Health Services Research Commons^™

Suppression Of Hypothalamic Oestrogenic Signal Sustains Hyperprolactinemia And Metabolic Adaptation In Lactating Mice, Meng Yu, Bing Feng, Jonathan C Bean, Qianru Zhao, Yongjie Yang, Hailan Liu, Yongxiang Li, Benjamin P Eappen, Hesong Liu, Longlong Tu, Kristine M Conde, Mengjie Wang, Xi Chen, Na Yin, Darah Ave Threat, Nathan Xu, Junying Han, Peiyu Gao, Yi Zhu, Darryl L Hadsell, Yang He, Pingwen Xu, Yanlin He, Chunmei Wang

Faculty, Staff and Students Publications

17β-oestradiol (E2) inhibits overeating and promotes brown adipose tissue (BAT) thermogenesis, whereas prolactin (PRL) does the opposite. During lactation, the simultaneous decline in E2 and surge in PRL contribute to maternal metabolic adaptations, including hyperphagia and suppressed BAT thermogenesis. However, the underlying neuroendocrine mechanisms remain unclear. Here, we find that oestrogen receptor alpha (ERα)-expressing neurons in the medial basal hypothalamus (MBH), specifically the arcuate nucleus of the hypothalamus and the ventrolateral subdivision of the ventromedial hypothalamus (vlVMH), are suppressed during lactation. Deletion of ERα from MBH neurons in virgin female mice induces metabolic phenotypes characteristic of lactation, including hyperprolactinemia, hyperphagia …

Il-12-Producing Cytokine Factories Induce Precursor Exhausted T Cells And Elimination Of Primary And Metastatic Tumors, Amanda Nash, Jonathon Debonis, Danna Murungi, Bertha Castillo, Boram Kim, Fangheng Hu, Courtney Chambers, Annie Nguyen, Andrea Hernandez, Zeshi Wang, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Ningbo Zheng, Weiyi Peng, Oleg A Igoshin, Jose Oberholzer, H Courtney Hodges, Nathan Reticker-Flynn, Omid Veiseh

Faculty, Staff and Students Publications

Background: Curative responses to immunotherapy require the generation of robust systemic immunity with limited toxicity. Recruitment of T cell populations such as precursor exhausted T cells (Tpex) from lymphoid tissues to tumors is a hallmark of effective treatment. However, the ability to efficiently induce this recruitment is lacking in current immunotherapy approaches. Furthermore, systemic administration of immunotherapies frequently results in dose-limiting toxicities, yielding an inadequate therapeutic window for eliciting durable responses.

Methods: In this investigation, we evaluated the safety and antitumor efficacy of locally administered interleukin 12 (IL-12) using a clinically translatable cytokine delivery platform (NCT05538624) to identify …

Single-Nucleus Transcriptional Profiling Of The Placenta Reveals The Syncytiotrophoblast Stress Response To Covid-19, Rachel A Keuls, Scott A Ochsner, Mary B O'Neill, Diana R O'Day, Akihiko Miyauchi, Kadeshia M Campbell, Natalie Lanners, Jeffery A Goldstein, Connor Yee, Neil J Mckenna, Ronald J Parchem, Jacqueline G Parchem

Faculty, Staff and Students Publications

Background: COVID-19 in pregnancy is associated with placental immune activation, inflammation, and vascular malperfusion, but its impact on syncytiotrophoblast biology and function is unclear.

Objective: This study aimed to determine the effects of maternal COVID-19 on placental syncytiotrophoblasts using single-nucleus transcriptional profiling and to compare placental stress responses in COVID-19 and preeclampsia.

Study design: For transcriptional characterization of syncytiotrophoblasts, we used the single-nucleus RNA sequencing platform, single-cell combinatorial indexing RNA sequencing (sci-RNA-seq3), to profile placental villi and fetal membranes from unvaccinated patients with symptomatic COVID-19 at birth (n = 4), gestational age-matched controls (n = 4), and a case of …

Warm-Ischemia And Cold Storage Induced Modulation Of Ferroptosis Observed In Human Hearts Donated After Circulatory Death And Brain Death, Shiyi Li, Katherine V Nordick, Abdussalam E Elsenousi, Rishav Bhattacharya, Randall P Kirby, Adel M Hassan, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

We investigated ferroptosis, a type of programmed cell death mechanism, in human hearts donated after brain death (DBD) and those donated after circulatory death (DCD), focusing on warm ischemia time (WIT) and cold storage. A total of 24 hearts were procured, with six from the DBD group and 18 from the DCD group. The DCD group was divided into three subgroups, each containing six hearts, based on different WITs of 20, 40, and 60 min. All procured hearts were placed in cold storage for up to 6 h. Left ventricular biopsies were performed at 0, 2, 4, and 6 h. …

Sialidase Fusion Protein Protects Against Influenza Infection In A Cigarette Smoke-Induced Model Of Copd, Cheng-Yen Chang, Dominique Armstrong, John M Knight, Trevor V Gale, Stephen Hawley, Max Wang, Nancy Chang, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

First- and secondhand smokers are at an increased risk for influenza virus (IFV)-related respiratory failure and death. Despite approved influenza antiviral treatments, there is an unmet need for treatments that can improve outcomes in populations at risk for respiratory failure, including tobacco users with Chronic Obstructive Pulmonary Disease (COPD). Here we show that the sialidase fusion protein, DAS181, reduced viral burden, mitigated inflammation, and attenuated lung function loss, consistent with broad-spectrum anti-influenza responses in a mouse model of COPD and IFV-A infection. Treatment with DAS181 reprogramed the sialic acid-binding immunoglobulin-like lectins (Siglecs) in alveolar macrophages, increased expression of phagocytic marker …

Insights Into Protection Against Mycobacterium Tuberculosis Infection: Time To Officially Confirm Another Phenotype?, Todia P Setiabudiawan, Philip C Hill, Andrew R Dinardo, Reinout Van Crevel

Faculty, Staff and Students Publications

Immune correlates of protection against infection with Mycobacterium tuberculosis (Mtb) remain elusive. In this issue of the JCI, Dallmann-Sauer and authors demonstrate that lack of tuberculin skin test (TST) and interferon γ release assay (IGRA) conversion among people with HIV despite years-long Mtb exposure is associated with alveolar lymphocytosis, including specific poly-cytotoxic T cells, and M1-type alveolar macrophages with a stronger ex vivo response to the pathogen. Studies in these rare individuals, termed "TB resisters" and in tuberculosis household contacts who are repeatedly IGRA negative in the months after a specific exposure event (known as "early clearers") help elucidate manipulatable …

Communicating Blood Test Results In Primary Care: A Mixed-Methods Systematic Review, Helen Nankervis, Alyson L Huntley, Penny Whiting, William Hamilton, Hardeep Singh, Sarah Dawson, Rachel O'Donnell, Jane Sprackman, Anna Ferguson Montague, Jessica Watson

Faculty, Staff and Students Publications

Background: Online records access, including test results, was rolled out as part of changes to the GP contract in England in 2023. Blood test result communication is important for patient-centred care, patient safety, and primary care workload. Evidence is needed to ensure that test results are communicated safely and efficiently to patients in primary care.

Aim: To summarise existing evidence for blood test result communication between primary care providers and their patients and carers.

Design and setting: A mixed-methods systematic review was undertaken.

Method: MEDLINE, Embase, PsycInfo (Ovid), CINAHL (EBSCOhost), and the Cochrane Library were searched from January 2013-September 2023. …

“Everything Is Electronic Health Record-Driven”: The Role Of The Electronic Health Record In The Emergency Department Diagnostic Process, Tyler G James, Courtney W Mangus, Sarah J Parker, P Paul Chandanabhumma, C M Cassady, Fernanda Bellolio, Kalyan Pasupathy, Milisa Manojlovich, Hardeep Singh, Prashant Mahajan

Faculty, Staff and Students Publications

Objectives: There is limited knowledge on how providers and patients in the emergency department (ED) use electronic health records (EHRs) to facilitate the diagnostic process. While EHRs can support diagnostic decision-making, EHR features that are not user-centered may increase the likelihood of diagnostic error. We aimed to identify how EHRs facilitate or impede the diagnostic process in the ED and to identify opportunities to reduce diagnostic errors and improve care quality.

Materials and methods: We conducted semistructured interviews with 10 physicians, 15 nurses, and 8 patients across 4 EDs. Data were analyzed using a hybrid thematic analysis approach, which blends …

Soluble Mesothelin-Related Peptide As A Prognosticator In Pleural Mesothelioma Patients Receiving Checkpoint Immunotherapy, Sonali Mitra, Hee-Jin Jang, Allen Kuncheria, Sung Wook Kang, Jong Min Choi, Ji Seon Shim, Claire Lee, Priyanka Ranchod, Peter Jindra, Maheshwari Ramineni, Meera Patel, R Taylor Ripley, Shawn S Groth, Shanda H Blackmon, Bryan M Burt, Hyun-Sung Lee

Faculty, Staff and Students Publications

Background: Immune checkpoint therapy (ICT) has significantly impacted the treatment of malignant pleural mesothelioma (MPM). Despite some promising results from combination therapies, nearly half of MPM patients do not benefit, underscoring the urgent need for reliable predictive biomarkers. This study assesses the prognostic value of serum soluble mesothelin-related peptide (SMRP) and PD-L1 levels in MPM patients receiving ICT.

Methods: We conducted a retrospective analysis of 125 MPM patients treated with ICT by measuring pre-ICT serum levels of SMRP and PD-L1. We also examined the correlation of these serum levels with tumor mRNA expressions of mesothelin and PD-L1. Both univariable and …

Limosilactobacillus Reuteri Promotes The Expression And Secretion Of Enteroendocrine- And Enterocyte-Derived Hormones, Sara C Di Rienzi, Heather A Danhof, Micah D Forshee, Ari Roberts, Robert A Britton

Faculty, Staff and Students Publications

Intestinal microbes can beneficially impact host physiology, prompting investigations into the therapeutic usage of such microbes in a range of diseases. For example, human intestinal microbe Limosilactobacillus reuteri strains ATCC PTA 6475 and DSM 17938 are being considered for use for intestinal ailments, including colic, infection, and inflammation, as well as for non-intestinal ailments, including osteoporosis, wound healing, and autism spectrum disorder. While many of their beneficial properties are attributed to suppressing inflammatory responses, we postulated that L. reuteri may also regulate intestinal hormones to affect physiology within and outside of the gut. To determine if L. reuteri secreted factors …

Uterine Pgrmc2 Deficiency Attenuates Endometrial Hyperplasia And Cancer And Prolongs Lifespan In A Pten Loss-Of-Function-Induced Cancer Model, Nicole C Kelp, Cindy A Pru, Sandeep Paudel, John P Lydon, J Julie Kim, John J Peluso, James K Pru

Faculty, Staff and Students Publications

The expression of members of the progesterone receptor membrane component (PGRMC) family, particularly PGRMC1, is elevated in diverse types of cancers, particularly those of the female reproductive system. While xenograft tumor studies using human transformed cell lines in immunocompromised mice have suggested that PGRMC1 enhances tumor growth and chemoresistance, the exact role of members of the PGRMC family in cancer development in vivo remains unclear. In this study, we examined the effect of deleting Pgrmc2 on the development of endometrial hyperplasia and cancer using a murine phosphatase and tensin homologue (Pten) conditional loss-of-function model. We previously established that …

Association Of Parental Oral Health Knowledge And Self-Efficacy With Early Childhood Caries And Oral Health Quality Of Life In Texas Schoolchildren, Shreela V Sharma, Jeanette E Deason, Mengxi Wang, Alejandra Garcia-Quintana, Ru-Jye Chuang, Kila Johnson, Shalisa Garner, Steven Kelder, Jose-Miguel Yamal

Faculty, Staff and Student Publications

Improving children's oral health is a national priority. Parental knowledge and self-efficacy influence children's health behaviors; however, the relationship between parental oral health-related knowledge, self-efficacy, child oral health-related quality of life (OHQoL), and dental caries remains unclear, especially among low-income, ethnically diverse U.S. families. This study assesses the relationship between parental oral health-related knowledge, self-efficacy, child dental caries, and OHQoL. This cross-sectional seco ndary analysis uses baseline data from a school-based cluster-randomized controlled trial among children (kindergarten-second grade). Dental assessments were conducted using the International Caries Detection and Assessment System (ICDAS) on site in schools at baseline (n = 34 …

Antimicrobial Performance Of A Novel Drug-Eluting Bioenvelope, Zerelda Esquer Garrigos, Sunil Kapur, Michelle Leroux Williams, M Rizwan Sohail

Faculty, Staff and Students Publications

No abstract provided.

Emerging Clostridioides Difficile Ribotypes Have Divergent Metabolic Phenotypes, Firas S Midani, Heather A Danhof, Nathanael Mathew, Colleen K Ardis, Kevin W Garey, Jennifer K Spinler, Robert A Britton

Faculty, Staff and Students Publications

Clostridioides difficile is a gram-positive spore-forming pathogen that commonly causes diarrheal infections in the developed world. Although C. difficile is a genetically diverse species, certain ribotypes are overrepresented in human infections, and it is unclear if metabolic adaptations are essential for the emergence of these epidemic ribotypes. To identify ribotype-specific metabolic differences, we therefore tested carbon substrate utilization by 88 C. difficile isolates and looked for differences in growth between 22 ribotypes. As expected, C. difficile was capable of growing on a variety of carbon substrates. Further, C. difficile strains clustered by phylogenetic relationship and displayed ribotype-specific and clade-specific …

Author Correction: Generation Of A Tree Shrew Breast Cancer Model Using Lentivirus Expressing Pik3ca-H1047r, Li Zeng, Hong-Yan Zhang, Chuan-Yu Yang, Zhuo Cheng, Qiu-Yun Jiang, Yao Luo, Yi Li, Fu-Bing Li, Ce-Shi Chen

Faculty, Staff and Students Publications

No abstract provided.

The Autophagy Protein Atg14 Safeguards Against Unscheduled Pyroptosis Activation To Enable Embryo Transport During Early Pregnancy, Pooja Popli, Arin K Oestreich, Vineet K Maurya, Marina N Rowen, Yong Zhang, Michael J Holtzman, Ramya Masand, John P Lydon, Shizuo Akira, Kelle Moley, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Recurrent pregnancy loss, characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage. However, our understanding of the biological processes that preserve the oviductal cellular structure and functional integrity is limited. Here, we report that autophagy-related protein ATG14 plays a crucial role in maintaining the cellular integrity of the oviduct by …

Control Of Clostridioides Difficile Virulence And Physiology By The Flagellin Homeostasis Checkpoint Flic-Fliw-Csra In The Absence Of Motility, Duolong Zhu, Katherine J Wozniak, Firas Midani, Shaohui Wang, Xingmin Sun, Robert A Britton

Faculty, Staff and Students Publications

Mutations affecting Clostridioides difficile flagellin (FliC) have been shown to be hypervirulent in animal models and display increased toxin production and alterations in central metabolism. The regulation of flagellin levels in bacteria is governed by a tripartite regulatory network involving fliC, fliW, and csrA, which creates a feedback system to regulate flagella production. Through genomic analysis of C. difficile clade 5 strains (non-motile), we identified they have jettisoned many of the genes required for flagellum biosynthesis yet retain the major flagellin gene fliC and regulatory gene fliW. We therefore investigated the roles of fliC, fliW …

Hematopoietic Cell Transplant Compared With Standard Care In Adolescents And Young Adults With Sickle Cell Disease, Mark C Walters, Mary Eapen, Yiwen Liu, Fuad El Rassi, Edmund K Waller, John E Levine, John J Strouse, Joseph H Antin, Suhag H Parikh, Nitya Bakshi, Carlton Dampier, Jennifer J Jaroscak, Shayla Bergmann, Trisha Wong, Vamsi Kota, Betty Pace, Lazaros J Lekakis, Premal Lulla, Robert S Nickel, Kimberly A Kasow, Uday Popat, Wally Smith, Lolie Yu, Nancy Difronzo, Nancy Geller, Naynesh Kamani, Elizabeth S Klings, Kathryn Hassell, Adam Mendizabal, Keith Sullivan, Donna Neuberg, Lakshmanan Krishnamurti

Faculty, Staff and Students Publications

Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2 years after biologic assignment to a donor or no donor (SOC) arm based on the availability of an HLA-matched sibling or unrelated donor (BMT CTN 1503). A donor search was commenced after eligibility confirmation. The primary end point was a comparison of survival between the treatment arms 2 years after biologic assignment. Power calculations required 60 participants in the donor arm and 140 in the no donor arm to determine if early transplant-related mortality …

Clinical And Genetic Markers Of Vascular Toxicity In Glioblastoma Patients: Insights From Nrg Oncology Rtog-0825, Joshua D Strauss, Mark R Gilbert, Minesh Mehta, Ang Li, Renke Zhou, Melissa L Bondy, Erik P Sulman, Ying Yuan, Yanhong Liu, Elizabeth Vera, Merideth M Wendland, Volker W Stieber, Vinay K Puduvalli, Serah Choi, Nina L Martinez, H Ian Robins, Grant K Hunter, Chi-Fan Lin, Vivian A Guedes, Melissa A Richard, Stephanie L Pugh, Terri S Armstrong, Michael E Scheurer

Faculty, Staff and Students Publications

Background: Glioblastoma (GBM) is an aggressive form of brain cancer in which treatment is associated with toxicities that can result in therapy discontinuation or death. This analysis investigated clinical and genetic markers of vascular toxicities in GBM patients during active treatment.

Methods: In total, 591 non-Hispanic White GBM patients with clinical data were included in the analysis from NRG RTOG-0825. Genome-wide association studies (GWAS) were performed from genotyped blood samples (N = 367) by occurrence of thrombosis or hypertension (grade ≥ 2). A clinical prediction model was produced for each vascular toxicity. Significant GWAS variants were then added to the …

Impact Of Primary Care Team Configuration On Access And Quality Of Care, Sylvia J Hysong, Kelley Arredondo, Houston F Lester, Richard Sorelle, Trang Pham, Frederick L Oswald, Lechauncy Woodard, Laura A Petersen, Joshua Hamer, Ashley M Hughes

Faculty, Staff and Students Publications

Background: Team-based primary care has become the norm within many large healthcare systems; however, limited guidance exists on how to optimally staff primary care teams in relationship to healthcare.

Objective: This paper examines the associations between variations in team staffing configurations on primary care access and clinical quality.

Design: Observational study linking national Veterans Health Administration (VHA) data from February 2020 on primary care team staffing configurations to data on access to and quality of care the teams delivered.

Participants: We examined data from 22,390 primary care personnel assigned to 7050 teams from 1050 VA Medical Centers and Community-Based Outpatient …

Pregnancy In Women Receiving Maintenance Dialysis, Cristina Popa, Priyadarshini John, Prasoon Verma, Sehrish Ali, Silvi Shah

Faculty, Staff and Students Publications

Women with kidney failure experience pathophysiological changes that frequently result in disruption of the hypothalamic-pituitary-ovarian axis. Because of these hormonal disturbances, women with kidney disease often experience oligomenorrhea, amenorrhea, sexual dysfunction, and infertility. Preconception counseling, partnered with the early identification and optimal management of risk factors, such as hypertension and discontinuation of teratogenic medications, should be pursued for females contemplating conception. Pregnancy in women receiving maintenance dialysis is associated with a high risk of adverse maternal and fetal outcomes and should be managed by a multidisciplinary team of providers. In this review article, we discuss pregnancy incidence, pregnancy outcomes, and …

Irisin-Mediated Muscle-Renal Crosstalk As A Protective Mechanism Against Contrast-Induced Acute Kidney Injury Via Cgas-Sting Signalling Inhibition, Long Peng, Suhua Li, Qiang Huang, Yuxiang Sun, Juan Sun, Ting Luo, Yanlin Wang, Zhaoyong Hu, Weiyan Lai, Hui Peng

Faculty, Staff and Students Publications

Background: Contrast-induced acute kidney injury (CI-AKI) continues to pose a pressing clinical challenge during invasive cardiovascular procedures due to the limited availability of preventative strategies. We aimed to demonstrate that irisin, a myokine induced by exercise, protects against CI-AKI by inhibiting the cGAS-STING inflammatory pathway.

Methods and results: We explored the relationship between serum irisin levels and CI-AKI incidence in patients administered the contrast media iohexol. Notably, lower serum irisin levels were strongly associated with an increased incidence of CI-AKI following contrast media administration. To establish a causal link between serum irisin levels and CI-AKI, we utilised a mouse model …

Epidemiology Of Diagnostic Errors In Pediatric Emergency Departments Using Electronic Triggers, Prashant Mahajan, Emily White, Kathy Shaw, Sarah J Parker, James Chamberlain, Richard M Ruddy, Elizabeth R Alpern, Jacqueline Corboy, Andrew Krack, Brandon Ku, Daphne Morrison Ponce, Asha S Payne, Elizabeth Freiheit, Gregor Horvath, Giselle Kolenic, Michele Carney, Nicole Klekowski, Karen J O'Connell, Hardeep Singh

Faculty, Staff and Students Publications

Objectives: We applied three electronic triggers to study frequency and contributory factors of missed opportunities for improving diagnosis (MOIDs) in pediatric emergency departments (EDs): return visits within 10 days resulting in admission (Trigger 1), care escalation within 24 h of ED presentation (Trigger 2), and death within 24 h of ED visit (Trigger 3).

Methods: We created an electronic query and reporting template for the triggers and applied them to electronic health record systems of five pediatric EDs for visits from 2019. Clinician reviewers manually screened identified charts and initially categorized them as "unlikely for MOIDs" or "unable to rule …

Advances In Idiopathic Pulmonary Fibrosis Diagnosis And Treatment, Hongli Liu, Jiaxi Shen, Chao He

Faculty, Staff and Students Publications

Significant advances have been made in diagnosing and treating idiopathic pulmonary fibrosis (IPF) in the last decade. The incidence and prevalence of IPF are increasing, and morbidity and mortality remain high despite the two Food and Drug Administration (FDA)-approved medications, pirfenidone and nintedanib. Hence, there is an urgent need to develop new diagnostic tools and effective therapeutics to improve early, accurate diagnosis of IPF and halt or reverse the progression of fibrosis with a better safety profile. New diagnostic tools such as transbronchial cryobiopsy and genomic classifier require less tissue and generally have good safety profiles, and they have been …

The Association Between Gulf War Illness And Suicidal Thoughts And Behaviors Among Gulf War Era Veterans, Rachele K Lipsky, Drew A Helmer, Jean C Beckham, Patrick S Calhoun, Mary Jo Pugh, Nathan A Kimbrel

Faculty, Staff and Students Publications

The rate of death by suicide is elevated among Veterans of all eras. Chronic symptoms of pain, depression, and sleep disturbances are also common among Veterans, and these symptoms are associated with suicidal thoughts and behaviors. About 25% of the 697,000 Gulf War Era Veterans deployed to the Persian Gulf theater in 1990-1991 remain afflicted with chronic, unexplained symptoms known as Gulf War Illness (GWI). This study used data from a national sample of Gulf War Veterans (N = 1142) who completed a survey of demographic, military, and health information. Multivariable logistic regression models, controlling for confounding variables, tested for …

Distinct Single-Cell Transcriptional Profile In Cd4+ T-Lymphocytes Among Obese Children With Asthma, Vickram Tejwani, Rulin Wang, Andres Villabona-Rueda, Karthik Suresh, Tianshi David Wu, Ian M Adcock, Nazanin Z Kermani, Joe Zein, Nadia N Hansel, Srinivasan Yegnasubramanian, Meredith C Mccormack, Franco R D'Alessio

Faculty, Staff and Students Publications

Obesity is a risk factor for asthma morbidity, associated with less responsiveness to inhaled corticosteroids. CD4+ T cells are central to the immunology of asthma and may contribute to the unique obese asthma phenotype. We sought to characterize the single-cell CD4+ transcriptional profile differences in obese children with asthma compared with normal-weight children with asthma. Eight normal-weight and obese participants with asthma were clinically phenotyped and matched based on asthma control. Peripheral blood (PB) CD4+ T cells were sorted, and single-cell RNA sequencing was conducted. Cell clusters were identified by canonical gene expression and differential gene expression and reactome pathway …

Canonical And Non-Canonical Functions Of The Non-Coding Rna Component (Terc) Of Telomerase Complex, Chongwen Cao, Weiyi Gong, Yuanlong Shuai, Sara Rasouli, Qianyun Ge, Anam Khan, Aleksandra Dakic, Nagireddy Putluri, Gennady Shvets, Yun-Ling Zheng, Danyal Daneshdoust, Rani Mahyoob, Jenny Li, Xuefeng Liu

Faculty, Staff and Students Publications

The telomerase complex consists of a protein component (TERT), which has reverse transcriptase activity, and an RNA component (TERC), which serves as a template for telomere synthesis. Evidence is rapidly accumulating regarding the non-canonical functions of these components in both normal or diseased cells. An oligonucleotide-based drug, the first telomerase inhibitor, secured FDA approval in June 2024. We recently summarized the non-canonical functions of TERT in viral infections and cancer. In this review, we expand on these non-canonical functions of TERC beyond telomere maintenance. Specifically, we explore TERC's roles in cellular aging and senescence, immune regulation, genetic diseases, human cancer, …

Multiscale 3d Spatial Analysis Of The Tumor Microenvironment Using Whole-Tissue Digital Histopathology, Daniel Shafiee Kermany, Ju Young Ahn, Matthew Vasquez, Weijie Zhang, Lin Wang, Kai Liu, Zhan Xu, Min Soon Cho, Wendolyn Carlos-Alcalde, Hani Lee, Raksha Raghunathan, Jianting Sheng, Xiaoxin Hao, Hong Zhao, Vahid Afshar-Kharghan, Xiang Hong-Fei Zhang, Stephen Tin Chi Wong

Faculty, Staff and Students Publications

No abstract provided.

Pitavastatin Is Well-Tolerated With No Detrimental Effects On Physical Function, Kristine M Erlandson, Triin Umbleja, Heather J Ribaudo, Jennifer A Schrack, Edgar T Overton, Carl J Fichtenbaum, Kathleen V Fitch, Jhoanna C Roa, Marissa R Diggs, Kenneth Wood, Markella V Zanni, Gerald S Bloomfield, Carlos Malvestutto, Judith A Aberg, Maria C Rodriguez-Barradas, Rosalba Gomez Morones, Katherine Breaux, Pamela S Douglas, Steven K Grinspoon, Todd T Brown

Faculty, Staff and Students Publications

Background: Little is known about the potential benefits or harms of statins on physical function among people with human immunodeficiency virus (PWH).

Methods: REPRIEVE was a double-blind randomized controlled trial evaluating pitavastatin for primary prevention of major adverse cardiovascular events in PWH. Time to complete 10 chair rises, 4-m gait speed, grip strength, and a modified short physical performance test were assessed annually for up to 5 years in the ancillary study PREPARE and analyzed using linear mixed models.

Findings: Of 602 PWH, 52% were randomized to pitavastatin and 48% to placebo. Median age was 51 years; 18% were female …

Invasion And Metastasis In Cancer: Molecular Insights And Therapeutic Targets, Yongxing Li, Fengshuo Liu, Qingjin Cai, Lijun Deng, Qin Ouyang, Xiang H-F Zhang, Ji Zheng

Faculty, Staff and Students Publications

The progression of malignant tumors leads to the development of secondary tumors in various organs, including bones, the brain, liver, and lungs. This metastatic process severely impacts the prognosis of patients, significantly affecting their quality of life and survival rates. Research efforts have consistently focused on the intricate mechanisms underlying this process and the corresponding clinical management strategies. Consequently, a comprehensive understanding of the biological foundations of tumor metastasis, identification of pivotal signaling pathways, and systematic evaluation of existing and emerging therapeutic strategies are paramount to enhancing the overall diagnostic and treatment capabilities for metastatic tumors. However, current research is …