Digital Commons Network^™

Combating Disparities In A Pandemic: Increasing Dissemination Of Coronavirus Disease 2019 Resources In Spanish., Romina Barral, Nicholas Clark, Fernando Zapata, Lines Vargas Collado, July Jean Cuevas, Cristina Fernandez Md

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Disparities exist in access to coronavirus disease 2019 (COVID-19)-related health information. We aimed to close a gap in online traffic between English and Spanish COVID-19-related health information on our institution's publicly-facing website by 50% within ten months.

METHODS: We used A3 improvement methodology. Outcome measures were the mean monthly difference between English and Spanish COVID-19 online traffic vis-a-vis (1) total webpage views and (2) unique webpage visits. Process measures were stratification of outcome measures by language. Plan-Do-Study-Act cycles included: Recurring advertisements on a local Spanish television station disseminating up-to-date COVID-19 information, including our institution's Spanish COVID-19 online resources, incorporation …

Tfeb Safeguards Trophoblast Syncytialization In Humans And Mice, Wanshan Zheng, Yue Zhang, Peiqun Xu, Zexin Wang, Xuan Shao, Chunyan Chen, Han Cai, Yinan Wang, Ming-An Sun, Wenbo Deng, Fan Liu, Jinhua Lu, Xueqin Zhang, Dunjin Cheng, Indira U Mysorekar, Haibin Wang, Yan-Ling Wang, Xiaoqian Hu, Bin Cao

Faculty, Staff and Students Publications

The formation of multinucleated syncytiotrophoblast (STB) through cell fusion of cytotrophoblast, also termed syncytialization, ensures the proper placental structure and functions. Nutrient insufficiency and inactivation of the mechanistic target of rapamycin complex 1 (mTORC1) in trophoblasts have been shown to enhance STB formation; however, the underlying mechanism remains elusive. Here, we showed that the deficiency of a mTORC1 downstream transcriptional factor, TFEB, significantly impaired STB formation in human trophoblasts and knock-out mice. TFEB conferred direct transcriptional activation of the fusogen ERVFRD-1 and thereby promoted trophoblast syncytialization. Additionally, TFEB expression positively correlated with the reinforced trophoblast syncytialization in human fetal growth …

Cardiovascular Disease In Adults With A History Of Out-Of-Home Care During Childhood: A Systematic Review And Meta-Analysis Of Prospective Cohort Studies, G. David Batty, Mika Kivimäki, Ylva B. Almquist, Johan G. Eriksson, Mika Gissler, Emmanuel S. Gnanamanickam, Mark Hamer, Josephine Jackisch, Hee-Soon Juon, Markus Keski-Säntti, Chaiquan Li, Tuija M. Mikkola, Emily Murray, Amanda Sacker, Leonie Segal, Philipp Frank

Department of Medical Oncology Faculty Papers

Background

While individuals who were separated from their biological family and placed into the care of the state during childhood (out-of-home care) are more prone to developing selected adverse health problems in adulthood, their risk of cardiovascular disease is uncertain. Our aim was to explore this association by pooling published and unpublished results from prospective cohort studies.

Methods

We used two approaches to identifying relevant data on childhood care and adult cardiovascular disease (PROSPERO registration CRD42021254665). First, to locate published studies, we searched PubMed (Medline) until November 2023. Second, with the objective of identifying unpublished studies with the potential to …

Ai-Assisted Segmentation Tool For Brain Tumor Mr Image Analysis, Myungeun Lee, Jong Hyo Kim, Wookjin Choi, Ki Hong Lee

Department of Radiation Oncology Faculty Papers

TumorPrism3D software was developed to segment brain tumors with a straightforward and user-friendly graphical interface applied to two- and three-dimensional brain magnetic resonance (MR) images. The MR images of 185 patients (103 males, 82 females) with glioblastoma multiforme were downloaded from The Cancer Imaging Archive (TCIA) to test the tumor segmentation performance of this software. Regions of interest (ROIs) corresponding to contrast-enhancing lesions, necrotic portions, and non-enhancing T2 high signal intensity components were segmented for each tumor. TumorPrism3D demonstrated high accuracy in segmenting all three tumor components in cases of glioblastoma multiforme. They achieved a better Dice similarity coefficient (DSC) …

Intratumoral Immune Triads Are Required For Immunotherapy-Mediated Elimination Of Solid Tumors, Gabriel Espinosa-Carrasco, Edison Chiu, Aurora Scrivo, Paul Zumbo, Asim Dave, Doron Betel, Sung Wook Kang, Hee-Jin Jang, Matthew D Hellmann, Bryan M Burt, Hyun-Sung Lee, Andrea Schietinger

Faculty, Staff and Students Publications

Tumor-specific CD8+ T cells are frequently dysfunctional and unable to halt tumor growth. We investigated whether tumor-specific CD4+ T cells can be enlisted to overcome CD8+ T cell dysfunction within tumors. We find that the spatial positioning and interactions of CD8+ and CD4+ T cells, but not their numbers, dictate anti-tumor responses in the context of adoptive T cell therapy as well as immune checkpoint blockade (ICB): CD4+ T cells must engage with CD8+ T cells on the same dendritic cell during the effector phase, forming a three-cell-type cluster (triad) to license CD8+ T cell cytotoxicity and cancer cell elimination. …

Protein Sumoylation Promotes Camp-Independent Epac1 Activation, Wenli Yang, Fang C Mei, Wei Lin, Mark A White, Li Li, Yue Li, Sheng Pan, Xiaodong Cheng

Faculty, Staff and Student Publications

Protein SUMOylation is a prevalent stress-response posttranslational modification crucial for maintaining cellular homeostasis. Herein, we report that protein SUMOylation modulates cellular signaling mediated by cAMP, an ancient and universal stress-response second messenger. We identify K561 as a primary SUMOylation site in exchange protein directly activated by cAMP (EPAC1) via site-specific mapping of SUMOylation using mass spectrometry. Sequence and site-directed mutagenesis analyses reveal that a functional SUMO-interacting motif in EPAC1 is required for the binding of SUMO-conjugating enzyme UBC9, formation of EPAC1 nuclear condensate, and EPAC1 cellular SUMOylation. Heat shock-induced SUMO modification of EPAC1 promotes Rap1/2 activation in a cAMP-independent manner. …

Hur Controls Glutaminase Rna Metabolism, Douglas Adamoski, Larissa M Dos Reis, Ana Carolina Paschoalini Mafra, Felipe Corrêa-Da-Silva, Pedro Manoel Mendes De Moraes-Vieira, Ioana Berindan-Neagoe, George A Calin, Sandra Martha Gomes Dias

Faculty, Staff and Student Publications

Glutaminase (GLS) is directly related to cell growth and tumor progression, making it a target for cancer treatment. The RNA-binding protein HuR (encoded by the ELAVL1 gene) influences mRNA stability and alternative splicing. Overexpression of ELAVL1 is common in several cancers, including breast cancer. Here we show that HuR regulates GLS mRNA alternative splicing and isoform translation/stability in breast cancer. Elevated ELAVL1 expression correlates with high levels of the glutaminase isoforms C (GAC) and kidney-type (KGA), which are associated with poor patient prognosis. Knocking down ELAVL1 reduces KGA and increases GAC levels, enhances glutamine anaplerosis into the TCA cycle, and …

Serum From Patients With Cirrhosis Undergoing Liver Transplantation Induces Permeability In Human Pulmonary Microvascular Endothelial Cells, Michael Bokoch, Fengyun Xu, Krishna Govindaraju, Elliot Lloyd, Kyle Tsutsui, Rishi Kothari, Dieter Adelmann, Jérémie Joffre, Judith Hellman

Department of Anesthesiology Faculty Papers

INTRODUCTION: Patients with cirrhosis undergoing liver transplantation frequently exhibit systemic inflammation, coagulation derangements, and edema, indicating endothelial dysfunction. This syndrome may worsen after ischemia-reperfusion injury of the liver graft, coincident with organ dysfunction that worsens patient outcomes. Little is known about changes in endothelial permeability during liver transplantation. We hypothesized that sera from these patients would increase permeability in cultured human endothelial cells

METHODS: Adults with cirrhosis presenting for liver transplantation provided consent for blood collection during surgery. Sera were prepared at five time points spanning the entire operation. The barrier function of human pulmonary microvascular endothelial cells in culture …

Controlled Delivery Of Rosuvastatin Or Rapamycin Through Electrospun Bismuth Nanoparticle-Infused Perivascular Wraps Promotes Arteriovenous Fistula Maturation, Allan John R Barcena, Joy Vanessa D Perez, Marvin R Bernardino, Erin Marie D San Valentin, Jossana A Damasco, Carleigh Klusman, Benjamin Martin, Karem A Court, Biana Godin, Gino Canlas, Natalie Fowlkes, Richard R Bouchard, Jizhong Cheng, Steven Y Huang, Marites P Melancon

Faculty, Staff and Student Publications

In the context of arteriovenous fistula (AVF) failure, local delivery enables the release of higher concentrations of drugs that can suppress neointimal hyperplasia (NIH) while reducing systemic adverse effects. However, the radiolucency of polymeric delivery systems hinders long-term in vivo surveillance of safety and efficacy. We hypothesize that using a radiopaque perivascular wrap to deliver anti-NIH drugs could enhance AVF maturation. Through electrospinning, we fabricated multifunctional perivascular polycaprolactone (PCL) wraps loaded with bismuth nanoparticles (BiNPs) for enhanced radiologic visibility and drugs that can attenuate NIH—rosuvastatin (Rosu) and rapamycin (Rapa). The following groups were tested onto the AVFs of a total …

Multidisciplinary Approach To Diagnostic Radiology Education: A Novel Educational Intervention For Turkish Medical Students, Parth Patel, Emre Altınmakas, Görkem Ayas, Rachel Stanietzky, Madeline L. Stewart, Abdelrahman Elshikh, Disha Ram, Hrishika Bhosale, Mohamed Eltaher, Serageldin Kamel, Munevver N. Duran, Umut Yücel, Mohamed Badawy, Scott Rohren, Khaled M. Elsayes

School of Medicine Faculty Publications

Teleconferencing can facilitate a multidisciplinary approach to teaching radiology to medical students. This study aimed to determine whether an online learning approach enables students to appreciate the interrelated roles of radiology and other specialties during the management of different medical cases. Turkish medical students attended five 60-90-minute online lectures delivered by radiologists and other specialists from the United States and Canada through Zoom meetings between November 2020 and January 2021. Student ambassadors from their respective Turkish medical schools recruited their classmates with guidance from the course director. Students took a pretest and posttest to assess the knowledge imparted from each …

Inhibition Of Malt1 And Bcl2 Induces Synergistic Antitumor Activity In Models Of B-Cell Lymphoma, Joshua P Plotnik, Adam E Richardson, Haopeng Yang, Estela Rojas, Velitchka Bontcheva, Colleen Dowell, Sydney Parsons, Ashley Wilson, Vida Ravanmehr, Christine Will, Paul Jung, Haizhong Zhu, Sarathy Karunan Partha, Sanjay C Panchal, Raghuveer Singh Mali, Frederick J Kohlhapp, Ryan A Mcclure, Cyril Y Ramathal, Mariam D George, Manisha Jhala, Nathaniel L Elsen, Wei Qiu, Russell A Judge, Chin Pan, Anthony Mastracchio, Jared Henderson, Jonathan A Meulbroek, Michael R Green, William N Pappano

Faculty, Staff and Student Publications

The activated B cell (ABC) subset of diffuse large B-cell lymphoma (DLBCL) is characterized by chronic B-cell receptor signaling and associated with poor outcomes when treated with standard therapy. In ABC-DLBCL, MALT1 is a core enzyme that is constitutively activated by stimulation of the B-cell receptor or gain-of-function mutations in upstream components of the signaling pathway, making it an attractive therapeutic target. We discovered a novel small-molecule inhibitor, ABBV-MALT1, that potently shuts down B-cell signaling selectively in ABC-DLBCL preclinical models leading to potent cell growth and xenograft inhibition. We also identified a rational combination partner for ABBV-MALT1 in the BCL2 …

Ocular Gene Transfer In The Spotlight: Implications Of Newspaper Content For Clinical Communications, Shelly Benjaminy, Tania M. Bubela

Office of the Provost

Background: Ocular gene transfer clinical trials are raising hopes for blindness treatments and attracting media attention. News media provide an accessible health information source for patients and the public, but are often criticized for overemphasizing benefits and underplaying risks of novel biomedical interventions. Overly optimistic portrayals of unproven interventions may influence public and patient expectations; the latter may cause patients to downplay risks and over-emphasize benefits, with implications for informed consent for clinical trials. We analyze the news media communications landscape about ocular gene transfer and make recommendations for improving communications between clinicians and potential trial participants in light of …

Assessing Association Between Socio-Demographic Variables And Contraceptive Usage In Married Men Residing In Korangi District, Karachi, Pakistan, Fahmida Khawaja, Gloria Noble Khan, Alia Nasir, Kiran Khowaja

Journal of Asian Midwives (JAM)

Background: Population growth remains an alarming concern for Pakistan as it not only exhausts scarce resources but further impedes socioeconomic development. One potential solution is to advance modern Family Planning (FP), which in the Pakistani context requires specific and rigorous attention towards male contraception in conjunction with female family planning usage. This study aims to determine the association between socio demographic factors and contraceptive use in married men of squatter settlement of Korangi Karachi.
Methods and Materials: A cross-sectional study was carried out from March, 2017 to June 2017, using a non-probability convenience sampling technique to select married men …

Multicountry Spread Of Influenza A(H1n1)Pdm09 Viruses With Reduced Oseltamivir Inhibition, May 2023-February 2024, Mira C Patel, Ha T Nguyen, Philippe Noriel Q Pascua, Rongyuan Gao, John Steel, Rebecca J Kondor, Larisa V Gubareva

Faculty, Staff and Student Publications

Since May 2023, a novel combination of neuraminidase mutations, I223V + S247N, has been detected in influenza A(H1N1)pdm09 viruses collected in countries spanning 5 continents, mostly in Europe (67/101). The viruses belong to 2 phylogenetically distinct groups and display ≈13-fold reduced inhibition by oseltamivir while retaining normal susceptibility to other antiviral drugs.

Epigenetic Activation Of Sox11 Is Associated With Recurrence And Progression Of Ductal Carcinoma In Situ To Invasive Breast Cancer, Warapen Treekitkarnmongkol, Vandna Shah, Kazuharu Kai, Hiroshi Katayama, Justin Wong, Farah A Ladha, Tristian Nguyen, Brian Menegaz, Wei Lu, Fei Yang, Barbara Mino, Ximing Tang, Mihai Gagea, Harsh Batra, Maria Gabriela Raso, Ignacio I Wistuba, Savitri Krishnamurthy, Sarah E Pinder, Elinor J Sawyer, Alastair M Thompson, Subrata Sen

Faculty, Staff and Student Publications

Background: Risk of recurrence and progression of ductal carcinoma in situ (DCIS) to invasive cancer remains uncertain, emphasizing the need for developing predictive biomarkers of aggressive DCIS.

Methods: Human cell lines and mouse models of disease progression were analyzed for candidate risk predictive biomarkers identified and validated in two independent DCIS cohorts.

Results: RNA profiling of normal mammary and DCIS tissues (n = 48) revealed that elevated SOX11 expression correlates with MKI67, EZH2, and DCIS recurrence score. The 21T human cell line model of DCIS progression to invasive cancer and two mouse models developing mammary intraepithelial neoplasia confirmed the findings. …

Dose-Dependent Effects Of Dnmt3a In An Inducible Murine Model Of Krasg12d-Driven Leukemia, Jason H Rogers, Allison Rosen, Jaime M Reyes, Shamika Ketkar, Shannon E Conneely, Rohit Gupta, Luibin Yang, Matthew B Miller, Geraldo Medrano, Rogelio Aguilar, Nneka Uchenda, Margaret A Goodell, Rachel E Rau

Children’s Nutrition Research Center Staff Publications

DNMT3A mutations are frequently found in clonal hematopoiesis and a variety of hematologic malignancies including acute myeloid leukemia (AML). An assortment of mouse models have been engineered to explore the tumorigenic potential and malignant lineage bias due to loss of function of DNMT3A in consort with commonly co-mutated genes in myeloid malignancies such as Flt3, Nras, Kras, and c-Kit. We employed several tamoxifen-inducible Cre-ER^T2 murine model systems to study the effects of constitutively active Kras^G12D-driven myeloid leukemia (Kras) development together with heterozygous (3aHet) or homozygous Dnmt3a deletion (3aKO). Due to the rapid generation of …

Nfatc1 Is Required For Vitamin D- And Phosphate-Mediated Regulation Of Osteocyte Lacuno-Canalicular Remodeling, Supriya Jagga, Ashleigh Hughes, Niusha Manoochehri Arash, Melissa Sorsby, Daniel J Brooks, Paola Divieti Pajevic, Eva S Liu

Staff and Researcher Publications

Osteocytes are embedded in lacunae and connected by canaliculi (lacuno-canalicular network, LCN). Bones from mice with X-linked hypophosphatemia (Hyp), which have impaired production of 1,25 dihydroxyvitamin D (1,25D) and hypophosphatemia, have abnormal LCN structure that is improved by treatment with 1,25D or an anti-FGF23 targeting antibody, supporting roles for 1,25D and phosphate in regulating LCN remodeling. Bones from mice lacking the vitamin D receptor (VDR) in osteocytes (Vdrf/f;Dmp1Cre+) and mice lacking the sodium phosphate transporter 2a (Npt2aKO), which have low serum phosphate with high serum 1,25D, have impaired LCN organization, demonstrating that osteocyte-specific actions of 1,25D and hypophosphatemia regulate LCN …

Examining Enrollment & Engagement In A Hospital-Based Violence Prevention Intervention Study At A Level 1 Trauma Center, Leigh Frederick

Electronic Theses and Dissertations

BACKGROUND: Violence is a significant healthcare issue that affects the health and well-being of individuals, families, and communities. Violence prevention and intervention programs are a powerful way to stop the revolving door of violent injury in our hospitals and communities. The Health Alliance for Violence Intervention (HAVI), develops and connects violence intervention programs, promotes equity for victims of violence globally, and is dedicated to engaging patients during the window of opportunity when they are recovering in the hospital after a violent injury to reduce the chance of retaliation (related to the injury) and recurrence. A small body of research shows …

Decentralized Clinical Trials For Medications To Reduce The Risk Of Dementia: Consensus Report And Guidance, Leanne Howard, Carla Abdelnour, Erin Abner, Ricardo F. Allegri, Hiroko H. Dodge, Serge Gauthier, Camilla M. Hoyos, Gregory Jicha, Patrick G. Kehoe, Catherine J. Mummery, Adesola Ogunniyi, Nikolaos Scarmeas, Xiaoying Chen, Jodie R. Titiner, Christopher R. Weber, Ruth Peters

Neurology Faculty Publications

INTRODUCTION: Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentralized medication trials, but we currently lack specific recommendations for their delivery in the dementia field.

METHODS: A modified Delphi method engaged an expert panel to develop recommendations for the conduct of decentralized medication trials in dementia prevention. A working group of researchers and clinicians with expertise in dementia trials further refined the recommendations.

RESULTS: Overall, the recommendations support the delivery of decentralized trials in dementia prevention …

Type-2 Diabetes, Pancreatic Amylin, And Neuronal Metabolic Remodeling In Alzheimer's Disease, Noah Leibold, James R. Bain, Florin Despa

Neurology Faculty Publications

Type-2 diabetes raises the risk for Alzheimer’s disease (AD)-type dementia and the conversion from mild cognitive impairment to dementia, yet mechanisms connecting type-2 diabetes to AD remain largely unknown. Amylin, a pancreatic 𝜷-cell hormone co-secreted with insulin, participates in the central regulation of satiation, but also forms pancreatic amyloid in persons with type-2 diabetes and synergistically interacts with brain amyloid 𝜷 (A𝜷) pathology, in both sporadic and familial Alzheimer’s disease (AD). Growing evidence from studies of tumor growth, together with early observations in skeletal muscle, indicates amylin as a potential trigger of cellular metabolic reprogramming. Because the blood, cerebrospinal fluid, …

Data Consistency Of Two National Registries In Iran: A Preliminary Assessment To Health Information Exchange., Mohammad Dashtkoohi, Mohammad Poursalehian, Zahra Azadmanjir, Masoomeh Vaeidi, Mahdi Mohammadzadeh, Mahdi Sharif-Alhoseini, Khatereh Naghdi, Marzieh Moniri Asl, James Harrop, Vafa Rahimi-Movaghar

Department of Neurosurgery Faculty Papers

BACKGROUND: The National Spinal Cord Injury Registry of Iran (NSCIR-IR) and the National Trauma Registry of Iran (NTRI) were established to meet the data needs for research and assessing trauma status in Iran. These registries have a group of patients shared by both registries, and it is expected that some identical data will be collected about them. A general question arises whether the spinal cord injury registry can receive part of the common data from the trauma registry and not collect them independently.

METHODS: We examined variables captured in both registries based on structure and concept, identified the overlapping period …

Ceramide-Mediated Orchestration Of Oxidative Stress Response Through Filopodia-Derived Small Extracellular Vesicles, Zainuddin Quadri, Ahmed Elsherbini, Simone M. Crivelli, Salim S. El-Amouri, Priyanka Tripathi, Zhihui Zhu, Xiaojia Ren, Liping Zhang, Stefka D. Spassieva, Mariana N. Nikolova‑Karakashian, Erhard Bieberich

Markey Cancer Center Faculty Publications

Extracellular vesicles (EVs) are shed from the plasma membrane, but the regulation and function of these EVs remain unclear. We found that oxidative stress induced by H 2 O 2 in Hela cells stimulated filopodia formation and the secretion of EVs. EVs were small (150 nm) and labeled for CD44, indicating that they were derived from filopodia. Filopodia-derived small EVs (sEVs) were enriched with the sphingolipid ceramide, consistent with increased ceramide in the plasma membrane of filopo- dia. Ceramide was colocalized with neutral sphingomyelinase 2 (nSMase2) and acid sphingomyelinase (ASM), two sphingomyelinases generating ceramide at the plasma membrane. Inhibition of …

Diffuse Reflectance Spectroscopy For Optical Characterizations Of Orthotopic Head And Neck Cancer Models In Vivo, Pranto Soumik Saha, Jing Yan, Caigang Zhu

Markey Cancer Center Faculty Publications

We demonstrated an easy-to-build, portable diffuse reflectance spectroscopy device along with a Monte Carlo inverse model to quantify tissue absorption and scattering-based parameters of orthotopic head and neck cancer models in vivo. Both tissue-mimicking phantom studies and animal studies were conducted to verify the optical spectroscopy system and Monte Carlo inverse model for the accurate extraction of tissue optical properties. For the first time, we reported the tissue absorption and scattering coefficients of mouse normal tongue tissues and tongue tumor tissues. Our in vivo animal studies showed reduced total hemoglobin concentration, lower tissue vascular oxygen saturation, and increased tissue scattering …

Foreign Body Ingestion, Children's Mercy Kansas City

Clinical Pathways

No abstract provided.

Mechanisms Of Gelofusine Protection In An In Vitro Model Of Polymyxin B-Associated Renal Injury, Cole S Hudson, Anirban Roy, Qingtian Li, Aniket S Joshi, Taijun Yin, Ashok Kumar, David Sheikh-Hamad, Vincent H Tam

Faculty, Staff and Students Publications

Polymyxins are a last-resort treatment option for multidrug-resistant gram-negative bacterial infections, but they are associated with nephrotoxicity. Gelofusine was previously shown to reduce polymyxin-associated kidney injury in an animal model. However, the mechanism(s) of renal protection has not been fully elucidated. Here, we report the use of a cell culture model to provide insights into the mechanisms of renal protection. Murine epithelial proximal tubular cells were exposed to polymyxin B. Cell viability, lactate dehydrogenase (LDH) release, polymyxin B uptake, mitochondrial superoxide production, nuclear morphology, and apoptosis activation were evaluated with or without concomitant gelofusine. A megalin knockout cell line was …

Social Media And Dermatology During The Covid-19 Pandemic: Analyzing User-Submitted Posts Seeking Dermatologic Advice On Reddit, Vivek V Shukla, Benjamin A Carper, Namasivayam Ambalavanan, Matthew A Rysavy, Edward F Bell, Abhik Das, Ravi M Patel, Carl T D'Angio, Kristi L Watterberg, C Michael Cotten, Stephanie L Merhar, Myra H Wyckoff, Pablo J Sánchez, Neha Kumbhat, Waldemar A Carlo, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network

Faculty, Staff and Student Publications

HYPOTHESIS: Increased social distancing was associated with a lower incidence of extremely preterm live births (EPLB) during the initial COVID-19 pandemic period.

STUDY DESIGN: Prospective study at the NICHD Neonatal Research Network sites comparing EPLB (22

RESULTS: EPLB and EPIS percentages did not significantly decrease (1.58-1.45%, p = 0.07, and 0.08-0.06%, p = 0.14, respectively). SDI was not significantly correlated with percent change of EPLB (CC = 0.29, 95% CI = -0.12, 0.71) or EPIS (CC = -0.23, 95% CI = -0.65, 0.18). Percent change in mean gestational age was positively correlated with SDI (CC = 0.49, 95% CI = …

Expanded-Access Use Of Elamipretide In A Patient With Membrane Protein-Associated Neurodegeneration, Jorge Patino, Anna Haertling Clearman, Lindsey Miller, Mary Kay Koenig

Faculty, Staff and Student Publications

This case report presents a progressively declining 17-year-old patient with membrane protein-associated neurodegeneration who demonstrated symptomatic improvements in her dysarthria, dysphagia, and gait, and objective improvements in her 6-minute walk test and 5 times sit-to-stand test during elamipretide treatment.

Use Of Ipsc-Derived Smooth Muscle Cells To Model Physiology And Pathology, Callie S Kwartler, Jose Emiliano Esparza Pinelo

Faculty, Staff and Student Publications

The implementation of human induced pluripotent stem cell (hiPSC) models has introduced an additional tool for identifying molecular mechanisms of disease that complement animal models. Patient-derived or CRISPR/Cas9-edited induced pluripotent stem cells differentiated into smooth muscle cells (SMCs) have been leveraged to discover novel mechanisms, screen potential therapeutic strategies, and model in vivo development. The field has evolved over almost 15 years of research using hiPSC-SMCs and has made significant strides toward overcoming initial challenges such as the lineage specificity of SMC phenotypes. However, challenges both specific (eg, the lack of specific markers to thoroughly validate hiPSC-SMCs) and general (eg, …

Intratumoral Injection Of Immunotherapeutics: State Of The Art And Future Directions, Rahul A Sheth, Eric Wehrenberg-Klee, Sapna P Patel, Kristy K Brock, Nicos Fotiadis, Thierry De Baère

Faculty, Staff and Student Publications

Systemic immunotherapies have led to tremendous progress across the cancer landscape. However, several challenges exist, potentially limiting their efficacy in the treatment of solid tumors. Direct intratumoral injection can increase the therapeutic index of immunotherapies while overcoming many of the barriers associated with systemic administration, including limited bioavailability to tumors and potential systemic safety concerns. However, challenges remain, including the lack of standardized approaches for administration, issues relating to effective drug delivery, logistical hurdles, and safety concerns specific to this mode of administration. This article reviews the biologic rationale for the localized injection of immunotherapeutic agents into tumors. It also …

Identification Of A Clinically Efficacious Car T Cell Subset In Diffuse Large B Cell Lymphoma By Dynamic Multidimensional Single-Cell Profiling, Ali Rezvan, Gabrielle Romain, Mohsen Fathi, Darren Heeke, Melisa Martinez-Paniagua, Xingyue An, Irfan N Bandey, Melisa J Montalvo, Jay R T Adolacion, Arash Saeedi, Fatemeh Sadeghi, Kristen Fousek, Nahum Puebla-Osorio, Laurence J N Cooper, Chantale Bernatchez, Harjeet Singh, Nabil Ahmed, Mike Mattie, Adrian Bot, Sattva Neelapu, Navin Varadarajan

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) T cells used for the treatment of B cell malignancies can identify T cell subsets with superior clinical activity. Here, using infusion products of individuals with large B cell lymphoma, we integrated functional profiling using timelapse imaging microscopy in nanowell grids with subcellular profiling and single-cell RNA sequencing to identify a signature of multifunctional CD8+ T cells (CD8-fit T cells). CD8-fit T cells are capable of migration and serial killing and harbor balanced mitochondrial and lysosomal volumes. Using independent datasets, we validate that CD8-fit T cells (1) are present premanufacture and are associated with clinical responses …