Digital Commons Network^™

Label-Free Macroscopic Fluorescence Lifetime Imaging Of Brain Tumors, Maria Lukina, Konstantin Yashin, Elena E Kiseleva, Anna Alekseeva, Varvara Dudenkova, Elena V Zagaynova, Evgenia Bederina, Igor Medyanic, Wolfgang Becker, Deependra Mishra, Mikhail Berezin, Vladislav I Shcheslavskiy, Marina Shirmanova

Open Access Publications

Advanced stage glioma is the most aggressive form of malignant brain tumors with a short survival time. Real-time pathology assisted, or image guided surgical procedures that eliminate tumors promise to improve the clinical outcome and prolong the lives of patients. Our work is focused on the development of a rapid and sensitive assay for intraoperative diagnostics of glioma and identification of optical markers essential for differentiation between tumors and healthy brain tissues. We utilized fluorescence lifetime imaging (FLIM) of endogenous fluorophores related to metabolism of the glioma from freshly excised brains tissues. Macroscopic time-resolved fluorescence images of three intracranial animal …

Inflammatory Pathophysiology As A Contributor To Myeloproliferative Neoplasms, Daniel Arthur Corpuz Fisher, Jared Scott Fowles, Amy Zhou, Stephen Tracy Oh

Open Access Publications

Myeloid neoplasms, including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), and myelodysplastic syndromes (MDS), feature clonal dominance and remodeling of the bone marrow niche in a manner that promotes malignant over non-malignant hematopoiesis. This take-over of hematopoiesis by the malignant clone is hypothesized to include hyperactivation of inflammatory signaling and overproduction of inflammatory cytokines. In the

Brown Adipose Tissue Monocytes Support Tissue Expansion, Alexandre Gallerand, Hannah P. Luehmann, Deborah H. Sultan, Yongjian Liu, Et Al

Open Access Publications

No abstract provided.

Familial History Of Autoimmune Disorders Among Patients With Pediatric Multiple Sclerosis, Benjamin M. Greenberg, Soe S. Mar, Shannon Liang, Manu Goyal, Et Al

Open Access Publications

No abstract provided.

A Machine Learning Approach For The Factorization Of Psychometric Data With Application To The Delis Kaplan Executive Function System, J.A. Camilleri, S.B. Eickhoff, S. Weis, J. Chen, J. Amunts, A. Sotiras, S. Genon

Open Access Publications

No abstract provided.

Genome Sequencing As An Alternative To Cytogenetic Analysis In Myeloid Cancers, Eric J. Duncavage, Molly C. Schroeder, Michele O'Laughlin, Roxanne Wilson, Sandra Macmillan, Andrew Bohannon, Scott Kruchowski, John Garza, Feiyu Du, Andrew E.O. Hughes, Josh Robinson, Emma Hughes, Sharon E. Heath, Jack D. Baty, Julie Neidich, Matthew J. Christopher, Meagan A. Jacoby, Geoffrey L. Uy, Robert S. Fulton, Christopher A. Miller, Jacqueline E. Payton, Daniel C. Link, Matthew J. Walter, Peter Westervelt, John F. Dipersio, Timothy J. Ley, David H. Spencer

Open Access Publications

No abstract provided.

Machine Learning Model With Physical Constraints For Diffuse Optical Tomography, Yun Zou, Yifeng Zeng, Shuying Li, Quing Zhu

Open Access Publications

No abstract provided.

Work Organization Factors Associated With Health And Work Outcomes Among Apprentice Construction Workers: Comparison Between The Residential And Commercial Sectors, Ann Marie Dale, Diane S Rohlman, Lisa Hayibor, Bradley A Evanoff

Open Access Publications

There are substantial differences in work organization between residential and commercial construction sectors. This paper examined differences in work factors between construction sectors and examined the association between sector and health behaviors, health outcomes, and work outcomes. We surveyed 929 male construction apprentices (44% residential and 56% commercial) and found that residential apprentices reported fewer workplace safety policies, higher frequency of heavy lifting, and greater likelihood of reporting musculoskeletal pain compared to apprentices in commercial work. Residential apprentices reported higher job strain, lower supervisor support, more lost workdays due to pain or injury, and lower productivity related to health than …

Reweighting Of Molecular Simulations With Explicit-Solvent Saxs Restraints Elucidates Ion-Dependent Rna Ensembles, Mattia Bernetti, Kathleen B. Hall, Giovanni Bussi

Open Access Publications

Small-angle X-ray scattering (SAXS) experiments are increasingly used to probe RNA structure. A number of forward models that relate measured SAXS intensities and structural features, and that are suitable to model either explicit-solvent effects or solute dynamics, have been proposed in the past years. Here, we introduce an approach that integrates atomistic molecular dynamics simulations and SAXS experiments to reconstruct RNA structural ensembles while simultaneously accounting for both RNA conformational dynamics and explicit-solvent effects. Our protocol exploits SAXS pure-solute forward models and enhanced sampling methods to sample an heterogenous ensemble of structures, with no information towards the experiments provided on-the-fly. …

Hif1Α Is Required For Nk Cell Metabolic Adaptation During Virus Infection, Francisco Victorino, Tarin M. Bigley, Eugene Park, Cong-Hui Yao, Jeanne Benoit, Li-Ping Yang, Sytse J. Piersma, Elvin J. Lauron, Rebecca M. Davidson, Gary J. Patti, Wayne M. Yokoyama

Open Access Publications

Natural killer (NK) cells are essential for early protection against virus infection and must metabolically adapt to the energy demands of activation. Here, we found upregulation of the metabolic adaptor hypoxia-inducible factor-1α (HIF1α) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infection in vivo. HIF1α-deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF1αKO NK cells; however, their numbers were significantly reduced. Loss of HIF1α did not affect NK cell proliferation during in vivo infection and in vitro cytokine stimulation. Instead, we found that HIF1α-deficient NK cells …

Cognitive Dysfunction After Analgesia And Sedation: Out Of The Operating Room And Into The Pediatric Intensive Care Unit, Ashley D Turner, Travis Sullivan, Kurt Drury, Trevor A Hall, Cydni N Williams, Kristin P Guilliams, Sarah Murphy, A M Iqbal O'Meara

Open Access Publications

In the midst of concerns for potential neurodevelopmental effects after surgical anesthesia, there is a growing awareness that children who require sedation during critical illness are susceptible to neurologic dysfunctions collectively termed pediatric post-intensive care syndrome, or PICS-p. In contrast to healthy children undergoing elective surgery, critically ill children are subject to inordinate neurologic stress or injury and need to be considered separately. Despite recognition of PICS-p, inconsistency in techniques and timing of post-discharge assessments continues to be a significant barrier to understanding the specific role of sedation in later cognitive dysfunction. Nonetheless, available pediatric studies that account for analgesia …

Decoding Neural Activity In Sulcal And White Matter Areas Of The Brain To Accurately Predict Individual Finger Movement And Tactile Stimuli Of The Human Hand, Chad Bouton, Nikunj Bhagat, Santosh Chandrasekaran, Jose Herrero, Noah Markowitz, Elizabeth Espinal, Joo-Won Kim, Richard Ramdeo, Junqian Xu, Matthew F Glasser, Stephan Bickel, Ashesh Mehta

Open Access Publications

Millions of people worldwide suffer motor or sensory impairment due to stroke, spinal cord injury, multiple sclerosis, traumatic brain injury, diabetes, and motor neuron diseases such as ALS (amyotrophic lateral sclerosis). A brain-computer interface (BCI), which links the brain directly to a computer, offers a new way to study the brain and potentially restore impairments in patients living with these debilitating conditions. One of the challenges currently facing BCI technology, however, is to minimize surgical risk while maintaining efficacy. Minimally invasive techniques, such as stereoelectroencephalography (SEEG) have become more widely used in clinical applications in epilepsy patients since they can …

Genomic Characterization And Therapeutic Targeting Of Hpv Undetected Cervical Carcinomas, Fiona J Ruiz, Aishwarya Sundaresan, Jin Zhang, Chandra S Pedamallu, Mari K Halle, Vinodh Srinivasasainagendra, Jianqing Zhang, Naoshad Muhammad, Jennifer Stanley, Stephanie Markovina, Hemant K Tiwari, Perry W Grigsby, Camilla Krakstad, Julie K Schwarz, Akinyemi I Ojesina

Open Access Publications

Cervical cancer tumors with undetectable HPV (HPV

Biological Resurfacing In A Canine Model Of Hip Osteoarthritis, Bradley T Estes, Masataka Enomoto, Franklin T Moutos, Megan A Carson, Jeffrey M Toth, Peter Eggert, Jonathan Stallrich, Vincent P Willard, Deborah J Veis, Dianne Little, Farshid Guilak, B Duncan X Lascelles

Open Access Publications

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The Genetic Architecture Of A Congenital Heart Defect Is Related To Its Fitness Cost, Ehiole Akhirome, Suk D Regmi, Rachel A Magnan, Nelson Ugwu, Yidan Qin, Claire E Schulkey, James M Cheverud, Patrick Y Jay

Open Access Publications

In newborns, severe congenital heart defects are rarer than mild ones. This epidemiological relationship between heart defect severity and incidence lacks explanation. Here, an analysis of ~10,000

Utility Of Social Media For Recruitment By Orthopaedic Surgery Residency Programs, Alisa Malyavko, Yumin Kim, Tara G. Harmon, Theodore Quan, Alex Gu, Simone A. Bernstein, Sean A. Tabaie, Savyasachi Thakkar

Open Access Publications

No abstract provided.

Basal Epithelial Stem Cells Cross An Alarmin Checkpoint For Postviral Lung Disease, Kangyun Wu, Kenji Kamimoto, Yong Zhang, Kuangying Yang, Shamus P Keeler, Benjamin J Gerovac, Eugene V Agapov, Stephen P Austin, Jennifer Yantis, Kelly A Gissy, Derek E Byers, Jennifer Alexander-Brett, Christy M Hoffmann, Matthew Wallace, Michael E Hughes, Erika C Crouch, Samantha A Morris, Michael J Holtzman

Open Access Publications

Epithelial cells are charged with protection at barrier sites, but whether this normally beneficial response might sometimes become dysfunctional still needs definition. Here, we recognized a pattern of imbalance marked by basal epithelial cell growth and differentiation that replaced normal airspaces in a mouse model of progressive postviral lung disease due to the Sendai virus. Single-cell and lineage-tracing technologies identified a distinct subset of basal epithelial stem cells (basal ESCs) that extended into gas-exchange tissue to form long-term bronchiolar-alveolar remodeling regions. Moreover, this cell subset was selectively expanded by crossing a cell-growth and survival checkpoint linked to the nuclear-localized alarmin …

Insights Into The Expanding Phenotypic Spectrum Of Inherited Disorders Of Biogenic Amines, Oya Kuseyri Hübschmann, Toni S. Pearson, Et Al

Open Access Publications

No abstract provided.

Tracheal Aspirate Rna Sequencing Identifies Distinct Immunological Features Of Covid-19 Ards, Aartik Sarma, Pratik Sinha, Et Al

Open Access Publications

No abstract provided.

Tissue Biodistribution And Tumor Targeting Of Near-Infrared Labelled Anti-Cd38 Antibody-Drug Conjugate In Preclinical Multiple Myeloma, Nicholas Cho, Sooah Ko, Monica Shokeen

Open Access Publications

Daratumumab (DARA) is an FDA-approved high-affinity monoclonal antibody targeting CD38 that has shown promising therapeutic efficacy in double refractory multiple myeloma (MM) patients. Despite the well-established clinical efficacy of DARA, not all heavily pretreated patients respond to single-agent DARA, and the majority of patients who initially respond eventually progress. Antibody-drug conjugates (ADCs) combine the highly targeted tumor antigen recognition of antibodies with the cell killing properties of chemotherapy for effective internalization and processing of the drug. In this study, we evaluated the anti-tumor efficacy of DARA conjugated to the maytansine derivative, mertansine (DM1), linked via a non-cleavable bifunctional linker. The …

Racial Disparities In The Sofa Score Among Patients Hospitalized With Covid-19, Benjamin Tolchin, Carol Oladele, Deron Galusha, Nitu Kashyap, Mary Showstark, Jennifer Bonito, Michelle C. Salazar, Jennifer L. Herbst, Steve Martino, Nancy Kim, Katherine A. Nash, Max Jordan Nguemeni Tiako, Shireen Roy, Rebeca Vergara Greeno, Karen Jubanyik

Open Access Publications

BACKGROUND: Sequential Organ Failure Assessment (SOFA) score predicts probability of in-hospital mortality. Many crisis standards of care suggest the use of SOFA scores to allocate medical resources during the COVID-19 pandemic.

RESEARCH QUESTION: Are SOFA scores elevated among Non-Hispanic Black and Hispanic patients hospitalized with COVID-19, compared to Non-Hispanic White patients?

STUDY DESIGN AND METHODS: Retrospective cohort study conducted in Yale New Haven Health System, including 5 hospitals with total of 2681 beds. Study population drawn from consecutive patients aged ≥18 admitted with COVID-19 from March 29th to August 1st, 2020. Patients excluded from the analysis if not their first …

Is Left-Behind A Real Reason For Children's Social Cognition Deficit? An Fnirs Study On The Effect Of Social Interaction On Left-Behind Preschooler's Prefrontal Activation, Keya Ding, Chuanjiang Li, Huibin Jia, Mingming Zhang, Dongchuan Yu

Open Access Publications

The left-behind phenomenon, caused by parent out-migration, has become a common social issue and might lead to long-term and potential risks for children in rural areas of China. It is important to investigate the effect of social interaction on prefrontal activation of left-behind children in China because of possible effects of parent out-migration on children's social cognition. We recruited 81 rural Chinese preschoolers aged 52-76 months (mean = 64.98 ± 6.321 months) preschoolers with three different statuses of parental out-migration (including non-, partially, and completely left-behind children). Using functional Near-Infrared Spectroscopy (fNIRS), we compared behavior and brain activation and in …

The Kanyakla Study: Randomized Controlled Trial Of A Microclinic Social Network Intervention For Promoting Engagement And Retention In Hiv Care In Rural Western Kenya, Matthew D. Hickey, Elvin H. Geng, Et Al

Open Access Publications

BACKGROUND: Existing social relationships are a potential source of "social capital" that can enhance support for sustained retention in HIV care. A previous pilot study of a social network-based 'microclinic' intervention, including group health education and facilitated HIV status disclosure, reduced disengagement from HIV care. We conducted a pragmatic randomized trial to evaluate microclinic effectiveness.

METHODS: In nine rural health facilities in western Kenya, we randomized HIV-positive adults with a recent missed clinic visit to either participation in a microclinic or usual care (NCT02474992). We collected visit data at all clinics where participants accessed care and evaluated intervention effect on …

Clinical Outcomes And Longitudinal Circulating Tumor Dna Changes After Treatment With Nivolumab And Olaparib In Immunotherapy Relapsed Melanoma With Detected Homologous Recombination Deficiency, Karam Khaddour, Michael Ansstas, George Ansstas

Open Access Publications

The treatment of immunotherapy relapsed cutaneous melanoma constitutes a challenge in both research and clinical practice fields given the lack of effective therapeutic options. Homologous recombination deficiency (HRD) has been identified in several solid cancers including cutaneous melanoma. However, the utility of medications targeting HRD cancer cells is an uncharted territory in melanoma. Moreover, preclinical evidence suggests a synergistic role of combining immune checkpoint blockade (ICB) with drugs targeting HRD cancer cells such as PARP inhibitors. Here, we present a case study of a patient with immunotherapy relapsed melanoma who was found to have detected HRD and was treated with …

Development And Assessment Of A Clinical Calculator For Estimating The Likelihood Of Recurrence And Survival Among Patients With Locally Advanced Rectal Cancer Treated With Chemotherapy, Radiotherapy, And Surgery, Martin R Weiser, William C. Chapman, Philip S. Bauer, Matthew G. Mutch, Parag J. Parikh, Et Al

Open Access Publications

Importance: Predicting outcomes in patients receiving neoadjuvant therapy for rectal cancer is challenging because of tumor downstaging. Validated clinical calculators that can estimate recurrence-free survival (RFS) and overall survival (OS) among patients with rectal cancer who have received multimodal therapy are needed.

Objective: To develop and validate clinical calculators providing estimates of rectal cancer recurrence and survival that are better for individualized decision-making than the American Joint Committee on Cancer (AJCC) staging system or the neoadjuvant rectal (NAR) score.

Design, Setting, and Participants: This prognostic study developed risk models, graphically represented as nomograms, for patients with incomplete pathological response using …

Quantification Of Sepsis Model Alerts In 24 Us Hospitals Before And During The Covid-19 Pandemic, Andrew Wong, Jie Cao, Patrick G. Lyons, Sayon Dutta, Vincent J. Major, Erkin Ötles, Karandeep Singh

Open Access Publications

No abstract provided.

Bcl6 Controls Meningeal Th17–B Cell Interaction In Murine Neuroinflammation, Maike Hartlehnert, Gregory F. Wu, Et Al

Open Access Publications

No abstract provided.

Acaricidal Activity Of Foeniculum Vulgare Against Rhipicephalus Annulatus Is Mainly Dependent On Its Constituent From Trans-Anethone, Shawky M. Aboelhadid, Waleed M. Arafa, Abdel-Azeem S. Abdel-Baki, Atalay Sokmen, Saleh Al-Quraishy, Ahmed O. Hassan, Asmaa A. Kamel

Open Access Publications

Globally, the economic losses due to hard ticks infestation and the control of the associated diseases have been calculated at USD $13.9-18.7 billion per year. The economic impact is related to its direct damage to the skins, blood loss, anemia, severe immunological reactions and indirect losses that related to the effects of hemoparasites, cost of treatment for clinical cases and expenses incurred in the control of ticks. The current study evaluated the acaricidal activities of fennel Foeniculum vulgare essential oil and its main components; trans-anethole and fenchone; against R. annulatus. GC-MS analysis revealed that this oil contained 16 components representing …

Harnessing The Potential Of Multiomics Studies For Precision Medicine In Infectious Disease, Rebecca A. Ward, Philip A. Mudd, Rachel M. Presti, Andrej Spec, Et Al

Open Access Publications

The field of infectious diseases currently takes a reactive approach and treats infections as they present in patients. Although certain populations are known to be at greater risk of developing infection (eg, immunocompromised), we lack a systems approach to define the true risk of future infection for a patient. Guided by impressive gains in "omics" technologies, future strategies to infectious diseases should take a precision approach to infection through identification of patients at intermediate and high-risk of infection and deploy targeted preventative measures (ie, prophylaxis). The advances of high-throughput immune profiling by multiomics approaches (ie, transcriptomics, epigenomics, metabolomics, proteomics) hold …

Inflammatory Myoglandular Polyps Presenting With Diarrhea, Cassandra D. L. Fritz, Pooja Navale, Matthew Mutch, Vladimir Kushnir

Open Access Publications

No abstract provided.