Medicine and Health Sciences Commons^™

First-In-Human Phase I/Ib Study Of Niz985, A Recombinant Heterodimer Of Il-15 And Il-15rα, As A Single Agent And In Combination With Spartalizumab In Patients With Advanced And Metastatic Solid Tumors, Rom Leidner, Kevin Conlon, Douglas G Mcneel, Andrea Wang-Gillam, Sumati Gupta, Robert Wesolowski, Monica Chaudhari, Nadia Hassounah, Jong Bong Lee, Lang Ho Lee, Jessica A O'Keeffe, Nancy Lewis, George N Pavlakis, John A Thompson

2020-Current year OA Pubs

BACKGROUND: Preclinically, interleukin-15 (IL-15) monotherapy promotes antitumor immune responses, which are enhanced when IL-15 is used in combination with immune checkpoint inhibitors (ICIs). This first-in-human study investigated NIZ985, a recombinant heterodimer comprising physiologically active IL-15 and IL-15 receptor α, as monotherapy and in combination with spartalizumab, an anti-programmed cell death protein-1 (anti-PD-1) monoclonal antibody, in patients with advanced solid tumors.

METHODS: This phase I/Ib study had two dose-escalation arms: single-agent NIZ985 administered subcutaneously thrice weekly (TIW, 2 weeks on/2 weeks off) or once weekly (QW, 3 weeks on/1 week off), and NIZ985 TIW or QW administered subcutaneously plus spartalizumab (400 …

Difelikefalin Suppresses Itch And Reduces Scratching Independent Of Inflammation In A Murine Model Of Atopic Dermatitis, Masato Tamari, Lydia Zamidar, Aaron M Ver Heul, Kristine Nograles, Joana Goncalves, Emma Guttman-Yassky, Mark Lebwohl, Brian S Kim

2020-Current year OA Pubs

BACKGROUND: Therapies specifically targeting nonhistaminergic pruritus are largely lacking. Difelikefalin (DFK) has been found to reduce itch in various chronic pruritic conditions, including atopic dermatitis (AD).

OBJECTIVE: We sought to investigate the ability of DFK to impact scratching behavior, inflammatory mediators, and neuronal signaling in a murine model of AD.

METHODS: The ears of C57BL/6 mice were topically treated with MC903 for 12 consecutive days to induce AD-like inflammation and itch. Before MC903 treatment, mice were treated with either DFK (0.5 mg/kg, intraperitoneal injection twice daily) or vehicle (saline). Skin ear thickness, histological analysis, flow cytometry, RNA-sequencing, and differential gene …

Virus Control Aboard A Commuter Bus, Hamid Rahai, Jeremy Bonifacio

Mineta Transportation Institute

A major health concern for public transit users is exposure to viruses from other passengers. This numerical study examines virus containment aboard a public bus with changes to the bus ventilation system. The virus was modeled as a 2.5 µm round solid particle released from the mouth of the infectious passenger at a rate of 21 particles per second at a mouth velocity of 0.278 m/sec. The air delivery to the cabin was two linear ceiling slots spanning the length of the bus delivering 59.38 m3/min (2,097 CFM) of air at a mean velocity of 1 m/sec. Two different axial …

Management Of Severe Tricuspid Valve Regurgitation Due To Ruptured Papillary Muscle In A Patient With Mediastinitis Early After Heart Transplant, Erin M Schumer, Kunal D Kotkar, M Faraz Masood, Tsuyoshi Kaneko, Ralph J Damiano, Amit Pawale

2020-Current year OA Pubs

OBJECTIVE: Even though severe tricuspid regurgitation is not uncommon after cardiac transplantation, primary severe tricuspid regurgitation is rare. We present such a case with additional complexities.

METHODS: The patient was 44-year-old man with a HeartWare durable left ventricular assist device (Heartware Inc) who received a temporary right ventricular assist device (RVAD) with a ProtekDuo cannula (LivaNova Inc USA) for refractory ventricular fibrillation and underwent a heart transplant as United Network for Organ Sharing Status 1, in the presence of partially compensated cardiogenic shock, renal failure. Given complex re-operative surgery in a volume-overloaded patient with unknown pulmonary vascular resistance, an RVAD …

Clinical Classification Of Variants In The Valosin-Containing Protein Gene Associated With Multisystem Proteinopathy, Marianela Schiava, Jil Daw, Conrad Chris Weihl, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Pathogenic variants in the valosin-containing protein (

METHODS: A 6-item clinical score was developed to evaluate the phenotypic level of evidence to support the pathogenicity of the novel variants. Each item is allocated a value, a score ranging from 0.5 to 5.5 points. A receiver-operating characteristic curve was used to identify a cutoff value of 3 to consider a variant as high likelihood disease associated. The scoring system results were confronted with results of in vitro ATPase activity assays and with in silico analysis.

RESULTS: All variants were missense, except for one small deletion-insertion, 18 led to …

Modeling X-Chromosome Inactivation And Reactivation During Human Development, Shafqat A Khan, Thorold W Theunissen

2020-Current year OA Pubs

Stem-cell-based embryo models generate much excitement as they offer a window into an early phase of human development that has remained largely inaccessible to scientific investigation. An important epigenetic phenomenon during early embryogenesis is the epigenetic silencing of one of the two X chromosomes in female embryos, which ensures an equal output of X-linked gene expression between the sexes. X-chromosome inactivation (XCI) is thought to be established within the first three weeks of human development, although the inactive X-chromosome is reactivated in primordial germ cells (PGCs) that migrate to the embryonic gonads. Here, we summarize our current understanding of X-chromosome …

The Association Of Long-Term Exposure To Criteria Air Pollutants, Fine Particulate Matter Components, And Airborne Trace Metals With Late-Life Brain Amyloid Burden In The Atherosclerosis Risk In Communities (Aric) Study, Erin E Bennett, Dean F Wong, Et Al.

2020-Current year OA Pubs

BACKGROUND: Studies suggest associations between long-term ambient air pollution exposure and outcomes related to Alzheimer's disease (AD). Whether a link exists between pollutants and brain amyloid accumulation, a biomarker of AD, is unclear. We assessed whether long-term air pollutant exposures are associated with late-life brain amyloid deposition in Atherosclerosis Risk in Communities (ARIC) study participants.

METHODS: We used a chemical transport model with data fusion to estimate ambient concentrations of PM

RESULTS: At PET imaging, eligible participants (N = 318) had a mean age of 78 years, 56% were female, 43% were Black, and 27% had mild cognitive impairment. We …

Comprehensive Mr Imaging Qa Of 0.35 T Mr-Linac Using A Multi-Purpose Large Fov Phantom: A Single-Institution Experience, Shanti Marasini, Hailei Zhang, Lara Dyke, Mike Cole, Benjamin Quinn, Austen Curcuru, Bruce Gu, Rocco Flores, Taeho Kim

2020-Current year OA Pubs

PURPOSE: Magnetic resonance-guided radiotherapy (MRgRT) is desired for the treatment of diseases in the abdominothoracic region, which has a broad imaging area and continuous motion. To ensure accurate treatment delivery, an effective image quality assurance (QA) program, with a phantom that covers the field of view (FOV) similar to a human torso, is required. However, routine image QA for a large FOV is not readily available at many MRgRT centers. In this work, we present the clinical experience of the large FOV MRgRT Insight phantom for periodic daily and monthly comprehensive magnetic resonance imaging (MRI)-QA and its feasibility compared to …

The Use Of The Agency Healthcare Research And Quality Patient Safety Indicator 11 Toolkit To Decrease Postoperative Respiratory Failure, Nancy Garcia

Electronic Theses and Dissertations

Postoperative respiratory failure incidents can lead to adverse outcomes, including prolonged hospitalizations, increased admissions to intensive care units, and the risk of complications such as ventilator-associated pneumonia, sepsis, and mortality. This project aimed to assess the effectiveness of implementing the Agency for Healthcare Research and Quality Patient Safety Indicator 11 toolkit intervention for noninvasive positive-pressure ventilation in reducing postoperative respiratory failure rates compared to traditional practices. Adopting evidence- based toolkits, such as those provided by the Agency for Healthcare Research and Quality, aids healthcare organizations in enhancing the quality of patient care. The quality improvement project employed a quasi-experimental design, …

Non-Small Cell Lung Cancer Epigenomes Exhibit Altered Dna Methylation In Smokers And Never-Smokers, Jennifer A Karlow, Erica C Pehrsson, Xiaoyun Xing, Mark Watson, Siddhartha Devarakonda, Ramaswamy Govindan, Ting Wang

2020-Current year OA Pubs

Epigenetic alterations are widespread in cancer and can complement genetic alterations to influence cancer progression and treatment outcome. To determine the potential contribution of DNAmethylation alterations to tumor phenotype in non-small cell lung cancer (NSCLC) in both smoker and never-smoker patients, we performed genome-wide profiling of DNA methylation in 17 primary NSCLC tumors and 10 matched normal lung samples using the complementary assays, methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation sensitive restriction enzyme sequencing (MRE-seq). We reported recurrent methylation changes in the promoters of several genes, many previously implicated in cancer, including FAM83A and SEPT9 (hypomethylation), as well as PCDH7, …

Allogeneic Hematopoietic Cell Transplantation Improves Outcome In Myelodysplastic Syndrome Across High-Risk Genetic Subgroups: Genetic Analysis Of The Blood And Marrow Transplant Clinical Trials Network 1102 Study, Jurjen Versluis, Peter Westervelt, Et Al.

2020-Current year OA Pubs

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndrome (MDS) improves overall survival (OS). We evaluated the impact of MDS genetics on the benefit of HCT in a biological assignment (donor

METHODS: We performed targeted sequencing in 309 patients age 50-75 years with International Prognostic Scoring System (IPSS) intermediate-2 or high-risk MDS, enrolled in the Blood and Marrow Transplant Clinical Trials Network 1102 study and assessed the association of gene mutations with OS. Patients with

RESULTS: The distribution of gene mutations was similar in the donor and no donor arms, with

CONCLUSION: HCT improved OS compared with non-HCT …

Dmrt1 Regulates Human Germline Commitment, Naoko Irie, Sun-Min Lee, Valentina Lorenzi, Haiqi Xu, Jinfeng Chen, Masato Inoue, Toshihiro Kobayashi, Carmen Sancho-Serra, Elena Drousioti, Sabine Dietmann, Roser Vento-Tormo, Chun-Xiao Song, M Azim Surani

2020-Current year OA Pubs

Germline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from human embryonic stem cells in vitro. We show that switching from BMP signalling for PGC specification to Activin A and retinoic acid resulted in DMRT1 and CDH5 expression, the indicators of migratory PGCs in vivo. Moreover, the induction of DMRT1 and SOX17 in PGC-like cells promoted epigenetic resetting with striking global enrichment of 5-hydroxymethylcytosine and locus-specific loss of 5-methylcytosine at DMRT1 binding sites and the expression of DAZL representing …

Interrater Reliability Of Motor Severity Scales For Hemifacial Spasm, Ha Yeon Lee, Ingyun Park, Minnie P Luu, Jerry Zhao, Jeanne P Vu, Elizabeth Cisneros, Brian D Berman, H A Jinnah, Han-Joon Kim, Catherine Y Liu, Joel S Perlmutter, Sarah Pirio Richardson, Anne Weissbach, Glenn T Stebbins, David A Peterson

2020-Current year OA Pubs

To compare the inter-rater reliability (IRR) of five clinical rating scales for video-based assessment of hemifacial spasm (HFS) motor severity. We evaluated the video recordings of 45 HFS participants recruited through the Dystonia Coalition. In Round 1, six clinicians with expertise in HFS assessed the participants' motor severity with five scales used to measure motor severity of HFS: the Jankovic rating scale (JRS), Hemifacial Spasm Grading Scale (HSGS), Samsung Medical Center (SMC) grading system for severity of HFS spasms (Lee's scale), clinical grading of spasm intensity (Chen's scale), and a modified version of the Abnormal Involuntary Movement Scale (Tunc's scale). …

Good Manufacturing Practice Production Of Cd34+ Progenitor-Derived Nk Cells For Adoptive Immunotherapy In Acute Myeloid Leukemia, P K J D De Jonge, P M M Van Hauten, L D Janssen, A L De Goede, M M Berrien-Elliott, J M R Van Der Meer, C M Mousset, M W H Roeven, M Foster, N Blijlevens, W Hobo, T A Fehniger, J H Jansen, N P M Schaap, H Dolstra

2020-Current year OA Pubs

Allogeneic natural killer (NK) cell-based immunotherapy is a promising, well-tolerated adjuvant therapeutic approach for acute myeloid leukemia (AML). For reproducible NK cell immunotherapy, a homogenous, pure and scalable NK cell product is preferred. Therefore, we developed a good manufacturing practice (GMP)-compliant, cytokine-based ex vivo manufacturing process for generating NK cells from CD34

Evaluating Adult Care In Dravet Syndrome Upon Transferring From Pediatrics In The U.S.: A Caregiver-Based Survey Study, Fábio A Nascimento, Veronica Hood, Samantha V Yap, Irfan S Sheikh, Mary Anne Meskis, Elizabeth A Thiele

2020-Current year OA Pubs

Patients with Dravet syndrome (DS) and their caregivers must navigate a complex process upon transitioning from pediatric to adult healthcare settings. Our study examines the state of care transfer of patients with DS in the U.S. A 34-question e-survey evaluating patient demographics, clinical features, and details of the transfer process was sent to caregivers of adults with DS (≥18 years old) residing in the U.S. through the Dravet Syndrome Foundation. Forty-six responses were included in the analysis. Twenty-nine patients (n = 29/46) did not undergo transfer of care - mostly because they were still followed by pediatric neurologists/epileptologists (71%), whereas …

Introduction To A Compendium Of Strategies To Prevent Healthcare-Associated Infections In Acute-Care Hospitals: 2022 Updates, Deborah S Yokoe, Hilary M Babcock, Erik R Dubberke, Jonas Marschall, Et Al.

2020-Current year OA Pubs

Since the initial publication of

Multimodal Study Of The Neural Sources Of Error Monitoring In Adolescents And Adults, Stefania Conte, John E. Richards, Nathan A. Fox, Emilio A. Valadez, Marco Mcsweeney, Enda Tan, Daniel Samuel Pine, Anderson M. Winkler, Lucrezia Liuzzi, Elise M. Cardinale, Lauren K. White, George A. Buzzell

School of Medicine Publications

The ability to monitor performance during a goal-directed behavior differs among children and adults in ways that can be measured with several tasks and techniques. As well, recent work has shown that individual differences in error monitoring moderate temperamental risk for anxiety and that this moderation changes with age. We investigated age differences in neural responses linked to performance monitoring using a multimodal approach. The approach combined functional MRI and source localization of event-related potentials (ERPs) in 12-year-old, 15-year-old, and adult participants. Neural generators of two components related to performance and error monitoring, the N2 and ERN, lay within specific …

A Special Message To You From Your Mda Dental Pac Chair, Elizabeth Ralstrom Dds, Ms

The Journal of the Michigan Dental Association

This article is a message from the chair of the Michigan Dental Association’s political action committee thanking members for their contributions and encouraging them to make a contribution with their 2024 dues statement. It includes a listing of all contributors to the PAC over the past year.

Mda Advocacy Report: 2023 To Date, And What’S Next, Jason Mashni Dds

The Journal of the Michigan Dental Association

This article is a recap of MDA legislative advocacy accomplishments and what is on the horizon for the remainder of 2023, written by the chair of the MDA Committee on Governmental and Insurance Affairs.

J Mich Dent Assoc October 2023

The Journal of the Michigan Dental Association

The October 2023 issue of the Journal of the Michigan Dental Association provides: A message from the chair of the Michigan Dental Association political action committee with a listing of donors and a report on MDA advocacy during 2023, which are this month’s cover stories. Also included is a Q&A feature on dealing with dental benefits companies. This month’s clinical article is a discussion of the management of a failing implant using guided bone regeneration and esthetic crown lengthening. Other features include a listing of 2023 MDA life members and a President’s Message on the dental workforce crisis in Michigan. …

Dentistry And The Law: Is This Patient Abandonment? Two Scenarios, Dan Schulte Jd

The Journal of the Michigan Dental Association

This article discusses two scenarios involving potential patient abandonment. This article is an installment of the MDA Journal’s monthly Dentistry and the Law department.

Dental Hygiene Students Reported Physiological Symptoms Associated With Wearing An N95 Respirator Mask, Peyton Shea Butler

Dental Hygiene Theses & Dissertations

Purpose: Physiological symptoms and comfort levels while wearing an N95 respiratory mask has not been examined with dental hygienists. The purpose of this study was to investigate dental hygiene students reported physiological symptoms and comfort perception while wearing an N95 respirator mask during patient care appointments. Methods: After IRB approval (IRB #1987754-2), a 16-item questionnaire was distributed through email to a convenience sample of 65 dental hygiene students. Questions assessed respiratory, dermatologic, cardiac, mask mouth and general physiological symptoms, as well as comfort levels. Additionally, participants were asked to respond to demographic questions and one open ended question inquiring about …

Nightmares And Self-Injury Among High-Risk Adolescents: Examining The Role Of Emotion Regulation, Kinjal K. Patel

Psychology Theses & Dissertations

Self-injurious thoughts and behaviors (SITBs) are a public health concern among youth. SITB rates rise drastically during adolescence -- a critical and sensitive developmental period characterized by dramatic changes in biological and social systems. Prior research has identified distal risk factors which tell us who is at risk for SITBs. Emerging research suggests proximal risk factors may be useful to identify when an individual may be at risk for SITBs. One promising proximal risk factor for SITBs is sleep problems. Although the relation between sleep problems and SITBs has been widely documented, little is known about the short-term, proximal links …

Use Of Tyk2 Inhibitor To Relieve Reactive Granulomatous Dermatitis Due To Myelodysplastic Syndrome, Christina Huang, Adar Berghoff, Jack L. Arbiser

Student Papers, Posters & Projects

No abstract provided.

Oral Pustular Lesions In The Setting Of Yersinia Enterocolitica Infection, Alberto D. Lopez Juarez, Kanisha Patel, Jordan Kishbaugh, Aaron Silva

School of Medicine Publications

Yersinia enterocolitica is a gram-negative, rod-shaped, pleomorphic bacteria that is a common source of infectious gastroenteritis. In the United States, Centers of Disease Control and Prevention note yearly 117,000 illnesses, 640 hospitalizations, and 35 deaths [1]. Termed Yersiniosis, the infection is most often acquired via fecal-oral transmission, with sources arising from contaminated pork and unpasteurized milk. Following the fecal-oral transmission, the pathogen invades the intestinal lumen and attaches to the brush border [2]. The clinical presentation includes low-grade fever, vomiting, and invasive diarrhea and further manifestations range from pseudoappendicitis and reactive arthritis [2-3]. Although well-known for its ability to cause …

Safety Outcomes Of Mechanical Thrombectomy Versus Combined Thrombectomy And Intravenous Thrombolysis In Tandem Lesions, Aaron Rodriguez-Calienes, Milagros Galecio-Castillo, Mudassir Farooqui, Ameer E. Hassan, Mouhammad A. Jumaa, Afshin A. Divani, Marc Ribo, Wondwossen G. Tekle, Hisham Alhajala, Sunil Sheth

School of Medicine Publications

Background: We aimed to describe the safety and efficacy of mechanical thrombectomy (MT) with or without intravenous thrombolysis (IVT) for patients with tandem lesions and whether using intraprocedural antiplatelet therapy influences MT's safety with IVT treatment.

Methods: This is a subanalysis of a pooled, multicenter cohort of patients with acute anterior circulation tandem lesions treated with MT from 16 stroke centers between January 2015 and December 2020. Primary outcomes included symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2. Additional outcomes included hemorrhagic transformation, successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), complete reperfusion (modified Thrombolysis in Cerebral Infarction …

Addressing Cervical Cancer Disparities In Texas: Expansion Of A Community-Based Prevention Initiative For Medically Underserved Populations, Samantha H. Batman, Melissa L. Varon, Maria Daheri, Tony Ogburn, Saul D. Rivas, Laura Guerra, Paul Toscano, Monica Gasca, Lori Campos, Savanah Foster

School of Medicine Publications

Although cervical cancer is preventable, significant disparities exist in access to screening and prevention services. In medically underserved areas (MUAs) of Texas, these rates are 55% higher compared to the remainder of the US. In 2019, we expanded a multicomponent, comprehensive program to improve cervical cancer prevention in partnership with 13 clinics and mobile vans in MUAs of Texas. Our multicomponent intervention program consists of community education and patient navigation coupled with a training/mentoring program for local medical providers to perform diagnostic procedures and treatment for patients with abnormal screening results. Hands-on training courses to learn these skills are coupled …

A Systematic Review And Meta-Analysis Of Resting-State Fmri In Anxiety Disorders: Need For Data Sharing To Move The Field Forward, André Zugman, Laura Jett, Chase Antonacci, Anderson M. Winkler, Daniel Samuel Pine

School of Medicine Publications

Highlights

• There are numerous studies investigating rs-fMRI and anxiety; however, the methodologies are inconsistent.

• Anxiety patients show hypoconnectivity between the amygdala and the medial prefrontal cortex.

• This finding is not robust against possible publication bias. Thus, no strong findings manifest in available literature.

• More studies are needed with standardized methods and larger sample sizes.

Abstract

Anxiety disorders are among the most prevalent psychiatric disorders. Neuroimaging findings remain uncertain, and resting state functional magnetic resonance (rs-fMRI) connectivity is of particular interest since it is a scalable functional imaging modality. Given heterogeneous past findings for rs-fMRI in anxious individuals, we characterize patterns …

Hypertrophic Cardiomyopathy Diagnosis And Treatment In High- And Low-Income Countries: A Narrative Review, Ernesto Calderon Martinez, Nancy Y. Ortiz-Garcia, Domenica A. Herrera Hernandez, David Arriaga Escamilla, Diana L. Diaz Mendoza, Diana Othon, Luz M. Ramirez, Jonathan Reyes-Rivera, Jinal Choudhari, George Michel

School of Medicine Publications

Hypertrophic cardiomyopathy (HCM) is a hereditary cardiac condition characterized by unexplained left ventricular hypertrophy without a hemodynamic cause. This condition is prevalent in the United States, resulting in various clinical manifestations, including diastolic dysfunction, left ventricular outflow obstruction, cardiac ischemia, and atrial fibrillation. HCM is associated with several genetic mutations, with sarcomeric mutations being the most common and contributing to a more complex disease course. Early diagnosis of HCM is essential for effective management, as late diagnosis often requires invasive treatments and creates a substantial financial burden. Disparities in HCM diagnosis and treatment exist between highincome and low-income countries. High-income …

Autophagy Modulation And Its Implications On Glioblastoma Treatment, Johnny Chen, Andrea Salinas Rodriguez, Maximiliano Arath Morales, Xiaoqian Fang

School of Medicine Publications

Autophagy is a vital cellular process that functions to degrade and recycle damaged organelles into basic metabolites. This allows a cell to adapt to a diverse range of challenging conditions. Autophagy assists in maintaining homeostasis, and it is tightly regulated by the cell. The disruption of autophagy has been associated with many diseases, such as neurodegenerative disorders and cancer. This review will center its discussion on providing an in-depth analysis of the current molecular understanding of autophagy and its relevance to brain tumors. We will delve into the current literature regarding the role of autophagy in glioma pathogenesis by exploring …