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2022

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Articles 31561 - 31590 of 32030

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Ancestral Sars-Cov-2, But Not Omicron, Replicates Less Efficiently In Primary Pediatric Nasal Epithelial Cells, Yanshan Zhu, Keng Yih Chew, Melanie Wu, Anjana C. Karawita, Georgina Mccallum, Lauren E. Steele, Ayaho Yamamoto, Larisa I. Labzin, Tejasri Yarlagadda, Alexander A. Khromykh, Xiaohui Wang, Julian D. J. Sng, Claudia J. Stocks, Yao Xia, Tobias R. Kollmann, David Martino, Merja Joensuu, Frédéric A. Meunier, Giuseppe Balistreri, Helle Bielefeldt-Ohmann, Asha C. Bowen, Anthony Kicic, Peter D. Sly, Kirsten M. Spann, Kirsty R. Short Jan 2022

Ancestral Sars-Cov-2, But Not Omicron, Replicates Less Efficiently In Primary Pediatric Nasal Epithelial Cells, Yanshan Zhu, Keng Yih Chew, Melanie Wu, Anjana C. Karawita, Georgina Mccallum, Lauren E. Steele, Ayaho Yamamoto, Larisa I. Labzin, Tejasri Yarlagadda, Alexander A. Khromykh, Xiaohui Wang, Julian D. J. Sng, Claudia J. Stocks, Yao Xia, Tobias R. Kollmann, David Martino, Merja Joensuu, Frédéric A. Meunier, Giuseppe Balistreri, Helle Bielefeldt-Ohmann, Asha C. Bowen, Anthony Kicic, Peter D. Sly, Kirsten M. Spann, Kirsty R. Short

Research outputs 2022 to 2026

Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air-liquid interface to …


Bioturbation By Echidna (Tachyglossus Aculeatus) In A Forest Habitat, South-Western Australia, Shannon J. Dundas, Lara Osborne, Anna J. M. Hopkins, Katinka X. Ruthrof, Patricia A. Fleming Jan 2022

Bioturbation By Echidna (Tachyglossus Aculeatus) In A Forest Habitat, South-Western Australia, Shannon J. Dundas, Lara Osborne, Anna J. M. Hopkins, Katinka X. Ruthrof, Patricia A. Fleming

Research outputs 2022 to 2026

Bioturbation by digging animals is important for key forest ecosystem processes such as soil turnover, decomposition, nutrient cycling, water infiltration, seedling recruitment, and fungal dispersal. Despite their widespread geographic range, little is known about the role of the short-beaked echidna (Tachyglossus aculeatus) in forest ecosystems. We measured the density and size of echidna diggings in the Northern Jarrah Forest, south-western Australia, to quantify the contribution echidna make to soil turnover. We recorded an overall density of 298 echidna diggings per hectare, 21 % of which were estimated to be less than 1 month old. The average size of digs was …


Editorial: Fire Regimes In Desert Ecosystems: Drivers, Impacts And Changes, Eddie J. B. Van Etten, Matthew L. Brooks, Aaron C. Greenville, Glenda M. Wardle Jan 2022

Editorial: Fire Regimes In Desert Ecosystems: Drivers, Impacts And Changes, Eddie J. B. Van Etten, Matthew L. Brooks, Aaron C. Greenville, Glenda M. Wardle

Research outputs 2022 to 2026

Although not commonly associated with fire, many desert ecosystems across the globe do occasionally burn, and there is evidence that fire incidences are increasing, leading to altered fire regimes in this biome. The increased prevalence of megafires (wildfires > 10,000 ha in size and typically damaging) in most global biomes is linked to climate change, although those occurring in deserts have received far less attention, from both a research and policy perspective, than that of forested ecosystems (Linley et al., 2022). Understanding the drivers of desert fires, from climate to landscape patterns of hydrology and soil, and how these may be …


Identification Of Leukocyte Surface P2x7 As A Biomarker Associated With Alzheimer's Disease, Yihan Li, Xin Huang, Christopher Fowler, Yen Y. Lim, Simon M. Laws, Noel Faux, James D. Doecke, Brett Trounson, Kelly Pertile, Rebecca Rumble, Vincent Doré, Victor L. Villemagne, Christopher C. Rowe, James S. Wiley, Paul Maruff, Colin L. Masters, Ben J. Gu Jan 2022

Identification Of Leukocyte Surface P2x7 As A Biomarker Associated With Alzheimer's Disease, Yihan Li, Xin Huang, Christopher Fowler, Yen Y. Lim, Simon M. Laws, Noel Faux, James D. Doecke, Brett Trounson, Kelly Pertile, Rebecca Rumble, Vincent Doré, Victor L. Villemagne, Christopher C. Rowe, James S. Wiley, Paul Maruff, Colin L. Masters, Ben J. Gu

Research outputs 2022 to 2026

Alzheimer's disease (AD) has shown altered immune responses in the periphery. We studied P2X7 (a proinflammatory receptor and a scavenger receptor) and two integrins, CD11b and CD11c, on the surface of circulating leukocytes and analysed their associations with Aβ-PET, brain atrophy, neuropsychological assessments, and cerebrospinal fluid (CSF) biomarkers. Total 287 age-matched, sex-balanced participants were recruited in a discovery cohort and two validation cohorts through the AIBL study and studied using tri-colour flow cytometry. Our results demonstrated reduced expressions of P2X7, CD11b, and CD11c on leukocytes, particularly monocytes, in Aβ +ve cases compared with Aβ -ve controls. P2X7 and integrin downregulation …


Polygenic Resilience Scores Capture Protective Genetic Effects For Alzheimer’S Disease, Jiahui Hou, Jonathan L. Hess, Nicola Armstrong, Joshua C. Bis, Benjamin Grenier-Boley, Ida K. Karlsson, Ganna Leonenko, Katya Numbers, Eleanor K. O’Brien, Alexey Shadrin, Anbupalam Thalamuthu, Qiong Yang, Ole A. Andreassen, Henry Brodaty, Margaret Gatz, Nicole A. Kochan, Jean Charles Lambert, Simon M. Laws, Colin L. Masters, Karen A. Mather, Nancy L. Pedersen, Danielle Posthuma, Perminder S. Sachdev, Julie Williams, Alzheimer’S Disease Neuroimaging Initiative, Chun Chieh Fan, Stephen V. Faraone, Christine Fennema-Notestine, Shu-Ju Lin, Valentina Escott-Price, Peter Holmans, Sudha Seshadri, Ming T. Tsuang, William S. Kremen, Stephen J. Glatt Jan 2022

Polygenic Resilience Scores Capture Protective Genetic Effects For Alzheimer’S Disease, Jiahui Hou, Jonathan L. Hess, Nicola Armstrong, Joshua C. Bis, Benjamin Grenier-Boley, Ida K. Karlsson, Ganna Leonenko, Katya Numbers, Eleanor K. O’Brien, Alexey Shadrin, Anbupalam Thalamuthu, Qiong Yang, Ole A. Andreassen, Henry Brodaty, Margaret Gatz, Nicole A. Kochan, Jean Charles Lambert, Simon M. Laws, Colin L. Masters, Karen A. Mather, Nancy L. Pedersen, Danielle Posthuma, Perminder S. Sachdev, Julie Williams, Alzheimer’S Disease Neuroimaging Initiative, Chun Chieh Fan, Stephen V. Faraone, Christine Fennema-Notestine, Shu-Ju Lin, Valentina Escott-Price, Peter Holmans, Sudha Seshadri, Ming T. Tsuang, William S. Kremen, Stephen J. Glatt

Research outputs 2022 to 2026

Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience …


Relationships Between Intrauterine Fetal Growth Trajectories And Markers Of Adiposity And Inflammation In Young Adults, Ashish Yadav, Lawrence J. Beilin, Rae Chi Huang, Phil Vlaskovsky, John P. Newnham, Scott W. White, Trevor A. Mori Jan 2022

Relationships Between Intrauterine Fetal Growth Trajectories And Markers Of Adiposity And Inflammation In Young Adults, Ashish Yadav, Lawrence J. Beilin, Rae Chi Huang, Phil Vlaskovsky, John P. Newnham, Scott W. White, Trevor A. Mori

Research outputs 2022 to 2026

Background: There is now good evidence that events during gestation significantly influence the developmental well-being of an individual in later life. This study aimed to investigate the relationships between intrauterine growth trajectories determined by serial ultrasound and subsequent markers of adiposity and inflammation in the 27-year-old adult offspring from the Raine Study, an Australian longitudinal pregnancy cohort. Methods: Ultrasound fetal biometric measurements including abdominal circumference (AC), femur length (FL), and head circumference (HC) from 1333 mother-fetal pairs (Gen1–Gen2) in the Raine Study were used to develop fetal growth trajectories using group-based trajectory modeling. Linear mixed modeling investigated the relationship between …


Voluntary Activation Of Muscle In Humans: Does Serotonergic Neuromodulation Matter?, Justin J. Kavanagh, Janet L. Taylor Jan 2022

Voluntary Activation Of Muscle In Humans: Does Serotonergic Neuromodulation Matter?, Justin J. Kavanagh, Janet L. Taylor

Research outputs 2022 to 2026

Ionotropic inputs to motoneurones have the capacity to depolarise and hyperpolarise the motoneurone, whereas neuromodulatory inputs control the state of excitability of the motoneurone. Intracellular recordings of motoneurones from in vitro and in situ animal preparations have provided extraordinary insight into the mechanisms that underpin how neuromodulators regulate neuronal excitability. However, far fewer studies have attempted to translate the findings from cellular and molecular studies into a human model. In this review, we focus on the role that serotonin (5-HT) plays in muscle activation in humans. 5-HT is a potent regulator of neuronal firing rates, which can influence the force …


Squat And Countermovement Jump Performance Across A Range Of Loads: A Comparison Between Smith Machine And Free Weight Execution Modes In Elite Sprinters, Irineu Loturco, Michael R. Mcguigan, Tomás T. Freitas, Fábio Y. Nakamura, Daniel A. Boullosa, Pedro L. Valenzuela, Lucas A. Pereira, Fernando Pareja-Blanco Jan 2022

Squat And Countermovement Jump Performance Across A Range Of Loads: A Comparison Between Smith Machine And Free Weight Execution Modes In Elite Sprinters, Irineu Loturco, Michael R. Mcguigan, Tomás T. Freitas, Fábio Y. Nakamura, Daniel A. Boullosa, Pedro L. Valenzuela, Lucas A. Pereira, Fernando Pareja-Blanco

Research outputs 2022 to 2026

The aims of this study were to: 1) provide and compare the height achieved during Smith machine (SM) and free weight (FW) loaded jumps executed over a wide spectrum of loads (40–120 % of body mass [BM]); and 2) test the difference between loaded and unloaded squat jump (SJ) and countermovement jump (CMJ) attempts in ten highly trained male sprinters. On the first visit, athletes performed unloaded SJ and CMJ, loaded SJ with loads corresponding to 40, 60, 80, 100, and 120 % BM, and loaded CMJ at 100% BM using an Olympic barbell (FW). On the second visit, they …


Streaminghub: Interactive Stream Analysis Workflows, Yasith Jayawardana, Vikas G. Ashok, Sampath Jayarathna Jan 2022

Streaminghub: Interactive Stream Analysis Workflows, Yasith Jayawardana, Vikas G. Ashok, Sampath Jayarathna

Computer Science Faculty Publications

Reusable data/code and reproducible analyses are foundational to quality research. This aspect, however, is often overlooked when designing interactive stream analysis workflows for time-series data (e.g., eye-tracking data). A mechanism to transmit informative metadata alongside data may allow such workflows to intelligently consume data, propagate metadata to downstream tasks, and thereby auto-generate reusable, reproducible analytic outputs with zero supervision. Moreover, a visual programming interface to design, develop, and execute such workflows may allow rapid prototyping for interdisciplinary research. Capitalizing on these ideas, we propose StreamingHub, a framework to build metadata propagating, interactive stream analysis workflows using visual programming. We conduct …


Completing Single-Cell Dna Methylome Profiles Via Transfer Learning Together With Kl-Divergence, Sanjeeva Dodlapati, Zongliang Jiang, Jiangwen Sun Jan 2022

Completing Single-Cell Dna Methylome Profiles Via Transfer Learning Together With Kl-Divergence, Sanjeeva Dodlapati, Zongliang Jiang, Jiangwen Sun

Computer Science Faculty Publications

The high level of sparsity in methylome profiles obtained using whole-genome bisulfite sequencing in the case of low biological material amount limits its value in the study of systems in which large samples are difficult to assemble, such as mammalian preimplantation embryonic development. The recently developed computational methods for addressing the sparsity by imputing missing have their limits when the required minimum data coverage or profiles of the same tissue in other modalities are not available. In this study, we explored the use of transfer learning together with Kullback-Leibler (KL) divergence to train predictive models for completing methylome profiles with …


Spaghetti Tracer: A Framework For Tracing Semiregular Filamentous Densities In 3d Tomograms, Salim Sazzed, Peter Scheible, Jing He, Willy Wriggers Jan 2022

Spaghetti Tracer: A Framework For Tracing Semiregular Filamentous Densities In 3d Tomograms, Salim Sazzed, Peter Scheible, Jing He, Willy Wriggers

Computer Science Faculty Publications

Within cells, cytoskeletal filaments are often arranged into loosely aligned bundles. These fibrous bundles are dense enough to exhibit a certain regularity and mean direction, however, their packing is not sufficient to impose a symmetry between—or specific shape on—individual filaments. This intermediate regularity is computationally difficult to handle because individual filaments have a certain directional freedom, however, the filament densities are not well segmented from each other (especially in the presence of noise, such as in cryo-electron tomography). In this paper, we develop a dynamic programming-based framework, Spaghetti Tracer, to characterizing the structural arrangement of filaments in the challenging 3D …


Effect Of Carbon Fibres On Electromagnetic-Interference-Shielding Properties Of Geopolymer Composites, Dimuthu Wanasinghe, Farhad Aslani, Guowei Ma Jan 2022

Effect Of Carbon Fibres On Electromagnetic-Interference-Shielding Properties Of Geopolymer Composites, Dimuthu Wanasinghe, Farhad Aslani, Guowei Ma

Research outputs 2022 to 2026

Many of the construction materials available are known to cause a drastic level of damage to the environment during their manufacturing stages. Hence, many researchers have attempted to formulate construction materials that are more environmentally friendly. Additionally, the rise in wireless communications in recent decades has seen a rapid increase in electromagnetic pollution and interference, which affects the functionality of sensitive electronic devices. This research is focused on fabricating a more sustainable construction material that could prevent electromagnetic interference for electronic devices housed inside. Carbon fibres of three different lengths were added in four variations to a geopolymer control mix …


Refinement Of Alphafold2 Models Against Experimental And Hybrid Cryo-Em Density Maps, Maytha Alshammari, Willy Wriggers, Jiangwen Sun, Jing He Jan 2022

Refinement Of Alphafold2 Models Against Experimental And Hybrid Cryo-Em Density Maps, Maytha Alshammari, Willy Wriggers, Jiangwen Sun, Jing He

Computer Science Faculty Publications

Recent breakthroughs in deep learning-based protein structure prediction show that it is possible to obtain highly accurate models for a wide range of difficult protein targets for which only the amino acid sequence is known. The availability of accurately predicted models from sequences can potentially revolutionise many modelling approaches in structural biology, including the interpretation of cryo-EM density maps. Although atomic structures can be readily solved from cryo-EM maps of better than 4 Å resolution, it is still challenging to determine accurate models from lower-resolution density maps. Here, we report on the benefits of models predicted by AlphaFold2 (the best-performing …


Summary Of Cannabis Use Among Aboriginal And Torres Strait Islander People, Australian Indigenous Healthinfonet Jan 2022

Summary Of Cannabis Use Among Aboriginal And Torres Strait Islander People, Australian Indigenous Healthinfonet

Research outputs 2022 to 2026

This Summary is based on the Review of cannabis use among Aboriginal and Torres Strait Islander people. The review summarises the evidence from journal publications, government reports, national data collections and national surveys accessed through the HealthInfoNet’s database of publications. Please note that statistics presented do not always include all states and territories, see sources for details. ...


The Nursing Care Of People With Class Iii Obesity In An Acute Care Setting: A Scoping Review, Bev Ewens, Vivien Kemp, Mandy (Amanda) Towell-Barnard, Lisa Whitehead Jan 2022

The Nursing Care Of People With Class Iii Obesity In An Acute Care Setting: A Scoping Review, Bev Ewens, Vivien Kemp, Mandy (Amanda) Towell-Barnard, Lisa Whitehead

Research outputs 2022 to 2026

Background

Patients with Class III obesity pose unique challenges to health care staff and organisations. Care requirements of this population are unique and require specialised equipment and knowledge to meet these needs, maintain the quality of care, as well as the safety of patients and staff.

Aim

To synthesise the evidence on the nursing care of Class III obese patients in acute care settings.

Methods

A scoping review informed by JBI. CINAHL Plus, Medline, Scopus, Proquest Central, Web of Science and Embase were searched for primary research articles about the nursing management of people classified as Class III obese in …


Cerebrospinal Fluid Levels Of Fatty Acid–Binding Protein 3 Are Associated With Likelihood Of Amyloidopathy In Cognitively Healthy Individuals, Kunal Dhiman, Victor L. Villemagne, Christopher Fowler, Pierrick Bourgeat, Qiao-Xin Li, Steven Collins, Christopher C. Rowe, Colin L. Masters, David Ames, Kaj Blennow, Henrik Zetterberg, Ralph N. Martins, Veer Gupta Jan 2022

Cerebrospinal Fluid Levels Of Fatty Acid–Binding Protein 3 Are Associated With Likelihood Of Amyloidopathy In Cognitively Healthy Individuals, Kunal Dhiman, Victor L. Villemagne, Christopher Fowler, Pierrick Bourgeat, Qiao-Xin Li, Steven Collins, Christopher C. Rowe, Colin L. Masters, David Ames, Kaj Blennow, Henrik Zetterberg, Ralph N. Martins, Veer Gupta

Research outputs 2022 to 2026

Introduction: Fatty acid–binding protein 3 (FABP3) is a biomarker of neuronal membrane disruption, associated with lipid dyshomeostasis—a notable Alzheimer's disease (AD) pathophysiological change. We assessed the association of cerebrospinal fluid (CSF) FABP3 levels with brain amyloidosis and the likelihood/risk of developing amyloidopathy in cognitively healthy individuals. Methods: FABP3 levels were measured in CSF samples of cognitively healthy participants, > 60 years of age (n = 142), from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL). Results: FABP3 levels were positively associated with baseline brain amyloid beta (Aβ) load as measured by standardized uptake value ratio (SUVR, standardized β …


Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann Jan 2022

Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann

Faculty, Staff and Student Publications

Background and aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.

Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are …


Recent Advances On Dna Base Flipping: A General Mechanism For Writing, Reading, And Erasing Dna Modifications, Ren Ren, John R Horton, Samuel Hong, Xiaodong Cheng Jan 2022

Recent Advances On Dna Base Flipping: A General Mechanism For Writing, Reading, And Erasing Dna Modifications, Ren Ren, John R Horton, Samuel Hong, Xiaodong Cheng

Faculty, Staff and Student Publications

The modification of DNA bases is a classic hallmark of epigenetics. Four forms of modified cytosine-5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine-have been discovered in eukaryotic DNA. In addition to cytosine carbon-5 modifications, cytosine and adenine methylated in the exocyclic amine-N4-methylcytosine and N6-methyladenine-are other modified DNA bases discovered even earlier. Each modified base can be considered a distinct epigenetic signal with broader biological implications beyond simple chemical changes. Since 1994, several crystal structures of proteins and enzymes involved in writing, reading, and erasing modified bases have become available. Here, we present a structural synopsis of writers, readers, and erasers of the modified …


A Phase I, Open-Label, Dose-Escalation Study Of The Ox40 Agonist Ivuxolimab In Patients With Locally Advanced Or Metastatic Cancers, Adi Diab, Omid Hamid, John A Thompson, Willeke Ros, Ferry A L M Eskens, Toshihiko Doi, Siwen Hu-Lieskovan, Samuel J Klempner, Bishu Ganguly, Catherine Fleener, Xiao Wang, Tenshang Joh, Ken Liao, Shahram Salek-Ardakani, Carrie Turich Taylor, Jeffrey Chou, Anthony B El-Khoueiry Jan 2022

A Phase I, Open-Label, Dose-Escalation Study Of The Ox40 Agonist Ivuxolimab In Patients With Locally Advanced Or Metastatic Cancers, Adi Diab, Omid Hamid, John A Thompson, Willeke Ros, Ferry A L M Eskens, Toshihiko Doi, Siwen Hu-Lieskovan, Samuel J Klempner, Bishu Ganguly, Catherine Fleener, Xiao Wang, Tenshang Joh, Ken Liao, Shahram Salek-Ardakani, Carrie Turich Taylor, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

PURPOSE: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4

PATIENTS AND METHODS: Adult patients (

RESULTS: The most common all-causality adverse events were fatigue (46.2%), nausea (28.8%), and decreased appetite (25.0%). Of 31 treatment-related adverse events, 30 (96.8%) were grade ≤2. No dose-limiting toxicities occurred. Ivuxolimab exposure increased in a dose-proportionate manner from 0.3 to 10 mg/kg. Full peripheral blood target engagement occurred at ≥0.3 mg/kg. Three (5.8%) patients achieved a partial response, and disease control was achieved in 56% of patients. Increased CD4

CONCLUSIONS: Ivuxolimab …


Cell-Directed Aptamer Therapeutic Targeting For Cancers Including Those Within The Central Nervous System, Jun Wei, Renduo Song, Aria Sabbagh, Anantha Marisetty, Neal Shukla, Dexing Fang, Hinda Najem, Martina Ott, James Long, Lijie Zhai, Maciej S Lesniak, Charles David James, Leonidas Platanias, Michael Curran, Amy B Heimberger Jan 2022

Cell-Directed Aptamer Therapeutic Targeting For Cancers Including Those Within The Central Nervous System, Jun Wei, Renduo Song, Aria Sabbagh, Anantha Marisetty, Neal Shukla, Dexing Fang, Hinda Najem, Martina Ott, James Long, Lijie Zhai, Maciej S Lesniak, Charles David James, Leonidas Platanias, Michael Curran, Amy B Heimberger

Faculty, Staff and Student Publications

Osteopontin (OPN) is produced by tumor cells as well as by myeloid cells and is enriched in the tumor microenvironment (TME) of many cancers. Given the roles of OPN in tumor progression and immune suppression, we hypothesized that targeting OPN with aptamers that have high affinity and specificity could be a promising therapeutic strategy. Bi-specific aptamers targeting ligands for cellular internalization were conjugated to siRNAs to suppress OPN were created, and therapeutic leads were selected based on target engagement and


Comparison Of Psma-Based 18f-Dcfpyl Pet/Ct And Pelvic Multiparametric Mri For Lesion Detection In The Pelvis In Patients With Prostate Cancer, Trinh T Nguyen, Priya R Bhosale, Guofan Xu, Tinsu Pan, Peng Wei, Yang Lu Jan 2022

Comparison Of Psma-Based 18f-Dcfpyl Pet/Ct And Pelvic Multiparametric Mri For Lesion Detection In The Pelvis In Patients With Prostate Cancer, Trinh T Nguyen, Priya R Bhosale, Guofan Xu, Tinsu Pan, Peng Wei, Yang Lu

Faculty, Staff and Student Publications

Purpose: To directly compare the performance of pelvic mpMRI versus recently approved and increasingly used PSMA-based 18F-DCFPyL PET/CT in intermediate-high risk and biochemical recurrent prostate cancer patient cohort while exploring their potential differing applications in specific clinical scenarios.

Methods: A retrospective analysis was performed on patients who had 18F-DCFPyL PET/CT and pelvic mpMRI done from September 2021 to January 2022 at a single institution. The inclusion criteria were paired exams within a 3-month interval. Exclusion criteria were intervening treatment between exams, a change in PSA by more than 50% and absolute difference more than 1 ng/mL, or concurrent history of …


A Yeast Model For Trichohepatoenteric Syndrome Suggests Strong Loss Of Ski2 Function In Most Causative Mutations, Luisa J Orlando, Matthew K Yim, Thomson Hallmark, Michael Cotner, Sean J Johnson, Ambro Van Hoof Jan 2022

A Yeast Model For Trichohepatoenteric Syndrome Suggests Strong Loss Of Ski2 Function In Most Causative Mutations, Luisa J Orlando, Matthew K Yim, Thomson Hallmark, Michael Cotner, Sean J Johnson, Ambro Van Hoof

Faculty, Staff and Student Publications

The intestinal and immune disorder trichohepatoenteric syndrome (THES) is characterized by mutations in human Ski2 and Ski3, also known as SKIV2L and TTC37, respectively. The mechanism by which these mutations leads to the immunodeficiency, chronic diarrhea, failure to thrive and liver disease associated with THES is unknown. To what degree THES patient mutations in Ski2 affect Ski2 function and how the differences in Ski2 function could lead to varying patient outcomes has not been studied. Here, we assayed function of THES ski2 mutants in the yeast homolog. Our results show that most THES patient mutations cause severe dysfunction in Ski2. …


An Autoencoder-Based Deep Learning Method For Genotype Imputation, Meng Song, Jonathan Greenbaum, Joseph Luttrell, Weihua Zhou, Chong Wu, Zhe Luo, Chuan Qiu, Lan Juan Zhao, Kuan-Jui Su, Qing Tian, Hui Shen, Huixiao Hong, Ping Gong, Xinghua Shi, Hong-Wen Deng, Chaoyang Zhang Jan 2022

An Autoencoder-Based Deep Learning Method For Genotype Imputation, Meng Song, Jonathan Greenbaum, Joseph Luttrell, Weihua Zhou, Chong Wu, Zhe Luo, Chuan Qiu, Lan Juan Zhao, Kuan-Jui Su, Qing Tian, Hui Shen, Huixiao Hong, Ping Gong, Xinghua Shi, Hong-Wen Deng, Chaoyang Zhang

Faculty, Staff and Student Publications

Genotype imputation has a wide range of applications in genome-wide association study (GWAS), including increasing the statistical power of association tests, discovering trait-associated loci in meta-analyses, and prioritizing causal variants with fine-mapping. In recent years, deep learning (DL) based methods, such as sparse convolutional denoising autoencoder (SCDA), have been developed for genotype imputation. However, it remains a challenging task to optimize the learning process in DL-based methods to achieve high imputation accuracy. To address this challenge, we have developed a convolutional autoencoder (AE) model for genotype imputation and implemented a customized training loop by modifying the training process with a …


Recurrent Hgnet-Mn1 Altered (Astroblastoma Mn1-Altered) Of The Foramen Magnum: Case Report And Molecular Classification, Sricharan Gopakumar, Malcolm F Mcdonald, Himanshu Sharma, Claudio E Tatsui, Gregory N Fuller, Ganesh Rao Jan 2022

Recurrent Hgnet-Mn1 Altered (Astroblastoma Mn1-Altered) Of The Foramen Magnum: Case Report And Molecular Classification, Sricharan Gopakumar, Malcolm F Mcdonald, Himanshu Sharma, Claudio E Tatsui, Gregory N Fuller, Ganesh Rao

Faculty, Staff and Student Publications

Background: Astroblastoma is a rare primary brain tumor of unclear origin, often occurring in young patients less than 30-years-old. It typically arises supratentorially and is diagnosed based on histological features including vascular hyalinization and perivascular pseudorosettes. Recent molecular characterization of primary CNS high-grade neuroepithelial tumors with meningioma I alteration (HGNET-MN1) found that HGNET-MN1 and tumors with morphological signatures of astroblastoma clustered together. Further analysis revealed such astroblastomas have MN1 alteration and the 2021 WHO classification of tumors of the CNS now recognizes astroblastoma MN1-altered as a new entity.

Case description: Here, we present the case of …


Loss Of H2r Signaling Disrupts Neutrophil Homeostasis And Promotes Inflammation-Associated Colonic Tumorigenesis In Mice, Zhongcheng Shi, Yuko Mori-Akiyama, Wa Du, Robert Fultz, Yanling Zhao, Wenly Ruan, Susan Venable, Melinda A Engevik, James Versalovic Jan 2022

Loss Of H2r Signaling Disrupts Neutrophil Homeostasis And Promotes Inflammation-Associated Colonic Tumorigenesis In Mice, Zhongcheng Shi, Yuko Mori-Akiyama, Wa Du, Robert Fultz, Yanling Zhao, Wenly Ruan, Susan Venable, Melinda A Engevik, James Versalovic

Faculty, Staff and Students Publications

BACKGROUND & AIMS: We previously showed that histamine suppressed inflammation-associated colonic tumorigenesis through histamine type 2 receptor (H2R) signaling in mice. This study aimed to precisely elucidate the downstream effects of H2R activation in innate immune cells.

METHODS: Analyses using online databases of single-cell RNA sequencing of intestinal epithelial cells in mice and RNA sequencing of mouse immune cells were performed to determine the relative abundances of 4 histamine receptors among different cell types. Mouse neutrophils, which expressed greater amounts of H2R, were collected from the peritoneum of wild-type and H2R-deficient mice, of which low-density and high-density neutrophils were extracted …


Current State Of The Art In Hypoplastic Left Heart Syndrome, Aditya K Birla, Sunita Brimmer, Walker D Short, Oluyinka O Olutoye, Jason A Shar, Suriya Lalwani, Philippe Sucosky, Anitha Parthiban, Sundeep G Keswani, Christopher A Caldarone, Ravi K Birla Jan 2022

Current State Of The Art In Hypoplastic Left Heart Syndrome, Aditya K Birla, Sunita Brimmer, Walker D Short, Oluyinka O Olutoye, Jason A Shar, Suriya Lalwani, Philippe Sucosky, Anitha Parthiban, Sundeep G Keswani, Christopher A Caldarone, Ravi K Birla

Faculty, Staff and Students Publications

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart condition in which a neonate is born with an underdeveloped left ventricle and associated structures. Without palliative interventions, HLHS is fatal. Treatment typically includes medical management at the time of birth to maintain patency of the ductus arteriosus, followed by three palliative procedures: most commonly the Norwood procedure, bidirectional cavopulmonary shunt, and Fontan procedures. With recent advances in surgical management of HLHS patients, high survival rates are now obtained at tertiary treatment centers, though adverse neurodevelopmental outcomes remain a clinical challenge. While surgical management remains the standard of care for …


Creating An Arcgis Dashboard For Climate Data Management And Visualization, Sydney Noel Case Jan 2022

Creating An Arcgis Dashboard For Climate Data Management And Visualization, Sydney Noel Case

Senior Independent Study Theses

The College of Wooster Department of Earth Sciences has collected over the past 12 years (and continues to collect) hourly local climate indicator data including stream level and temperature, air temperature and pressure, precipitation levels, and relative humidity. This data is collected at the College’s research station, Fern Valley, located in Holmes County, Ohio and serves as a storytelling component for regional climate change. Upon initial investigation, the extensive dataset revealed a fundamental data storage problem within Earth Sciences, as there lacked a singular location to store complex datasets. Several technological solutions were explored to create a long-term data storage, …


Unearthing The Effects Of European-American Settlement On A Northeast Ohio Kettle Lake Through Diatom Stratigraphy, Justine Paul A. Berina Jan 2022

Unearthing The Effects Of European-American Settlement On A Northeast Ohio Kettle Lake Through Diatom Stratigraphy, Justine Paul A. Berina

Senior Independent Study Theses

Recently, wetland conservation has highlighted the necessity for assessing limnological changes following European-American settlement. A prior study at Brown's Lake (northeast Ohio) identified a stratigraphic sequence that shows an abrupt transition from organic-rich muds to several centimeters of a bright loess layer, then a recovery to organic-rich sediments near the top. Based on 210Pb dates, the loess deposition occurred before 1846 CE, when a growing population cleared trees and farmed intensively. Likewise, organics had recovered after 1950 CE, when people abandoned farmland and practiced conservation tillage. However, the effects of settlement on limnology are poorly known. Diatoms (microscopic algae; …


Puffins, The Charismatic Clowns Of The Sea: Examining The Relationship Between Community Identity And The Social Construction Of Animals, Megan Henry Tuennerman Jan 2022

Puffins, The Charismatic Clowns Of The Sea: Examining The Relationship Between Community Identity And The Social Construction Of Animals, Megan Henry Tuennerman

Senior Independent Study Theses

This study analyzes the factors, internal and external, that affect the relationship between community identity and the social construction of animals, and the ways in which that social construction impacts the environment. Studied through the lens of the relationship between Atlantic Puffins and the human communities they live near, these questions situate our understanding of human societies as within, as opposed to above, the environment. Without this perspective, enacting environmental protections across the globe is ineffective. The study was conducted using ethnographic methods, including 11 formal interviews with community members and experts, along with observations in Iceland and Canada. Results …


Visual Looming Cues Increases The Auditory Looming Bias, Maggie K. Mccracken Jan 2022

Visual Looming Cues Increases The Auditory Looming Bias, Maggie K. Mccracken

Senior Independent Study Theses

Looming objects have been environmentally relevant cues throughout human evolution due to potential danger. Observers integrate both auditory and visual signals emitted by moving objects. While visual arrival time estimates are relatively more accurate, auditory estimates are anticipatory as observers perceive a moving sound source as arriving before it actually does. In the present study, participants made loudness change judgments of sounds presented unimodally or with visual motion. The sounds consisted of two intensity ranges and conditions included both looming and receding motion. The results showed that listeners perceived looming sounds as changing more in loudness than equivalent receding sounds. …