Medicine and Health Sciences Commons^™

Induction Of Viral Mimicry Upon Loss Of Dhx9 And Adar1 In Breast Cancer Cells, Kyle A Cottrell, Sua Ryu, Jackson R Pierce, Luisangely Soto Torres, Holly E Bohlin, Angela M Schab, Jason D Weber

2020-Current year OA Pubs

UNLABELLED: Detection of viral double-stranded RNA (dsRNA) is an important component of innate immunity. However, many endogenous RNAs containing double-stranded regions can be misrecognized and activate innate immunity. The IFN-inducible ADAR1-p150 suppresses dsRNA sensing, an essential function for adenosine deaminase acting on RNA 1 (ADAR1) in many cancers, including breast. Although ADAR1-p150 has been well established in this role, the functions of the constitutively expressed ADAR1-p110 isoform are less understood. We used proximity labeling to identify putative ADAR1-p110-interacting proteins in breast cancer cell lines. Of the proteins identified, the RNA helicase DHX9 was of particular interest. Knockdown of DHX9 in …

Perioperative Mental Health Intervention For Depression And Anxiety Symptoms In Older Adults Study Protocol: Design And Methods For Three Linked Randomised Controlled Trials, Katherine J Holzer, Kimberly A Bartosiak, Ryan P Calfee, Chet W Hammill, Simon Haroutounian, Benjamin D Kozower, Theresa A Cordner, Emily M Lenard, Kenneth E Freedland, Bethany R Tellor Pennington, J Philip Miller, Mary C Politi, Yi Zhang, Michael D Yingling, Ana A Baumann, Thomas Kannampallil, Julia A Schweiger, Sherry L Mckinnon, Michael S Avidan, Eric J Lenze, Joanna Abraham, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Preoperative anxiety and depression symptoms among older surgical patients are associated with poor postoperative outcomes, yet evidence-based interventions for anxiety and depression have not been applied within this setting. We present a protocol for randomised controlled trials (RCTs) in three surgical cohorts: cardiac, oncological and orthopaedic, investigating whether a perioperative mental health intervention, with psychological and pharmacological components, reduces perioperative symptoms of depression and anxiety in older surgical patients.

METHODS AND ANALYSIS: Adults ≥60 years undergoing cardiac, orthopaedic or oncological surgery will be enrolled in one of three-linked type 1 hybrid effectiveness/implementation RCTs that will be conducted in tandem …

A Compendium Of Multi-Omics Data Illuminating Host Responses To Lethal Human Virus Infections, Amie J Eisfeld, Larissa B Thackray, Qing Tan, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For …

Nfĸb Signaling Drives Myocardial Injury Via Ccr2+ Macrophages In A Preclinical Model Of Arrhythmogenic Cardiomyopathy, Stephen P. Chelko, Vinay R. Penna, Morgan Engel, Emily A. Shiel, Ann M. Centner, Waleed Farra, Elisa N. Cannon, Maicon Landim-Vieira, Niccole Schaible, Kory Lavine, Jeffrey E. Saffitz

2020-Current year OA Pubs

Nuclear factor κ-B (NFκB) is activated in iPSC-cardiac myocytes from patients with arrhythmogenic cardiomyopathy (ACM) under basal conditions, and inhibition of NFκB signaling prevents disease in Dsg2mut/mut mice, a robust mouse model of ACM. Here, we used genetic approaches and single-cell RNA-Seq to define the contributions of immune signaling in cardiac myocytes and macrophages in the natural progression of ACM using Dsg2mut/mut mice. We found that NFκB signaling in cardiac myocytes drives myocardial injury, contractile dysfunction, and arrhythmias in Dsg2mut/mut mice. NFκB signaling in cardiac myocytes mobilizes macrophages expressing C-C motif chemokine receptor-2 (CCR2+ cells) to affected areas within the …

Cardiometabolic Characteristics Of People With Metabolically Healthy And Unhealthy Obesity, Max C Petersen, Gordon I Smith, Hector H Palacios, Sarah S Farabi, Mihoko Yoshino, Jun Yoshino, Kevin Cho, Victor G Davila-Roman, Ruteja A Barve, Jinsheng Yu, Jennifer H Stern, Bruce W Patterson, Gary J Patti, Samuel Klein, Et Al.

2020-Current year OA Pubs

There is considerable heterogeneity in the cardiometabolic abnormalities associated with obesity. We evaluated multi-organ system metabolic function in 20 adults with metabolically healthy obesity (MHO; normal fasting glucose and triglycerides, oral glucose tolerance, intrahepatic triglyceride content, and whole-body insulin sensitivity), 20 adults with metabolically unhealthy obesity (MUO; prediabetes, hepatic steatosis, and whole-body insulin resistance), and 15 adults who were metabolically healthy lean. Compared with MUO, people with MHO had (1) altered skeletal muscle biology (decreased ceramide content and increased expression of genes involved in BCAA catabolism and mitochondrial structure/function); (2) altered adipose tissue biology (decreased expression of genes involved in …

Using The Consolidated Framework For Implementation Research (Cfir) To Guide Implementation Of Cardio-Oncology Services, Jessica Miller Clouser, Colleen A Mcmullen, Akosua K Adu, Gretchen Wells, Amit Arbune, Jing Li

2020-Current year OA Pubs

INTRODUCTION: Cardio-oncology focuses on diagnosing and preventing adverse cardiovascular outcomes in cancer patients. Interdisciplinary cardio-oncology services address the spectrum of prevention, detection, monitoring, and treatment of cancer patients at risk of cardio-toxicity and aim to improve the continuum of cardiac care for oncology patients. The goal of this study was to engage clinician and administrative stakeholders to assess multilevel needs, barriers, and expectations regarding cardio oncology services.

METHODS: We interviewed clinicians and administrators at an academic medical center using the Consolidated Framework for Implementation Research (CFIR) to understand multilevel determinants influencing cardio-oncology service implementation. We also conducted a web-based survey …

Quality Assurance For Focused Ultrasound-Induced Blood-Brain Barrier Opening Procedure Using Passive Acoustic Detection, Chih-Yen Chien, Lu Xu, Jinyun Yuan, Siaka Fadera, Andrew H Stark, Umeshkumar Athiraman, Eric C Leuthardt, Hong Chen

2020-Current year OA Pubs

BACKGROUND: Focused ultrasound (FUS) combined with microbubbles is a promising technique for noninvasive, reversible, and spatially targeted blood-brain barrier opening, with clinical trials currently ongoing. Despite the fast development of this technology, there is a lack of established quality assurance (QA) strategies to ensure procedure consistency and safety. To address this challenge, this study presents the development and clinical evaluation of a passive acoustic detection-based QA protocol for FUS-induced blood-brain barrier opening (FUS-BBBO) procedure.

METHODS: Ten glioma patients were recruited to a clinical trial for evaluating a neuronavigation-guided FUS device. An acoustic sensor was incorporated at the center of the …

Adipose Tissue Peroxisomal Lipid Synthesis Orchestrates Obesity And Insulin Resistance Through Lxr-Dependent Lipogenesis, Brian Kleiboeker, Anyuan He, Min Tan, Dongliang Lu, Donghua Hu, Xuejing Liu, Parniyan Goodarzi, Fong-Fu Hsu, Babak Razani, Clay F Semenkovich, Irfan J Lodhi

2020-Current year OA Pubs

OBJECTIVE: Adipose tissue mass is maintained by a balance between lipolysis and lipid storage. The contribution of adipose tissue lipogenesis to fat mass, especially in the setting of high-fat feeding, is considered minor. Here we investigated the effect of adipose-specific inactivation of the peroxisomal lipid synthetic protein PexRAP on fatty acid synthase (FASN)-mediated lipogenesis and its impact on adiposity and metabolic homeostasis.

METHODS: To explore the role of PexRAP in adipose tissue, we metabolically phenotyped mice with adipose-specific knockout of PexRAP. Bulk RNA sequencing was used to determine transcriptomic responses to PexRAP deletion and

RESULTS: Adipose-specific PexRAP deletion promoted diet-induced …

Severity Of Respiratory Syncytial Virus Vs Covid-19 And Influenza Among Hospitalized Us Adults, Diya Surie, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making.

OBJECTIVE: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively …

Highly Accurate Blood Test For Alzheimer's Disease Is Similar Or Superior To Clinical Cerebrospinal Fluid Tests, Nicolas R Barthélemy, Suzanne E Schindler, Yingxin He, Benjamin Saef, Rachel L Henson, Charles D Chen, Brian A Gordon, Yan Li, Tammie L S Benzinger, John C Morris, Randall J Bateman, Et Al.

2020-Current year OA Pubs

With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. In this study, we evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n = 1,422) and the US Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC) cohort (n = 337). Matched CSF samples were analyzed with clinically used and FDA-approved automated immunoassays for Aβ42/40 …

Cholesterol 25-Hydroxylase Mediates Neuroinflammation And Neurodegeneration In A Mouse Model Of Tauopathy, Danira Toral-Rios, Justin M Long, Jason D Ulrich, Jinsheng Yu, Michael R Strickland, Xianlin Han, David M Holtzman, Anil G Cashikar, Steven M Paul

2020-Current year OA Pubs

Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles, in addition to neuroinflammation and changes in brain lipid metabolism. 25-Hydroxycholesterol (25-HC), a known modulator of both inflammation and lipid metabolism, is produced by cholesterol 25-hydroxylase encoded by Ch25h expressed as a "disease-associated microglia" signature gene. However, whether Ch25h influences tau-mediated neuroinflammation and neurodegeneration is unknown. Here, we show that in the absence of Ch25h and the resultant reduction in 25-HC, there is strikingly reduced age-dependent neurodegeneration and neuroinflammation in the hippocampus and entorhinal/piriform cortex of PS19 mice, which express the P301S mutant human tau transgene. Transcriptomic analyses of …

Threat Experiences Moderate The Link Between Hippocampus Volume And Depression Symptoms Prospectively In Adolescence, Max P Herzberg, Meriah L Dejoseph, Joan Luby, Deanna M Barch

2020-Current year OA Pubs

Identifying neuroimaging risk markers for depression has been an elusive goal in psychopathology research. Despite this, smaller hippocampal volume has emerged as a potential risk marker for depression, with recent research suggesting this association is moderated by family income. The current pre-registered study aimed to replicate and extend these findings by examining the moderating role of family income and three dimensions of environmental experience on the link between hippocampus volume and later depression. Data were drawn from the Adolescent Brain Cognitive Development (ABCD) study and were comprised of 6693 youth aged 9-10 years at baseline. Results indicated that psychosocial threat …

Medicaid Eligibility Loss Among Dual-Eligible Beneficiaries Before And During Covid-19 Public Health Emergency, Yanlei Ma, Eric T Roberts, Kenton J Johnston, E John Orav, Jose F Figueroa

2020-Current year OA Pubs

IMPORTANCE: Medicaid coverage loss can substantially compromise access to and affordability of health care for dual-eligible beneficiaries. The extent to which this population lost Medicaid coverage before and during the COVID-19 public health emergency (PHE) and the characteristics of beneficiaries more at risk for coverage loss are currently not well known.

OBJECTIVE: To assess the loss of Medicaid coverage among dual-eligible beneficiaries before and during the first year of the PHE, and to examine beneficiary-level and plan-level factors associated with heightened likelihood of losing Medicaid.

DESIGN, SETTING, AND PARTICIPANTS: This repeated cross-sectional study used national Medicare data to estimate annual …

Interstate Highway Connections And Traced Gun Transfers Between The 48 Contiguous United States, Leah Roberts, Mark H Hoofnagle, Brady Bushover, Ariana N Gobaud, Christina A Mehranbod, Carolyn Fish, Christopher N Morrison

2020-Current year OA Pubs

IMPORTANCE: Interstate gun flow has critical implications for gun violence prevention, as gun transfers across state lines can undermine local gun control policies.

OBJECTIVE: To identify possible gun trafficking routes along interstate highways in the US.

DESIGN, SETTING, AND PARTICIPANTS: This repeated-measures, ecological, cross-sectional study used data from the Bureau of Alcohol, Tobacco, Firearms and Explosives from January 1, 2010, to December 31, 2019, to examine associations between interstate connections via 13 highways that each spanned at least 1000 miles and interstate traced gun transfer counts for the 48 contiguous United States. Analyses were completed in November 2023.

EXPOSURES: Characteristics …

Cannabis Oil Extracts For Chronic Pain: What Else Can Be Learned From Another Structured Prospective Cohort?, Dorit Pud, Suhail Aamar, Bareket Schiff-Keren, Roee Sheinfeld, Silviu Brill, Dror Robinson, Yaakov Fogelman, George Habib, Haggai Sharon, Howard Amital, Boris Boltyansky, Simon Haroutounian, Elon Eisenberg

2020-Current year OA Pubs

INTRODUCTION: The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials.

OBJECTIVES: This structured, prospective questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain.

METHODS: Adult Israeli patients licensed to use cannabis oil extracts for chronic pain were followed prospectively for 6 months. The primary outcome measure was change from baseline in average weekly pain intensity, and secondary outcomes were changes in related symptoms and quality of life, recorded before treatment initiation and 1, 3, and 6 …

Mysm1 Attenuates Dna Damage Signals Triggered By Physiologic And Genotoxic Dna Breaks, Brendan Mathias, David O'Leary, Nermina Saucier, Faiz Ahmad, Lynn S White, Le'mark Russell, Marwan Shinawi, Matthew J Smith, Roshini S Abraham, Megan A Cooper, Maleewan Kitcharoensakkul, Abby M Green, Jeffrey J Bednarski

2020-Current year OA Pubs

BACKGROUND: Patients with deleterious variants in MYSM1 have an immune deficiency characterized by B-cell lymphopenia, hypogammaglobulinemia, and increased radiosensitivity. MYSM1 is a histone deubiquitinase with established activity in regulating gene expression. MYSM1 also localizes to sites of DNA injury but its function in cellular responses to DNA breaks has not been elucidated.

OBJECTIVES: This study sought to determine the activity of MYSM1 in regulating DNA damage responses (DDRs) to DNA double-stranded breaks (DSBs) generated during immunoglobulin receptor gene (Ig) recombination and by ionizing radiation.

METHODS: MYSM1-deficient pre- and non-B cells were used to determine the role of MYSM1 in DSB …

Novel Sgce Mutation In A Patient With Myoclonus-Dystonia: A Case Report, Eva Klinman, Catherine Gooch, Joel S. Perlmutter, Albert A. Davis, Baijayanta Maiti

2020-Current year OA Pubs

OBJECTIVES: Characterize the presentation, workup, and management of

METHODS: A woman with myoclonus and dystonia was identified based on clinical history and physical examination. Workup was conducted to determine the cause of her symptoms, including whole-exome sequencing. Myoclonus-dystonia is associated with more than 100 distinct mutations in MYC/DYT

RESULTS: Childhood onset myoclonus and worsening dystonia with age were identified in a young woman. She underwent screening for common causes of twitching movements, followed by whole-exome sequencing which identified a de novo novel variant in the

DISCUSSION: Myoclonus-dystonia should be considered in patients with symptoms of head and upper extremity myoclonus …

A Targeted Proteomics Method For Quantifying Plasma Apolipoprotein Kinetics In Individual Mice Using Stable Isotope Labeling, Baohai Shao, Masami Shimizu-Albergine, Farah Kramer, Jenny E Kanter, Jay W Heinecke, Tomas Vaisar, Bettina Mittendorfer, Bruce W Patterson, Karin E Bornfeldt

2020-Current year OA Pubs

Altered apolipoprotein kinetics play a critical role in promoting dyslipidemia and atherogenesis. Human apolipoprotein kinetics have been extensively evaluated, but similar studies in mice are hampered by the lack of robust methods suitable for the small amounts of blood that can be collected at sequential time points from individual mice. We describe a targeted liquid chromatography tandem mass spectrometry method for simultaneously quantifying the stable isotope enrichment of several apolipoproteins represented by multiple peptides in serial blood samples (15 μl each) obtained after retro-orbital injection of

Safety And Effectiveness Of Diazepam Nasal Spray In Male And Female Patients: Post Hoc Analysis Of Data From A Phase 3 Safety Study, James W Wheless, Robert Edward Hogan, Charles S Davis, Enrique Carrazana, Adrian L Rabinowicz

2020-Current year OA Pubs

Sex differences in drug pharmacokinetics include variations in the expression of the cytochrome P450 enzymes, which are involved in the metabolism of benzodiazepines. It is unclear whether sex influences outcomes associated with intranasally administered drugs. A post hoc analysis of sex differences was conducted to evaluate the effectiveness and safety of diazepam nasal spray, which included examining changes in the number of days between seizure clusters over time (SEIzure interVAL [SEIVAL]). Diazepam nasal spray is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Data from a phase 3 safety study were used to determine …

Enhancing Impact: A Call To Action For Equitable Implementation Science, Rachel C Shelton, Ross C Brownson

2020-Current year OA Pubs

Despite investments in evidence-based interventions and Implementation Science, most evidence-based interventions are not widely or routinely adopted, delivered, or sustained in many real-world community and healthcare settings. This gap is even greater in settings and populations experiencing numerous social and structural barriers to health, with important implications for persistent patterns in health inequities. In this Viewpoint, as part of a Special Issue on Advancing the Adaptability of Chronic Disease Prevention and Management through Implementation Science, we outline seven calls to action for the field of Implementation Science, with the goal of encouraging researchers, practitioners, and funders to be more intentional …

Neighborhood Disadvantage And Breast Cancer-Specific Survival In The Us, Neha Goel, Alexandra E Hernandez, Angela Mazul

2020-Current year OA Pubs

IMPORTANCE: Despite improvements in breast cancer screening, treatment, and survival, disparate breast cancer-specific survival outcomes persist, particularly in disadvantaged neighborhoods. Most of these disparities are attributed to disparities in individual, tumor, and treatment characteristics. However, a critical knowledge gap exists as to whether disparities in breast cancer-specific survival remain after accounting for individual, tumor, and treatment characteristics.

OBJECTIVE: To evaluate if neighborhood disadvantage is associated with shorter breast cancer-specific survival after controlling for individual, tumor, and treatment characteristics in a national population.

DESIGN, SETTING, AND PARTICIPANTS: This national retrospective cohort study included patients with breast cancer diagnosed from 2013 to …

A Protective Role For Type I Interferon Signaling Following Infection With Mycobacterium Tuberculosis Carrying The Rifampicin Drug Resistance-Conferring Rpob Mutation H445y, Suhas Bobba, Kuldeep S. Chauhan, Sadia Akter, Shibali Das, Ekansh Mittal, Barun Mathema, Jennifer A. Philips, Shabaana A. Khader

2020-Current year OA Pubs

Interleukin-1 (IL-1) signaling is essential for controlling virulent Mycobacterium tuberculosis (Mtb) infection since antagonism of this pathway leads to exacerbated pathology and increased susceptibility. In contrast, the triggering of type I interferon (IFN) signaling is associated with the progression of tuberculosis (TB) disease and linked with negative regulation of IL-1 signaling. However, mice lacking IL-1 signaling can control Mtb infection if infected with an Mtb strain carrying the rifampin-resistance conferring mutation H445Y in its RNA polymerase β subunit (rpoB-H445Y Mtb). The mechanisms that govern protection in the absence of IL-1 signaling during rpoB-H445Y Mtb infection are unknown. In this study, …

Cognitive Outcomes Of Children With Sagittal Craniosynostosis Treated With Either Endoscopic Or Open Calvarial Vault Surgery, Suresh N Magge, Annahita R Fotouhi, Virginia Allhusen, Brent R Collett, Gary B Skolnick, Sybill D Naidoo, Matthew D Smyth, Robert F Keating, Raj Vyas, Gary F Rogers, Kamlesh B Patel

2020-Current year OA Pubs

IMPORTANCE: Several studies have reported a higher incidence of neurodevelopmental delays and cognitive deficits in patients with single-suture craniosynostosis; however, there are few studies examining the associations of repair type with cognitive outcomes.

OBJECTIVE: To measure differences in neuropsychological outcomes between school-age children who were treated for sagittal craniosynostosis and unaffected controls and explore differences in cognitive function among children with sagittal craniosynostosis who were previously treated with either endoscopic strip craniectomy or open calvarial vault surgery.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was performed between 2018 and 2022. Eligible participants included patients aged 5 to 17 years who …

Abatacept Pharmacokinetics And Exposure Response In Patients Hospitalized With Covid-19: A Secondary Analysis Of The Activ-1 Im Randomized Clinical Trial, Stephen J Balevic, Daniel K Benjamin, William G Powderly, P Brian Smith, Daniel Gonzalez, Matthew W Mccarthy, Linda K Shaw, Christopher J Lindsell, Sam Bozzette, Daphne Williams, Benjamin P Linas, John Blamoun, Heta Javeri, Christoph P Hornik, Activ-1 Im Study Group

2020-Current year OA Pubs

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 …

Brain High-Throughput Multi-Omics Data Reveal Molecular Heterogeneity In Alzheimer's Disease, Abdallah M. Eteleeb, Brenna C. Novotny, Carolina Soriano Tarraga, Christopher Sohn, Eliza Dhungel, Logan Brase, Aasritha Nallapu, Jared Buss, Fabiana Farias, Kristy Bergmann, Joseph Bradley, Joanne Norton, Jen Gentsch, Fengxian Wang, Albert A. Davis, John C. Morris, Celeste M. Karch, Richard J. Perrin, Bruno A. Benitez, Oscar Harari

2020-Current year OA Pubs

Unbiased data-driven omic approaches are revealing the molecular heterogeneity of Alzheimer disease. Here, we used machine learning approaches to integrate high-throughput transcriptomic, proteomic, metabolomic, and lipidomic profiles with clinical and neuropathological data from multiple human AD cohorts. We discovered 4 unique multimodal molecular profiles, one of them showing signs of poor cognitive function, a faster pace of disease progression, shorter survival with the disease, severe neurodegeneration and astrogliosis, and reduced levels of metabolomic profiles. We found this molecular profile to be present in multiple affected cortical regions associated with higher Braak tau scores and significant dysregulation of synapse-related genes, endocytosis, …

Feasibility Of Surface-Guidance Combined With Cbct For Intra-Fractional Breath-Hold Motion Management During Ethos Rt, Taeho Kim, Eric Laugeman, Kendall Kiser, Joshua Schiff, Shanti Marasini, Alex Price, H Michael Gach, Nels Knutson, Pamela Samson, Clifford Robinson, Casey Hatscher, Lauren Henke

2020-Current year OA Pubs

PURPOSE: High-quality CBCT and AI-enhanced adaptive planning techniques allow CBCT-guided stereotactic adaptive radiotherapy (CT-STAR) to account for inter-fractional anatomic changes. Studies of intra-fractional respiratory motion management with a surface imaging solution for CT-STAR have not been fully conducted. We investigated intra-fractional motion management in breath-hold Ethos-based CT-STAR and CT-SBRT (stereotactic body non-adaptive radiotherapy) using optical surface imaging combined with onboard CBCTs.

METHODS: Ten cancer patients with mobile lower lung or upper abdominal malignancies participated in an IRB-approved clinical trial (Phase I) of optical surface image-guided Ethos CT-STAR/SBRT. In the clinical trial, a pre-configured gating window (± 2 mm in AP …

Automated Model Building And Protein Identification In Cryo-Em Maps, Kiarash Jamali, Lukas Käll, Rui Zhang, Alan Brown, Dari Kimanius, Sjors H W Scheres

2020-Current year OA Pubs

Interpreting electron cryo-microscopy (cryo-EM) maps with atomic models requires high levels of expertise and labour-intensive manual intervention in three-dimensional computer graphics programs

Degenerative Meniscus Tears Treated Nonoperatively With Platelet-Rich Plasma Yield Variable Clinical And Imaging Outcomes: A Systematic Review, Varun Gopinatth, Anjay K Batra, Jorge Chahla, Matthew V Smith, Matthew J Matava, Robert H Brophy, Derrick M Knapik

2020-Current year OA Pubs

PURPOSE: To perform a systematic review on clinical and radiologic outcomes for meniscus tears treated nonoperatively with platelet-rich plasma (PRP).

METHODS: A literature search was performed according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using keywords and Boolean operators in SCOPUS, PubMed, Medline, and the Cochrane Central Register for Controlled Trials in April 2023. Inclusion criteria were limited to Level I to IV human studies reporting on outcomes of meniscus tears treated nonoperatively with PRP.

RESULTS: A total of 6 studies, consisting of 184 patients, were identified. There was 1 Level I study and 5 …

Hspa9/Mortalin Inhibition Disrupts Erythroid Maturation Through A Tp53-Dependent Mechanism In Human Cd34+ Hematopoietic Progenitor Cells, Christopher Butler, Morgan Dunmire, Jaebok Choi, Gabor Szalai, Anissa Johnson, Wei Lei, Xin Chen, Liang Liu, Wei Li, Matthew J Walter, Tuoen Liu

2020-Current year OA Pubs

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies characterized by abnormal hematopoietic cell maturation, increased apoptosis of bone marrow cells, and anemia. They are the most common myeloid blood cancers in American adults. The full complement of gene mutations that contribute to the phenotypes or clinical symptoms in MDS is not fully understood. Around 10%-25% of MDS patients harbor an interstitial heterozygous deletion on the long arm of chromosome 5 [del(5q)], creating haploinsufficiency for a large set of genes, including HSPA9. The HSPA9 gene encodes for the protein mortalin, a highly conserved heat shock protein …

Practical Considerations For Delandistrogene Moxeparvovec Gene Therapy In Patients With Duchenne Muscular Dystrophy, Jerry R Mendell, Crystal Proud, Craig M Zaidman, Stefanie Mason, Eddie Darton, Shufang Wang, Christoph Wandel, Alexander P Murphy, Eugenio Mercuri, Francesco Muntoni, Craig M Mcdonald

2020-Current year OA Pubs

BACKGROUND: Delandistrogene moxeparvovec is a gene transfer therapy approved in the United States, United Arab Emirates, and Qatar for the treatment of ambulatory patients aged four through five years with a confirmed Duchenne muscular dystrophy (DMD)-causing mutation in the DMD gene. This therapy was developed to address the underlying cause of DMD through targeted skeletal, respiratory, and cardiac muscle expression of delandistrogene moxeparvovec micro-dystrophin, an engineered, functional dystrophin protein.

METHODS: Drawing on clinical trial experience from Study 101 (NCT03375164), Study 102 (NCT03769116), and ENDEAVOR (Study 103; NCT04626674), we outline practical considerations for delandistrogene moxeparvovec treatment.

RESULTS: Before infusion, the following …