Digital Commons Network^™

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 …

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) …

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 …

Effects Of Maternal Anthropometry On Infant Anthropometry: A Cross-Sectional Study At Public Hospital X In Ternate, Indonesia, Yuni Nurwati, Hardinsyah Hardinsyah, Sri Anna Marliyati, Budi Iman Santoso, Dewi Anggraini

Kesmas

Infant anthropometry is an indicator of neonatal survival. This study aimed to determine the effects of maternal anthropometry on estimating infant anthropom­etry. This cross-sectional study on 173 pregnant women at Public Hospital X in Ternate, Indonesia, was conducted from August 2018 to March 2023. The el­igible criteria were pregnant women aged ≥18 years, single pregnancy, and antenatal care (ANC) visits to the same hospital. The variables used included ma­ternal anthropometric measurements (body weight, body height, third-trimester weight (TTW)), gestational weight gain (GWG), education, age, ANC visits, and gestational age at delivery (GAD). A logistic regression model was employed to estimate …

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 …

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

Faculty, Staff and Students Publications

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 …

Impact And Prevalence Of Comorbidities And Complications On The Severity Of Covid-19 In Association With Age, Gender, Obesity, And Pre-Existing Smoking: A Meta-Analysis, Soulandi Djorwé, Amale Bousfiha, Néhémie Nzoyikorera, Joseph Nyandwi, Bellamine Kawthar, Abderrahim Malki

BioMedicine

Background: COVID-19 patients usually present multiple comorbidities and complications associated with severe forms of SARS-CoV-2 infection. This study aimed to assess the risk factors and prevalence of comorbidities and complications contributing to the severity of COVID-19.

Methods: This meta-analysis was performed according to PRISMA guidelines. We searched various databases, including PubMed, Google Scholar, and Scopus (between 2020 and 2023), for eligible studies for this meta-analysis.

Results: Thirty-three studies were eligible, including 85812 patients, of which 36% (30634/85812) had severe disease, whereas 64% (55178/85812) had non-severe disease. Severe cases were potentially correlated with the following factors: gender (male) (odd ratio (OR) …

Paired Single-B-Cell Transcriptomics And Receptor Sequencing Reveal Activation States And Clonal Signatures That Characterize B Cells In Acute Myeloid Leukemia, Shengnan Guo, Gopi S Mohan, Bofei Wang, Tianhao Li, Naval Daver, Yuting Zhao, Patrick K Reville, Dapeng Hao, Hussein A Abbas

Faculty, Staff and Student Publications

BACKGROUND: Acute myeloid leukemia (AML) is associated with a dismal prognosis. Immune checkpoint blockade (ICB) to induce antitumor activity in AML patients has yielded mixed results. Despite the pivotal role of B cells in antitumor immunity, a comprehensive assessment of B lymphocytes within AML's immunological microenvironment along with their interaction with ICB remains rather constrained.

METHODS: We performed an extensive analysis that involved paired single-cell RNA and B-cell receptor (BCR) sequencing on 52 bone marrow aspirate samples. These samples included 6 from healthy bone marrow donors (normal), 24 from newly diagnosed AML patients (NewlyDx), and 22 from 8 relapsed or …

Scurvy: A Rare Disease Or A Rare Diagnosis?, David F. Gaieski

Department of Emergency Medicine Faculty Papers

Introduction:

Scurvy, the disease state caused by ascorbic acid deficiency, was once an extremely common disease but is now thought to be a rare disease in postmodern societies. Physicians are not trained to consider scurvy as a possible diagnosis in patients at risk; rather, it is considered a rare diagnosis to add to a differential for completeness’s sake.

Methods:

We sought to describe the scorbutic patients seen by one physician during a busy academic emergency medicine career. Case series of patients seen by one physician between 1993 and 2023 at five academic teaching hospitals with Emergency Departments (EDs) in the …

Bactericidal Efficacy Of The Combination Of Maresin-Like Proresolving Mediators And Carbenicillin Action On Biofilm-Forming Burn Trauma Infection-Related Bacteria, Anbu Mozhi Thamizhchelvan, Abdul Razak Masoud, Shanchun Su, Yan Lu, Hongying Peng, Yuichi Kobayashi, Yu Wang, Nathan K. Archer, Song Hong

School of Medicine Faculty Publications

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage, and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading …

Integrative Genomic Insights Into Coral Resilience: Adaptive And Acclimatory Responses To Seasonal Environmental Shifts, Tasnim Ghanim

Theses and Dissertations

Coral reefs, critical to marine biodiversity and coastal protection, face escalating threats from climate change-related phenomena such as ocean warming. This warming is leading to widespread thermal stress that contributes to coral bleaching and infectious disease in corals, leading to the disruption of marine ecosystems and the economies that depend on them. Focusing on the brain coral Platygyra daedalea, known for its thermal resilience in the Persian Arabian Gulf—a region that exemplifies the extreme stressors of climate change—our study aims to dissect the genetic, transcriptomic, and microbiological underpinnings of coral survival in high-temperature environments predicted for the end of …

Current And Emerging Antiviral Agents In The Prevention And Treatment Of Cytomegalovirus In Pediatric Transplant Recipients, Kristen G Valencia Deray, Lara A Danziger-Isakov, Kevin J Downes

Faculty, Staff and Students Publications

Despite current prophylaxis regimens, cytomegalovirus (CMV) is common in hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT) and remains a significant cause of morbidity and mortality. Newer antiviral medications are reshaping the landscape for prevention and treatment of CMV DNAemia, infection, and disease. Letermovir is approved for CMV prevention in adult HCT patients and is attractive due to the absence of marrow suppression seen with ganciclovir/valganciclovir. Letermovir should not be routinely used for CMV treatment due to its low threshold for resistance. Maribavir is approved for the treatment of refractory or resistant CMV disease in HCT and SOT recipients …

Gamma Delta T Cells In Acute Myeloid Leukemia: Biology And Emerging Therapeutic Strategies, Adishwar Rao, Akriti Agrawal, Gautam Borthakur, Venkata Lokesh Battula, Abhishek Maiti

Faculty, Staff and Student Publications

γδ T cells play an important role in disease control in acute myeloid leukemia (AML) and have become an emerging area of therapeutic interest. These cells represent a minor population of T lymphocytes with intrinsic abilities to recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface. AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, respectively, leading to γδ T cell-mediated cytotoxicity. Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of …

Returning To School After A Pandemic: K-12 School Mental Health Practitioners’ Perspectives Returning To School In Regard To Mindset, Behavior, Performance, And Social Connections, Viridiana Benitez Esparza

Dissertations

Purpose: The purpose of this phenomenological study was to determine K-12 school mental health practitioners’ perceptions of their experiences working with students following the 2-year educational/social/emotional trauma of the COVID-19 pandemic with regard to the mental health practitioners’ mindset, behavior, performance, and social connections. Methodology: The researcher conducted a phenomenological study examining particular experiences of participants to understand their perspective during a phenomenon (McMillan & Schumacher, 2006). This qualitative study interviewed 12 school mental health practitioners who served in K-12 public schools after the pandemic in Los Angeles County, California. Semi-structured interview questions were used for data collection and aligned …

Caregivers' Attachment Relationships With Infants And Toddlers During The Covid-19 Pandemic, Rebecca Ellen Roth

Walden Dissertations and Doctoral Studies

Health and safety protocols related to the COVID-19 pandemic and its variants continue to influence practices in infant–toddler programs one western state in the United States; caregivers in the state are concerned about attachment relationships with infants and toddlers. The purpose of this basic qualitative study was to explore caregiver perceptions of attachment relationships related to the COVID-19 pandemic and its variants and the influence of health and safety protocols on caregiver practices. The conceptual framework combined attachment and biobehavioral theories. Data from interviews with four infant and six toddler caregivers were recorded, transcribed, and analyzed by searching for patterns …

The Future Of Targeted Therapy For Leiomyosarcoma, Ryan A Denu, Amanda M Dann, Emily Z Keung, Michael S Nakazawa, Elise F Nassif Haddad

Faculty, Staff and Student Publications

Leiomyosarcoma (LMS) is an aggressive subtype of soft tissue sarcoma that arises from smooth muscle cells, most commonly in the uterus and retroperitoneum. LMS is a heterogeneous disease with diverse clinical and molecular characteristics that have yet to be fully understood. Molecular profiling has uncovered possible targets amenable to treatment, though this has yet to translate into approved targeted therapies in LMS. This review will explore historic and recent findings from molecular profiling, highlight promising avenues of current investigation, and suggest possible future strategies to move toward the goal of molecularly matched treatment of LMS. We focus on targeting the …

Evidence Review And Considerations For Use Of First Line Genome Sequencing To Diagnose Rare Genetic Disorders, Kristen M Wigby, Deanna Brockman, Gregory Costain, Caitlin Hale, Stacie L Taylor, John Belmont, David Bick, David Dimmock, Susan Fernbach, John Greally, Vaidehi Jobanputra, Shashikant Kulkarni, Elizabeth Spiteri, Ryan J Taft

Center for Medical Ethics and Health Policy Staff Publications

Early use of genome sequencing (GS) in the diagnostic odyssey can reduce suffering and improve care, but questions remain about which patient populations are most amenable to GS as a first-line diagnostic test. To address this, the Medical Genome Initiative conducted a literature review to identify appropriate clinical indications for GS. Studies published from January 2011 to August 2022 that reported on the diagnostic yield (DY) or clinical utility of GS were included. An exploratory meta-analysis using a random effects model evaluated DY based on cohort size and diagnosed cases per cohort. Seventy-one studies met inclusion criteria, comprising over 13,000 …

No. 16: Evolving Food Security Challenges Facing Internal Migrants During The Covid-19 Pandemic In Chinese Cities, Zhenzhong Si, Taiyang Zhong

Migration and Food Security (MiFOOD) Network

The COVID-19 pandemic has significantly exacerbated the economic, social and political vulnerabilities of internal and international migrants and increased their food insecurity in several cities of the Global South. So far, very little attention has been paid to the dynamics of internal migrants’ food security in urban China since the emergence of the pandemic. Based on the results of an online survey conducted in the cities of Wuhan and Nanjing in early 2020 and a review of secondary materials, this paper identifies the major phases of China’s COVID-19 containment policies and evaluates their effects on the food security of internal …

Contribution Of Hfq To Gene Regulation And Virulence In Histophilus Somni, Dianjun Cao, Bindu Subhadra, Yue-Jia Lee, Merrilee Thoresen, Santiago Cornejo, Alicia Oliver, Amelia Woolums, Thomas J. Inzana

Faculty Publications - Biological Sciences

Histophilus somni is one of the predominant bacterial pathogens responsible for bovine respiratory and systemic diseases in cattle. Despite the identification of numerous H. somni virulence factors, little is known about the regulation of such factors. The post-transcriptional regulatory protein Hfq may play a crucial role in regulation of components that affect bacterial virulence. The contribution of Hfq to H. somni phenotype and virulence was investigated following creation of an hfq deletion mutant of H. somni strain 2336 (designated H. somni 2336Δhfq). A comparative analysis of the mutant to the wild-type strain was carried out by examining protein and carbohydrate …

Sustainability Of Simplified Sewer Systems: A Case Study Of Vingunguti Urban Settlement, Dar Es Salaam Region In Tanzania, Neema Kijazi

Tanzania Journal of Engineering and Technology (TJET)

The universal access to safely managed sanitation remains one of the challenges to achieving the UN SDG target 6.2 in unplanned urban settlements including the Vingunguti area in Dar es Salaam City which is high-density populated. In an attempt to address this challenge, a simplified sewer system was piloted as an option for achieving safely managed sanitation in this particular area. The objective of this study was to assess the sustainability of the piloted simplified sewer system for its potentiality to up-scale and replication in areas with similar sanitation challenges in the country. Methodology involved collection of data on performance …

A Two-Stage Based Life Cycle And Principal Component Analysis For Decision Support Of Potential Municipal Solid Wastes Management Scenarios, Case Study Dar Es Salaam, Tanzania, Edwin Richard Ndibalema Dr

Tanzania Journal of Engineering and Technology (TJET)

In most of the urban areas of Tanzania, poor and inadequate solid waste management is a growing environmental and public health concern. Despite an array of solid waste management options, choosing an appropriate one remains a challenge. This study applied a novel two-stage-based approach to assess the environmental impacts and sustainability performance of the 27 scenarios for municipal solid wastes (MSW) management of Dar es Salaam City, Tanzania. In the first stage, the study utilized a life cycle analysis (LCA) to quantify the environmental impacts of MSW scenarios. In the second stage, the study used the principal component analysis (PCA) …

Tau And Aβ42 In Lavage Fluid Of Pneumonia Patients Are Associated With End-Organ Dysfunction: A Prospective Exploratory Study, Phoibe Renema, Jean-Francois Pittet, Angela P. Brandon, Sixto M. Leal Jr, Steven Gu, Grace Promer, Andrew Hackney, Phillip Braswell, Andrew Pickering, Grace Rafield, Sarah Voth, Ron Balczon, Mike T. Lin, K. Adam Morrow, Jessica Bell, Jonathon P. Audia, Diego Alvarez, Troy Stevens, Brant M. Wagener

University Faculty and Staff Publications

Bacterial pneumonia and sepsis are both common causes of end-organ dysfunction, especially in immunocompromised and critically ill patients. Pre-clinical data demonstrate that bacterial pneumonia and sepsis elicit the production of cytotoxic tau and amyloids from pulmonary endothelial cells, which cause lung and brain injury in naïve animal subjects, independent of the primary infection. The contribution of infection-elicited cytotoxic tau and amyloids to end-organ dysfunction has not been examined in the clinical setting. We hypothesized that cytotoxic tau and amyloids are present in the bronchoalveolar lavage fluid of critically ill patients with bacterial pneumonia and that these tau/amyloids are associated with …

Isothiocyanates Potentiate Tazemetostat-Induced Apoptosis By Modulating The Expression Of Apoptotic Genes, Members Of Polycomb Repressive Complex 2, And Levels Of Tri-Methylating Lysine 27 At Histone 3 In Human Malignant Melanoma Cells, Ioannis Anestopoulos, Ioannis Paraskevaidis, Sotiris Kyriakou, Lambrini E. Giova, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Aglaia Pappa, Mihalis L. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

In this study, we utilized an in vitro model consisting of human malignant melanoma as well as non-tumorigenic immortalized keratinocyte cells with the aim of characterizing the therapeutic effectiveness of the clinical epigenetic drug Tazemetostat alone or in combination with various isothiocyanates. In doing so, we assessed markers of cell viability, apoptotic induction, and expression levels of key proteins capable of mediating the therapeutic response. Our data indicated, for the first time, that Tazemetostat caused a significant decrease in viability levels of malignant melanoma cells in a dose- and time-dependent manner via the induction of apoptosis, while non-malignant keratinocytes were …

Notes From The Field: Reemergence Of Mycoplasma Pneumoniae Infections In Children And Adolescents After The Covid-19 Pandemic, United States, 2018-2024., Chris Edens, Benjamin R. Clopper, Jourdan Devies, Alvaro Benitez, Erin R. Mckeever, Dylan Johns, Bernard Wolff, Rangaraj Selvarangan, Jennifer E. Schuster, Geoffrey A. Weinberg, Peter G. Szilagyi, Fatimah S. Dawood, Lakshmi Radhakrishnan, Christina Quigley, Leila C. Sahni, Natasha Halasa, Laura S. Stewart, Meredith L. Mcmorrow, Brett Whitaker, Danielle M. Zerr, Vasanthi Avadhanula, John V. Williams, Marian G. Michaels, Aaron Kite-Powell, Janet A. Englund, Mary Allen Staat, Kathleen Hartnett, Heidi L. Moline, Adam L. Cohen, Maureen Diaz

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Tailoring T Fh Profiles Enhances Antibody Persistence To A Clade C Hiv-1 Vaccine In Rhesus Macaques, Anil Verma, Chase E. Hawes, Sonny R. Elizaldi, Justin C. Smith, Dhivyaa Rajasundaram, Gabriel Kristian Pedersen, Xiaoying Shen, La Tonya D. Williams, Georgia D. Tomaras, Pamela A. Kozlowski, Rama R. Amara, Smita S. Iyer

School of Medicine Faculty Publications

CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the Tfh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a Tfh1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques. Using a DNA-prime encoding gp160 antigen and Tfh polarizing cytokines …

Immunotherapy Resistance In Solid Tumors: Mechanisms And Potential Solutions, Daniel Lefler, Steven Manobianco, Babar Bashir

Kimmel Cancer Center Faculty Papers

While the emergence of immunotherapies has fundamentally altered the management of solid tumors, cancers exploit many complex biological mechanisms that result in resistance to these agents. These encompass a broad range of cellular activities - from modification of traditional paradigms of immunity via antigen presentation and immunoregulation to metabolic modifications and manipulation of the tumor microenvironment. Intervening on these intricate processes may provide clinical benefit in patients with solid tumors by overcoming resistance to immunotherapies, which is why it has become an area of tremendous research interest with practice-changing implications. This review details the major ways cancers avoid both natural …

Immunostimulatory Short Non-Coding Rnas In The Circulation Of Patients With Tuberculosis Infection, Justin Gumas, Takuya Kawamura, Megumi Shigematsu, Yohei Kirino

Computational Medicine Center Faculty Papers

Mycobacterium tuberculosis (Mtb) infection is among the world's deadliest infectious diseases. Developing effective treatments and biomarkers for tuberculosis requires a deeper understanding of its pathobiology and host responses. Here, we report a comprehensive characterization of circulating short non-coding RNAs (sncRNAs) in plasma samples from Mtb-infected patients. We achieved this by pre-treating plasma RNAs with T4 polynucleotide kinase to convert all RNA ends to those compatible with sncRNA sequencing. We discovered a global and drastic upregulation of plasma sncRNAs in Mtb-infected patients, with tRNA-derived sncRNAs representing the most dramatically elevated class. Most of these tRNA-derived sncRNAs originated from a limited subset …

Application Of Dna Barcodes In The Genetic Diversity Of Hard Ticks (Acari: Ixodidae) In Kazakhstan, Ziwei Zheng, Weixin Zeng, Suwen Wang, Wenbo Tan, Xiaobo Lu, Kenesbay Kairullayev, Ligu Mi, Wurelihazi Hazihan, Gang Liu, Meihua Yang, Yuanzhi Wang

Harold W. Manter Laboratory of Parasitology: Library Materials

Forty-five tick species have been recorded in Kazakhstan. However, their genetic diversity and evolutionary relationships, particularly when compared to ticks in neighbouring countries, remain unclear. In the present study, 148 mitochondrial cytochrome c oxidase subunit I (COI) sequence data from our laboratory and NCBI (National Center for Biotechnology Information; https://www.ncbi.nlm.nih.gov/) data were used to address this knowledge gap. Phylogenetic analyses showed that i) Hyalomma anatolicum anatolicum (Koch, 1844) ticks from Jambyl Oblast (southeastern Kazakhstan) and Gansu Province (northwestern China) constituted a newly deviated clade; and ii) Dermacentor reticulatus (Fabricius, 1974) ticks from South Kazakhstan Oblast were closer …

Factors Associated With Reduced Depression And Suicide Risk Among Mäori High School Students In New Zealand, Terryann C. Clark

Dissertations

Mäori adolescents, indigenous to New Zealand (NZ), have among the highest rates of depression and suicide in the industrialized world. Fortunately, resilience research demonstrates that promotive factors, such as family and school connections, can markedly reduce mental health problems for vulnerable youth populations. However, to date, this research has never focused on risk and promotive mechanisms related to mental health outcomes for Mäori youth. Such knowledge is a prerequisite for addressing the persistent mental health inequities faced by Mäori young people.

Exploring The Antibacterial Potential And Underlying Mechanisms Of Prunella Vulgaris L On Methicillin-Resistant Staphylococcus Aureus, Ziyin Li, Qiqi He, Feifei Xu, Xinxin Yin, Zhuofan Guan, Jia Song, Zhini He, Xingfen Yang, Chen Situ

Faculty, Staff and Student Publications

Prunella vulgaris L. (PV) is a widely distributed plant species, known for its versatile applications in both traditional and contemporary medicine, as well as in functional food development. Despite its broad-spectrum antimicrobial utility, the specific mechanism of antibacterial action remains elusive. To fill this knowledge gap, the present study investigated the antibacterial properties of PV extracts against methicillin-resistant Staphylococcus aureus (MRSA) and assessed their mechanistic impact on bacterial cells and cellular functions. The aqueous extract of PV demonstrated greater anti-MRSA activity compared to the ethanolic and methanolic extracts. UPLC-ESI-MS/MS tentatively identified 28 phytochemical components in the aqueous extract of PV. …