorized unique genomic, epigenetic, transcriptomic, and proteomic changes associated with each subtype. Further leveraging the deep phosphoproteomic data, we studied kinase activities in different immune subtypes, which revealed potential subtype-specific therapeutic targets. Insights from this work will facilitate the development of future immunotherapy strategies and enhance precision targeting with existing agents.

The Card8 Inflammasome Dictates Hiv/Siv Pathogenesis And Disease Progression, Qiankun Wang, Kolin M Clark, Ritudhwaj Tiwari, Nagarajan Raju, Gregory K Tharp, Jeffrey Rogers, R Alan Harris, Muthuswamy Raveendran, Steven E Bosinger, Tricia H Burdo, Guido Silvestri, Liang Shan

Faculty, Staff and Students Publications

While CD4+ T-cell depletion is key to disease progression in people living with HIV and SIV-infected macaques, the mechanisms underlying this depletion remain incompletely understood, with most cell death involving uninfected cells. In contrast, SIV infection of “natural” hosts such as sooty mangabeys do not cause CD4+ depletion and AIDS despite high-level viremia. Here, we report that the CARD8 inflammasome is activated immediately after HIV entry by the viral protease encapsulated in incoming virions. Sensing of HIV protease activity by CARD8 leads to rapid pyroptosis of quiescent cells without productive infection, while T-cell activation abolishes CARD8 function and increases permissiveness …