Digital Commons Network^™

Neurofilament Light Chain In Serum Of Cancer Patients With Acute Neurological Complications, Amulya Gottiparthy, Keng Lam, Suprateek Kundu, Zixi Yang, Ivo Tremont-Lukats, Sudhakar Tummala

Student and Faculty Publications

Aim: Neurofilament light chain (NfL) is a nonspecific sensitive biomarker of axonal damage.

Methods: This case series identified cancer patients with neurological complications who had serum NfL measurements and paired these results to outcomes.

Results: NfL serum levels were available in 15 patients with hematological malignancies or solid tumors. The neurological complications studied were immune effector cell-associated neurotoxicity syndrome, immune checkpoint inhibitor-related encephalopathy, anoxic brain injury, Guillain-Barre syndrome, hemophagocytic lymphohistiocytosis, transverse myelitis, paraneoplastic syndrome, central nervous system demyelinating disorder and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. All patients but one with serum NfL >900 pg/ml died …

Cohort Expansion And Genotype-Phenotype Analysis Of Rab11a-Associated Neurodevelopmental Disorder., Maria Carla Borroto, Heena Patel, Siddharth Srivastava, Lindsay C. Swanson, Boris Keren, Sandra Whalen, Cyril Mignot, Xiaodong Wang, Qian Chen, Jill A. Rosenfeld, Scott Mclean, Rebecca O. Littlejohn, Undiagnosed Diseases Network, Lisa Emrick, Lindsay C. Burrage, Ruben Attali, Gaetan Lesca, Cecile Acquaviva-Bourdain, Catherine Sarret, Laurie H. Seaver, Konrad Platzer, Tobias Bartolomaeus, Cornelia Wünsch, Susann Fischer, Ana Maria Rodriguez Barreto, Jorge L. Granadillo, Elisabeth Schreiner, Theresa Brunet, Ulrich A. Schatz, Isabelle Thiffault, Sureni V. Mullegama, Jacques L. Michaud, Fadi F. Hamdan, Elsa Rossignol, Philippe M. Campeau

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: GTPases of the Rab family are important orchestrators of membrane trafficking, and their dysregulation has been linked to a variety of neuropathologies. In 2017, we established a causal link between RAB11A variants and developmental and epileptic encephalopathy. In this study, we expand the phenotype of RAB11A-associated neurodevelopmental disorder and explore genotype-phenotype correlations.

METHODS: We assessed 16 patients with pathogenic or likely pathogenic RAB11A variants, generally de novo, heterozygous missense variants. One individual had a homozygous nonsense variant, although concomitant with a pathogenic LAMA2 variant, which made their respective contributions to the phenotype difficult to discriminate.

RESULTS: We reinforce the …

Influenza C Virus In U.S. Children With Acute Respiratory Infection 2016-2019., Bethany K. Sederdahl, Geoffrey A. Weinberg, Angela P. Campbell, Rangaraj Selvarangan, Jennifer E. Schuster, Joana Y. Lively, Samantha M. Olson, Julie A. Boom, Pedro A. Piedra, Natasha B. Halasa, Laura Stewart, Peter G. Szilagyi, G K Balasubramani, Theresa Sax, Judith M. Martin, Robert W. Hickey, Marian G. Michaels, John V. Williams, New Vaccine Surveillance Network

Manuscripts, Articles, Book Chapters and Other Papers

Influenza C virus (ICV) is an orthomyxovirus related to influenza A and B, yet due to few commercial assays, epidemiologic studies may underestimate incidence of ICV infection and disease. We describe the epidemiology and characteristics of ICV within the New Vaccine Surveillance Network (NVSN), a Centers for Disease Control and Prevention (CDC)-led network that conducts population-based surveillance for pediatric acute respiratory illness (ARI). Nasal or/combined throat swabs were collected from emergency department (ED) or inpatient ARI cases, or healthy controls, between 12/05/2016-10/31/2019 and tested by molecular assays for ICV and other respiratory viruses. Parent surveys and chart review were used …

Intracranial Aneurysms In Sickle Cell Disease Are Associated With Hemodynamic Stress And Anemia, Yan Wang, Jared S Garland, Slim Fellah, Martin N Reis, Matthew S Parsons, Kristin P Guilliams, Melanie E Fields, Amy E Mirro, Josiah B Lewis, Chunwei Ying, Rachel A Cohen, Monica L Hulbert, Allison A King, Yasheng Chen, Jin-Moo Lee, Hongyu An, Andria L Ford

2020-Current year OA Pubs

Although hemodynamic stress plays a key role in aneurysm formation outside of sickle cell disease (SCD), its role is understudied in patients with SCD. We hypothesized that tissue-based markers of hemodynamic stress are associated with aneurysm presence in a prospective SCD cohort. Children and adults with SCD, with and without aneurysms, underwent longitudinal brain magnetic resonance imaging/magnetic resonance angiography (MRA) to assess cerebral blood flow (CBF) and oxygen extraction fraction (OEF). Baseline characteristics were recorded. In the subgroup of adults, stepwise mixed-effect logistic regression examined clinical variables, CBF, and OEF as predictors of aneurysm presence. Cumulative rates of new aneurysm …

Evaluating The Impact Of A Year-Long External Mentorship Pilot Program In Classical Hematology, Zoya Qureshy, Pooja Nair, Sara K Vesely, Allison A King, Alfred I Lee, Nathan T Connell, Annette Von Drygalski, Ida Wong-Sefidan, Martina C Murphy, Ronak H Mistry, Rebecca L Zon, Erin G Reid, Josel Fritz, Soo J Park

2020-Current year OA Pubs

Effective mentorship is a pivotal factor in shaping the career trajectory of trainees interested in classical hematology (CH), which is of critical importance due to the anticipated decline in the CH workforce. However, there is a lack of mentorship opportunities within CH compared with medical oncology. To address this need, a year-long external mentorship program was implemented through the American Society of Hematology Medical Educators Institute. Thirty-five hematology/oncology fellows interested in CH and 34 academically productive faculty mentors from different institutions across North America were paired in a meticulous process that considered individual interests, experiences, and background. Pairs were expected …

Complex Trait Associations In Rare Diseases And Impacts On Mendelian Variant Interpretation., Craig Smail, Bing Ge, Marissa R. Keever-Keigher, Carl F. Schreck, Warren A. Cheung, Jeffrey J. Johnston, Cassandra Barrett, Genomic Answers For Kids Consortium, Keith Feldman, Ana S A Cohen, Emily G. Farrow, Isabelle Thiffault, Elin Grundberg, Tomi Pastinen

Manuscripts, Articles, Book Chapters and Other Papers

Emerging evidence implicates common genetic variation - aggregated into polygenic scores (PGS) - in the onset and phenotypic presentation of rare diseases. Here, we comprehensively map individual polygenic liability for 1102 open-source PGS in a cohort of 3059 probands enrolled in the Genomic Answers for Kids (GA4K) rare disease study, revealing widespread associations between rare disease phenotypes and PGSs for common complex diseases and traits, blood protein levels, and brain and other organ morphological measurements. Using this resource, we demonstrate increased polygenic liability in probands with an inherited candidate disease variant (VUS) compared to unaffected carrier parents. Further, we show …

14-Month-Old Female With Anti-Mda5 Juvenile Dermatomyositis Complicated By Liver Disease: A Case Report., Mitch Kinkor, Sameena Hameed, Alexander Kats, Voytek Slowik, Emily Fox, Maria Ibarra

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Juvenile Dermatomyositis (JDM) is a rare disorder with subtypes associated with different myositis-specific antibodies (MSAs) including anti-MDA5. Hepatic involvement in JDM is rare and has not previously been documented in anti-MDA5 JDM. There is a lack of formal research on treatment protocols for anti-MDA5 JDM, though tofacitinib is a highly regarded emerging therapy.

CASE PRESENTATION: A previously healthy 14-month-old Hispanic female presented to a pediatric rheumatology clinic with eight months of worsening rash, weakness, periorbital edema, intermittent fevers, and weight loss. Her physical exam was notable for fever, thinning of hair, heliotrope rash, periorbital edema, violaceous macules on her …

Perceptions Of Peer And Parental Support: Feasibility Of A Physical Activity Intervention For Adolescent Girls, Avery G. Douglas, Deirdre Dlugonski, Johanna M. Hoch

International Journal of Exercise Science

International Journal of Exercise Science 17(5): 1352-1360, 2024. Physical activity (PA) has a wide range of health benefits. Children with high levels of social support are more likely to achieve adequate levels of PA. The purposes of this pilot study were to examine the impact of an after-school intervention on perceived peer and parental support among adolescent girls and to identify correlates of support to explore in future studies to increase PA. Seventeen low-active girls in 6th–7th grade were recruited from a local middle school to participate in an 8-week intervention where they were exposed to various types of PA …

Building Gender Equity In Forestry Education: The Benefits Of Oregon’S Women Owning Woodlands Network, Lauren A. Grand, Tiffany Hopkins

The Journal of Extension

The Women Owning Woodlands Network was launched in 2005 as a way to provide collaborative and hands-on peer learning education to women who felt uncomfortable participating in traditional Extension programs. Since its inception the program as grown to provide education and resources for over 300 women. We surveyed these women to identify if the program continues to meet their needs. It is evident that WOWNet has continued to be an important part of OSU FNR’s outreach education program and continues to meet the needs of a historically undeserved group of landowners in ways that traditional programming does not.

The Roles Of Cd4+ T Cell Help, Sex, And Dose In The Induction Of Protective Cd8+ T Cells Against A Lethal Poxvirus By Mrna-Lnp Vaccines, Samita Kafle, Brian Montoya, Lingjuan Tang, Ying Tam, Hiromi Muramatsu, Norbert Pardi, Luis Sigal

Department of Microbiology and Immunology Faculty Papers

The role of CD4⁺ T cells in the induction of protective CD8⁺ T cells by mRNA lipid nanoparticle (LNP) vaccines is unknown. We used B6 or Tlr9^−/− mice depleted or not of CD4⁺ T cells and LNP vaccines loaded with mRNAs encoding the ectromelia virus (ECTV) MHC class I H-2 K^b-restricted immunodominant CD8⁺ T cell epitope TSYKFESV (TSYKFESV mRNA-LNPs) or the ECTV EVM158 protein, which contains TSYKFESV (EVM-158 mRNA-LNPs). Following prime and boost with 10 μg of either vaccine, K^b-TSYKFESV-specific CD8⁺ T cells fully protected male and female mice from …

Final Outcomes From A Phase 2 Trial Of Posoleucel In Allogeneic Hematopoietic Cell Transplant Recipients., Sanjeet S. Dadwal, Rajat Bansal, Michael W. Schuster, Jean A. Yared, Douglas Myers, Michelle Matzko, Sama Adnan, David Mcneel, Julie Ma, Sarah A. Gilmore, Spyridoula Vasileiou, Ann M. Leen, Joshua A. Hill, Jo-Anne H. Young

Manuscripts, Articles, Book Chapters and Other Papers

Allogeneic hematopoietic cell transplantation (allo-HCT) recipients are susceptible to viral infections. We conducted a phase 2 trial evaluating the safety and rate of clinically significant infections (CSIs; viremia requiring treatment or end-organ disease) after infusion of posoleucel, a partially HLA-matched, allogeneic, off-the-shelf, multivirus-specific T-cell investigational product for preventing CSIs with adenovirus, BK virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, or JC virus. This open-label trial enrolled allo-HCT recipients at high risk based on receiving grafts from umbilical cord blood, haploidentical, mismatched, or matched unrelated donors; post-HCT lymphocytes of <180/mm3; or use of T-cell depletion. Posoleucel dosing was initiated within 15 to 49 days of allo-HCT and subsequently every 14 days for up to 7 doses. The primary end point was the number of CSIs due to the 6 target viruses by week 14. Of the 26 patients enrolled, only 3 (12%) had a CSI by week 14, each with a single target virus. In vivo expansion of functional virus-specific T cells detected via interferon-γ enzyme-linked immunosorbent spot assay was associated with viral control. Persistence of posoleucel-derived T-cell clones for up to 14 weeks after the last infusion was confirmed by T-cell-receptor deep sequencing. Five patients (19%) had acute graft-versus-host disease grade 2 to 4. No patient experienced cytokine release syndrome. All 6 deaths were due to relapse or disease progression. allo-HCT recipients at high risk who received posoleucel had low rates of CSIs from 6 targeted viruses. Repeat posoleucel dosing was generally safe and well tolerated and associated with functional immune reconstitution. This trial was registered at www.ClinicalTrials.gov as #NCT04693637.

Variants In Lrrc7 Lead To Intellectual Disability, Autism, Aggression And Abnormal Eating Behaviors., Jana Willim, Daniel Woike, Daniel Greene, Sarada Das, Kevin Pfeifer, Weimin Yuan, Anika Lindsey, Omar Itani, Amber L. Böhme, Debora Tibbe, Hans-Hinrich Hönck, Fatemeh Hassani Nia, Undiagnosed Diseases Network, Michael Zech, Theresa Brunet, Laurence Faivre, Arthur Sorlin, Antonio Vitobello, Thomas Smol, Cindy Colson, Kristin Baranano, Krista Schatz, Allan Bayat, Kelly Schoch, Rebecca Spillmann, Erica E. Davis, Erin Conboy, Francesco Vetrini, Konrad Platzer, Sonja Neuser, Janina Gburek-Augustat, Alexandra Noel Grace, Bailey Mitchell, Alexander Stegmann, Margje Sinnema, Naomi Meeks, Carol Saunders, Maxime Cadieux-Dion, Juliane Hoyer, Julien Van-Gils, Jean-Madeleine De Sainte-Agathe, Michelle L. Thompson, E Martina Bebin, Monika Weisz-Hubshman, Anne-Claude Tabet, Alain Verloes, Jonathan Levy, Xenia Latypova, Sönke Harder, Gary A. Silverman, Stephen C. Pak, Tim Schedl, Kathleen Freson, Andrew Mumford, Ernest Turro, Christian Schlein, Vandana Shashi, Hans-Jürgen Kreienkamp

Manuscripts, Articles, Book Chapters and Other Papers

Members of the leucine rich repeat (LRR) and PDZ domain (LAP) protein family are essential for animal development and histogenesis. Densin-180, encoded by LRRC7, is the only LAP protein selectively expressed in neurons. Densin-180 is a postsynaptic scaffold at glutamatergic synapses, linking cytoskeletal elements with signalling proteins such as the α-subunit of Ca²⁺/calmodulin-dependent protein kinase II. We have previously observed an association between high impact variants in LRRC7 and Intellectual Disability; also three individual cases with variants in LRRC7 had been described. We identify here 33 individuals (one of them previously described) with a dominant neurodevelopmental disorder due …

Targeting Igf2 To Reprogram The Tumor Microenvironment For Enhanced Viro-Immunotherapy, Min Hye Noh, Jin Muk Kang, Alexandra A Miller, Grace Nguyen, Minxin Huang, Ji Seon Shim, Alberto J Bueso-Perez, Sara A Murphy, Kimberly A Rivera-Caraballo, Yoshihiro Otani, Eunju Kim, Seung-Hee Yoo, Yuanqing Yan, Yeshavanth Banasavadi-Siddegowda, Hiroshi Nakashima, E Antonio Chiocca, Balveen Kaur, Zhongming Zhao, Tae Jin Lee, Ji Young Yoo

Student and Faculty Publications

BACKGROUND: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME).

METHODS: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance.

RESULTS: Transcriptome analysis identified IGF2 as one of the top-secreted proteins following oHSV treatment. …

Physiological And Communicative Emotional Disconcordance In Children On The Autism Spectrum, Emma Finkel, Eric Sah, Mckenna Spaulding, John Herrington, Liza Tomczuk, Aaron Masino, Xueqin Pang, Anushua Bhattacharya, Darren Hedley, Yelena Kushleyeva, Phoebe Thomson, Natalie Doppelt, Jessica Tan, Jeffrey Pennington, Cheryl Dissanayake, Christopher Bonafide, Heather Nuske

SKMC Student Presentations and Publications

BACKGROUND: Individuals on the autism spectrum commonly have differences from non-autistic people in expressing their emotions using communicative behaviors, such as facial expressions. However, it is not yet clear if this reduced expressivity stems from reduced physiological reactivity in emotional contexts or if individuals react internally, but do not show these reactions externally to others. We hypothesized that autism is characterized by a discordance between in-the-moment internal psychophysiological arousal and external communicative expressions of emotion.

METHODS: Forty-one children on the autism spectrum and 39 non-autistic, typically developing (TD) children of two age groups (2-4 and 8-12 years) participated in a …

Different Sensory Information Is Used For State Estimation When Stationary Or Moving., Aaron Wong, Alyssa Eyssalenne, Luke Carter, Amanda S Therrien

Moss-Magee Rehabilitation Papers

The accurate estimation of limb state is necessary for movement planning and execution. While state estimation requires both feedforward and feedback information, we focus here on the latter. Prior literature has shown that integrating visual and proprioceptive feedback improves estimates of static limb position. However, differences in visual and proprioceptive feedback delays suggest that multisensory integration could be disadvantageous when the limb is moving. We formalized this hypothesis by modeling feedback-based state estimation using the long-standing maximum likelihood estimation model of multisensory integration, which we updated to account for sensory delays. Our model predicted that the benefit of multisensory integration …

Residual Stroke Risk Among Patients With Atrial Fibrillation Prescribed Oral Anticoagulants: A Patient-Level Meta-Analysis From Combine Af, Linda Johnson, Alexander Benz, Ashkan Shoamanesh, John W Eikelboom, Michael Ezekowitz, Robert Giugliano, Lars Wallentin, Christian Ruff, Renato Lopes, Sanjit Jolly, Richard Whitlock, Christopher Granger, Stuart Connolly, Jeffrey Healey

Division of Cardiology Faculty Papers

Background: Despite oral anticoagulation, patients with atrial fibrillation (AF) remain at risk of ischemic stroke and systemic embolism (SE) events. For patients whose residual risk is sufficiently high, additional therapies might be useful to mitigate stroke risk.

Methods and results: Individual patient data from 5 landmark trials testing oral anticoagulation in AF were pooled in A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in AF (COMBINE AF). We calculated the rate of ischemic stroke/SE among oral anticoagulation-treated patients with a CHA₂DS₂-VASc score≥2, across strata of CHA₂DS₂-VASc …

Keratin 17 Is A Prognostic And Predictive Biomarker In Pancreatic Ductal Adenocarcinoma, Lyanne Delgado-Coka, Lucia Roa-Peña, Sruthi Babu, Michael Horowitz, Emanuel Petricoin, Lynn Matrisian, Edik Blais, Natalia Marchenko, Felicia Allard, Ali Akalin, Wei Jiang, Md, Phd, Brent Larson, Andrew Hendifar, Vincent Picozzi, Minsig Choi, Kenneth Shroyer, Luisa Escobar-Hoyos

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVES: To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC).

METHODS: We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses.

RESULTS: …

Racial And Ethnic Representation In Food Allergen Immunotherapy Trial Participants: A Systematic Review., Hannah Suffian, Aarti Pandya, Lauren Davidson, Vincent Staggs, Bridgette Jones

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: The lack of inclusion of diverse population samples in food allergy immunotherapy clinical trials not only leads to decreased applicability to the general population in terms of results and treatments but can also be seen as a broader social injustice contributing to inequity within the health care system.

OBJECTIVES: To investigate the racial and ethnic distribution of participants included in food allergy immunotherapy clinical trials, and determine whether the racial and ethnic representation in trials accurately reflects the patients who experience food allergy.

EVIDENCE REVIEW: Data were collected from articles found on PubMed and ClinicalTrials.gov using key terms of …

Fetal Mavs And Type I Ifn Signaling Pathways Control Zikv Infection In The Placenta And Maternal Decidua, Yael Alippe, Leran Wang, Reyan Coskun, Stéfanie P Muraro, Fang R Zhao, Michelle Elam-Noll, J Michael White, Daiana M Vota, Vanesa C Hauk, Jeffrey I Gordon, Scott A Handley, Michael S Diamond

2020-Current year OA Pubs

The contribution of placental immune responses to congenital Zika virus (ZIKV) syndrome remains poorly understood. Here, we leveraged a mouse model of ZIKV infection to identify mechanisms of innate immune restriction exclusively in the fetal compartment of the placenta. ZIKV principally infected mononuclear trophoblasts in the junctional zone, which was limited by mitochondrial antiviral-signaling protein (MAVS) and type I interferon (IFN) signaling mechanisms. Single nuclear RNA sequencing revealed MAVS-dependent expression of IFN-stimulated genes (ISGs) in spongiotrophoblasts but not in other placental cells that use alternate pathways to induce ISGs. ZIKV infection of Ifnar1-/- or Mavs-/- placentas was associated with greater …

Utilization Of Blood Flow Restriction Therapy With A Former Triathlete After Total Knee Arthroplasty: A Case Report, Christopher Keating, Stephanie Muth, Pt, Phd, Cameron Hui, Lisa T. Hoglund

Department of Physical Therapy Faculty Papers

INTRODUCTION AND PURPOSE: Knee osteoarthritis (OA) is a common condition that limits function and reduces quality of life. Total knee arthroplasty (TKA) is a surgical procedure that replaces the joint surfaces to address anatomical changes due to knee OA. While TKA improves symptoms and function, postoperative impairments are common, including reduced quadriceps strength. Blood flow restriction (BFR) may be a viable option for patients following TKA, as it can improve strength with a minimal amount of joint loading compared to traditional strength training. The purpose of this case report is to describe the impact of BFR use in an individual …

American Association Of Plastic Surgeons Consensus On Breast Implant-Associated Anaplastic Large-Cell Lymphoma, Mark W Clemens, Terence M Myckatyn, Arianna Di Napoli, Andrew L Feldman, Elaine S Jaffe, Cara L Haymaker, Steven M Horwitz, Kelly K Hunt, Marshall E Kadin, Colleen M Mccarthy, Roberto N Miranda, H Miles Prince, Fabio Santanelli Di Pompeo, Sari D Holmes, Linda G Phillips

Student and Faculty Publications

BACKGROUND: In the absence of high-quality evidence, there is a need for guidelines and multidisciplinary consensus recommendations on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). The purpose of this expert consensus conference was to evaluate the existing evidence regarding the diagnosis and management of BIA-ALCL caused by textured implants. This article aims to provide evidence-based recommendations regarding the management and prevention of BIA-ALCL.

METHODS: A comprehensive search was conducted in the MEDLINE, Cochrane Library, and Embase databases, and supplemented by manual searches of relevant English-language articles and "related articles" sections. Studies focusing on breast surgery and lymphoma associated with breast implants …

Targeting Undruggable Phosphatase Overcomes Trastuzumab Resistance By Inhibiting Multi-Oncogenic Kinases., Lu Wang, Yusheng Lin, Zhimeng Yao, Nipun Babu, Wan Lin, Chaoying Chen, Liang Du, Songwang Cai, Yunlong Pan, Xiao Xiong, Qiantao Ye, Hongzheng Ren, Dianzheng Zhang, Yexi Chen, Sai-Ching Jim Yeung, Edwin Bremer, Hao Zhang

PCOM Scholarly Works

AIMS: Resistance to targeted therapy is one of the critical obstacles in cancer management. Resistance to trastuzumab frequently develops in the treatment for HER2

METHODS: Four public datasets were used to screen PTP candidates in relation to trastuzumab responsiveness in HER2

RESULTS: PTPRO was identified as the key PTP which influences trastuzumab responsiveness and patient survival. PTPRO de-phosphorated several TKs, including the previously overlooked substrate ERBB3, thereby inhibiting multiple oncogenic pathways associated with drug resistance. Notably, PTPRO, previously deemed "undruggable," was effectively upregulated by saRNA-loaded nanoparticles. The upregulated PTPRO simultaneously inhibited ERBB3, ERBB2, and downstream SRC signaling pathways, thereby counteracting …

Pembrolizumab Plus Carboplatin And Paclitaxel As First-Line Therapy For Recurrent/Metastatic Head And Neck Squamous Cell Carcinoma (Keynote-B10): A Single-Arm Phase Iv Trial, Marcin Dzienis, Peter Oppelt, Et Al.

2020-Current year OA Pubs

PURPOSE: Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.gov identifier: NCT04489888).

METHODS: Eligible adults had previously untreated, histologically or cytologically confirmed R/M HNSCC regardless of PD-L1 status, measurable disease per RECIST v1.1 by blinded independent central review …

Early Therapeutic Drug Monitoring Of Methotrexate And Its Association With Acute Kidney Injury: A Retrospective Cohort Study., Nicolás Tentoni, Miriam Hwang, Gabriela Villanueva, Ryan Combs, Jennifer Lowe, Laura Ramsey, Zachary L. Taylor, Thais Murciano Carrillo, María Dolores Aumente, Teresa López-Viñau López, Carmelo Rizzari, Scott C. Howard

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: High-dose methotrexate (HDMTX) use can be limited by the development of acute kidney injury (AKI). Early AKI detection is paramount to prevent further renal injury and irreversible toxicities. This study sought to determine whether early elimination patterns of MTX would be useful as a biomarker of AKI in HDMTX treatment.

METHODS: This retrospective cohort study included two sites that collected ≥2 MTX levels within 16 h from completion of MTX infusion. Early levels were tagged and MTX elimination half-life (t_½) were calculated from combinations of two of three different early time periods. Receiver operating characteristic (ROC) curves …

Beta-Hydroxybutyrate Levels And Risk Of Diabetic Ketoacidosis In Adults With Type 1 Diabetes Treated With Sotagliflozin, Schafer Boeder, Michael J Davies, Janet B Mcgill, Richard Pratley, Manon Girard, Phillip Banks, Jeremy Pettus, Satish Garg

2020-Current year OA Pubs

No abstract provided.

Comprehensive Molecular Profiling Of Multiple Myeloma Identifies Refined Copy Number And Expression Subtypes, Sheri Skerget, Ravi Vij, Et Al.

2020-Current year OA Pubs

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation's Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are …

Utilization Of Geospatial Distribution In The Measurement Of Study Cohort Representativeness., Keith Feldman, Natalie J. Kane, Stacey Daniels-Young, Bruce Reed, Jessica Welch, Lauren Fitzpatrick, Mark A. Hoffman, Andrea Bradley-Ewing, Elin Grundberg

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: The ability to apply results from a study to a broader population remains a primary objective in translational science. Distinct from intrinsic elements of scientific rigor, the extrinsic concept of generalization requires there be alignment between a study cohort and population in which results are expected to be applied. Widespread efforts have been made to quantify representativeness of study cohorts. These techniques, however, often consider the study and target cohorts as monolithic collections that can be directly compared. Overlooking known impacts to health from socio-demographic and environmental factors tied to individual's geographical location, and potentially obfuscating misalignment in underrepresented …

The Placement Of A Single-Incision Mini-Sling For The Treatment Of Complete Intrinsic Sphincter Deficiency In An Adolescent Female: A Case Report, Norman Bebla, Dylan Gallegos

HCA Healthcare Journal of Medicine

Introduction

Intrinsic sphincter deficiency (ISD) is associated with a patient history of urethral injury or childbirth. Suburethral sling placement for ISD has been found to be beneficial in patients with this diagnosis. ISD in the pediatric population is rare and surgical management may prove difficult. ISD requires intensive counseling on available treatment options for this unique population.

Case Presentation

This report is on the use of the single-incision mini-sling for complete ISD in an adolescent patient. The patient was a 15-year-old nulligravid female who was found to have idiopathic complete intrinsic deficiency based on a multi-channel urodynamic study. Despite conservative …

Brief Report: Incidence And Outcomes Of Pediatric Tracheal Intubation-Associated Cardiac Arrests In The Icu-Resus Clinical Trial, Akira Nishisaki, Ron Reeder, Elizabeth Laverriere Mcgovern, Tageldin Ahmed, Michael Bell, Robert Bishop, Matthew Bochkoris, Candice Burns, Joseph Carcillo, Todd Carpenter, Wesley Diddle, Myke Federman, Ericka Fink, Deborah Franzon, Aisha Frazier, Stuart Friess, Kathryn Graham, Mark Hall, David Hehir, Christopher M Horvat, Leanna Huard, Tensing Maa, Arushi Manga, Patrick Mcquillen, Kathleen Meert, Ryan Morgan, Peter Mourani, Vinay Nadkarni, Maryam Naim, Daniel Notterman, Chella Palmer, Anil Sapru, Carleen Schneiter, Matthew Sharron, Neeraj Srivastava, Shirley Viteri, David Wessel, Heather Wolfe, Andrew Yates, Athena Zuppa, Robert Sutton, Robert Berg

Department of Pediatrics Faculty Papers

BACKGROUND: Tracheal intubation (TI)-associated cardiac arrest (TI-CA) occurs in 1.7% of pediatric ICU TIs. Our objective was to evaluate resuscitation characteristics and outcomes between cardiac arrest patients with and without TI-CA.

METHODS: Secondary analysis of cardiac arrest patients in both ICU-RESUS trial and ancillary CPR-NOVA study. The primary exposure was TI-CA, defined as cardiac arrest occurred during TI procedure or within 20 min after endotracheal tube placement. The primary outcome was survival to hospital discharge with favorable neurological outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged).

RESULTS: Among 315 children with cardiac arrests, 48 (15.2%) met criteria for TI-CA. …

Shared And Distinct Cortical Morphometric Alterations In Five Neuropsychiatric Symptoms Of Parkinson’S Disease, Qianling Lu, Zhuang Zhu, Heng Zhang, Caiting Gan, Aidi Shan, Mengxi Gao, Huimin Sun, Xingyue Cao, Yongsheng Yuan, Joseph I Tracy, Qirui Zhang, Kezhong Zhang

Farber Institute for Neuroscience Faculty Papers

Neuropsychiatric symptoms (including anxiety, depression, apathy, impulse–compulsive behaviors and hallucinations) are among the most common non-motor features of Parkinson’s disease. Whether these symptoms should be considered as a direct consequence of the pathophysiologic mechanisms of Parkinson’s disease is controversial. Morphometric similarity network analysis and epicenter mapping approach were performed on T1-weighted images of 505 patients with Parkinson’s disease and 167 age- and sex-matched healthy participants from Parkinson’s Progression Markers Initiative database to reveal the commonalities and specificities of distinct neuropsychiatric symptoms. Abnormal cortical co-alteration pattern in patients with neuropsychiatric symptoms was in somatomotor, vision and frontoparietal regions, with epicenters in …