Digital Commons Network^™

Diagnostic Pearls And Pitfalls In The Interpretation Of Small Biopsies And Frozen Sections Of The Pancreatobiliary Tract, Huamin Wang, Olca Basturk

Faculty, Staff and Student Publications

No abstract provided.

Anesthetic Considerations For Repair Of Thoracoabdominal Aortic Aneurysms, David A Lyubashevsky, Thomas Powell, Ali Khalifa, Vicente Orozco-Sevilla, Daniel A Tolpin

Faculty, Staff and Students Publications

Anesthetic management of open thoracoabdominal aneurysm (TAAA) repair poses a number of challenges for even the most experienced of cardiovascular anesthesiologists. This procedure encompasses a large number of unique anesthetic techniques, including one-lung ventilation, invasive hemodynamic monitoring, left-heart bypass, massive transfusion, selective renal and visceral perfusion, and central nervous system monitoring with CSF drainage. In this article, we aim to describe the anesthetic management for thoracoabdominal aortic aneurysm repair, including preoperative workup, intraoperative management, as well as postoperative concerns in the intensive care unit.

Understaffed Home Nursing And Wellbeing Of Families Of Children With Medical Complexity, Margaret Wright, Brian Lee, Leslee Belzer, Emily J. Goodwin, Jeffrey D. Colvin

Manuscripts, Articles, Book Chapters and Other Papers

Background/Objectives: Some children with medical complexity (CMC) require home nursing (HN) to maintain their health, but many families have difficulty staffing approved HN hours. Little is known about the relationship between understaffed HN, the acute care encounter rate, and family wellbeing. This study examined the association between understaffed HN, acute care encounters, and family wellbeing among CMC. Methods: We completed a cross-sectional survey study of caregivers of CMC age 0–17 years at a children’s hospital in the Midwest US. The primary predictors were the proportion of staffed to approved HN hours and the acute care rate. The primary outcome was …

Learning Soft Tissue Deformation From Incremental Simulations, Nathan Lampen, Daeseung Kim, Xuanang Xu, Xi Fang, Jungwook Lee, Tianshu Kuang, Hannah H Deng, Michael A K Liebschner, Jaime Gateno, Pingkun Yan

Faculty, Staff and Students Publications

Background: Surgical planning for orthognathic procedures demands swift and accurate biomechanical modeling of facial soft tissues. Efficient simulations are vital in the clinical pipeline, as surgeons may iterate through multiple plans. Biomechanical simulations typically use the finite element method (FEM). Prior works divide FEM simulations into increments to enhance convergence and accuracy. However, this practice elongates simulation time, thereby impeding clinical integration. To accelerate simulations, deep learning (DL) models have been explored. Yet, previous efforts either perform simulations in a single step or neglect the temporal aspects in incremental simulations.

Purpose: This study investigates the use of spatiotemporal incremental modeling …

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 …

Altered Thermal Preference By Preoptic Estrogen Receptor Alpha Neurons In Postpartum Females, Nan Zhang, Meng Yu, Qianru Zhao, Bing Feng, Yue Deng, Jonathan C Bean, Qingzhuo Liu, Benjamin P Eappen, Yang He, Kristine M Conde, Hailan Liu, Yongjie Yang, Longlong Tu, Mengjie Wang, Yongxiang Li, Na Yin, Hesong Liu, Junying Han, Darah Ave Threat, Nathan Xu, Taylor Smiley, Pingwen Xu, Lulu Chen, Tianshu Zeng, Yanlin He, Chunmei Wang

Faculty, Staff and Students Publications

OBJECTIVE: This study aims to investigate how reproductive experience (RE) alters thermal preference and thermoregulation in female mice, with a focus on estrogen receptor alpha (ERα)-expressing neurons in the preoptic area (POA).

METHODS: Thermal preference and body temperature were measured in female mice with and without RE, and virgin female mice with selective deletion of ERα from the POA (ERα

RESULTS: We showed that female mice prefer a cooler environment starting from late pregnancy and persisting long term postpartum. Female mice with RE (>4 weeks post-weaning) displayed lower body temperature and a lower thermal preferred temperature, and lost preference …

Meeting Report: 1st International Conference On Polyploid Giant Cancer Cells-Biology, Clinical Applications, And The Birth Of A New Field In Cancer Research, Tao P Wu, Xiaoran Li, Sujuan Ba, Phil Jones, Donna E Hansel, Jinsong Liu

Faculty, Staff and Students Publications

No abstract provided.

Shifting Tuberculosis Dynamics In The Eu/Eea: Geographical And Drug Resistance Trends Among People Of Foreign Origin, 2019 To 2023, Anca Vasiliu, Veronica Cristea, Krista Stoycheva, Senia Rosales-Klintz, Christoph Lange, Dominik Zenner, Csaba Ködmön

Faculty, Staff and Students Publications

We observed shifting trends in tuberculosis (TB) epidemiology in the EU/EEA between 2019 and 2023. In 2023, TB notifications among people of foreign origin increased by 24.6% after decreasing between 2019 and 2020. The majority originated from African and East Mediterranean regions, with a 316.4% upsurge in TB among Ukrainians in 2022-23. Rifampicin-resistant/multidrug-resistant TB increased by ≥ 60% in 2019-23, mainly among Ukrainians. Rapid response to shifting epidemiological patterns is crucial for efficient TB prevention and control within the EU/EEA.

Unveiling Vaginal Fibrosis: A Novel Murine Model Using Bleomycin And Epithelial Disruption, Jennifer M Mccracken, Gisele A Calderon, Felipe Rivas, Dorothea Erxleben, Taylor Moseley, Lishore A Kumar, Daniel E Kennedy, Swathi Balaji, Adam Hall, Julie C E Hakim

Faculty, Staff and Students Publications

Vaginal fibrosis induced by cancer therapy continues to take a physical and psychoemotional burden. To advance the efforts to generate a reproducible and cost-effective animal model, we tested the effect of repeated bleomycin instillations with mucosal layer disruption on induction of vaginal fibrosis. Tissue samples collected at various time points were analyzed for fibrosis-related gene expression changes and collagen content. Low (1.5 U/kg) and high-dose (2.5 U/kg) bleomycin instillations alone did not induce fibrosis, but when high-dose bleomycin was combined with epithelial disruption, increased profibrotic gene expression and trichrome staining were observed. To evaluate spatial and temporal changes in the …

Ethical Considerations Of Percutaneous Endoscopic Gastrostomy Tube Placement In A Patient With Creutzfeldt-Jakob Disease And Advanced Dementia, Toni Habib, Niamh Siobhán Mulrooney, Yisroel Grabie, Mohammad Maruf, Sophia Kasapira

HCA Healthcare Journal of Medicine

Background

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive neurodegenerative condition that is not easily diagnosed and has no curative treatments available, essentially requiring palliative measures, including tube feeding. Nonetheless, data shows that the endoscope used for percutaneous endoscopic gastrostomy (PEG) tube insertion can be a vector for CJD transmission.

Case Presentation

We discuss the case of an elderly patient diagnosed with CJD, requiring tube feeding. Multiple specialists were consulted, and they were unable to reach an agreement on the best approach. Eventually, the hospital ethics committee intervened, and the family agreed to comfort measures only. This case report sheds light …

Updating A Rural Clinic In Tiburón, Haiti, Akankcha Alok, Mohamed Bakhit, Djenie Helne, Philipe Milord, Marcellas Socrate, Camil Clermont, Marie A. Kima

HCA Healthcare Journal of Medicine

Background

Tiburón is a small fishing village in Haiti with a clinic overseen by the Oblate missionaries and the Ministry of Public Health and Population (MSPP). This village was hugely impacted by Hurricane Matthew in 2016, leading to increased health care demands. The clinic was inaccessible from the furthest parts of the village and lacked basic medication supplies and adequate manpower. We aimed to reinforce the infrastructure and update the clinic using a multifaceted approach.

Methods

We developed a quality improvement project to strengthen the clinic's infrastructure and modernize its facilities with a comprehensive approach focused on enhancing health care …

Impact Of A Comprehensive Palliative Quality Improvement Initiative (Icu-Pal) In A Medical-Surgical Intensive Care Unit, Aunie M. Danyalian, Michele M. Iguina, Manjot Malhi, Umair Shaikh, Sanaz B. Kashan, Dionne Morgan, Daniel Heller, Mauricio Danckers

HCA Healthcare Journal of Medicine

Background

Early palliative care practice implementation in the intensive care unit (ICU) improves advance care planning, promotes patient and family satisfaction, and decreases health care costs. The consensus for protocolized palliative care delivery is unknown. We assessed the impact of a qualitive improvement educational intervention that promotes the identification of critically ill patients who will benefit from early expert palliative care interventions.

Methods

In this observational study, we examined the impact of an educational intervention that promoted (1) early detection of palliative care triggers (PCT) during ICU multidisciplinary rounds (MDRs), (2) admission and 48-hour pain assessment, and (3) family meetings …

Families' Experiences Of End-Of-Life Care In An Acute Private Hospital: A Qualitative Study, Rosemary Saunders, Susan Alexander, Julie Andrew, Anne Wilkinson, Karen Gullick, Ashwini Davray, Manonita Ghosh, Karla Seaman, Michelle Gay

Research outputs 2022 to 2026

Objectives This study explored bereaved relatives' experiences of end-of-life care (EoL care) in the last 3 days in an acute private hospital in Australia. Methods An interpretative qualitative study was conducted. Semi-structured interviews with 8 bereaved relatives whose family member had died at an acute private hospital shared their experiences of the EoL care during the last 3 days of life. The transcribed interviews were analyzed using inductive thematic analysis. Results Bereaved family members had mixed experiences, and their primary concerns related to the need for improvements in support for the family; communication; and clinicians partnering with families. The need …

Echocardiography And Heart Failure: An Echocardiographic Decision Aid For The Diagnosis And Management Of Cardiomyopathies., Ashley Pender, Jessica Lewis-Owona, Abdulmojeed Ekiyoyo, Marcus Stoddard

Division of Cardiology Faculty Papers

PURPOSE OF REVIEW: The purpose of this review is to highlight the utility of echocardiography in the diagnosis and management of cardiomyopathies.

RECENT FINDINGS: Echocardiographic parameters function synergistically to guide decision-making ranging from early detection of disease and screening to risk stratification of complex disease. The collective wealth of information available from 2D/3D assessment, Doppler, diastology and strain makes echocardiography an invaluable decision aid.

Biosocial Determinants Of Health Among Patients With Chronic Liver Disease And Liver Cancer, Tagari Samanta, Jun Hyoung Park, Benny Abraham Kaipparettu

Faculty, Staff and Students Publications

Background: Metabolic disorders and chronic liver disease (CLD) play crucial roles in the development and progression of liver cancer (LC). Since the ethnic minority population increasingly suffers from CLD and LC, it is vital to understand the biosocial factors contributing to CLD and LC. The 'All of Us' database, with significant participation from minority populations, provides a valuable tool for studies in different racial/ethnic groups. Using different databases, including the 'All of Us' and 'The Cancer Genome Atlas', this study aimed to understand the biosocial factors contributing to CLD and LC.

Methods: Using 'All of Us' data, confounding factors like …

A Review Of Gut Failure As A Cause And Consequence Of Critical Illness, Danielle E. Soranno, Craig M. Coopersmith, Jessica F. Brinkworth, Faith N. F. Factora, Julia H. Muntean, Monty G. Mythen, Jacob Raphael, Andrew D. Shaw, Vidula Vachharajani, Jeannette S. Messer

Department of Anesthesiology Faculty Papers

In critical illness, all elements of gut function are perturbed. Dysbiosis develops as the gut microbial community loses taxonomic diversity and new virulence factors appear. Intestinal permeability increases, allowing for translocation of bacteria and/or bacterial products. Epithelial function is altered at a cellular level and homeostasis of the epithelial monolayer is compromised by increased intestinal epithelial cell death and decreased proliferation. Gut immunity is impaired with simultaneous activation of maladaptive pro- and anti-inflammatory signals leading to both tissue damage and susceptibility to infections. Additionally, splanchnic vasoconstriction leads to decreased blood flow with local ischemic changes. Together, these interrelated elements of …

Intersect Between Brain Mechanisms Of Conditioned Threat, Active Avoidance, And Reward, Muhammad Badarnee, Zhenfu Wen, Mira Z Hammoud, Paul Glimcher, Christopher K Cain, Mohammed R Milad

Faculty, Staff and Student Publications

Active avoidance is a core behavior for human coping, and its excess is common across psychiatric diseases. The decision to actively avoid a threat is influenced by cost and reward. Yet, threat, avoidance, and reward have been studied in silos. We discuss behavioral and brain circuits of active avoidance and the interactions with fear and threat. In addition, we present a neural toggle switch model enabling fear-to-anxiety transition and approaching reward vs. avoiding harm decision. To fully comprehend how threat, active avoidance, and reward intersect, it is paramount to develop one shared experimental approach across phenomena and behaviors, which will …

Cold Snare Polypectomy In Pediatric Polyposis: A Multicenter Experience., Hunter J. Friesen, Thomas M. Attard, Andrew Y J Liman, Osamu W. Yasui, Catharine M. Walsh, Roberto Gugig, Monique T. Barakat

Manuscripts, Articles, Book Chapters and Other Papers

Background: Cold snare polypectomy (CSP) is a well-established and recommended technique in adult gastroenterology for the safe, efficient and complete removal of nonpedunculated lesions up to 10 mm, with piecemeal excision possible for larger lesions. However, the application of CSP in pediatric patients remains underexplored. This study summarizes a multicenter experience of CSP in pediatric polyposis patients, focusing on safety, efficacy and clinical outcomes. Methods: This retrospective study was conducted at two pediatric tertiary centers, encompassing patients aged 1 to 21 years with polyposis who underwent colonoscopy with CSP and hot snare polypectomy (HSP) between January 2022 and …

Pskh1 Kinase Activity Is Differentially Modulated Via Allosteric Binding Of Ca2+ Sensor Proteins, Christopher R Horne, Toby A Dite, Samuel N Young, Lucy J Mather, Laura F Dagley, Jared L Johnson, Tomer M Yaron-Barir, Emily M Huntsman, Leonard A Daly, Dominic P Byrne, Antonia L Cadell, Boaz H Ng, Jumana Yousef, Dylan H Multari, Lianju Shen, Luke M Mcaloon, Gerard Manning, Mark A Febbraio, Anthony R Means, Lewis C Cantley, Maria C Tanzer, David R Croucher, Claire E Eyers, Patrick A Eyers, John W Scott, James M Murphy

Children’s Nutrition Research Center Staff Publications

Protein Serine Kinase H1 (PSKH1) was recently identified as a crucial factor in kidney development and is overexpressed in prostate, lung, and kidney cancers. However, little is known about PSKH1 regulatory mechanisms, leading to its classification as a “dark” kinase. Here, we used biochemistry and mass spectrometry to define PSKH1’s consensus substrate motif, protein interactors, and how interactors, including Ca2+ sensor proteins, promote or suppress activity. Intriguingly, despite the absence of a canonical Calmodulin binding motif, Ca2+-Calmodulin activated PSKH1 while, in contrast, the ER-resident Ca2+ sensor of the Cab45, Reticulocalbin, Erc55, Calumenin (CREC) family, Reticulocalbin-3, suppressed PSKH1 catalytic activity. In …

Mapping Snorna-Target Rna Interactions In An Rna-Binding Protein-Dependent Manner With Chimeric Eclip, Zhuoyi Song, Bongmin Bae, Simon Schnabl, Fei Yuan, Thareendra De Zoysa, Maureen V Akinyi, Charlotte A Le Roux, Karine Choquet, Amanda J Whipple, Eric L Van Nostrand

Faculty, Staff and Students Publications

Background: Small nucleolar RNAs (snoRNAs) are non-coding RNAs that function in ribosome and spliceosome biogenesis, primarily by guiding modifying enzymes to specific sites on ribosomal RNA (rRNA) and spliceosomal RNA (snRNA). However, many orphan snoRNAs remain uncharacterized, with unidentified or unvalidated targets, and studies on additional snoRNA-associated proteins are limited.

Results: We adapted an enhanced chimeric eCLIP approach to comprehensively profile snoRNA-target RNA interactions using both core and accessory snoRNA-binding proteins as baits. Using core snoRNA-binding proteins, we confirmed most annotated snoRNA-rRNA and snoRNA-snRNA interactions in mouse and human cell lines and called novel, high-confidence interactions for orphan snoRNAs. While …

Clostridioides Difficile Colonization Is Not Mediated By Bile Salts And Utilizes Stickland Fermentation Of Proline In An In Vitro Model, Xiaoyun Huang, April E Johnson, Joshua N Brehm, Thi Van Thanh Do, Thomas A Auchtung, Hugh C Mccullough, Armando I Lerma, Sigmund J Haidacher, Kathleen M Hoch, Thomas D Horvath, Joseph A Sorg, Anthony M Haag, Jennifer M Auchtung

Faculty, Staff and Students Publications

Treatment with antibiotics is a major risk factor for Clostridioides difficile infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit C. difficile colonization include the conversion of conjugated primary bile salts into secondary bile salts toxic to C. difficile growth and competition between the microbiota and C. difficile for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with 6 clinically used antibiotics influenced susceptibility to C. difficile infection in 12 different microbial communities cultivated from healthy individuals. Antibiotic treatment reduced microbial richness; …

Noncanonical Wnt/Ror2 Signaling Regulates Basal Cell Fidelity And Branching Morphogenesis In The Mammary Gland, Hongjiang Si, Erika Mendoza Mendoza, Madelyn Esquivel, Chad J Creighton, Jianming Xu, Kevin Roarty

Faculty, Staff and Students Publications

The mammary gland epithelium relies on a delicate balance between basal and luminal cell lineages to maintain tissue homeostasis and enable proper development. While the role of canonical Wnt signaling in mammary biology is well-established, the contribution of noncanonical Wnt signaling to lineage identity has remained unclear. Noncanonical Wnt pathways are primarily associated with morphogenesis, cytoskeletal regulation, and cell migration, but whether they are required for maintaining epithelial cell fate remains largely unexplored. Here, we demonstrate that the noncanonical Wnt receptor Ror2 is expressed in both basal and luminal lineages, yet selectively maintained in basal cells throughout development, suggesting a …

Author Correction: Assessment Of Human Leukocyte Antigen-Based Neoantigen Presentation To Determine Pan-Cancer Response To Immunotherapy, Jiefei Han, Yiting Dong, Xiuli Zhu, Alexandre Reuben, Jianjun Zhang, Jiachen Xu, Hua Bai, Jianchun Duan, Rui Wan, Jie Zhao, Jing Bai, Xuefeng Xia, Xin Yi, Chao Cheng, Jie Wang, Zhijie Wang

Faculty, Staff and Students Publications

No abstract provided.

Novel Device Therapies In Heart Failure: Focus On Patient Selection, Amrita Balgobind, Daniel Asemota, Emily Rodriguez, Phuuwadith Wattanachayakul, Marat Fudim, Miguel Alvarez Villela

Einstein Health Papers

The increasing prevalence of heart failure (HF) has led to advancements in therapeutic strategies, including the development of new pharmacological treatments and the expansion of guideline recommendations across the spectrum of left ventricular ejection fractions. Despite these advancements, the full benefits of guideline-directed medical therapy (GDMT) are often limited by various barriers that result in incomplete implementation or suboptimal responses. For patients who cannot tolerate or only partially respond to GDMT, therapeutic options remain limited. This gap is particularly significant for those with contraindications to heart replacement therapies (HRT), such as left ventricular assist device (LVAD) or heart transplant. In …

Ultra-Low Extracorporeal Volume Microfluidic Leukapheresis Is Safe And Effective In A Rat Model, Mubasher Iqbal, Alexandra L Mclennan, Anton Mukhamedshin, Mai T P Dinh, Qisheng Liu, Jacob J Junco, Arvind Mohan, Poyyapakkam R Srivaths, Karen R Rabin, Thomas P Fogarty, Sean C Gifford, Sergey S Shevkoplyas, Fong W Lam

Faculty, Staff and Students Publications

Leukapheresis is a potentially life-saving therapy for children with symptomatic hyperleukocytosis. However, the standard centrifugation-based approach exposes pediatric patients to significant complications due to its large extracorporeal volume, high flow rates, and considerable platelet loss. Here, we tested whether performing cell separation with a high-throughput microfluidic technology could alleviate these limitations. In vitro, our microfluidic devices removed ~85% of large leukocytes and ~90% of spiked leukemic blasts from undiluted human whole blood, while minimizing platelet losses. Multiplexed devices connected in parallel allowed for faster, clinically relevant flow rates in vitro with no difference in leukocyte collection efficiency. When connected to …

Memorability Of Novel Words Correlates With Anterior Fusiform Activity During Reading, Oscar Woolnough, Nitin Tandon

Faculty, Staff and Student Publications

Our memory for the words we already know is best predicted by their associated meanings. However, the factors that influence whether we will remember a new word after we see it for the first time are unclear. We record memory performance for 2100 novel pseudowords across 1804 participants during a continuous recognition task. Participants show significant agreement across individuals for which novel words were memorable or forgettable, suggesting an intrinsic memorability for individual pseudowords. Pseudowords that are similar to low-frequency known words, with sparse orthographic neighbourhoods and rarely occurring letter pairs, are more memorable. Further, using intracranial recordings in 36 …

Aberrant Choroid Plexus Formation Drives The Development Of Treatment-Related Brain Toxicity, Tamara Bender, Esther Schickel, Celine Schielke, Jürgen Debus, David R Grosshans, Marco Durante, Insa S Schroeder

Faculty, Staff and Student Publications

Brain tumors are commonly treated with radiotherapy, but the efficacy of the treatment is limited by its toxicity to the normal tissue including post-irradiation contrast enhanced lesions often linked to necrosis. The poorly understood mechanisms behind such brain lesions were studied using cerebral organoids. Here we show that irradiation of such organoids leads to dose-dependent growth retardation and formation of liquid-filled cavities but is not correlated with necrosis. Instead, the radiation-induced changes comprise of an enhancement of cortical hem markers, altered neuroepithelial stem cell differentiation, and an increase of ZO1+/AQP1+/CLDN3+-choroid plexus (CP)-like structures accompanied by an upregulation of IGF2 mRNA, …

The Bacterial Microbiome Modulates The Initiation Of Brain Metastasis By Impacting The Gut-To-Brain Axis, Matteo Massara, Michelle Ballabio, Bastien Dolfi, Golnaz Morad, Vladimir Wischnewski, Eleni Lamprou, Joao Lourenco, Stéphanie Claudinot, Hector Gallart-Ayala, Rui Santalla Méndez, Annamaria Kauzlaric, Nadine Fournier, Ashish V Damania, Matthew C Wong, Julijana Ivanisevic, Nadim J Ajami, Jennifer A Wargo, Johanna A Joyce

Faculty, Staff and Student Publications

Brain metastases (BrMs) are the most common brain tumors in patients and are associated with poor prognosis. Investigating the systemic and environmental factors regulating BrM biology represents an important strategy to develop effective treatments. Toward this goal, we explored the contribution of the gut microbiome to BrM development by using in vivo breast-BrM models under germ-free conditions or antibiotic treatment. This revealed a detrimental role of gut microbiota in fostering BrM initiation. We thus evaluated the impact of antibiotics and BrM outgrowth on the gut-brain axis. We found the bacterial genus Alistipes was differentially present under antibiotic treatment and BrM …

Immune Checkpoint Inhibitors Plus Debulking Surgery For Patients With Metastatic Renal Cell Carcinoma: Clinical Outcomes And Immunological Correlates Of A Prospective Pilot Trial, Sangeeta Goswami, Jianjun Gao, Sreyashi Basu, Daniel D Shapiro, Jose A Karam, Rebecca Slack Tidwell, Kamran Ahrar, Matthew T Campbell, Yu Shen, Alexandro E Trevino, Aaron T Mayer, Alexsandra B Espejo, Christian Seua, Marc D Macaluso, Yulong Chen, Wenbin Liu, Zhong He, Shalini S Yadav, Ying Wang, Priya Rao, Li Zhao, Jianhua Zhang, Sonali Jindal, Nizar M Tannir, Andrew Futreal, Linghua Wang, Padmanee Sharma

Faculty, Staff and Student Publications

Surgical removal of primary tumors reverses tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT), is not understood. We report the first prospective, pilot, non-comparative clinical trial (NCT02210117) to evaluate the feasibility, clinical benefits, and immunologic changes of combining three different ICT-containing strategies with cytoreductive surgery or biopsy for patients with metastatic clear cell renal cell carcinoma. Primary safety endpoint of this trial has been met, with 43 patients completing cytoreductive surgery, 36 patients undergoing …

Zika Virus Ns1 Drives Tunneling Nanotube Formation For Mitochondrial Transfer And Stealth Transmission In Trophoblasts, Rafael T Michita, Long B Tran, Steven J Bark, Deepak Kumar, Shay A Toner, Joyce Jose, Indira U Mysorekar, Anoop Narayanan

Faculty, Staff and Students Publications

Zika virus (ZIKV) is unique among orthoflaviviruses in its vertical transmission capacity in humans, yet the underlying mechanisms remain incompletely understood. Here, we show that ZIKV induces tunneling nanotubes (TNTs) in placental trophoblasts which facilitate transfer of viral particles, proteins, mitochondria, and RNA to neighboring uninfected cells. TNT formation is driven exclusively via ZIKV non-structural protein 1 (NS1). Specifically, the N-terminal 1-50 amino acids of membrane-bound ZIKV NS1 are necessary for triggering TNT formation in host cells. Trophoblasts infected with TNT-deficient ZIKV