Medicine and Health Sciences Commons^™

Cell-Type-Specific Alternative Polyadenylation Promotes Oncogenic Gene Expression In Non-Small Cell Lung Cancer Progression, Kexin Huang, Yun Zhang, Xiaorui Shi, Zhiqin Yin, Weiling Zhao, Liyu Huang, Fu Wang, Xiaobo Zhou

Faculty, Staff and Student Publications

Disrupted alternative polyadenylation (APA) is frequently involved in tumorigenesis and cancer progression by regulating the gene expression of oncogenes and tumor suppressors. However, limited knowledge of tumor-type- and cell-type-specific APA events may lead to novel APA events and their functions being overlooked. Here, we compared APA events across different cell types in non-small cell lung cancer (NSCLC) and normal tissues and identified functionally related APA events in NSCLC. We found several cell-specific 3'-UTR alterations that regulate gene expression changes showed prognostic value in NSCLC. We further investigated the function of APA-mediated 3'-UTR shortening through loss of microRNA (miRNA)-binding sites, and …

Disease Modeling And Gene Correction Of Lgmdr21 Ipscs Elucidates The Role Of Poglut1 In Skeletal Muscle Maintenance, Regeneration, And The Satellite Cell Niche, Jose L Ortiz-Vitali, Jianbo Wu, Nasa Xu, Annie W Shieh, Nima Niknejad, Megumi Takeuchi, Carmen Paradas, Chunru Lin, Hamed Jafar-Nejad, Robert S Haltiwanger, Sidney H Wang, Radbod Darabi

Faculty, Staff and Student Publications

Autosomal recessive limb-girdle muscular dystrophy 21 (LGMDR21) is caused by pathogenic variants in protein O-glucosyltransferase 1 (POGLUT1), which is responsible for O-glucosylation of specific epidermal growth factor (EGF) repeats found in ∼50 mammalian proteins, including Notch receptors. Previous data from patient biopsies indicated that impaired Notch signaling, reduction of muscle stem cells, and accelerated differentiation are probably involved in disease etiopathology. Using patient induced pluripotent stem cells (iPSCs), their corrected isotypes, and control iPSCs, gene expression profiling indicated dysregulation of POGLUT1, NOTCH, muscle development, extracellular matrix (ECM), cell adhesion, and migration as involved pathways. They also exhibited reduced in vitro …

Description Of A New Pavlovskyella Species (Acari: Argasidae) From Chile, Sebastián Muñoz-Leal, José M Venzal, Alexander R Kneubehl, Job E Lopez, Thiago F Martins, Marcelo B Labruna

Faculty, Staff and Students Publications

Soft ticks (Argasidae) of the Pavlovskyella Pospelova-Shtrom subgenus are important vectors of relapsing fever spirochetes, which are agents of disease globally. South American representatives of the Pavlovskyella subgenus include 3 species: Ornithodoros (Pavlovskyella) brasiliensis Aragão, Ornithodoros (Pavlovskyella) furcosus Neumann, and Ornithodoros (Pavlovskyella) rostratus Aragão. Here, we describe a fourth species based on morphological and mitogenomic evidence of ticks collected in burrows of unknown hosts in central Chile. The larva of the new species separates from other South American soft ticks by the following combination of characters: 13 pairs of dorsolateral setae, dorsal plate hexagonal, hypostome blunt with denticles from apex …

Clinical Outcomes Following Bifurcation Techniques For Percutaneous Coronary Intervention, Chayakrit Krittanawong, Hafeez Ul Hassan Virk, Yusuf Kamran Qadeer, Umer Irshad, Zhen Wang, Mahboob Alam, Samin Sharma

Faculty, Staff and Students Publications

Bifurcation lesions account for 20% of all percutaneous coronary interventions and represent a complex subset which are associated with lower procedural success and higher rates of restenosis [...].

Lifetime Aortic Management In Marfan Syndrome: Puzzle Pieces And Rare Diseases, Joseph S Coselli, Lauren M Barron

Faculty, Staff and Students Publications

No abstract provided.

Impact Of Integrating A Unified Population Health And Systems Thinking Curriculum Into A Pa Program, Halley Barke, Georgia Luckey, Christy Hamilton, Taylor Sutton, Tracey Smith, Janet Albers

SIU Journal of Medical Science Scholarly Works

Purpose

This study shows the impact of a 3-part population health and interprofessional education (IPE) curriculum on Physician Assistant (PA) students’ knowledge and experience of population health and systems thinking (PHST) and to promote a team-based approach to patient care and improve patient health and preventative services.

Methods

Human Resources and Services Administration funded a 5-year Primary Care and Training Enhancement grant in PHST. With this funding, the Department of Family and Community Medicine developed a three-part plan emphasizing interprofessional learning. The impact was measured using a 22-item survey measuring knowledge and experience of PHST delivered to PA students annually. …

Severe Covid-19 Infection In An Infant With 8p Inverted Duplication/Deletion Syndrome: Is Vaccination Still A Debate?, Andrew M. Joseph, Monica Karas, Ernesto Joubran, Yaseen O. Ramadan, Blakley A. Fowler

HPD Articles

Despite having a milder course of coronavirus disease 2019 (COVID-19) in comparison to adults, children are at risk for more significant complications, including acute neurological, renal, respiratory, and cardiovascular complications. Acute complications can manifest as encephalopathy, renal injury, interstitial pneumonia, and heart failure. However, the most severe complication is multisystem inflammatory syndrome in children, which often requires intensive care to manage the subsequent respiratory failure. Moreover, children with comorbidities such as chronic lung disease, neurological disorders, and cardiovascular disease are at an elevated risk of morbidity and mortality. Here, we present the case of an 11- month-old white female patient, …

Ada News - 09/11/2023, American Dental Association, Publishing Division

ADA News

Established in 1970 as the official newspaper of the American Dental Association, the ADA News serves practicing dentists and others allied to the dental profession in the U.S. and internationally. It is the No. 1 source of news and information about the many benefits and services the ADA delivers to members daily as well as timely information on scientific, social, political and economic developments affecting dentistry and health care.

The Effects Of Inhaled Anesthetic Agents On Long-Term Cognitive Decline, Viktor Kunder, Matthew Tayem, Sneh Parekh

HPD Articles

Background: Anesthesia is generally considered safe, but studies have shown the potential relationship between anesthetic agents and dementia after surgery. Several studies have pointed out how the commonly used anesthetic drugs induce cytotoxicity, ultimately leading to neurodegeneration and even Alzheimer's Disease (AD). Specifically, inhaled anesthetics such as isoflurane, sevoflurane, and desflurane have been shown to impact the neurophysiology of the brain. However, there is no established relationship between aesthetics and long-term postoperative cognitive decline.

Objective: The objective of this study is to explore the available research on anesthetic agents and the potential role that they have played in postoperative cognitive …

Supporting Vulnerable Older Adults With Telehealth Through Wellness Calls And Tablet Distribution During Covid-19: Quality Improvement Project, Sweta Tewary, Nicole J. Cook, Marie Dezine, Oksana Shnayder, Naushira Pandya

HPD Articles

BACKGROUND: Loneliness, social isolation, and lack of technical literacy are associated with poorer health outcomes. To help improve social connection during the COVID-19 pandemic, Nova Southeastern University's South Florida Geriatric Workforce Enhancement Program partnered with a community-based organization to provide educational resources to promote telehealth services.

OBJECTIVE: This study aimed to provide educational resources to older adults with limited resources and promote the use of telehealth services in this population.

METHODS: Through this pilot project, we contacted 66 vulnerable older adults who expressed interest in telehealth support through wellness calls, with 44 participants moving on to participate in tablet usage. …

Improving Small-Volume Antibiotic Administration For Surgical Prophylaxis, Benjamin Thomas

Doctor of Nursing Practice (DNP) Student Projects

Background: Small-volume IV antibiotics are commonly administered for surgical prophylaxis, but no clear policy on administration method exists, leading to wide variation in anesthesia provider practice at a large academic medical center. Administration via a secondary tubing set is the recommended practice to minimize significant medication losses which could lead to poor patient outcomes. This large academic medical center performed below the national benchmark for one of these outcomes–surgical site infections.

Goals and Objectives: Objectives of this project included eliminating a potential systematic shortcoming in the administration of prophylactic antibiotics. The goal was to increase the use of …

Evaluating The Effectiveness Of The Clinical Care Of The Pediatric Patient Course: A Quality Improvement Project, Cassandra Elliot

Doctor of Nursing Practice Projects

The Clinical Care of the Pediatric Patient (CCPP) is a two-day course held monthly as part of the onboarding process. This mandatory course is intended to prepare onboarding clinical staff for the provision of evidence-based care to pediatric patients. CCPP contains over 17 hours of didactic and hands-on instruction in the assessment, management, and treatment of pediatric conditions. The goal of this quality improvement project was to determine the perceived effectiveness of the CCPP course and its impact on the confidence level of clinical staff as pediatric providers during their first few months of employment. A regression analysis was used …

Utilizing The Phq9 Survey To Improve Depressive Symptoms In Opioid Dependent Adults: A Quality Improvement Project, Taylor Fuhr

DNP Projects

Significance and Background: Opioid dependence continues to be a fighting battle in our country. While many individuals do well on maintenance therapy such as suboxone, they often are faced with comorbid challenges including depression and anxiety. Research shows that the risk for depressive symptoms in opioid dependent adults increases along with the duration of use and increase of dosage (Semenkovich et al., 2014). There is no consistency among depression screening for opioid dependent adults despite the research that suggests the two often coincide with one another. The goal of this quality improvement project was to implement routine depression screening using …

Integrative Multi-Omic Cancer Profiling Reveals Dna Methylation Patterns Associated With Therapeutic Vulnerability And Cell-Of-Origin, Wen-Wei Liang, Rita Jui-Hsien Lu, Reyka G Jayasinghe, Steven M Foltz, Michael C Wendl, Yizhe Song, Akshay Govindan, Xiang Li, Yize Li, Sunantha Sethuraman, Li Ding, Et Al.

2020-Current year OA Pubs

DNA methylation plays a critical role in establishing and maintaining cellular identity. However, it is frequently dysregulated during tumor development and is closely intertwined with other genetic alterations. Here, we leveraged multi-omic profiling of 687 tumors and matched non-involved adjacent tissues from the kidney, brain, pancreas, lung, head and neck, and endometrium to identify aberrant methylation associated with RNA and protein abundance changes and build a Pan-Cancer catalog. We uncovered lineage-specific epigenetic drivers including hypomethylated FGFR2 in endometrial cancer. We showed that hypermethylated STAT5A is associated with pervasive regulon downregulation and immune cell depletion, suggesting that epigenetic regulation of STAT5A …

Proteogenomic Insights Suggest Druggable Pathways In Endometrial Carcinoma, Yongchao Dou, Rita Jui-Hsien Lu, Yige Wu, Matthew A Wyczalkowski, David Mutch, Li Ding, Et Al.

2020-Current year OA Pubs

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render …

Forensic Evaluation Of A Single Episode Of A Disorder Of Arousal In A Sleepwalking Defense: Cognitive Function Versus Prior Clinical History, Mark R. Pressman

Department of Medicine Faculty Papers

Introduction

The clinical diagnosis of disorders of arousal (DOA) is based primarily on a clinical history including amnesia for episodes. The presence of amnesia means the patient cannot provide direct evidence. In a forensic setting, when the defendant has been charged criminally with violent actions or sexual related assaults allegedly during sleep, a sleepwalking defense may be presented. As opposed to clinical history, the prosecution generally focuses on the single episode of alleged DOA that resulted in the criminal charges against the defendant. The prosecution will argue that this episode of complex behavior was not consistent with a DOA. A …

Perceptions Of Facilitators And Barriers To Smoking Cessation Among Patients And Providers In A Cancer Center: A Single Institution Qualitative Exploratory Study, Luke M. Shenton, Udara Perera, Amy Leader, Ann C. Klassen

College of Population Health Faculty Papers

PURPOSE: Cancer patients who remain tobacco users have poorer outcomes, including increased mortality and decreased treatment tolerance; however, cessation post-diagnosis is challenging. Our formative research explored cessation-related perspectives among patients and staff at one National Cancer Institute-designated cancer center, to inform improving cessation services within oncology care.

METHODS: Using a descriptive phenomenological approach, a purposive sample of current cancer patients (n = 13) and cancer center physicians and cessation program staff (n = 9) were recruited to complete one-on-one audio-recorded in-depth qualitative interviews, to explore experiences providing or receiving cessation support, and perspectives on patients' readiness and needs regarding cessation. …

Collagene Enables Privacy-Aware Federated And Collaborative Genomic Data Analysis, Wentao Li, Miran Kim, Kai Zhang, Han Chen, Xiaoqian Jiang, Arif Harmanci

Faculty, Staff and Student Publications

Growing regulatory requirements set barriers around genetic data sharing and collaborations. Moreover, existing privacy-aware paradigms are challenging to deploy in collaborative settings. We present COLLAGENE, a tool base for building secure collaborative genomic data analysis methods. COLLAGENE protects data using shared-key homomorphic encryption and combines encryption with multiparty strategies for efficient privacy-aware collaborative method development. COLLAGENE provides ready-to-run tools for encryption/decryption, matrix processing, and network transfers, which can be immediately integrated into existing pipelines. We demonstrate the usage of COLLAGENE by building a practical federated GWAS protocol for binary phenotypes and a secure meta-analysis protocol. COLLAGENE is available at https://zenodo.org/record/8125935 …

Weight Loss And The Effects On Blood Pressure, Ashiqua Jackson

Doctor of Nursing Practice Projects

Obesity and hypertension directly contribute to cardiovascular disease, which is modifiable and preventable with lifestyle modification. Blood pressure (BP) control directly impacts mortality from heart disease. The literature suggests that weight reduction is associated with a decrease in BP. The project’s purpose is to assess the effect of a weight management plan on obese or overweight adults with hypertension. The best practice identified was the DASH diet for weight loss and BP reduction, followed by a medication regimen such as Semaglutide. The inclusion criteria comprised adults >18 years with a BMI > 25 and exclusion criteria of < 18 years old, BMI < 25, and a diagnosis of diabetes. Based on the inclusion criteria, a convenience sample of 27 patients was obtained from an outpatient clinic through a retrospective chart review. Obesity, hypertension, and DASH diet education were provided to the clinic staff. During the initial weight management consultation, the provider educated patients about the DASH diet. A baseline BP and weight were obtained and compared four weeks later. A two-tailed Wilcoxon and paired t-test revealed a significant systolic and diastolic BP reduction. The results were statistically significant, indicating that a comprehensive weight management plan is essential to reducing both BP and weight in overweight, obese, and hypertensive patients.

Proteomics-Based Approach For Detailing The Allergenic Profile Of Cannabis Chemotypes, Cali Loblundo, Jenna Severa, Gabrielle A Peruggia, Kristina Reid Black, Suman Chandra, Hemant Lata, Mahmoud Elsohly, Martin D Chapman, Deepak A. Deshpande, Ajay P. Nayak

Center for Translational Medicine Faculty Papers

Allergic sensitization to cannabis is an emerging public health concern and is difficult to clinically establish owing to lack of standardized diagnostic approaches. Attempts to develop diagnostic tools were largely hampered by the Schedule I restrictions on cannabis, which limited accessibility for research. Recently, however, hemp was removed from the classified list, and increased accessibility to hemp allows for the evaluation of its practical clinical value for allergy diagnosis. We hypothesized that the proteomic profile is preserved across different cannabis chemotypes and that hemp would be an ideal source of plant material for clinical testing. Using a proteomics-based approach, we …

Adapting Shift Work Schedules For Sleep Quality, Sleep Duration, And Sleepiness In Shift Workers., Gerben Hulsegge, Pieter Coenen, Gregg M Gascon, Manisha Pahwa, Birgit Greiner, Ciarán Bohane, Imelda S Wong, Juha Liira, Rachel Riera, Daniela V Pachito

Ambulatory and Primary Care Articles

BACKGROUND: Shift work is associated with insufficient sleep, which can compromise worker alertness with ultimate effects on occupational health and safety. Adapting shift work schedules may reduce adverse occupational outcomes.

OBJECTIVES: To assess the effects of shift schedule adaptation on sleep quality, sleep duration, and sleepiness among shift workers.

SEARCH METHODS: We searched CENTRAL, PubMed, Embase, and eight other databases on 13 December 2020, and again on 20 April 2022, applying no language restrictions.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) and non-RCTs, including controlled before-after (CBA) trials, interrupted time series, and cross-over trials. Eligible trials evaluated any of …

Global Proteomic Identifies Multiple Cancer-Related Signaling Pathways Altered By A Gut Pathobiont Associated With Colorectal Cancer, Ewa Pasquereau-Kotula, Giulia Nigro, Florent Dingli, Damarys Loew, Patrick Poullet, Yi Xu, Scott Kopetz, Jennifer Davis, Lucie Peduto, Catherine Robbe-Masselot, Philippe Sansonetti, Patrick Trieu-Cuot, Shaynoor Dramsi

Faculty, Staff and Student Publications

In this work, we investigated the oncogenic role of Streptococcus gallolyticus subsp. gallolyticus (SGG), a gut bacterium associated with colorectal cancer (CRC). We showed that SGG UCN34 accelerates colon tumor development in a chemically induced CRC murine model. Full proteome and phosphoproteome analysis of murine colons chronically colonized by SGG UCN34 revealed that 164 proteins and 725 phosphorylation sites were differentially regulated. Ingenuity Pathway Analysis (IPA) indicates a pro-tumoral shift specifically induced by SGG UCN34, as ~ 90% of proteins and phosphoproteins identified were associated with digestive cancer. Comprehensive analysis of the altered phosphoproteins using ROMA software revealed up-regulation of …

Elimination Of Oncogenic Kras In Genetic Mouse Models Eradicates Pancreatic Cancer By Inducing Fas-Dependent Apoptosis By Cd8+ T Cells, Krishnan K Mahadevan, Valerie S Lebleu, Elena V Ramirez, Yang Chen, Bingrui Li, Amari M Sockwell, Mihai Gagea, Hikaru Sugimoto, Lakshmi Kavitha Sthanam, Desiree Tampe, Michael Zeisberg, Haoqiang Ying, Abhinav K Jain, Ronald A Depinho, Anirban Maitra, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Oncogenic KRASG12D (KRAS∗) is critical for the initiation and maintenance of pancreatic ductal adenocarcinoma (PDAC) and is a known repressor of tumor immunity. Conditional elimination of KRAS∗ in genetic mouse models of PDAC leads to the reactivation of FAS, CD8+ T cell-mediated apoptosis, and complete eradication of tumors. KRAS∗ elimination recruits activated CD4+ and CD8+ T cells and promotes the activation of antigen-presenting cells. Mechanistically, KRAS∗-mediated immune evasion involves the epigenetic regulation of Fas death receptor in cancer cells, via methylation of its promoter region. Furthermore, analysis of human RNA sequencing identifies that high KRAS expression in PDAC tumors shows …

Unfolding The Secrets Of Small Cell Lung Cancer Progression: Novel Approaches And Insights Through Rapid Autopsies, Zsolt Megyesfalvi, Simon Heeke, Benjamin J Drapkin, Anna Solta, Ildiko Kovacs, Kristiina Boettiger, Lilla Horvath, Busra Ernhofer, Janos Fillinger, Ferenc Renyi-Vamos, Clemens Aigner, Karin Schelch, Christian Lang, Gyorgy Marko-Varga, Carl M Gay, Lauren A Byers, Benjamin B Morris, John V Heymach, Peter Van Loo, Fred R Hirsch, Balazs Dome

Faculty, Staff and Student Publications

The understanding of small cell lung cancer (SCLC) biology has increased dramatically in recent years, but the processes that allow SCLC to progress rapidly remain poorly understood. Here, we advocate the integration of rapid autopsies and preclinical models into SCLC research as a comprehensive strategy with the potential to revolutionize current treatment paradigms.

Early Onset Horizontal Gaze Palsy And Progressive Scoliosis Due To A Noncanonical Splicing-Site Variant And A Missense Variant In The Robo3 Gene, Sheng Yi, Zailong Qin, Xunzhao Zhou, Junjie Chen, Shang Yi, Qiuli Chen, Limei Huang, Qinle Zhang, Biyan Chen, Jingsi Luo

Faculty, Staff and Student Publications

BACKGROUND: Homozygous or compound heterozygous ROBO3 gene mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS). This is an autosomal recessive disorder that is characterized by congenital absence or severe restriction of horizontal gaze and progressive scoliosis. To date, almost 100 patients with HGPPS have been reported and 55 ROBO3 mutations have been identified.

METHODS: We described an HGPPS patient and performed whole-exome sequencing (WES) to identify the causative gene.

RESULTS: We identified a missense variant and a splice-site variant in the ROBO3 gene in the proband. Sanger sequencing of cDNA revealed the presence of an aberrant transcript with retention …

Preface: Causes Of Obesity, Theories, Conjectures And Evidence, David B Allison, Thorkild I A Sørensen, Kevin D Hall, John R Speakman

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Endogenous Fluctuations In Cortical State Selectively Enhance Different Modes Of Sensory Processing In Human Temporal Lobe, Arun Parajuli, Diego Gutnisky, Nitin Tandon, Valentin Dragoi

Faculty, Staff and Student Publications

The degree of synchronized fluctuations in neocortical network activity can vary widely during alertness. One influential idea that has emerged over the past few decades is that perceptual decisions are more accurate when the state of population activity is desynchronized. This suggests that optimal task performance may occur during a particular cortical state - the desynchronized state. Here we show that, contrary to this view, cortical state can both facilitate and suppress perceptual performance in a task-dependent manner. We performed electrical recordings from surface-implanted grid electrodes in the temporal lobe while human subjects completed two perceptual tasks. We found that …

Enhanced Phenotypes For Identifying Opioid Overdose In Emergency Department Visit Electronic Health Record Data, Ralph Ward, Jihad S. Obeid, Lindsey Jennings, Elizabeth Szwast, William Garrett Hayes, Royal Pipaliya, Cameron Bailey, Skylar Faul, Brianna Polyak, George Hamilton Baker

School of Medicine Publications

Background

Accurate identification of opioid overdose (OOD) cases in electronic healthcare record (EHR) data is an important element in surveillance, empirical research, and clinical intervention. We sought to improve existing OOD electronic phenotypes by incorporating new data types beyond diagnostic codes and by applying several statistical and machine learning methods.

Materials and Methods

We developed an EHR dataset of emergency department visits involving OOD cases or patients considered at risk for an OOD and ascertained true OOD status through manual chart reviews. We developed and validated prediction models using Random Forest, Extreme Gradient Boost, and Elastic Net models that incorporated …

Intouch Week Of September 11, 2023, New York Medical College

InTouch

• Intranasal Immunization Offers Stronger Protection Against COVID-19
• Campus Playground Gets a Makeover
• SOM Student Publishes Research Conducted In Prestigious Fellowship Program
• NYMC and TU Hosts “Ninety Minutes: The Medical Magazine of the Web”
• Calling Artists For The Asprinio Fitness Center Wall Project
• NYMC Research: Patric K. Stanton, Ph.D.

Treatment Of Older Adults With Flt3-Mutated Aml: Emerging Paradigms And The Role Of Frontline Flt3 Inhibitors, Nicholas J Short, Daniel Nguyen, Farhad Ravandi

Faculty, Staff and Student Publications

FLT3 is the most frequently mutated gene in acute myeloid leukemia (AML), with FLT3 internal tandem duplication (ITD) mutations being associated with a more aggressive clinical course. While two large, randomized clinical trials have shown a survival benefit with the frontline use of an oral FLT3 inhibitor (midostaurin or quizartinib) in patients with FLT3-mutated AML, the role of FLT3 inhibitors in older adults with newly diagnosed FLT3-mutated AML remains unclear. A definitive improvement in survival has not been observed in intensively treated patients over 60 years of age receiving frontline FLT3 inhibitors. Furthermore, many patients with FLT3-mutated AML are unsuitable …