Digital Commons Network^™

Abundance Of Acvr1b Transcript Is Elevated During Septic Conditions: Perspectives Obtained From A Hands-On Reductionist Investigation, Anucha Preechanukul, Thatcha Yimthin, Sarunporn Tandhavanant, Tobias Brummaier, Chalita Chomkatekaew, Sukanta Das, Basirudeen Syed Ahamed Kabeer, Mohammed Toufiq, Darawan Rinchai, T Eoin West, Damien Chaussabel, Narisara Chantratita, Mathieu Garand

2020-Current year OA Pubs

Sepsis is a complex heterogeneous condition, and the current lack of effective risk and outcome predictors hinders the improvement of its management. Using a reductionist approach leveraging publicly available transcriptomic data, we describe a knowledge gap for the role of ACVR1B (activin A receptor type 1B) in sepsis. ACVR1B, a member of the transforming growth factor-beta (TGF-beta) superfamily, was selected based on the following: 1) induction upon

Predicting Incident Cardiovascular Disease Among African-American Adults: A Deep Learning Approach To Evaluate Social Determinants Of Health In The Jackson Heart Study, Matthew C. Morris, Hamidreza Moradi, Maryam Aslani, Mario Sims, David Schlundt, Chrystyna D. Kouros, Burel Goodin, Crystal Lim, Kerry Kinney

2020-Current year OA Pubs

The present study sought to leverage machine learning approaches to determine whether social determinants of health improve prediction of incident cardiovascular disease (CVD). Participants in the Jackson Heart study with no history of CVD at baseline were followed over a 10-year period to determine first CVD events (i.e., coronary heart disease, stroke, heart failure). Three modeling algorithms (i.e., Deep Neural Network, Random Survival Forest, Penalized Cox Proportional Hazards) were used to evaluate three feature sets (i.e., demographics and standard/biobehavioral CVD risk factors [FS1], FS1 combined with psychosocial and socioeconomic CVD risk factors [FS2], and FS2 combined with environmental features [FS3]) …

Expression Of Non-Phosphorylatable S5a-L-Plastin Exerts Phenotypes Distinct From L-Plastin Deficiency During Podosome Formation And Phagocytosis, Xue Lin, Praveen Krishnamoorthy, Emma C Walker, Hemant Joshi, Sharon Celeste Morley

2020-Current year OA Pubs

No abstract provided.

The Relationship Of Trait-Like Compassion With Epigenetic Aging: The Population-Based Prospective Young Finns Study, Henrik Dobewall, Liisa Keltikangas-Järvinen, Saara Marttila, Pashupati P Mishra, Aino Saarinen, C Robert Cloninger, Igor Zwir, Mika Kähönen, Mikko Hurme, Olli Raitakari, Terho Lehtimäki, Mirka Hintsanen

2020-Current year OA Pubs

INTRODUCTION: Helping others within and beyond the family has been related to living a healthy and long life. Compassion is a prosocial personality trait characterized by concern for another person who is suffering and the motivation to help. The current study examines whether epigenetic aging is a potential biological mechanism that explains the link between prosociality and longevity.

METHODS: We used data from the Young Finns Study that follows six birth-cohorts from age 3-18 to 19-49. Trait-like compassion for others was measured with the Temperament and Character Inventory in the years 1997 and 2001. Epigenetic age acceleration and telomere length …

Treg-Specific Deletion Of The Phosphatase Shp-1 Impairs Control Of Inflammation In Vivo, Qinlei Gu, Kenneth S Tung, Ulrike M Lorenz

2020-Current year OA Pubs

INTRODUCTION: To achieve a healthy and functional immune system, a delicate balance exists between the activation of conventional T cells (Tcon cells) and the suppression by regulatory T cells (Treg). The tyrosine phosphatase SHP-1, a negative regulator of TCR signaling, shapes this 'activation-suppression' balance by modulating Tcon cell resistance to Treg-mediated suppression. Treg cells also express SHP-1, but its role in influencing Treg function is still not fully understood.

METHODS: We generated a Treg-specific SHP-1 deletion model,

RESULTS: We show that SHP-1 modulates Treg suppressive function at different levels. First, at the intracellular signaling level in Treg cells, SHP-1 attenuates …

The In Vivo Study Of Cardiac Mechano-Electric And Mechano-Mechanical Coupling During Heart Development In Zebrafish, Jonathan S Baillie, Alex Gendernalik, Deborah M Garrity, David Bark Jr, T Alexander Quinn

2020-Current year OA Pubs

In the adult heart, acute adaptation of electrical and mechanical activity to changes in mechanical load occurs

Phagocytosis Is A Primary Determinant Of Pulmonary Clearance Of Clinical Klebsiella Pneumoniae Isolates, Rick Van Der Geest, Hongye Fan, Hernán F Peñaloza, William G Bain, Zeyu Xiong, Naina Kohli, Emily Larson, Mara L G Sullivan, Jonathan M Franks, Donna B Stolz, Ryota Ito, Kong Chen, Yohei Doi, Melanie J Harriff, Janet S Lee

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We screened 19 clinical respiratory

RESULTS: The respiratory

CONCLUSION: Altogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical

Qunex-An Integrative Platform For Reproducible Neuroimaging Analytics, Jie Lisa Ji, Matthew F Glasser, Michael P Harms, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Neuroimaging technology has experienced explosive growth and transformed the study of neural mechanisms across health and disease. However, given the diversity of sophisticated tools for handling neuroimaging data, the field faces challenges in method integration, particularly across multiple modalities and species. Specifically, researchers often have to rely on siloed approaches which limit reproducibility, with idiosyncratic data organization and limited software interoperability.

METHODS: To address these challenges, we have developed Quantitative Neuroimaging Environment & Toolbox (QuNex), a platform for consistent end-to-end processing and analytics. QuNex provides several novel functionalities for neuroimaging analyses, including a "turnkey" command for the reproducible deployment …

What Is Operative? Conceptualizing Neuralgia: Neuroma, Compression Neuropathy, Painful Hyperalgesia, And Phantom Nerve Pain, Elspeth J R Hill, J Megan M Patterson, Andrew Yee, Lara W Crock, Susan E Mackinnon

2020-Current year OA Pubs

Neuralgia, or nerve pain, is a common presenting complaint for the hand surgeon. When the nerve at play is easily localized, and the cause of the pain is clear (eg, carpal tunnel syndrome), the patient may be easily treated with excellent results. However, in more complex cases, the underlying pathophysiology and cause of neuralgia can be more difficult to interpret; if incorrectly managed, this leads to frustration for both the patient and surgeon. Here we offer a way to conceptualize neuralgia into 4 categories-compression neuropathy, neuroma, painful hyperalgesia, and phantom nerve pain-and offer an illustrative clinical vignette and strategies for …

Disease-Causing Mutations In Genes Encoding Transcription Factors Critical For Photoreceptor Development, Chi Sun, Shiming Chen

2020-Current year OA Pubs

Photoreceptor development of the vertebrate visual system is controlled by a complex transcription regulatory network. OTX2 is expressed in the mitotic retinal progenitor cells (RPCs) and controls photoreceptor genesis. CRX that is activated by OTX2 is expressed in photoreceptor precursors after cell cycle exit. NEUROD1 is also present in photoreceptor precursors that are ready to specify into rod and cone photoreceptor subtypes. NRL is required for the rod fate and regulates downstream rod-specific genes including the orphan nuclear receptor NR2E3 which further activates rod-specific genes and simultaneously represses cone-specific genes. Cone subtype specification is also regulated by the interplay of …

Whole-Brain Imaging Of Freely-Moving Zebrafish, Hamid Hasani, Jipeng Sun, Shuyu I Zhu, Qiangzhou Rong, Florian Willomitzer, Rumelo Amor, Gail Mcconnell, Oliver Cossairt, Geoffrey J Goodhill

2020-Current year OA Pubs

One of the holy grails of neuroscience is to record the activity of every neuron in the brain while an animal moves freely and performs complex behavioral tasks. While important steps forward have been taken recently in large-scale neural recording in rodent models, single neuron resolution across the entire mammalian brain remains elusive. In contrast the larval zebrafish offers great promise in this regard. Zebrafish are a vertebrate model with substantial homology to the mammalian brain, but their transparency allows whole-brain recordings of genetically-encoded fluorescent indicators at single-neuron resolution using optical microscopy techniques. Furthermore zebrafish begin to show a complex …

A Novel Approach For Assessing Bias During Team-Based Clinical Decision-Making, Natalie Pool, Megan Hebdon, Esther De Groot, Ryan Yee, Kathryn Herrera-Theut, Erika Yee, Larry A Allen, Ayesha Hasan, Joann Lindenfeld, Elizabeth Calhoun, Molly Carnes, Nancy K Sweitzer, Khadijah Breathett

2020-Current year OA Pubs

Many clinical processes include multidisciplinary group decision-making, yet few methods exist to evaluate the presence of implicit bias during this collective process. Implicit bias negatively impacts the equitable delivery of evidence-based interventions and ultimately patient outcomes. Since implicit bias can be difficult to assess, novel approaches are required to detect and analyze this elusive phenomenon. In this paper, we describe how the de Groot Critically Reflective Diagnoses Protocol (DCRDP) can be used as a data analysis tool to evaluate group dynamics as an essential foundation for exploring how interactions can bias collective clinical decision-making. The DCRDP includes 6 distinct criteria: …

Precision Neuromodulation: Promises And Challenges Of Spinal Stimulation For Multi-Modal Rehabilitation, Maria F Bandres, Jefferson L Gomes, Gerson N Moreno Romero, Avery R Twyman, Jacob Graves Mcpherson

2020-Current year OA Pubs

Spinal cord injury results in multiple, simultaneous sensorimotor deficits. These include, but are not limited to, full or partial paralysis of muscles below the lesion, muscle spasms, spasticity, and neuropathic pain. Bowel, bladder, and sexual dysfunction are also prevalent. Yet, the majority of emerging spinal stimulation-based therapies focus on a single issue: locomotor rehabilitation. Despite the enormous potential of these translational advances to transform the lives of people living with spinal cord injury, meaningful recovery in other domains deemed critical priorities remains lacking. Here, we highlight the importance of considering the diverse patterns of neural transmission that underlie clinically similar …

Designing Implementation Strategies To Improve Identification, Cascade Testing, And Management Of Families With Familial Hypercholesterolemia: An Intervention Mapping Approach, Laney K Jones, Ross C Brownson, Anne C Goldberg, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Familial hypercholesterolemia (FH) is a common inherited cholesterol disorder that, without early intervention, leads to premature cardiovascular disease. Multilevel strategies that target all components of FH care including identification, cascade testing, and management are needed to address gaps that exist in FH care. We utilized intervention mapping, a systematic implementation science approach, to identify and match strategies to existing barriers and develop programs to improve FH care.

METHODS: Data were collected utilizing two methods: a scoping review of published literature, related to any component of FH care, and a parallel mixed method study using interviews and surveys. The scientific …

The Function Of Histone Methylation And Acetylation Regulators In Gbm Pathophysiology, Colin Mccornack, Timothy Woodiwiss, Angela Hardi, Hiroko Yano, Albert H Kim

2020-Current year OA Pubs

Glioblastoma (GBM) is the most common and lethal primary brain malignancy and is characterized by a high degree of intra and intertumor cellular heterogeneity, a starkly immunosuppressive tumor microenvironment, and nearly universal recurrence. The application of various genomic approaches has allowed us to understand the core molecular signatures, transcriptional states, and DNA methylation patterns that define GBM. Histone posttranslational modifications (PTMs) have been shown to influence oncogenesis in a variety of malignancies, including other forms of glioma, yet comparatively less effort has been placed on understanding the transcriptional impact and regulation of histone PTMs in the context of GBM. In …

Vigorous-Intensity Exercise As A Modulator Of Cardiac Adipose Tissue In Women With Obesity: A Cross-Sectional And Randomized Pilot Study, Sumsen Thapa, Bharath S Selvaraj, Paige N Davis, Bryan Smith, Amy H Givan, Jose A Perez-Rivera, Pamela K Woodard, Jon D Klingensmith, Maria Fernandez-Del-Valle

2020-Current year OA Pubs

Cardiac adipose tissue (CAT) has become an important target for the reduction of disease risk. Supervised exercise programs have shown potential to "significantly" reduce CAT; however, the impact of different exercise modalities is not clear, and the relationships between CAT, physical activity (PA) levels and fitness (PFit) remain unknown. Therefore, the purpose of this study was to analyze the relationships between CAT, PA and PFit, and to explore the effects of different exercise modalities in a group of women with obesity. A total of 26 women (age: 23.41 ± 5.78 years-old) were enrolled in the cross-sectional study. PA, cardiorespiratory fitness, …

Nrg/Rtog 0837: Randomized, Phase Ii, Double-Blind, Placebo-Controlled Trial Of Chemoradiation With Or Without Cediranib In Newly Diagnosed Glioblastoma, Tracy T Batchelor, Clifford G Robinson, Et Al.

2020-Current year OA Pubs

BACKGROUND: A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma.

METHODS: Patients with newly diagnosed glioblastoma were randomly assigned 2:1 to receive (1) cediranib (20 mg) in combination with radiation and temozolomide; (2) placebo in combination with radiation and temozolomide. The primary endpoint was 6-month progression-free survival (PFS) based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans and was tested using a 1-sided …

Proteins In Tumor-Derived Plasma Extracellular Vesicles Indicate Tumor Origin, Meltem Barlin, Petra Erdmann-Gilmore, Jacqueline L Mudd, Qiang Zhang, Robert W Seymour, Zhanfang Guo, Julia R Miessner, S Peter Goedegebuure, Ye Bi, Omar A Osorio, Jennifer Alexander-Brett, Shunqiang Li, Cynthia X Ma, Ryan C Fields, R Reid Townsend, Jason M Held

2020-Current year OA Pubs

Cancer-derived extracellular vesicles (EVs) promote tumorigenesis, premetastatic niche formation, and metastasis via their protein cargo. However, the proteins packaged by patient tumors into EVs cannot be determined in vivo because of the presence of EVs derived from other tissues. We therefore developed a cross-species proteomic method to quantify the human tumor-derived proteome of plasma EVs produced by patient-derived xenografts of four cancer types. Proteomic profiling revealed individualized packaging of novel protein cargo, and machine learning accurately classified the type of the underlying tumor.

Direct Proteomic Detection And Prioritization Of 19 Onchocerciasis Biomarker Candidates In Humans, Bruce A Rosa, Kurt Curtis, Petra Erdmann Gilmore, John Martin, Qiang Zhang, Robert Sprung, Gary J Weil, R Reid Townsend, Peter U Fischer, Makedonka Mitreva

2020-Current year OA Pubs

Onchocerca volvulus, the causative agent of onchocerciasis, infects over 20 million people and can cause severe dermatitis and ocular conditions including blindness. Current treatments employed in mass drug administration programs do not kill adult female worms, and common diagnostic tests cannot reliably assess viability of adult worms. There is an urgent need for better diagnostic tests to facilitate monitoring the efficacy of new treatments and disease elimination efforts. Here, eight plasma samples collected from individuals infected with O. volvulus and seven from uninfected individuals were analyzed by MS/MS spectrometry to directly identify O. volvulus proteins present in infected but absent …

Down Syndrome And Alzheimer's Disease: A Scoping Review Of Functional Performance And Fall Risk, Selena E Washington, Emily Cler, Cameron Lowery, Susan L Stark

2020-Current year OA Pubs

INTRODUCTION: Alzheimer's disease (AD) occurs in aging adults with Down syndrome (DS) at a higher prevalence and an earlier age than in typical aging adults. As with the general aging adult population, there is an urgent need to understand the preclinical and early phases of AD progression in the adult population with DS. The aim of this scoping review was to synthesize the current state of the evidence and identify gaps in the literature regarding functional activity performance and falls and their significance to disease staging (i.e., mild, moderate, and severe defined staging criteria) in relation to Alzheimer's disease and …

Sleep Deprivation, Sleep Fragmentation, And Social Jet Lag Increase Temperature Preference In Drosophila, S Tanner Roach, Melanie C Ford, Vikram Simhambhatla, Vasilios Loutrianakis, Hamza Farah, Zhaoyi Li, Erica M Periandri, Dina Abdalla, Irene Huang, Arjan Kalra, Paul J Shaw

2020-Current year OA Pubs

Despite the fact that sleep deprivation substantially affects the way animals regulate their body temperature, the specific mechanisms behind this phenomenon are not well understood. In both mammals and flies, neural circuits regulating sleep and thermoregulation overlap, suggesting an interdependence that may be relevant for sleep function. To investigate this relationship further, we exposed flies to 12 h of sleep deprivation, or 48 h of sleep fragmentation and evaluated temperature preference in a thermal gradient. Flies exposed to 12 h of sleep deprivation chose warmer temperatures after sleep deprivation. Importantly, sleep fragmentation, which prevents flies from entering deeper stages of …

Feasibility And Acceptability Of Remote Smartphone Cognitive Testing In Frontotemporal Dementia Research, Jack Carson Taylor, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Remote smartphone assessments of cognition, speech/language, and motor functioning in frontotemporal dementia (FTD) could enable decentralized clinical trials and improve access to research. We studied the feasibility and acceptability of remote smartphone data collection in FTD research using the ALLFTD Mobile App (ALLFTD-mApp).

METHODS: A diagnostically mixed sample of 214 participants with FTD or from familial FTD kindreds (asymptomatic: CDR®+NACC-FTLD = 0 [

RESULTS: It was feasible for participants to complete the ALLFTD-mApp on their own smartphones. Participants reported high smartphone familiarity, completed ∼ 70% of tasks, and considered the time commitment acceptable (98% of respondents). Greater disease severity …

Genotype And Clinical Characteristics Of Patients With Wolfram Syndrome And Wfs1-Related Disorders, Evan M Lee, Megha Verma, Nila Palaniappan, Emiko M Pope, Sammie Lee, Lindsey Blacher, Pooja Neerumalla, William An, Toko Campbell, Cris Brown, Stacy Hurst, Bess Marshall, Tamara Hershey, Fumihiko Urano, Et Al.

2020-Current year OA Pubs

No abstract provided.

Clinical Characteristics And Outcomes Of Infection With Human T-Lymphotropic Virus In A Non-Endemic Area: A Single Institution Study, Margery Gang, Feng Gao, Sneha Poondru, Theodore Thomas, Lee Ratner

2020-Current year OA Pubs

INTRODUCTION: Understanding of human T-lymphotropic virus (HTLV) remains largely based on epidemiologic and clinical data from endemic areas. Globalization has resulted in migration of persons living with HTLV (PLHTLV) from endemic to non-endemic areas, and a rise of HTLV infection in the United States. Yet, due to the historical rarity of this disease, affected patients are often under- and mis-diagnosed. Thus, we sought to characterize the epidemiology, clinical features, comorbidities, and survival of HTLV-1- or HTLV-2-positive individuals identified in a non-endemic area.

METHODS: Our study was a single institution, retrospective case-control analysis of HTLV-1 or HTLV-2 patients between 1998 and …

T-Cell Redirecting Therapies For B-Cell Non-Hodgkin Lymphoma: Recent Progress And Future Directions, David A Russler-Germain, Armin Ghobadi

2020-Current year OA Pubs

Several key advances in the treatment of B-cell non-Hodgkin lymphoma (B-NHL) over the past two decades have strategically exploited B-cell lineage markers suitable for targeting by immunotherapies. First, the addition of the anti-CD20 monoclonal antibody (mAb) rituximab to a range of standard therapies conferred remarkable outcomes improvements in diverse settings, perhaps most prominently an overall survival advantage in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Subsequently, multiple chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have revolutionized the treatment of relapsed/refractory (rel/ref) DLBCL and are active in other B-NHL subtypes as well. Most recently, the longstanding aspiration to exploit patients' …

Financial Burden Of Men With Localized Prostate Cancer: A Process Paper, Ashley J Housten, Hannah E Rice, Su-Hsin Chang, Allison J L'Hotta, Eric H Kim, Bettina F Drake, Robin Wright-Jones, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Many individuals undergoing cancer treatment experience substantial financial hardship, often referred to as financial toxicity (FT). Those undergoing prostate cancer treatment may experience FT and its impact can exacerbate disparate health outcomes. Localized prostate cancer treatment options include: radiation, surgery, and/or active surveillance. Quality of life tradeoffs and costs differ between treatment options. In this project, our aim was to quantify direct healthcare costs to support patients and clinicians as they discuss prostate cancer treatment options. We provide the transparent steps to estimate healthcare costs associated with treatment for localized prostate cancer among the privately insured population using a …

Locus Specific Endogenous Retroviral Expression Associated With Alzheimer's Disease, Tyson Dawson, Uzma Rentia, Jessie Sanford, Carlos Cruchaga, John S K Kauwe, Keith A Crandall

2020-Current year OA Pubs

INTRODUCTION: Human endogenous retroviruses (HERVs) are transcriptionally-active remnants of ancient retroviral infections that may play a role in Alzheimer's disease.

METHODS: We combined two, publicly available RNA-Seq datasets with a third, novel dataset for a total cohort of 103 patients with Alzheimer's disease and 45 healthy controls. We use telescope to perform HERV quantification for these samples and simultaneously perform gene expression analysis.

RESULTS: We identify differentially expressed genes and differentially expressed HERVs in Alzheimer's disease patients. Differentially expressed HERVs are scattered throughout the genome; many of them are members of the HERV-K superfamily. A number of HERVs are correlated …

Cell Wall Composition In Cryptococcus Neoformans Is Media Dependent And Alters Host Response, Inducing Protective Immunity, Rajendra Upadhya, Woei C Lam, Camaron R Hole, Joseph G Vasselli, Jennifer K Lodge

2020-Current year OA Pubs

INTRODUCTION:

OBJECTIVE: The purpose of this study was to determine how different media influenced the amount of chitin and chitosan in the cell wall, which in turn impacted the cell wall architecture and host response.

METHODS: Yeast extract, peptone, and dextrose (YPD) and yeast nitrogen base (YNB) are two commonly used media for growing Cryptococcus before use in in vitro or in vivo experiments. As a result,

RESULTS: We observed that the growth of wild-type

CONCLUSION: These findings emphasize the importance of culture media and pH during growth in shaping the content and organization of the

Changes In Patient-Reported Pain Interference After Surgical Treatment Of Painful Lower Extremity Neuromas, Adam Liebendorfer, Esther Ochoa, Christopher J Dy

2020-Current year OA Pubs

PURPOSE: Painful neuromas commonly cause neuropathic pain, in up to 1 in 20 cases of traumatic or iatrogenic nerve injury. Despite the multiple surgical treatment types that reduce pain, no type has been universally accepted.

METHODS: We performed a retrospective cohort study by administering follow-up surveys to all surgical patients treated in our department for lower-extremity neuroma from September 1, 2015, to October 22, 2021, that could be contacted, excluding those with Morton neuroma. In addition to the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) questionnaire, survey questions covered the time to pain reduction, use of physical or …

Conditional Protein Degradation In Yarrowia Lipolytica Using The Auxin-Inducible Degron, Zhenlin Han, Jessica Maruwan, Yinjie Tang, Wei Wen Su

2020-Current year OA Pubs

Conditional protein degradation is a powerful tool for controlled protein knockdown. The auxin-inducible degron (AID) technology uses a plant auxin to induce depletion of degron-tagged proteins, and it has been shown to be functional in several non-plant eukaryotes. In this study, we demonstrated AID-based protein knockdown in an industrially important oleaginous yeast