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Contraceptive Uptake In Postpartum People With And Without Opioid Use Disorder And Opioid Use With Co-Occurring Substance Use, Jennifer K Bello, Kevin Y Xu, Joanne Salas, Jeannie Kelly, Richard A Grucza Sep 2024

Contraceptive Uptake In Postpartum People With And Without Opioid Use Disorder And Opioid Use With Co-Occurring Substance Use, Jennifer K Bello, Kevin Y Xu, Joanne Salas, Jeannie Kelly, Richard A Grucza

2020-Current year OA Pubs

BACKGROUND: Using contraception to delay pregnancy allows people with opioid use disorder (OUD) to choose when they are ready to continue their families. Yet, postpartum contraceptive uptake among people with OUD has not been well characterized.

METHODS: Analyses used 73,811 pregnancy episodes among 61,221 people (2016-2021) from the St. Louis University-SSM Virtual Data Warehouse. OUD was defined from the year prior and through pregnancy. Contraceptive uptake was defined within 90-days after delivery. We used Generalized Estimating Equations-type multinomial logit models to assess association of OUD +/- co-occurring substance use disorders (SUDs) with any contraception (yes/no) and type of contraception (effective …


Dynamic Changes In Circulating Tumor Fraction As A Predictor Of Real-World Clinical Outcomes In Solid Tumor Malignancy Patients Treated With Immunotherapy, Ryan D Gentzler, Aadel A Chaudhuri, Et Al. Sep 2024

Dynamic Changes In Circulating Tumor Fraction As A Predictor Of Real-World Clinical Outcomes In Solid Tumor Malignancy Patients Treated With Immunotherapy, Ryan D Gentzler, Aadel A Chaudhuri, Et Al.

2020-Current year OA Pubs

INTRODUCTION: A dynamic molecular biomarker that can identify early efficacy of immune checkpoint inhibitor (ICI) therapy remains an unmet clinical need. Here we evaluate if a novel circulating tumor DNA (ctDNA) assay, xM, used for treatment response monitoring (TRM), that quantifies changes in ctDNA tumor fraction (TF), can predict outcome benefits in patients treated with ICI alone or in combination with chemotherapy in a real-world (RW) cohort.

METHODS: This retrospective study consisted of patients with advanced cancer from the Tempus de-identified clinical genomic database who received longitudinal liquid-based next-generation sequencing. Eligible patients had a blood sample ≤ 40 days prior …


Genetic Risk Accentuates Dietary Effects On Hepatic Steatosis, Inflammation And Fibrosis In A Population-Based Cohort, Vincent L Chen, Xiaomeng Du, Antonino Oliveri, Yanhua Chen, Annapurna Kuppa, Brian D Halligan, Michael A Province, Elizabeth K Speliotes Sep 2024

Genetic Risk Accentuates Dietary Effects On Hepatic Steatosis, Inflammation And Fibrosis In A Population-Based Cohort, Vincent L Chen, Xiaomeng Du, Antonino Oliveri, Yanhua Chen, Annapurna Kuppa, Brian D Halligan, Michael A Province, Elizabeth K Speliotes

2020-Current year OA Pubs

BACKGROUND & AIMS: Steatotic liver disease (SLD), characterized by elevated liver fat content (LFC), is influenced by genetics and diet. However, whether diet has a differential effect based on genetic risk is not well-characterized. We aimed to determine how genetic factors interact with diet to affect SLD in a large national biobank.

METHODS: We included UK Biobank participants with dietary intake measured by 24-hour recall and genotyping. The primary predictors were dietary pattern, PNPLA3-rs738409-G, TM6SF2-rs58542926-T, a 16-variant hepatic steatosis polygenic risk score (PRS), and gene-environment interactions. The primary outcome was LFC, and secondary outcomes were iron-controlled T1 time (cT1, a …


The Long And Winding Road Towards New Treatments Against Lymphatic Filariasis And Onchocerciasis, Frederic Risch, Alexander Kazakov, Sabine Specht, Kenneth Pfarr, Peter U Fischer, Achim Hoerauf, Marc P Hübner Sep 2024

The Long And Winding Road Towards New Treatments Against Lymphatic Filariasis And Onchocerciasis, Frederic Risch, Alexander Kazakov, Sabine Specht, Kenneth Pfarr, Peter U Fischer, Achim Hoerauf, Marc P Hübner

2020-Current year OA Pubs

Although lymphatic filariasis and onchocerciasis have been targeted for global elimination, these helminth infections are still a major public health problem across the tropics and subtropics. Despite decades of research, treatment options remain limited and drugs that completely clear the infections, and can be used on a large scale, are still unavailable. In the present review we discuss the strengths and weaknesses of currently available treatments and new ones in development. Novel candidates (corallopyronin A, DNDi-6166, emodepside, and oxfendazole) are currently moving through (pre)clinical development, while the development of two candidates (AWZ1066S and ABBV-4083/flubentylosin) was recently halted. The preclinical R&D …


The Physiologic Basis Of Molecular Therapeutics For Peripheral Nerve Injury: A Primer, Marie C Spezia, Christopher J Dy, David M Brogan Sep 2024

The Physiologic Basis Of Molecular Therapeutics For Peripheral Nerve Injury: A Primer, Marie C Spezia, Christopher J Dy, David M Brogan

2020-Current year OA Pubs

Peripheral nerve injuries affect a significant number of patients who experience trauma affecting the hand and upper extremity. Improving unsatisfactory outcomes from repair of these injuries remains a clinical challenge despite advancements in microsurgical repair. Imperfections of the nerve regeneration process, including imprecise reinnervation, distal axon degradation, and muscular atrophy, complicate the repair process. However, the capacity for peripheral nerves to regenerate offers an avenue for therapeutic advancement. Regeneration is a temporally and spatially dynamic process coordinated by Schwann cells and neurons among other cell types. Neurotrophic factors are a primary means of controlling cell growth and differentiation in the …


Endogenous Base Damage As A Driver Of Genomic Instability In Homologous Recombination-Deficient Cancers, Lindsey N Aubuchon, Priyanka Verma Sep 2024

Endogenous Base Damage As A Driver Of Genomic Instability In Homologous Recombination-Deficient Cancers, Lindsey N Aubuchon, Priyanka Verma

2020-Current year OA Pubs

Homologous recombination (HR) is a high-fidelity DNA double-strand break (DSB) repair pathway. Both familial and somatic loss of function mutation(s) in various HR genes predispose to a variety of cancer types, underscoring the importance of error-free repair of DSBs in human physiology. While environmental sources of DSBs have been known, more recent studies have begun to uncover the role of endogenous base damage in leading to these breaks. Base damage repair intermediates often consist of single-strand breaks, which if left unrepaired, can lead to DSBs as the replication fork encounters these lesions. This review summarizes various sources of endogenous base …


Cyclic Testing Of Six-Strand Suture Techniques For Zone 2 Flexor Tendon Lacerations, Nozomu Kusano, Melissa A Zaegel, Matthew J Silva Sep 2024

Cyclic Testing Of Six-Strand Suture Techniques For Zone 2 Flexor Tendon Lacerations, Nozomu Kusano, Melissa A Zaegel, Matthew J Silva

2020-Current year OA Pubs

BACKGROUND: Biomechanical analysis using cyclic testing for repaired flexor tendons is a clinically relevant method. The aim of this study was to evaluate the tensile properties of two six-strand suture techniques, the triple looped suture and Yoshizu #1 suture techniques using cyclic testing under simulating early active mobilization conditions.

METHODS: Twenty-five flexor digitorum profundus tendons harvested from fresh frozen human cadaver hands were repaired in zone 2 utilizing one of three repair techniques: the 2-strand modified Kessler (MK) technique as a control, the triple looped suture (TLS) and Yoshizu #1 suture (Y1) techniques. In each suture technique, 4-0 monofilament nylon …


Tissue-Specific Features Of Innate Lymphoid Cells In Antiviral Defense, Sytse J Piersma Sep 2024

Tissue-Specific Features Of Innate Lymphoid Cells In Antiviral Defense, Sytse J Piersma

2020-Current year OA Pubs

Innate lymphocytes (ILCs) rapidly respond to and protect against invading pathogens and cancer. ILCs include natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer (LTi) cells and include type I, type II, and type III immune cells. While NK cells have been well recognized for their role in antiviral immunity, other ILC subtypes are emerging as players in antiviral defense. Each ILC subset has specialized functions that uniquely impact the antiviral immunity and health of the host depending on the tissue microenvironment. This review focuses on the specialized functions of each ILC subtype and their roles in antiviral …


First Case Of Hiv Seroconversion With Integrase Resistance Mutations On Long-Acting Cabotegravir For Prevention In Routine Care, Catherine A Koss, Rupa R Patel, Et Al. Sep 2024

First Case Of Hiv Seroconversion With Integrase Resistance Mutations On Long-Acting Cabotegravir For Prevention In Routine Care, Catherine A Koss, Rupa R Patel, Et Al.

2020-Current year OA Pubs

BACKGROUND: Long-acting cabotegravir (CAB-LA) is highly effective for HIV prevention, but delayed HIV diagnoses and integrase strand transfer inhibitor (INSTI) resistance were observed in trials. We report the first case in routine clinical care of HIV infection on CAB-LA with INSTI resistance.

METHODS: The SeroPrEP study enrolls individuals in the United States who acquire HIV on pre-exposure prophylaxis modalities to assess diagnostics, antiretroviral (ARV) drug levels, resistance, and treatment outcomes. Resistance mutations in full-length HIV-1 integrase were identified by single-genome sequencing (SGS). Cabotegravir concentrations in plasma and hair segments were measured by liquid chromatography-tandem mass spectrometry.

RESULTS: A 23-year-old gender-nonbinary …


Comprehensive Molecular Profiling Of Multiple Myeloma Identifies Refined Copy Number And Expression Subtypes, Sheri Skerget, Ravi Vij, Et Al. Sep 2024

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

2020-Current year OA Pubs

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


Influenza Vaccination Stimulates Maturation Of The Human T Follicular Helper Cell Response, Stefan A Schattgen, Jackson S Turner, Aaron J Schmitz, Julian Q Zhou, Wooseob Kim, Katherine M Mcintire, Alem Haile, Michael K Klebert, Teresa Suessen, William D Middleton, Sharlene A Teefey, Rachel M Presti, Ali H Ellebedy, Et Al. Sep 2024

Influenza Vaccination Stimulates Maturation Of The Human T Follicular Helper Cell Response, Stefan A Schattgen, Jackson S Turner, Aaron J Schmitz, Julian Q Zhou, Wooseob Kim, Katherine M Mcintire, Alem Haile, Michael K Klebert, Teresa Suessen, William D Middleton, Sharlene A Teefey, Rachel M Presti, Ali H Ellebedy, Et Al.

2020-Current year OA Pubs

The differentiation and specificity of human CD4


Frontostriatal Salience Network Expansion In Individuals In Depression, Charles J Lynch, Evan M Gordon, Et Al. Sep 2024

Frontostriatal Salience Network Expansion In Individuals In Depression, Charles J Lynch, Evan M Gordon, Et Al.

2020-Current year OA Pubs

Decades of neuroimaging studies have shown modest differences in brain structure and connectivity in depression, hindering mechanistic insights or the identification of risk factors for disease onset


Repeat Modules And N-Linked Glycans Define Structure And Antigenicity Of A Critical Enterotoxigenic E. Coli Adhesin, Zachary T. Berndsen, Marjahan Akhtar, Mahima Thapa, Tim J. Vickers, Aaron Schmitz, Pardeep Kumar, Nazia Khatoon, Alaullah Sheikh, Melissa Hamrick, Jackson S. Turner, Ali H. Ellebedy, James M. Fleckenstein, Et Al. Sep 2024

Repeat Modules And N-Linked Glycans Define Structure And Antigenicity Of A Critical Enterotoxigenic E. Coli Adhesin, Zachary T. Berndsen, Marjahan Akhtar, Mahima Thapa, Tim J. Vickers, Aaron Schmitz, Pardeep Kumar, Nazia Khatoon, Alaullah Sheikh, Melissa Hamrick, Jackson S. Turner, Ali H. Ellebedy, James M. Fleckenstein, Et Al.

2020-Current year OA Pubs

Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of cases of infectious diarrhea annually, predominantly in children from low-middle income regions. Notably, in children, as well as volunteers challenged with ETEC, diarrheal severity is significantly increased in blood group A (bgA) individuals. EtpA, is a secreted glycoprotein adhesin that functions as a blood group A lectin to promote critical interactions between ETEC and blood group A glycans on intestinal epithelia for effective bacterial adhesion and toxin delivery. EtpA is highly immunogenic resulting in robust antibody responses following natural infection and experimental challenge of volunteers with ETEC. To understand how EtpA …


Rhesus Rotavirus Nsp1 Mediates Extra-Intestinal Infection And Is A Contributing Factor For Biliary Obstruction, Enkai Li, Ningguo Feng, Qiru Zeng, Liliana Sanchez-Tacuba, Takahiro Kawagishi, Grace Branham, Gaopeng Hou, Zemin Wang, Harry B. Greenberg, Siyuan Ding Sep 2024

Rhesus Rotavirus Nsp1 Mediates Extra-Intestinal Infection And Is A Contributing Factor For Biliary Obstruction, Enkai Li, Ningguo Feng, Qiru Zeng, Liliana Sanchez-Tacuba, Takahiro Kawagishi, Grace Branham, Gaopeng Hou, Zemin Wang, Harry B. Greenberg, Siyuan Ding

2020-Current year OA Pubs

We previously demonstrated that in Ifnar1-/-Ifngr1-/- or Stat1-/- suckling mice lacking intact type I and type II interferon (IFN) signaling, rhesus rotavirus (RRV) infection causes a lethal disease with clinical manifestations similar to biliary atresia, including acholic stools, oily fur, growth retardation, and excess mortality. Elevated levels of viral RNA are detected in the bile ducts and liver of diseased pups together with severe inflammatory responses in these tissues. However, the viral determinants and the molecular mechanisms driving this process remain incompletely understood. Using an optimized rotavirus (RV) reverse genetics system, we generated a panel of recombinant RVs that encode …


Outcomes Of Double-Valve Surgery For Infective Endocarditis Are Improving In The Modern Era, Paighton C Miller, Linda J Schulte, Theodore Marghitu, Shengxiang Huang, Tsuyoshi Kaneko, Ralph J Damiano, Puja Kachroo Sep 2024

Outcomes Of Double-Valve Surgery For Infective Endocarditis Are Improving In The Modern Era, Paighton C Miller, Linda J Schulte, Theodore Marghitu, Shengxiang Huang, Tsuyoshi Kaneko, Ralph J Damiano, Puja Kachroo

2020-Current year OA Pubs

BACKGROUND: The incidence of infective endocarditis (IE) is rapidly increasing. Contemporary outcomes following high-risk double valve surgery (DVS) for IE are not well described.

METHODS: Between 2001 and 2021, 211 patients with IE underwent combined aortic and mitral valve surgery at a tertiary care referral center. Data from the Society of Thoracic Surgeons registry, including demographics, operative details, and outcomes, were collected. Risk factors for 30-day and 1-year-mortality were analyzed. Survival was analyzed using Kaplan-Meier and Cox proportional hazards modeling.

RESULTS: The study cohort had a male preponderance (73%), with a median age of 56 years (interquartile range [IQR], 44 …


Teaching Application Of 3d-Printed Models For Nasal Analysis, Nneoma S. Wamkpah, Robert T. Cristel, Zachary O'Connor, Andrea Hanick, Dennis Nguyen, John J. Chi Sep 2024

Teaching Application Of 3d-Printed Models For Nasal Analysis, Nneoma S. Wamkpah, Robert T. Cristel, Zachary O'Connor, Andrea Hanick, Dennis Nguyen, John J. Chi

2020-Current year OA Pubs

BACKGROUND: A major challenge in learning rhinoplasty is correlating patients' external and internal nasal structures. We aim to explore the application of three dimensional (3D)-printed models of nasal bony-cartilaginous structures in identifying accurate nasal anatomy.

METHODS: Otolaryngology-head and neck surgery and plastic and reconstructive surgery residents matched patient photograph models, described relative nasal bony-cartilaginous anatomy, completed pre- and postactivity self-evaluations (based on otolaryngology "nasal deformity" milestones including "anatomy," "function," "aesthetic," and "etiology"), and rated the 3D-printed models' usefulness. Descriptive statistics were measured.

RESULTS: Thirty-seven residents correctly matched four of six model-photograph pairs and correctly described 15 of 30 anatomic relationships, …


Trem2 On Microglia Cell Surface Binds To And Forms Functional Binary Complexes With Heparan Sulfate Modified With 6-O-Sulfation And Iduronic Acid, Ilayda Ozsan Mcmillan, Li Liang, Guowei Su, Xuehong Song, Kelly Drago, Hua Yang, Claudia Alvarez, Amika Sood, James Gibson, Robert J Woods, Chunyu Wang, Jian Liu, Fuming Zhang, Tom J Brett, Lianchun Wang Sep 2024

Trem2 On Microglia Cell Surface Binds To And Forms Functional Binary Complexes With Heparan Sulfate Modified With 6-O-Sulfation And Iduronic Acid, Ilayda Ozsan Mcmillan, Li Liang, Guowei Su, Xuehong Song, Kelly Drago, Hua Yang, Claudia Alvarez, Amika Sood, James Gibson, Robert J Woods, Chunyu Wang, Jian Liu, Fuming Zhang, Tom J Brett, Lianchun Wang

2020-Current year OA Pubs

The triggering receptor expressed on myeloid cells-2 (TREM2), a pivotal innate immune receptor, orchestrates functions such as inflammatory responses, phagocytosis, cell survival, and neuroprotection. TREM2 variants R47H and R62H have been associated with Alzheimer's disease, yet the underlying mechanisms remain elusive. Our previous research established that TREM2 binds to heparan sulfate (HS) and variants R47H and R62H exhibit reduced affinity for HS. Building upon this groundwork, our current study delves into the interplay between TREM2 and HS and its impact on microglial function. We confirm TREM2's binding to cell surface HS and demonstrate that TREM2 interacts with HS, forming HS-TREM2 …


Malignant Peripheral Nerve Sheath Tumor, A Heterogeneous, Aggressive Cancer With Diverse Biomarkers And No Targeted Standard Of Care: Review Of The Literature And Ongoing Investigational Agents, Neeta Somaiah, Bishnuhari Paudyal, Robert E Winkler, Brian A Van Tine, Angela C Hirbe Sep 2024

Malignant Peripheral Nerve Sheath Tumor, A Heterogeneous, Aggressive Cancer With Diverse Biomarkers And No Targeted Standard Of Care: Review Of The Literature And Ongoing Investigational Agents, Neeta Somaiah, Bishnuhari Paudyal, Robert E Winkler, Brian A Van Tine, Angela C Hirbe

2020-Current year OA Pubs

BACKGROUND: Malignant peripheral sheath tumor (MPNST) is a rare, aggressive form of soft-tissue sarcoma that presents a unique set of diagnostic and treatment challenges and is associated with major unmet treatment medical needs.

OBJECTIVE: The chief aim of this review is to consider the epidemiology, histology, anatomic distribution, pathologic signaling pathways, diagnosis, and management of MPNST, with a focus on potential targeted therapies. A subordinate objective was to establish benchmarks for the antitumor activity of such treatments.

RESULTS: MPNST has an incidence of 1:100,000 in the general population and 1:3500 among patients with the inherited condition of neurofibromatosis-1. Spindle-cell sarcomas …


A Podcast On Practical Considerations In Patients With Advanced Urothelial Cancer Receiving First-Line Cisplatin- Or Carboplatin-Based Chemotherapy Followed By Avelumab Maintenance In A Changing Therapeutic Landscape, Jun Gong, Melissa A Reimers Sep 2024

A Podcast On Practical Considerations In Patients With Advanced Urothelial Cancer Receiving First-Line Cisplatin- Or Carboplatin-Based Chemotherapy Followed By Avelumab Maintenance In A Changing Therapeutic Landscape, Jun Gong, Melissa A Reimers

2020-Current year OA Pubs

Platinum-based chemotherapy has been the cornerstone of first-line treatment for advanced urothelial carcinoma for decades, based on its proven efficacy and well-characterized safety profile. Although enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy versus platinum-based chemotherapy in the EV-302 phase 3 trial, common and potentially cumulative toxicities associated with EV plus pembrolizumab may make this combination less suitable for some patients, such as those with pre-existing neuropathy, hyperglycemia, or hepatic impairment, or patients likely to have favorable outcomes with platinum-based chemotherapy. The availability of EV plus pembrolizumab in various countries may also be limited by financial considerations. Thus, platinum-based chemotherapy …


Expert Panel Curation Of 31 Genes In Relation To Limb Girdle Muscular Dystrophy, Shruthi Mohan, Kelly Macalalad, Amanda R Clause, Conrad C Weihl, Et Al. Sep 2024

Expert Panel Curation Of 31 Genes In Relation To Limb Girdle Muscular Dystrophy, Shruthi Mohan, Kelly Macalalad, Amanda R Clause, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD.

METHODS: The ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene-disease relationships (GDR) using the ClinGen gene-disease clinical validity framework to evaluate 31 …


Mutant Nrf2e79q Enhances The Promotion And Progression Of A Subset Of Oncogenic Ras Keratinocytes And Skin Tumors, John G Witherspoon, Jonathan R Hall, Dereje Jima, Hannah M Atkins, Nathan T Wamsley, Michael B Major, Bernard E Weissman, Robert C Smart Sep 2024

Mutant Nrf2e79q Enhances The Promotion And Progression Of A Subset Of Oncogenic Ras Keratinocytes And Skin Tumors, John G Witherspoon, Jonathan R Hall, Dereje Jima, Hannah M Atkins, Nathan T Wamsley, Michael B Major, Bernard E Weissman, Robert C Smart

2020-Current year OA Pubs

Squamous cell carcinomas (SCCs), including lung, head & neck, bladder, and skin SCCs often display constitutive activation of the KEAP1-NRF2 pathway. Constitutive activation is achieved through multiple mechanisms, including activating mutations in NFE2L2 (NRF2). To determine the functional consequences of Nrf2 activation on skin SCC development, we assessed the effects of mutant Nrf2


Leveraging Machine Learning To Study How Temperament Scores Predict Pre-Term Birth Status, Erich Seamon, Shannon N Lenze, Et Al. Sep 2024

Leveraging Machine Learning To Study How Temperament Scores Predict Pre-Term Birth Status, Erich Seamon, Shannon N Lenze, Et Al.

2020-Current year OA Pubs

BACKGROUND: Preterm birth (birth at < 37 completed weeks gestation) is a significant public heatlh concern worldwide. Important health, and developmental consequences of preterm birth include altered temperament development, with greater dysregulation and distress proneness.

AIMS: The present study leveraged advanced quantitative techniques, namely machine learning approaches, to discern the contribution of narrowly defined and broadband temperament dimensions to birth status classification (full-term vs. preterm). Along with contributing to the literature addressing temperament of infants born preterm, the present study serves as a methodological demonstration of these innovative statistical techniques.

STUDY DESIGN: This study represents a metanalysis conducted with multiple samples (

SUBJECTS: Participants included infants born preterm and term-born comparison children, either matched on chronological age or age adjusted for prematurity.

OUTCOME MEASURES: Infant Behavior Questionnaire-Revised Very Short Form …


Structure Of A Truncated Human Glcnac-1-Phosphotransferase Variant Reveals The Basis For Its Hyperactivity, Hua Li, Balraj Doray, Benjamin C Jennings, Wang-Sik Lee, Lin Liu, Stuart Kornfeld, Huilin Li Sep 2024

Structure Of A Truncated Human Glcnac-1-Phosphotransferase Variant Reveals The Basis For Its Hyperactivity, Hua Li, Balraj Doray, Benjamin C Jennings, Wang-Sik Lee, Lin Liu, Stuart Kornfeld, Huilin Li

2020-Current year OA Pubs

Mutations that cause loss of function of GlcNAc-1-phosphotransferase (PTase) lead to the lysosomal storage disorder mucolipidosis II. PTase is the key enzyme of the mannose 6-phosphate (M6P) targeting system that is responsible for tagging lysosomal hydrolases with the M6P moiety for their delivery to the lysosome. We had previously generated a truncated hyperactive form of PTase termed S1S3 which was shown to notably increase the phosphorylation level of secreted lysosomal enzymes and enhance their uptake by cells. Here, we report the 3.4 Å cryo-EM structure of soluble S1S3 lacking both transmembrane domains and cytosolic tails. The structure reveals a high …


Evaluating The Psychometric Structure Of The Hamilton Rating Scale For Depression Pre- And Post-Treatment In Antidepressant Randomised Trials: Secondary Analysis Of 6843 Individual Participants From 20 Trials, David Byrne, Frank Doyle, Susan Brannick, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Emma Wallace, Fiona Boland Sep 2024

Evaluating The Psychometric Structure Of The Hamilton Rating Scale For Depression Pre- And Post-Treatment In Antidepressant Randomised Trials: Secondary Analysis Of 6843 Individual Participants From 20 Trials, David Byrne, Frank Doyle, Susan Brannick, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Emma Wallace, Fiona Boland

2020-Current year OA Pubs

BACKGROUND: The 17-item Hamilton Rating Scale for Depression (HRSD-17) is the most popular depression measure in antidepressant clinical trials. Prior evidence indicates poor replicability and inconsistent factorial structure. This has not been studied in pooled randomised trial data, nor has a psychometrically optimal model been developed.

AIMS: To examine the psychometric properties of the HRSD-17 for pre-treatment and post-treatment clinical trial data in a large pooled database of antidepressant randomised controlled trial participants, and to determine an optimal abbreviated version.

METHOD: Data for 6843 participants were obtained from the data repository Vivli.org and randomly split into groups for exploratory (n …


A Systematic Review To Compare Electrical, Magnetic, And Optogenetic Stimulation For Peripheral Nerve Repair, Priya Kaluskar, Dhruv Bharadwaj, K Swaminathan Iyer, Christopher Dy, Minghao Zheng, David M Brogan Sep 2024

A Systematic Review To Compare Electrical, Magnetic, And Optogenetic Stimulation For Peripheral Nerve Repair, Priya Kaluskar, Dhruv Bharadwaj, K Swaminathan Iyer, Christopher Dy, Minghao Zheng, David M Brogan

2020-Current year OA Pubs

The purpose of this systematic review was to assess the currently available evidence for the use of external stimulation to modulate neural activity and promote peripheral nerve regeneration. The most common external stimulations are electrical stimulation (ES), optogenetic stimulation (OS), and magnetic stimulation (MS). Understanding the comparative effectiveness of these stimulation methods is pivotal in advancing therapeutic interventions for peripheral nerve injuries. This systematic review focused on these three external stimulation modalities as potential strategies to enhance peripheral nerve repair (PNR). We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework to systematically evaluate and compare the efficiency …


Low-Dose Ondansetron: A Candidate Prospective Precision Medicine To Treat Alcohol Use Disorder Endophenotypes, Bankole Johnson, Hannu Alho, Giovanni Addolorato, Otto Michael Lesch, Jonathan Chick, Lei Liu, Vinzant Schuyler Sep 2024

Low-Dose Ondansetron: A Candidate Prospective Precision Medicine To Treat Alcohol Use Disorder Endophenotypes, Bankole Johnson, Hannu Alho, Giovanni Addolorato, Otto Michael Lesch, Jonathan Chick, Lei Liu, Vinzant Schuyler

2020-Current year OA Pubs

BACKGROUND: Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The estimated heritability of AUD is 50-60 %, and multiple genes are thought to contribute to various endophenotypes of the disease. Previous clinical trials support a precision medicine approach using ondansetron (AD04, a 5-HT3 antagonist) by segregating AUD populations by the bio-genetic endophenotype of specific serotonergic genotypes and the bio-psychosocial endophenotype of the severity of drinking or both. By targeting the modulation of biogenetic signaling within the biopsychosocial context of AUD, low-dose AD04 holds promise …


Utility Of Eosinophil Peroxidase As A Biomarker Of Eosinophilic Inflammation In Asthma, Monica Tang, Kaharu Sumino, Et Al. Sep 2024

Utility Of Eosinophil Peroxidase As A Biomarker Of Eosinophilic Inflammation In Asthma, Monica Tang, Kaharu Sumino, Et Al.

2020-Current year OA Pubs

BACKGROUND: The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain.

OBJECTIVE: We sought to determine the utility of EPX as a biomarker of systemic and airway eosinophilic inflammation in asthma.

METHODS: EPX protein was measured by immunoassay in serum and sputum in 110 healthy controls to establish a normal reference range and in repeated samples of serum and sputum collected during 3 years of observation in 480 participants in the Severe Asthma Research Program 3.

RESULTS: Over 3 years, EPX levels in patients with asthma were higher than normal …


Concepts Of Pain Management Following Nerve Injuries: Multidisciplinary Approach, Amanda Faust, Stephen J Demartini, Abigail Carey-Ewend, Lara W Crock, Sarah K Buday, David M Brogan, Christopher J Dy Sep 2024

Concepts Of Pain Management Following Nerve Injuries: Multidisciplinary Approach, Amanda Faust, Stephen J Demartini, Abigail Carey-Ewend, Lara W Crock, Sarah K Buday, David M Brogan, Christopher J Dy

2020-Current year OA Pubs

PURPOSE: A systematic review to identify treatment approaches for the management of pain following peripheral nerve injury.

METHODS: A published literature search was performed for the concepts of peripheral nerve injury and pain management with related synonyms. The strategies were created using a combination of controlled vocabulary terms and keywords and were executed in Embase.com, Ovid-Medline All, and Scopus from database inception. Database searches were completed on August 22, 2023.

RESULTS: The initial search resulted in a total of 1,793 citations. In total, 724 duplicates were removed, leaving 1,069 unique citations remaining for analysis. This review excluded all papers that …


Single-Isocenter, Multiple-Target Abdominal Cone-Beam Computed Tomography (Cbct)-Guided Online Adaptive Stereotactic Body Radiotherapy (Sbrt), Chipo Raranje, Thomas R. Mazur, Allen Mo, Eric Laugeman Sep 2024

Single-Isocenter, Multiple-Target Abdominal Cone-Beam Computed Tomography (Cbct)-Guided Online Adaptive Stereotactic Body Radiotherapy (Sbrt), Chipo Raranje, Thomas R. Mazur, Allen Mo, Eric Laugeman

2020-Current year OA Pubs

Stereotactic body radiotherapy (SBRT) is increasingly being prescribed for treating patients with multiple metastases, especially in the setting of oligometastatic disease. Treating multiple targets presents unique challenges in radiotherapy planning and delivery, including practical considerations relating to treatment time, resource allocation, and treatment planning complexity. Treating targets in a common isocenter reduces the time required for treatment and simplifies planning, but historically, it has often not been feasible due to inter- and intra-fractional variation in relative target positions. With online adaptation, individual targets can be re-contoured on each treatment fraction to obviate inter-fractional variation, and with appropriate margin selection intra-fractional …


Manifested U-Waves Prior To Seizure Attacks In A Patient Who Had Remote Subarachnoid Hemorrhage: A Case Report, Nao Kaneko, Masao Watanabe, Shusuke Mori, Isik Turker, Ken Okamoto, Takao Urabe, Tomohiko Ai Sep 2024

Manifested U-Waves Prior To Seizure Attacks In A Patient Who Had Remote Subarachnoid Hemorrhage: A Case Report, Nao Kaneko, Masao Watanabe, Shusuke Mori, Isik Turker, Ken Okamoto, Takao Urabe, Tomohiko Ai

2020-Current year OA Pubs

Sudden unexpected death in epilepsy (SUDEP) refers to unpredictable demise of a person following a seizure. Electroencephalograms can directly measure electrical activity in the brain; however, it cannot predict when seizures will occur. The use of electrocardiograms (ECGs) to monitor changes in brain electrical activity has gained attention, recently. In this case report, we retrospectively reviewed ECGs taken before and after seizure activity in a 75-year-old male who had a remote subarachnoid hemorrhage. Interestingly, U-waves appeared prior to his seizures and disappeared afterward, which suggests ECGs can be used to predict epilepsy in a certain population.