Digital Commons Network^™

Preemptive Analgesic Effect Of Intrathecal Applications Of Neuroactive Steroids In A Rodent Model Of Post-Surgical Pain: Evidence For The Role Of T-Type Calcium Channels, Quy L Tat, Srdjan M Joksimovic, Kathiresan Krishnan, Douglas F Covey, Slobodan M Todorovic, Vesna Jevtovic-Todorovic

Open Access Publications

Preemptive management of post-incisional pain remains challenging. Here, we examined the role of preemptive use of neuroactive steroids with activity on low-voltage activated T-type Ca

Ten-Year Experience With Percutaneous Cryoablation Of Renal Tumors: Tumor Size Predicts Disease Progression, Nicholas A. Pickersgill, Joel M. Vetter, Eric H. Kim, Sky J. Cope, Kefu Du, Ramakrishna Venkatesh, Joseph Daniel Giardina, Nael E. S. Saad, Sam B. Bhayani, Robert S. Figenshau

Open Access Publications

No abstract provided.

The Validity And Reliability Of The Microsoft Kinect For Measuring Trunk Compensation During Reaching, Matthew H Foreman, Jack R Engsberg

Open Access Publications

Compensatory movements at the trunk are commonly utilized during reaching by persons with motor impairments due to neurological injury such as stroke. Recent low-cost motion sensors may be able to measure trunk compensation, but their validity and reliability for this application are unknown. The purpose of this study was to compare the first (K1) and second (K2) generations of the Microsoft Kinect to a video motion capture system (VMC) for measuring trunk compensation during reaching. Healthy participants (n = 5) performed reaching movements designed to simulate trunk compensation in three different directions and on two different days while being measured …

From Stigma To Validation: A Qualitative Assessment Of A Novel National Program To Improve Retention Of Physician-Scientists With Caregiving Responsibilities, Rochelle D. Jones, Victoria J. Fraser, Et Al.

Open Access Publications

No abstract provided.

Approach To The Pan-Brachial Plexus Injury: Variation In Surgical Strategies Among Surgeons, Steven T. Lanier, J. Ryan Hill, Aimee S. James, Liz Rolf, David M. Brogan, Christopher J. Dy

Open Access Publications

No abstract provided.

Roles Of The Vagina And The Vaginal Microbiota In Urinary Tract Infection: Evidence From Clinical Correlations And Experimental Models, Amanda L Lewis, Nicole M Gilbert

Open Access Publications

Mounting evidence indicates that the vagina can harbor uropathogenic bacteria. Here, we consider three roles played by the vagina and its bacterial inhabitants in urinary tract infection (UTI) and urinary health. First, the vagina can serve as a reservoir for

Nanoscale Integrin Cluster Dynamics Controls Cellular Mechanosensing Via Faky397 Phosphorylation, Bo Cheng, Wanting Wan, Guoyou Huang, Yuhui Li, Guy M Genin, Mohammad R K Mofrad, Tian Jian Lu, Feng Xu, Min Lin

Open Access Publications

Transduction of extracellular matrix mechanics affects cell migration, proliferation, and differentiation. While this mechanotransduction is known to depend on the regulation of focal adhesion kinase phosphorylation on Y397 (FAKpY397), the mechanism remains elusive. To address this, we developed a mathematical model to test the hypothesis that FAKpY397-based mechanosensing arises from the dynamics of nanoscale integrin clustering, stiffness-dependent disassembly of integrin clusters, and FAKY397 phosphorylation within integrin clusters. Modeling results predicted that integrin clustering dynamics governs how cells convert substrate stiffness to FAKpY397, and hence governs how different cell types transduce mechanical signals. Existing experiments on MDCK cells and HT1080 cells, …

Pancreatic Triglyceride Lipase Mediates Lipotoxic Systemic Inflammation, Cristiane De Oliveira, Mark E Lowe, Et Al

Open Access Publications

Visceral adipose tissue plays a critical role in numerous diseases. Although imaging studies often show adipose involvement in abdominal diseases, their outcomes may vary from being a mild self-limited illness to one with systemic inflammation and organ failure. We therefore compared the pattern of visceral adipose injury during acute pancreatitis and acute diverticulitis to determine its role in organ failure. Acute pancreatitis-associated adipose tissue had ongoing lipolysis in the absence of adipocyte triglyceride lipase (ATGL). Pancreatic lipase injected into mouse visceral adipose tissue hydrolyzed adipose triglyceride and generated excess nonesterified fatty acids (NEFAs), which caused organ failure in the absence …

Metabolic Dysfunction In Hutchinson-Gilford Progeria Syndrome, Ray Kreienkamp, Susana Gonzalo

Open Access Publications

Hutchinson-Gilford Progeria Syndrome (HGPS) is a segmental premature aging disease causing patient death by early teenage years from cardiovascular dysfunction. Although HGPS does not totally recapitulate normal aging, it does harbor many similarities to the normal aging process, with patients also developing cardiovascular disease, alopecia, bone and joint abnormalities, and adipose changes. It is unsurprising, then, that as physicians and scientists have searched for treatments for HGPS, they have targeted many pathways known to be involved in normal aging, including inflammation, DNA damage, epigenetic changes, and stem cell exhaustion. Although less studied at a mechanistic level, severe metabolic problems are …

Multiple Network Disconnection In Anosognosia For Hemiplegia, Elena Monai, Francesca Bernocchi, Marta Bisio, Antonio Luigi Bisogno, Alessandro Salvalaggio, Maurizio Corbetta

Open Access Publications

Anosognosia for hemiplegia (AHP) is a complex syndrome whose neural correlates are still under investigation. One hypothesis, mainly based on lesion mapping studies, is that AHP reflects a breakdown of neural systems of the right hemisphere involved in motor function. However, more recent theories have suggested that AHP may represent a disorder of cognitive systems involved in belief updating, self-referential or body processing. Two recent studies, using a method to estimate the degree of white matter disconnection from lesions, have indeed shown that patients with AHP suffer from damage of several long-range white matter pathways in association cortex. Here, we …

Development Of Volumetric Independent Dose Calculation System For Verification Of The Treatment Plan In Image-Guided Adaptive Brachytherapy, Sang-Won Kang, Jin-Beom Chung, Kyeong-Hyeon Kim, Ji-Yeon Park, Hae-Jin Park, Woong Cho, Sven Olberg, Tae Suk Suh, Justin C Park

Open Access Publications

No abstract provided.

Sequencing-Based Measurable Residual Disease Testing In Acute Myeloid Leukemia, Jennifer M Yoest, Cara Lunn Shirai, Eric J Duncavage

Open Access Publications

Next generation sequencing (NGS) methods have allowed for unprecedented genomic characterization of acute myeloid leukemia (AML) over the last several years. Further advances in NGS-based methods including error correction using unique molecular identifiers (UMIs) have more recently enabled the use of NGS-based measurable residual disease (MRD) detection. This review focuses on the use of NGS-based MRD detection in AML, including basic methodologies and clinical applications.

Dopamine Buffering Capacity Imaging: A Pharmacodynamic Fmri Method For Staging Parkinson Disease, Kevin J Black, Haley K Acevedo, Jonathan M Koller

Open Access Publications

We propose a novel pharmacological fMRI (phMRI) method for objectively quantifying disease severity in Parkinson disease (PD). It is based on the clinical observation that the benefit from a dose of levodopa wears off more quickly as PD progresses. Biologically this has been thought to represent decreased buffering capacity for dopamine as nigrostriatal cells die. Buffering capacity has been modeled based on clinical effects, but clinical measurements are influenced by confounding factors. The new method proposes to measure the effect objectively based on the timing of the known response of several brain regions to exogenous levodopa. Such responses are robust …

Positive Allosteric Modulation Of Cd11b As A Novel Therapeutic Strategy Against Lung Cancer, Terese Geraghty, Anugraha Rajagopalan, Rabail Aslam, Alexander Pohlman, Ishwarya Venkatesh, Andrew Zloza, David Cimbaluk, David G Denardo, Vineet Gupta

Open Access Publications

Lung cancer is one of the leading causes of cancer-related deaths in the United States. A major hurdle for improved therapies is immune suppression mediated by the tumor and its microenvironment. The lung tumor microenvironment (TME) contains large numbers of tumor-associated macrophages (TAMs), which suppress the adaptive immune response, increase neo-vascularization of the tumor, and provide pro-tumor factors to promote tumor growth. CD11b is highly expressed on myeloid cells, including TAMs, where it forms a heterodimeric integrin receptor with CD18 (known as CD11b/CD18, Mac-1, CR3, and αMβ2), and plays an important role in recruitment and biological functions of these cells, …

The Role Of Ct-Quantified Body Composition On Longitudinal Health-Related Quality Of Life In Colorectal Cancer Patients: The Colocare Study, Biljana Gigic, Graham A Colditz, Adetunji T Toriola, Et Al

Open Access Publications

BACKGROUND: Obesity, defined by body mass index (BMI), measured at colorectal cancer (CRC) diagnosis has been associated with postoperative complications and survival outcomes. However, BMI does not allow for a differentiation between fat and muscle mass. Computed tomography (CT)-defined body composition more accurately reflects different types of tissue and their associations with health-related quality of life (HRQoL) during the first year of disease, but this has not been investigated yet. We studied the role of visceral and subcutaneous fat area (VFA and SFA) and skeletal muscle mass (SMM) on longitudinally assessed HRQoL in CRC patients.

METHODS: A total of 138 …

Matriptase Cleaves Epcam And Trop2 In Keratinocytes, Destabilizing Both Proteins And Associated Claudins, Chuan-Jin Wu, Michael Lu, Xu Feng, Gaku Nakato, Mark C Udey

Open Access Publications

The homologs EpCAM and TROP2, which both interact with claudin-1 and claudin-7, are frequently coexpressed in epithelia including skin. Intestine uniquely expresses high levels of EpCAM but not TROP2. We previously identified EpCAM as a substrate of the membrane-anchored protease matriptase and linked HAI-2, matriptase, EpCAM and claudin-7 in a pathway that is pivotal for intestinal epithelial cells (IEC) homeostasis. Herein, we reveal that TROP2 is also a matriptase substrate. Matriptase cleaved TROP2 when purified recombinant proteins were mixed in vitro. TROP2, like EpCAM, was also cleaved after co-transfection of matriptase in 293T cells. Neither EpCAM nor TROP2 cleavage was …

Development And Evaluation Of Machine Learning Models For Voxel Dose Predictions In Online Adaptive Magnetic Resonance Guided Radiation Therapy, M Allan Thomas, Yabo Fu, Deshan Yang

Open Access Publications

PURPOSE: Daily online adaptive plan quality in magnetic resonance imaging guided radiation therapy (MRgRT) is difficult to assess in relation to the fully optimized, high quality plans traditionally established offline. Machine learning prediction models developed in this work are capable of predicting 3D dose distributions, enabling the evaluation of online adaptive plan quality to better inform adaptive decision-making in MRgRT.

METHODS: Artificial neural networks predicted 3D dose distributions from input variables related to patient anatomy, geometry, and target/organ-at-risk relationships in over 300 treatment plans from 53 patients receiving adaptive, linac-based MRgRT for abdominal cancers. The models do not include any …

Neutron Activation Of Gadolinium For Ion Therapy: A Monte Carlo Study Of Charged Particle Beams, Kurt W. Van Delinder, Rao Khan, James L. Gräfe

Open Access Publications

No abstract provided.

Structural Mechanism For Gating Of A Eukaryotic Mechanosensitive Channel Of Small Conductance, Zengqin Deng, Grigory Maksaev, Angela M. Schlegel, Jingying Zhang, Michael Rau, James A. J. Fitzpatrick, Elizabeth S. Haswell, Peng Yuan

Open Access Publications

No abstract provided.

Use Of The Theory Of Planned Behavior Framework To Understand Breastfeeding Decision-Making Among Mothers Of Preterm Infants, Margaret G. Parker, Sunah S. Hwang, Emma S. Forbes, Bryanne N. Colvin, Kyria R. Brown, Eve R. Colson

Open Access Publications

No abstract provided.

Tumor Burden, Inflammation, And Product Attributes Determine Outcomes Of Axicabtagene Ciloleucel In Large B-Cell Lymphoma, Frederick L. Locke, Armin Ghobadi, Et Al.

Open Access Publications

No abstract provided.

Enhanced Recovery With Paravertebral And Transversus Abdominis Plane Blocks In Microvascular Breast Reconstruction, Ryan Guffey, Grace Keane, Austin Y. Ha, Rajiv Parikh, Elizabeth Odom, Li Zhang, Terence M. Myckatyn

Open Access Publications

No abstract provided.

The Gut Microbiome Defines Social Group Membership In Honey Bee Colonies, Cassondra L Vernier, Iris M Chin, Boahemaa Adu-Oppong, Joshua J Krupp, Joel Levine, Gautam Dantas, Yehuda Ben-Shahar

Open Access Publications

In the honey bee, genetically related colony members innately develop colony-specific cuticular hydrocarbon profiles, which serve as pheromonal nestmate recognition cues. Yet, despite high intracolony relatedness, the innate development of colony-specific chemical signatures by individual colony members is largely determined by the colony environment, rather than solely relying on genetic variants shared by nestmates. Therefore, it is puzzling how a nongenic factor could drive the innate development of a quantitative trait that is shared by members of the same colony. Here, we provide one solution to this conundrum by showing that nestmate recognition cues in honey bees are defined, at …

Association Of Radial Longitudinal Deficiency And Thumb Hypoplasia: An Update Using The Could Registry, Malka Forman, Maria F Canizares, Deborah Bohn, Michelle A James, Julie Samora, Suzanne Steinman, Lindley B Wall, Andrea S Bauer, Could Study Group

Open Access Publications

BACKGROUND: Deficiency of the radial aspect of the forearm and hand is the most common congenital longitudinal deficiency of the upper limb. Radial longitudinal deficiency is associated with several named syndromes. The purpose of the present study was to explore patterns of radial longitudinal deficiency and thumb hypoplasia in syndromes and to examine the severity of these differences across various syndromes.

METHODS: Data were collected from the Congenital Upper Limb Differences (CoULD) registry. Congenital differences are classified in the registry with use of the Oberg-Manske-Tonkin (OMT) classification system. Diagnosis of a syndrome by a physician as noted in the CoULD …

Using Digital Technology To Reduce The Prevalence Of Mental Health Disorders In Populations: Time For A New Approach, C Barr Taylor, Josef I Ruzek, Ellen E Fitzsimmons-Craft, Shiri Sadeh-Sharvit, Naira Topooco, Ruth Striegel Weissman, Daniel Eisenberg, David Mohr, Andrea Graham, Corinna Jacobi, Brian Oldenburg

Open Access Publications

Digital technology, which includes the collection, analysis, and use of data from a variety of digital devices, has the potential to reduce the prevalence of disorders and improve mental health in populations. Among the many advantages of digital technology is that it allows preventive and clinical interventions, both of which are needed to reduce the prevalence of mental health disorders, to be feasibly integrated into health care and community delivery systems and delivered at scale. However, the use of digital technology also presents several challenges, including how systems can manage and implement interventions in a rapidly changing digital environment and …

Transcriptome Analysis Of Alternative Splicing In The Pathogen Life Cycle In Human Foreskin Fibroblasts Infected With Trypanosoma Cruzi, Hyeim Jung, Seonggyun Han, Younghee Lee

Open Access Publications

No abstract provided.

Canonical Signaling By Tgf Family Members In Mesenchymal Stromal Cells Is Dispensable For Hematopoietic Niche Maintenance Under Basal And Stress Conditions, Joseph Ryan Krambs, Grazia Abou Ezzi, Juo-Chin Yao, Daniel C. Link

Open Access Publications

Mesenchymal stromal cells are an important component of the bone marrow hematopoietic niche. Prior studies showed that signaling from members of the transforming growth factor (TGF) superfamily in mesenchymal stromal cells is required for normal niche development. Here, we assessed the impact of TGF family signaling on niche maintenance and stress responses by deleting Smad4 in mesenchymal stromal cells at birth, thereby abrogating canonical TGF signaling. No alteration in the number or spatial organization of CXCL12-abundant reticular (CAR) cells, osteoblasts, or adipocytes was observed in Osx-Cre, Smad4fl/fl mice, and expression of key niche factors was normal. Basal hematopoiesis and stress …

Diet-Induced Metabolic Dysregulation In Female Mice Causes Osteopenia In Adult Offspring, Yu Shi, Jessica L. Saben, Guangxu He, Kelle H. Moley, Fanxin Long

Open Access Publications

Bone mass and quality in humans are controlled by numerous genetic and environmental factors that are not fully understood. Increasing evidence has indicated that maternal metabolic dysregulation impairs multiple physiological processes in the adult offspring, but a similar effect on bone health is yet to be established. Here, we have analyzed the bones of first-generation offspring from murine dams that present metabolic syndrome due to a high-fat and high-sugar (HF/HS) diet. Micro-CT analyses show that the long bones of HF/HS offspring possess lower cortical bone mass and weaker mechanical strength than normal, even though the trabecular bone is not affected. …

Rev-Erb Agonism Improves Liver Pathology In A Mouse Model Of Nash, Kristine Griffett, Gonzalo Bedia-Diaz, Bahaa Elgendy, Thomas P. Burris

Open Access Publications

Non-alcoholic fatty liver disease (NAFLD) affects a significant number of people worldwide and currently there are no pharmacological treatments. NAFLD often presents with obesity, insulin resistance, and in some cases cardiovascular diseases. There is a clear need for treatment options to alleviate this disease since it often progresses to much more the much more severe non-alcoholic steatohepatitis (NASH). The REV-ERB nuclear receptor is a transcriptional repressor that regulates physiological processes involved in the development of NAFLD including lipogenesis and inflammation. We hypothesized that pharmacologically activating REV-ERB would suppress the progression of fatty liver in a mouse model of NASH. Using …

Functional Profiling Of Fsh And Estradiol In Ovarian Granulosa Cell Tumors, Ulla-Maija Haltia, Marjut Pihlajoki, Noora Andersson, Lotta Mäkinen, Johanna Tapper, Alejandra Cervera, Hugo M. Horlings, Ursula Turpeinen, Mikko Anttonen, Ralf Bützow, Leila Unkila-Kallio, Olli Carpén, David B. Wilson, Markku Heikinheimo, Anniina Färkkilä

Open Access Publications

Adult-type granulosa cell tumors (AGCTs) are sex-cord derived neoplasms with a propensity for late relapse. Hormonal modulators have been used empirically in the treatment of recurrent AGCT, albeit with limited success. To provide a more rigorous foundation for hormonal therapy in AGCT, we used a multimodal approach to characterize the expressions of key hormone biomarkers in 175 tumor specimens and 51 serum samples using RNA sequencing, immunohistochemistry, RNA