Digital Commons Network^™

A Comparison Of Poly(Methyl Methacrylate) And Silorane-Based Cements As Carriers For Local Doxorubicin Delivery., Grahmm A. Funk, Elizabeth M. Menuey, Zachary D. Denton, Dalan M. Pittz, Alejandro Parrales, Tomoo Iwakuma, Kathleen V. Kilway, Terence E. Mciff

Manuscripts, Articles, Book Chapters and Other Papers

Orthopedic osteosarcomas and metastatic lesions can be difficult to treat with systemically delivered chemotherapy agents alone. Following removal of the primary tumor, implantation of cement to fill the lesion is often done to stabilize weight-bearing bones. One of the commonly used treatments to address osteosarcoma is systemic delivery of doxorubicin. Therefore, research on the incorporation and release of efficacious doxorubicin for local delivery from cement is important. Poly(methyl methacrylate) (PMMA)-based bone cements are the gold standard in orthopedics but have inherent disadvantages. Efforts to overcome some of these deficiencies led to the development of a novel silorane-based biomaterial (SBB). This …

Hiv Testing In African American Churches: Results From The Taking It To The Pews Cluster-Randomized Trial., Jannette Berkley-Patton, Carole Bowe Thompson, Alexandria G. Bauer, Marcie Berman, Kelsey Christensen, Andrea Bradley-Ewing, Kathy Goggin, Delwyn Catley, Eric Williams, Cassandra Wainright, Kathryn P. Derose, Alex Geyer, Frank Thompson, Lesha Dennis, Stephen Smith, Jenifer E. Allsworth

Manuscripts, Articles, Book Chapters and Other Papers

To examine effects of a multilevel, religiously-tailored HIV testing intervention, Taking It to the Pews (TIPS), on receipt of HIV testing with African American church-affiliated populations, 14 African American churches (N = 1,491) were randomized to TIPS or a multilevel, non-tailored HIV education attention-control arm in a cluster-randomized trial (Kansas City urban area, 2013 to 2019). Receipt of an HIV test was examined using objective data and participant self-reports (last 12 months), including self-reported exposure to intervention components. Overall, 471 HIV tests were completed; TIPS intervention churches conducted significantly more tests than controls (339 versus 132, p = 0.003). Also, …

Infant Sensory Gating And A Developmental Cascade To Autistic Traits And Anxiety, Rebecca F Schwarzlose

2020-Current year OA Pubs

Disruptions to the infant sensory environment can have lasting effects on neural response properties and behavior in both humans and animals. Recent work has begun to highlight an additional factor in infant sensory experience: differences in inhibitory signaling and sensory gating. Converging work from human and animal studies has begun to implicate a developmental cascade by which impaired sensory gating during a sensitive period of neonatal neurodevelopment promotes a phenotype of sensory over-responsivity, autistic traits, anxiety, and other psychiatric challenges. In this Review, I propose a model for this developmental cascade and highlight how differences in infant sensory responsivity represent …

Preparing For Long-Acting Technologies: A Multistate Analysis Of Prep Persistence And Hiv And Sti Lab Coverage Among Oral Prep Initiators In St. Louis, Missouri (2014-2021), Lindsey M Filiatreau, Rupa Patel, Kate Curoe, Ashley Underwood, Joseph Cherabie, Elvin H Geng, Aditi Ramakrishnan, Rachel Presti, Aaloke Mody

2020-Current year OA Pubs

BACKGROUND: Engagement in pre-exposure prophylaxis (PrEP) care and routine screening for HIV and sexually transmitted infections (STIs) is critical to realizing the full benefits of this HIV prevention strategy.

METHODS: We enrolled a cohort of individuals seeking PrEP services in two clinics in Missouri, an Ending the HIV Epidemic priority state, from June 2014 to November 2021. We used electronic health record and survey data to explore outcomes in the 2 years following linkage to care using multistate methods. We assessed transitions between eight mutually exclusive care states differentiated by receipt of a prescription, lab coverage status, and retention. We …

Epithelial-Mesenchymal Transition And Stress Adaptations Underlie Yttrium-90 Resistance In Liver Cancer Cell Lines, Alexander Zheleznyak, Dhanusha Duraiyan, Prasanth Thunuguntla, Jessica Camacho, Shuang Wu, Jingxia Liu, Jason D Weber, Daniel L J Thorek, Benjamin S Strnad, Ryan C Fields, Matthew A Ciorba, Christine Yoon, Valerie Blanc, Nicholas Davidson, Jessica Silva-Fisher, Christopher D Malone

2020-Current year OA Pubs

UNLABELLED: Molecular signatures predict prognosis in hepatocellular carcinoma, but their relevance to transarterial radioembolization (TARE) with yttrium-90 (90Y) is unknown. We aimed to identify baseline and treatment-induced pathways associated with response and nominate biomarkers. Ten transcriptomically diverse human liver cancer cell lines were exposed to escalating activities of glass 90Y microspheres for 10 days. Normalized AUC values quantified sensitivity. Whole-transcriptome RNA sequencing at baseline and after treatment was analyzed with elastic net regression and gene set enrichment. Findings were corroborated by qRT-qPCR and exploratory analysis of pretreatment tumor samples from patients undergoing TARE. Liver cancer cell line responses to 90Y …

The Cognitive-Affective Social Processing And Emotion Regulation (Casper) Model, M Catalina Camacho, Elina Deshpande, Michael T Perino

2020-Current year OA Pubs

Humans are intensely social creatures. It is therefore not surprising that many psychiatric disorder criteria include social dysfunctions; however, overlapping presentations and diverse, complex etiologies make treating social dysfunctions difficult. Here, we introduce the Cognitive Affective Social Processing and Emotion Regulation (CASPER) model. CASPER integrates research from social psychology, cognitive neuroscience, and developmental science to describe how real-world social processing unfolds and is associated with differing psychiatric social cognitive neurophenotypes. Briefly, social processing can be broken down into the following cognitive steps: identifying relevant social cues, attending to related cues, interpreting cues, and adjusting behavior appropriately. Each of these steps …

The Impact Of Fixation Method And Surgical Approach On Outcomes Following Hip Hemiarthroplasty For Femoral Neck Fracture, Brian D Rust, Mitchel R Obey, Jenna-Leigh Wilson, Christopher M Mcandrew, Marschall B Berkes

2020-Current year OA Pubs

INTRODUCTION: Hip hemiarthroplasty is commonly performed for displaced femoral neck fractures in older adults, with implants placed either cemented or uncemented. While cemented fixation offers immediate stability, uncemented fixation reduces operative time and pulmonary complications. Large single-center analyses comparing these techniques remain limited, and this study aims to assess this.

METHODS: We conducted a retrospective case-control study of 634 adult patients undergoing hip hemiarthroplasty at a single Level 1 trauma center from 2019 to 2025. Patients were classified by cemented (n=403) or uncemented (n=231) fixation and further stratified by surgical approach (anterolateral vs posterior). Outcomes included length of stay, postoperative …

Sonobiopsy For Enrichment Of Circulating Micrornas In Glioma Patients, Jinyun Yuan, Yuanxiang Li, Chih-Yen Chien, Lu Xu, Andrew H Stark, Siaka Fadera, Zhaoning Gu, Yu Xuan Chin, Kevin Xu, Arash Nazeri, Umeshkumar Athiraman, Xiaowei Wang, Hong Chen, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Sonobiopsy is a promising new technique that employs focused ultrasound (FUS) to noninvasively enrich brain tumor-derived biomarkers from spatially targeted brain location into the bloodstream. Building upon our recent first-in-human sonobiopsy trial demonstrating enrichment of circulating tumor DNA (ctDNA), here we investigated whether sonobiopsy can enhance the release and detection of tumor-derived microRNAs (miRNAs).

METHODS: Eleven patients with glioma underwent FUS sonication immediately prior to surgical resection. Peripheral blood samples were collected 5 min before and 5, 10, and 30 min after sonication. Plasma and brain tissue miRNA levels were quantified through small RNA sequencing and compared among different …

Characteristics Of Cerebral Palsy In The Midwestern Us, Susie Kim, Kelsey Steffen, Lauren Gottschalk-Henneberry, Jennifer Miros, Amy Robichaux-Viehoever, Karen Taca, Bhooma R Aravamuthan

2020-Current year OA Pubs

OBJECTIVE: Cerebral palsy (CP) is the most common lifelong motor disability worldwide. Yet, data is limited on how CP manifests in the US. Our objective was to characterize and determine factors affecting functional outcomes in a large population of young people with CP in the Midwestern US.

METHODS: We integrated caregiver and clinician-facing standardized data entry into routine clinical care at a tertiary care CP center (https://bit.ly/CP-Intake-Methodology). We extracted this data for people with an ICD10 diagnosis of CP seen between March 22, 2023 and December 28, 2023 and used it to describe CP characteristics and determine factors affecting the …

Perception Of Dementia Risk Among Black Adults: An Ecological Analysis Of Causal Loop Diagrams With A Structural And Social Determinant Of Health Composite Index, Jean-Francois Trani, Ramkrishna K Singh, Alexis Ib Walker, Semere Bekena, Yiqi Zhu, Ganesh M Babulal, Robbie Hart

2020-Current year OA Pubs

INTRODUCTION: To investigate drivers of dementia risk disparities among older Black Americans using a community-based system dynamics (CBSD) approach.

METHODS: Over 18 months, 234 participants created 36 causal loop diagrams (CLDs) on dementia risk. An ecological analysis compared structural differences across groups based on scores on a structural and social determinants of health composite index (S/SDOH-CI).

RESULTS: Groups in the highest SDOH-CI quantile were more likely to identify key protective pathways linking mental health, substance use, exercise, medication, and community support to reduce dementia risk. In contrast, fewer than 25% of low-SDOH-CI groups identified these connections, and under 15% recognized …

Development Of Colonic Polyposis In A Woman With Chronic Myeloid Leukemia Treated With Dasatinib, Guido Pelaez, Behram Suha Yildiz, Mert Candan, Mohammad Ismail, Francesca Vacca, Marianna B Ruzinova, Samuel Ballentine, Kathleen Byrnes, Armin Ghobadi

2020-Current year OA Pubs

INTRODUCTION: Chronic myeloid leukemia (CML) is a hematopoietic malignancy driven by constitutive tyrosine kinase activity. Dasatinib, a second-generation (2G) tyrosine kinase inhibitor (TKI), is a preferred treatment due to its superior, durable, and rapid response rates. While dasatinib has known gastrointestinal (GI) side effects, colonic polyposis is a rare complication, not well described in the literature.

CASE PRESENTATION: Upon routine colonoscopy, a 66-year-old woman with chronic-phase CML was incidentally discovered to have asymptomatic colonic polyposis after 11 months of dasatinib therapy. Histopathology revealed reactive inflammatory changes without evidence of dysplasia or neoplasia. The polyposis resolved completely after cessation of dasatinib. …

Biological Aging Acceleration In Major Depressive Disorder: A Multi-Omics Analysis, Breno Satler Diniz, Shangshu Zhao, Gabin Drouard, Eero Vuoksimaa, Miina Ollikainen, Eric J Lenze, Ming Xu, Richard H Fortinsky, George A Kuchel, Jaakko Kaprio, Chia-Ling Kuo

2020-Current year OA Pubs

Major depressive disorder (MDD) is linked to a higher risk of premature aging, but the mechanisms underlying this association remain unclear. Using data from two population cohorts (UK Biobank and Finnish Twin Cohort), we evaluate the relationship between systemic and organ-specific proteomic and epigenetic aging acceleration and MDD. A lifetime history of MDD was associated with accelerated proteomic aging at both systemic and organ-specific levels-including the brain-in both cohorts, with stronger associations than those observed with systemic epigenetic aging. Systemic and brain-specific proteomic aging acceleration were linked to higher risks of incident MDD and a greater risk of Alzheimer's disease, …

Excellent Survival Following Low-Intensity Approaches Prior To Allo-Hsct In Ph+ All: A Comprehensive Meta-Analysis, Lacey S. Williams, Wenners Ballard Iii, Deniz Ozisik, Charles Scott Dorris, Kepher Makambi, Scott Rowley, Kieron Dunleavy, John Dipersio, Alaa Ali

2020-Current year OA Pubs

No abstract provided.

Comparison Of Positive Dysphotopsia Rates Between Au00t0, Mx60e, Pcb00/Zcb00, And Sn60wf Intraocular Lenses, Jonathan L. Tong, Maggie J. Xing, Arsham Sheybani

2020-Current year OA Pubs

No abstract provided.

The Association Between Major Depressive Disorder, Plasma Biomarkers Of Alzheimer's Disease, And Mild Behavioral Impairment Among Older Adults, Yiqi Zhu, Jean-Francois Trani, Ramkrishna K Singh, Semere Bekena, Jonathan Williams, Eric J Lenze, Ganesh M Babulal

2020-Current year OA Pubs

INTRODUCTION: Plasma biomarkers and mild behavioral impairment (MBI) are associated with dementia risk, but their relationships with major depressive disorder (MDD) are understudied. This study aimed to examine associations between plasma biomarkers of Alzheimer's disease (AD) and MBI among older adults with and without MDD.

METHODS: Older adults aged ≥65 were recruited from longitudinal studies of depression and AD (

RESULTS: Older adults with MDD were more likely to endorse MBI. After adjustment, Aβ42/Aβ40 and p-tau217/np-tau217 positivity were associated with MBI among those with MDD but not among those without.

DISCUSSION: Neuropsychatric symptoms (NPS) and biomarkers are AD risk factors. …

The Impact Of Congenital Heart Disease On The Timing Of Alzheimer's Disease In Down Syndrome, Julianne G Clina, Beau Ances, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The incidence of Alzheimer's disease (AD) in Down syndrome (DS) exceeds 90%. Approximately 50% of people with DS have congenital heart disease (CHD). Having CHD increases risk for early-onset AD in populations without DS, but it is unclear if CHD influences AD in DS.

METHODS: Data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) were used. Participants with CHD (

RESULTS: People with CHD scored lower for visuospatial ability (

DISCUSSION: Presence of CHD may influence AD progression in DS.

HIGHLIGHTS: In adults with Down syndrome (DS), those with congenital heart disease (CHD) had higher amyloid beta and reached the …

Eligibility For Anti-Amyloid Treatment In A Multiethnic Community-Based Study, Lydia Trudel, Joseph Therriault, Arthur C Macedo, Karin L Meeker, Meredith N Braskie, Arthur W Toga, Serge Gauthier, Paolo Vitali, Suzanne E Schindler, Sid E O'Bryant, Pedro Rosa-Neto

2020-Current year OA Pubs

INTRODUCTION: The approval of anti-amyloid monoclonal antibodies (mAbs), including lecanemab and donanemab, represents a significant advance in disease-modifying therapies (DMTs) for early Alzheimer's disease (AD). While appropriate use recommendations (AURs) have been established to guide clinical decision-making, the proportion of individuals with cognitive impairment in real-world, multiethnic populations meeting eligibility criteria remains unknown, as do potential differences in treatment-related risks across ethnic groups.

METHODS: We included 513 cognitively impaired individuals from the Health and Aging Brain Study-Health Disparities study, a multiethnic community-based cohort. Eligibility for lecanemab and donanemab was determined using published AUR criteria. Counts of amyloid-related imaging abnormalities were …

Effect Of A Pregnancy Lifestyle Intervention Embedded Into A Home Visiting Program On Child Neurodevelopment, Sarah S Farabi, Rosemary Bass, Amit Mathur, Cindy Schwarz, Candice Woolfolk, Richard Stein, Samuel Klein, Debra Haire-Joshu, Alison G Cahill

2020-Current year OA Pubs

Maternal obesity is associated with a higher risk of abnormal child neurodevelopment. The aim of this study was to determine the effect of a lifestyle intervention embedded into a home visiting program, Parents as Teachers (PAT), on 18-month neurodevelopment in the offspring. Pregnant women (9-15 weeks) of African American Race, 18-45 years old, first-trimester BMI 25.0-45.0 kg/m

The Role Of Home Visiting In Addressing Postpartum Care Gaps: Evidence From A Large Community Sample, Aishwarya Vijay, Allison Kemner, Karen Hoerchler, Abigail Edwards, Jeannie C Kelly, Rachel G Tabak, Mark D Huffman, Zainab Mahmoud

2020-Current year OA Pubs

BackgroundMaternal mortality in the United States has doubled over the last two decades, primarily due to cardiovascular disease, with more than half of deaths occurring postpartum. Despite national calls to action, attendance at postpartum clinic visits remains low. The role of alternative care delivery strategies, such as home visiting, remains insufficiently studied.ObjectiveTo describe postpartum clinic visit attendance among participants in a large national home visiting program, identify sociodemographic and clinical factors associated with attendance, and examine how timing and duration of enrollment relate to postpartum follow-up.DesignWe conducted a retrospective cohort study of pregnancy episodes among mothers enrolled in the Parents …

Thwartings, Lee Anne Fennell

Coase-Sandor Institute for Law & Economics Research Paper Series

No abstract provided.

Phase I Trial Of Adp-A2afp Tcr T-Cell Therapy In Patients With Advanced Hepatocellular Or Gastric Hepatoid Carcinoma, Tim Meyer, Benjamin R Tan, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Patients with advanced hepatocellular carcinoma (HCC) generally experience poor outcomes despite current therapies, necessitating the development of alternative treatments. ADP-A2AFP is an investigational autologous T-cell therapy with an affinity-enhanced T-cell receptor (TCR) targeting alpha-fetoprotein (AFP).

METHODS: We describe a phase I, open-label, first-in-human clinical trial of ADP-A2AFP (NCT03132792) in human leukocyte antigen-eligible participants with AFP-expressing HCC (or other tumor) not amenable to transplant/resection who progressed on, were intolerant to, or refused prior systemic therapy. Participants received lymphodepletion chemotherapy (cyclophosphamide 500 mg/m

RESULTS: Twenty-one participants, 20 with advanced HCC and one with gastric hepatoid carcinoma received ≥1 ADP-A2AFP …

Cutibacterium Adaptation To Life On Humans Provides A Potential C Acnes Infection Biomarker, Md Shafiuddin, Wen-Chi Huang, Gabriel William Prather, Jeffrey Ryan Anton, Andrew Lawrence Martin, Sydney Brianna Sillart, Jonathan Z Tang, Michael R Vittori, Michael J Prinsen, Jessica Jane Ninneman, Chandrashekhara Manithody, Jeffrey P Henderson, Alexander W Aleem, Ma Xenia Garcia Ilagan, William H Mccoy 4th

2020-Current year OA Pubs

Propionibacteriaceae appear to have adapted to life on humans during the domestication of cattle. These microbial immigrants formed the genus Cutibacterium, and a descendent of those microbial trailblazers (C acnes) now dominates 25% of human skin. C acnes colonization of human skin requires the protein RoxP. Although all Cutibacteria encode this adaptation to life on humans, nothing like RoxP has been found in any other organism. In this study, we report an extensive assessment of 21 RoxP orthologs, which identified conserved molecular surfaces linked to heme-dependent oligomerization and low pH stability. Our investigation suggests how RoxP helps C acnes dominate …

Diverse Misfolding Mutant Digestive Enzymes Cause Chronic Pancreatitis Through Common Pathways, Steven J Wilhelm, Grace E Curry, Neel Matiwala, Jianguo Lin, Tran Quach, Mark E Lowe, Miklós Sahin-Tóth, Xunjun K Xiao

2020-Current year OA Pubs

BACKGROUND & AIMS: Increasing evidence suggests that protein misfolding and proteotoxicity is an important mechanism of chronic pancreatitis (CP) in patients with genetic variants. Two mouse models carrying misfolding digestive enzyme variants, CPA1 N256K and PNLIP T221M, recapitulate the human CP phenotype. We hypothesized that both models develop CP through similar disease mechanisms.

METHODS: We conducted a comprehensive analysis of mice aged 1 to 6 months using histology, immunohistochemistry, protein immunoblotting, quantitative polymerase chain reaction (qPCR), transmission electron microscopy (TEM), and RNA sequencing (RNA-seq) analysis to characterize pancreatic pathological changes.

RESULTS: Both homozygous models exhibited CP hallmarks, including progressive acinar …

A Deep Learning Model To Guide Personalized Mechanical Circulatory Support Use In Cardiogenic Shock Patients Undergoing Pci, Amit P Amin, Richard G Bach, Darren C Tsang, Weili S Zheng, Raed A Qarajeh, Emmanouil S Brilakis, Hemant Kulkarni

2020-Current year OA Pubs

BACKGROUND: Cardiogenic shock (CS) in patients undergoing percutaneous coronary intervention (PCI) involves rapidly changing clinical, hemodynamic, and metabolic factors that current models cannot effectively integrate.

OBJECTIVES: The purpose of this study was to develop and validate a deep learning (DL) model to guide personalized use of mechanical circulatory support (MCS) devices in CS patients undergoing PCI.

METHODS: The authors analyzed data from 1,408 CS patients treated with intra-aortic balloon pump (IABP) or microaxial flow-pump (mAFP) at multiple hospitals (2004-2019). Clinical, hemodynamic, and metabolic variables from admission to MCS placement were compiled into longitudinal vectors. Using Python 3.7 and TabNet in …

Genome-Wide Gene-Sleep Interaction Study Identifies Novel Lipid Loci In 732,564 Participants, Raymond Noordam, Karen Schwander, Lisa De Las Fuentes, Mary F Feitosa, Anh Do, C Charles Gu, Changwei Li, Michael A Province, Dabeeru C Rao, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets.

METHODS: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) …

Foot-Specific Exercise Intervention For Forefoot Deformity In Individuals With Type 2 Diabetes And Peripheral Neuropathy: A Randomized Controlled Clinical Trial With 3-Year Follow-Up, J A Zellers, K Steger-May, P K Commean, H-J Jeong, E M Bullard, M J Mueller, M K Hastings

2020-Current year OA Pubs

BACKGROUND: Diabetes with peripheral neuropathy can lead to metatarsophalangeal joint (MTPJ) deformity. The purpose of this study was to estimate the effect of a foot-specific intervention on MTPJ deformity. Secondary aims were determining MTPJ deformity progression over 3 years and predictors of MTPJ deformity progression.

METHODS: Sixty people with type 2 diabetes and peripheral neuropathy were recruited for this randomized controlled clinical trial. Participants were assessed at baseline, 6 months (post-intervention), 1.5 years, and 3 years. A 6-month, foot-specific intervention in the experimental group was compared to a shoulder intervention in the control group. The primary outcome was change in …

A Catecholamine-Independent Pathway Controlling Adaptive Adipocyte Lipolysis, Xiao Zhang, Sreejith S Panicker, Jordan M Bollinger, Anurag Majumdar, Rami Kheireddine, Lila F Dabill, Clara Kim, Brian Kleiboeker, Fengrui Zhang, Kristann L Magee, Adam Kepecs, Gretchen A Meyer, Irfan J Lodhi, Erica L Scheller, Et Al.

2020-Current year OA Pubs

Several adipose depots, including constitutive bone marrow adipose tissue, resist conventional lipolytic cues. However, under starvation, wasting or cachexia, the body eventually catabolizes stable adipocytes through unknown mechanisms. Here we developed a mouse model of brain-evoked depletion of all fat, including stable constitutive bone marrow adipose tissue, independent of food intake, to study this phenomenon. Genetic, surgical and chemical approaches demonstrated that catabolism of stable adipocytes required adipose triglyceride lipase-dependent lipolysis but was independent of local nerves, the sympathetic nervous system and catecholamines. Instead, concurrent hypoglycaemia and hypoinsulinaemia activated a potent catabolic state by suppressing lipid storage and increasing catecholamine-independent …

Atomic Models Of The Toxoplasma Cell Invasion Machinery, Jianwei Zeng, Yong Fu, Pengge Qian, Wei Huang, Qingwei Niu, Wandy L Beatty, Alan Brown, L David Sibley, Rui Zhang

2020-Current year OA Pubs

Apicomplexan parasites, responsible for toxoplasmosis, cryptosporidiosis and malaria, invade host cells through a unique gliding motility mechanism powered by actomyosin motors and a dynamic organelle called the conoid. Here, using cryo-electron microscopy, we determined structures of four essential complexes of the Toxoplasma gondii conoid: the preconoidal P2 ring, tubulin-based conoid fibers, and the subpellicular and intraconoidal microtubules. Our analysis identified 40 distinct conoid proteins, several of which are essential for parasite lytic growth, as revealed through genetic disruption studies. Comparative analysis of the tubulin-containing complexes sheds light on their functional specialization by microtubule-associated proteins, while the structure of the preconoidal …

Mapping The Genetic Landscape Across 14 Psychiatric Disorders, Andrew D. Grotzinger, Alexander S. Hatoum, Emma C. Johnson, Et Al.

2020-Current year OA Pubs

No abstract provided.

An Integrated Analysis Of Three Medulloblastoma Clinical Trials Refines Risk-Stratification Approaches For Reducing Toxicity And Improving Survival, Kyle S Smith, Jeff M Michalski, Et Al.

2020-Current year OA Pubs

BACKGROUND: The identification of clinical and molecular heterogeneity in medulloblastoma has produced risk-stratified therapy, but establishing the most effective yet least toxic regimens has remained elusive owing to numerous treatment options. To improve risk-stratification, we performed an integrated analysis from three clinical trials.

METHODS: Medulloblastoma patients from ACNS0331/NCT00085735, ACNS0332/NCT00392327, and SJMB03/NCT00085202 were included if they had methylation profiling. Molecular groups [WNT, SHH, Group 3 (G3), and Group 4 (G4)], subgroups, and copy number variations were procured from methylation profiles and mutations from next-generation sequencing. Data was assembled into an interactive portal to capture patient characteristics. Cross-trial comparisons, univariable, and multivariable …