Medicine and Health Sciences Commons^™

Gene Therapy Ameliorates Spontaneous Seizures Associated With Cortical Neuron Loss In A Cln2r207x Mouse Model, Keigo Takahashi, Elizabeth M. Eultgen, Sophie H. Wang, Nicholas R. Rensing, Hemanth R. Nelvagal, Joshua T. Dearborn, Olivier Danos, Nicholas Buss, Mark S. Sands, Michael Wong, Jonathan D. Cooper

2020-Current year OA Pubs

Although a disease-modifying therapy for classic late infantile neuronal ceroid lipofuscinosis (CLN2 disease) exists, poor understanding of cellular pathophysiology has hampered the development of more effective and persistent therapies. Here, we investigated the nature and progression of neurological and underlying neuropathological changes in Cln2R207X mice, which carry one of the most common pathogenic mutations in human patients but are yet to be fully characterized. Long-term electroencephalography recordings revealed progressive epileptiform abnormalities, including spontaneous seizures, providing a robust, quantifiable, and clinically relevant phenotype. These seizures were accompanied by the loss of multiple cortical neuron populations, including those stained for interneuron markers. …

Antigen-Driven Colonic Inflammation Is Associated With Development Of Dysplasia In Primary Sclerosing Cholangitis, Dustin G Shaw, Kelly Monroe, Rodney Newberry, Et Al.

2020-Current year OA Pubs

Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time …

Evaluation Of The Ng-Test Carba 5 Lateral Flow Assay With An Imp-2-Producing Morganella Morganii And Other Morganellaceae, Nicole J. Tarlton, Meghan A. Wallace, Robert F. Potter, Kailun Zhang, Gautam Dantas, Erik R. Dubberke, Carey-Ann D. Burnham, Melanie L. Yarbrough

2020-Current year OA Pubs

An isolate of Morganella morganii (MMOR1) that tested susceptible to 3

Poly(Adp-Ribose) Polymerase 9 Mediates Early Protection Against Mycobacterium Tuberculosis Infection By Regulating Type I Ifn Production, Shyamala Thirunavukkarasu, Mushtaq Ahmed, Bruce A. Rosa, Mark Boothby, Sung Hoon Cho, Javier Rangel-Moreno, Stanley K. Mbandi, Valérie Schreiber, Ananya Gupta, Joaquin Zuniga, Makedonka Mitreva, Deepak Kaushal, Thomas J. Scriba, Shabaana A. Khader

2020-Current year OA Pubs

The ADP ribosyltransferases (PARPs 1-17) regulate diverse cellular processes, including DNA damage repair. PARPs are classified on the basis of their ability to catalyze poly-ADP-ribosylation (PARylation) or mono-ADP-ribosylation (MARylation). Although PARP9 mRNA expression is significantly increased in progressive tuberculosis (TB) in humans, its participation in host immunity to TB is unknown. Here, we show that PARP9 mRNA encoding the MARylating PARP9 enzyme was upregulated during TB in humans and mice and provide evidence of a critical modulatory role for PARP9 in DNA damage, cyclic GMP-AMP synthase (cGAS) expression, and type I IFN production during TB. Thus, Parp9-deficient mice were susceptible …

Shank2 Identifies A Subset Of Glycinergic Neurons Involved In Altered Nociception In An Autism Model, Florian Olde Heuvel, Sanjay Jain, Et Al.

2020-Current year OA Pubs

BACKGROUND: Autism Spectrum Disorders (ASD) patients experience disturbed nociception in the form of either hyposensitivity to pain or allodynia. A substantial amount of processing of somatosensory and nociceptive stimulus takes place in the dorsal spinal cord. However, many of these circuits are not very well understood in the context of nociceptive processing in ASD.

METHODS: We have used a Shank2

RESULTS: We determined that Shank2

LIMITATIONS: Our investigation is limited to male mice, in agreement with the higher representation of ASD in males; therefore, caution should be applied to extrapolate the findings to females. Furthermore, ASD is characterized by extensive …

Large, Nested Variant Of Urothelial Carcinoma S Enriched With Activating Mutations In Fibroblast Growth Factor Receptor-3 Among Other Targetable Mutations, Yaser Gamallat, Mitra Afsharpad, Soufiane El Hallani, Christopher A Maher, Nimira Alimohamed, Eric Hyndman, Tarek A Bismar

2020-Current year OA Pubs

The large, nested variant of urothelial carcinoma (LNVUC) is characterized by bland histomorphology mimicking that of benign von Brunn nests. In the current study, we aimed to investigate the

Basal Type I Interferon Signaling Has Only Modest Effects On Neonatal And Juvenile Hematopoiesis, Yanan Li, Wei Yang, Helen C Wang, Riddhi M Patel, Emily B Casey, Elisabeth Denby, Jeffrey A Magee

2020-Current year OA Pubs

Type I interferon (IFN-1) regulates gene expression and hematopoiesis both during development and in response to inflammatory stress. We previously showed that during development in mice, hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) induce IFN-1 target genes shortly before birth. This coincides with the onset of a transition to adult hematopoiesis, and it drives the expression of genes associated with antigen presentation. However, it is not clear whether perinatal IFN-1 modulates hematopoietic output, as has been observed in contexts of inflammation. We have characterized hematopoiesis at several different stages of blood formation, from HSCs to mature blood cells, and …

Embryonic Vitamin D Deficiency Programs Hematopoietic Stem Cells To Induce Type 2 Diabetes, Jisu Oh, Amy E Riek, Kevin T Bauerle, Adriana Dusso, Kyle P Mcnerney, Ruteja A Barve, Isra Darwech, Jennifer E Sprague, Clare Moynihan, Rong M Zhang, Greta Kutz, Ting Wang, Xiaoyun Xing, Daofeng Li, Marguerite Mrad, Nicholas M Wigge, Esmeralda Castelblanco, Monika Bambouskova, Richard D Head, Mark S Sands, Carlos Bernal-Mizrachi, Et Al.

2020-Current year OA Pubs

Environmental factors may alter the fetal genome to cause metabolic diseases. It is unknown whether embryonic immune cell programming impacts the risk of type 2 diabetes in later life. We demonstrate that transplantation of fetal hematopoietic stem cells (HSCs) made vitamin D deficient in utero induce diabetes in vitamin D-sufficient mice. Vitamin D deficiency epigenetically suppresses Jarid2 expression and activates the Mef2/PGC1a pathway in HSCs, which persists in recipient bone marrow, resulting in adipose macrophage infiltration. These macrophages secrete miR106-5p, which promotes adipose insulin resistance by repressing PIK3 catalytic and regulatory subunits and down-regulating AKT signaling. Vitamin D-deficient monocytes from …

Dnajb6 Isoform Specific Knockdown: Therapeutic Potential For Limb Girdle Muscular Dystrophy D1, Andrew R Findlay, May M Paing, Jil A Daw, Meade Haller, Rocio Bengoechea, Sara K Pittman, Shan Li, Feng Wang, Timothy M Miller, Heather L True, Tsui-Fen Chou, Conrad C Weihl

2020-Current year OA Pubs

Dominant missense mutations in DNAJB6, a co-chaperone of HSP70, cause limb girdle muscular dystrophy (LGMD) D1. No treatments are currently available. Two isoforms exist, DNAJB6a and DNAJB6b, each with distinct localizations in muscle. Mutations reside in both isoforms, yet evidence suggests that DNAJB6b is primarily responsible for disease pathogenesis. Knockdown treatment strategies involving both isoforms carry risk, as DNAJB6 knockout is embryonic lethal. We therefore developed an isoform-specific knockdown approach using morpholinos. Selective reduction of each isoform was achieved

Safety Of Fecal Microbiota, Live-Jslm (Rebyota™) In Individuals With Recurrent Clostridioides Difficile Infection: Data From Five Prospective Clinical Trials, Christine Lee, Thomas Louie, Lindy Bancke, Beth Guthmueller, Adam Harvey, Paul Feuerstadt, Sahil Khanna, Robert Orenstein, Erik R Dubberke

2020-Current year OA Pubs

BACKGROUND: Microbiota-based treatments reduce the incidence of recurrent

OBJECTIVES: We provide cumulative safety data from five prospective clinical trials evaluating fecal microbiota, live-jslm (RBL) - the first microbiota-based live biotherapeutic product approved by the US Food and Drug Administration - for preventing rCDI in adults.

DESIGN: Integrated safety analysis includes three phase II trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and two phase III trials (PUNCH CD3, PUNCH CD3-OLS) of RBL.

METHODS: Trial participants were at least 18 years of age with documented rCDI who completed standard-of-care antibiotic therapy before treatment with RBL. Assigned study treatment regimen was one or …

Single Cell And Spatial Sequencing Define Processes By Which Keratinocytes And Fibroblasts Amplify Inflammatory Responses In Psoriasis, Feiyang Ma, Eynav Klechevsky, Et Al.

2020-Current year OA Pubs

The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is incompletely understood. Here we demonstrate, using a combination of single cell and spatial RNA sequencing, IL-36 dependent amplification of IL-17A and TNF inflammatory responses in the absence of neutrophil proteases, which primarily occur within the supraspinous layer of the psoriatic epidermis. We further show that a subset of SFRP2

Three-Dimensional Imaging And Quantification Of Mouse Ovarian Follicles Via Optical Coherence Tomography, Marcello Magri Amaral, Aixia Sun, Yilin Li, Chao Ren, Anh Blue Truong, Saumya Nigam, Zexu Jiao, Ping Wang, Chao Zhou

2020-Current year OA Pubs

Ovarian tissue cryopreservation has been successfully applied worldwide for fertility preservation. Correctly selecting the ovarian tissue with high follicle loading for freezing and reimplantation increases the likelihood of restoring ovarian function, but it is a challenging process. In this work, we explore the use of three-dimensional spectral-domain optical coherence tomography (SD-OCT) to identify different follicular stages, compare the identifications with H&E images, and measure the size and age-related follicular density distribution differences in mice ovaries. We use the thickness of the layers of granulosa cells to differentiate primordial and primary follicles from secondary follicles. The measured dimensions and age-related follicular …

In Vitro And In Vivo Efficacy Of A Stroma-Targeted, Tumor Microenvironment Responsive Oncolytic Adenovirus In Different Preclinical Models Of Cancer, Ana Alfano, Eduardo G A Cafferata, Mariela Gangemi, Alejandro Nicola Candia, Cristian M Malnero, Ismael Bermudez, Mauricio Vargas Lopez, Gregorio David Ríos, Cecilia Rotondaro, Nicasio Cuneo, David T Curiel, Osvaldo L Podhajcer, Maria Veronica Lopez

2020-Current year OA Pubs

More than one million women are diagnosed annually worldwide with a gynecological cancer. Most gynecological cancers are diagnosed at a late stage, either because a lack of symptoms, such as in ovarian cancer or limited accessibility to primary prevention in low-resource countries, such as in cervical cancer. Here, we extend the studies of AR2011, a stroma-targeted and tumor microenvironment responsive oncolytic adenovirus (OAdV), whose replication is driven by a triple hybrid promoter. We show that AR2011 was able to replicate and lyse in vitro fresh explants obtained from human ovarian cancer, uterine cancer, and cervical cancer. AR2011 was also able …

Zinc Cluster Transcription Factors Frequently Activate Target Genes Using A Non-Canonical Half-Site Binding Mode, Pamela S Recio, Nikhil J Mitra, Christian A Shively, David Song, Grace Jaramillo, Kristine Shady Lewis, Xuhua Chen, Robi D Mitra

2020-Current year OA Pubs

Gene expression changes are orchestrated by transcription factors (TFs), which bind to DNA to regulate gene expression. It remains surprisingly difficult to predict basic features of the transcriptional process, including in vivo TF occupancy. Existing thermodynamic models of TF function are often not concordant with experimental measurements, suggesting undiscovered biology. Here, we analyzed one of the most well-studied TFs, the yeast zinc cluster Gal4, constructed a Shea-Ackers thermodynamic model to describe its binding, and compared the results of this model to experimentally measured Gal4p binding in vivo. We found that at many promoters, the model predicted no Gal4p binding, yet …

Adaptation Of A Mobile Interactive Obesity Treatment Approach For Early Severe Mental Illness: Protocol For A Mixed Methods Implementation And Pilot Randomized Controlled Trial, Ginger E Nicol, Madeline O Jansen, Amanda R Ricchio, Julia A Schweiger, Katie E Keenoy, J Philip Miller, Elaine H Morrato, Zhaohua Guo, Bradley A Evanoff, Joseph J Parks, John W Newcomer

2020-Current year OA Pubs

BACKGROUND: Obesity is common in individuals with severe mental illness (SMI), contributing to a significantly shortened lifespan when compared to the general population. Available weight loss treatments have attenuated efficacy in this population, underscoring the importance of prevention and early intervention.

OBJECTIVE: Here, we describe a type 1 hybrid study design for adapting and pilot-testing an existing mobile health intervention for obesity prevention in individuals with early SMI and Class I or early-stage obesity, defined as a BMI of 30-35.

METHODS: An existing, evidence-based interactive obesity treatment approach using low-cost, semiautomated SMS text messaging was selected for adaptation. Community mental …

The Child's Age And The Size Of The Curvature Do Not Affect The Accuracy Of Screw Placement With The Free-Hand Technique In Spinal Deformities In Children And Adolescents, Pawel Grabala, Ilkka J Helenius, Piotr Kowalski, Michal Grabala, Slawomir Zacha, Jaroslaw M Deszczynski, Tomasz Albrewczynski, Michael A Galgano, Jacob M Buchowski, Kelly Chamberlin, Suken A Shah

2020-Current year OA Pubs

BACKGROUND: The current method of treatment of spinal deformities would be almost impossible without pedicle screws (PS) placement. There are only a few studies evaluating the safety of PS placement and possible complications in children during growth. The present study was carried out to evaluate the safety and accuracy of PS placement in children with spinal deformities at any age using postoperative computed tomography (CT) scans.

METHODS: 318 patients (34 males and 284 females) who underwent 6358 PS fixations for pediatric spinal deformities were enrolled in this multi-center study. The patients were divided into three age groups: less than 10 …

Histone H2a Lys130 Acetylation Epigenetically Regulates Androgen Production In Prostate Cancer, Thanh Nguyen, Dhivya Sridaran, Surbhi Chouhan, Cody Weimholt, Audrey Wilson, Jingqin Luo, Tiandao Li, John Koomen, Bin Fang, Nagireddy Putluri, Arun Sreekumar, Felix Y Feng, Kiran Mahajan, Nupam P Mahajan

2020-Current year OA Pubs

The testicular androgen biosynthesis is well understood, however, how cancer cells gauge dwindling androgen to dexterously initiate its de novo synthesis remained elusive. We uncover dual-phosphorylated form of sterol regulatory element-binding protein 1 (SREBF1), pY673/951-SREBF1 that acts as an androgen sensor, and dissociates from androgen receptor (AR) in androgen deficient environment, followed by nuclear translocation. SREBF1 recruits KAT2A/GCN5 to deposit epigenetic marks, histone H2A Lys130-acetylation (H2A-K130ac) in SREBF1, reigniting de novo lipogenesis & steroidogenesis. Androgen prevents SREBF1 nuclear translocation, promoting T cell exhaustion. Nuclear SREBF1 and H2A-K130ac levels are significantly increased and directly correlated with late-stage prostate cancer, reversal of …

The Effect Of Dnaaf5 Gene Dosage On Primary Ciliary Dyskinesia Phenotypes, Amjad Horani, Deepesh Kumar Gupta, Jian Xu, Huihui Xu, Lis Del Carmen Puga-Molina, Celia M. Santi, Sruthi Ramagiri, Steven K. Brennan, Jiehong Pan, Jeffrey R. Koenitzer, Tao Huang, Rachael M. Hyland, Sean P. Gunsten, Shin-Cheng Tzeng, Jennifer M. Strahle, Pleasantine Mill, Moe R. Mahjoub, Susan K Dutcher, Steven L Brody

2020-Current year OA Pubs

DNAAF5 is a dynein motor assembly factor associated with the autosomal heterogenic recessive condition of motile cilia, primary ciliary dyskinesia (PCD). The effects of allele heterozygosity on motile cilia function are unknown. We used CRISPR-Cas9 genome editing in mice to recreate a human missense variant identified in patients with mild PCD and a second, frameshift-null deletion in Dnaaf5. Litters with Dnaaf5 heteroallelic variants showed distinct missense and null gene dosage effects. Homozygosity for the null Dnaaf5 alleles was embryonic lethal. Compound heterozygous animals with the missense and null alleles showed severe disease manifesting as hydrocephalus and early lethality. However, animals …

Guidance On The Use Of Convalescent Plasma To Treat Immunocompromised Patients With Coronavirus Disease 2019, Evan M Bloch, Jeffrey P Henderson, Brenda J Grossman, Et Al.

2020-Current year OA Pubs

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immunocompromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease, and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP …

Pembrolizumab Plus Chemotherapy In Advanced Endometrial Cancer, Ramez N Eskander, Premal H Thaker, Matthew A Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear.

METHODS: In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had …

Dostarlimab For Primary Advanced Or Recurrent Endometrial Cancer, Mansoor R Mirza, Carolyn Mccourt, Matthew A Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: Dostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer.

METHODS: We conducted a phase 3, global, double-blind, randomized, placebo-controlled trial. Eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomly assigned in a 1:1 ratio to receive either dostarlimab (500 mg) or placebo, plus carboplatin (area under the concentration-time curve, 5 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area), every 3 weeks (six cycles), followed by …

Skeletal Muscle Delimited Myopathy And Verapamil Toxicity In Sur2 Mutant Mouse Models Of Aims, Conor Mcclenaghan, Maya A Mukadam, Jacob Roeglin, Robert C Tryon, Manfred Grabner, Anamika Dayal, Gretchen A Meyer, Colin G Nichols

2020-Current year OA Pubs

ABCC9-related intellectual disability and myopathy syndrome (AIMS) arises from loss-of-function (LoF) mutations in the ABCC9 gene, which encodes the SUR2 subunit of ATP-sensitive potassium (K

Standardized Immunoprecipitation Protocol For Efficient Isolation Of Native Apolipoprotein E Particles Utilizing Hj15.4 Monoclonal Antibody, Justin O'Leary, Ana-Caroline Raulin, Zonghua Li, Yuka Martens, Yasuteru Inoue, Michael R Strickland, Xianlin Han, David M Holtzman, Guojun Bu, Na Zhao

2020-Current year OA Pubs

The apolipoprotein E protein (apoE) confers differential risk for Alzheimer's disease depending on which isoforms are expressed. Here, we present a 2-day immunoprecipitation protocol using the HJ15.4 monoclonal apoE antibody for the pull-down of native apoE particles. We describe major steps for apoE production via immortalized astrocyte culture and HJ15.4 antibody bead coupling for apoE particle pull-down, elution, and characterization. This protocol could be used to isolate native apoE particles from multiple model systems or human biospecimens.

Skeletal Muscle Delimited Myopathy And Verapamil Toxicity In Sur2 Mutant Mouse Models Of Aims, Conor Mcclenaghan, Maya A Mukadam, Jacob Roeglin, Robert C Tryon, Manfred Grabner, Anamika Dayal, Gretchen A Meyer, Colin G Nichols

2020-Current year OA Pubs

ABCC9-related intellectual disability and myopathy syndrome (AIMS) arises from loss-of-function (LoF) mutations in the ABCC9 gene, which encodes the SUR2 subunit of ATP-sensitive potassium (K

Validation Of The Adolescent Binge Eating Disorder Measure (Ado-Bed) Among Transgender Youth And Young Adults, Whitney Linsenmeyer, Dana Stiles, Sarah Garwood, Andrea Giedinghagen, Christopher Lewis, Gretta Strand

2020-Current year OA Pubs

BACKGROUND: Transgender youth and young adults are at increased risk for eating disorders, including binge eating disorder, yet few measures have been validated for screening purposes with the transgender population.

METHODS: The purpose of this study was to provide initial evidence for the internal consistency and convergent validity of the Adolescent Binge Eating Disorder questionnaire (ADO-BED) in a sample of transgender youth and young adults. 208 participants completed the ADO-BED as part of a routine nutrition screening protocol at a gender center. Exploratory factor analysis and confirmatory factor analysis was used to establish the factor structure of the ADO-BED. Relationships …

Novel Vaccine Against Pathological Pyroglutamate-Modified Amyloid Beta For Prevention Of Alzheimer's Disease, Karen Zagorski, Olga King, Armine Hovakimyan, Irina Petrushina, Tatevik Antonyan, Gor Chailyan, Manush Ghazaryan, Krzysztof L Hyrc, Jean Paul Chadarevian, Hayk Davtyan, Mathew Blurton-Jones, David H Cribbs, Michael G Agadjanyan, Anahit Ghochikyan

2020-Current year OA Pubs

Post-translationally modified N-terminally truncated amyloid beta peptide with a cyclized form of glutamate at position 3 (pE

Sustained Alternate-Day Fasting Potentiates Doxorubicin Cardiotoxicity, Mualla Ozcan, Zhen Guo, Carla Valenzuela Ripoll, Ahmed Diab, Antonino Picataggi, David Rawnsley, Aynaz Lotfinaghsh, Carmen Bergom, Jeff Szymanski, Daniel Hwang, Jie Zheng, Robert J Hayashi, Pamela K Woodard, Attila Kovacs, Joel Schilling, Babak Razani, Abhinav Diwan, Ali Javaheri, Et Al.

2020-Current year OA Pubs

Fasting strategies are under active clinical investigation in patients receiving chemotherapy. Prior murine studies suggest that alternate-day fasting may attenuate doxorubicin cardiotoxicity and stimulate nuclear translocation of transcription factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis. In this study, human heart tissue from patients with doxorubicin-induced heart failure demonstrated increased nuclear TFEB protein. In mice treated with doxorubicin, alternate-day fasting or viral TFEB transduction increased mortality and impaired cardiac function. Mice randomized to alternate-day fasting plus doxorubicin exhibited increased TFEB nuclear translocation in the myocardium. When combined with doxorubicin, cardiomyocyte-specific TFEB overexpression provoked cardiac remodeling, while systemic …

Inequities In Treatments And Outcomes Among Patients Hospitalized With Hypertrophic Cardiomyopathy In The United States, Daniel Y Johnson, R J Waken, Daniel K Fox, Gmerice Hammond, Karen E Joynt Maddox, Sharon Cresci

2020-Current year OA Pubs

Background Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiac disease. In small studies, sociodemographic factors have been associated with disparities in septal reduction therapy, but little is known about the association of sociodemographic factors with HCM treatments and outcomes more broadly. Methods and Results Using the National Inpatient Survey from 2012 to 2018, HCM diagnoses and procedures were identified by

Brain Abscess And Stroke In Children And Adults With Hereditary Hemorrhagic Telangiectasia: Analysis Of A Large National Claims Database, Andrew J. White, Itay Marmor, Kate M. Peacock, Katelin B. Nickel, Jessica Zavadil, Margaret A. Olsen

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is an inherited disease associated with pathogenic variants in transforming growth factor-β signaling pathway-related genes, resulting in abnormal vascular development in various organs. Brain arteriovenous malformations (AVMs) may lead to intracranial hemorrhage, and brain abscess or ischemic stroke may result from right to left shunting via pulmonary AVMs. We aimed to investigate the risk for these severe complications in both adults and children with HHT.

METHODS: We conducted a case-control study among participants aged 1-64 years in the MarketScan Commercial (2006-2019) and Multistate Medicaid Databases (2011-2019). We identified cases with HHT using

RESULTS: …

Stromal And Therapy-Induced Macrophage Proliferation Promotes Pdac Progression And Susceptibility To Innate Immunotherapy, Chong Zuo, John M Baer, Brett L Knolhoff, Jad I Belle, Xiuting Liu, Angela Alarcon De La Lastra, Graham D Hogg, Natalie L Kingston, Marcus A Breden, Paarth B Dodhiawala, Daniel Cui Zhou, Varintra E Lander, C Alston James, Li Ding, Kian-Huat Lim, Ryan C Fields, William G Hawkins, Jason D Weber, Guoyan Zhao, David G Denardo, Et Al.

2020-Current year OA Pubs

Tumor-associated macrophages (TAMs) are abundant in pancreatic ductal adenocarcinomas (PDACs). While TAMs are known to proliferate in cancer tissues, the impact of this on macrophage phenotype and disease progression is poorly understood. We showed that in PDAC, proliferation of TAMs could be driven by colony stimulating factor-1 (CSF1) produced by cancer-associated fibroblasts. CSF1 induced high levels of p21 in macrophages, which regulated both TAM proliferation and phenotype. TAMs in human and mouse PDACs with high levels of p21 had more inflammatory and immunosuppressive phenotypes. p21 expression in TAMs was induced by both stromal interaction and/or chemotherapy treatment. Finally, by modeling …