Digital Commons Network^™

Parallel Use Of Low-Complexity Automated Nucleic Acid Amplification Tests On Respiratory Samples And Stool With Or Without Lateral Flow Lipoarabinomannan Assays To Detect Pulmonary Tuberculosis Disease In Children, Laura Olbrich, Alexander W Kay, Stephanie Bjerrum, Bada Yang, Johanna Åhsberg, Ruvandhi R Nathavitharana, Andreas Lundh, Maunank Shah, Devan Jaganath

Faculty, Staff and Students Publications

This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To compare the diagnostic accuracy of the parallel use of low-complexity automated nucleic acid amplification tests on respiratory and stool specimens in children and lateral flow urine lipoarabinomannan amongst children with HIV versus each assay alone for detecting pulmonary tuberculosis. Secondary objectives To compare the diagnostic accuracy of low-complexity automated nucleic acid amplification tests on respiratory and stool specimens in combination versus each sample type alone. To investigate the following sources of heterogeneity: clinical setting, signs and symptoms of pulmonary tuberculosis disease, screening positivity by chest …

Parental Factors Associated With Covid-19 Vaccine Uptake For Children Over 5 Years Of Age In Texas, Paula M Cuccaro, Jihye Choi, Yordanos M Tiruneh, Journey Martinez, Jing Xie, Michelle Crum, Mark Owens, Jose-Miguel Yamal

Faculty, Staff and Student Publications

The COVID-19 vaccine is safe and effective for children, yet parental hesitancy towards vaccinating children against the virus persists. We conducted a telephone-administered weighted survey in Texas to examine parents' sociodemographic factors and medical conditions associated with COVID-19 vaccination intention for parents with unvaccinated children ages 5-17 years. We collected responses from 19,502 participants, of which 4879 were parents of children ages 5-17 years. We conducted multiple logistic regression with Lasso-selected variables to identify factors associated with children's vaccination status and parents' intention to vaccinate their children. From the unweighted sample, less than half of the parents (46.8%) had at …

Evaluation Of Fusobacterium Nucleatum Enoyl-Acp Reductase (Fabk) As A Narrow-Spectrum Drug Target, Jacob T Rutherford, Kristiana Avad, Chetna Dureja, Krissada Norseeda, Bibek Gc, Chenggang Wu, Dianqing Sun, Kirk E Hevener, Julian G Hurdle

Faculty, Staff and Student Publications

Fusobacterium nucleatum, a pathobiont inhabiting the oral cavity, contributes to opportunistic diseases, such as periodontal diseases and gastrointestinal cancers, which involve microbiota imbalance. Broad-spectrum antimicrobial agents, while effective against F. nucleatum infections, can exacerbate dysbiosis. This necessitates the discovery of more targeted narrow-spectrum antimicrobial agents. We therefore investigated the potential for the fusobacterial enoyl-ACP reductase II (ENR II) isoenzyme FnFabK (C4N14_ 04250) as a narrow-spectrum drug target. ENRs catalyze the rate-limiting step in the bacterial fatty acid synthesis pathway. Bioinformatics revealed that of the four distinct bacterial ENR isoforms, F. nucleatum specifically encodes FnFabK. Genetic studies revealed …

Effect Of An Hpv Vaccination Multi-Level, Multi-Component Program On Hpv Vaccination Initiation And Completion In A Pediatric Clinic Network, Lara S Savas, Ross Shegog, Erica L Frost, C Mary Healy, Dale S Mantey, Sharon P Coan, L Aubree Shay, Travis A Teague, Juan J Ferreris, Sharice M Preston, Sally W Vernon

Faculty, Staff and Student Publications

Despite clear evidence of the public health benefits of the human papillomavirus (HPV) vaccine in preventing HPV-related cancers and genital warts, underutilization of HPV vaccination in the United States persists. Interventions targeting multi-level determinants of vaccination behavior are crucial for improving HPV vaccination rates. The study's purpose was to implement and evaluate the adapted Adolescent Vaccination Program (AVP), a clinic-based, multi-level, multi-component intervention aimed at increasing HPV vaccine initiation and completion rates in a five-clinic pediatric network in Bexar County, Texas. The adaptation process was guided by established frameworks and involved formative work with clinic stakeholders. The study utilized a …

Correction: Horne Et Al White Matter Correlates Of Domain-Specific Working Memory, Autumn Horne, Junhua Ding, Tatiana T Schnur, Randi C Martin

Faculty, Staff and Student Publications

In the original publication [...].

Optimization Of The Antifungal Properties Of The Bacterial Peptide Entv By Variant Analysis, Shantanu Guha, Shane A Cristy, Giuseppe Buda De Cesare, Melissa R Cruz, Michael C Lorenz, Danielle A Garsin

Faculty, Staff and Student Publications

Fungal resistance to commonly used medicines is a growing public health threat, and there is a dire need to develop new classes of antifungals. We previously described a peptide produced by Enterococcus faecalis, EntV, that restricts Candida albicans to a benign form rather than having direct fungicidal activity. Moreover, we showed that one 12-amino acid (aa) alpha helix of this peptide retained full activity, with partial activity down to the 10aa alpha helix. Using these peptides as a starting point, the current investigation sought to identify the critical features necessary for antifungal activity and to screen for new variants …

Single Extracellular Vesicle Imaging And Computational Analysis Identifies Inherent Architectural Heterogeneity, Kshipra S Kapoor, Seoyun Kong, Hikaru Sugimoto, Wenhua Guo, Vivek Boominathan, Yi-Lin Chen, Sibani Lisa Biswal, Tanguy Terlier, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Evaluating the heterogeneity of extracellular vesicles (EVs) is crucial for unraveling their complex actions and biodistribution. Here, we identify consistent architectural heterogeneity of EVs using cryogenic transmission electron microscopy (cryo-TEM), which has an inherent ability to image biological samples without harsh labeling methods while preserving their native conformation. Imaging EVs isolated using different methodologies from distinct sources, such as cancer cells, normal cells, immortalized cells, and body fluids, we identify a structural atlas of their dominantly consistent shapes. We identify EV architectural attributes by utilizing a segmentation neural network model. In total, 7,576 individual EVs were imaged and quantified by …

Expanding Complex Morpholines Using Systematic Chemical Diversity, Sunny Ann Tang, Afton Fults, Shelton R Boyd, Nikhil Gattu, Kevin A Tran, Jiayi Fan, Kevin R Mackenzie, Timothy Palzkill, Damian W Young, Srinivas Chamakuri

Faculty, Staff and Students Publications

The morpholine heterocycle is a structural unit found in many bioactive compounds and FDA-approved drugs, but the generation of more complex C-functionalized morpholine derivatives remains considerably underexplored. Using systematic chemical diversity (SCD), a concept that guides the expansion of saturated drug-like scaffolds through regiochemical and stereochemical variation, we describe the synthesis of a collection of methyl-substituted morpholine acetic acid esters starting from enantiomerically pure amino acids and amino alcohols. In total, 24 diverse substituted morpholines were produced that vary systematically in regiochemistry and stereochemistry (relative and absolute). These diverse C-substituted morpholines can be directly applied in fragment screening or incorporated …

Kras G12c Inhibitor Combination Therapies: Current Evidence And Challenge, Hirotaka Miyashita, Shumei Kato, David S Hong

Faculty, Staff and Student Publications

Although KRAS G12C inhibitors have proven that KRAS is a "druggable" target of cancer, KRAS G12C inhibitor monotherapies have demonstrated limited clinical efficacy due to primary and acquired resistance mechanisms. Multiple combinations of KRAS G12C inhibitors with other targeted therapies, such as RTK, SHP2, and MEK inhibitors, have been investigated in clinical trials to overcome the resistance. They have demonstrated promising efficacy especially by combining KRAS G12C and EGFR inhibitors for KRAS G12C-mutated colorectal cancer. Many clinical trials of combinations of KRAS G12C inhibitors with other targeted therapies, such as SOS1, ERK, CDK4/6, and wild-type RAS, are ongoing. Furthermore, preclinical …

Tsyn-Seq: A T-Cell Synapse-Based Antigen Identification Platform, Yimei Jin, Takahiko Miyama, Alexandria Brown, Tomo Hayase, Xingzhi Song, Anand K Singh, Licai Huang, Ivonne I Flores, Lauren K Mcdaniel, Israel Glover, Taylor M Halsey, Rishika Prasad, Valerie Chapa, Saira Ahmed, Jianhua Zhang, Kunal Rai, Christine B Peterson, Gregory Lizee, Jennifer Karmouch, Eiko Hayase, Jeffrey J Molldrem, Chia-Chi Chang, Wen-Bin Tsai, Robert R Jenq

Faculty, Staff and Student Publications

Tools for genome-wide rapid identification of peptide-major histocompatibility complex targets of T-cell receptors (TCR) are not yet universally available. We present a new antigen screening method, the T-synapse (Tsyn) reporter system, which includes antigen-presenting cells (APC) with a Fas-inducible NF-κB reporter and T cells with a nuclear factor of activated T cells (NFAT) reporter. To functionally screen for target antigens from a cDNA library, productively interacting T cell-APC aggregates were detected by dual-reporter activity and enriched by flow sorting followed by antigen identification quantified by deep sequencing (Tsyn-seq). When applied to a previously characterized TCR specific for the E7 antigen …

Community-Acquired Pneumonia: A Us Perspective On The Guideline Gap, Maricar Malinis, Lilian Abbo, Jose A Vazquez, Luis Ostrosky-Zeichner

Faculty, Staff and Student Publications

Community-acquired pneumonia continues to be one of the most common causes of morbidity and mortality due to infectious disease. The aetiologies, clinical presentations, diagnostic modalities and therapeutic options are changing and outpacing the creation of management guidelines. This educational article summarizes a roundtable activity sponsored by an unrestricted educational grant by Paratek that included US experts discussing these changes and identifying gaps in the current guidelines.

Mismatch Repair Deficient Neoantigen And Associated Circulating T-Cell Receptor Repertoires In Lynch Syndrome, Ana Bolivar

Dissertations and Theses (Open Access)

Lynch Syndrome (LS) is the most common inherited colorectal cancer (CRC) syndrome. It constitutes the perfect model to understand DNA mismatch repair deficient (MMRd) carcinogenesis, which underlies 15% of early-stage CRC. LS patients develop MMRd tumors with high loads of shared neoantigens (neoAgs), which are recognized by the immune system. Previous research has concentrated on discovering neoAgs and their potential as targets for vaccines in LS patients. However, these studies have primarily identified shared neoAgs from cancers, lacking detailed information on targetable neoAgs present in precancerous lesions. Understanding this landscape of pre-cancer derived neoAgs is crucial for intercepting cancer development …

The Constitutively Active Form Of A Key Cholesterol Synthesis Enzyme Is Lipid Droplet-Localized And Upregulated In Endometrial Cancer Tissues, Hudson W Coates, Tina B Nguyen, Ximing Du, Ellen M Olzomer, Rhonda Farrell, Frances L Byrne, Hongyuan Yang, Andrew J Brown

Faculty, Staff and Student Publications

Cholesterol is essential for both normal cell viability and cancer cell proliferation. Aberrant activity of squalene monooxygenase (SM, also known as squalene epoxidase), the rate-limiting enzyme of the committed cholesterol synthesis pathway, is accordingly implicated in a growing list of cancers. We previously reported that hypoxia triggers the truncation of SM to a constitutively active form, thus preserving sterol synthesis during oxygen shortfalls. Here, we show SM truncation is upregulated and correlates with the magnitude of hypoxia in endometrial cancer tissues, supporting the in vivo relevance of our earlier work. To further investigate the pathophysiological consequences of SM truncation, we …

Neoadjuvant Chemoimmunotherapy For Nsclc: A Systematic Review And Meta-Analysis, Mark Sorin, Connor Prosty, Louis Ghaleb, Kathy Nie, Khaled Katergi, Muhammad H Shahzad, Laurie-Rose Dubé, Aline Atallah, Anikka Swaby, Matthew Dankner, Trafford Crump, Logan A Walsh, Pierre O Fiset, Boris Sepesi, Patrick M Forde, Tina Cascone, Mariano Provencio, Jonathan D Spicer

Faculty, Staff and Student Publications

IMPORTANCE: To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%.

OBJECTIVE: To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials.

DATA SOURCES: MEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of …

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 …

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 …

Oxidative Phosphorylation In Melanoma Brain Metastases: A Regulator Of The Tumor Immune Landscape, Renato A. Guerrieri

Dissertations and Theses (Open Access)

Previously, we demonstrated via RNA-sequencing analysis of murine intracranial melanoma tumors that pharmacologic inhibition of oxidative phosphorylation (OXPHOS) results in increased expression of genes consistent with activated anti-tumor immune responses. The central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis and immune regulation of melanoma brain metastases (MBMs).

The functional significance of OXPHOS was assessed through genetic inhibition, involving knockout (KO) of key regulatory genes such as Ppargc1a (PGC1a) and Ndfus4 (NDUFS4), a component of mitochondrial complex I. PGC1a KO in an RCAS-TVA mouse model of autochthonous lung and brain tumors developing from primary …

Novel Roles Of Microtubule-Associated Tau In Radiation-Induced Brain Injury, Riya Thomas, Riya Thomas

Dissertations and Theses (Open Access)

Injury responses in cells lacking proliferation capacity such as terminally differentiated neurons consists of complex mechanisms to ensure cellular homeostasis. Brain tumor patients undergoing radiation therapy experience cognitive impairments similar to those seen in patients suffering from neurodegenerative diseases. Despite the plethora of research into radiation effects on proliferating brain cells, the impact of radiation on differentiated, post-mitotic neurons, including their structural and functional alterations, remain largely elusive. However, microtubule-associated tau, an important partner of cytoskeletal structural stability emerges as a pivotal player in the radiation-induced neuronal injury response, demonstrating compartmentalized functions such as repair-centric mechanisms and synaptic homeostasis. This …

The Role Of Anti-Viral Immune Response On The Therapeutic Efficacy Of Oncolytic Virotherapy For High-Grade Gliomas, Dong Ho Shin Phd

Dissertations and Theses (Open Access)

Currently, there is no effective treatment for high-grade gliomas that are resistant to conventional treatments and immune checkpoint blockade therapies. Oncolytic viruses offer a new treatment modality by selectively replicating in cancer cells and inducing anti-tumor immunity. Among these viruses, the oncolytic adenovirus Delta-24-RGD has shown safety and efficacy in clinical trials for high-grade gliomas. Strategies to improve the efficacy of oncolytic virotherapy have aimed to heighten the immunogenicity of oncolytic viruses, either by incorporating immune-stimulating transgenes or by combining treatments with immune checkpoint blockades. However, such strategies may inadvertently trigger heightened immune responses to viral antigens, which may not …

Investigating The Role Of The Gut Microbiota On Immune Checkpoint Inhibitor-Mediated Colitis, Taylor Halsey, Robert Jenq

Dissertations and Theses (Open Access)

Immune checkpoint inhibitors (ICIs) have been revolutionary in the fight against cancer by recruiting the host immune system as an agent for attack on malignant cells. Unfortunately, immune-related adverse events (irAEs), including ICI-mediated colitis (IMC), are common side effects that result from immune cell mediated damage on healthy tissues. Recent studies have highlighted a role for the gut microbiota in modulating ICI-mediated anti-tumor responses, but less is known regarding how the gut microbiota may impact on irAEs. Considering that the gastrointestinal tract harbors thousands of unique microbial species, many of which are known to modulate the immune system, microbes and …

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 …

Model Tuning Or Prompt Tuning? A Study Of Large Language Models For Clinical Concept And Relation Extraction, Cheng Peng, Xi Yang, Kaleb E Smith, Zehao Yu, Aokun Chen, Jiang Bian, Yonghui Wu

Faculty, Staff and Student Publications

Objective: To develop soft prompt-based learning architecture for large language models (LLMs), examine prompt-tuning using frozen/unfrozen LLMs, and assess their abilities in transfer learning and few-shot learning.

Methods: We developed a soft prompt-based learning architecture and compared 4 strategies including (1) fine-tuning without prompts; (2) hard-prompting with unfrozen LLMs; (3) soft-prompting with unfrozen LLMs; and (4) soft-prompting with frozen LLMs. We evaluated GatorTron, a clinical LLM with up to 8.9 billion parameters, and compared GatorTron with 4 existing transformer models for clinical concept and relation extraction on 2 benchmark datasets for adverse drug events and social determinants of health (SDoH). …

Immune-Monitoring Of Myelodysplastic Neoplasms: Recommendations From The I4mds Consortium, Cristina A Tentori, Lin P Zhao, Benedetta Tinterri, Kathryn E Strange, Katharina Zoldan, Konstantinos Dimopoulos, Xingmin Feng, Elena Riva, Benjamin Lim, Yannick Simoni, Vidhya Murthy, Madeline J Hayes, Antonella Poloni, Eric Padron, Bruno A Cardoso, Michael Cross, Susann Winter, Aida Santaolalla, Bhavisha A Patel, Emma M Groarke, Daniel H Wiseman, Katy Jones, Lauren Jamieson, Charles Manogaran, Naval Daver, Laura Gallur, Wendy Ingram, P Brent Ferrell, Katja Sockel, Nicolas Dulphy, Nicolas Chapuis, Anne S Kubasch, Astrid M Olsnes, Austin Kulasekararaj, Hugues De Lavellade, Wolfgang Kern, Mieke Van Hemelrijck, Dominique Bonnet, Theresia M Westers, Sylvie Freeman, Uta Oelschlaegel, David Valcarcel, Marco G Raddi, Kirsten Grønbæk, Michaela Fontenay, Sanam Loghavi, Valeria Santini, Antonio M Almeida, Jonathan M Irish, David A Sallman, Neal S Young, Arjan A Van De Loosdrecht, Lionel Adès, Matteo G Della Porta, Catherine Cargo, Uwe Platzbecker, Shahram Kordasti, I4mds Consortium

Faculty, Staff and Student Publications

Advancements in comprehending myelodysplastic neoplasms (MDS) have unfolded significantly in recent years, elucidating a myriad of cellular and molecular underpinnings integral to disease progression. While molecular inclusions into prognostic models have substantively advanced risk stratification, recent revelations have emphasized the pivotal role of immune dysregulation within the bone marrow milieu during MDS evolution. Nonetheless, immunotherapy for MDS has not experienced breakthroughs seen in other malignancies, partly attributable to the absence of an immune classification that could stratify patients toward optimally targeted immunotherapeutic approaches. A pivotal obstacle to establishing "immune classes" among MDS patients is the absence of validated accepted immune …

High-Grade Pleomorphic Sarcomas Treated With Immune Checkpoint Blockade: The Md Anderson Cancer Center Experience, Lewis F Nasr, Marianne Zoghbi, Rossana Lazcano, Michael Nakazawa, Andrew J Bishop, Ahsan Farooqi, Devarati Mitra, Beverly Ashleigh Guadagnolo, Robert Benjamin, Shreyaskumar Patel, Vinod Ravi, Dejka M Araujo, Andrew Livingston, Maria A Zarzour, Anthony P Conley, Ravin Ratan, Neeta Somaiah, Alexander J Lazar, Christina Roland, Emily Z Keung, Elise F Nassif Haddad

Faculty, Staff and Student Publications

BACKGROUND: Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available.

PURPOSE: The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution.

METHODS: This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in …

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.