Medicine and Health Sciences Commons^™

Highly Reusable Electrochemical Immunosensor For Ultrasensitive Protein Detection, Kavya L Singampalli, Camille Neal-Harris, Cassian Yee, Jamie S Lin, Peter B Lillehoj

Faculty, Staff and Student Publications

The detection and quantification of protein biomarkers in bodily fluids is important for many clinical applications, including disease diagnosis and health monitoring. Current techniques for ultrasensitive protein detection, such as enzyme-linked immunosorbent assay (ELISA) and electrochemical sensing, involve long incubation times (1.5-3 hr) and rely on single-use sensing electrodes which can be costly and generate excessive waste. This work demonstrates a reusable electrochemical immunosensor employing magnetic nanoparticles (MNPs) and dually labeled gold nanoparticles (AuNPs) for ultrasensitive measurements of protein biomarkers. As proof of concept, this platform was used to detect C-X-C motif chemokine ligand 9 (CXCL9), a biomarker associated with …

Communities Disproportionately Affected By Carbon Monoxide Exposure After Winter Storm Uri, Elyse N Portillo, Casandra Quiñones, Zachary C Foughty, Ryan Ramphul, Asha T Morrow, Kathryn Fisher, Stephen A Harding, Elizabeth A Camp, Shubhada Hooli, Eric A Russell

Faculty, Staff and Students Publications

Extreme cold in February 2021 precipitated prolonged power failure in Texas. In Houston, many patients presented for carbon monoxide exposure from neighborhoods with lower per capita income, higher rates of limited English proficiency, and greater median Social Vulnerability Indices than Greater Houston. Weather-related disasters disproportionately affect socially vulnerable communities.

The Cerebellum Modulates Thirst, Ila Mishra, Bing Feng, Bijoya Basu, Amanda M Brown, Linda H Kim, Tao Lin, Mir Abbas Raza, Amelia Moore, Abigayle Hahn, Samantha Bailey, Alaina Sharp, Juan C Bournat, Claire Poulton, Brian Kim, Amos Langsner, Aaron Sathyanesan, Roy V Sillitoe, Yanlin He, Atul R Chopra

Duncan NRI Faculty and Staff Publications

The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin's dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by …

Psychosocial Outcomes Of Pain And Pain Management In Adults With Osteogenesis Imperfecta: A Qualitative Study, Whitney S Shepherd, Andrew D Wiese, Hannah E Cho, W Conor Rork, M Usman Baig, Kristin M Kostick, Dianne Nguyen, Erin M Carter, Members Of The Bbdc, Chaya N Murali, Marie-Eve Robinson, Sophie C Schneider, Brendan Lee, V Reid Sutton, Eric A Storch

Faculty, Staff and Students Publications

Objectives

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and fractures, short stature, dental abnormalities, hearing loss, scoliosis, and chronic pain. Despite a growing literature on the functional outcomes of OI, limited research has explicitly examined the psychosocial outcomes of pain within OI.

Methods

Adults with OI (N=15) were interviewed to understand pain-related experiences through a thematic analysis of semi-structured interview data. Research team members, genetic research experts, and OI clinicians developed an interview guide focused on topics related to pain and mental health challenges. Participants’ transcripts were coded by two independent coders; codes were then merged …

Methicillin-Resistant Staphylococcus Aureus In Diabetic And Non-Diabetic Foot Infections, Lawrence A Lavery, Mario C Reyes, Mehmet Suludere, Bijan Najafi, Matthew Sideman, Michael C Siah, Arthur N Tarricone

Center on Aging Staff Publications

To identify the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection, reinfection and clinical outcomes. Four hundred forty-six patients that were admitted to the hospital with moderate or severe foot infections were retrospectively reviewed. Tissue and bone cultures were obtained from the index hospital admission. Conversion was defined as methicillin susceptible Staphylococcus aureus in the first culture and subsequently MRSA when there was a reinfection. The incidence of MRSA was 7.8% (n = 35), with no significant difference between soft tissue infections (7.7%) and osteomyelitis (8.0%). MRSA incidence was 9.4 times higher in non-diabetics (23.8% vs. 3.2%, p = < 0.01). The incidence of reinfection was 40.8% (n = 182). Conversion to MRSA was seen in 2.2% (n = 4) total, occurring in 5.4%. Non-diabetics were 20.1 times more likely to have MRSA reinfection than people with diabetes (28.6% vs. 1.9%, p <  0.001). MRSA patients had a higher proportion of healed wounds (82.4% vs. 69.3%, p = 0.02). There were no differences in other clinical outcomes in MRSA vs. other infections in reinfection (28.6% vs. 24.3%, p = 0.11), amputation (48.6% vs. 52.0%, p = 0.69) or hospitalization (28.6% vs. 42.6, p = 0.11). The incidence of MRSA for the first infection (7.8%), reinfection (6.0%) and conversion to MRSA (2.2%) was low. MRSA was 9.4 times more common in people without diabetes.

Clinical Features Of Chagas Disease Progression And Severity, Maria Carmo P Nunes, Caryn Bern, Eva H Clark, Antonio L Teixeira, Israel Molina

Faculty, Staff and Students Publications

Chagas disease, the most common form of nonischaemic cardiomyopathy globally, is one of the leading causes of morbidity and mortality in Latin America. Chagas cardiomyopathy has a wide clinical spectrum and prognosis, which is primarily determined by the severity of left ventricular dysfunction. Chagas disease also affects the brain, particularly manifesting as cardioembolic strokes and cognitive impairments. Disease progression is influenced by various factors such as anti-parasite treatments, host-parasite interactions, and other determinants. This review explores Chagas disease, covering clinical presentations, the range of severity of Chagas cardiomyopathy, and neurological manifestations. We investigate factors that influence the progression of cardiomyopathy, …

The Impact Of Margins And Re-Resection In Pediatric Synovial Sarcoma, Andres F Espinoza, Priya B Shetty, Jillian C Jacobson, Hannah Todd, Kelley Harrell, Alfred F Trappey, John Doski, Eumenia C Castro, Nicole I Montgomery, M Fatih Okcu, Rajkumar Venkatramani, Dai H Chung, Sanjeev A Vasudevan

Faculty, Staff and Students Publications

INTRODUCTION: Synovial sarcoma is one of the most common soft tissue sarcomas in children. Guidelines regarding the adequate extent of resection margins and the role of re-resection are lacking. We sought to evaluate the adequate resection margin and the role of re-resection in predicting outcomes in children with synovial sarcomas.

METHODS: A cohort of 36 patients less than 18 years of age at diagnosis who were treated for localized synovial sarcoma at three tertiary pediatric hospitals between January 2004 and December 2020 were included in this study. Patient and tumor demographics, treatment information, and margin status after surgical resection were …

Spatio-Temporal Patterns Of Heat Index And Heat-Related Emergency Medical Services (Ems), Kijin Seong, Junfeng Jiao, Akhil Mandalapu, Dev Niyogi

Research Collection College of Integrative Studies

Despite growing concerns about heat waves due to climate change and their health impacts, there has been limited research on patterns of extreme heat during summertime and their association with heat-related Emergency Medical Services (EMS) incidents. This study examines spatiotemporal patterns of the heat index (HI) and its relationship to heat-related EMS incidents in Austin-Travis County, Texas, focusing on the summers of 2020 and 2021. Collecting 47,838 heat-related EMS incidence cases and aggregating them at the tract level (N = 290), the research employs spatiotemporal analysis, spatial autocorrelation, K-means clustering, and geographically weighted Poisson regression to identify disparities in heat-related …

Examining The Most Important Risk Factors For Predicting Youth Persistent And Distressing Psychotic-Like Experiences, Nicole R Karcher, Aristeidis Sotiras, Tara A Niendam, Elaine F Walker, Joshua J Jackson, Deanna M Barch

2020-Current year OA Pubs

BACKGROUND: Persistence and distress distinguish more clinically significant psychotic-like experiences (PLEs) from those that are less likely to be associated with impairment and/or need for care. Identifying risk factors that identify clinically relevant PLEs early in development is important for improving our understanding of the etiopathogenesis of these experiences. Machine learning analyses were used to examine the most important baseline factors distinguishing persistent distressing PLEs.

METHODS: Using Adolescent Brain Cognitive Development (ABCD) Study data on PLEs from 3 time points (ages 9-13 years), we created the following groups: individuals with persistent distressing PLEs (n = 305), individuals with transient distressing …

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. …

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 …

Quantitative Gradient Recalled Echo (Qgre) Mri Enables In Vivo Measurement Of Pre-Atrophic Neurodegeneration In A Mouse Model Of Alzheimer's Disease, Michal R Tomaszewski, Alexander L Sukstanskii, Hyking Haley, Xiangjun Meng, Corin O Miller, Dmitriy A Yablonskiy

2020-Current year OA Pubs

Robust methods are needed for preclinical evaluation of novel Alzheimer Disease (AD) therapies to accelerate drug discovery. Quantitative Gradient Recalled Echo (qGRE) MRI has shown promise to provide insight into neurodegeneration in AD prior to atrophy development in humans, highlighting areas of low neuronal density. In this study a novel qGRE method (20 echoes, TE=2-40ms) is shown to non-invasively measure the longitudinal neuronal loss in the hippocampus of a mouse model of AD tauopathy Tg4510. Tg4510 (n=10) and wild type (WT, n=6) mice underwent MRI (7T field strength) at 3-7 months old. 3D qGRE approach was used to generate brain-specific …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Psychological Aspects Of Nerve Gap Reconstruction: Addressing Patient Perspectives And Expectations, Stephen Demartini, Amanda Faust, Brendan Navarro, Christopher J Dy

2020-Current year OA Pubs

PURPOSE: Preoperative expectations play a major role in determining patient satisfaction after surgery. The aim of this study was to characterize patient's preoperative expectations and postoperative perceptions of nerve gap repair surgery.

METHODS: We conducted a search of Embase, Scopus, and Web of Science databases for peer-reviewed articles that studied patient expectations, perceptions, and impressions of nerve gap repair in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies related to lumbar plexus radiculopathy, reimplantation, or patient satisfaction scores without patient testimony were excluded. Primary and secondary outcomes were patient's preoperative expectations and postoperative perceptions of …

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.

An Expert Discussion On The Atypical Hemolytic Uremic Syndrome Nomenclature-Identifying A Road Map To Precision: A Report Of A National Kidney Foundation Working Group, Carla M Nester, Anuja Java, Et Al.

2020-Current year OA Pubs

The term atypical hemolytic uremic syndrome has been in use since the mid-1970s. It was initially used to describe the familial or sporadic form of hemolytic uremic syndrome as opposed to the epidemic, typical form of the disease. Over time, the atypical hemolytic uremic syndrome term has evolved into being used to refer to anything that is not Shiga toxin-associated hemolytic uremic syndrome. The term describes a heterogeneous group of diseases of disparate causes, a circumstance that makes defining disease-specific natural history and/or targeted treatment approaches challenging. A working group of specialty-specific experts in the thrombotic microangiopathies was convened to …

Tauroursodeoxycholic Acid Ameliorates Renal Injury Induced By Col4a3 Mutation, Shuwen Yu, Teija Suhas, Meei-Hua Lin, Jeffrey H Miner, Et Al.

2020-Current year OA Pubs

COL4A3/A4/A5 mutations have been identified as critical causes of Alport syndrome and other genetic chronic kidney diseases. However, the underlying pathogenesis remains unclear, and specific treatments are lacking. Here, we constructed a transgenic Alport syndrome mouse model by generating a mutation (Col4a3 p.G799R) identified previously from one large Alport syndrome family into mice. We observed that the mutation caused a pathological decrease in intracellular and secreted collagen IV α3α4α5 heterotrimers. The mutant collagen IV α3 chains abnormally accumulated in the endoplasmic reticulum and exhibited defective secretion, leading to persistent endoplasmic reticulum stress in vivo and in vitro. RNA-seq analysis revealed …

"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:

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

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 …

An Interpretable Machine Learning-Based Cerebrospinal Fluid Proteomics Clock For Predicting Age Reveals Novel Insights Into Brain Aging, Justin Melendez, Yun Ju Sung, Miranda Orr, Andrew Yoo, Suzanne Schindler, Carlos Cruchaga, Randall Bateman

2020-Current year OA Pubs

Machine learning can be used to create "biologic clocks" that predict age. However, organs, tissues, and biofluids may age at different rates from the organism as a whole. We sought to understand how cerebrospinal fluid (CSF) changes with age to inform the development of brain aging-related disease mechanisms and identify potential anti-aging therapeutic targets. Several epigenetic clocks exist based on plasma and neuronal tissues; however, plasma may not reflect brain aging specifically and tissue-based clocks require samples that are difficult to obtain from living participants. To address these problems, we developed a machine learning clock that uses CSF proteomics to …

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 …

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 …