Digital Commons Network^™

Impact Of Select Actionable Genomic Alterations On Efficacy Of Neoadjuvant Immunotherapy In Resectable Non-Small Cell Lung Cancer, Nicolas Zhou, Cheuk H Leung, William N William, Annikka Weissferdt, Apar Pataer, Myrna C B Godoy, Brett W Carter, Frank V Fossella, Anne S Tsao, George R Blumenschein, Xiuning Le, Jianjun Zhang, Ferdinandos Skoulidis, Jonathan M Kurie, Mehmet Altan, Charles Lu, Bonnie S Glisson, Lauren A Byers, Yasir Y Elamin, Reza J Mehran, David C Rice, Garrett L Walsh, Wayne L Hofstetter, Jack A Roth, Hai T Tran, Jia Wu, Luisa M Solis Soto, Humam Kadara, Stephen G Swisher, Ara A Vaporciyan, Don L Gibbons, Heather Y Lin, J Jack Lee, John V Heymach, Marcelo V Negrao, Boris Sepesi, Tina Cascone

Faculty, Staff and Student Publications

Background: Neoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy of neoadjuvant ICIs remains unclear. We report the influence of AGAs on treatment failure (TF) in patients with resectable NSCLC treated with neoadjuvant ICIs.

Methods: Tumor molecular profiles were obtained from patients with stage I-IIIA resectable NSCLC (American Joint Committee on Cancer seventh edition) treated with either neoadjuvant nivolumab (N, n=23) or nivolumab+ipilimumab (NI, n=21) followed by surgery in a previously reported phase-2 randomized study (NCT03158129). TF …

Preparation And Efficacy Evaluation Of Chicken Egg Yolk Sourced Igy Against The Venoms Of Cobra, Krait, Russell’S Viper, And Saw-Scaled Viper, Gayathri G

Theses and Dissertations

Envenomation resulting from snakebites is widely recognized as an alarming health risk in tropical and sub-tropical areas. The big four snakes including Naja naja, Bungarus caeruleus, Daboia russelli, Echis carinatus are responsible for most of the envenomation in India. The current therapy for snake envenomation is immunoglobulins, produced from serum or plasma of horses or sheep. To overcome the drawbacks of current antivenom, chicken egg yolk (IgY) antibodies have recently emerged as one of the most promising research avenues.

In this study, the efficacy of chicken egg yolk sourced antisnake venom (ASV) IgY against the big four venoms was evaluated …

Perioperative Chemoimmunotherapy Induces Strong Immune Responses And Long-Term Survival In Patients With Hla Class I-Deficient Non-Small Cell Lung Cancer, Marta Molina-Alejandre, Francisco Perea, Virginia Calvo, Cristina Martinez-Toledo, Ernest Nadal, Belén Sierra-Rodero, Marta Casarrubios, Joaquín Casal-Rubio, Alex Martinez-Martí, Amelia Insa, Bartomeu Massuti, Santiago Viteri, Isidoro Barneto Aranda, Delvys Rodriguez-Abreu, Javier De Castro, Joaquín Mosquera Martínez, Manuel Cobo, Ignacio I Wistuba, Edwin R Parra, Javier Martín-López, Diego Megías, Rafael Muñoz-Viana, Federico Garrido, Natalia Aptsiauri, Francisco Ruiz-Cabello, Mariano Provencio, Alberto Cruz-Bermúdez

Faculty, Staff and Student Publications

BACKGROUND: Loss of human leukocyte antigen (HLA) class I expression and loss of heterozygosity (LOH) are common events implicated in the primary resistance of non-small cell lung cancer (NSCLC) to immunotherapy. However, there is no data on perioperative chemoimmunotherapy (ChIO) efficacy or response mechanisms in the context of HLA class I defects.

METHODS: Baseline HLA class I tumor status (HLA-deficient (HLA-DEF) or HLA-proficient (HLA-PRO)) was determined by DNA LOH combined with immunohistochemistry for protein levels in tissue of 24 patients with NSCLC treated with perioperative nivolumab plus chemotherapy from NADIM trial (NCT03081689). We integrated HLA tumor status with molecular data …

Electric Potential Energy Optimized 3d Radial Sampling Trajectories For Mri, Christopher Huynh, Datta Singh Goolaub, Christopher K Macgowan

Faculty, Staff and Students Publications

A novel method for creating “golden” 3D center-out radial MRI sampling trajectories was developed and analyzed. This method, called ELECTRO (ELECTRic potential energy Optimized), uses repulsive forces to minimize electric potential energy. An objective function , the electric potential energies of all subsets of consecutive readouts in a 3D radial trajectory, and its reduced form were minimized using a multi-stage optimization strategy. A metric called normalized mean nearest neighbor angular distance (NMNA) was proposed for describing distributions of points on a sphere. ELECTRO and other relevant golden trajectories were compared in silico using NMNA and point spread function analysis. Consecutive …

Immune System, Your Very Favorite, Children's Health

English

single-page

Immune System (Spanish), Your Very Favorite, Children's Health

Spanish

single-page, Spanish

Low Prevalence Of Soil Transmitted Helminth Infection In Ugandan Children Hospitalized With Severe Malaria, Drew Capone, Nuzrath Jahan, Ruth Namazzi, Robert Opoka, Chandy John

Paediatrics and Child Health, East Africa

Co-infection by intestinal helminths and Plasmodium spp. may be common in endemic communities. Several studies have identified a relationship between helminth infection, Plasmodium spp. infection and malaria severity. However, the relationship is not well defined, and results are inconclusive. We analyzed stool samples from a cohort of children with severe malaria enrolled in two hospitals in Uganda from 2014-2017 and asymptomatic community children from the same household or neighborhood and enrolled at the same time, all 6 months to 48 months of age. We investigated if intestinal helminth infection modified risk of severe malaria. We extracted nucleic acids from stool …

Health Matters! Coloring And Activity Book (80-Pages), Your Very Favorite, Children's Health, Lorraine Sheldon, May Bressler

English

Health Matters! is a English-language health literacy resource designed for pediatric patients and their families. Written at an approximately 6th-grade reading level, it supports patient education through engaging coloring and activity pages.

The content covers a wide range of health and wellness topics, including body systems, nutrition, mental wellness, patient safety, and social-emotional skills such as building friendships and navigating conversations when returning to school. Developed for use in both hospital settings and the broader community, the resource promotes learning through interactive, age-appropriate activities.

This printable PDF version contains the complete collection of activities and comprises 80 pages. The resource …

La Salud Es Importante: Libro De Actividades (80-Pages), Your Very Favorite, Children's Health, Lorraine Sheldon, May Bressler

Spanish

Health Matters! is a Spanish-language health literacy resource designed for pediatric patients and their families. Written at an approximately 6th-grade reading level, it supports patient education through engaging coloring and activity pages.

The content covers a wide range of health and wellness topics, including body systems, nutrition, mental wellness, patient safety, and social-emotional skills such as building friendships and navigating conversations when returning to school. Developed for use in both hospital settings and the broader community, the resource promotes learning through interactive, age-appropriate activities.

This printable PDF version contains the complete collection of activities and comprises 80 pages. The resource …

Insect Pests And Their Management In Oats, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

Field pests

Damage from invertebrate pests is generally not a major factor for oat crops, however there is a zero tolerance to live pests in export hay.

Significant damage can occur if pest populations build up. Planning rotations to minimise pest carryover, timely sowing, adequate crop nutrition, and good control of weed and root diseases will assist in reducing the likelihood of crop damage by insect pests. Check crops regularly throughout their growth for field insects.

• Control redlegged earth mite and lucerne flea during the seedling stage if necessary.

• Aphids should be checked for and controlled from flag …

The Dengue Vaccine Initiative: A Bibliometric Analysis Of Research Publications, Festus Mulakoli, Abednego Ongeso, Horatius Musembi

School of Nursing & Midwifery, East Africa

Dengue fever has become a significant public health problem in tropical and subtropical regions and affects millions of people annually. Approximately 390 million people worldwide are estimated to be infected with dengue every year, of which 96 million develop dengue fever. Recently, there has been a noticeable increase in dengue cases, primarily in areas with tropical and subtropical climates. Vaccines have been developed to prevent or reduce the severity of the disease. This study reviews the number of publications on dengue vaccines and related topics worldwide. We aimed to evaluate the research output and create a narrative on global vaccine …

Tcellsi: A Novel Method For T Cell State Assessment And Its Applications In Immune Environment Prediction, Jing-Min Yang, Nan Zhang, Tao Luo, Mei Yang, Wen-Kang Shen, Zhen-Lin Tan, Yun Xia, Libin Zhang, Xiaobo Zhou, Qian Lei, An-Yuan Guo

Faculty, Staff and Student Publications

T cell is an indispensable component of the immune system and its multifaceted functions are shaped by the distinct T cell types and their various states. Although multiple computational models exist for predicting the abundance of diverse T cell types, tools for assessing their states to characterize their degree of resting, activation, and suppression are lacking. To address this gap, a robust and nuanced scoring tool called T cell state identifier (TCellSI) leveraging Mann-Whitney

Integrated Safety And Efficacy Analyses Of Phase 3 Trials Of A Microbiome Therapeutic For Recurrent Cdi, Colleen S Kraft, Matthew Sims, Michael Silverman, Thomas J Louie, Paul Feuerstadt, Edward S Huang, Sahil Khanna, Charles S Berenson, Elaine E L Wang, Stuart H Cohen, Louis Korman, Christine Lee, Colleen R Kelly, Alberto Odio, Paul P Cook, Bret Lashner, Mayur Ramesh, Princy Kumar, Ananya De, Asli Memisoglu, David A Lombardi, Brooke R Hasson, Barbara H Mcgovern, Lisa Von Moltke, Darrell S Pardi, Ecospor Iii And Ecospor Iv Investigators

Faculty, Staff and Students Publications

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI.

OBJECTIVE, DESIGN, AND PATIENTS: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities.

METHODS: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest …

High Fat, High Sucrose Diet Promotes Increased Expression Of Ace2 Receptor In The Siv-Infected Host: Implications For Sars-Cov-2 Infection, Elizabeth C. Delery, Danielle E. Levitt, Angela M. Amedee, Patricia E. Molina, Liz Simon

School of Graduate Studies Faculty Publications

Introduction: People with pre-existing conditions, including metabolic comorbidities, are at greater risk for complications of SARS-CoV-2 infection and expression of machinery required for viral entry into host cells may be a contributing factor. This study tested the hypothesis that high fat, high sucrose diet (HFSD) and alcohol use increase expression of angiotensin converting enzyme 2 (ACE2) receptor and transmembrane serine protease 2 (TMPRSS2) in tissues isolated from simian immunodeficiency virus (SIV) infected macaques, the most clinically relevant model for the study of HIV. Methods: Biospecimens obtained from a longitudinal study of SIV-infected, antiretroviral therapy (ART)-treated female rhesus macaques (Macaca mulatta) …

Broad Applicability Of The Goldspire™ Platform For The Treatment Of Solid Tumors, Jenny Zilberberg, Christopher Uhl, Charles B Scott, David W. Andrews, Mark A Exley

Department of Neurosurgery Faculty Papers

Goldspire™ is a personalized immunotherapy platform that combines whole tumor-derived cells with antisense oligonucleotide (IMV-001) against Insulin-Like Growth Factor-1 Receptor (IGF-1R) in biodiffusion chambers (BDCs; 0.1 μm pore). BDCs are exposed to 5-6 Gy and implanted at abdominal sites for ∼48 h to deliver an antigenic payload and immunostimulatory factors to train the immune system. Lead product IGV-001 was evaluated in newly diagnosed glioblastoma (ndGBM) patients in Phase 1a and 1b trials (NCT02507583). A Phase 2b study (NCT04485949) recently completed enrollment. Preventative treatment with tumor-specific products manufactured with Goldspire limited tumor progression and extended overall survival in mice challenged with …

Mta-Cooperative Prmt5 Inhibitors Enhance T Cell-Mediated Antitumor Activity In Mtap-Loss Tumors, Si Chen, Jiakai Hou, Roshni Jaffery, Ashley Guerrero, Rongjie Fu, Leilei Shi, Ningbo Zheng, Ritu Bohat, Nicholas A Egan, Chengtai Yu, Sana Sharif, Yue Lu, Wei He, Shuyue Wang, Donjeta Gjuka, Everett M Stone, Pooja Anil Shah, Jordi Rodon Ahnert, Taiping Chen, Xinli Liu, Mark T Bedford, Han Xu, Weiyi Peng

Faculty, Staff and Student Publications

BACKGROUND: Hyperactivated protein arginine methyltransferases (PRMTs) are implicated in human cancers. Inhibiting tumor intrinsic PRMT5 was reported to potentiate antitumor immune responses, highlighting the possibility of combining PRMT5 inhibitors (PRMT5i) with cancer immunotherapy. However, global suppression of PRMT5 activity impairs the effector functions of immune cells. Here, we sought to identify strategies to specifically inhibit PRMT5 activity in tumor tissues and develop effective PRMT5i-based immuno-oncology (IO) combinations for cancer treatment, particularly for methylthioadenosine phosphorylase (MTAP)-loss cancer.

METHODS: Isogeneic tumor lines with and without MTAP loss were generated by CRISPR/Cas9 knockout. The effects of two PRMT5 inhibitors (GSK3326595 and MRTX1719) were …

Fatal Disseminated Toxoplasmosis In Captive Red Kangaroo (Macropus Rufus) And Parma Wallaby (Macropus Parma): Pathological And Immunohistochemical Investigations, Sawang Kesdangsakonwut

The Thai Journal of Veterinary Medicine

Abstract

Toxoplasmosis is a protozoan zoonosis caused by Toxoplasma gondii. Marsupials are considered a susceptible intermediate host. T. gondii is mainly transmitted to intermediate hosts via the fecal-oral route. A captive red kangaroo was diagnosed with disseminated toxoplasmosis based on clinicopathological and immunohistochemical (IHC) investigations. Two years later, a five-year-old Parma wallaby was kept in the same area as the red kangaroo and showed clinical signs of depression, withdrawal from the troop, and weakness. The wallaby died within two days after showing the clinical signs. Pathological findings in this wallaby were compatible with disseminated toxoplasmosis. Tachyzoites and tissue cysts …

Novel Hamster Models Of Chikungunya Viral Arthritis, Tian Wang, Zhongde Wang

Funded Research Records

No abstract provided.

Molecular Detection Of Mycoplasma Spp. And Its Associated Risk Factors In Domestic Cats In The City Of Ibagué, Tolima, Karen D. Osorio Muñoz Dr., Iang S. Rondon Barragan Prof.

The Thai Journal of Veterinary Medicine

Feline hemoplasmosis is a disease with worldwide distribution, mainly in tropical countries, where its transmission is favored by the presence of vectors such as fleas and ticks. In Colombia, the diagnosis of the disease in small animals has been limited to the identification of the pathogen in blood smears, which have low sensitivity and specificity, demanding methods of higher diagnostic value, such as those based on molecular techniques. The objective of the present study was to investigate the prevalence of Mycoplasma spp. in felines from the city of Ibagué using the PCR and the associated risk factors. Briefly, blood samples …

The Roles Of Cd4+ T Cell Help, Sex, And Dose In The Induction Of Protective Cd8+ T Cells Against A Lethal Poxvirus By Mrna-Lnp Vaccines, Samita Kafle, Brian Montoya, Lingjuan Tang, Ying Tam, Hiromi Muramatsu, Norbert Pardi, Luis Sigal

Department of Microbiology and Immunology Faculty Papers

The role of CD4⁺ T cells in the induction of protective CD8⁺ T cells by mRNA lipid nanoparticle (LNP) vaccines is unknown. We used B6 or Tlr9^−/− mice depleted or not of CD4⁺ T cells and LNP vaccines loaded with mRNAs encoding the ectromelia virus (ECTV) MHC class I H-2 K^b-restricted immunodominant CD8⁺ T cell epitope TSYKFESV (TSYKFESV mRNA-LNPs) or the ECTV EVM158 protein, which contains TSYKFESV (EVM-158 mRNA-LNPs). Following prime and boost with 10 μg of either vaccine, K^b-TSYKFESV-specific CD8⁺ T cells fully protected male and female mice from …

Cognition And Inflammation In Youth With Perinatal Hiv, Megan Niehaus, Julie Mannarino, Jacob Bolzenius, Tori Frerichs, Robert Paul

Undergraduate Research Symposium

Background: Perinatally acquired HIV (PHIV) remains a major global health challenge. Approximately 90% of the global population of PHIV reside in low- or middle-income countries (LMICs) where access to antiretroviral therapy (ART) remains incomplete, particularly for PHIV. With PHIV, the brain is exposed to the virus during critical periods of brain development without the immunological benefits from ART. Unlike adults with horizontally acquired HIV whose nadir CD4+ Tcell count is a strong correlate of cognitive difficulties that persist after sustained use of ART, cognitive symptoms among PHIV youth are independent of traditional HIV disease metrics. Prior studies indicate that PHIV …

Root Lesion And Burrowing Nematodes And Their Management, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

Nematodes are common soil pests that feed on the roots of a wide range of crops in all agricultural areas of Western Australia, resulting in significant crop yield loss. Root lesion nematode can be managed but not eradicated.

This factsheet summarises the biology of the root lesion nematode (RLN, Pratylenchus spp.) and burrowing nematode (Radopholus spp.) species that damage Western Australian (WA) crops, and their diagnosis and management.

Armyworms And Their Management In Cereal Crops, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

Armyworms are pests of cereals crops. They are frequently found along the south coast of Western Australia and occasionally in other grainbelt locations.

When barley crops are maturing in spring, large armyworm caterpillars climb plants and can chew through the stems, causing the heads to fall to the ground. Damage to wheat and oat crops occurs less frequently and is usually minor compared to damage in barley. Armyworms are seldom a serious problem in pastures.

Aphid Feeding Damage And Its Management In Cereal Crops, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

Adult and nymph aphids suck sap from cereal crops, with large populations, especially in winter and spring, limiting grain yield and size. This page relates to feeding damage from oat aphid (Rhopalosiphon padi) and corn aphid (Rhopalosiphon maidis) in the absence of virus, and Russian wheat aphid (Diuraphis noxia).

Understanding Primate Immunity To African Trypanosomes Through The Characterization Of Trypanosome Lytic Factor Formation And Function, Sara Fresard

Dissertations, Theses, and Capstone Projects

African trypanosomes cause an annual loss of over 1 billion USD due to their economic and agricultural burden in Sub-Saharan Africa. These parasites are unicellular, extracellular parasites, that infect humans, cattle, and other livestock. Humans and some non-human primates are protected against most species of trypanosomes due to an innate immunity factor, Trypanosome Lytic Factor (TLF). This modified High Density Lipoprotein (HDL) contains two unique proteins, Haptoglobin Related Protein (HPR), a ligand to a trypanosome surface receptor, and Apolipoprotein-L1 (APOL1), the lytic component. Our overall goal is to use our understanding of primate immunity to create genetically modified cattle that …

Characterization Of High-Risk-Other Human Papillomavirus Genotypes In Papanicolaou Tests, High-Grade Squamous Intraepithelial Lesions, And Cervical Cancer, Caitlin E. Witt, Elizabeth F. Sutton, Ashley M. Stansbury, Ashley N. Winters, Luke C. Konur, Meng Luo, Jennifer E. Cameron, Beverly Ogden

School of Medicine Faculty Publications

Background: The objective of this study was to determine the human papillomavirus (HPV) genotypes of high-risk-other HPV Papanicolaou (Pap) tests and of biopsy tissues from patients with high-grade squamous intraepithelial lesion (HGSIL) or cervical cancer. High-risk-other HPV status was determined with the cobas HPV Test (Roche Diagnostics, North America) that identifies 12 high-risk, non-16/18 HPV genotypes. We hypothesized that we would find genotypes of HPV in our population that are not covered by the 9-valent HPV vaccine. Methods: For this retrospective cohort study, we randomly selected 50 high-risk-other HPV Pap test samples from 2018 from our pathology department registries for …

Exploring Berberine As A Novel Therapeutic Agent Against Staphylococcus Aureus Infections: Targeting Inflammation And Antibiotic Resistance, Daniel Kopulos

NYMC Student Theses and Dissertations

Staphylococcus aureus is a versatile Gram-positive bacterium commonly found on human skin. While often harmless, it can cause various infections when the skin is compromised, ranging from minor issues to life-threatening conditions in immunocompromised individuals.

The bacterium’s ability to resist antibiotics, particularly methicillin, underscores its clinical challenge. Staphylococcus aureus can also acquire vancomycin resistance. It evades immune responses through multiple mechanisms, including capsule formation, interference with immune proteins like staphylococcal protein A, and secretion of toxins such as Panton-Valentine Leukocidin. Understanding these mechanisms is crucial for developing effective strategies against Staphylococcus aureus infections.

The immune response to Staphylococcus aureus infections …

Combination Therapy Of Ido1 Inhibition And Anti-Pd1 Mediates Anti-Tumor Immunity By Promoting Memory Immunity Development And Cytotoxicity Of Γδ T And Nk Cells Via Il-2 Signaling And By Overcoming Pro-Tumor Effects Of Tgf-Β Signaling, Hyuk Jee

Dartmouth College Master’s Theses

Cutaneous melanoma is the most aggressive form of skin cancer even though it takes only about 1% of all skin cancers. Even among all cutaneous melanomas, NRAS-mutant melanoma is more aggressive than any other, and about 10-25% of all cutaneous melanoma cases have mutations in NRAS. NRAS is a member of the RAS family of proto-oncogenic GTPase proteins, and it plays a key role in signal transduction pathways responsible for cellular survival, proliferation, and metabolism. Immunotherapy is the first line of defense against NRAS-mutant melanoma because, despite tremendous efforts made for decades, it has not been successful to develop small …

Testing Strategies To Develop A Mucosal T Cell Inducing Vaccine For Hiv-1, Reynolds Boone

Master's Theses

Despite numerous efforts, HIV vaccine is still not available. Because HIV Envelop protein varies among subtypes and isolates, it is impossible for one vaccine against HIV Env to induce neutralizing antibodies against all subtypes and isolates. Previous vaccine attempts inducing HIV-specific CD4+ T cells have even been shown to enhance the HIV infection because HIV preferentially infects activated CD4+ T cells. It is known that CD8+ cytotoxic T cells (CTLs) play an important role in controlling HIV infections. We hypothesize that a vaccine inducing only CD8+ CTLs but not CD4+ T cells will be effective in preventing HIV infections. Thus, …

The Anti-Inflammatory Properties Of Exopolysaccharide From Bacillus Subtilis, Nikolay Todorov

Master's Theses

Commensal microorganisms can be used therapeutically to ameliorate a variety of diseases. The laboratory of Dr. Katherine L. Knight studies these therapeutic properties in the commensal microorganism known as Bacillus subtilis. Previously, the Knight lab has demonstrated that B. subtilis can protect against colitis caused by Citrobacter rodentium suggesting that B. subtilis possesses anti-inflammatory properties. These properties are specific to the polysaccharide capsule of the microorganism known as exopolysaccharide or EPS. EPS can be produced and purified for study. EPS has been demonstrated to be protective in a variety of diseases such as allergic eosinophilia, sepsis, Graft versus Host disease, …