Digital Commons Network^™

Spatially Interacting Phosphorylation Sites And Mutations In Cancer, Kuan-Lin Huang, Adam D. Scott, Daniel Cui Zhou, Liang-Bo Wang, Amila Weerasinghe, Ruiyang Liu, Yige Wu, Michael C. Wendl, Matthew A. Wyczalkowski, Jessika Baral, Sohini Sengupta, Chin-Wen Lai, Li Ding, Et Al.

Open Access Publications

No abstract provided.

Adolescent Animal Product Intake In Relation To Later Prostate Cancer Risk And Mortality In The Nih-Aarp Diet And Health Study, Tuo Lan, Yikyung Park, Graham A Colditz, Jingxia Liu, Rashmi Sinha, Molin Wang, Kana Wu, Edward Giovannucci, Siobhan Sutcliffe

Open Access Publications

BACKGROUND: Adolescent intake of animal products has been proposed to contribute to prostate cancer (PCa) development because of its potentially carcinogenic constituents and influence on hormone levels during adolescence.

METHODS: We used data from 159,482 participants in the NIH-AARP Diet and Health Study to investigate associations for recalled adolescent intake of red meat (unprocessed beef and processed red meat), poultry, egg, canned tuna, animal fat and animal protein at ages 12-13 years with subsequent PCa risk and mortality over 14 years of follow-up. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of …

Bispecific T Cell Engagers For The Treatment Of Multiple Myeloma: Achievements And Challenges, Kinan Alhallak, Jennifer Sun, Amanda Jeske, Chaelee Park, Jessica Yavner, Hannah Bash, Berit Lubben, Ola Adebayo, Ayah Khaskiah, Abdel Kareem Azab

Open Access Publications

MM is the second most common hematological malignancy and represents approximately 20% of deaths from hematopoietic cancers. The advent of novel agents has changed the therapeutic landscape of MM treatment; however, MM remains incurable. T cell-based immunotherapy such as BTCEs is a promising modality for the treatment of MM. This review article discusses the advancements and future directions of BTCE treatments for MM.

Microbial Sharing Between Pediatric Patients And Therapy Dogs During Hospital Animal-Assisted Intervention Programs, Kathryn R Dalton, Kathy Ruble, Laurel E Redding, Daniel O Morris, Noel T Mueller, Roland J Thorpe, Jacqueline Agnew, Karen C Carroll, Paul J Planet, Ronald C Rubenstein, Allen R Chen, Elizabeth A Grice, Meghan F Davis

Open Access Publications

Microbial sharing between humans and animals has been demonstrated in a variety of settings. However, the extent of microbial sharing that occurs within the healthcare setting during animal-assisted intervention programs is unknown. Understanding microbial transmission between patients and therapy dogs can provide important insights into potential health benefits for patients, in addition to addressing concerns regarding potential pathogen transmission that limits program utilization. This study evaluated for potential microbial sharing between pediatric patients and therapy dogs and tested whether patient-dog contact level and a dog decolonization protocol modified this sharing. Patients, therapy dogs, and the hospital environment were sampled before …

Etv4 And Etv5 Drive Synovial Sarcoma Through Cell Cycle And Dux4 Embryonic Pathway Control, Joanna Desalvo, Yuguang Ban, Luyuan Li, Xiaodian Sun, Zhijie Jiang, Darcy A Kerr, Mahsa Khanlari, Maria Boulina, Mario R Capecchi, Juha M Partanen, Lin Chen, Tadashi Kondo, David M Ornitz, Jonathan C Trent, Josiane E Eid

Open Access Publications

Synovial sarcoma is an aggressive malignancy with no effective treatments for patients with metastasis. The synovial sarcoma fusion SS18-SSX, which recruits the SWI/SNF-BAF chromatin remodeling and polycomb repressive complexes, results in epigenetic activation of FGF receptor (FGFR) signaling. In genetic FGFR-knockout models, culture, and xenograft synovial sarcoma models treated with the FGFR inhibitor BGJ398, we show that FGFR1, FGFR2, and FGFR3 were crucial for tumor growth. Transcriptome analyses of BGJ398-treated cells and histological and expression analyses of mouse and human synovial sarcoma tumors revealed prevalent expression of two ETS factors and FGFR targets, ETV4 and ETV5. We further demonstrate that …

Pir-B Regulates Cd4+ Il17a+ T-Cell Survival And Restricts T-Cell–Dependent Intestinal Inflammatory Responses, Jazib Uddin, Rodney Newberry, Et Al

Open Access Publications

BACKGROUND & AIMS: CD4

METHODS: We used Il10

RESULTS: We identified PIR-B expression on memory CD4

CONCLUSIONS: Our findings show an intrinsic role for PIR-B/LILRB3 in the regulation of CD4

Bnp Facilitates Nmb-Encoded Histaminergic Itch Via Nprc-Nmbr Crosstalk, Qing-Tao Meng, Xian-Yu Liu, Xue-Ting Liu, Juan Liu, Admire Munanairi, Devin M. Barry, Benlong Liu, Hua Jin, Yu Sun, Qianyi Yang, Fang Gao, Li Wan, Jiahang Peng, Jin-Hua Jin, Kai-Feng Shen, Ray Kim, Jun Yin, Ailin Tao, Zhou-Feng Chen

Open Access Publications

Histamine-dependent and -independent itch is conveyed by parallel peripheral neural pathways that express gastrin-releasing peptide (GRP) and neuromedin B (NMB), respectively, to the spinal cord of mice. B-type natriuretic peptide (BNP) has been proposed to transmit both types of itch via its receptor NPRA encoded by

Response To Ibudilast Treatment According To Progressive Multiple Sclerosis Disease Phenotype, Andrew D Goodman, Janel K Fedler, Jon Yankey, Elizabeth A Klingner, Dixie J Ecklund, Christopher V Goebel, Robert A Bermel, Marianne Chase, Christopher S Coffey, Eric C Klawiter, Robert T Naismith, Robert J Fox, Sprint-Ms Investigators

Open Access Publications

OBJECTIVE: Determine whether a treatment effect of ibudilast on brain atrophy rate differs between participants with primary (PPMS) and secondary (SPMS) progressive multiple sclerosis.

BACKGROUND: Progressive forms of MS are both associated with continuous disability progression. Whether PPMS and SPMS differ in treatment response remains unknown.

DESIGN/METHODS: SPRINT-MS was a randomized, placebo-controlled 96-week phase 2 trial in both PPMS (n = 134) and SPMS (n = 121) patients. The effect of PPMS and SPMS phenotype on the rate of change of brain atrophy measured by brain parenchymal fraction (BPF) was examined by fitting a three-way interaction linear-mixed model. Adjustment for …

Despite Increasing Aldosterone, Elevated Potassium Is Not Necessary For Activating Aldosterone-Sensitive Hsd2 Neurons Or Sodium Appetite, Frederico S Fazan, Eduardo Colombari, Arthur D Loewy, Joel C Geerling

Open Access Publications

Restricting dietary sodium promotes sodium appetite in rats. Prolonged sodium restriction increases plasma potassium (pK), and elevated pK is largely responsible for a concurrent increase in aldosterone, which helps promote sodium appetite. In addition to increasing aldosterone, we hypothesized that elevated potassium directly influences the brain to promote sodium appetite. To test this, we restricted dietary potassium in sodium-deprived rats. Potassium restriction reduced pK and blunted the increase in aldosterone caused by sodium deprivation, but did not prevent sodium appetite or the activation of aldosterone-sensitive HSD2 neurons. Conversely, supplementing potassium in sodium-deprived rats increased pK and aldosterone, but did not …

Rna-Seq Identifies Genes Whose Proteins Are Upregulated During Syncytia Development In Murine C2c12 Myoblasts And Human Bewo Trophoblasts, Christopher Azar, Mark C Valentine, Julie Trausch-Azar, Lisa Rois, Moe Mahjoub, D Michael Nelson, Alan L Schwartz

Open Access Publications

The fusion of villous cytotrophoblasts into the multinucleated syncytiotrophoblast is critical for the essential functions of the mammalian placenta. Using RNA-Seq gene expression, quantitative protein expression, and siRNA knockdown we identified genes and their cognate proteins which are similarly upregulated in two cellular models of mammalian syncytia development (human BeWo cytotrophoblast to syncytiotrophoblast and murine C2C12 myoblast to myotube). These include DYSF, PDE4DIP, SPIRE2, NDRG1, PLEC, GPR146, HSPB8, DHCR7, and HDAC5. These findings provide avenues for further understanding of the mechanisms underlying mammalian placental syncytiotrophoblast development.

Lack Of Association Between Acute Stroke, Post-Stroke Dementia, Race, And Β-Amyloid Status, Lauren N Koenig, Lena M Mccue, Elizabeth Grant, Parinaz Massoumzadeh, Catherine M Roe, Chengjie Xiong, Krista L Moulder, Liang Wang, Allyson R Zazulia, Peggy Kelly, Aylin Dincer, Aiad Zaza, Joshua S Shimony, Tammie L S Benzinger, John C Morris

Open Access Publications

INTRODUCTION: Stroke and Alzheimer disease share risk factors and often co-occur, and both have been reported to have a higher prevalence in African Americans as compared to non-Hispanic whites. However, their interaction has not been established. The objective of this study was to determine if preclinical Alzheimer disease is a risk factor for stroke and post-stroke dementia and whether racial differences moderate this relationship.

METHODS: This case-control study was analyzed in 2019 using retrospective data from 2007 to 2013. Participants were adults age 65 and older with and without acute ischemic stroke. Recruitment included word of mouth and referrals in …

Test-Retest Reliability Of Neural Correlates Of Response Inhibition And Error Monitoring: An Fmri Study Of A Stop-Signal Task, Ozlem Korucuoglu, Michael P Harms, Serguei V Astafiev, Semyon Golosheykin, James T Kennedy, Deanna M Barch, Andrey P Anokhin

Open Access Publications

Response inhibition (RI) and error monitoring (EM) are important processes of adaptive goal-directed behavior, and neural correlates of these processes are being increasingly used as transdiagnostic biomarkers of risk for a range of neuropsychiatric disorders. Potential utility of these purported biomarkers relies on the assumption that individual differences in brain activation are reproducible over time; however, available data on test-retest reliability (TRR) of task-fMRI are very mixed. This study examined TRR of RI and EM-related activations using a stop signal task in young adults (

Video Feedback Intervention For Cognitively Impaired Older Drivers: A Randomized Clinical Trial, Brian R Ott, George D Papandonatos, Erin M Burke, Donna Erdman, David B Carr, Jennifer D Davis

Open Access Publications

Introduction: This clinical trial aimed to determine whether in-car video feedback about unsafe driving events (UDE) to cognitively impaired older drivers and family members leads to a reduction in such driving behaviors.

Methods: We randomized 51 cognitively impaired older drivers to receive either (1) a weekly progress report with recommendations and access to their videos, or (2) video monitoring alone without feedback over 3 months.

Results: UDE frequency/1000 miles was reduced by 12% in feedback (rate ratio [RR] = 0.88, 95% confidence interval [CI] = .58-1.34), while remaining constant with only monitoring (RR = 1.01, 95% CI = .68-1.51). UDE …

Application Of Electrical Stimulation For Peripheral Nerve Regeneration: Stimulation Parameters And Future Horizons, Saad Javeed, Amir H. Faraji, Christopher Dy, Wilson Z. Ray, Matthew R. Macewan

Open Access Publications

No abstract provided.

Substance Use Disorders And Behavioral Addictions During The Covid-19 Pandemic And Covid-19-Related Restrictions, Nicole M Avena, Julia Simkus, Anne Lewandowski, Mark S Gold, Marc N Potenza

Open Access Publications

COVID-19 was first identified in Wuhan, China in December of 2019 and appeared in the United States 1 month later. Between the onset of the pandemic and January 13, 2021, over 92 million people have tested positive for the virus and over 1.9 million people have died globally. Virtually every country in the world has been impacted by this virus. Beginning in March 2020, many U.S. state governments enforced a "quarantine" to respond to the growing health crisis. Citizens were required to remain at home; schools, restaurants, and non-essential businesses were forced to close, and large gatherings were prohibited. Americans' …

The Kinase Specificity Of Protein Kinase Inhibitor Peptide, Yao Chen, Bernardo L Sabatini

Open Access Publications

G-protein-coupled-receptor (GPCR) signaling is exquisitely controlled to achieve spatial and temporal specificity. The endogenous protein kinase inhibitor peptide (PKI) confines the spatial and temporal spread of the activity of protein kinase A (PKA), which integrates inputs from three major types of GPCRs. Despite its wide usage as a pharmaceutical inhibitor of PKA, it was unclear whether PKI only inhibits PKA activity. Here, the effects of PKI on 55 mouse kinases were tested in

Survival Predictors Of Heart Rate Variability After Myocardial Infarction With And Without Low Left Ventricular Ejection Fraction, Junichiro Hayano, Norihiro Ueda, Masaya Kisohara, Emi Yuda, Robert M Carney, James A Blumenthal

Open Access Publications

Background: Heart rate variability (HRV) and heart rate (HR) dynamics are used to predict the survival probability of patients after acute myocardial infarction (AMI), but the association has been established in patients with mixed levels of left ventricular ejection fraction (LVEF).

Objective: We investigated whether the survival predictors of HRV and HR dynamics depend on LVEF after AMI.

Methods: We studied 687 post-AMI patients including 147 with LVEF ≤35% and 540 with LVEF >35%, of which 23 (16%) and 22 (4%) died during the 25 month follow-up period, respectively. None had an implanted cardioverter-defibrillator. From baseline 24 h ECG, the …

Whole-Genome Characterization Of Lung Adenocarcinomas Lacking The Rtk/Ras/Raf Pathway, Jian Carrot-Zhang, Siddhartha Devarakonda, Wen-Wei Liang, Li Ding, Ramaswamy Govindan, Et Al

Open Access Publications

No abstract provided.

Stroke-Related Alterations In Inter-Areal Communication, Michele Allegra, Chiara Favaretto, Nicholas Metcalf, Maurizio Corbetta, Andrea Brovelli

Open Access Publications

Beyond causing local ischemia and cell damage at the site of injury, stroke strongly affects long-range anatomical connections, perturbing the functional organization of brain networks. Several studies reported functional connectivity abnormalities parallelling both behavioral deficits and functional recovery across different cognitive domains. FC alterations suggest that long-range communication in the brain is altered after stroke. However, standard FC analyses cannot reveal the directionality and time scale of inter-areal information transfer. We used resting-state fMRI and covariance-based Granger causality analysis to quantify network-level information transfer and its alteration in stroke. Two main large-scale anomalies were observed in stroke patients. First, inter-hemispheric …

Immunological Findings And Clinical Outcomes Of Infants With Positive Newborn Screening For Severe Combined Immunodeficiency From A Tertiary Care Center In The U.S., Vasudha Mantravadi, Jeffrey J Bednarski, Michelle A Ritter, Hongjie Gu, Ana L Kolicheski, Caroline Horner, Megan A Cooper, Maleewan Kitcharoensakkul

Open Access Publications

The implementation of severe combined immunodeficiency (SCID) newborn screening has played a pivotal role in identifying these patients early in life as well as detecting various milder forms of T cell lymphopenia (TCL). In this study we reviewed the diagnostic and clinical outcomes, and interesting immunology findings of term infants referred to a tertiary care center with abnormal newborn SCID screens over a 6-year period. Key findings included a 33% incidence of non-SCID TCL including infants with novel variants in

Frontotemporal Dementias In Latin America: History, Epidemiology, Genetics, And Clinical Research, Jorge J Llibre-Guerra, Angela Hardi, Et Al

Open Access Publications

No abstract provided.

Excessive White Matter Hyperintensity Increases Susceptibility To Poor Functional Outcomes After Acute Ischemic Stroke, Sungmin Hong, Laura Heitsch, Chia-Ling Phuah, Et Al

Open Access Publications

No abstract provided.

Trajectory Of Long-Term Outcome In Severe Pediatric Diffuse Axonal Injury: An Exploratory Study, Shih-Shan Lang, Todd Kilbaugh, Stuart Friess, Susan Sotardi, Chong Tae Kim, Vanessa Mazandi, Bingqing Zhang, Phillip B Storm, Gregory G Heuer, Alexander Tucker, Steve B Ampah, Heather Griffis, Ramesh Raghupathi, Jimmy W Huh

Open Access Publications

No abstract provided.

Reproductive Aging In Caenorhabditis Elegans: From Molecules To Ecology, Andrea Scharf, Franziska Pohl, Brian M Egan, Zuzana Kocsisova, Kerry Kornfeld

Open Access Publications

Aging animals display a broad range of progressive degenerative changes, and one of the most fascinating is the decline of female reproductive function. In the model organism

Longitudinal Prediction Of Infant Mr Images With Multi-Contrast Perceptual Adversarial Learning, Liying Peng, Robert C Mckinstry, Kelly N Botteron, Et Al

Open Access Publications

The infant brain undergoes a remarkable period of neural development that is crucial for the development of cognitive and behavioral capacities (Hasegawa et al., 2018). Longitudinal magnetic resonance imaging (MRI) is able to characterize the developmental trajectories and is critical in neuroimaging studies of early brain development. However, missing data at different time points is an unavoidable occurrence in longitudinal studies owing to participant attrition and scan failure. Compared to dropping incomplete data, data imputation is considered a better solution to address such missing data in order to preserve all available samples. In this paper, we adapt generative adversarial networks …

Distinct And Dissociable Eeg Networks Are Associated With Recovery Of Cognitive Function Following Anesthesia-Induced Unconsciousness, Alexander Rokos, Bratislav Mišić, Kathleen Berkun, Catherine Duclos, Vijay Tarnal, Ellen Janke, Paul Picton, Goodarz Golmirzaie, Mathias Basner, Michael S Avidan, Max B Kelz, George A Mashour, Stefanie Blain-Moraes

Open Access Publications

The temporal trajectories and neural mechanisms of recovery of cognitive function after a major perturbation of consciousness is of both clinical and neuroscientific interest. The purpose of the present study was to investigate network-level changes in functional brain connectivity associated with the recovery and return of six cognitive functions after general anesthesia. High-density electroencephalograms (EEG) were recorded from healthy volunteers undergoing a clinically relevant anesthesia protocol (propofol induction and isoflurane maintenance), and age-matched healthy controls. A battery of cognitive tests (motor praxis, visual object learning test, fractal-2-back, abstract matching, psychomotor vigilance test, digital symbol substitution test) was administered at baseline, …

Antigen Presenting Cells Link The Female Genital Tract Microbiome To Mucosal Inflammation, With Hormonal Contraception As An Additional Modulator Of Inflammatory Signatures, Elizabeth H Byrne, Barry L Hykes, Scott A Handley, Et Al

Open Access Publications

The microbiome of the female genital tract (FGT) is closely linked to reproductive health outcomes. Diverse, anaerobe-dominated communities with low

Targeting Host Glycolysis As A Strategy For Antimalarial Development, Andrew J Jezewski, Yu-Hsi Lin, Julie A Reisz, Rachel Culp-Hill, Yasaman Barekatain, Victoria C Yan, Angelo D'Alessandro, Florian L Muller, Audrey R Odom John

Open Access Publications

Glycolysis controls cellular energy, redox balance, and biosynthesis. Antiglycolytic therapies are under investigation for treatment of obesity, cancer, aging, autoimmunity, and microbial diseases. Interrupting glycolysis is highly valued as a therapeutic strategy, because glycolytic disruption is generally tolerated in mammals. Unfortunately, anemia is a known dose-limiting side effect of these inhibitors and presents a major caveat to development of antiglycolytic therapies. We developed specific inhibitors of enolase - a critical enzyme in glycolysis - and validated their metabolic and cellular effects on human erythrocytes. Enolase inhibition increases erythrocyte susceptibility to oxidative damage and induces rapid and premature erythrocyte senescence, rather …

Oromandibular Dystonia: A Clinical Examination Of 2,020 Cases, Laura M Scorr, Randal C Paniello, Scott A Norris, Joel S Perlmutter, Et Al

Open Access Publications

No abstract provided.

Rectal Cancer Treatment Management: Deep-Learning Neural Network Based On Photoacoustic Microscopy Image Outperforms Histogram-Feature-Based Classification, Xiandong Leng, Eghbal Amidi, Sitai Kou, Hassam Cheema, Ebunoluwa Otegbeye, William Chapman Jr, Matthew Mutch, Quing Zhu

Open Access Publications

We have developed a novel photoacoustic microscopy/ultrasound (PAM/US) endoscope to image post-treatment rectal cancer for surgical management of residual tumor after radiation and chemotherapy. Paired with a deep-learning convolutional neural network (CNN), the PAM images accurately differentiated pathological complete responders (pCR) from incomplete responders. However, the role of CNNs compared with traditional histogram-feature based classifiers needs further exploration. In this work, we compare the performance of the CNN models to generalized linear models (GLM) across 24