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Articles 71401 - 71430 of 325295

Full-Text Articles in Medicine and Health Sciences

Spontaneous Collapse As A Prognostic Marker For Human Blastocysts: A Systematic Review And Meta-Analysis, Kate Bickendorf, Fang Qi, Kelli Peirce, Jay Natalwala, Vincent Chapple, Yanhe Liu Oct 2023

Spontaneous Collapse As A Prognostic Marker For Human Blastocysts: A Systematic Review And Meta-Analysis, Kate Bickendorf, Fang Qi, Kelli Peirce, Jay Natalwala, Vincent Chapple, Yanhe Liu

Research outputs 2022 to 2026

STUDY QUESTION: Is spontaneous collapse (SC) by human blastocysts a prognostic factor in IVF treatment? SUMMARY ANSWER: SC in human blastocyst is associated with reduced euploid embryo and pregnancy rates. WHAT IS KNOWN ALREADY: SC of the human blastocyst is a phenomenon that was revealed relatively recently following the clinical application of time-lapse monitoring in IVF laboratories. The ploidy and clinical prognosis of affected blastocysts are still poorly understood, with inconsistent reports. Systematic reviews and meta-analyses on this topic are currently absent in the literature but its potential as a marker of embryo viability holds great clinical value. In this …


“I Believe…” - Graduating Midwifery Students’ Midwifery Philosophies And Intentions For Their Graduate Year: A Longitudinal Descriptive Study, Kate Dawson, Heather Wallace, Sara Bayes Oct 2023

“I Believe…” - Graduating Midwifery Students’ Midwifery Philosophies And Intentions For Their Graduate Year: A Longitudinal Descriptive Study, Kate Dawson, Heather Wallace, Sara Bayes

Research outputs 2022 to 2026

Objective: Midwifery graduates may experience transition shock that makes them question their fit for their workplace and the profession and in extreme cases, may lead to them leaving. Understanding graduate midwives’ worldviews, job intentions and work experiences is important to inform retention strategies. Factors such as having a strong professional identity and experiencing strong job satisfaction are important for midwife retention. Conversely, stress, trauma and work-life imbalances are examples of factors that lead to attrition from midwifery. Transition shock experienced by some graduates can exacerbate these factors if not managed effectively. This study aimed to identify causes and impact of …


Investigating Weekend Effect In The Management Of Upper And Lower Extremity Degloving Injuries, Kaamya Varagur, Janessa Sullivan, Sarah N. Chiang, Gary B. Skolnick, Justin M. Sacks, Joani M. Christensen Oct 2023

Investigating Weekend Effect In The Management Of Upper And Lower Extremity Degloving Injuries, Kaamya Varagur, Janessa Sullivan, Sarah N. Chiang, Gary B. Skolnick, Justin M. Sacks, Joani M. Christensen

2020-Current year OA Pubs

BACKGROUND: Weekend presentation has been associated with adverse outcomes in emergent conditions, including stroke, myocardial infarction, and critical limb ischemia. We examine whether a weekend effect exists in the management of and outcomes after extremity degloving injuries.

METHODS: The cohort included adults presenting with open extremity degloving injuries to a tertiary level one trauma center between June 2018 and May 2022. We collected demographics, comorbidities, injury information, interventions, and complications. Propensity score weighting was used to minimize confounding differences between those presenting on weekends (Sat-Sun) versus weekdays (Mon-Fri). Weighted regressions were used to examine differences in interventions by day of …


A Drosophila Glial Cell Atlas Reveals A Mismatch Between Transcriptional And Morphological Diversity, Inês Lago-Baldaia, Maia Cooper, Austin Seroka, Chintan Trivedi, Gareth T. Powell, Stephen W. Wilson, Sarah D. Ackerman, Vilaiwan M. Fernandes Oct 2023

A Drosophila Glial Cell Atlas Reveals A Mismatch Between Transcriptional And Morphological Diversity, Inês Lago-Baldaia, Maia Cooper, Austin Seroka, Chintan Trivedi, Gareth T. Powell, Stephen W. Wilson, Sarah D. Ackerman, Vilaiwan M. Fernandes

2020-Current year OA Pubs

Morphology is a defining feature of neuronal identity. Like neurons, glia display diverse morphologies, both across and within glial classes, but are also known to be morphologically plastic. Here, we explored the relationship between glial morphology and transcriptional signature using the Drosophila central nervous system (CNS), where glia are categorised into 5 main classes (outer and inner surface glia, cortex glia, ensheathing glia, and astrocytes), which show within-class morphological diversity. We analysed and validated single-cell RNA sequencing data of Drosophila glia in 2 well-characterised tissues from distinct developmental stages, containing distinct circuit types: the embryonic ventral nerve cord (VNC) (motor) …


Pancreatic Tail Cancer In The Setting Of Pancreatitis With A Review Of The Literature: A Case Report, Shinji Rho, Sooyoung Martin, Zack Nigogosyan, Vladimir Kushnir, Aaron J Mintz, Zishuo Ian Hu Oct 2023

Pancreatic Tail Cancer In The Setting Of Pancreatitis With A Review Of The Literature: A Case Report, Shinji Rho, Sooyoung Martin, Zack Nigogosyan, Vladimir Kushnir, Aaron J Mintz, Zishuo Ian Hu

2020-Current year OA Pubs

Environmental risk factors for pancreatic cancer include acute and chronic pancreatitis, obesity, and tobacco use. Differentiating a pancreatic neoplasm in a patient with pancreatitis can be challenging due to their similar presentations. A 57-year-old African American man with a history of congestive heart failure, pancreatitis, and incomplete pancreas divisum presented with an epigastric abdominal pain that radiated to his back. Imaging showed necrotizing pancreatitis, a developing splenic infarct, and a mass at the pancreas tail. The patient was discharged with pain medications and was recommended follow-up imaging after resolution of his pancreatitis. He was readmitted to the emergency department 2 …


Knowledge, Beliefs, And Practices Related To Coronavirus Disease 2019 (Covid-19) Infection And Vaccination In Healthcare Personnel Working At Nonacute Care Facilities, Armaghan-E-Rehman Mansoor, Caroline A O'Neil, David Mcdonald, Victoria J Fraser, Hilary M Babcock, Jennie H Kwon, Cdc Prevention Epicenters Program Oct 2023

Knowledge, Beliefs, And Practices Related To Coronavirus Disease 2019 (Covid-19) Infection And Vaccination In Healthcare Personnel Working At Nonacute Care Facilities, Armaghan-E-Rehman Mansoor, Caroline A O'Neil, David Mcdonald, Victoria J Fraser, Hilary M Babcock, Jennie H Kwon, Cdc Prevention Epicenters Program

2020-Current year OA Pubs

OBJECTIVE: To characterize experiences, beliefs, and perceptions of risk related to coronavirus disease 2019 (COVID-19), infection prevention practices, and COVID-19 vaccination among healthcare personnel (HCP) at nonacute care facilities.

DESIGN: Anonymous survey.

SETTING: Three non-acute-care facilities in St. Louis, Missouri.

PARTICIPANTS: In total, 156 HCP responded to the survey, for a 25.6% participation rate). Among them, 32% had direct patient-care roles.

METHODS: Anonymous surveys were distributed between April-May 2021. Data were collected on demographics, work experience, COVID-19 exposure, knowledge, and beliefs about infection prevention, personal protective equipment (PPE) use, COVID-19 vaccination, and the impact of COVID-19.

RESULTS: Nearly all respondents …


Is Retention Of The Acetabular Component At Revision Surgery A Long-Term Solution?, Elizabeth Lieberman, Lee Sasala, Tanner Thornton, Robert Barrack, Ryan Nunley, Susan Thapa, John Clohisy Oct 2023

Is Retention Of The Acetabular Component At Revision Surgery A Long-Term Solution?, Elizabeth Lieberman, Lee Sasala, Tanner Thornton, Robert Barrack, Ryan Nunley, Susan Thapa, John Clohisy

2020-Current year OA Pubs

BACKGROUND: Acetabular retention in revision total hip arthroplasty (THA) may be advantageous, yet long-term survival data is limited. Thus, we investigated long-term survivorship of retained acetabular components in revision THA with analysis of rerevision rate, instability risk, and clinical outcomes.

METHODS: We reviewed 98 hips with polyethylene wear and/or osteolysis that were revised with retained acetabular components. Acetabular inclination and anteversion were measured from prerevision radiographs. A retrospective chart review was performed, collecting outcomes of interest including Harris hip score, instability events, and rerevision surgery. Kaplan-Meier analysis was used to calculate the risk of revision over time. Predictors of survival …


N7-Methylguanosine Methylation Of Trnas Regulates Survival To Stress In Cancer, Raquel García-Vílchez, Ana M Añazco-Guenkova, Judith López, Sabine Dietmann, Mercedes Tomé, Sonia Jimeno, Mikel Azkargorta, Félix Elortza, Laura Bárcena, Monika Gonzalez-Lopez, Ana M Aransay, Manuel A Sánchez-Martín, Pablo Huertas, Raúl V Durán, Sandra Blanco Oct 2023

N7-Methylguanosine Methylation Of Trnas Regulates Survival To Stress In Cancer, Raquel García-Vílchez, Ana M Añazco-Guenkova, Judith López, Sabine Dietmann, Mercedes Tomé, Sonia Jimeno, Mikel Azkargorta, Félix Elortza, Laura Bárcena, Monika Gonzalez-Lopez, Ana M Aransay, Manuel A Sánchez-Martín, Pablo Huertas, Raúl V Durán, Sandra Blanco

2020-Current year OA Pubs

Tumour progression and therapy tolerance are highly regulated and complex processes largely dependent on the plasticity of cancer cells and their capacity to respond to stress. The higher plasticity of cancer cells highlights the need for identifying targetable molecular pathways that challenge cancer cell survival. Here, we show that N


Human Intestinal Organoids As Models To Study Enteric Bacteria And Viruses, Grace Adeniyi-Ipadeola, Hephzibah Nwanosike, Sasirekha Ramani Oct 2023

Human Intestinal Organoids As Models To Study Enteric Bacteria And Viruses, Grace Adeniyi-Ipadeola, Hephzibah Nwanosike, Sasirekha Ramani

Faculty, Staff and Students Publications

Laboratory studies of host-microbe interactions have historically been carried out using transformed cell lines and animal models. Although much has been learned from these models, recent advances in the development of multicellular, physiologically active, human intestinal organoid (HIO) cultures are allowing unprecedented discoveries of host-microbe interactions. Here, we review recent literature using HIOs as models to investigate the pathogenesis of clinically important enteric bacteria and viruses and study commensal intestinal microbes. We also discuss limitations of current HIO culture systems and how technical advances and innovative engineering approaches are providing new directions to improve the model. The studies discussed here …


The Improving Medication Adherence In Adolescents And Young Adults Following Liver Transplantation (Imalt) Multisite Trial: Design And Trial Implementation Considerations, Eyal Shemesh, Sarah Duncan-Park, George Mazariegos, Rachel Annunziato, Ravinder Anand, Miguel Reyes-Mugica, Jeff Mitchell, Benjamin L Shneider Oct 2023

The Improving Medication Adherence In Adolescents And Young Adults Following Liver Transplantation (Imalt) Multisite Trial: Design And Trial Implementation Considerations, Eyal Shemesh, Sarah Duncan-Park, George Mazariegos, Rachel Annunziato, Ravinder Anand, Miguel Reyes-Mugica, Jeff Mitchell, Benjamin L Shneider

Faculty, Staff and Students Publications

BACKGROUND/AIMS: Medication non-adherence is a leading cause of transplant rejection, organ loss, and death; yet no rigorous controlled study to date has shown compelling clinical benefits from an adherence-improving intervention. Non-adherent patients are less likely to participate in trials, and therefore, most studies enroll a majority of adherent patients who do not stand to benefit from the intervention, as they do not have the condition (non-adherence) under investigation. The improving Medication Adherence in adolescent Liver Transplant recipients trial specifically targets non-adherent patients to investigate whether a remote intervention to improve adherence results in reduced incidence of biopsy-confirmed rejection.

METHODS: Improving …


Pediatric Drug-Associated Pancreatitis Reveals Concomitant Risk Factors And Poor Reliability Of Causality Scoring: Report From Insppire, Veronique D Morinville, Sohail Z Husain, Fuchenchu Wang, Gretchen A Cress, Maisam Abu-El-Haija, Ankur Chugh, Elissa Downs, Kate Ellery, Douglas S Fishman, Alvin Jay Freeman, Cheryl E Gariepy, Matthew Giefer, Tanja Gonska, Quin Liu, Asim Maqbool, Jacob Mark, Brian Arthur Mcferron, Megha Mehta, Jaimie D Nathan, Ken Ng, Chee Y Ooi, Emily Perito, Wenly Ruan, Sarah Jane Schwarzenberg, Zachary M Sellers, Jose Serrano, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer (Cpdpc) Oct 2023

Pediatric Drug-Associated Pancreatitis Reveals Concomitant Risk Factors And Poor Reliability Of Causality Scoring: Report From Insppire, Veronique D Morinville, Sohail Z Husain, Fuchenchu Wang, Gretchen A Cress, Maisam Abu-El-Haija, Ankur Chugh, Elissa Downs, Kate Ellery, Douglas S Fishman, Alvin Jay Freeman, Cheryl E Gariepy, Matthew Giefer, Tanja Gonska, Quin Liu, Asim Maqbool, Jacob Mark, Brian Arthur Mcferron, Megha Mehta, Jaimie D Nathan, Ken Ng, Chee Y Ooi, Emily Perito, Wenly Ruan, Sarah Jane Schwarzenberg, Zachary M Sellers, Jose Serrano, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

OBJECTIVES: Drug-associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co-risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE-2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children.

METHODS: Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non-Medication cases, and ARP-Med …


Guidelines On Cholangioscopy For Indeterminate Biliary Strictures: One Step Closer To Consensus, Fares Ayoub, Mohamed O Othman Oct 2023

Guidelines On Cholangioscopy For Indeterminate Biliary Strictures: One Step Closer To Consensus, Fares Ayoub, Mohamed O Othman

Faculty, Staff and Students Publications

No abstract provided.


Tuberculosis Incidence In Foreign-Born People Residing In European Countries In 2020, Anca Vasiliu, Niklas Köhler, Ekkehardt Altpeter, Tinna Rán Ægisdóttir, Marina Amerali, Wouter Arrazola De Oñate, Ágnes Bakos, Stefania D'Amato, Daniela Maria Cirillo, Reinout Van Crevel, Edita Davidaviciene, Irène Demuth, Jose Domínguez, Raquel Duarte, Gunar Günther, Jean-Paul Guthmann, Sophia Hatzianastasiou, Louise Hedevang Holm, Zaida Herrador, Urška Hribar, Conny Huberty, Elmira Ibraim, Sarah Jackson, Mogens Jensenius, Kamilla Sigridur Josefsdottir, Anders Koch, Maria Korzeniewska-Kosela, Liga Kuksa, Heinke Kunst, Christian Lienhardt, Beatrice Mahler, Mateja Janković Makek, Inge Muylle, Johan Normark, Analita Pace-Asciak, Goranka Petrović, Despo Pieridou, Giulia Russo, Olena Rzhepishevska, Helmut J F Salzer, Marta Sá Marques, Daniela Schmid, Ivan Solovic, Mariya Sukholytka, Petra Svetina, Mariya Tyufekchieva, Tuula Vasankari, Piret Viiklepp, Kersti Villand, Jiri Wallenfels, Stefan Wesolowski, Anna-Maria Mandalakas, Leonardo Martinez, Dominik Zenner, Christoph Lange, Tbnet Oct 2023

Tuberculosis Incidence In Foreign-Born People Residing In European Countries In 2020, Anca Vasiliu, Niklas Köhler, Ekkehardt Altpeter, Tinna Rán Ægisdóttir, Marina Amerali, Wouter Arrazola De Oñate, Ágnes Bakos, Stefania D'Amato, Daniela Maria Cirillo, Reinout Van Crevel, Edita Davidaviciene, Irène Demuth, Jose Domínguez, Raquel Duarte, Gunar Günther, Jean-Paul Guthmann, Sophia Hatzianastasiou, Louise Hedevang Holm, Zaida Herrador, Urška Hribar, Conny Huberty, Elmira Ibraim, Sarah Jackson, Mogens Jensenius, Kamilla Sigridur Josefsdottir, Anders Koch, Maria Korzeniewska-Kosela, Liga Kuksa, Heinke Kunst, Christian Lienhardt, Beatrice Mahler, Mateja Janković Makek, Inge Muylle, Johan Normark, Analita Pace-Asciak, Goranka Petrović, Despo Pieridou, Giulia Russo, Olena Rzhepishevska, Helmut J F Salzer, Marta Sá Marques, Daniela Schmid, Ivan Solovic, Mariya Sukholytka, Petra Svetina, Mariya Tyufekchieva, Tuula Vasankari, Piret Viiklepp, Kersti Villand, Jiri Wallenfels, Stefan Wesolowski, Anna-Maria Mandalakas, Leonardo Martinez, Dominik Zenner, Christoph Lange, Tbnet

Faculty, Staff and Students Publications

Background

European-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.

Aim

We aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.

Methods

The Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries …


Review Of Toxocariasis At A Children's Hospital Prompting Need For Public Health Interventions, Mary B Fortini, Timothy A Erickson, Lauren M Leining, Karina M Robinson, Megan N Carey, Sarah J Smith, Brendan Sullivan, Alisa R Nelson, Sarah M Gunter, Jill E Weatherhead Oct 2023

Review Of Toxocariasis At A Children's Hospital Prompting Need For Public Health Interventions, Mary B Fortini, Timothy A Erickson, Lauren M Leining, Karina M Robinson, Megan N Carey, Sarah J Smith, Brendan Sullivan, Alisa R Nelson, Sarah M Gunter, Jill E Weatherhead

Faculty, Staff and Students Publications

BACKGROUND: Toxocariasis, caused the by dog and cat roundworm, is one of the most common zoonotic helminth infections in the United States and can lead to severe lifelong morbidity in children. Although historical seroprevalence studies have identified a high frequency of toxocariasis regionally in the United States, there are few studies linking epidemiology and clinical disease in children. The study objective was to examine the contemporary epidemiology of pediatric toxocariasis within an endemic US region.

METHODS: We conducted an epidemiologic study analyzing children diagnosed with toxocariasis presenting to a tertiary pediatric hospital in Texas from 2010 to 2021. We examined …


A Novel Pathogenic Mutation Of Mecp2 Impairs Chromatin Association Independent Of Protein Levels, Jian Zhou, Claudia Cattoglio, Yingyao Shao, Harini P Tirumala, Carlo Vetralla, Sameer S Bajikar, Yan Li, Hu Chen, Qi Wang, Zhenyu Wu, Bing Tang, Mahla Zahabiyon, Aleksandar Bajic, Xiangling Meng, Jack J Ferrie, Anel Lagrone, Ping Zhang, Jean J Kim, Jianrong Tang, Zhandong Liu, Xavier Darzacq, Nathaniel Heintz, Robert Tjian, Huda Y Zoghbi Oct 2023

A Novel Pathogenic Mutation Of Mecp2 Impairs Chromatin Association Independent Of Protein Levels, Jian Zhou, Claudia Cattoglio, Yingyao Shao, Harini P Tirumala, Carlo Vetralla, Sameer S Bajikar, Yan Li, Hu Chen, Qi Wang, Zhenyu Wu, Bing Tang, Mahla Zahabiyon, Aleksandar Bajic, Xiangling Meng, Jack J Ferrie, Anel Lagrone, Ping Zhang, Jean J Kim, Jianrong Tang, Zhandong Liu, Xavier Darzacq, Nathaniel Heintz, Robert Tjian, Huda Y Zoghbi

Faculty, Staff and Students Publications

Loss-of-function mutations in MECP2 cause Rett syndrome (RTT), a severe neurological disorder that mainly affects girls. Mutations in MECP2 do occur in males occasionally and typically cause severe encephalopathy and premature lethality. Recently, we identified a missense mutation (c.353G>A, p.Gly118Glu [G118E]), which has never been seen before in MECP2, in a young boy who suffered from progressive motor dysfunction and developmental delay. To determine whether this variant caused the clinical symptoms and study its functional consequences, we established two disease models, including human neurons from patient-derived iPSCs and a knock-in mouse line. G118E mutation partially reduces MeCP2 abundance …


Atrial Septal Defect Closure Is Associated With Improved Clinical Status In Patients ≤ 10 Kg With Bronchopulmonary Dysplasia, Melissa K Webb, Milenka Cuevas Guaman, S Kristen Sexson Tejtel, Neil Cambronero, Ryan D Coleman, Corey A Chartan, Betul Yilmaz Furtun, Shaine A Morris, Nidhy P Varghese, Natalie M Villafranco Oct 2023

Atrial Septal Defect Closure Is Associated With Improved Clinical Status In Patients ≤ 10 Kg With Bronchopulmonary Dysplasia, Melissa K Webb, Milenka Cuevas Guaman, S Kristen Sexson Tejtel, Neil Cambronero, Ryan D Coleman, Corey A Chartan, Betul Yilmaz Furtun, Shaine A Morris, Nidhy P Varghese, Natalie M Villafranco

Faculty, Staff and Students Publications

Patients with bronchopulmonary dysplasia (BPD) have shown clinical improvement after secundum atrial septal defect (ASD) closure. We sought to determine if this post‐ASD closure improvement is secondary to the expected course in BPD patients or related to the closure itself. A novel BPD‐ASD score was created to assess patients' clinical status (higher score = worse disease) and applied to 10 BPD‐ASD inpatients weighing ≤ 10 kg who underwent ASD closure. The score and its subcomponents were retrospectively calculated serially ranging from 8 weeks pre‐ to 8 weeks post‐intervention, and pre‐ and post‐intervention score slopes were created. These slopes were compared …


Intraductal Suture Leading To Biliary Stone Formation And Recurrent Obstruction And Cholangitis: Cholangioscopy-Guided Forceps Removal, Najib Nassani, Fares Ayoub, Grace Kim, Uzma D Siddiqui Oct 2023

Intraductal Suture Leading To Biliary Stone Formation And Recurrent Obstruction And Cholangitis: Cholangioscopy-Guided Forceps Removal, Najib Nassani, Fares Ayoub, Grace Kim, Uzma D Siddiqui

Faculty, Staff and Students Publications

Intraductal suture leading to biliary stone formation.


A Pancreatic Player In Dementia: Pathological Role For Islet Amyloid Polypeptide Accumulation In The Brain, Angelina S Bortoletto, Ronald J Parchem Oct 2023

A Pancreatic Player In Dementia: Pathological Role For Islet Amyloid Polypeptide Accumulation In The Brain, Angelina S Bortoletto, Ronald J Parchem

Faculty, Staff and Students Publications

Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia. While multiple factors contribute to this predisposition, one of these involves the increased secretion of amylin, or islet amyloid polypeptide, that accompanies the pathophysiology of type 2 diabetes mellitus. Islet amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia, including Alzheimer’s disease and vascular dementia, but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are unclear. In this review, we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage, ultimately leading to …


Mammalian Aging Driven By Transcription Going Awry, Brenna S Mccauley, Weiwei Dang Oct 2023

Mammalian Aging Driven By Transcription Going Awry, Brenna S Mccauley, Weiwei Dang

Faculty, Staff and Students Publications

The mechanisms that underlie increased cryptic transcription during senescence and aging have been poorly understood. Sen et al. recently identified cryptic transcription start sites (cTSSs) and chromatin state changes that may contribute to cTSS activation in mammals. Their results indicate that enhancer-promoter conversion may drive cryptic transcription in senescence.


Prevalence Of Pathogenic Germline Variants In Adult-Type Diffuse Glioma, Malcolm F Mcdonald, Lyndsey L Prather, Cassandra R Helfer, Ethan B Ludmir, Alfredo E Echeverria, Shlomit Yust-Katz, Akash J Patel, Benjamin Deneen, Ganesh Rao, Ali Jalali, Shweta U Dhar, Chris I Amos, Jacob J Mandel Oct 2023

Prevalence Of Pathogenic Germline Variants In Adult-Type Diffuse Glioma, Malcolm F Mcdonald, Lyndsey L Prather, Cassandra R Helfer, Ethan B Ludmir, Alfredo E Echeverria, Shlomit Yust-Katz, Akash J Patel, Benjamin Deneen, Ganesh Rao, Ali Jalali, Shweta U Dhar, Chris I Amos, Jacob J Mandel

Faculty, Staff and Students Publications

BACKGROUND: No consensus germline testing guidelines currently exist for glioma patients, so the prevalence of germline pathogenic variants remains unknown. This study aims to determine the prevalence and type of pathogenic germline variants in adult glioma.

METHODS: A retrospective review at a single institution with paired tumor/normal sequencing from August 2018-April 2022 was performed and corresponding clinical data were collected.

RESULTS: We identified 152 glioma patients of which 15 (9.8%) had pathogenic germline variants. Pathogenic germline variants were seen in 11/84 (13.1%) of Glioblastoma, IDH wild type; 3/42 (7.1%) of Astrocytoma, IDH mutant; and 1/26 (3.8%) of Oligodendroglioma, IDH mutant, …


Scalable Nanopore Sequencing Of Human Genomes Provides A Comprehensive View Of Haplotype-Resolved Variation And Methylation, Mikhail Kolmogorov, Kimberley J Billingsley, Mira Mastoras, Melissa Meredith, Jean Monlong, Ryan Lorig-Roach, Mobin Asri, Pilar Alvarez Jerez, Laksh Malik, Ramita Dewan, Xylena Reed, Rylee M Genner, Kensuke Daida, Sairam Behera, Kishwar Shafin, Trevor Pesout, Jeshuwin Prabakaran, Paolo Carnevali, Jianzhi Yang, Arang Rhie, Sonja W Scholz, Bryan J Traynor, Karen H Miga, Miten Jain, Winston Timp, Adam M Phillippy, Mark Chaisson, Fritz J Sedlazeck, Cornelis Blauwendraat, Benedict Paten Oct 2023

Scalable Nanopore Sequencing Of Human Genomes Provides A Comprehensive View Of Haplotype-Resolved Variation And Methylation, Mikhail Kolmogorov, Kimberley J Billingsley, Mira Mastoras, Melissa Meredith, Jean Monlong, Ryan Lorig-Roach, Mobin Asri, Pilar Alvarez Jerez, Laksh Malik, Ramita Dewan, Xylena Reed, Rylee M Genner, Kensuke Daida, Sairam Behera, Kishwar Shafin, Trevor Pesout, Jeshuwin Prabakaran, Paolo Carnevali, Jianzhi Yang, Arang Rhie, Sonja W Scholz, Bryan J Traynor, Karen H Miga, Miten Jain, Winston Timp, Adam M Phillippy, Mark Chaisson, Fritz J Sedlazeck, Cornelis Blauwendraat, Benedict Paten

Faculty, Staff and Students Publications

Long-read sequencing technologies substantially overcome the limitations of short-reads but have not been considered as a feasible replacement for population-scale projects, being a combination of too expensive, not scalable enough or too error-prone. Here we develop an efficient and scalable wet lab and computational protocol, Napu, for Oxford Nanopore Technologies long-read sequencing that seeks to address those limitations. We applied our protocol to cell lines and brain tissue samples as part of a pilot project for the National Institutes of Health Center for Alzheimer's and Related Dementias. Using a single PromethION flow cell, we can detect single nucleotide polymorphisms with …


Current Perspectives On Mass Spectrometry-Based Immunopeptidomics: The Computational Angle To Tumor Antigen Discovery, Bing Zhang, Michal Bassani-Sternberg Oct 2023

Current Perspectives On Mass Spectrometry-Based Immunopeptidomics: The Computational Angle To Tumor Antigen Discovery, Bing Zhang, Michal Bassani-Sternberg

Faculty, Staff and Students Publications

Identification of tumor antigens presented by the human leucocyte antigen (HLA) molecules is essential for the design of effective and safe cancer immunotherapies that rely on T cell recognition and killing of tumor cells. Mass spectrometry (MS)-based immunopeptidomics enables high-throughput, direct identification of HLA-bound peptides from a variety of cell lines, tumor tissues, and healthy tissues. It involves immunoaffinity purification of HLA complexes followed by MS profiling of the extracted peptides using data-dependent acquisition, data-independent acquisition, or targeted approaches. By incorporating DNA, RNA, and ribosome sequencing data into immunopeptidomics data analysis, the proteogenomic approach provides a powerful means for identifying …


Neurodevelopmental Deficits And Cell-Type-Specific Transcriptomic Perturbations In A Mouse Model Of Hnrnpu Haploinsufficiency, Sarah A Dugger, Ryan S Dhindsa, Gabriela De Almeida Sampaio, Andrew K Ressler, Elizabeth E Rafikian, Sabrina Petri, Verity A Letts, Jiajie Teoh, Junqiang Ye, Sophie Colombo, Yueqing Peng, Mu Yang, Michael J Boland, Wayne N Frankel, David B Goldstein Oct 2023

Neurodevelopmental Deficits And Cell-Type-Specific Transcriptomic Perturbations In A Mouse Model Of Hnrnpu Haploinsufficiency, Sarah A Dugger, Ryan S Dhindsa, Gabriela De Almeida Sampaio, Andrew K Ressler, Elizabeth E Rafikian, Sabrina Petri, Verity A Letts, Jiajie Teoh, Junqiang Ye, Sophie Colombo, Yueqing Peng, Mu Yang, Michael J Boland, Wayne N Frankel, David B Goldstein

Faculty, Staff and Students Publications

Heterozygous de novo loss-of-function mutations in the gene expression regulator HNRNPU cause an early-onset developmental and epileptic encephalopathy. To gain insight into pathological mechanisms and lay the potential groundwork for developing targeted therapies, we characterized the neurophysiologic and cell-type-specific transcriptomic consequences of a mouse model of HNRNPU haploinsufficiency. Heterozygous mutants demonstrated global developmental delay, impaired ultrasonic vocalizations, cognitive dysfunction and increased seizure susceptibility, thus modeling aspects of the human disease. Single-cell RNA-sequencing of hippocampal and neocortical cells revealed widespread, yet modest, dysregulation of gene expression across mutant neuronal subtypes. We observed an increased burden of differentially-expressed genes in mutant excitatory …


Views Of Adolescents And Young Adults With Cancer And Their Oncologists Toward Patients' Participation In Genomic Research, Amanda M Gutierrez, Jill O Robinson, Robin Raesz-Martinez, Isabel Canfield, Mary A Majumder, Sarah Scollon, Lauren R Desrosiers, Rebecca L Hsu, Wendy Allen-Rhoades, D Williams Parsons, Sharon E Plon, Amy L Mcguire, Janet Malek Oct 2023

Views Of Adolescents And Young Adults With Cancer And Their Oncologists Toward Patients' Participation In Genomic Research, Amanda M Gutierrez, Jill O Robinson, Robin Raesz-Martinez, Isabel Canfield, Mary A Majumder, Sarah Scollon, Lauren R Desrosiers, Rebecca L Hsu, Wendy Allen-Rhoades, D Williams Parsons, Sharon E Plon, Amy L Mcguire, Janet Malek

Faculty, Staff and Students Publications

Purpose:

With increased use of genomic testing in cancer research and clinical care, it is important to understand the perspectives and decision-making preferences of adolescents and young adults (AYAs) with cancer and their treating oncologists.

Methods:

We conducted an interview substudy of the BASIC3 Study, which enrolled newly diagnosed cancer patients <18 years of age with assent. Of 32 young adults (YAs) with cancer who reached the age of majority (AOM; 18 years) while on study, 12 were successfully approached and all consented to study continuation at AOM. Of those, seven completed an interview. Patients' oncologists, who enrolled and participated in return of clinical genomic results, were also interviewed (n = 12). Interviews were transcribed, deidentified, and analyzed using thematic analysis.

Results:

YAs cited the possibility of helping others and advancing science as major reasons for their assent to initial study enrollment and their willingness to consent at AOM. YAs thought obtaining informed consent from research participants for …


Cardiac Magnetic Resonance Imaging To Determine Single Ventricle Function In A Pediatric Population Is Feasible In A Large Trial Setting: Experience From The Single Ventricle Reconstruction Trial Longitudinal Follow Up, Jon Detterich, Michael D Taylor, Timothy C Slesnick, Michael Dilorenzo, Anthony Hlavacek, Christopher Z Lam, Shagun Sachdeva, Sean M Lang, M Jay Campbell, Jennifer Gerardin, Kevin K Whitehead, Rahul H Rathod, Mark Cartoski, Shaji Menon, Felicia Trachtenberg, Russell Gongwer, Jane Newburger, Caren Goldberg, Adam L Dorfman, The Pediatric Heart Network Investigators Oct 2023

Cardiac Magnetic Resonance Imaging To Determine Single Ventricle Function In A Pediatric Population Is Feasible In A Large Trial Setting: Experience From The Single Ventricle Reconstruction Trial Longitudinal Follow Up, Jon Detterich, Michael D Taylor, Timothy C Slesnick, Michael Dilorenzo, Anthony Hlavacek, Christopher Z Lam, Shagun Sachdeva, Sean M Lang, M Jay Campbell, Jennifer Gerardin, Kevin K Whitehead, Rahul H Rathod, Mark Cartoski, Shaji Menon, Felicia Trachtenberg, Russell Gongwer, Jane Newburger, Caren Goldberg, Adam L Dorfman, The Pediatric Heart Network Investigators

Faculty, Staff and Students Publications

The Single Ventricle Reconstruction (SVR) Trial was a randomized prospective trial designed to determine survival advantage of the modified Blalock-Taussig-Thomas shunt (BTTS) vs the right ventricle to pulmonary artery conduit (RVPAS) for patients with hypoplastic left heart syndrome. The primary aim of the long-term follow-up (SVRIII) was to determine the impact of shunt type on RV function. In this work, we describe the use of CMR in a large cohort follow up from the SVR Trial as a focused study of single ventricle function. The SVRIII protocol included short axis steady-state free precession imaging to assess single ventricle systolic function …


A Retrospective Review Of Social Deprivation Index And Maternal Outcomes With Placenta Accreta Spectrum From A Single Referral Center, Alison N Goulding, Karin A Fox, Christina C Reed, Bahram Salmanian, Alireza A Shamshirsaz, Kjersti M Aagaard Oct 2023

A Retrospective Review Of Social Deprivation Index And Maternal Outcomes With Placenta Accreta Spectrum From A Single Referral Center, Alison N Goulding, Karin A Fox, Christina C Reed, Bahram Salmanian, Alireza A Shamshirsaz, Kjersti M Aagaard

Faculty, Staff and Students Publications

Objective

Little is known about how community characteristics influence placenta accreta spectrum (PAS) outcomes. Our objective was to evaluate whether adverse maternal outcomes among pregnant people (gravidae) with PAS delivering at a single referral center differ by community-level measures of social deprivation.

Study Design

We conducted a retrospective cohort study of singleton gravidae with histopathology confirmed PAS delivering from January 2011 to June 2021 at a referral center. Data abstraction collected relevant patient information, including resident zip code, which was linked to Social Deprivation Index (SDI) score (a measure of area-level social deprivation). SDI scores were divided into quartiles for …


Single Cell Analysis Of Short-Term Dry Eye Induced Changes In Cornea Immune Cell Populations, Brandon D Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K Gupta, Edward Holland, Paul M Karpecki, Richard Lindstrom, Kelly K Nichols, Stephen C Pflugfelder, Christopher E Starr, Elizabeth Yeu Oct 2023

Single Cell Analysis Of Short-Term Dry Eye Induced Changes In Cornea Immune Cell Populations, Brandon D Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K Gupta, Edward Holland, Paul M Karpecki, Richard Lindstrom, Kelly K Nichols, Stephen C Pflugfelder, Christopher E Starr, Elizabeth Yeu

Faculty, Staff and Students Publications

BACKGROUND: Twelve ocular surface disease experts convened to achieve consensus about Demodex blepharitis (DB) using a modified Delphi panel process.

METHODS: Online surveys were administered using scaled, open-ended, true/false, and multiple-choice questions. Consensus for questions using a 1 to 9 Likert scale was predefined as median scores of 7-9 and 1-3. For other question types, consensus was achieved when 8 of 12 panellists agreed. Questions were randomized, and results of each survey informed the following survey.

RESULTS: Twelve practitioners comprised the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH). Following 3 surveys, experts agreed that DB is chronic (n …


Leveraging Cd4 Cell Count At Entry Into Care To Monitor Success Of Human Immunodeficiency Virus Prevention, Treatment, And Public Health Programming In The Greater St Louis Area Between 2017 And 2020, Lindsey M Filiatreau, Aaloke Mody, Daniel Vo, Cory Bradley, Aditi Ramakrishnan, Julia López, Jane O'Halloran, Anne Trolard, William G Powderly, Elvin H Geng Oct 2023

Leveraging Cd4 Cell Count At Entry Into Care To Monitor Success Of Human Immunodeficiency Virus Prevention, Treatment, And Public Health Programming In The Greater St Louis Area Between 2017 And 2020, Lindsey M Filiatreau, Aaloke Mody, Daniel Vo, Cory Bradley, Aditi Ramakrishnan, Julia López, Jane O'Halloran, Anne Trolard, William G Powderly, Elvin H Geng

2020-Current year OA Pubs

CD4 cell count at entry into human immunodeficiency virus (HIV) care is a useful indicator of success of multiple steps in HIV public health programming. We demonstrate that CD4 cell count at care initiation was stable in St Louis between 2017 and 2019 but declined in 2020. Missouri efforts in the Ending the HIV Epidemic plan should focus on rapidly identifying individuals with undiagnosed HIV infection.


Clinical Classification Of Variants In The Valosin-Containing Protein Gene Associated With Multisystem Proteinopathy, Marianela Schiava, Jil Daw, Conrad Chris Weihl, Et Al. Oct 2023

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 …


The Vcam1-Apoe Pathway Directs Microglial Chemotaxis And Alleviates Alzheimer's Disease Pathology, Shun-Fat Lau, Wei Wu, Hiu Yi Wong, Li Ouyang, Yi Qiao, Jiahui Xu, Jessica Hiu-Yan Lau, Carlton Wong, Yuanbing Jiang, David M Holtzman, Amy K Y Fu, Nancy Y Ip Oct 2023

The Vcam1-Apoe Pathway Directs Microglial Chemotaxis And Alleviates Alzheimer's Disease Pathology, Shun-Fat Lau, Wei Wu, Hiu Yi Wong, Li Ouyang, Yi Qiao, Jiahui Xu, Jessica Hiu-Yan Lau, Carlton Wong, Yuanbing Jiang, David M Holtzman, Amy K Y Fu, Nancy Y Ip

2020-Current year OA Pubs

In Alzheimer's disease (AD), sensome receptor dysfunction impairs microglial danger-associated molecular pattern (DAMP) clearance and exacerbates disease pathology. Although extrinsic signals, including interleukin-33 (IL-33), can restore microglial DAMP clearance, it remains largely unclear how the sensome receptor is regulated and interacts with DAMP during phagocytic clearance. Here, we show that IL-33 induces VCAM1 in microglia, which promotes microglial chemotaxis toward amyloid-beta (Aβ) plaque-associated ApoE, and leads to Aβ clearance. We show that IL-33 stimulates a chemotactic state in microglia, characterized by Aβ-directed migration. Functional screening identified that VCAM1 directs microglial Aβ chemotaxis by sensing Aβ plaque-associated ApoE. Moreover, we found …