Medicine and Health Sciences Commons^™

Etomoxir-Carnitine, A Novel Pharmaco-Metabolite Of Etomoxir, Inhibits Phospholipases A2 And Mitochondrial Respiration, Sung Ho Moon, Xinping Liu, Christopher M Jenkins, Beverly Gibson Dilthey, Gary J Patti, Richard W Gross

2020-Current year OA Pubs

Mitochondrial fatty acid oxidation serves as an essential process for cellular survival, differentiation, proliferation, and energy metabolism. Numerous studies have utilized etomoxir (ETO) for the irreversible inhibition of carnitine palmitoylcarnitine transferase 1 (CPT1), which catalyzes the rate-limiting step for mitochondrial long-chain fatty acid β-oxidation to examine the bioenergetic roles of mitochondrial fatty acid metabolism in many tissues in multiple diverse disease states. Herein, we demonstrate that intact mitochondria robustly metabolize ETO to etomoxir-carnitine (ETO-carnitine) prior to nearly complete ETO-mediated inhibition of CPT1. The novel pharmaco-metabolite, ETO-carnitine, was conclusively identified by accurate mass, fragmentation patterns, and isotopic fine structure. On the …

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 …

Endovascular Thrombectomy With And Without Preceding Thrombolysis In Posterior Circulation Stroke-Insights From Star, Ev-Christin Heide, Joshua Osbun, Et Al.

2020-Current year OA Pubs

BACKGROUND: Multiple randomized trials could not establish the noninferiority of endovascular thrombectomy (EVT) alone without preceding intravenous thrombolysis (IVT) or superiority of IVT followed by EVT in anterior circulation large-vessel occlusion stroke. The role of prior IVT in posterior circulation large-vessel occlusion remains controversial.

METHODS: In this multicenter, retrospective study, patients with stroke with large-vessel occlusion in the posterior circulation who received EVT alone or with IVT were selected from the stroke thrombectomy and aneurysm registry between 2013 and 2022. Effects of IVT followed by thrombectomy on favorable functional outcome (defined as modified Rankin scale≤3 at 90 days) and safety …

Iron Accumulation And Metabolic Alterations In Aneurysmal Subarachnoid Hemorrhage, Gardenia Pacheco, Joao A Gomes, Kevin Cho, Daniel L Morris, Maddison I Segal, Kayla R Adkins-Travis, Ethan Stancliffe, Gary J Patti, Christopher J Ziegler, Leah P Shriver

2020-Current year OA Pubs

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of stroke that is associated with poor outcome. A subset of patients with aSAH will develop secondary complications, most notably delayed cerebral ischemia (DCI), which potentiates neurological injury. In this study, we investigate the relationship between cerebrospinal fluid (CSF) iron accumulation, brain metabolism, and neuronal injury in patients with aSAH with or without DCI.

METHODS: We collected longitudinal CSF samples of patients immediately after hospitalization and 5 to 8 days after onset of ictus. CSF was analyzed with electron paramagnetic resonance spectroscopy and metabolomics to determine the presence of redox-active iron …

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.

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 …

Comparison Of Outcomes Of Abdominoperineal Resection Vs Low Anterior Resection In Very-Low Rectal Cancer, Roberta L Muldoon, Alva J Bethurum, Adriana C Gamboa, Kevin Zhang, Fei Ye, Scott E Regenbogen, Sherif Abdel-Misih, Aslam Ejaz, Paul E Wise, Matthew Silviera, Jennifer Holder-Murray, Glen C Balch, Alexander T Hawkins

2020-Current year OA Pubs

BACKGROUND: The management of very-low rectal cancer is one of the most challenging issues faced by general and colorectal surgeons. Many feel compelled to pursue abdominoperineal resection (APR) over low anterior resection (LAR) to optimize oncologic outcomes. This study aimed to determine differences in long-term oncologic outcomes between patients undergoing APR or LAR for very-low rectal cancer.

METHODS: The United States Rectal Cancer Consortium (2010-2016) was queried for adults who underwent either APR or LAR for stage I-III rectal cancers < 5 cm from anorectal junction and met inclusion criteria. The primary outcome was disease-free survival. Secondary outcomes included overall survival, length of stay, complications, recurrence location, and perioperative factors.

RESULTS: A total of 431 patients with very-low rectal cancer who underwent APR or LAR were identified; 154 (35.7%) underwent …

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 …

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 …

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 …

Generation Of A Gene-Corrected Human Isogenic Ipsc Line From An Alzheimer's Disease Ipsc Line Carrying The Psen1 H163r Mutation, Damián Hernández, Stephanie Morgan Schlicht, Jordan Elli Clarke, Maciej Daniszewski, Celeste M Karch, Dominantly Inherited Alzheimer Network (Dian), Alison M Goate, Alice Pébay

2020-Current year OA Pubs

We report the generation of a gene-edited human induced pluripotent stem cell (iPSC) line from an Alzheimer's disease patient-derived iPSC line harbouring the PSEN1 H163R mutation. This line demonstrates pluripotent stem cell morphology, expression of pluripotency markers, and maintains a normal karyotype.

"Allowing Space For Voice…All Our Voices:" Understanding Ho'ouna Pono Implementation Through Educational Leadership Perspectives In Rural Hawai'i Schools, Kelsie H Okamura, Tessa Palafu, Katlyn An, Sarah Momilani Marshall, Steven Keone Chin, Kelly A Stern, Byron J Powell, Sara J Becker, David S Mandell, Scott K Okamoto

2020-Current year OA Pubs

Epidemiological research over the past two decades has highlighted substance use disparities that affect Native Hawaiian and Pacific Islander youth, and the lack of effective approaches to address such disparities (Okamoto et al., 2019). The Ho'ouna Pono curriculum is a culturally grounded, teacher-implemented, video-enhanced substance use prevention program that has demonstrated efficacy in rural Hawai'i in a large-scale trial (Okamoto et al., 2019). Despite its potential to ameliorate health disparities and address youth substance use, prevention programs such as Ho'ouna Pono have been poorly disseminated and implemented across Hawai'i, raising the question:

Investigating The Use Of Signal Detection Information In Supervised Learning-Based Image Denoising With Consideration Of Task-Shift, Kaiyan Li, Hua Li, Mark A Anastasio

2020-Current year OA Pubs

PURPOSE: Recently, learning-based denoising methods that incorporate task-relevant information into the training procedure have been developed to enhance the utility of the denoised images. However, this line of research is relatively new and underdeveloped, and some fundamental issues remain unexplored. Our purpose is to yield insights into general issues related to these task-informed methods. This includes understanding the impact of denoising on objective measures of image quality (IQ) when the specified task at inference time is different from that employed for model training, a phenomenon we refer to as "task-shift."

APPROACH: A virtual imaging test bed comprising a stylized computational …

Antiretroviral Therapy And Cardiovascular Risk In People With Hiv In The United States-An Updated Analysis, Luis Parra-Rodriguez, John M Sahrmann, Anne M Butler, Margaret A Olsen, William G Powderly, Jane A O'Halloran

2020-Current year OA Pubs

BACKGROUND: Several antiretroviral therapy (ART) medications have been associated with increased cardiovascular risk, but less is known about the safety of modern ART. We sought to compare the risk of major adverse cardiac events (MACEs) among different ART regimens.

METHODS: Using insurance claims databases from 2008 to 2020, we identified adults aged <65 years who newly initiated ART. We compared non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens to protease inhibitors (PI)- and integrase inhibitors (INSTI)-based regimens. We used propensity score-weighted Kaplan-Meier functions to estimate the 6, 12, 18, 24, 36, and 48 months' risk and risk differences (RD) of MACE.

RESULTS: Among 37 935 ART initiators (median age, 40 years; 23% female; 26% Medicaid-insured), 45% started INSTI-, 16% PI-, and 39% NNRTI-based regimens. MACE occurred in 418 individuals (1.1%) within 48 months after ART initiation. Compared to NNRTI initiators, the risk of MACE was higher at 12 months …

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.

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

Pfas Levels, Early Life Factors, And Mammographic Breast Density In Premenopausal Women, Yitao S Ning, Kayla R Getz, Joy K Kyeyune, Myung Sik Jeon, Chongliang Luo, Jingqin Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: Mammographic breast density (MBD) is a strong risk factor and an intermediate phenotype for breast cancer, yet there are limited studies on how environmental pollutants are associated with MBD.

OBJECTIVE: We investigated associations of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS) levels with measures of MBD and evaluated if early life factors modified any associations.

METHODS: Metabolon performed metabolomics analysis using ultrahigh-performance liquid chromatography/tandem accurate mass spectrometry in fasting blood from 705 premenopausal women completing their annual screening mammogram in St. Louis, Missouri. We calculated least square means (LSM) of mammographic volumetric percent density (VPD), dense …

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

2020-Current year OA Pubs

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

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

Surgeon Recommendations For Physical Activity In Patients With Pediatric Hip Conditions, Jacqueline Li, Emily K. Schaeffer, Stacey Miller, Verena M. Schreiber, Yasmin D. Hailer, John C. Clohisy, Harry K. W. Kim, Kishore Mulpuri

2020-Current year OA Pubs

BACKGROUND: While physical activity (PA) is important during youth, it is unclear if children and adolescents with developmental dysplasia of the hip (DDH), Legg-Calvé-Perthes disease (LCPD), or slipped capital femoral epiphysis (SCFE) are expected or encouraged to return to PA once they have healed. This study examines the orthopaedic surgeons' role in advising pediatric hip patients on the PA they should engage in, assessing their practice, opinions, and consensus when making recommendations.

METHODS: Orthopaedic surgeons were invited from member lists of 4 hip study groups. The survey included demographics, opinions regarding PA, and 10 case scenarios that queried respondents on …

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 …

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, …

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 …

A Damaging Col6a3 Variant Alters The Mir31hg-Regulated Response Of Chondrocytes In Neocartilage Organoids To Hyperphysiologic Mechanical Loading, Niek Gc Bloks, Zainab Harissa, Giorgia Mazzini, Shaunak S Adkar, Amanda R Dicks, Ghazaleh Hajmousa, Nancy Steward, Roman I Koning, Aat Mulder, Berend B R De Koning, Margreet Kloppenburg, Rodrigo Coutinho De Almeida, Yolande Fm Ramos, Farshid Guilak, Ingrid Meulenbelt

2020-Current year OA Pubs

The pericellular matrix (PCM), with its hallmark proteins collagen type VI (COLVI) and fibronectin (FN), surrounds chondrocytes and is critical in transducing the biomechanical cues. To identify genetic variants that change protein function, exome sequencing is performed in a patient with symptomatic OA at multiple joint sites. A predicted damaging variant in COL6A3 is identified and introduced by CRISPR-Cas9 genome engineering in two established human induced pluripotent stem cell-derived in-vitro neocartilage organoid models. The downstream effects of the COL6A3 variant on the chondrocyte phenotypic state are studied by a multi-omics (mRNA and lncRNA) approach in interaction with hyper-physiological mechanical loading …

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 …

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 …

The Use Of Transvaginal Ultrasound Alters Physiologic Uterine Peristalsis In Gynecologic Participants, Kelsey Anderson, Sicheng Wang, Stephanie Pizzella, Qing Wang, Yong Wang, Valerie Ratts

2020-Current year OA Pubs

OBJECTIVE: To study whether transvaginal ultrasound (TVUS) affected the uterine peristalsis (UP) patterns in nonpregnant participants.

DESIGN: Institutional review board-approved, prospective observational cohort study. The noninvasive UP imaging (UPI) system uses electrode patches placed on the patient's skin just above the pubic bone and on the low back to quantify the 3-dimensional electrical activation pattern during UP by calculating peristalsis frequency, duration, magnitude, and activation ratio. A 20-minute UPI scan was completed without TVUS followed by a 10-minute UPI scan acquired simultaneously during TVUS examination as a comparison.

SETTING: University medical center.

PATIENTS: Twenty-eight participants with regular menstrual cycles not …

An Ordinal Clinical Score Predicts Seizure Freedom After Minimally Invasive Epilepsy Surgery, Adam S Dickey, Katie L Bullinger, Dayton Grogan, Melissa M Asmar, Abdulrahman Alwaki, Ammar Kheder, Veeresh Kumar N Shivamurthy, Razan R Faraj, Alexander Greven, Jon T Willie, Daniel L Drane, Robert E Gross

2020-Current year OA Pubs

OBJECTIVE: To predict one-year seizure freedom, using a combination of relevant clinical variables, following stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy in a series of 101 patients.

METHODS: Eight predictors of seizure freedom were selected based on their association with medial temporal lobe epilepsy: (1) MRI evidence of mesial temporal sclerosis (MTS); (2) unitemporal interictal epileptiform discharges; (3) absence of generalized tonic-clonic seizures; (4) history of febrile seizures; (5) onset of epilepsy ≤16 years; (6) absence of an auditory, visual, or vertiginous aura; and (7) unitemporal ictal onset; (8) unitemporal PET hypometabolism. We compared four multivariate models: "MTS," using …

Neural Correlates Of Novelty-Evoked Distress In 4-Month-Old Infants: A Synthetic Cohort Study, Courtney A Filippi, Anderson M Winkler, Dana Kanel, Jed T Elison, Hannah Hardiman, Chad Sylvester, Daniel S Pine, Nathan A Fox

2020-Current year OA Pubs

BACKGROUND: Observational assessments of infant temperament have provided unparalleled insight into prediction of risk for social anxiety. However, it is challenging to administer and score these assessments alongside high-quality infant neuroimaging data. In the current study, we aimed to identify infant resting-state functional connectivity associated with both parent report and observed behavioral estimates of infant novelty-evoked distress.

METHODS: Using data from the OIT (Origins of Infant Temperament) study, which includes deep phenotyping of infant temperament, we identified parent-report measures that were associated with observed novelty-evoked distress. These parent-report measures were then summarized into a composite score used for imaging analysis. …

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

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 …