Digital Commons Network^™

An Integrated Cell Atlas Of The Lung In Health And Disease, Lisa Sikkema, Ciro Ramírez-Suástegui, Daniel C Strobl, Tessa E Gillett, Luke Zappia, Elo Madissoon, Nikolay S Markov, Laure-Emmanuelle Zaragosi, Yuge Ji, Meshal Ansari, Marie-Jeanne Arguel, Leonie Apperloo, Martin Banchero, Christophe Bécavin, Marijn Berg, Evgeny Chichelnitskiy, Mei-I Chung, Antoine Collin, Aurore C A Gay, Janine Gote-Schniering, Baharak Hooshiar Kashani, Kemal Inecik, Manu Jain, Theodore S Kapellos, Tessa M Kole, Sylvie Leroy, Christoph H Mayr, Amanda J Oliver, Michael Von Papen, Lance Peter, Chase J Taylor, Thomas Walzthoeni, Chuan Xu, Linh T Bui, Carlo De Donno, Leander Dony, Alen Faiz, Minzhe Guo, Austin J Gutierrez, Lukas Heumos, Ni Huang, Ignacio L Ibarra, Nathan D Jackson, Preetish Kadur Lakshminarasimha Murthy, Mohammad Lotfollahi, Tracy Tabib, Carlos Talavera-López, Kyle J Travaglini, Anna Wilbrey-Clark, Kaylee B Worlock, Masahiro Yoshida, Maarten Van Den Berge, Yohan Bossé, Tushar J Desai, Oliver Eickelberg, Naftali Kaminski, Mark A Krasnow, Robert Lafyatis, Marko Z Nikolic, Joseph E Powell, Jayaraj Rajagopal, Mauricio Rojas, Orit Rozenblatt-Rosen, Max A Seibold, Dean Sheppard, Douglas P Shepherd, Don D Sin, Wim Timens, Alexander M Tsankov, Jeffrey Whitsett, Yan Xu, Nicholas E Banovich, Pascal Barbry, Thu Elizabeth Duong, Christine S Falk, Kerstin B Meyer, Jonathan A Kropski, Dana Pe'er, Herbert B Schiller, Purushothama Rao Tata, Joachim L Schultze, Sara A Teichmann, Alexander V Misharin, Martijn C Nawijn, Malte D Luecken, Fabian J Theis

Faculty, Staff and Student Publications

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity …

Vagus Nerve Stimulation Paired With Rehabilitation For Upper Limb Motor Impairment And Function After Chronic Ischemic Stroke: Subgroup Analysis Of The Randomized, Blinded, Pivotal, Vns-Rehab Device Trial, Jesse Dawson, Navzer D Engineer, Steven C Cramer, Steven L Wolf, Rushna Ali, Michael W O'Dell, David Pierce, Cecília N Prudente, Jessica Redgrave, Wuwei Feng, Charles Y Liu, Gerard E Francisco, Benjamin L Brown, Anand Dixit, Jen Alexander, Louis Demark, Vibor Krishna, Steven A Kautz, Arshad Majid, Brent Tarver, Duncan L Turner, Teresa J Kimberley

Faculty, Staff and Student Publications

BACKGROUND: Vagus Nerve Stimulation (VNS) paired with rehabilitation improved upper extremity impairment and function in a recent pivotal, randomized, triple-blind, sham-controlled trial in people with chronic arm weakness after stroke.

OBJECTIVE: We aimed to determine whether treatment effects varied across candidate subgroups, such as younger age or less injury.

METHODS: Participants were randomized to receive rehabilitation paired with active VNS or rehabilitation paired with sham stimulation (Control). The primary outcome was the change in impairment measured by the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score on the first day after completion of 6-weeks in-clinic therapy. We explored the effect of VNS …

Adult Female With A Painful And Pruritic Lower Extremity Skin Lesion., Chase Silvers, Christopher Lloyd

Ambulatory and Primary Care Articles

No abstract provided.

Use Of Telemedicine For Postdischarge Assessment Of The Surgical Wound: International Cohort Study, And Systematic Review With Meta-Analysis, Nihr Global Health Research Unit On Global Surgery, Globalsurg Collaborative

Faculty, Staff and Student Publications

OBJECTIVE: This study aimed to determine whether remote wound reviews using telemedicine can be safely upscaled, and if standardized assessment tools are needed.

BACKGROUND: Surgical site infection (SSI) is the most common complication of surgery worldwide, and frequently occurs after hospital discharge. Evidence to support implementation of telemedicine during postoperative recovery will be an essential component of pandemic recovery.

METHODS: The primary outcome of this study was SSI reported up to 30 days after surgery (SSI), comparing rates reported using telemedicine (telephone and/or video assessment) to those with in-person review. The first part of this study analyzed primary data from …

Effects Of Different Spectrum Of Leds On Retinal Degeneration Through Regulating Endoplasmic Reticulum Stress, Wenyi Chen, Rong Lin, Kunhong Xiao, Kun Yuan, Zhongjiang Chen, Yan Huang

Faculty, Staff and Student Publications

PURPOSE: To evaluate the impact of full-spectrum light-emitting diodes (LEDs) on albino guinea pigs' retina and investigate the roles of short-wavelength opsin (S-opsin) and endoplasmic reticulum (ER) stress in light-induced retinal degeneration (LIRD).

METHODS: Three-week-old albino guinea pigs (n = 30) were distributed into five groups under 12/12 light/dark cycles with indoor natural light (NC; 300-500 lux, n = 6), full-spectrum LEDs (FL; 300 lux, n = 6; 3000 lux, n = 6), and commercial cold-white LEDs (CL; 300 lux, n = 6; 3000 lux, n = 6) and raised for 28 days. Hematoxylin and eosin staining and transmission electron …

Ccr7 Mediated Mimetic Dendritic Cell Vaccine Homing In Lymph Node For Head And Neck Squamous Cell Carcinoma Therapy, Jiabin Xu, Hong Liu, Tao Wang, Zhenfu Wen, Haolin Chen, Zeyu Yang, Liyan Li, Shan Yu, Siyong Gao, Le Yang, Kan Li, Jingyuan Li, Xiang Li, Lixin Liu, Guiqing Liao, Yongming Chen, Yujie Liang

Faculty, Staff and Student Publications

Immunotherapy has been recognized as one of the most promising treatment strategies for head and neck squamous cell carcinoma (HNSCC). As a pioneering trend of immunotherapy, dendritic cell (DC) vaccines have displayed the ability to prime an immune response, while the insufficient immunogenicity and low lymph node (LN) targeting efficiency, resulted in an unsubstantiated therapeutic efficacy in clinical trials. Herein, a hybrid nanovaccine (Hy-M-Exo) is developed via fusing tumor-derived exosome (TEX) and dendritic cell membrane vesicle (DCMV). The hybrid nanovaccine inherited the key protein for lymphatic homing, CCR7, from DCMV and demonstrated an enhanced efficiency of LN targeting. Meanwhile, the …

Evolving Antibiotic Resistance In Group B Streptococci Causing Invasive Infant Disease: 1970–2021, Elizabeth Marie Sabroske, Misu Ailin Sanson Iglesias, Marcia Rench, Trevor Moore, Hanna Harvey, Morven Edwards, Carol J Baker, Anthony R Flores

Faculty, Staff and Student Publications

BACKGROUND: We sought to define the frequency of antibiotic resistance over time in a collection of invasive GBS isolates derived from infant early-onset disease (EOD), late-onset disease (LOD), and late-late onset disease (LLOD).

METHODS: A multicenter retrospective review of infants born from 1970 to 2021 with GBS isolated from blood, cerebrospinal fluid, synovial fluid, cellulitis, or bone. All isolates were serotyped and antimicrobial susceptibility testing performed using disk diffusion.

RESULTS: The most common serotypes in our 2017 isolates were III (n = 1112, 55.1%), Ia (n = 445, 22%), Ib (n = 182, 9%) and II (n = 146, 7.2%). …

The Tempo And Mode Of Gene Regulatory Programs During Bacterial Infection, Rocio Diaz Escarcega, Abhijeet A Patil, Matthew D Meyer, Jose F Moruno-Manchon, Alexander D Silvagnoli, Louise D Mccullough, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Tardigrades are microscopic invertebrates, which are capable of withstanding extreme environmental conditions, including high levels of radiation. A Tardigrade protein, Dsup (Damage Suppressor), protects the Tardigrade's DNA during harsh environmental stress and X-rays. When expressed in cancer cells, Dsup protects DNA from single- and double-strand breaks (DSBs) induced by radiation, increases survival of irradiated cells, and protects DNA from reactive oxygen species. These unusual properties of Dsup suggested that understanding how the protein functions may help in the design of small molecules that could protect humans during radiotherapy or space travel. Here, we investigated if Dsup is protective in cortical …

Heart And Timi Scores Predict Severe Coronary Atherosclerosis In Patients With End-Stage Renal Disease, Trishna B Parikh, Moez Aziz, Samuel P Mackoff, Gabriel M Aisenberg

Faculty, Staff and Student Publications

Objectives History, EKG, age, risk factors, and troponin (HEART) and thrombolysis in myocardial infarction (TIMI) risk calculators have been validated to predict the risk of subsequent acute coronary syndromes and in some studies, severe coronary atherosclerosis in patients with a concerning clinical history. Their performance in patients with end-stage renal disease (ESRD), a population with a high pretest probability for the condition, is unknown. We aimed to determine whether HEART and TIMI scores can predict severe coronary atherosclerosis in patients with end-stage renal disease (ESRD). Methods A single-center retrospective cohort of admitted patients aged 18 years or older with ESRD …

Impact Of Transfused Citrate On Pathophysiology In Massive Transfusion, Jacob B Schriner, J Michael Van Gent, M Adam Meledeo, Scott D Olson, Bryan A Cotton, Charles S Cox, Brijesh S Gill

Faculty, Staff and Student Publications

This narrative review article seeks to highlight the effects of citrate on physiology during massive transfusion of the bleeding patient.

DATA SOURCES: A limited library of curated articles was created using search terms including "citrate intoxication," "citrate massive transfusion," "citrate pharmacokinetics," "hypocalcemia of trauma," "citrate phosphate dextrose," and "hypocalcemia in massive transfusion." Review articles, as well as prospective and retrospective studies were selected based on their relevance for inclusion in this review.

STUDY SELECTION: Given the limited number of relevant studies, studies were reviewed and included if they were written in English. This is not a systematic review nor a …

An End-To-End In-Silico And In-Vitro Drug Repurposing Pipeline For Glioblastoma, Ko-Hong Lin, Jay-Jiguang Zhu, Judith A Smith, Yejin Kim, Xiaoqian Jiang

Faculty, Staff and Student Publications

Our study aims to address the challenges in drug development for glioblastoma, a highly aggressive brain cancer with poor prognosis. We propose a computational framework that utilizes machine learning-based propensity score matching to estimate counterfactual treatment effects and predict synergistic effects of drug combinations. Through our in-silico analysis, we identified promising drug candidates and drug combinations that warrant further investigation. To validate these computational findings, we conducted in-vitro experiments on two GBM cell lines, U87 and T98G. The experimental results demonstrated that some of the identified drugs and drug combinations indeed exhibit strong suppressive effects on GBM cell growth. Our …

Neurobehavioral And Biochemical Effects Of Choline Chloride Administration In Rats, Lubna Anis, Irfan Sajid, Shoaib Ahmad, Saida Haider

Pakistan Journal of Neurological Sciences (PJNS)

Background and Objective:

Choline is an essential nutrient related to vitamin B complex activity. It can be received through different food sources. It is an important component of acetylcholine which is involved in different brain functions. The present study is designed to assess the behavioral effects of choline chloride in animal models.

Methods:This case-control study was performed in the Department of Biochemistry, Federal Urdu University, Karachi for eight months from May 2022 to December 2022. Twenty-four adult male albino Wister rats were divided into four groups, one control and three test groups. Choline chloride dissolved in saline was given …

Cest-Mri For Body Oncologic Imaging: Are We There Yet?, Elena Vinogradov, Jochen Keupp, Ivan E Dimitrov, Stephen Seiler, Ivan Pedrosa

Faculty, Staff and Student Publications

Chemical exchange saturation transfer (CEST) MRI has gained recognition as a valuable addition to the molecular imaging and quantitative biomarker arsenal, especially for characterization of brain tumors. There is also increasing interest in the use of CEST-MRI for applications beyond the brain. However, its translation to body oncology applications lags behind those in neuro-oncology. The slower migration of CEST-MRI to non-neurologic applications reflects the technical challenges inherent to imaging of the torso. In this review, we discuss the application of CEST-MRI to oncologic conditions of the breast and torso (i.e., body imaging), emphasizing the challenges and potential solutions to address …

Flt3 Inhibitors Upregulate Cxcr4 And E-Selectin Ligands Via Erk Suppression In Aml Cells And Cxcr4/E-Selectin Inhibition Enhances Anti-Leukemia Efficacy Of Flt3-Targeted Therapy In Aml, Yannan Jia, Weiguo Zhang, Mahesh Basyal, Kyung Hee Chang, Lauren Ostermann, Jared K Burks, Charlie Ly, Hong Mu-Mosley, Qi Zhang, Xin Han, William E Fogler, John L Magnani, Arnaud Lesegretain, Anna A Zal, Tomasz Zal, Michael Andreeff

Faculty, Staff and Student Publications

No abstract provided.

Enhancement Of Immunotherapies In Head And Neck Cancers Using Biomaterial-Based Treatment Strategies, Gemalene M Sunga, Jeffrey Hartgerink, Andrew G Sikora, Simon Young

Faculty, Staff and Student Publications

Head and neck squamous cell carcinoma (HNSCC) is a challenging disease to treat because of typically late-stage diagnoses and tumor formation in difficult-to-treat areas, sensitive to aggressive or invasive treatments. To date, HNSCC treatments have been limited to surgery, radiotherapy, and chemotherapy, which may have significant morbidity and often lead to long-lasting side effects. The development of immunotherapies has revolutionized cancer treatment by providing a promising alternative to standard-of-care therapies. However, single-agent immunotherapy has been only modestly effective in the treatment of various cancers, including HNSCC, with most patients receiving no overall benefit or increased survival. In addition, single-agent immunotherapy's …

Facial Analytics Based On A Coordinate Extrapolation System (Zface) For Morphometric Phenotyping Of Developing Zebrafish, Lorena Maili, Oscar E Ruiz, Philip H Kahan, Frankie Chiu, Stephen T Larson, S Shahrukh Hashmi, Jacqueline T Hecht, George T Eisenhoffer

Faculty, Staff and Student Publications

Facial development requires a complex and coordinated series of cellular events that, when perturbed, can lead to structural birth defects. A quantitative approach to quickly assess morphological changes could address how genetic or environmental inputs lead to differences in facial shape and promote malformations. Here, we report on a method to rapidly analyze craniofacial development in zebrafish embryos using facial analytics based on a coordinate extrapolation system, termed zFACE. Confocal images capture facial structures and morphometric data are quantified based on anatomical landmarks present during development. The quantitative morphometric data can detect phenotypic variation and inform on changes in facial …

Aibp Regulates Trpv1 Activation In Chemotherapy-Induced Peripheral Neuropathy By Controlling Lipid Raft Dynamics And Proximity To Tlr4 In Dorsal Root Ganglion Neurons, Juliana M Navia-Pelaez, Julia Borges Paes Lemes, Leonardo Gonzalez, Lauriane Delay, Luciano Dos Santos Aggum Capettini, Jenny W Lu, Gilson Gonçalves Dos Santos, Ann M Gregus, Patrick M Dougherty, Tony L Yaksh, Yury I Miller

Faculty, Staff and Student Publications

Nociceptive afferent signaling evoked by inflammation and nerve injury is mediated by the opening of ligand-gated and voltage-gated receptors or channels localized to cholesterol-rich lipid raft membrane domains. Dorsal root ganglion (DRG) nociceptors express high levels of toll-like receptor 4 (TLR4), which also localize to lipid rafts. Genetic deletion or pharmacologic blocking of TLR4 diminishes pain associated with chemotherapy-induced peripheral neuropathy (CIPN). In DRGs of mice with paclitaxel-induced CIPN, we analyzed DRG neuronal lipid rafts, expression of TLR4, activation of transient receptor potential cation channel subfamily V member 1 (TRPV1), and TLR4-TRPV1 interaction. Using proximity ligation assay, flow cytometry, and …

Impact Of Covid-19 On Latinx And Black Communities, Carolina Zuluaga

Dissertations

This critical literature review project explored the impact of COVID-19 on Latinx and Black communities. According to the Centers for Disease Control and Prevention, as of September 28, 2022, around 16% of COVID-19 cases in the United States were among Latinx people, and 14% of cases were among Black people (Centers for Disease Control and Prevention, 2022). Since COVID-19 began, clinicians have become more conscious of the effects of health disparities within racial and ethnic minorities, which has warranted increased advocacy by educating health and mental health providers and creating and providing resources to these communities and clinicians. The review …

Forging New Therapeutic Targets: Efforts Of Tumor Derived Exosomes To Prepare The Pre-Metastatic Niche For Cancer Cell Dissemination And Dormancy, Ranvir Bhatia, Joanna Chang, Jessian L Munoz, Nykia D Walker

Faculty, Staff and Students Publications

Tumor-derived exosomes play a multifaceted role in preparing the pre-metastatic niche, promoting cancer dissemination, and regulating cancer cell dormancy. A brief review of three types of cells implicated in metastasis and an overview of other types of extracellular vesicles related to metastasis are described. A central focus of this review is on how exosomes influence cancer progression throughout metastatic disease. Exosomes are crucial mediators of intercellular communication by transferring their cargo to recipient cells, modulating their behavior, and promoting tumor pro-gression. First, their functional role in cancer cell dissemination in the peripheral blood by facilitating the establishment of a pro-angiogenic …

Magnesium Increases Numbers Of Foxp3+ Treg Cells And Reduces Arthritis Severity And Joint Damage In An Il-10-Dependent Manner Mediated By The Intestinal Microbiome, Teresina Laragione, Carolyn Harris, Nasim Azizgolshani, Christine Beeton, Gerold Bongers, Percio S Gulko

Faculty, Staff and Students Publications

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease with emerging environmental and microbiome risk factors. The western diet is typically deficient in magnesium (Mg), and there is some evidence suggesting that Mg may have anti-inflammatory properties. But the actual role of Mg supplementation in arthritis or in T cell subsets has not been explored.

METHODS: We investigated the role of a high Mg diet in two different mouse models of RA induced with the KRN serum, and collagen-induced arthritis. We also characterized the phenotypes of splenocytes, gene expression, and an extensive intestinal microbiome analyses including fecal material transplantation (FMT). …

Clinical Spectrum And Genetic Causes Of Mitochondrial Hepatopathy Phenotype In Children, James E Squires, Alexander G Miethke, C Alexander Valencia, Kieran Hawthorne, Lisa Henn, Johan L K Van Hove, Robert H Squires, Kevin Bove, Simon Horslen, Rohit Kohli, Jean P Molleston, Rene Romero, Estella M Alonso, Jorge A Bezerra, Stephen L Guthery, Evelyn Hsu, Saul J Karpen, Kathleen M Loomes, Vicky L Ng, Philip Rosenthal, Krupa Mysore, Kasper S Wang, Marisa W Friederich, John C Magee, Ronald J Sokol, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

BACKGROUND: Alterations in both mitochondrial DNA (mtDNA) and nuclear DNA genes affect mitochondria function, causing a range of liver-based conditions termed mitochondrial hepatopathies (MH), which are subcategorized as mtDNA depletion, RNA translation, mtDNA deletion, and enzymatic disorders. We aim to enhance the understanding of pathogenesis and natural history of MH.

METHODS: We analyzed data from patients with MH phenotypes to identify genetic causes, characterize the spectrum of clinical presentation, and determine outcomes.

RESULTS: Three enrollment phenotypes, that is, acute liver failure (ALF, n = 37), chronic liver disease (Chronic, n = 40), and post-liver transplant (n = 9), were analyzed. …

A 3d-Printable, Low-Cost Obturator For Less Invasive Gynecologic Brachytherapy, Sanika Rane, Alexander Hanania, Elisa Arango, Krithika Kumar, Lauren Payne, Susannah Dittmar, Gaurav Gomber, Vincent Ugarte, Michelle Ludwig

Faculty, Staff and Students Publications

The purpose of this report is to design, develop, and evaluate a cost-effective applicator for interstitial brachytherapy (ISBT) to minimize patient morbidity and facilitate access to curative radiation treatment for gynecologic cancers, especially in low-resource settings. A computer-aided design and prototype were developed of a proposed applicator that incorporates 44 slotted channels to gently guide needles, with or without a tandem, through the vaginal canal, effectively eliminating the need for transcutaneous needle insertions typically employed during ISBT of advanced gynecologic cancer and thus reducing the risk of vaginal laceration and bladder or rectal injury. The tested prototype was developed using …

Birth Weight Moderates The Association Between Obesity And Mortality Rate, Gregory Pavela, Nengjun Yi, Luis Mestre, Pengcheng Xun, David B Allison

Children’s Nutrition Research Center Staff Publications

Purpose: The strength of the association between obesity and mortality rate (MR) varies by body mass index (BMI) and sociodemographic groups. We test the hypothesis that the association between obesity and MR varies, in part, due to the moderating effect of parental BMI and birth weight.

Methods: Data come from the 1958 National Child Development Study, an ongoing longitudinal dataset initiated in 1958 with baseline measures of birth weight from 18,059 infants born in Great Britain over 1 week. We tested whether the association between BMI and MR was moderated by parental BMI and birth weight using generalized additive proportional …

Particle Arc Single-Isocenter Stereotactic Radiosurgery Of Multiple Brain Metastases, L Volz, S Mein, T Tessonnier, Peilin Liu, A Mairani, M Durante, Xuanfeng Ding, C Graeff, T Li

Conference Presentation Abstracts

Purpose: To develop spot-scanning proton (SPArc) and heavy ion (SHArc) arc therapy for single-isocenter stereotatic radiosurgery (SISRS) of multiple brain metastases (MBMs). First results achieved with dedicated planning infrastructure are compared to state-of-the -art volumetric modulated photon arc therapy (HA-VMAT). Methods: A multi-institutional collaboration was established to develop bespoke SPArc and SHArc SISRS infrastructure with available research and commercial treatment planning systems. Devised planning and delivery methods considered dedicated energy, spot, and multi-arc selection strategies. SPArc and SHArc (carbon and helium ions) plans were generated for MBM patients exhibiting 3-12 intracranial lesions with GTV volumes between 0.03ccm and 19.8ccm, at …

A Highly Selective Humanized Ddr1 Mab Reverses Immune Exclusion By Disrupting Collagen Fiber Alignment In Breast Cancer, Junquan Liu, Huai-Chin Chiang, Wei Xiong, Victor Laurent, Samuel C Griffiths, Jasmin Dülfer, Hui Deng, Xiujie Sun, Y Whitney Yin, Wenliang Li, Laurent P Audoly, Zhiqiang An, Thomas Schürpf, Rong Li, Ningyan Zhang

Faculty, Staff and Student Publications

BACKGROUND: Immune exclusion (IE) where tumors deter the infiltration of immune cells into the tumor microenvironment has emerged as a key mechanism underlying immunotherapy resistance. We recently reported a novel role of discoidin domain-containing receptor 1 (DDR1) in promoting IE in breast cancer and validated its critical role in IE using neutralizing rabbit monoclonal antibodies (mAbs) in multiple mouse tumor models.

METHODS: To develop a DDR1-targeting mAb as a potential cancer therapeutic, we humanized mAb9 with a complementarity-determining region grafting strategy. The humanized antibody named PRTH-101 is currently being tested in a Phase 1 clinical trial. We determined the binding …

Maternal Embryonic Leucine Zipper Kinase Is Associated With Metastasis In Triple-Negative Breast Cancer, Xuemei Xie, Gaurav B Chauhan, Ramakrishna Edupuganti, Takahiro Kogawa, Jihyun Park, Moises Tacam, Alex W Tan, Mohd Mughees, Fnu Vidhu, Diane D Liu, Juliana M Taliaferro, Mary Kathryn Pitner, Luke S Browning, Ju-Hyeon Lee, Yu Shen, Jian Wang, Naoto T Ueno, Savitri Krishnamurthy, Gabriel N Hortobagyi, Debu Tripathy, Steven J Van Laere, Geoffrey Bartholomeusz, Kevin N Dalby, Chandra Bartholomeusz

Faculty, Staff and Student Publications

UNLABELLED: Triple-negative breast cancer (TNBC) has high relapse and metastasis rates and a high proportion of cancer stem-like cells (CSC), which possess self-renewal and tumor initiation capacity. MELK (maternal embryonic leucine zipper kinase), a protein kinase of the Snf1/AMPK kinase family, is known to promote CSC maintenance and malignant transformation. However, the role of MELK in TNBC metastasis is unknown; we sought to address this in the current study. We found that

SIGNIFICANCE: These findings indicate that MELK is a driver of aggressiveness and metastasis in TNBC.

Antioxidant Activity And Total Phenolic Compounds Of Commiphora Gileadensis Extracts Obtained By Ultrasonic-Assisted Extraction, With Monitoring Antiaging And Cytotoxicity Activities, Hani Ahmed, Marwan M A Rashed, Marwan Almoiliqy, Mohammed Abdalla, Mohanad Bashari, Mohamed Y Zaky, Zhu Hailin, Taha A A Naji, Ahmed Eibaid, Jinpeng Wang, Li-Ping Jiang

Faculty, Staff and Student Publications

Commiphora gileadensis (C. gileadensis) has been identified and linked with various health benefits and pharmaceutical potential for its phytochemical activities and chemical constituents. This study aimed to evaluate ultrasonic‐assisted extraction (USE) technique for total phenols content from C. gileadensis leaf compared to the hydrodistillation extraction (HDE). Our results showed that the USE operating conditions were identified as: MeOH·H2O solvent‐to‐fresh sample ratio of 80:20 (v/v); ultrasonic power/frequency at 150 W/20 kHz; and a temperature of 40 ± 1°C; subjected to acoustic waves intermittently for a calculated time (5 min) during the total programmed time of 12 min. The USE …

Cellular Senescence And Frailty In Transplantation, Elizabeth C Lorenz, Latonya J Hickson, Pascale Khairallah, Bijan Najafi, Cassie C Kennedy

Center on Aging Staff Publications

Purpose of review: To summarizes the literature on cellular senescence and frailty in solid-organ transplantation and highlight the emerging role of senotherapeutics as a treatment for cellular senescence.

Recent findings: Solid-organ transplant patients are aging. Many factors contribute to aging acceleration in this population, including cellular senescence. Senescent cells accumulate in tissues and secrete proinflammatory and profibrotic proteins which result in tissue damage. Cellular senescence contributes to age-related diseases and frailty. Our understanding of the role cellular senescence plays in transplant-specific complications such as allograft immunogenicity and infections is expanding. Promising treatments, including senolytics, senomorphics, cell-based regenerative therapies, and behavioral …

Highlights Of The 2022 Brano Heart Failure Forum: Part One, Ugo Livi, Rajko Radovancevic, Bojan Vrtovec, Igor D. Gregoric

The VAD Journal

Since 2007, the Branislav “Brano” Radovancevic Heart Failure Forum (BHFF) has been held annually to provide a venue for experts to present and discuss “Innovations and New Treatment Strategies in Heart Failure.” Clinicians and researchers gather yearly in a different Eastern European city to discuss the latest in heart failure diagnostics and therapeutics. The 2022 BHHF forum was held on the 6^th thru 8^th of September 2022 in Trieste, Italy. It was attended by over 94 faculty from 14 countries. In addition, participation through online streaming was available. Throughout the forum, 17 sessions focused on challenges and solutions …

Therapeutic Strategies Targeting Respiratory Recovery After Spinal Cord Injury: From Preclinical Development To Clinical Translation, Pauline Michel-Flutot, Michael A. Lane, Angelo C. Lepore, Stéphane Vinit

Farber Institute for Neuroscience Faculty Papers

High spinal cord injuries (SCIs) lead to permanent functional deficits, including respiratory dysfunction. Patients living with such conditions often rely on ventilatory assistance to survive, and even those that can be weaned continue to suffer life-threatening impairments. There is currently no treatment for SCI that is capable of providing complete recovery of diaphragm activity and respiratory function. The diaphragm is the main inspiratory muscle, and its activity is controlled by phrenic motoneurons (phMNs) located in the cervical (C3–C5) spinal cord. Preserving and/or restoring phMN activity following a high SCI is essential for achieving voluntary control of breathing. In this review, …