Digital Commons Network^™

Decentralized Clinical Trials For Medications To Reduce The Risk Of Dementia: Consensus Report And Guidance, Leanne Howard, Carla Abdelnour, Erin Abner, Ricardo F. Allegri, Hiroko H. Dodge, Serge Gauthier, Camilla M. Hoyos, Gregory Jicha, Patrick G. Kehoe, Catherine J. Mummery, Adesola Ogunniyi, Nikolaos Scarmeas, Xiaoying Chen, Jodie R. Titiner, Christopher R. Weber, Ruth Peters

Neurology Faculty Publications

INTRODUCTION: Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentralized medication trials, but we currently lack specific recommendations for their delivery in the dementia field.

METHODS: A modified Delphi method engaged an expert panel to develop recommendations for the conduct of decentralized medication trials in dementia prevention. A working group of researchers and clinicians with expertise in dementia trials further refined the recommendations.

RESULTS: Overall, the recommendations support the delivery of decentralized trials in dementia prevention …

Type-2 Diabetes, Pancreatic Amylin, And Neuronal Metabolic Remodeling In Alzheimer's Disease, Noah Leibold, James R. Bain, Florin Despa

Neurology Faculty Publications

Type-2 diabetes raises the risk for Alzheimer’s disease (AD)-type dementia and the conversion from mild cognitive impairment to dementia, yet mechanisms connecting type-2 diabetes to AD remain largely unknown. Amylin, a pancreatic 𝜷-cell hormone co-secreted with insulin, participates in the central regulation of satiation, but also forms pancreatic amyloid in persons with type-2 diabetes and synergistically interacts with brain amyloid 𝜷 (A𝜷) pathology, in both sporadic and familial Alzheimer’s disease (AD). Growing evidence from studies of tumor growth, together with early observations in skeletal muscle, indicates amylin as a potential trigger of cellular metabolic reprogramming. Because the blood, cerebrospinal fluid, …

A Mini-Review Of Strategies For Recruiting Older African Americans To Alzheimer's Disease Research., Darlingtina Esiaka, Christina C Yarborough, Bernadette A Fausto, Mark A Gluck

Behavioral Science Faculty Publications

African Americans experience higher incidence and prevalence of Alzheimer's disease (AD). Yet, they continue to be underrepresented in AD research, limiting the ability to generalize findings to the increasingly diverse US population. To reduce AD disparities, targeted efforts are needed to increase the representation of African Americans in AD research. This mini review identified evidence-based strategies that increased research participation among older African Americans. Four recruitment strategies emerged from eight published peer-reviewed studies that directly evaluated the effectiveness of strategies aimed at increasing the number of African American participants in Alzheimer's research. The strategies include community outreach and education, face-to-face …

Extended-Release 7-Day Injectable Buprenorphine For Patients With Minimal To Mild Opioid Withdrawal., Gail D'Onofrio, Andrew A. Herring, Jeanmarie Perrone, Kathryn Hawk, Elizabeth A. Samuels, Ethan Cowan, Erik Anderson, Ryan Mccormack, Kristen Huntley, Patricia Owens, Shara Martel, Mark Schactman, Michelle R. Lofwall, Sharon L. Walsh, James Dziura, David A. Fiellin

Behavioral Science Faculty Publications

IMPORTANCE: Buprenorphine is an effective yet underused treatment for opioid use disorder (OUD).

OBJECTIVE: To evaluate the feasibility (acceptability, tolerability, and safety) of 7-day injectable extended-release buprenorphine in patients with minimal to mild opioid withdrawal.

DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized trial comprising 4 emergency departments in the Northeast, mid-Atlantic, and Pacific geographic areas of the US included adults aged 18 years or older with moderate to severe OUD and Clinical Opiate Withdrawal Scale (COWS) scores less than 8 (minimal to mild), in which scores range from 0 to 7, with higher scores indicating increasing withdrawal. Exclusion criteria included methadone-positive …

A Pathologic Study Of Perivascular Ptdp-43 Lin Bodies In Late-Nc, Ryan K. Shahidehpour, Peter T. Nelson, Adam D. Bachstetter

Neurology Faculty Publications

Background TAR DNA-Binding Protein 43 (TDP-43) pathological inclusions are a distinctive feature in dozens of neurodegenerative pathologies, including limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Prior investigations identified vascular-associated TDP-43-positive micro-lesions, known as “Lin bodies,” located on or near the brain capillaries of some individuals with LATE-NC. This study aimed to investigate the relationship between the accumulation of Lin bodies and glial cells in LATE-NC and the potential co-localization with ferritin, a protein associated with iron storage. Using multiplexed immunohistochemistry and digital pathology tools, we conducted pathological analyses to investigate the relationship between Lin bodies and glial markers (GFAP for …

Applying Machine Learning Models Derived From Administrative Claims Data To Predict Medication Nonadherence In Patients Self-Administering Biologic Medications For Inflammatory Bowel Disease, Christian Rhudy, Courtney Perry, Michael Wesley, David Fardo, Cody Bumgardner, Syed Hassan, Terrence Barrett, Jeffery Talbert

Biostatistics Faculty Publications

BACKGROUND: Adherence to self-administered biologic therapies is important to induce remission and prevent adverse clinical outcomes in Inflammatory bowel disease (IBD). This study aimed to use administrative claims data and machine learning methods to predict nonadherence in an academic medical center test population.

METHODS: A model-training dataset of beneficiaries with IBD and the first unique dispense of a self-administered biologic between June 30, 2016 and June 30, 2019 was extracted from the Commercial Claims and Encounters and Medicare Supplemental Administrative Claims Database. Known correlates of medication nonadherence were identified in the dataset. Nonadherence to biologic therapies was defined as a …

Β-Aminopropionitrile Induces Distinct Pathologies In The Ascending And Descending Thoracic Aortic Regions Of Mice, Michael K. Franklin, Hisashi Sawada, Sohei Ito, Deborah A. Howatt, Naofumi Amioka, Ching Ling Liang, Nancy Zhang, David B. Graf, Jessica J. Moorleghen, Yuriko Katsumata, Hong S. Lu, Alan Daugherty

Biostatistics Faculty Publications

BACKGROUND: β-aminopropionitrile (BAPN) is a pharmacological inhibitor of LOX (lysyl oxidase) and LOXLs (LOX-like proteins). Administration of BAPN promotes aortopathies, although there is a paucity of data on experimental conditions to generate pathology. The objective of this study was to define experimental parameters and determine whether equivalent or variable aortopathies were generated throughout the aortic tree during BAPN administration in mice. METHODS: BAPN was administered in drinking water for a period ranging from 1 to 12 weeks. The impacts of BAPN were first assessed with regard to BAPN dose, and mouse strain, age, and sex. BAPN-induced aortic pathological characterization was …

Dual Light Emission Of Cssni3-Based Powders Synthesized Via A Mechanochemical Process, Xuan Huang, Xiaobing Tang, Xiyu Wen, Yuebin Charles Lu, Fuqian Yang

Chemical and Materials Engineering Faculty Publications

Lead toxicity has hindered the wide applications of lead halide perovskites in optoelec- tronics and bioimaging. A significant amount of effort has been made to synthesize lead-free halide perovskites as alternatives to lead halide perovskites. In this work, we demonstrate the feasibility of synthesizing CsSnI3-based powders mechanochemically with dual light emissions under ambi- ent conditions from CsI and SnI2 powders. The formed CsSnI3-based powders are divided into CsSnI3-dominated powders and CsSnI3-contained powders. Under the excitation of ultraviolet light of 365 nm in wavelength, the CsSnI3-dominated powders emit green light with a wavelength centered at 540 nm, and the CsSnI3-contained powders …

Ceramide-Mediated Orchestration Of Oxidative Stress Response Through Filopodia-Derived Small Extracellular Vesicles, Zainuddin Quadri, Ahmed Elsherbini, Simone M. Crivelli, Salim S. El-Amouri, Priyanka Tripathi, Zhihui Zhu, Xiaojia Ren, Liping Zhang, Stefka D. Spassieva, Mariana N. Nikolova‑Karakashian, Erhard Bieberich

Markey Cancer Center Faculty Publications

Extracellular vesicles (EVs) are shed from the plasma membrane, but the regulation and function of these EVs remain unclear. We found that oxidative stress induced by H 2 O 2 in Hela cells stimulated filopodia formation and the secretion of EVs. EVs were small (150 nm) and labeled for CD44, indicating that they were derived from filopodia. Filopodia-derived small EVs (sEVs) were enriched with the sphingolipid ceramide, consistent with increased ceramide in the plasma membrane of filopo- dia. Ceramide was colocalized with neutral sphingomyelinase 2 (nSMase2) and acid sphingomyelinase (ASM), two sphingomyelinases generating ceramide at the plasma membrane. Inhibition of …

Soxb1 Transcription Factors Are Essential For Initiating And Maintaining Neural Plate Border Gene Expression, Elizabeth Schock, Joshua R. York, Austin P. Li, Ashlyn Y. Tu, Carole Labonne

Markey Cancer Center Faculty Publications

SoxB1 transcription factors (Sox2/3) are well known for their role in early neural fate specification in the embryo, but little is known about functional roles for SoxB1 factors in non-neural ectodermal cell types, such as the neural plate border (NPB). Using Xenopus laevis, we set out to determine whether SoxB1 transcription factors have a regulatory function in NPB formation. Here, we show that SoxB1 factors are necessary for NPB formation, and that prolonged SoxB1 factor activity blocks the transition from a NPB to a neural crest state. Using ChIP-seq, we demonstrate that Sox3 is enriched upstream of NPB genes in …

14-3-3Ζ Suppresses Rankl Signaling By Destabilizing Traf6, R. Ayyasamy, S. Fan, P. Czernik, B. Lecka-Czernik, Somsubhra Chattopadhyay, R. Chakravarti

Markey Cancer Center Faculty Publications

Macrophages are essential regulators of inflammation and bone loss. Receptor activator of nuclear factor-κβ ligand (RANKL), a pro-inflammatory cytokine, is responsible for macrophage differentiation to osteoclasts and bone loss. We recently showed that 14-3-3ζ-knockout (Ywhaz^KO) rats exhibit increased bone loss in the inflammatory arthritis model. 14-3-3ζ is a cytosolic adaptor protein that actively participates in many signaling transductions. However, the role of 14-3-3ζ in RANKL signaling or bone remodeling is unknown. We investigated how 14-3-3ζ affects osteoclast activity by evaluating its role in RANKL signaling. We utilized 14-3-3ζ-deficient primary bone marrow–derived macrophages obtained from wildtype and Ywhaz^{KO …}

Discussions Of Cancer Survivorship Care Needs: Are There Rural Versus Urban Inequities?, Tyrone F. Borders, Lindsey R. Hammerslag

Markey Cancer Center Faculty Publications

Background: Rural cancer survivors may face greater challenges receiving survivorship care than urban cancer survivors.

Purpose: To test for rural versus urban inequities and identify other correlates of discussions about cancer survivorship care with healthcare professionals.

Methods: Data are from the 2017 Medical Expenditure Panel Survey (MEPS), which included a cancer survivorship supplement. Adult survivors were asked if they discussed with a healthcare professional 5 components of survivorship care: need for follow-up services, lifestyle/health recommendations, emotional/social needs, long-term side effects, and a summary of treatments received. The Behavioral Model of Health Services guided the inclusion of predisposing, enabling, and need …

Diffuse Reflectance Spectroscopy For Optical Characterizations Of Orthotopic Head And Neck Cancer Models In Vivo, Pranto Soumik Saha, Jing Yan, Caigang Zhu

Markey Cancer Center Faculty Publications

We demonstrated an easy-to-build, portable diffuse reflectance spectroscopy device along with a Monte Carlo inverse model to quantify tissue absorption and scattering-based parameters of orthotopic head and neck cancer models in vivo. Both tissue-mimicking phantom studies and animal studies were conducted to verify the optical spectroscopy system and Monte Carlo inverse model for the accurate extraction of tissue optical properties. For the first time, we reported the tissue absorption and scattering coefficients of mouse normal tongue tissues and tongue tumor tissues. Our in vivo animal studies showed reduced total hemoglobin concentration, lower tissue vascular oxygen saturation, and increased tissue scattering …

A Probabilistic Approach To Estimate The Temporal Order Of Pathway Mutations Accounting For Intra-Tumor Heterogeneity, Menghan Wang, Yanqi Xie, Jinpeng Liu, Austin Li, Li Chen, Arnold Stromberg, Susanne Arnold, Chunming Liu, Chi Wang

Markey Cancer Center Faculty Publications

The development of cancer involves the accumulation of somatic mutations in several essential biological pathways. Delineating the temporal order of pathway mutations during tumori- genesis is crucial for comprehending the biological mechanisms underlying cancer development and identifying potential targets for therapeutic intervention. Several computational and statistical methods have been introduced for estimating the order of somatic mutations based on mutation profile data from a cohort of patients. However, one major issue of current methods is that they do not take into account intra-tumor heterogeneity (ITH), which limits their ability to accurately discern the order of pathway mutations. To address this …

Response To Replication Stress And Maintenance Of Genome Stability By Wrn, The Werner Syndrome Protein, David K. Orren, Amrita Machwe

Markey Cancer Center Faculty Publications

Werner syndrome (WS) is an autosomal recessive disease caused by loss of function of WRN. WS is a segmental progeroid disease and shows early onset or increased frequency of many characteristics of normal aging. WRN possesses helicase, annealing, strand exchange, and exonuclease activities and acts on a variety of DNA substrates, even complex replication and re- combination intermediates. Here, we review the genetics, biochemistry, and probably physiological functions of the WRN protein. Although its precise role is unclear, evidence suggests WRN plays a role in pathways that respond to replication stress and maintain genome stability particularly in telomeric regions.

Serotonin Receptor-Mediated Vasorelaxation Occurs Primarily Through 5-Ht4 Activation In Bovine Lateral Saphenous Vein, Ronald J. Trotta, David L. Harmon, James L. Klotz

Animal and Food Sciences Faculty Publications

To better understand mechanisms of serotonin- (5-HT) mediated vasorelaxation, isolated lateral saphenous veins from cattle were assessed for vasoactivity using myography in response to increasing concentrations of 5-HT or selective 5-HT receptor agonists. Vessels were pre-contracted with 1 × 10⁻⁴ M phenylephrine and exposed to increasing concentrations of 5-HT or 5-HT receptor agonists that were selective for 5-HT_1B, 5-HT_2B, 5-HT₄, and 5-HT₇. Vasoactive response data were normalized as a percentage of the maximum contractile response induced by the phenylephrine pre-contraction. At 1 × 10⁻⁷ M 5-HT, a relaxation was observed …

Discussions Of Cancer Survivorship Care Needs: Are There Rural Versus Urban Inequities?, Tyrone F. Borders, Lindsey R. Hammerslag

Nursing Faculty Publications

Background: Rural cancer survivors may face greater challenges receiving survivorship care than urban cancer survivors.

Purpose: To test for rural versus urban inequities and identify other correlates of discussions about cancer survivorship care with healthcare professionals.

Methods: Data are from the 2017 Medical Expenditure Panel Survey (MEPS), which included a cancer survivorship supplement. Adult survivors were asked if they discussed with a healthcare professional 5 components of survivorship care: need for follow-up services, lifestyle/health recommendations, emotional/social needs, long-term side effects, and a summary of treatments received. The Behavioral Model of Health Services guided the inclusion of predisposing, enabling, and need …

The Potential Impact Of Endangered Species Legislation On Federal Grazing Lands And The Livestock Industry, G M. Luciuk, B Bristol, T W. Weins, D M. Boyle

IGC Proceedings (1977-2023)

Crown based grazing is an integral part of the management structure of cattle operations, and is very important to the economic fabric of rural communities. Federal crown lands, such as the PFRA operated community pastures are an integral part of the resource conservation efforts in western Canada. These lands represent a significant reservoir of the remaining natural lands which are important for wildlife habitat. Sustainable management of such contiguous blocks of land is essential for the maintenance of biodiversity. Proposed endangered species legislation would require the development of recovery plans on federal lands for endangered, threatened and extirpated species. Rural …

Concepts For Mining Landscape Development In Eastern Germany With Grazing Animals And Agroforestry, S Eichler, F Herzog

IGC Proceedings (1977-2023)

Leipzig South (Saxony) has been heavily transformed by open cast lignite mining. Alternative forms of land use are sought which contribute to an increase of biodiversity and an improvement of soil quality. This could be achieved by the selective introduction of grazing animals and perennials. Specific scenarios for open pits, dumping areas, open pits’ slopes and land reclaimed for agriculture are proposed. Socio-economic drawbacks are outlined.

The Use Of Grasslands To Improve Water Quality In The New York City Watershed, D J. Flaherty, J Drelich Jr

IGC Proceedings (1977-2023)

The purpose of this paper is to demonstrate how grasslands are used in the New York City (NYC) Watershed to improve water quality. A Watershed Agricultural Program was established to voluntarily implement Pollution Prevention Best Management Practices on watershed farms. Grasslands have been used in Whole Farm Plans to reduce nutrients, sediments and other toxic materials reaching New York City’s water supply. Rotational grazing has been used to limit access to streams and stream banks and improve nutrient distribution on pastures. Improved grassland management also helps correct the nutrient balance on the farm and facilitates better nutrient management. Brush removal …

Objective Indicators For Monitoring Drought In Grasslands, D H. White, S M. Howden

IGC Proceedings (1977-2023)

Australia’s National Drought Policy was ratified by the Commonwealth (Federal), State and Territory governments in 1992. However, a sequence of El Niño-based events that started in Queensland in 1991 culminated in much of Australia experiencing abnormally low rainfall throughout 1994 and into 1995. Many farmers experienced substantial loss of income. The Commonwealth government therefore devised measures to determine which areas had been exposed to exceptional drought so that financial assistance could be directed as effectively as possible. In this paper we discuss progress in developing regionally-sensitive indicators and methodologies to aid in future assessments of drought exceptional circumstances.

Are We Ignoring Science In Our Quest For Simplicity In Range Management?, W A. Laycock

IGC Proceedings (1977-2023)

Accurate determination of range condition and trend is essential for proper range management. In the United States, the range condition model currently used is not based on up-to-date ecological knowledge. It assumes a single stable state (climax) and linear pathways. Multiple stable state models more accurately depict community dynamics but have not been widely accepted. U.S. Federal land management agencies are using surrogates, such as qualitative “instant trend” measures and substitution of utilization for measured condition and trend to guide management. Most of these short cuts are not based on science. Attacks on livestock grazing by environmentalists are based on …

Socio-Economic And Climate Change In Mongolia - Effects On Grassland Ecosystems, C Opp

IGC Proceedings (1977-2023)

In Mongolia, in combination with strong changes of the whole society during the past 76 years, from the feudal system to socialism and from the socialist system of planned development to the market economy, there are a lot of changes in the use of natural resources all over the country. In consequence of this a lot of effects on grassland ecosystems, caused by socio-economic and climate driving factors, were observed and studied in different scales: zonal, regional, local.

Integrating Biophysical And Economic Models For Assessing Impacts Of Change On Grazingland Ecosystems, J De Souza Neto, J R. Conner, J W. Stuth, W T. Hamilton, J W. Richardson

IGC Proceedings (1977-2023)

PHYGROW, a hydrologic-based forage simulation model, was parameterized to represent a typical South Texas ranch engaged in the production of cattle and meat goats with an indigenous population of white-tailed deer. Forage production and associated stocking rates for two cattle: goat ratios were simulated for 20 years. Two, ten-year weather scenarios, one representing normal conditions (30% drought years) and one representing dryer weather conditions (50% drought years) were analyzed. Management decision rules were developed for the region to produce estimates of annual animal production and operating cost for the enterprises in each of the four scenarios. These performance and cost …

Linear And Community-Based Processes Of Ethical Decision Making For Grassland Workers, Gary W. Fick

IGC Proceedings (1977-2023)

Grasslands are basic elements in sustainable development, but few grassland workers are familiar with concepts of ethical decision making useful in integrating ecological, economic, and sociological components of sustainability. Most published procedures for ethical decision making are based on linear models for individualized social systems with modern technologies. In the context of sustainable agriculture, nonlinear community-based procedures may be more appropriate. In this paper, a nonlinear model from the Haudenosaunee (Iroquois) Indians is compared to more conventional linear procedures. After identification of a problem, linear models often leave the solution of the ethical dilemma (ranking ethical goals when they conflict) …

Policy Options For Decreasing N And P2o5 Losses From Grassland Based Dairy Farms, P.B M. Berentsen, G.W J. Giesen

IGC Proceedings (1977-2023)

Policy instruments for reducing nutrient losses include extension and education, research, financial incentives such as subsidies and levies, and regulations. The potential of these instruments for reducing nitrogen (N), phosphate (P2O5), and ammonia (NH3) losses is examined for Dutch specialized dairy farms on sandy soils. A linear programming model is used to estimate policy impacts. Results indicate that efficiency improvements through extension, education, and research alone have the potential to decrease total N losses to government target levels in 2005 and to erase 92% of the gap between base and target P2O5 losses, but only 24% of the corresponding NH3 …

Production V Conservation: A Policy Dilemma In The Tree Clearing Debate In Queensland, Australia, J C. Scanlan, E J. Turner

IGC Proceedings (1977-2023)

A process for developing policy for tree clearing that meets the competing goals of conservation and production has been followed. There were two levels at which policy was developed. An overall Statewide policy outlined general targets to meet commitments of the Queensland Government. Local guidelines were developed by a large number of groups containing representatives of government and interested conservation movement and industry representatives. The policy and the local guidelines are an important part of the process used to assess applications for permits to clear woody vegetation.

Forage Production And Performance Of Beef Yearlings Grazing Diploid And Tetraploid Crested Wheatgrass, J D. Bruynooghe, R.D H. Cohen, N W. Holt, P G. Jefferson

IGC Proceedings (1977-2023)

A series of experiments were conducted during 1994 and 1995 at Swift Current, Saskatchewan, Canada to evaluate forage production and animal performance on tetraploid Kirk (Agropyron cristatum (L.) Gaertn.) and diploid Fairway (Agropyron cristatum (L.) Gaertn.) crested wheatgrass pastures under grazing conditions imposed by beef (Bos taurus) yearling steers at four stock density levels (3, 4, 6 and 8 steers ha-1). Total ungrazed forage production for Kirk was greater (<0.05) than Fairway (6302 kg ha-1 vs. 5235 kg ha-1) in 1994 but less (P<0.05) than Fairway in 1995 (3709 kg ha-1 vs. 4633 kg ha-1). Animal performance (average daily gain, animal grazing days and total animal production) did not differ (P>0.05) for steers grazing either Kirk or Fairway pastures. Plant vigour and available energy reserves following one season of grazing were evaluated through etiolated growth with …

Vertical Distribution In Grass Swards: Interactions Between Dry Matter And Nutritional Quality, D R. Buckmaster, R H. Mohtar, S L. Fales

IGC Proceedings (1977-2023)

A field experiment was conducted to study the distribution of mass and quality over plant height throughout the growing season in a pure stand of orchardgrass (Dactylis glomerata L.). When plant density (expressed as kg DM/ha per cm height) is plotted against a height of strata, all treatments show a similar linear shape distribution. ADF and NDF concentrations declined with sward height. Fall treatments had lower ADF and NDF concentrations than summer treatments. Conversely, CP concentrations showed an increase with plant height. Fall treatments showed higher CP than spring and summer treatments. Defoliation management did not affect orchardgrass quality. …

Application Of The Phygrow Forage Production- Runoff Model For Regional Stocking Analysis, J W. Stuth, J R. Conner, W T. Hamilton, D M. Schmitt

IGC Proceedings (1977-2023)

A hydrologic-based forage production model, PHYGROW, was used to simulate forage production and carrying capacity of a subtropical shrubland complex of over 34 species grazed by various ratios of cattle and goats with a population of indigenous white-tailed deer over a 20-yr simulated weather profile. The diet selection algorithm allowed the three animal populations to selectively graze preferred foods based on preferences of plant species, plant parts, and live:dead status by phenological stage. A level of maximum utilization of key species was specified. An incremental analysis of cattle:goat demand ratio was analyzed to determine how different combinations of livestock were …