Medicine and Health Sciences Commons^™

Update On Pediatric Surveillance Recommendations For Pten Hamartoma Tumor Syndrome, Dicer1-Related Tumor Predisposition, And Tuberous Sclerosis Complex, Kris Ann P Schultz, Suzanne P Macfarland, Melissa R Perrino, Sarah G Mitchell, Junne Kamihara, Alexander T Nelson, Paige H R Mallinger, Jack J Brzezinski, Kara N Maxwell, Emma R Woodward, Bailey Gallinger, Sun Young Kim, Mary-Louise C Greer, Kami Wolfe Schneider, Sarah R Scollon, Anirban Das, Jonathan D Wasserman, Charis Eng, David Malkin, William D Foulkes, Orli Michaeli, Andrew J Bauer, Douglas R Stewart

Faculty, Staff and Students Publications

Phosphate and tensin homolog hamartoma tumor syndrome, DICER1-related tumor predisposition, and tuberous sclerosis complex are rare conditions, which each increases risk for distinct spectra of benign and malignant neoplasms throughout childhood and adulthood. Surveillance considerations for each of these conditions focus on patient and family education, early detection, and multidisciplinary care. In this article, we present updated surveillance recommendations and considerations for children and adolescents with phosphate and tensin homolog hamartoma tumor syndrome, DICER1-related tumor predisposition, and tuberous sclerosis complex and provide suggestions for further research in each of these conditions.

Evolution Of The Umbilical Cord Blood Proteome Across Gestational Development, Leena B Mithal, Nicola Lancki, Ted Ling-Hu, Young Ah Goo, Sebastian Otero, Nathaniel J Rhodes, Byoung-Kyu Cho, William A Grobman, Judd F Hultquist, Denise Scholtens, Karen K Mestan, Patrick C Seed

2020-Current year OA Pubs

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth. In this study, we comprehensively characterized the cord blood proteome of infants born between 25 to 42 weeks using untargeted mass spectrometry and functional enrichment analysis. We determined that the cord blood proteome at birth varies significantly across gestational development. …

Process Evaluation Of The Hockey Fans In Training Lifestyle Intervention (For Men With Overweight Or Obesity)., Wendy M Blunt, Marisa L Kfrerer, Dawn P. Gill, Katie J Shillington, Brendan Riggin, Jennifer D Irwin, Brooke Bliss, Robert J Petrella

Department of Medicine Publications

BACKGROUND: Despite the proven relationship between lifestyle and morbidity and mortality, rates of chronic disease (e.g. obesity) continue to rise in paradox to the myriad of studies supporting lifestyle behaviour change. Men have been less likely to seek out preventative care or lifestyle programs, putting them at risk. In response, Hockey Fans In Training (Hockey FIT) was developed as a group-based, lifestyle intervention leveraging the draw of hockey fandom to engage middle-aged men with overweight or obesity in lifestyle change. Encouraging pilot study results informed the optimization and delivery of the intervention through a cluster randomized controlled trial in 42 …

Molecular Determinants Of Condensate Composition, Alex S Holehouse, Simon Alberti

2020-Current year OA Pubs

Cells use membraneless compartments to organize their interiors, and recent research has begun to uncover the molecular principles underlying their assembly. Here, we explore how site-specific and chemically specific interactions shape the properties and functions of condensates. Site-specific recruitment involves precise interactions at specific sites driven by partially or fully structured interfaces. In contrast, chemically specific recruitment is driven by complementary chemical interactions without the requirement for a persistent bound-state structure. We propose that site-specific and chemically specific interactions work together to determine the composition of condensates, facilitate biochemical reactions, and regulate enzymatic activities linked to metabolism, signaling, and gene …

A Yeast-Based Oral Therapeutic Delivers Immune Checkpoint Inhibitors To Reduce Intestinal Tumor Burden, Olivia N Rebeck, Miranda J Wallace, Jerome Prusa, Jie Ning, Esse M Evbuomwan, Sunaina Rengarajan, Lemoyne Habimana-Griffin, Suryang Kwak, David Zahrah, Jason Tung, James Liao, Bejan Mahmud, Skye R S Fishbein, Erick S Ramirez Tovar, Rehan Mehta, Bin Wang, Mark G Gorelik, Gautam Dantas, Et Al.

2020-Current year OA Pubs

Engineered probiotics are an emerging platform for in situ delivery of therapeutics to the gut. Herein, we developed an orally administered, yeast-based therapeutic delivery system to deliver next-generation immune checkpoint inhibitor (ICI) proteins directly to gastrointestinal tumors. We engineered Saccharomyces cerevisiae var. boulardii (Sb), a probiotic yeast with high genetic tractability and innate anticancer activity, to secrete "miniature" antibody variants that target programmed death ligand 1 (Sb_haPD-1). When tested in an ICI-refractory colorectal cancer (CRC) mouse model, Sb_haPD-1 significantly reduced intestinal tumor burden and resulted in significant shifts to the immune cell profile and microbiome composition. This oral therapeutic platform …

N-Glycosylation In The Serpin Domain Of The C1-Esterase Inhibitor In Hereditary Angioedema, Zhen Ren, John Bao, Shuangxia Zhao, Nicola Pozzi, H. James Wedner, John P. Atkinson

2020-Current year OA Pubs

Hereditary angioedema is an autosomal dominant disorder caused by defects in C1-esterase inhibitor (C1-INH), resulting in poorly controlled activation of the kallikrein-kinin system and bradykinin overproduction. C1-INH is a heavily glycosylated protein in the serine protease inhibitor (SERPIN) family, yet the role of these glycosylation sites remains unclear. To elucidate the functional impact of N-glycosylation in the SERPIN domain of C1-INH, we engineered 4 sets consisting of 26 variants at or near the N-linked sequon (NXS/T). Among these, 6 are reported in patients with hereditary angioedema and 5 are known C1-INH variants without accessible clinical histories. We systematically evaluated their …

Hiv Associated Epigenetic Trends And Chronic Diseases: Insights Into The Hidden Burden Of Chronic Infection, Courtney G. Wallace, Zachary Capriotti, Zachary Klase

Kimmel Cancer Center Faculty Papers

Human Immunodeficiency Virus (HIV) remains a major health challenge despite dramatic advances in treatment and prevention. People living with HIV (PLWH) continue to experience high rates of non-AIDS comorbidities, including cardiovascular, renal, pulmonary, oncologic, and neurocognitive disorders. These conditions persist under viral suppression, underscoring the lasting biological impact of infection. Epigenetic dysregulation has emerged as a key driver of these outcomes. HIV integration, viral proteins, chronic inflammation, and ART exposure have all been reported to alter DNA methylation, histone modifications, transcription factor networks, and noncoding RNA regulation. These changes extend beyond infected cells, reprogramming uninfected immune and tissue compartments. Long-lived …

Atrial Fibrillation Recurrence Risk After Catheter Ablation In Patients With Rheumatoid Arthritis: A Systematic Review And Meta-Analysis, Pongprueth Rujirachun, Phuuwadith Wattanachayakul, Svita Taveeamornrat, Patompong Ungprasert, Nithi Tokavanich, Krit Jongnarangsin

Einstein Health Papers

BACKGROUND: The association between rheumatoid arthritis (RA) and the risk of developing atrial fibrillation (AF) is well-established. However, data on the impact of RA on AF recurrence postcatheter ablation (CA) remain unclear. This current study aimed to assess the impact of RA on AF recurrence after catheter-based pulmonary vein isolation.

METHODS: Potentially eligible studies were identified from Medline and EMBASE databases from inception to December 20, 2023. Eligible study must consist of two cohorts of patients with and without RA who underwent catheter ablation for AF. Pooled risk ratio (RR) and 95% CI were calculated using Dersimonian and Laird's random-effect, …

Using Implementation Mapping To Design An Implementation Strategy For Classroom-Based Physical Activity Approaches In Elementary Schools, Timothy J Walker, Derek W Craig, Christopher D Pfledderer, Kempson Onadeko, Emma E Saving, Hildi M Nicksic, Krista Patlovich, Keisey Fumero, John B Bartholomew, Maria E Fernández

Faculty, Staff and Student Publications

Background: Physically active breaks and lessons are evidence-based approaches to improving student's physical activity. Yet, schools and teachers face implementation challenges, requiring the need for effective implementation strategies.

Purpose: Use Implementation Mapping to develop an implementation strategy for physically active breaks and lessons in elementary schools.

Methods: With our partner school district, we assembled a planning group with expertise in education, public health, and implementation science. The group completed five Implementation Mapping tasks: (i) conduct needs and assets assessment and identify adopters and implementers, (ii) identify implementation outcomes, performance objectives, and determinants, and create matrices of change objectives, (iii) choose …

Improving Cooking Skills, Lifestyle Behaviors, And Clinical Outcomes For Adults At Risk For Cardiometabolic Disease: Protocol For A Randomized Teaching Kitchen Multisite Trial (Tk-Mt), Jennifer Massa, Candace Sapp, Kate Janisch, Mopelola A Adeyemo, Auden Mcclure, Natalia I Heredia, Deanna M Hoelscher, Tannaz Moin, Shaista Malik, Wendelin Slusser, David M Eisenberg

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVES: This protocol describes a study to investigate the feasibility and preliminary efficacy of a novel Teaching Kitchen Multisite Trial (TK-MT) for adults with cardiometabolic abnormalities. The TK-MT protocol describes a hybrid lifestyle intervention combining in-person and virtual instruction in culinary skills, nutrition education, movement, and mindfulness with community support and behavior change strategies. This 18-month-long randomized controlled trial aims to evaluate the feasibility of implementing a 12-month, 24 class program, assess preliminary study efficacy, and identify barriers and facilitators to implementation.

METHODS: The intervention program includes 16 weeks of intensive hands-on culinary and lifestyle education classes followed by eight …

Phase I Study Of Bms-986299, An Nlrp3 Agonist, As Monotherapy And In Combination With Nivolumab And Ipilimumab In Patients With Advanced Solid Tumors, Blessie E Nelson, Shaun O'Brien, Rahul A Sheth, David S Hong, Aung Naing, Xiaoping Zhang, Amy Xu, Lora Hamuro, Rasika Suryawanshi, Derrick Mckinley, Ruslan D Novosiadly, Sarina A Piha-Paul

Faculty, Staff and Student Publications

Purpose: BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune and T-cell memory responses.

Materials and methods: This was a phase-I (NCT03444753) study that assessed the safety and tolerability of intra-tumoral BMS-986299 monotherapy (part 1A) and in combination (part 1B) with nivolumab, and ipilimumab in advanced solid tumors. Reported here are single-center results.

Results: 36 patients were enrolled, with breast (31%), colorectal (17%), and head and neck (14%) being the more commonly enrolled cancers. Most patients (58%) had received prior immunotherapy. Therapy was well-tolerated, with G1-G2 fever (70%), neutrophilia (36%), and leukocytosis …

Protein Translation Rates Are Negatively Correlated With Lifespan In Inbred Drosophila Strains, Harper S Kim, Madison M Hardiman, Andrew M Pickering

Faculty, Staff and Student Publications

No abstract provided.

Discontiguous Recurrences Of Idh-Wildtype Glioblastoma Share A Common Origin With The Initial Tumor And Are Frequently Hypermutated, Malcolm F Mcdonald, Sricharan Gopakumar, Tareq A Juratli, Ilker Y Eyüpoglu, Ganesh Rao, Jacob J Mandel, Ali Jalali

Faculty, Staff and Students Publications

Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences. In our institutional database, we identified 22 patients with targeted exome sequencing of pairs of initial and recurrent IDH-wildtype glioblastoma. Recurrences were classified as contiguous or discontiguous based on the presence or absence of T2 FLAIR signal connection to the initial site of disease on MRI. Exome analysis revealed shared driver and passenger mutations between discontiguous recurrences …

Synesis As A Framework To Enable Safety Interventions In Complex Healthcare Environments, Aarti Bavare, Tiffany Wrenn, Anne Lam, Jamie Cargill, Lauren Salinas, Itode Idowu, Asma Razavi, Venessa Lynn Pinto, Eric Williams

Faculty, Staff and Students Publications

BACKGROUND: Despite wide adoption in the healthcare of safety event report (SER) systems, there is a paucity of unified structures for prompt analysis and action while retaining reporter confidentiality. We used a synesis framework to change siloed reviews of safety reports to a comprehensive appraisal of quality, safety, productivity and reliability to facilitate interventions.

METHODS: After a needs assessment survey, we launched serial plan-do-study-act cycles to (1) enhance teams' ability to access SERs, (2) facilitate regular multidisciplinary review of SERs to identify actionable opportunities, (3) allocate action priority using failure mode and effects analysis, and (4) launch actions and summarise …

Associations Between Deficit Accumulation Frailty And Baseline Markers Of Lifestyle In The Us Pointer Trial, Mark A Espeland, Yitbarek N Demesie, Kayloni Olson, Samuel N Lockhart, Sarah E Tomaszewski Farias, Maryjo L Cleveland, Christy C Tangney, Lucia Crivelli, Heather M Snyder, Michele K York, Laura D Baker, Rachel A Whitmer, Rena R Wing, Katelyn R Garcia, Kathryn E Callahan

Faculty, Staff and Students Publications

BACKGROUND: Multidomain lifestyle interventions may have the potential to slow biological aging as captured by deficit accumulation frailty indices. We describe the distribution and composition of the 49-component frailty index developed by the U.S. POINTER clinical trial team of investigators and assess its cross-sectional associations with sociodemographic factors and markers chosen to be representative of behaviors targeted by the trial's multidomain interventions.

METHODS: We draw baseline data from the 2 111 volunteers enrolled in U.S. POINTER who were ages 60-79 years and at increased risk for cognitive decline. Frailty components were grouped into 9 domains. Associations that frailty index scores …

Rsk1 Is An Exploitable Dependency In Myeloproliferative Neoplasms And Secondary Acute Myeloid Leukemia, Tim Kong, Angelo B A Laranjeira, Christopher T Letson, Layow Yu, Shuyang Lin, Jared S Fowles, Daniel A C Fisher, Sherwin Ng, Wei Yang, Fan He, Jingxian Liu, Alexander B Kim, Maggie J Cox, Mary C Fulbright, Stacey L Rentschler, Li Ding, Grant A Challen, Stephen T Oh, Et Al.

2020-Current year OA Pubs

Myeloid malignancies are heterogenous disorders characterized by distinct molecular drivers but share convergence of oncogenic signaling pathways and propagation by ripe pro-inflammatory niches. Here, we establish a comprehensive transcriptional atlas across the spectrum of myeloproliferative neoplasms (MPN) and secondary acute myeloid leukemia (sAML) through RNA-sequencing of 158 primary samples encompassing CD34+ hematopoietic stem/progenitor cells and CD14+ monocytes. Supported by mass cytometry (CyTOF) profiling, we reveal aberrant networks of PI3K/AKT/mTOR signalling and NFκB-mediated hyper-inflammation. Combining ATAC-Seq, CUT&Tag, RNA-seq, and CyTOF, we demonstrate that targeting of ribosomal protein S6 kinase A1 (RSK1) suppresses NFκB activation and diminishes pro-inflammatory mediators including tumor necrosis …

Detection Of Elder Abuse Through Emergency Care Technicians Screening Tool Revision For Home-Based Primary Care (Detect-Rpc): A Cluster Randomised Controlled Trial Study Protocol, Brad Cannell, Nicholas Sevey, Melvin D Livingston, Jason Burnett, Kristin Lees Haggerty, Carolyn Pickering

Faculty, Staff and Student Publications

Introduction: The annual prevalence of elder mistreatment (EM) in cognitively intact older adults is estimated to be 11%, yet the annual prevalence in older adults with Alzheimer's disease and related dementias (AD/ADRD) is estimated to be as high as 75%. Associated with a decrease in quality of life and increase in risk of mortality, EM represents a significant public health burden. Home-based primary care (HBPC) providers are uniquely positioned to address the critical need for robust EM screening and reporting, especially among individuals with AD/ADRD. This protocol seeks to adapt the Detection of Elder mistreatment Through Emergency Care Technicians (DETECT) …

Electrostatic Force-Enabled Microneedle Patches That Exploit Photoredox Catalysis For Transdermal Phototherapy, Hang Zhang, Wen-Chuan Xie, Yuhang Yao, Zi-Yi Tang, Wen-Xiu Ni, Bingwu Wang, Song Gao, Jonathan L Sessler, Jun-Long Zhang

Faculty, Staff and Student Publications

Microneedle patches for topical administration of photodynamic therapy (PDT) sensitizers are attractive owing to their safety, selectivity, and noninvasiveness. However, low-efficiency photosensitizer delivery coupled with the limitations of the hypoxic tumor microenvironment remains challenging. To overcome these issues, we developed an effective microneedle patch based on intermolecular electrostatic interactions within a photosensitizer matrix containing a zinc-containing porphyrin analogue, ZnBP (w). This design improved the mechanical strength of the microneedle patch and enhanced the photosensitizer loading efficiency in aqueous environments. A key feature of the system is efficient electron transfer between ZnBP (w) and NADH upon photoirradiation. Electrostatic interactions between ZnBP …

A Case For Broadening Our View Of Mechanism In Developmental Biology, B Duygu Özpolat, Swathi Arur, Mansi Srivastava

Faculty, Staff and Student Publications

Developmental biologists can perform studies that describe a phenomenon (descriptive work) and/or explain how the phenomenon works (mechanistic work). There is a prevalent perception that molecular/genetic explanations achieved via perturbations of gene function are the primary means of advancing mechanistic knowledge. We believe this to be a limited perspective, one that does not effectively represent the breadth of work in our field. We surveyed a representative and diverse group of colleagues to share their views on what it takes to infer mechanism. Here, we briefly examine the factors that have shaped the dominant view of mechanism, summarize responses to the …

A Human Single-Neuron Dataset For Object Recognition, Runnan Cao, Peter Brunner, Nicholas J Brandmeir, Jon T Willie, Shuo Wang

2020-Current year OA Pubs

Object recognition is fundamental to how we interact with and interpret the world around us. The human amygdala and hippocampus play a key role in object recognition, contributing to both the encoding and retrieval of visual information. Here, we recorded single-neuron activity from the human amygdala and hippocampus when neurosurgical epilepsy patients performed a one-back task using naturalistic object stimuli. We employed two sets of naturalistic object images from leading datasets extensively used in primate neural recordings and computer vision models: we recorded 1204 neurons using the ImageNet stimuli, which included broader object categories (10 different images per category for …

Precision Fetal Cardiology Detects Cyanotic Congenital Heart Disease Using Maternal Saliva Metabolome And Artificial Intelligence, Ray Bahado-Singh, Nadia Ashrafi, Amin Ibrahim, Buket Aydas, Ali Yilmaz, Perry Friedman, Stewart F Graham, Onur Turkoglu

Faculty, Staff and Students Publications

Prenatal sonographic diagnosis of congenital heart disease (CHD) can lead to improved morbidity and mortality. However, the diagnostic accuracy of ultrasound, the sole prenatal screening tool, remains limited. Failed prenatal or early newborn detection of cyanotic CHD (CCHD) can have disastrous consequences. We therefore sought to use a Precision Fetal Cardiology based approach combining metabolomic profiling of maternal saliva and machine learning, a major branch of artificial intelligence (AI), for the prenatal detection of isolated, non-syndromic cyanotic CHD. Metabolomic analyses using Ultra-High Performance Liquid Chromatography/Mass Spectrometry identified 468 metabolites in the saliva. Six different AI platforms were utilized for the …

Foxr2 Targets Lhx6+/Dlx+ Neural Lineages To Drive Central Nervous System Neuroblastoma, Selin Jessa, Antonella De Cola, Bhavyaa Chandarana, Michael Mcnicholas, Steven Hébert, Adam Ptack, Damien Faury, Jessica W Tsai, Andrey Korshunov, Timothy N Phoenix, Benjamin Ellezam, David T W Jones, Michael D Taylor, Pratiti Bandopadhayay, Manav Pathania, Nada Jabado, Claudia L Kleinman

Faculty, Staff and Students Publications

Central nervous system neuroblastoma with forkhead box R2 (FOXR2) activation (NB-FOXR2) is a high-grade tumor of the brain hemispheres and a newly identified molecular entity. Tumors express dual neuronal and glial markers, leading to frequent misdiagnoses, and limited information exists on the role of FOXR2 in their genesis. To identify their cellular origins, we profiled the transcriptomes of NB-FOXR2 tumors at the bulk and single-cell levels and integrated these profiles with large single-cell references of the normal brain. NB-FOXR2 tumors mapped to LHX6+/DLX+ lineages derived from the medial ganglionic eminence, a progenitor domain in the ventral telencephalon. In vivo prenatal …

Helminth Infections Affect Host Immune Responses To Viral Infections And Vaccines, Juan García-Bernalt Diego, Pritesh Desai, Stephen T Yeung, Payal Damani-Yokota, Kamal M Khanna, Michael S Diamond, Michael Schotsaert

2020-Current year OA Pubs

Helminths are highly prevalent in many regions of the world. Due to the chronic nature of most helminth infections, these parasites are proficient immunomodulators of their hosts. This modulation often leads to skewed or even impaired immune responses against unrelated antigens, such as viruses and vaccines, which can be both beneficial and detrimental for the host. The extent of these effects and the impact on the outcomes of viral infection depends on a variety of factors including timing and tropism of both infections, pathological mechanisms, genetic background, and environmental factors. In this review, we dissect these complex interactions between virus …

Sialylated Igg Induces The Transcription Factor Rest In Alveolar Macrophages To Protect Against Lung Inflammation And Severe Influenza Disease, Saborni Chakraborty, Derek E Byers, Philip A Mudd, Michael S Diamond, Et Al.

2020-Current year OA Pubs

While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model. Mechanistic studies show that sialylated IgG mediated this protection by inducing the transcription factor repressor element-1 silencing transcription factor (REST), which repressed nuclear factor κB (NF-κB)-driven responses, preventing severe lung …

Engaging Dystonia Networks With Subthalamic Stimulation, Konstantin Butenko, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Deep brain stimulation is an efficacious treatment for dystonia. While the internal pallidum serves as the primary target, recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its surroundings have not been studied in depth. Indeed, historical targets that have been used for surgical treatment of dystonia are directly adjacent to the STN. Further, multiple types of dystonia exist, and outcomes are variable, suggesting that not all types would profit maximally from the same target. Therefore, a thorough investigation of neural substrates underlying stimulation effects on dystonia signs and symptoms is warranted. …

A Proposed Mhealth Intervention To Address Patient Barriers To Colposcopy Attendance: Qualitative Interview Study Of Clinic Staff And Patient Perspectives, Jennifer Hemler, Rachel Wagner, Brittany Sullivan, Myneka Macenat, Erin Tagai, Jazmarie Vega, Enrique Hernandez, Suzanne Miller, Kuang-Yi Wen, Charletta Ayers, Mark Einstein, Shawna Hudson, Racquel Kohler

Department of Medical Oncology Faculty Papers

BACKGROUND: Cervical cancer disparities persist among minoritized women due to infrequent screening and poor follow-up. Structural and psychosocial barriers to following up with colposcopy are problematic for minoritized women. Evidence-based interventions using patient navigation and tailored telephone counseling, including the Tailored Communication for Cervical Cancer Risk (TC3), have modestly improved colposcopy attendance. However, the efficacious TC3 intervention is human resource-intense and could have greater reach if adapted for mobile health, which increases convenience and access to health information.

OBJECTIVE: This study aimed to describe feedback from clinic staff members involved in colposcopy processes and patients referred for colposcopy regarding adaptions …

Myristoylated Eepd1 Enhances Lipolysis And Thermogenesis Through Pka Activation To Combat Obesity, Suzhen Chen, Yanping Wang, Qian Zhou, Qiqi Qian, Quanxin Jiang, Chuchu Liu, Yan Liu, Peihui Zhou, Jie Xiong, Yao Zhang, Ning Wang, Yang Emma Li, Limin Yin, Hongyuan Yang, Junli Liu

Faculty, Staff and Student Publications

Middle-aged obesity, characterized by excessive fat accumulation and systemic energy imbalance, often precedes various health complications. Recent research has unveiled a surprising link between DNA damage response and energy metabolism. Here, we explore the role of Eepd1, a DNA repair enzyme, in regulating adipose tissue function and obesity onset. Eepd1 is primarily expressed in adipose tissue, where its downregulation or deletion accelerates obesity development. We show that Eepd1 ablation hinders PKA activation, thereby inhibiting lipolysis and thermogenesis in adipose tissue. Notably, cold exposure enhances Eepd1's myristoylation, facilitating its anchorage to adipocyte membranes and subsequent activation of PKA, while a mutation …

Pre-Emptive Treatment For Cytomegalovirus Viraemia To Prevent Cytomegalovirus Disease In Solid Organ Transplant Recipients, Robin Wm Vernooij, Mini Michael, Julia Mt Colombijn, Daniel S Owers, Angela C Webster, Giovanni Fm Strippoli, Elisabeth M Hodson

Faculty, Staff and Students Publications

Background: Cytomegalovirus (CMV) is a significant cause of morbidity and death in solid organ transplant recipients. Pre-emptive treatment of patients with CMV viraemia using antiviral agents has been suggested as an alternative to routine prophylaxis to prevent CMV disease. This is an update of a Cochrane review first published in 2006 and updated in 2013.

Objectives: To determine the benefits and harms of pre-emptive treatment of CMV viraemia to prevent CMV disease and death (any cause) and the indirect effects of CMV infection (acute rejection, graft loss, opportunistic infections) in solid organ transplant recipients.

Search methods: The Cochrane Kidney and …

Surgical Outcomes And Associated Morbidity Of Active And Expectant Management Of Second-Trimester Placenta Accreta Spectrum (Pas), Jessian L Munoz, Rachel Counts, Amanda E Lacue, Kayla E Ireland, Patrick S Ramsey, Kristyn Brandi

Faculty, Staff and Students Publications

Background and Objectives: Management of second-trimester placenta accreta spectrum (PAS) is currently center-dependent with minimal evidence-based practices. This study aims to analyze outcomes of hysterectomy as second-trimester active management (AM) versus cesarean hysterectomy as expectant management (EM) in cases of PAS with intraoperative and postoperative outcomes. Materials and Methods: This study is a retrospective case-control study of patients with a pathology-confirmed diagnosis of PAS managed at a single center over 16 years (2005–2020). All cases were diagnosed during the first or second trimester by ultrasonography and managed by the same multidisciplinary team with delivery within the second trimester. Results: …

Animal Models Of Non-Respiratory, Post-Acute Sequelae Of Covid-19, Abigail Vanderheiden, Michael S Diamond

2020-Current year OA Pubs

Post-acute sequelae of COVID-19 (PASC) are a diverse set of symptoms and syndromes driven by dysfunction of multiple organ systems that can persist for years and negatively impact the quality of life for millions of individuals. We currently lack specific therapeutics for patients with PASC, due in part to an incomplete understanding of its pathogenesis, especially for non-pulmonary sequelae. Here, we discuss three animal models that have been utilized to investigate PASC: non-human primates (NHPs), hamsters, and mice. We focus on neurological, gastrointestinal, and cardiovascular PASC and highlight advances in mechanistic insight that have been made using these animal models, …