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Parp Inhibitors In Melanoma Treatment: Potential, Challenges, And Future Directions, Angela Anaeme, Karen Moussa, Abdallah N Mansour, George Nassief, George Ansstas

2020-Current year OA Pubs

Genome integrity is a critical driver of cellular stability, and defects in the processes that maintain genome health are potent sources of cancer progression. Homologous recombination deficiency (HRD), which damages cells through absent or erroneous repair of double-stranded DNA breaks, is a prime example of such cellular dysfunction. Poly(ADP-ribose) polymerase (PARP) inhibitors exploit these aberrancies in the cellular repair process by arresting the ability of the PARP enzyme to repair cellular and genetic damage, inducing the accumulation of DNA damage and cancer cell death. While the utility of PARP inhibitors has been established in many HRD-associated tumors - particularly breast, …

Assessing The Efficacy Of The Natural Disaccharide Trehalose In Ameliorating Diet-Induced Obesity And Metabolic Dysfunction, Yu-Sheng Yeh, Trent D Evans, Se-Jin Jeong, Ziyang Liu, Ali Ajam, Carlos Cosme, Jun Huang, Doureradjou Peroumal, Xiangyu Zhang, Ali Javaheri, Jaehyung Cho, Irfan J Lodhi, Babak Razani

2020-Current year OA Pubs

Trehalose is a naturally occurring disaccharide with versatile commercial applications and health benefits, including promise as a therapeutic for obesity and diabetes. Although numerous previous reports purport the therapeutic uses of orally ingested trehalose, the abundance of glycosidases in the gastrointestinal tract suggest the potential for significant limitations of oral trehalose that have not been addressed. We first fed mice a high-fat diet (HFD) while providing trehalose by both oral and intraperitoneal routes. This combined strategy was broadly efficacious in reversing HFD-induced weight gain, fat mass, insulin resistance, and the development of hepatosteatosis. In contrast, oral-only trehalose failed to improve …

Characterization Of Tlr9 Responsiveness In Cell Subsets Derived From In Vitro Pdc Differentiation Of Hematopoietic Stem And Progenitor Cells, Sabina Sánchez Hernández, Tobias Wang Bjerg, Ian Helstrup Nielsen, Anders Laustsen, Hai Q Tang, Lars Henning Pedersen, Eynav Klechevsky, Martin R Jakobsen, Rasmus O Bak

2020-Current year OA Pubs

Plasmacytoid dendritic cells (pDCs) are multifunctional immune cells with roles in both the innate and adaptive immune system. Their hallmark function is production of large amounts of type I interferons in response to viral infections, but they are also capable of producing a range of other cytokines, antigen presentation, and cytotoxicity. Their potential as an immunotherapy for cancer and infectious disease is being explored, but broad application of these cells is challenged by low frequency in the blood and low viability during

Hookworm Infection Modulates Lung And Intestinal Transcriptomic Responses To Sars-Cov-2 In Syrian Hamsters, Bruce A Rosa, Mahdiyeh Bigham, Tamarand L Darling, Ashutosh Arun, Kumar Sachin Singh, John Martin, Adrianus C M Boon, Makedonka Mitreva

2020-Current year OA Pubs

BACKGROUND: Helminth infections are widespread in resource-limited settings, and modulate host immune responses, with potential implications for viral coinfections. Intestinal helminths can alter susceptibility to respiratory viruses, but the mechanisms influencing SARS-CoV-2 infection outcomes remain poorly understood.

METHODS: Using the Syrian hamster model, we investigated the impact of prior infection with the human hookworm

RESULTS: Prior hookworm infection did not significantly alter viral titers or weight loss compared to SARS-CoV-2 infection alone, but distinct transcriptional signatures compared were identified compared to either single infection. Coinfection uniquely differentially regulated hematopoiesis and B cell-associated genes (e.g.,

CONCLUSION: Our findings demonstrate that

Hydroxyurea Utilization Among Individuals With Sickle Cell Disease In Tennessee: A Pooled Analysis Of Claims Data, Ayesha Mukhopadhyay, Matthew P Smeltzer, Judy Dudley, Sherif M Badawy, Joacy G Mathias, Allison P Plaxco, Meredith A Ray, Andrew D Wiese, Walter I Stevens, James G Gurney, Chinonyelum Nwosu, Jerlym S Porter, Lisa M Klesges, Jane S Hankins, William O Cooper

2020-Current year OA Pubs

IMPORTANCE: Hydroxyurea reduces severe disease among individuals living with sickle cell disease (SCD). These individuals experience high acute care utilization, but the associations between patterns of hydroxyurea utilization and healthcare utilization are not well investigated.

OBJECTIVE: This study aimed to determine the association between hydroxyurea use and healthcare utilization among individuals with SCD in Tennessee (TN).

DESIGN: We conducted a population-based, retrospective cohort study of individuals with SCD using secondary data analysis of Tennessee Medicaid, Medicare, and BlueCross BlueShield of Tennessee (BCBS-TN).

PARTICIPANTS: A total of 4,901 individuals with SCD were included in the study.

EXPOSURE: Hydroxyurea adherence was estimated …

New Perspectives On Extracorporeal Life Support: Expert Teams And Precise Selection Of Candidates Are Transforming Pediatric Cancer And Hematopoietic Cell Transplantation Care, Caitlin Hurley, Matteo Di Nardo, Matthew Rees, Diego R Hijano, Ahmed Said, Akshay Sharma, Lama Elbahlawan, Melissa R Hines, Jennifer A Mcarthur, Hitesh Sandhu, Saad Ghafoor

2020-Current year OA Pubs

Extra Corporeal Life Support (ECLS) for pediatric oncology and stem cell transplant patients over the past two decades has made progress. Substantial improvements in ECLS, Continuous Renal Replacement Therapy (CRRT), and mechanical ventilation techniques, along with enhanced anticoagulation management and infection control, have contributed to better patient outcomes. Additionally, advancements in HLA matching, donor selection, and the management of chemotherapy and transplant complications have further improved survival rates. The authors propose establishing an expert team and a standardized process to evaluate ECLS candidacy, addressing past controversies and optimizing outcomes for this vulnerable population. The criteria for candidacy have evolved significantly, …

Stimulating Training And Access To Hiv Research Experiences (Star Program): A Protocol For A Crowdsourced, Project-Based, Implementation Science Training Program Using Mixed-Methods Design, Juliet Iwelunmor, Idia Thurston, Collins Airhihenbuwa, Weiming Tang, Ucheoma Catherine Nwaozuru, Onyekachukwu Anikamadu, David Oladele, Bryce Takenaka, Khadijah Ameen, Olufunto A Olusanya, Temitope Ojo, Joseph D Tucker

2020-Current year OA Pubs

BACKGROUND: HIV is more common among underrepresented minority adolescents and young adults (AYA, 13-24 years old) in the United States. Low uptake of HIV prevention services suggests a missed opportunity for implementing evidence-based interventions such as pre-exposure prophylaxis (PrEP) and sexually transmitted infection testing among this important population. Most research institutions in the United States also have limited opportunities for AYA training, mentorship, and capacity-building activities.

METHODS: The "Stimulating Training and Access to HIV Research Experiences" (STAR) program brings together a highly qualified group of research mentors to achieve three specific aims: (1) identify and recruit underrepresented minority AYA interested …

Unveiling Sub-Populations In Critical Care Settings: A Real-World Data Approach In Covid-19, Wesley Anderson, Andrew P Michelson, Et Al.

2020-Current year OA Pubs

BACKGROUND: Disease presentation and progression can vary greatly in heterogeneous diseases, such as COVID-19, with variability in patient outcomes, even within the hospital setting. This variability underscores the need for tailored treatment approaches based on distinct clinical subgroups.

OBJECTIVES: This study aimed to identify COVID-19 patient subgroups with unique clinical characteristics using real-world data (RWD) from electronic health records (EHRs) to inform individualized treatment plans.

MATERIALS AND METHODS: A Factor Analysis of Mixed Data (FAMD)-based agglomerative hierarchical clustering approach was employed to analyze the real-world data, enabling the identification of distinct patient subgroups. Statistical tests evaluated cluster differences, and machine …

High-Resolution Single-Cell Rna Sequencing Using Canfam4 Reveals Novel Immune Subsets And Checkpoint Programs In Healthy Dogs, Myung-Chul Kim, Taeeun Gu, Hyeewon Seo, Yewon Moon, Nicholas Borcherding, Ryan Kolb, Yubin Kim, Youngmin Yun, Woo-Jin Song, Chung-Young Lee, Hyun Je Kim, Weizhou Zhang

2020-Current year OA Pubs

INTRODUCTION: Single-cell RNA sequencing (scRNA-seq) enables high-resolution profiling of immune heterogeneity. Although previous studies have mapped the single-cell transcriptomic atlases of peripheral leukocytes in healthy dogs, the identification and functional characterization of distinct immune subsets remain incomplete.

METHODS: We constructed a single-cell atlas of peripheral leukocytes from six healthy small-breed dogs using the 10x Genomics platform and the updated canFam4 genome.

RESULTS AND DISCUSSION: Analysis of 30,040 high-quality transcriptomes revealed 51 distinct immune subsets, including

CONCLUSION: To our knowledge, this study represents the first comprehensive, gene-resolved single-cell analysis to reveal immunoregulatory checkpoint mechanisms underlying immune homeostasis in healthy dogs. Our …