Digital Commons Network^™

Anabolic Resistance Of Muscle Protein Turnover Comes In Various Shapes And Sizes, Kevin J M Paulussen, Colleen F Mckenna, Joseph W Beals, Kenneth R Wilund, Amadeo F Salvador, Nicholas A Burd

2020-Current year OA Pubs

Anabolic resistance is defined by a blunted stimulation of muscle protein synthesis rates (MPS) to common anabolic stimuli in skeletal muscle tissue such as dietary protein and exercise. Generally, MPS is the target of most exercise and feeding interventions as muscle protein breakdown rates seem to be less responsive to these stimuli. Ultimately, the blunted responsiveness of MPS to dietary protein and exercise underpins the loss of the amount and quality of skeletal muscle mass leading to decrements in physical performance in these populations. The increase of both habitual physical activity (including structured exercise that targets general fitness characteristics) and …

Convalescent Plasma Therapy For Covid-19: A Graphical Mosaic Of The Worldwide Evidence, Stephen A Klassen, Brenda J Grossman, Jeffrey P Henderson, Et Al.

2020-Current year OA Pubs

Convalescent plasma has been used worldwide to treat patients hospitalized with coronavirus disease 2019 (COVID-19) and prevent disease progression. Despite global usage, uncertainty remains regarding plasma efficacy, as randomized controlled trials (RCTs) have provided divergent evidence regarding the survival benefit of convalescent plasma. Here, we argue that during a global health emergency, the mosaic of evidence originating from multiple levels of the epistemic hierarchy should inform contemporary policy and healthcare decisions. Indeed, worldwide matched-control studies have generally found convalescent plasma to improve COVID-19 patient survival, and RCTs have demonstrated a survival benefit when transfused early in the disease course but …

Temozolomide Chronotherapy In Patients With Glioblastoma: A Retrospective Single-Institute Study, Anna R Damato, Jingqin Luo, Ruth G N Katumba, Grayson R Talcott, Joshua B Rubin, Erik D Herzog, Jian L Campian

2020-Current year OA Pubs

BACKGROUND: Chronotherapy is an innovative approach to improving survival through timed delivery of anti-cancer treatments according to patient daily rhythms. Temozolomide (TMZ) is a standard-of-care chemotherapeutic agent for glioblastoma (GBM). Whether timing of TMZ administration affects GBM patient outcome has not previously been studied. We sought to evaluate maintenance TMZ chronotherapy on GBM patient survival.

METHODS: This retrospective study reviewed patients with newly diagnosed GBM from January 1, 2010 to December 31, 2018 at Washington University School of Medicine who had surgery, chemoradiation, and were prescribed TMZ to be taken in the morning or evening. The Kaplan-Meier method and Cox …

Immune Cell Analysis Of Pilocytic Astrocytomas Reveals Sexually Dimorphic Brain Region-Specific Differences In T-Cell Content, Jie Chen, Namita Sinha, Olivia Cobb, Collin Liu, Ayca Ersen, Joanna J Phillips, Tarik Tihan, David H Gutmann, Sonika Dahiya

2020-Current year OA Pubs

No abstract provided.

Salvage Therapies For Radiation-Relapsed Isocitrate Dehydrogenase-Mutant Astrocytoma And 1p/19q Codeleted Oligodendroglioma, Sirui Ma, Soumon Rudra, Jian L Campian, Milan G Chheda, Tanner M Johanns, George Ansstas, Christopher D Abraham, Michael R Chicoine, Eric C Leuthardt, Joshua L Dowling, Gavin P Dunn, Albert H Kim, Jiayi Huang

2020-Current year OA Pubs

BACKGROUND: Optimal management for recurrent IDH-mutant glioma after radiation therapy (RT) is not well-defined. This study assesses practice patterns for managing recurrent IDH-mutant astrocytoma (Astro) and 1p/19q codeleted oligodendroglioma (Oligo) after RT and surveys their clinical outcomes after different salvage approaches.

METHODS: Ninety-four recurrent Astro or Oligo patients after RT who received salvage systemic therapy (SST) between 2001 and 2019 at a tertiary cancer center were retrospectively analyzed. SST was defined as either alkylating chemotherapy (AC) or nonalkylating therapy (non-AC). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method from the start of SST. Multivariable analysis …

Validation Of Diffusion Mri As A Biomarker For Efficacy Using Randomized Phase Iii Trial Of Bevacizumab With Or Without Vb-111 In Recurrent Glioblastoma, Benjamin M Ellingson, Jian L Campian, Et Al.

2020-Current year OA Pubs

BACKGROUND: Evidence from single and multicenter phase II trials have suggested diffusion MRI is a predictive imaging biomarker for survival benefit in recurrent glioblastoma (rGBM) treated with anti-VEGF therapy. The current study confirms these findings in a large, randomized phase III clinical trial.

METHODS: Patients with rGBM were enrolled in a phase III randomized (1:1), controlled trial (NCT02511405) to compare the efficacy and safety of bevacizumab (BV) versus BV in combination with ofranergene obadenovec (BV+VB-111), an anti-cancer viral therapy. In 170 patients with diffusion MRI available, pretreatment enhancing tumor volume and ADC histogram analysis were used to phenotype patients as …

Profiles Of Hiv Care Disruptions Among Adult Patients Lost To Follow-Up In Zambia: A Latent Class Analysis, Aaloke Mody, Kombatende Sikombe, Laura K. Beres, Sandra Simbeza, Njekwa Mukamba, Ingrid Eshun-Wilson, Sheree Schwartz, Jake Pry, Nancy Padian, Charles B. Holmes, Carolyn Bolton-Moore, Izukanji Sikazwe, Elvin H. Geng

2020-Current year OA Pubs

BACKGROUND: Patients report varied barriers to HIV care across multiple domains, but specific barrier patterns may be driven by underlying, but unobserved, behavioral profiles.

METHODS: We traced a probability sample of patients lost to follow-up (>90 days late) as of July 31, 2015 from 64 clinics in Zambia. Among those found alive, we ascertained patient-reported reasons for care disruptions. We performed latent class analysis to identify patient subgroups with similar patterns of reasons reported and assessed the association between class membership and care status (ie, disengaged versus silently transferred to a new site).

RESULTS: Among 547 patients, we identified …

Homotopic Functional Connectivity Disruptions In Glioma Patients Are Associated With Tumor Malignancy And Overall Survival, Andy G S Daniel, Carl D Hacker, John J Lee, Donna Dierker, Joseph B Humphries, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Gliomas exhibit widespread bilateral functional connectivity (FC) alterations that may be associated with tumor grade. Limited studies have examined the connection-level mechanisms responsible for these effects. Given the typically strong FC observed between mirroring/homotopic brain regions in healthy subjects, we hypothesized that homotopic connectivity (HC) is altered in low-grade and high-grade glioma patients and the extent of disruption is associated with tumor grade and predictive of overall survival (OS) in a cohort of

METHODS: We used a mirrored FC-derived cortical parcellation to extract blood-oxygen-level-dependent (BOLD) signals and to quantify FC differences between homotopic pairs in normal-appearing brain in a …

Exploring Intentional Medication Non-Adherence In Patients With Systemic Lupus Erythematosus: The Role Of Physician-Patient Interactions, Jerik Leung, Elizabeth A Baker, Alfred H J Kim

2020-Current year OA Pubs

OBJECTIVE: Medication non-adherence contributes to worse health outcomes among SLE patients. The underlying mechanisms that drive medication non-adherence are poorly understood. The purpose of this study was to explore possible mechanisms of medication non-adherence by eliciting patient experiences.

METHODS: Consented adult patients with ACR- or SLICC-classified SLE were recruited. Ten semi-structured interviews were conducted across six participants. Interviews were audio recorded, transcribed, and analysed using an iterative process. The findings were presented to an interactive public forum with SLE patients, family members and friends of patients, and health-care professionals to assess validity and for elaboration of the concepts developed.

RESULTS: …

A Genetic Mouse Model With Postnatal Nf1 And P53 Loss Recapitulates The Histology And Transcriptome Of Human Malignant Peripheral Nerve Sheath Tumor, Akira Inoue, Laura J Janke, Brian L Gudenas, Hongjian Jin, Yiping Fan, Joshua Paré, Michael R Clay, Paul A Northcott, Angela C Hirbe, Xinwei Cao

2020-Current year OA Pubs

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas. Somatic inactivation of

METHODS: We combined 2 genetically modified alleles, an

RESULTS: Postnatal

CONCLUSIONS: The NP-Plp model recapitulates human MPNST genetically, histologically, and molecularly.

A Phase Ii Study Of Laser Interstitial Thermal Therapy Combined With Doxorubicin In Patients With Recurrent Glioblastoma, Omar H Butt, Alice Y Zhou, Jiayi Huang, William A Leidig, Alice E Silberstein, Milan G Chheda, Tanner M Johanns, George Ansstas, Jingxia Liu, Grayson Talcott, Ruth Nakiwala, Joshua S Shimony, Albert H Kim, Eric C Leuthardt, Jian L Campian, Et Al.

2020-Current year OA Pubs

BACKGROUND: The blood-brain barrier (BBB) is a major limiting factor for drug delivery in brain tumors. Laser interstitial thermal therapy (LITT) disrupts the peritumoral BBB. In this study, we examine survival in patients with recurrent glioblastoma (GBM) treated with LITT followed by low-dose doxorubicin, a potent anti-neoplastic drug with poor BBB permeability.

METHODS: Forty-one patients with recurrent GBM were enrolled; thirty patients were evaluable. Participants underwent LITT followed by 6 weekly doxorubicin treatments starting within one week (Early Arm) or at 6-8 weeks (Late Arm) after LITT. The overall survival (OS), local progression-free survival (PFS), and any PFS were compared …

The Next Generation Of Ocular Pathogen Detection, Sharon L. Sabapathypillai, Hayley R. James, Rachael R. L. Lyerla, Lynn Hassman

2020-Current year OA Pubs

Metagenomic next-generation sequencing is a powerful method for pathogen detection that combines advanced genome sequencing technology with cutting-edge bioinformatics to analyze microbial populations. Metagenomic next-generation sequencing has the potential to identify uncommon, unculturable, and even previously unidentified pathogens from a clinical isolate. Of particular interest to ophthalmology, this robust data extraction can occur from very small volume clinical samples. Here we discuss the opportunities and limitations of this technique and their current and future application to ophthalmic diagnostics.

Inhibition Of Nox1 Mitigates Blood Pressure Increases In Elastin Insufficiency, Angela Troia, Russell H Knutsen, Carmen M Halabi, Daniela Malide, Zu Xi Yu, Amanda Wardlaw-Pickett, Elise K Kronquist, Kit Man Tsang, Attila Kovacs, Robert P Mecham, Beth A Kozel

2020-Current year OA Pubs

Elastin (ELN) insufficiency leads to the cardiovascular hallmarks of the contiguous gene deletion disorder, Williams-Beuren syndrome, including hypertension and vascular stiffness. Previous studies showed that Williams-Beuren syndrome deletions, which extended to include the

Detection Of Β-Amyloid Positivity In Alzheimer's Disease Neuroimaging Initiative Participants With Demographics, Cognition, Mri And Plasma Biomarkers, Duygu Tosun, James Bollinger, Vitaliy Ovod, Kwasi G Mawuenyega, Randall J Bateman, Et Al.

2020-Current year OA Pubs

No abstract provided.

Nonliteral Language Processing Across The Lifespan, Kathrin Rothermich, Cristal Giorio, Sharon Falkins, Lindsay Leonard, Angela Roberts

2020-Current year OA Pubs

Studies investigating the effects of aging on nonliteral language processing have mainly focused on one sensory modality, for example written vignettes. In the current study, we used a video-based task to examine the effect of healthy aging on social communication perception using a novel database called RISC (Relation Inference in Social Communication). By means of an online recruitment platform, we asked young, middle-aged, and older adults between the ages of 18 and 76 (N = 100) to evaluate videos of actors using different forms of literal and nonliteral language, such as sarcasm or teasing. The participants' task was to infer …

Context-Responsive Anticoagulation Reduces Complications In Pediatric Extracorporeal Membrane Oxygenation, John C Lin, Lauren M Barron, Adam M Vogel, Ryan M Colvin, Sirine A Baltagi, Allan Doctor, Avihu Z Gazit, Mary Mehegan, Nicole O'Connor, Ahmed S Said, Mark Shepard, Michael Wallendorf, Philip C Spinella

2020-Current year OA Pubs

No abstract provided.

Electrophysiological And Molecular Mechanisms Of Sinoatrial Node Mechanosensitivity, Daniel Turner, Chen Kang, Pietro Mesirca, Juan Hong, Matteo E Mangoni, Alexey V Glukhov, Rajan Sah

2020-Current year OA Pubs

The understanding of the electrophysiological mechanisms that underlie mechanosensitivity of the sinoatrial node (SAN), the primary pacemaker of the heart, has been evolving over the past century. The heart is constantly exposed to a dynamic mechanical environment; as such, the SAN has numerous canonical and emerging mechanosensitive ion channels and signaling pathways that govern its ability to respond to both fast (within second or on beat-to-beat manner) and slow (minutes) timescales. This review summarizes the effects of mechanical loading on the SAN activity and reviews putative candidates, including fast mechanoactivated channels (Piezo, TREK, and BK) and slow mechanoresponsive ion channels …

The Genomics Of Heart Failure: Design And Rationale Of The Hermes Consortium, R. Thomas Lumbers, Douglas Mann, Et Al.

2020-Current year OA Pubs

No abstract provided.

Clinical Challenges In The Management Of Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: A Literature Review, Gayathri Nagaraj, Cynthia X Ma

2020-Current year OA Pubs

Endocrine therapy (ET) is integral to the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Aromatase inhibitors (AIs; e.g., anastrozole, letrozole, exemestane), selective estrogen receptor modulators (e.g., tamoxifen), and the selective estrogen receptor degrader, fulvestrant, inhibit tumor cell proliferation by targeting ER signaling. However, the efficacy of ET could be limited by intrinsic and acquired resistance mechanisms, which has prompted the development of targeted agents and combination strategies. In recent years, the treatment landscape for HR+, HER2- MBC has evolved rapidly. AIs, historically the first-line treatment for postmenopausal patients with HR+, HER2- …